Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Modern drugs have changed epilepsy, which affects people of all ages. But for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people <18y antiseizure medications (ASMs) need separate proof of efficacy and safety (E&S), overall called “pediatric drug development.” This has been corrected to some extent. Authorities accept that ASMs are effective in <18y as well, but they still require "extrapolation of efficacy," as if minors were another species. In our view, the real problem is less that relevant parts of pediatric clinical epilepsy research over the past decades were useless, but that this has hampered research on meaningful challenges. We do not need to show that ASMs work also before the 18th birthday. But we need to learn how to best use ASMs to prevent brain damage in young patients and optimize ASMs use considering a broader range of aspects

An analysis of the performance of Automatic Dependent Surveillance-Broadcast (ADS-B) data received from the Grand Forks, North Dakota International Airport was carried out in this study. The purpose was to understand the vulnerabilities of Universal Access Transceiver (UAT) ADS-B system and recognize the effects on present and future Air Traffic Control (ATC) operation. The Federal Aviation Administration (FAA) mandated all the General Aviation aircraft to be equipped with ADS-B. The aircraft flying within United States and below the transition altitude (18,000 feet) are more likely to install an UAT ADS-B. At present unmanned aircraft systems (UAS) and autonomous air traffic control (ATC) towers are being integrated into the aviation industry and UAT ADS-B is a basic sensor for both class 1 and class 2 Detect and Avoid (DAA) systems. As a fundamental component of future surveillance system, the anomalies and vulnerabilities of ADS-B system need to be identified to enable a fully utilized airspace with enhanced situational awareness. The data received was archived in GDL-90 format, which was parsed into readable data. The anomaly detection of ADS-B messages was based on the FAA ADS-B performance assessment report. The data investigation revealed ADS-B message suffered from different anomalies including drop out; missing payload; data jump; low confident data and altitude discrepancy. Among those studied, the most severe was drop out and 32.49% of messages suffered from this anomaly. Dropout is an incident where ADS-B failed to update within a specified rate. Considering the potential danger being imposed, an in-depth analysis was carried out to characterize message dropout. Three flight parameters were selected to investigate their effect on drop out. Statistical analysis was carried out and Friedman Statistical Test identified that altitude affected drop out more than any other flight parameters.

This work analyzes the severity and risk associated with Automatic Dependent Surveillance-Broadcast (ADS-B) message drop out in Detect and Avoid (DAA) function of Unmanned Aircraft System (UAS). Performance assessment of the Universal Access Transceiver (UAT) ADS-B message implies that in some cases ADS-B fails to update within a specified update interval, which is referred to as drop out in this work. ADS-B is a fundamental surveillance sensor for both class 1 and class 2 DAA systems. Message loss or drop out has been found as one of the common limitations of the ADS-B system. The key feature of this study is incorporating the update rate of real ADS-B data transmitted from the manned aircraft. The data were received from the Grand Forks International Airport, North Dakota. Monte Carlo method has been adopted to resolve encounter scenarios in the presence of drop out. The change in the alert triggered by the UAS DAA in the presence of ADS-B drop out has been investigated. Furthermore, the risk matrices are created to quantify the associated risk with drop out affected alerts. Simulation results depict that both the duration of drop out and DAA look-ahead time affect the alert-triggering function of UAS. With a small look- ahead window and longer duration of drop out, the number of warning alerts increases. Also, alerts are affected more during an overtaking encounter than that of a head-to-head encounter. A system-level analysis is also carried out to recognize the potential reasons behind the ADS-B drop out.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.

We assume that poetic devices have an implicit goal: producing an overall sound scheme that will induce the reader to associate intended and expressed meaning to the sound of the poem. Sounds may be organized into categories and assigned presumed meaning as suggested by traditional literary studies. In my work, I have extracted automatically the sound grids of all the sonnets by William Shakespeare and have combined them with the themes expressed by their contents. In a first experiment I have computed lexically and semantically based sentiment analysis obtaining an 80% of agreement. In a second experiment sentiment analysis has been substituted by Appraisal Theory thus obtaining a more fine-grained interpretation which in some cases contradicts the first one. The computation for the second poet - regarded by many critics the best of last century - includes both vowels and consonants. In addition, it combines automatic semantically and lexically based sentiment analysis with sound grids. The results produce visual maps that clearly separate poems into three clusters: negative harmony, positive harmony and disharmony where the latter instantiates the need by the poet to encompass the opposites in a desperate attempt to reconcile them.

Percutaneous aortic valve replacement (TAVI) has become the treatment of choice for elderly patients with severe aortic valve stenosis because of its less invasiveness compared to surgery. However, it introduces new complications, such as vascular lesions, access site problems, paravalvular leaks, and aortic dissection. Aortic dissection after TAVI is rare but serious, occurring in 0.2% to 0.3% of cases, with both intraprocedural and late cases reported. This case study concerns a 68-year-old woman who developed Stanford B aortic dissection, external iliac artery dissection, and right common femoral artery occlusion after TAVI. Treatment included stenting of the iliac and common femoral arteries, followed by a staged procedure: debranching, thoracic endovascular aortic repair (TEVAR) and endovascular aneurysm repair (EVAR), with satisfactory results. This case, underscores the importance of vigilance in the management of TAVI-related complications to optimize patient care and outcomes.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

Moose (Alces alces) are generalist herbivores but are important aquatic-terrestrial ecotone specialists. Aquatic macrophytes are a high-quality food source for moose during the summer, however their relative importance to moose diet is difficult to study. We used stable isotope analysis of carbon and nitrogen from moose hooves and forage (terrestrial plants, aquatic macrophytes, and arboreal lichen) to estimate the diet of moose at Isle Royale National Park, Michigan, USA, and to evaluate the isotopic variability along chronologies of serially sampled hooves. We hypothesized that aquatic macrophyte consumption and winter body condition (as measured by bone marrow fat content) would be greater at the eastern end of the island where aquatic habitats were most abundant. We were unable to evaluate spatial differences in aquatic macrophyte consumption, but overall, our mixing model results suggest that between 13% and 27% of summer moose diet was from aquatic sources. Among moose that died during winter, body condition was impaired and hoof δ¹⁵N (measured at the hairline) was higher at the western end of the island, where aquatic habitats are sparse. Although isotope chronologies preserved in hooves could significantly enhance our understanding of ungulate foraging ecology, interpretation of such chronologies is presently limited by our lack of knowledge pertaining to hoof growth rate and seasonal dynamics in relation to age and health. Significant isotope distinction among terrestrial plants, aquatic macrophytes, and arboreal lichens indicate that continued methodological advances in stable isotope ecology will lead to more precise estimates of the contribution of aquatic feeding to moose population dynamics.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

This study explores the dynamics of transparency and accountability in supplier relationship management (SRM) within the e-commerce sector. It investigates how e-commerce platforms and their suppliers navigate complexities to foster trust, enhance collaboration, and ensure ethical practices in global supply chains. The research employs a qualitative approach, utilizing semi-structured interviews with industry stakeholders to gather insights into current practices, challenges, and strategies in SRM. Findings highlight transparency as pivotal for sharing critical information such as sales forecasts, inventory levels, and pricing strategies, enabling suppliers to align operations with market demands effectively. However, achieving transparency faces hurdles including data privacy concerns and competitive sensitivities, necessitating robust data security measures and clear communication protocols. Accountability mechanisms, such as formal agreements and governance frameworks, emerge as essential for mitigating risks, resolving disputes, and ensuring compliance with ethical and regulatory standards across diverse contexts. Technological innovations like AI, blockchain, and big data analytics are transforming SRM by enhancing supply chain visibility, operational efficiency, and decision-making capabilities. Cultural factors and regulatory compliance also significantly influence SRM practices, shaping communication styles, relationship dynamics, and legal considerations. Emerging trends such as sustainable sourcing practices and collaborative partnerships are reshaping SRM, emphasizing sustainability and responsible business practices. This study contributes to the understanding of effective SRM strategies, offering insights and recommendations for stakeholders navigating the complexities of e-commerce supply chains.

This qualitative study explores the dynamics of Supplier Relationship Management (SRM) and its impact on innovation within the e-commerce sector. Through in-depth interviews and documentary analysis of three case study firms known for their innovative practices, the study examines how collaborative SRM practices influence innovation outcomes, organizational resilience, and competitive advantage in dynamic market environments. Key themes include the pivotal role of trust, transparency, and joint problem-solving in fostering effective SRM relationships, enabling knowledge sharing and co-development of innovative products and services. Innovation outcomes observed encompass product innovation, process improvements, and technological advancements facilitated by close collaboration between e-commerce firms and their suppliers. Challenges such as managing supplier diversity, navigating regulatory complexities, and mitigating geopolitical risks highlight the complexities and strategic imperatives of SRM implementation in global supply chains. The study also emphasizes the transformative role of digital technologies, including real-time data exchange, predictive analytics, and agile supply chain management, in enhancing SRM effectiveness and innovation capabilities. Strategic alignment with organizational goals and market strategies further enhances the impact of SRM, enabling firms to prioritize innovation initiatives, allocate resources effectively, and sustain growth amidst economic uncertainties. The findings contribute to theoretical understanding and practical insights into SRM strategies that promote innovation excellence and competitive positioning within e-commerce. The implications for practice underscore the importance of fostering collaborative supplier relationships, investing in digital transformation, and adopting proactive strategies to manage risks and regulatory compliance.

This study investigates the critical factors of trust, commitment, and adaptation within supplier relationship management (SRM) in the context of e-commerce. Through qualitative research methods, including semi-structured interviews and documentary analysis, the study explores how these factors influence relationship dynamics and organizational outcomes in digital business environments. Trust is examined as foundational to effective SRM, encompassing integrity, reliability, and shared values between buyers and suppliers. Commitment is analyzed in terms of long-term orientation, resource allocation, and relationship-specific investments aimed at mutual growth and sustainability. Adaptation emerges as essential for navigating the dynamic e-commerce landscape, encompassing proactive strategies, flexibility, and innovation to respond to market changes and technological advancements. The findings highlight the interplay and mutual reinforcement among trust, commitment, and adaptation, contributing synergistically to relationship resilience and organizational performance. However, challenges such as information asymmetry, cybersecurity risks, and organizational inertia are identified as barriers to effective SRM. Practical implications include strategies for enhancing trust, fostering commitment, and cultivating adaptive capabilities through continuous learning, collaborative innovation, and technology integration. By integrating these insights, businesses can strengthen supplier relationships, drive sustainable growth, and achieve competitive advantage in the digital economy.

This qualitative study explores the pivotal roles of trust and communication in supplier relationship management (SRM) within the e-commerce sector. Drawing on interviews and thematic analysis, the study examines how trust, comprising dimensions of competence, benevolence, integrity, and reliability, underpins collaborative partnerships and operational resilience between e-commerce platforms and suppliers. Effective communication strategies, including proactive engagement, transparent feedback mechanisms, and real-time updates via digital platforms, are identified as critical enablers for enhancing information exchange and fostering mutual understanding in SRM. Challenges such as cultural differences, technological complexities, and regulatory compliance requirements are also discussed, highlighting the need for strategic management and investment to mitigate risks and maintain trust in supplier engagements. Relational competencies such as empathy, active listening, conflict resolution, and trust-building skills are recognized as essential for navigating interpersonal dynamics and fostering collaborative relationships in e-commerce SRM. Strategically, integrating these findings into comprehensive SRM frameworks is emphasized to cultivate a positive organizational culture characterized by openness, ethical integrity, collaboration, and adaptability. This approach aims to enhance supplier relationships, drive innovation, and achieve sustainable growth in a competitive marketplace.

This qualitative study explores the intricacies of building sustainable supplier relationships in the e-commerce sector, focusing on best practices and strategic approaches. Through in-depth interviews with procurement managers, supply chain experts, and supplier representatives, the research identifies four critical themes: trust, technology integration, ethical practices, and performance measurement. Trust is found to be the foundation of effective supplier relationships, fostering open communication and collaboration, which are essential for addressing challenges and co-creating solutions. The integration of digital technologies such as supply chain management software, blockchain, and the Internet of Things significantly enhances transparency, decision-making, and operational efficiency, providing a competitive edge. Ethical practices, including adherence to fair labor standards and environmental sustainability, are increasingly crucial as consumer and regulatory expectations evolve, necessitating alignment between e-commerce companies and their suppliers. Performance measurement and continuous improvement are vital for maintaining quality and efficiency, with clear metrics and regular evaluations driving constructive feedback and optimization of supply chain processes. The study underscores the interdependence of these elements in fostering resilient and adaptable supplier relationships. The findings offer practical guidance for e-commerce businesses and suppliers, emphasizing the need for a holistic approach to supplier management that balances trust, technology, ethics, and performance. This approach not only enhances operational effectiveness but also ensures the long-term sustainability of supplier relationships in the dynamic e-commerce landscape. The research contributes to the theoretical understanding of supplier relationship management, providing a comprehensive framework for future studies and practical applications in the e-commerce industry.

Recent advancements in vascular organoid (VO) and vessel-on-chip (VoC) technologies have revolutionized our approach to studying cardiovascular diseases (CVDs), offering unprecedented insights through more physiologically relevant models. VOs generated from human pluripotent stem cells exhibit remarkable self-organization capabilities, forming complex three-dimensional structures that closely mimic human blood vessel architecture and function, while VoCs engineered with groundbreaking microfluidic systems that meticulously recreate the physical and functional attributes of blood vessels. These innovative constructs serve as powerful tools for investigating vascular development, disease progression, and therapeutic efficacy. By enabling the creation of patient-specific VOs and VoCs, they pave the way for personalized medicine approaches, allowing researchers to delve into genetic variations, intricate cellular interactions, and dynamic processes with exceptional resolution. The synergy between VOs and VoCs with cutting-edge technologies such as single-cell sequencing and high-resolution imaging has further amplified their potential, unveiling novel mechanisms underlying CVDs and identifying promising therapeutic targets. Herein, we summarize different types of VOs and VoCs and present an extensive overview on the generation and applications of VOs and VoCs in CVDs. We will also highlight clinical and translational challenges and future perspectives around VOs and VoCs.

In radiotherapy, accurate deposition of energy to the targeted volume is vital to ensure effective treatment. Gel dosimeters are attractive detection systems, as tissue substitutes with potential to yield three-dimensional dose distributions. Radio-fluorogenesis is creation fluorescent chemical products in response to energy deposition from high-energy radiation. This report shares studies of a radio-fluorogenic gel dosimetry system, gelatin with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission, following UV to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated for this system. The response of the system was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship with a dose-rate dependency and no energy or type dependencies. This report supports the utility of gelatin-C3CA for phantom studies of radio-fluorogenic processes.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Simple Summary: 200 words Will biology, including humans, benefit or harm from new developments in information such as artificial intelligence (AI). First, are biology and information different? Life is an ordered form that can reproduce, maybe with variation; and any ordered arrangement, biological or not, potentially contains information. There have been ordered forms since earth was just a ball of chemicals, and some such chemicals can reproduce. So biological and non-biological information might be components of a unified process, ‘PanEvolution’ or ‘Pan-Evo’, based on the same four operations for living or non-living entities - Innovation; Transmission and replication; Adaptation; and Movement. This can produce separate groups called ‘species’. In a current Panspeciation event, information held in biology - especially our brains - is moving into its own environment. Harm to biology might be minimal if humans and AI both behave intelligently, because vastly different environments are optimal for humans and machines containing AI. This would be the first speciation-like event involving humans for millennia, but will not be particularly hostile to humans, if humans learn how to evaluate information and cooperate, to minimize the effect of both human stupidity and artificial simulated stupidity (ASS – a failure of AI). Abstract: 200 words Many people wonder whether biology, including humans, will benefit or harm from new developments in information such as artificial intelligence (AI). Biological and non-biological information might be components of a unified process, ‘Pan-Evolution’ or ‘Pan-Evo’, based on four basic operations – Innovation, Transmission, Adaptation, and Movement. Pan-Evo contains many types of variable objects, from molecules to ecosystems. Biological innovation includes mutations and behavioural changes; non-biological innovation includes naturally-occuring physical innovations, and innovation in software. Replication is commonplace in and outside biology, including autocatalytic chemicals, and autonomous software replication. Adaptation includes biological selection, autocatalytic chemicals and ‘evolutionary programming’ used in AI. Extension of biological speciation to non-biological information, creates a concept called ‘Panspeciation’. Panevolution might benefit or harm biology, but harm might be minimal if AI and the humans behave intelligently, because humans, and the machines in which AI resides, might split to the vastly different environments that suit them. That is a possible example of panspeciation, and would be the first speciation event involving humans for thousands of years. This event will not be particularly hostile to humans, if humans learn to evaluate information and cooperate better, to minimize both human stupidity and artificial simulated stupidity (ASS – a failure of AI).

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

We estimated the risk of blood clots after COVID-19 vaccination accounting for the roles of vaccination in reducing the infection rate, and indirectly lowering the risk of blood clots caused by infection. A self-controlled case series method was used to examine the association between blood clots and COVID-19 vaccination. To deal with the bias due to under-reported infection among non-hospitalized subjects, a case-control study was used to compare the risk of blood clots in infected subjects to control subjects who were hospitalized due to physical injury. We found increased risks of blood clots after vaccination (incidence rate ratio is 1.13, 95% confidence interval (CI): [1.03, 1.24] after the first dose and 1.23, 95% CI: [1.13,1.34] after the second dose). Furthermore, vaccination attenuated the increased risk of blood clots associated with infection (odds ratio (OR) = 2.16, 95% CI: [1.93, 2.42] in unvaccinated versus OR=1.46, 95% CI: [1.25, 1.70] in vaccinated). A causal model was used to explain and weigh up possible risk factors for blood clots after COVID-19 vaccination. After accounting for vaccine efficacy against infection and the protection against infection-associated blood clots, receiving the COVID-19 vaccines decreases the risk of blood clots, especially during high infection rate period.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

This study investigates the critical role of Supplier Relationship Management (SRM) in enhancing the e-commerce user experience. In an increasingly competitive digital marketplace, effective SRM practices are essential for optimizing supply chain operations and meeting customer expectations. The research employs a qualitative approach, combining semi-structured interviews with industry stakeholders, extensive literature review, and case studies to explore various dimensions of SRM. Key findings reveal that strategic supplier selection criteria, including quality, cost efficiency, reliability, innovation, and sustainability, are pivotal in ensuring a robust and adaptable supply chain. Effective communication practices, such as transparency, frequent updates, and digital tools, foster strong supplier relationships and enable timely issue resolution. Performance management strategies, centered on KPI monitoring and continuous improvement, support operational excellence and customer satisfaction. Risk management practices, including diversification, contingency planning, and advanced analytics, are crucial for mitigating disruptions and ensuring supply chain resilience, as highlighted by the challenges posed during the COVID-19 pandemic. Technological integration with blockchain, AI, IoT, data analytics, and automation enhances efficiency, transparency, and decision-making capabilities in SRM. Furthermore, the study underscores the evolving integration of sustainability and ethical sourcing into SRM strategies, reflecting broader corporate responsibility goals. Ultimately, this research contributes to understanding how effective SRM strategies drive competitive advantage in e-commerce by enhancing supply chain reliability, responsiveness, and customer-centricity. As e-commerce continues to evolve, adapting and innovating SRM practices will be vital for companies aiming to sustain growth and meet the dynamic demands of global markets.

This study explores the influence of cultural differences on Supplier Relationship Management (SRM) within global e-commerce, examining communication styles, trust-building, negotiation strategies, and strategic alignment across diverse cultural contexts. Through qualitative research including interviews with e-commerce professionals, the study identifies how cultural factors shape SRM practices and outcomes, highlighting the importance of cultural sensitivity and adaptive strategies in fostering effective supplier relationships. Findings underscore the significance of communication preferences, trust norms, and strategic orientations in navigating cultural complexities to enhance operational efficiency and mitigate risks in global markets. Practical implications suggest integrating cultural dimensions into SRM frameworks, prioritizing cultural competence development, and leveraging cultural diversity for innovation and collaboration. Future research directions include exploring digitalization's impact on cross-cultural SRM and longitudinal studies on evolving cultural dynamics in global business. By advancing understanding in this area, e-commerce firms can enhance resilience, maintain competitive advantage, and achieve sustainable growth in the global marketplace.

This qualitative research explores Supplier Relationship Management (SRM) practices within the e-commerce fashion industry, aiming to uncover key strategies and their impacts. Through semi-structured interviews with supply chain managers, procurement officers, and supplier representatives, critical themes emerged: communication, trust, risk management, sustainability, and digital technologies. Effective communication, characterized by transparency and regular updates, emerged as pivotal for aligning expectations and resolving issues promptly. Trust-building practices, including fair dealings and formal agreements, were essential in fostering long-term partnerships, reducing transaction costs, and enhancing collaboration. Robust risk management strategies, such as supplier diversification and contingency planning, were identified as crucial for mitigating disruptions and ensuring supply chain resilience. Sustainability was highlighted as a strategic imperative, driven by ethical sourcing and environmental standards, supported by technologies like blockchain for transparency. The transformative role of digital technologies—supply chain management software, blockchain, IoT, and data analytics—was evident in enhancing visibility and decision-making across global supply chains. Viewing suppliers as strategic partners, rather than mere vendors, promoted collaborative innovation and mutual growth. Despite challenges like cultural differences and regulatory complexities, opportunities exist to enhance SRM through integrated best practices. By prioritizing effective communication, trust-building, risk management, sustainability, and digital innovation, companies can strengthen supplier relationships, optimize supply chain performance, and achieve competitive advantage in the e-commerce fashion sector.

This qualitative study explores supplier collaboration in e-commerce product development, examining motivations, challenges, strategies, outcomes, and ethical considerations. Through in-depth interviews with stakeholders from diverse e-commerce sectors, the study identifies key themes shaping collaboration dynamics. Motivations include innovation, operational efficiency, and strategic partnerships, driving companies to integrate supplier expertise early in product development. Challenges such as global supply chain complexities, goal misalignment, and communication barriers underscore the need for robust governance and cultural sensitivity. Strategies for success include technology adoption, supplier development programs, and collaborative decision-making, enhancing supply chain visibility and mutual benefits. Effective collaboration yields improved product quality, cost efficiencies, and enhanced customer satisfaction, supporting competitive advantage. Ethical sourcing practices and sustainability initiatives are crucial for maintaining trust and regulatory compliance. Cultural and organizational factors, including leadership support and change management, significantly influence collaboration outcomes. The study concludes with implications for theory and practice, emphasizing the role of innovative strategies and continuous improvement in supplier relationships. Future research could explore digital transformation, sustainability trends, and technological impacts on supplier collaboration in e-commerce. Practical applications include optimizing supply chain strategies to navigate complexities and capitalize on market opportunities.

This qualitative research explores the impact of Supplier Relationship Management (SRM) on e-commerce brand reputation, focusing on the strategic imperatives, operational challenges, and economic implications within digital supply chains. Trust emerges as a foundational element in effective SRM practices, facilitating consistent product quality, timely delivery, and consumer trust, thereby enhancing brand credibility and loyalty. Strategic alignment of SRM with organizational goals enables e-commerce brands to leverage supplier capabilities for mutual growth and innovation. Operational challenges such as technological constraints and logistical complexities underscore the importance of digital integration and proactive risk management strategies to optimize SRM effectiveness. Digital technologies, including AI and blockchain, play a transformative role in enhancing transparency, efficiency, and resilience in SRM strategies, enabling e-commerce firms to mitigate risks and capitalize on market opportunities. Emotional intelligence (EI) competencies among supply chain professionals facilitate effective communication, conflict resolution, and sustainable supplier relationships that bolster brand reputation resilience. Economically, effective SRM practices yield cost efficiencies, improved financial performance, and resilience against supply chain disruptions, supporting sustainable growth in competitive digital markets. This study contributes valuable insights for practitioners and scholars aiming to enhance SRM strategies, optimize supplier relationships, and strengthen brand reputation management in e-commerce. By prioritizing trust, strategic alignment, digital innovation, EI competencies, and proactive risk management, e-commerce brands can navigate complexities, capitalize on opportunities, and foster positive brand reputations in the evolving landscape of digital commerce.

This qualitative research explores Supplier Relationship Management (SRM) within the context of subscription-based e-commerce models. Through in-depth interviews and thematic analysis, the study investigates key elements such as trust, collaboration, technology integration, sustainability, risk management, cultural alignment, innovation, cost management, globalization, supplier selection, and performance measurement. Findings reveal that trust is foundational in fostering reliable interactions and open communication between e-commerce businesses and suppliers. Collaboration emerges as crucial for innovation and operational efficiency, facilitating co-development and shared risk management. Technology integration, including AI and blockchain, enhances supply chain visibility and decision-making capabilities. Sustainability considerations drive businesses to engage with suppliers adhering to environmental standards, enhancing brand reputation and consumer loyalty. Effective risk management strategies mitigate disruptions and ensure supply chain resilience. Cultural alignment fosters harmonious partnerships and mutual understanding across diverse global markets. Innovation through supplier collaboration drives product development and market responsiveness. Cost management practices optimize operational efficiency and strategic supplier relationships. Globalization necessitates adaptive strategies to manage diverse cultural and regulatory landscapes. Strategic supplier selection and continuous performance measurement drive ongoing improvement and alignment with business objectives. This study contributes empirical insights and practical implications for enhancing SRM in subscription-based e-commerce, informing strategies to navigate challenges and leverage opportunities in a competitive marketplace.

This qualitative study explores the pivotal role of Supplier Relationship Management (SRM) in enhancing resilience within e-commerce supply chains. In an era marked by rapid digital transformation and global interconnectedness, the resilience of supply chains has become a strategic imperative for organizations striving to maintain operational efficiency and meet customer expectations. Through semi-structured interviews with supply chain managers, procurement officers, and strategic sourcing specialists across diverse industries, this research investigates the strategies, challenges, and outcomes associated with SRM practices. Findings reveal that effective communication and collaboration are fundamental to successful SRM, fostering trust, transparency, and responsiveness in supplier relationships. Strategic risk management through proactive identification and mitigation strategies enables organizations to navigate uncertainties such as economic fluctuations and geopolitical tensions. SRM implementation yields significant organizational benefits, including improved supply chain efficiencies, enhanced product quality, and increased customer satisfaction. However, challenges such as technological complexities, cultural differences among global suppliers, and regulatory compliance issues underscore the need for adaptive strategies and digital investments. The integration of digital technologies such as AI and blockchain enhances SRM effectiveness by enabling real-time data exchange, predictive insights, and decision-making capabilities. Ultimately, SRM emerges as a cornerstone of sustainable growth and competitive advantage in e-commerce, empowering organizations to optimize supply chain performance and resilience amidst dynamic market conditions.

This qualitative study explores Supplier Relationship Management (SRM) in the context of digital transformation within e-commerce businesses, focusing on the implications of emerging digital technologies. Through semi-structured interviews and documentary analysis, the study examines how organizations leverage technologies like artificial intelligence (AI), blockchain, and Internet of Things (IoT) to enhance SRM practices. Findings reveal that digitalization enables improved operational efficiencies, real-time data analytics, and expanded supplier networks through platforms such as Amazon Business and Alibaba. Strategic shifts are noted towards collaborative supplier relationships, emphasizing joint innovation, technology co-investment, and shared risk management strategies. However, the implementation of digital SRM strategies presents challenges, including data privacy concerns, integration complexities, cybersecurity threats, and regulatory compliance issues. Organizations must navigate these challenges by developing robust governance frameworks and cybersecurity protocols to protect sensitive information and ensure regulatory adherence. Key performance indicators (KPIs) such as supplier performance, cost savings, innovation impact, risk management effectiveness, and sustainability integration are critical for evaluating the success of digital SRM initiatives. Strategically, businesses are advised to prioritize leadership commitment, cross-functional collaboration, and continuous learning to optimize digital SRM practices effectively. Future research should explore emerging trends in digital SRM, investigate technological impacts on supplier dynamics and organizational performance, and examine ethical considerations in digitalization. By integrating these insights into strategic decision-making, businesses can enhance supplier relationships, mitigate operational risks, and achieve sustainable growth in the global marketplace.

This qualitative research investigates the influence of Corporate Social Responsibility (CSR) on Supplier Relationship Management (SRM) within the e-commerce sector. Through semi-structured interviews and secondary data analysis, the study explores motivations, challenges, impacts, and strategic outcomes of integrating CSR practices into supplier relationships. Motivations for adopting CSR include ethical considerations, regulatory compliance, and meeting stakeholder expectations, reflecting a strategic alignment with corporate values and societal demands. Challenges such as resource constraints, regulatory complexities, and cultural differences highlight operational hurdles and strategic considerations e-commerce firms face in implementing CSR initiatives effectively. The study reveals that CSR enhances trust, collaboration, and risk mitigation within e-commerce supply chains through transparent communication, shared values, and ethical practices. Strategically, CSR contributes to enhanced brand equity, competitive advantage, and long-term value creation by differentiating firms in competitive markets and attracting socially conscious consumers and investors. However, economic trade-offs, stakeholder divergence, and operational complexities require firms to adopt adaptive strategies that balance short-term financial goals with long-term sustainability objectives. The findings suggest avenues for future research exploring longitudinal impacts of CSR on supplier relationships, cross-sectoral comparisons, and technological advancements in CSR-driven SRM practices. Practically, e-commerce firms should prioritize strategic alignment of CSR initiatives with core business objectives, engage stakeholders in CSR strategy development, and embrace continuous improvement to foster ethical conduct, stakeholder trust, and sustainable business practices.

Supplier diversity has emerged as a critical strategy for enhancing e-commerce operations by fostering inclusivity and innovation within supply chains. This qualitative research explores the role of supplier diversity in e-commerce, examining its impact on organizational strategies, competitive advantage, and stakeholder perceptions. Through semi-structured interviews with procurement managers, diversity officers, and supply chain executives from diverse e-commerce platforms, this study identifies key themes related to the benefits, challenges, and strategic implications of supplier diversity initiatives. Findings indicate that supplier diversity significantly enhances innovation and creativity within supply chains by integrating diverse perspectives and expertise. This diversity not only enriches product development and market responsiveness but also strengthens corporate reputation and brand equity, demonstrating organizational commitment to ethical business practices and community engagement. However, the study reveals persistent challenges, including financial barriers, systemic biases, and scalability issues, which hinder the effective implementation and scalability of supplier diversity programs. Effective supplier relationship management emerges as critical for maximizing the benefits of supplier diversity, fostering trust, collaboration, and long-term partnerships with diverse suppliers. Looking forward, the future of supplier diversity lies in digital transformation, globalization of supplier networks, and integration of sustainable sourcing practices to enhance transparency, efficiency, and resilience in supply chain operations. This study contributes to the growing literature on supplier diversity by providing empirical insights and practical implications for organizations aiming to leverage diversity as a strategic asset in e-commerce and global supply chain management.

This qualitative research explores Supplier Relationship Management (SRM) as a pivotal driver of sustainable practices in the e-commerce sector. Through in-depth interviews with industry experts, practitioners, and scholars, the study investigates how SRM strategies integrate sustainability criteria into procurement processes, mitigate environmental and ethical risks, and enhance operational efficiencies. Key findings highlight the strategic importance of collaborative relationships with suppliers, technological innovations such as blockchain and data analytics in promoting transparency and accountability, and the influence of consumer preferences for sustainable products on market dynamics. Despite challenges such as regulatory complexities and global supply chain dynamics, businesses are increasingly adopting sustainable SRM practices to strengthen brand reputation, achieve cost savings, and align with evolving sustainability standards. The study underscores the interconnected nature of sustainability within e-commerce operations and calls for continued research to advance technological solutions, refine regulatory frameworks, and foster industry-wide collaboration. By embracing sustainability as a strategic imperative, businesses can navigate complexities, drive innovation, and contribute to a more resilient and sustainable future for the e-commerce industry.

This study explores the strategic importance of leveraging supplier relationships for competitive advantage in the e-commerce industry. Strong supplier relationships are crucial for enhancing operational efficiencies, cost management, quality assurance, innovation, sustainability, and overall supply chain resilience. Through collaborative partnerships, e-commerce companies can streamline logistics, reduce costs, ensure consistent product quality, and foster innovation through joint development initiatives. Ethical sourcing and sustainable practices play a pivotal role in supplier relationship management (SRM), aligning with consumer expectations and enhancing brand reputation. Advanced technologies such as AI, blockchain, and IoT further transform SRM practices by improving transparency, efficiency, and decision-making capabilities across the supply chain. The study also discusses challenges in managing global supplier relationships, emphasizing the importance of effective communication, cultural sensitivity, and strategic risk management. By addressing these challenges and nurturing trust-based relationships with suppliers, e-commerce firms can navigate market complexities and achieve sustainable growth. This research provides insights for e-commerce companies seeking to optimize their supplier relationships and maintain competitive advantage in a dynamic market environment.

This qualitative study investigates the management of supplier risks in e-commerce through relationship management strategies, focusing on trust-building, communication practices, digital technology integration, risk assessment methodologies, challenges, innovation initiatives, and ethical considerations. The research aims to provide nuanced insights into how e-commerce companies navigate the complexities of global supply chains to mitigate operational, financial, and reputational risks associated with supplier relationships. Through semi-structured interviews with 20 key stakeholders in the e-commerce sector, data were collected and analyzed using thematic analysis. The findings underscored the foundational role of trust in establishing resilient supplier relationships, facilitated by transparent communication, consistent performance evaluation, and mutual respect for contractual obligations. Effective communication practices, supported by digital platforms and technologies such as AI, blockchain, IoT, and cloud computing, enhanced operational transparency and decision-making capabilities across supply chains. The study identified diverse approaches to risk assessment, from qualitative evaluations to quantitative models utilizing predictive analytics and scenario planning. However, participants highlighted challenges including geopolitical uncertainties, trade disruptions, regulatory changes, and cultural barriers, necessitating adaptive strategies and diversified sourcing options. Innovation initiatives such as joint product development and technology adoption were crucial in enhancing supply chain agility and competitive advantage. Ethical considerations emerged as a critical aspect, influencing supplier selection criteria, CSR initiatives, environmental sustainability practices, and labor standards compliance. Integrating ethical guidelines into supplier contracts reinforced corporate values and enhanced brand reputation. Overall, this study contributes practical implications for e-commerce practitioners seeking to enhance supply chain resilience, mitigate supplier risks, and sustain competitive advantage in a dynamic global marketplace.

This research investigates the pivotal role of Supplier Relationship Management (SRM) in enhancing e-commerce scalability. SRM practices are essential for optimizing supply chain operations and fostering strategic partnerships with suppliers, crucial in the dynamic and competitive e-commerce landscape. Through a comprehensive analysis of case studies, expert interviews, and secondary data, the study examines how leading e-commerce companies such as Amazon and Alibaba implement effective SRM strategies to achieve scalability. Key findings reveal that strategic supplier selection based on capabilities and alignment with business goals, coupled with continuous evaluation and development programs, ensures consistent supply chain performance and customer satisfaction. Technological advancements, including data analytics, artificial intelligence, and blockchain, play a transformative role in modern SRM by enhancing transparency, efficiency, and decision-making capabilities. These technologies enable real-time monitoring, automated processes, and risk mitigation strategies that bolster supply chain resilience and operational efficiency. Best practices in SRM, such as clear performance metrics, a culture of continuous improvement, and ethical sourcing policies, are critical for driving supplier accountability, innovation, and sustainability. Moreover, sustainability emerges as a growing priority in SRM, with businesses integrating environmental and social considerations into supplier management strategies to meet regulatory requirements and stakeholder expectations. Theoretical frameworks like the Resource-Based View and Transaction Cost Economics provide insights into the strategic implications of SRM, emphasizing its role in fostering competitive advantage and long-term business success. As e-commerce continues to evolve, businesses must adapt and innovate in their SRM approaches to navigate global supply chain complexities effectively. By prioritizing effective SRM practices, leveraging advanced technologies, and embracing sustainability, businesses can enhance their scalability, resilience, and competitiveness in the digital economy.

Effective management of supplier relationships is crucial for e-commerce companies to navigate complex supply chain dynamics and mitigate risks associated with supplier disputes. This qualitative study explores the strategies and challenges involved in resolving supplier disputes through relationship management in the context of e-commerce. Through semi-structured interviews with supply chain managers, procurement officers, and executives from diverse e-commerce firms, the study investigates key themes including communication strategies, trust-building initiatives, negotiation dynamics, technological integration, organizational culture, and global supply chain alignment. Findings reveal that clear and transparent communication plays a foundational role in preventing misunderstandings and fostering collaboration with suppliers. Trust-building initiatives, such as consistency in commitments and transparency in business dealings, are essential for cultivating resilient supplier relationships. Negotiation strategies emphasizing principled negotiation and collaborative problem-solving facilitate the resolution of disputes while preserving long-term partnerships. Technological integration through data analytics, automation, and digital platforms enhances operational efficiency and decision-making capabilities in managing supplier relationships. Organizational culture characterized by collaboration, innovation, and leadership commitment to strategic alignment with global supply chains promotes resilience and responsiveness to market dynamics. Challenges including power dynamics, operational constraints, and cultural differences underscore the importance of proactive risk management and cultural sensitivity in supplier relationship management. This study contributes actionable insights for practitioners to enhance supplier relationship management practices, navigate disputes effectively, and foster sustainable competitive advantage in e-commerce. By integrating these findings into strategic planning, e-commerce firms can strengthen supplier partnerships, optimize supply chain performance, and mitigate risks in a dynamic business environment.

This qualitative research explores the transformative role of Artificial Intelligence (AI) in Supplier Relationship Management (SRM) within the e-commerce sector. SRM is critical for e-commerce platforms to maintain efficient supply chains, optimize supplier interactions, and ensure competitive advantage in a dynamic marketplace. AI technologies offer advanced capabilities such as predictive analytics, machine learning algorithms, and natural language processing, which revolutionize traditional SRM practices by enhancing decision-making accuracy, mitigating supply chain risks, and fostering personalized supplier relationships. Through semi-structured interviews with 20 e-commerce professionals and industry experts, this study investigates AI's impact on supplier selection, operational efficiencies, and strategic supplier relationships. Findings highlight AI's ability to streamline supplier evaluation processes, improve demand forecasting accuracy, and optimize inventory management strategies. AI also facilitates personalized supplier engagement through sentiment analysis and real-time insights, promoting collaboration and trust. Ethical considerations, including algorithmic bias and data privacy, emerge as significant concerns in AI adoption for SRM. Addressing these challenges is crucial to maintaining stakeholder trust and ensuring responsible AI deployment. Furthermore, technological integration barriers and organizational readiness are identified as critical factors influencing successful AI implementation. Looking forward, the study underscores the potential of AI to drive innovation and competitiveness in e-commerce SRM, emphasizing the importance of ethical AI practices, technological infrastructure investments, and organizational preparedness for sustainable growth.

This qualitative research explores the integration of digital technologies to enhance supplier engagement in e-commerce, examining the transformative impact of AI, blockchain, and IoT on supplier relationship management (SRM). Through semi-structured interviews and documentary analysis with 15 industry experts, the study reveals that digital technologies enable organizations to optimize supply chain operations, improve transparency, and foster collaborative partnerships with suppliers. Strategic initiatives such as co-development projects and joint innovation efforts are pivotal in accelerating product development cycles and enhancing market competitiveness. Emotional intelligence (EI) emerges as critical in cultivating trust, empathy, and effective communication, underscoring the human dimension of supplier relationships amidst technological advancements. Challenges identified include technological complexity, data privacy concerns, and resistance to change, necessitating robust cybersecurity measures and proactive compliance strategies. Economically, organizations benefit from significant cost savings, improved efficiency, and enhanced profitability through digital transformation initiatives in SRM. By leveraging digital platforms and data-driven insights, organizations can optimize procurement processes, streamline operations, and mitigate risks to achieve sustainable growth and resilience.

Supplier Relationship Management (SRM) plays a pivotal role in enhancing delivery performance within the e-commerce sector, yet understanding its nuanced impacts remains crucial for optimizing operational efficiencies and customer satisfaction. This qualitative research explores the intricate dynamics of SRM in e-commerce, focusing on strategic alignment, technological integration, trust, collaboration, and risk management as key determinants of delivery reliability. Through in-depth interviews and thematic analysis, the study reveals that strategic alignment of supplier capabilities with firm objectives is fundamental for maintaining a responsive and synchronized supply chain. Technological integration, including AI-driven analytics and blockchain applications, emerges as critical for real-time monitoring and adaptive decision-making, thereby improving delivery accuracy and efficiency. Trust and collaboration are identified as essential pillars for building resilient supplier relationships, fostering transparent communication and joint problem-solving. Effective risk management practices, such as supplier diversification and contingency planning, mitigate disruptions and ensure consistent delivery performance. Despite these benefits, challenges such as technological adoption barriers, cultural differences, communication complexities, resource constraints, and supplier reliability issues persist, necessitating strategic interventions. Recommendations include investing in advanced SRM technologies, promoting cultural understanding, enhancing communication protocols, allocating adequate resources, and fostering collaborative initiatives with suppliers. These strategies aim to overcome challenges and optimize SRM practices, ultimately enhancing delivery performance and competitiveness in the e-commerce landscape.

This qualitative study explores collaborative supplier relationships within the context of e-commerce, aiming to uncover the dynamics, challenges, strategies, impacts, and future trends shaping these partnerships. Through thematic analysis of interviews with e-commerce platform managers, supplier representatives, and industry experts, the study identifies three primary types of relationships: transactional, relational, and strategic. Critical factors influencing these relationships include trust, effective communication, technological integration, and regulatory compliance. Challenges such as information asymmetry, cultural differences, logistical complexities, and competitive pressures are examined, alongside strategies for enhancing collaboration, including clear communication protocols, performance evaluations, and technological advancements. The findings highlight the significant impact of collaborative supplier relationships on business performance, including cost efficiencies, supply chain resilience, innovation capacity, customer satisfaction, and market competitiveness. Looking forward, trends in digital transformation, sustainability initiatives, global supply chain networks, resilience-building strategies, and industry collaboration are discussed as shaping the future landscape of e-commerce partnerships. Embracing these trends presents opportunities for organizations to innovate, adapt, and sustain growth in the competitive digital marketplace.

Supplier Relationship Management (SRM) tools play a crucial role in enhancing efficiency and competitiveness within e-commerce supply chains. This qualitative research explores the effectiveness of SRM tools in optimizing procurement processes, mitigating risks, and fostering collaborative partnerships with suppliers. The study employs semi-structured interviews with key stakeholders in diverse e-commerce sectors to gather insights into the implementation and outcomes of SRM tools. Findings reveal that technological advancements, including AI, blockchain, and data analytics, facilitate real-time communication, decision-making, and supply chain visibility, thereby enabling organizations to achieve cost savings and operational efficiencies. Enhanced supplier relationships through SRM tools contribute to collaborative innovation, faster product development cycles, and improved customer satisfaction. However, challenges such as technological complexity, regulatory compliance, and supplier resistance necessitate strategic management and investment in cybersecurity and compliance frameworks. The research underscores the importance of executive sponsorship, stakeholder engagement, and continuous improvement in driving successful SRM implementations.

This qualitative research explores Supplier Relationship Management (SRM) strategies within the context of e-commerce customization, aiming to understand how businesses effectively manage relationships with suppliers to meet personalized consumer demands. Through semi-structured interviews with industry professionals, key themes such as trust, communication, technological integration, strategic alignment, sustainability, and collaboration emerged as critical factors influencing SRM effectiveness. Trust was found to be foundational, fostering cooperation and commitment between e-commerce businesses and suppliers through transparent interactions. Effective communication and the integration of advanced technologies like AI and blockchain enhanced operational efficiency and innovation capabilities, enabling businesses to deliver tailored customer experiences. Strategic alignment between businesses and suppliers proved essential for shared success and mutual benefit, while sustainability practices increasingly shaped consumer preferences and brand reputation. Collaboration facilitated joint innovation and accelerated product customization, underscoring the importance of partnerships in achieving strategic goals. However, challenges including supply chain complexity, managing consumer expectations, and regulatory compliance highlighted the need for continuous improvement and adaptive strategies. Overall, this research contributes valuable insights for e-commerce businesses seeking to optimize SRM strategies, enhance supply chain efficiency, and navigate the complexities of customization in a competitive digital marketplace. By leveraging trust, communication, technology, strategic alignment, sustainability, and collaboration, businesses can effectively meet evolving consumer demands and achieve sustainable growth.

This qualitative research investigates the impact of Supplier Relationship Management (SRM) on e-commerce innovation adoption. Through semi-structured interviews and document analysis, the study explores how SRM practices influence organizational capabilities to innovate in the context of digital commerce. Key themes emerged, emphasizing the critical role of trust, communication, collaboration, strategic alignment, technology integration, organizational culture, leadership, and external factors in shaping e-commerce innovation. Trust was found to be foundational, fostering transparent communication and collaborative relationships that facilitate innovation. Effective communication channels and collaborative initiatives enabled organizations and suppliers to leverage combined expertise, driving the development of innovative e-commerce solutions. Strategic alignment ensured that both parties worked towards shared goals, supported by technology integration that enhanced operational efficiency and decision-making. Organizational culture and leadership were identified as crucial in creating environments conducive to continuous innovation. External factors such as market dynamics, regulatory requirements, and technological advancements influenced innovation strategies, highlighting the need for adaptive and responsive SRM practices. The findings underscore the interconnectedness of these factors within the SRM framework, offering insights into how organizations can enhance their innovation capabilities and competitiveness in the digital economy. By strategically managing SRM practices and integrating sustainable initiatives, organizations can navigate challenges, seize opportunities, and achieve sustained success in e-commerce innovation.

This qualitative study explores how businesses are adapting their Supplier Relationship Management (SRM) strategies to address the challenges and capitalize on the opportunities presented by evolving e-commerce trends. Through in-depth interviews with key industry stakeholders, the research investigates the integration of advanced technologies such as artificial intelligence (AI), blockchain, and the Internet of Things (IoT) into SRM practices. Findings reveal that these technologies enhance efficiency, transparency, and responsiveness within supply chains, enabling businesses to navigate complexities such as supply chain dynamics, fluctuating consumer demand, and regulatory compliance. The study identifies effective strategies employed by businesses, including enhancing communication channels with suppliers, diversifying supplier bases, and investing in technological advancements. These strategies enable businesses to mitigate risks, improve collaboration, and drive innovation, thereby maintaining competitive advantage in the digital marketplace. Collaborative practices such as joint product development, shared risk management, and co-investment in technology emerge as critical drivers of successful SRM. Ultimately, this research contributes to a deeper understanding of SRM in the context of e-commerce, offering insights into how businesses can optimize their supply chain operations amidst technological disruptions and market fluctuations. The findings underscore the importance of proactive adaptation and strategic alignment with suppliers to foster resilient and agile supply chains. As e-commerce continues to evolve, businesses must leverage these insights to refine their SRM strategies and sustain growth in an increasingly competitive environment.

This qualitative study explores the transformative role of Supplier Relationship Management (SRM) in the context of e-commerce, focusing on the integration of digital technologies and evolving supplier interactions. As digital advancements such as artificial intelligence, blockchain, data analytics, cloud computing, and the Internet of Things (IoT) reshape traditional SRM practices, e-commerce companies are experiencing significant improvements in efficiency, transparency, and collaboration. This research employs semi-structured interviews, document analysis, and case studies to examine the impact of these technologies on SRM, identify key collaborative practices, and assess risk management strategies. Findings indicate that digital integration enhances decision-making, streamlines operations, and fosters deeper, trust-based supplier relationships. AI facilitates predictive analytics and automates processes, while blockchain provides transparency and reduces fraud. Data analytics supports informed sourcing decisions and risk mitigation, and cloud platforms improve real-time collaboration. IoT enhances supply chain visibility, allowing for better inventory management. Despite these benefits, challenges such as high implementation costs, integration difficulties, data privacy concerns, and security risks remain significant barriers. Collaboration practices, including joint development, shared resources, and coordinated marketing, contribute to innovation and mutual growth, emphasizing the need for effective communication and trust. Risk management strategies, such as scenario planning and supplier diversification, are crucial for maintaining supply chain resilience. Strategic alignment between e-commerce companies and suppliers, including goal congruence and capability matching, is essential for seamless coordination and competitive advantage. The study underscores the importance of a holistic approach to SRM, integrating technology, collaboration, risk management, and strategic alignment to navigate the complexities of supplier relationships in the digital age. These insights provide a framework for e-commerce companies to optimize their SRM practices and achieve sustainable growth in a dynamic marketplace.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.

Tropical forest and savanna biomes are pivotal in the functioning of the Earth system. Tropical forests are one of the largest terrestrial biosphere carbon pools, whereas savannas exchange carbon between the biosphere and atmosphere via frequent and extensive landscape fires. Both are biodiverse and under increasing threat due to land clearing and anthropogenic climate change. Reliable mapping of tropical forest and savanna is essential to provide understanding of how anthropogenic impacts are affecting the extent of these biomes. Using Google Maps satellite imagery, we manually classified 24,239 random points as forest, savanna, or anthropogenic landscapes within the tropics. Because fire and climate are correlated, we developed separate geospatial models to rank the importance of climate, topography, and human influence on vegetation present. This modelling confirmed that those areas with more fires had lower probabilities of tropical forest, that forest was most likely in areas with high mean annual rainfall with little seasonal variation in precipitation, and that anthropogenic factors disrupt this environmental predictability. We found there were environments where tropical forest and savanna were equally probable are geographically restricted. These relationships suggest that future drier climates projected under anthropogenic climate change, combined with clearing and burning that have reduced tropical forest extent to a subset of its theoretical distribution, will lead to irreversible loss of tropical forests. Our modelling provides global mapping that can be used track further changes to distribution of rainforests.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+)ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.

Relativistic atomic and molecular structure calculations start from very different premises to quantum electrodynamics (QED). QED predicts radiative corrections that can nly be approximated crudely in today's atomic structure programs. This paper describes rigorous simple algorithms for including accurate vacuum polarization and self-energy corrections in the GRASP programs.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Fire risk can be defined as the probability that a fire will spread. Reliable monitoring of fire risk is essential for effective landscape management. Compilation of fire risk records enable identification of seasonal and inter-annual patterns and provide a baseline to evaluate the trajectories in response to climate change. Typically, fire risk is estimated from meteorological data. In regions with sparse meteorological station coverage environmental proxies provide important additional data stream for estimating past and current fire risk. Here we use a 60-year record of daily flows from two rivers (Franklin and Davey) in the remote Tasmanian Wilderness World Heritage Area (TWWHA) to characterize seasonal patterns in fire risk in temperate Eucalyptus and rainforests. We show that river flows are strongly related to landscape soil moisture estimates derived from down-scaled re-analysis of meteorological data available since 1990. To identify river flow thresholds where forests are likely to burn, we relate river flows to known forest fires that have occurred in the previously defined ecohydrological domains that surround the Franklin and Davey catchments. Our analysis shows that the fire season in the TWWHA is centered on February (70% of all years below the median threshold), with shoulders on December-January and March. Since 1954 forest fire can occur in at least one month for all but four summers in the ecohydrological domain that includes the Franklin catchment, and since 1964 fire fires could occur in at least one month in every summer in the ecohydrological domain that includes the Davey catchment. Our analysis shows that mangers can use river flows as a simple index that provide a landscape-scale forest fire risk in the TWWHA.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using the mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England from March 2020 to March 2021. The research proposed the time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risk based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population's dynamic risk perceptions and lockdown duration. The case study at Leeds fits data well and shows that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results prove that simulated risk perceptions and policy decay could explain urban mobility behaviour during the mobility well during lockdown periods, which could be a reference for future decision-making processes.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

The minimum energy structures of the Si3C5 and Si4C8 clusters are planar and contain planar tetracoordinate carbons (ptCs). These species have been classified, qualitatively, as global () and local () aromatics according to the adaptive natural density partitioning (AdNDP) method, which is an orbital localization method. This work evaluates these species' aromaticity, focusing on confirming and quantifying their global and local aromatic character. For this purpose, we use an orbital localization method based on the partitioning of the molecular space according to the topology of the electronic localization function (LOC-ELF). In addition, the magnetically induced current density is analyzed. The LOC-ELF-based analysis coincides with the AdNDP study (double aromaticity, global and local). Besides, the current density analysis detects global and local ring currents. The strength of the global and local current circuit is significant, involving 4n+2 - and -electrons, respectively. The latter implicates the Si-ptC-Si fragment, which would be related to the 3c-2e -bond detected by the orbital localization methods in this fragment.

Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.

A neglected dimension of the fire regime concept is fire patchiness. Habitat mosaics that emerge from the grain of burned and unburned patches (pyrodiversity) are critical for the persistence of a diverse range of plant and animal species. This issue is of particular importance in frequently burned tropical Eucalyptus savannas, where coarse fire mosaics have been hypothesized to have caused the recent drastic population declines of small mammals. Satellites routinely used for fire mapping in these systems are unable to accurately map fine-grained fire mosaics, frustrating our ability to determine whether declines in biodiversity are associated with local pyrodiversity. To advance this problem, we have developed a novel method (we call ‘double-differenced dNBR’) that combines the infrequent (c. bi-monthly) detailed spatial resolution Landsat with daily coarse scale coverage of MODIS and VIIRS to map pyrodiversity in the savannas of Kakadu National Park. We used seasonal Landsat mosaics and differenced Normalized Burn Ratio (dNBR) to define burned areas, with a modification to dNBR that subtracts long-term average dNBR to increase contrast. Our results show this approach is effective in mapping fine-scale fire mosaics in the homogenous lowland savannas, although inappropriate for nearby heterogenous landscapes. Comparison of this methods to other fire metrics (e.g., area burned, seasonality) based on Landsat and MODIS imagery suggest this method is likely accurate and better at quantifying fine-scale patchiness of fire, albeit it demands detailed field validation.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

The companion paper (Rice 2020) found that the centromeric repeats of the Western European house mouse (Mus musculus domesticus) have unusual structure: i) despite moderate pairwise sequence divergence (average = 5.9%), no monomer sequence was common and many hundreds of monomer sequences were observed, ii) local sequence divergence among neighboring monomers was nearly as high as genome-wide divergence, and iii) matching sequences were rare between side-by-side monomers. Here I integrate information from many published studies to formulate a hypothesis for the evolution of this structure. Non-matching sequences of neighboring centromeric monomers is hypothesized to be selectively favored in the context of molecular drive because it reduces the rate of monomer deletion during repair of double strand breaks (DSBs) via the Single Strand Annealing (SSA) pathway. The foundation for the hypothesis is the observation that centromeres of most populations of M. m. domestics reside close to the telomere, i.e., all their chromosomes are telocentrics. This proximity influences repair of centromeric DSBs because it places at least part of the centromere within the Telomere-Affected Repair Region (TARR; a location with increased concentrations of the shelterin-complex proteins that bind telomeres, especially TRF2). Shelterin proteins increase the level of 5’→3’ end resection at DSBs and thereby: i) decrease the frequency of repair via the c- NHEJ pathway, and ii) increase the frequency of homology-directed repair (HD-repair) –including the SSA repair pathway. It is hypothesized that certain ‘trigger’ events (e.g., sub-telomeric deletions) occur in local populations that increase the influence of TARR on the centromere. This increase elevates the occurrence of SSA repair of centromeric DSBs to a level that causes centromeres to begin to gradually shrink. Chronic shrinkage leads to coevolution between centromere size and karyotype number. Once centromeres shrink to a size below a critical minimum (that causes substantially reduced kinetochore size), fusions between non- homologous telocentrics with undersized centromeres produces metacentrics with an expanded centromere size (and a corresponding ‘quantum-jump’ in kinetochore size). These metacentrics: i) accumulate to fixation because they are favored by centromere drive, and ii) are released from the influence of TARR and thereby gradually recover larger centromere size. Fission of metacentrics with enlarged centromeres can next plausibly regenerate pairs of telocentrics with sufficiently large centromeres (which recruit normal-sized kinetochores) to be favored by centromere drive and accumulate to fixation. This fixation completes a cycle of coevolution within genomes that oscillate between two extremes: i) high karyotype number (2N = 40; all telocentrics) with larger centromeres, and ii) low karyotype number (2N << 40; mainly metacentrics) with initially small centromeres that gradually increase in size.

Studies into the cognitive effects of alcohol have been mixed. They also present methodological challenges, often relying on self-report of alcohol consumption leading to hangover. The current study used BAC (obtained via breathalyser) and self-reported drinking behavior during a night out and related these to hangover severity and cognitive function measured over the internet in the same subjects the following morning. Volunteers were breathalysed and interviewed as they left a central entertainment district of an Australian state capital. They were provided with a unique identifier and, the following morning, logged on to a website. This included an online version of the Alcohol Hangover Severity Scale (AHSS), and number and type of drinks consumed the previous night and the eTMT-B - a validated, online analogue of the Trail Making Test B of executive function and working memory. Hangover severity was significantly correlated with one measure only, namely the previous night’s BAC (r = .228, p = .019). Completion time on the eTMT-B was significantly correlated with hangover severity ( r = .245, p = .012), previous night’s BAC (r = .197, p = .041) and time spent dinking (r = .376, p < .001). These findings confirm that alcohol hangover negatively affects cognitive functioning and that poorer working memory and executive performance correlates with hangover severity. The results also support the utility of using online measures in hangover research.

When animals evolve sufficient intelligence and dexterity to be able to learn to fabricate utility products (UPs) like tools, the UP's they produce become part of an induced-reproduction system that intrinsically shares many life-like traits with biological organisms, including genome-like fabrication and operation information that is physically-encoded in the animal fabricator’s neural networks. When this set of life- like traits includes a sufficient capacity for system-improving cultural evolution (UP-evolvability), the UPs become ‘para-alive’, i.e., nearly alive, or a form of non-biological UP-paralife that is equivalent to the life- status of biological viruses, plasmids, and transposons. In the companion paper I focus on the evolution of UP-paralife in the context of modern, language-capable humans and its predicted evolution going forward in time (Rice 2022). Here I look backward in time and focus on the origin of UP-paralife and its subsequent coevolution with human intelligence. I begin by determining the pathways leading to the evolution of large brains in the rare lineages of biological life that have sufficient intelligence to learn to fabricate tools –a critical first step in the evolution of UP-paralife. The simplest forms of these learning- based UPs, made by species like chimpanzees and New Caledonian crows, represent only proto-UP- paralife because they lack sufficient UP-evolvability. Expanded UP-evolvability required a combination of three attributes that enabled continuous niche-expansion of the animal fabricator via a new and advanced form of UP-mediated teamwork (TW): i) self-domestication that facilitated TW among low-related individuals, ii) learned volitional words (protolanguage) that represent ephemeral UPs that coordinate TW, and iii) learned fabrication of simple flaked-stone tools with cutting and chopping capabilities (a UP to make other structural UPs) that expanded teammate phenotypes and TW capabilities. This specific triad of attributes is synergistic because each one acts as a TW-enhancer that can gradually erode different components of the three major constraints on TW operation and expansion: too much selfishness, insufficient coordination signals, and insufficient physical traits of teammates. The increase in UP- evolvability was transformative and marked the origin of UP-paralife and the initiation of coevolution between UP-paralife (cultural evolution) and the intelligence of its hominin/human symbiont (genetic evolution) that fostered 2.5 million years of: i) continuous brain size increase and niche-expansion within the genus Homo, and ii) parallel advances in the diversity, complexity and uses of UP-paralife. This coevolution also fostered evolutionary expansion of word-based communication, and eventually language, that acted in a catalyst-like manner to facilitate the evolution of increasingly complex forms of imagination, reasoning, mentalizing, and UP-generating technology. I next focus on the evolution of creativity in the human lineage –in the form of divergent thinking and creative imagination. I conclude that the evolution of this advanced cognitive feature required a preadaptation of sufficient intelligence and is the component of human cognition that was the major causal factor generating the greatly expanded diversity and complexity of UP-paralife currently associated with modern humans. Lastly, I apply my findings to the issue of the prevalence of extraterrestrial intelligent life. I conclude that any exoplanets with detected chemical life will very rarely (e.g., probability ~10-5 for a planet closely matching Earth’s characteristics) have evolved intelligence equalling or exceeding that of humans.

Centromeres are among the fastest evolving genomic regions in a diverse array of organisms. The evolutionary process driving this rapid evolution has not been unambiguously established. Here I integrate diverse information to motivate a model in which centromeres evolve rapidly because of their intrinsic molecular phenotype: they tightly bind centromeric proteins throughout the cell cycle. DNA-bound proteins have been shown to cause stalling and collapse of DNA replication forks in many genomic regions, including centromeres. Collapsed replication forks generate one-sided double strand breaks (DSBs) that are repaired by the Break-Induced Repair (BIR) pathway. Here I show why this repair is expected to generate tandem repeat structure and three key features at centromeres: i) increased nucleotide substitution mutation rates, ii) out-of- register re-initiation of replication that leads to indels spanning one or more repeat units, and iii) elevated rates of large and small transpositions within centromeres and between genomic regions. These phenotypes lead to: i) a rapid rate of nucleotide substitutions within a clade of centromeric sequences, ii) continual turnover of monomers within centromeres that fosters molecular-drift and molecular-drive, and iii) recurrent quantum leaps in centromere sequence due to the formation of mosaic monomers and new sequences transposed into non-homologous centromeres. These features are plausibly the major reason centromeres evolve so rapidly. I also speculate on how the DNA sequence of centromeres might perpetually coevolve with the protein sequence of histone CENH3 –the major epigenetic mark of centromeres.

Here I describe an overlooked form of non-biological paralife (i.e., near-life) that has been evolving on Earth for millions of years, and is currently in the final stages of transitioning into a new form of life. Any consideration of non-biological life or paralife is complicated by the fact that there is no consensus among biologists for the definition of life. This ambiguity has caused disagreement about whether subcellular reproduction systems like viruses are a form of life, despite having genomes, mutations, heritable phenotypes and system-improving evolution. To resolve this problem, I develop a definition of life that is entirely functional and independent of any of the structural idiosyncrasies of biological life on Earth: an order-generating system controlled by internally-encoded information that perpetuates itself by functioning to counteract its entropic decay. Using this definition, subcellular transposons, plasmids, and viruses are paralife because they match the definition of life in all ways except that they induce their order-generating functioning by a living host rather through their own self-sustaining production system. Using this functional definition of life, I show that utility- products (UPs) like fabricated hand tools are part of induced-reproduction systems that have features equivalent to biological genomes, mutations, heritable phenotypes, and a process of system-improving evolution. The perceived benefit of utility-products causes them to induce their reproduction by a biological life-form (humans). For these reasons, human utility products are functionally just as close to being a form of life as subcellular transposons, plasmids, and viruses, i.e., they are Utility-Product paralife (UP-parlife). I also show that some forms of UP-paralife are currently evolving into mechanical life that is capable of both self- sustaining reproduction and system-improving evolution without outside assistance. This transition requires the development of a high level of factory and/or UP automation and artificial intelligence (AI) that is capable of complex reasoning, imagination and creativity. Finally, I consider the influence of UP-life and UP-paralife on the development of the level of structural complexity in the universe, and I briefly speculate about how these non-biological forms of life and paralife will influence the expansion of scientific knowledge about the universe.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Food security (FS) during infancy is associated with lifelong outcomes. New Zealand is a developed economy that reports poor childhood nutrition-related health statistics, particularly among minority children, yet has no measure of FS applicable to infancy. The objective was to develop a FS index for New Zealand infants and examine its association with demographic covariates and health outcomes. Within a large (n=6853) nationally representative cohort, variables describing infant food consumption, breastfeeding, and maternal food-related coping methods were collected from mothers during late infancy. A FS index was derived using confirmatory factor analysis. Associations were assessed by logistic regressions and described using odds ratios (OR) and ≥95% confidence intervals (CI). 15% of the cohort was highly FS, 43% tenuously food insecure (FIS), and 16% highly food insecure (FIS). Infants from minority ethnic groups had lower odds of being food secure, as did those born to the youngest mothers, mothers who smoked, or lived in low-income households. FIS infants had higher odds of morbidity. Interventions to improve infant FS should focus on improving dietary quality, and give particular consideration to minority infants. We identified that FIS shows wide ethnic and socioeconomic inequity, and is associated with poorer health. The most important driving factors of FIS included poor quality weaning diets, and poverty and its proxies. Any interventions to improve infant FS should focus on increasing fruit and vegetable consumption to recommended intake levels, and give particular consideration to minority infants.

The North American Monsoon (NAM) in southern Arizona continues to be a topic of interest to ecologists, climatologists, and citizens as well as the triggers and characteristics of plant growth and reproduction in relation to the onset of the monsoon. In researching the onset of the North American Monsoon (NAM) in south-central Arizona relative to the phenology of Saguaro cactus (Carnegiea gigantea) and other Sonoran Desert species we identified interesting and previously unreported features in the NAM rainfall data. We present preliminary descriptive analyses of (1) monsoon onset as measured by the first day after June 1 with precipitation ≥10 mm (1990-2022), (2) first day of year warming of Sea Surface temperatures (SST) in the Gulf of California to ≥29º C measured across five open-sea blocks (mean 9452 km2), and (3) El Niño Southern Oscillation (ENSO) anomaly with a threshold of +/- 0.5º C for the Oceanic Niño Index (ONI) in the Niño 3.4 region (5ºN-5ºS, 120º-170ºW). Three patterns emerge from our analyses: (1) The day of the year of monsoon onset occurs approximately 12 days earlier in the year from 1990-2022 in south-central Arizona. (2) There appears to be a signal in the rainfall onset data very roughly approximating cycles of ENSO Oceanic Niño Index (ONI) anomalies in Niño region 3.4. (3) Gulf of California sea surface temperature (SST) and monsoon onset data support an expected link between the timing of SST warming and monsoon rainfall onset.

Sexual Issues played a significant role in Judaism’s engagement with its Greco-Roman world. This paper will examine that engagement in the Hellenistic Greco-Roman era to the end of the first century CE. In part sexual issues were a key element of demarcation between Jews and the wider community, alongside such matters as circumcision, food laws, sabbath keeping and idolatry. Jewish writers, such as Philo of Alexandria, make much of the alleged sexual profligacy of their Gentile contemporaries, not least in association with wild drunken parties, same-sex relations and pederasty. Jews, including the emerging Christian movement, claimed the moral high ground. In part, however, matters of sexuality were also areas where intercultural influence is evident, such as in the shift in Jewish tradition from polygyny to monogyny, but also in the way Jewish and Christian writers adapted the suspicion and sometimes rejection of passions characteristic of some popular philosophies of their day, seeing them as allies in their moral crusade.

We develop new theory from a broad case-study approach to explore a better understanding of what constitutes knowledge and its value as identifiable to human-machine teams. From past research, this trail of exploration will lead to these initial questions: What is the value of debate in the furtherance of knowledge? Will machines with AI be able to contribute to a debate if we humans cannot define it or determine its value sufficiently for a machine’s understanding, contribution, exploration and identification? Like humans, as teammates, machines must be able to determine with AI what constitutes the usable knowledge that contributes to a team’s success in the field (e.g., testing "knowledge" in the field, identifying new knowledge, using knowledge to develop innovation) or its failure (viz., trouble shooting; identifying weaknesses; discovering vulnerabilities, hiding by deception). It matters not whether a debate is public, private or unexpressed by an individual human or machine agent alone; we speculate in this exploration that the process advances the science of autonomous human-machine teams and assists in interpretable machine learning. We conclude with questions and a speculation: How does a human become aware or express its awareness of knowledge? Can a machine be as expressive as its human teammates? And how does a human-machine teammate become aware that its teammates possess sufficient knowledge to perform a task? We speculate that the structure of “knowledge," once found, is resistant to alternatives (i.e., it is ordered); that its functional utility is generalizable; and that its applications are multifaceted (akin to maximum entropy production). The complexity of the team is taken into consideration in our search for knowledge, which can also be used as an information metric.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Transporting water from one side of a valley or gorge to the other requires construction of an aqueduct bridge or elevated aqueduct. These features are striking elements on cultural landscapes. Unlike previous research that emphasized architecture or design and relied on documentary sources and published works, this study focuses on details of construction and first-hand observation. Roman and Medieval elevated aqueducts in Spain were subjected to rigorous field examination. Marked variations were found to exist between structures of each age. No two aqueduct bridges are alike indicating the absence of standard designs. Locally available materials were used. Construction seems to have been overseen and carried out by individuals who possessed inconsistent degrees of skill. Roman treatises discussed aqueduct bridges, but not how to build them. Many palaces were clearly designed and built by highly skilled personnel during Medieval times, but more mundane public works projects such as aqueducts appear to have been carried out by less-skilled individuals. These findings have implications regarding the construction of elevated aqueducts by Spaniards in the Americas during the 16th century.

We review our theory of interdependence applied to autonomous human-machine teams, with which we have made several generalizations based on theory that have led to new discoveries, compared to social science which is struggling to break free of its validation crisis, but also has no generalizations to new discoveries with human teams, let alone to human-machine teams. In this invited article, based around the stability of a team, of our discoveries, we review the uncertainty between a team's structure and its performance, our first finding. We generalize that finding to deception, vulnerability, innovation and fittedness. From there, our next generalization is to the quantum likeness of interdependence and quantum mechanics; we move on to Shannon holes, knowledge, and conclude with the value of debate and the need for boundaries to contain debate, to reduce interference, and to protect states of interdependence. After the introduction, we extend our model in Section 2 to energy and time, and we close with a brief review of innovation and future plans.

Mortality rates in sub-Saharan Africa remains unacceptably high, and disproportionately affecting economically disadvantaged communities. And healthcare delivery which is considered a major contributor to this is challenged by the limited resources and high service costs, prompting many patients to opt for outpatient department services. This study addresses the need for a data-driven approach to healthcare policy formulation by proposing a model for the implementation of a data warehousing system that integrates outpatients into the national healthcare framework. By leveraging data warehousing, healthcare delivery can be made more efficient through a robust repository that supports decision-making and policy formulation. The research focuses on the outpatient department in resource-scarce settings, proposing a novel multidimensional data model and practical framework implementation. The benefits include improved patient experiences, cost-effective service delivery, and enhanced patient management through electronic health records. Additionally, mobile apps are explored for patient navigation and reminders to enhance treatment adherence. The study’s results indicate that data warehousing can significantly improve healthcare delivery by consolidating critical data and facilitating better planning, resource allocation, and policy formulation. Ultimately, this approach offers valuable insights for optimizing healthcare systems in resource-constrained environments, enabling data-driven policies, and improving health outcomes across sub-Saharan Africa.

Electrical microgrids are deemed to be the future of modern power systems. Microgrids are sophisticated, decentralized, and self-sufficient small-scale power systems consisting of various resources ranging from wind turbines, solar photovoltaics, electric vehicles, smart energy storage, and complex communication infrastructure. However, renewable energy sources such as solar photovoltaics and wind-based generators are highly intermittent, and if not appropriately planned, they can compromise the stability of the grid. Formal methods can define and analyze the functionality and behavior of any system and show if the system design is correct before the actual system is implemented. Although formal methods have been around for many years, it is surprising that little to none are utilized in the design of safety-critical electrical power systems. Currently, in modeling microgrids, few to no attempts of formalization are being used to improve the design reliability and reduce system operating costs and time. This work demonstrates how complex systems such as microgrids can be modeled elegantly using a formal specification method. In this work, the Z state-based formal specification language (Z-Method) is used to model and verify microgrid designs. In this work, 3-interconnected microgrid systems with a high penetration level of solar and wind-based renewable energy sources with plugin hybrid electric vehicles (PHEV) as battery energy storage systems (BESS) are modeled using the Z-method. To the best of authors, the knowledge presented formal method is one of the first reported attempts in modeling microgrid communities using Software Engineering formalism.

Purpose: To explore how race and residential zip codes' socioeconomic index (SES) influenced COVID-19 testing rates in St. Louis during the early and peak phases of the pandemic. Method: An ecological study was conducted using COVID-19 testing data from March to November 2020 in St. Louis City. The study included 16,915 individual tests from 30 residential zip codes. Results: The overall testing rate in St. Louis was 303.97 per 10,000 population. Testing rates among Blacks, Whites, American Indian/Alaskan Natives, and Asians were 374.26, 247.77, 360.63, and 242.41 per 10,000, respectively. Higher testing rates were observed in low and middle SES zip codes compared to high SES zip codes. Adjusted for SES, testing rates were 1.68% higher among Blacks and 0.43% higher among American Indian/Alaskan Natives compared to Whites, and 0.033% lower among Asians. Geographical mapping showed higher testing rates in the inner core and lower rates in the periphery of St. Louis. Conclusion: Race and SES influence testing rates. Areas with low testing rates should be targeted for intervention in St. Louis.

Wastewater (WW) analysis is a critical step in various operations such as control of a WW treatment facility, and speeding-up the analysis of WW quality can significantly improve such operations. This work demonstrates the capability of neural network (NN) regression models to estimate WW characteristic properties such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), ammonia (NH3-N), total dissolved substances (TDS), total alkalinity (TA), and total hardness (TH) by training on WW spectral reflectance in the visible to near-infrared spectrum (400nm-2000nm). The dataset contains samples of spectral reflectance intensity, which were the inputs, and the WW parameter levels (BOD, COD, NH3-N, TDS, TA, and TH), which were the outputs. Various NN model configurations were evaluated in terms of regression model fitness. The mean-absolute-error (MAE) was used as the metric for training and testing the NN models, and the coefficient of determination (R2) between the model predictions and true values was also computed to measure how well the NN models predict the true values. With online spectral measurements, the trained neural network model can provide non-contact and real-time estimation of WW quality at minimum estimation error.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Continuous-variable quantum key distribution (CV-QKD) shows potential for the rapid development of an information-theoretic secure global communications network; however, the complexities of CV-QKD implementation remain a restrictive factor. Machine learning (ML) has recently shown promise in alleviating these complexities. ML has been applied to almost every stage of CV-QKD protocols, including ML-assisted phase error estimation, excess noise estimation, state discrimination, parameter estimation and optimization, key sifting, information reconciliation, and key rate estimation. This survey provides a comprehensive analysis of the current literature on ML-assisted CV-QKD. In addition, the survey compares the ML algorithms assisting CV-QKD with the traditional algorithms they aim to augment, as well as providing recommendations for future directions for ML-assisted CV-QKD research.

Equine-assisted services (EAS) are being increasingly used as complementary interventions for military veterans who have experienced trauma. However, there is limited evidence of benefit for this population and almost no literature describing desired potential outcomes and possible mechanisms of action. The aim of this article is to address these gaps by reviewing the extant literature of animal-assisted interventions in general, and equine-assisted services in particular, with the goal of providing guidance for future investigations in the field. Currently, the field is in the early stage of scientific development, but published results are promising. Interventions that enhance treatment compliance and/or outcomes could benefit this population. Preliminary results, reviewed herein, indicate that EAS interventions might benefit the military veteran population by enhancing treatment engagement and therapeutic alliance, as well as contributing to symptom reduction and resulting in various transdiagnostic benefits. It is recommended that future studies include exploration of potential beneficial outcomes discussed herein as well as investigate suggested mechanisms of action.

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. Similar to higher organisms, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence and pathogen extrinsic incubation period all influence pathogen transmission. Interestingly, the mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps in the biology of the mosquito – microbe symbiosis that need to be addressed in order to understand these interactions more thoroughly and exploit them efficiently. Here, we review current evidence of the impacts of the microbiome on aspects of vectorial capacity highlighting opportunities for novel vector control strategies and areas where further studies are required.

Snow crab replaced groundfish fisheries as the primary focus of the Newfoundland and Labrador (NL) fishing industry in the mid-1990s. Over the past three decades, management philosophies in this male-only fishery have shifted from promoting industry expansion to promoting industry rationalization to implementing Precautionary Approach (PA) management. Until the mid-2010s, there were regionalized management strategies characterized by higher exploitation rates in northern than southern sub-stock units along the NL marine shelves. However, in the late 2010s, exploitation rates were permitted to elevate to high levels across the entire stock range in association with a large resource decline and evidence of biological harm through fishing emerged in chronically depleted areas. In 2019, when stock and fishery productivity were near historic lows, a multi-indicator PA system was informally introduced into management of the resource. This event coincided with anticipated improvements in stock and fishery performance. This paper examines the extent to which the multi-indicator PA management system, focused on promotion of both biological protection and maximization of fishing efficiency, may have contributed to recent improvements in stock and fishery status. A suite of indicators from areas implementing PA guidance into management in 2019 prior to formal adoption of the PA system in 2023 suggest the system has been highly beneficial in promoting rapid recovery, improving stock and fishery performance metrics to levels matching or exceeding historic levels under similar conditions. We discuss capacity of the system to better safeguard biological aspects of resource and fisheries productivity moving forward under a scenario of an expectant resource decline.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls as they are similar and generally regarded as safe (GRAS) for canine diets. Thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and body weight (BW) of 27.4 ± 14.0 were used. After a 4-week wash-in period using sunflower oil and kibble, dogs were blocked by breed, age, and size, and randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All data were analyzed with ANOVA using PROC GLIMMIX of SAS. No biologically significant differences were seen between treatment groups for BW, BCS, FI, hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and due to normal biological variation. These results support a conclusion that camelina oil is safe for use in canine nutrition.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

Milk fat production is important in the New Zealand (NZ) dairy industry. Elsewhere, an amino acid substitution (K232A) in the enzyme diacylglycerol acyl-CoA acyltransferase (DGAT1) has been reported to explain variation in some milk traits, including variation in milk fatty acid (FA) profile. In this study, associations between K232A, and milk traits including milk FA composition, were studied in wholly pasture-fed NZ Holstein-Friesian × Jersey (HF×J) cross-bred dairy cows. With a high frequency of K variant (61.9%), the KK cows produced more milk fat than the AA cows (5.41 ± 0.04 % vs 4.42 ± 0.05 %). The milk volume, fat concentration and protein concentration of AK cows were between the genotypes, AA and KK. More C16:0, CLA and C18:3 cis-9, 12, 15 FA were found in the milk of Kiwi-cross cows feed in outdoor pasture grazing system., and the influence of DGAT1 K232A, on these FAs from mid- and late lactation stages were significant. The AA cows produced (P < 0.001) more CLA and C18:3 cis-9, 12, 15, but less C16:0 (1.137 ± 0.047, 0.855 ± 0.015 and 35.170 ± 0.355) than the KK cows (0.934 ± 0.025, 0.778 ± 0.009 and 38.010 ± 0.250).

This article aims to determine the different factors that are associated with anxiety symptoms among Filipino farmers in Central Luzon. Eligible participants were screened for anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), while the Data Collection Tool for Factors Associated with Anxiety Symptoms (DCFAAS) was constructed and validated to determine the exposure of these factors. Among the 113 eligible farmers, only 19 (16.8%) experienced anxiety symptoms, with excessive worrying (39.8%) being the most frequent anxiety symptom. The mental health of Filipino farmers was significantly affected by the presence of physical illness (OR = 10.70 [1.367, 83.773]) and having relatives affecting work completion (OR = 6.45 [1.346, 30.896]). Therefore, policies must be focused on tackling these issues to address the mental health issues faced by farmers. The low prevalence of anxiety symptoms may stem from existing perceptions and barriers encountered in confiding psychological issues, and the Filipino’s religiosity and resiliency. Keywords: Farmers, Agriculture, Central Luzon, Generalized Anxiety Disorder, GAD-7