The digital format opens up new possibilities for interaction with monographic publications. In particular, annotation tools make it possible to broaden the discussion on the content of a book, to suggest new ideas, to report errors or inaccuracies, and to conduct open peer reviews. However, this requires the support of the users who might not yet be familiar with the annotation of digital documents. This paper will give concrete examples and recommendations for exploiting the potential of annotation in academic research and teaching. After presenting the annotation tool of Hypothesis, the article focuses on its use in the context of HIRMEOS (High Integration of Research Monographs in the European Open Science Infrastructure), a project aimed to improve the Open Access digital monograph. The general line and the aims of a post-peer review experiment with the annotation tool, as well as its usage in didactic activities concerning monographic publications are presented and proposed as potential best practices for similar annotation activities.

Understanding how novel structures arise is a central question in evolution. The carapace of the waterflea Daphnia is a bivalved “cape” of exoskeleton that surrounds the animal, and has been proposed to be one of many novel structures that arose through repeated co-option of genes that also pattern insect wings. To determine whether the Daphnia carapace is a novel structure, the expression of pannier, the Iroquois gene aurucan, and vestigial are compared between Daphnia, Parhyale, and Tribolium. The results suggest that the Daphnia carapace did not arise by cooption, but instead represents an elongated ancestral exite (lateral lobe or plate) that emerges from a proximal leg segment that was incorporated into the Daphnia body wall. The Daphnia carapace therefore appears to be homologous to the Parhyale tergal plate and the insect wing. In addition, the vg-positive region that gives rise to the Daphnia carapace also appears to be present in Parhyale and Tribolium, which do not form a carapace. Thus, rather than a novel structure resulting from gene co-option, the carapace appears to have arisen from an ancient, conserved developmental field that persists in a cryptic state in other arthropod lineages, but in Daphnia became elaborated into the carapace. Cryptic persistence of serially homologous developmental fields may thus be a general solution for the origin of many novel structures.

The North China Plain is among the regions most afflicted by ground fissure disasters in China. Recent urbanization has accelerated ground fissure activity in the three counties of the northern North China Plain, posing significant threats to both the natural environment and socioeconomic sustainability. Despite the increased attention, a lack of comprehensive understanding persists due to delayed recognition and limited research. This study conducted field visits and geological surveys across 43 villages and 80 sites to elucidate the spatial distribution patterns of ground fissures in the aforementioned counties. By integrating these findings with regional geological data, we formulated a causative model to explain ground fissure formation. Our analysis reveals a concentration of ground fissures near the Niuxi and Rongxi faults, with the former exhibiting the most extensive distribution. The primary manifestations of ground fissures include linear cracks and patch-shaped collapse pits, predominantly oriented in east-west and north-south directions, indicating tensile failure with minimal vertical displacement. Various factors contribute to ground fissure development, including fault activity, ancient river channel distribution, bedrock undulations, rainfall, and ground settlement. Fault activity establishes a concealed fracture system in shallow geotechnical layers, laying the groundwork for ground fissure formation. Additionally, the distribution of ancient river channels and bedrock undulations modifies regional stress fields, further facilitating ground fissure emergence. Rainfall and differential ground settlement serve as triggering mechanisms, exposing ground fissures at the surface. This research offers novel insights into the causative mechanisms of ground fissures in the northern North China Plain, providing valuable scientific evidence for mitigating ground fissure disasters during the urbanization process in the region.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Dampers provide safety by control of unwanted motion, due to conversion of mechanical work into another form of energy (e.g., heat). State of the art materials are elastomers including thermoplastic-elastomers. For polymer-appropriate replacement of multi-component shock absorbers comprising mounts, rods, hydraulic fluids, pneumatic devices, or electro-magnetic devices, among others, deep insights of the dynamic thermo-mechanical characteristics of damper materials have to be gained. The ultimate objective is to reduce complexity by utilizing inherent material damping rather than structural (multi-component) damping properties. The objective of this work was to compare the damping behavior of different elastomeric materials including thermoplastic poly(urethane) (TPU), and silicone rubber blends (mixtures of different poly(dimethylsiloxane) (PDMS)). Therefore, the materials were hyper- and viscoelastic characterized, a finite element calculation of a ball-drop test was performed, and for validation the rebound resilience was measured experimentally. In an attempt, the coil-over shock absorber of a model car was replaced by a damper made of the examined and modeled materials. The results revealed that the material parameter determination methodology is reliable, and the data applied for simulation lead to realistic predictions. Interestingly, the rebound resilience of the mixture of soft and hard PDMS (50:50)w% is the highest and the lowest values were measured for TPU.

Damage and fibre misalignment of woven fabrics during discontinuous polymer processing remain challenging. To overcome these, a promising switchable elastomeric adherence gripper is introduced here. The inherent surface tackiness is utilized for picking and placing large sheets. Due to the elastomer’s viscoelastic material behavior, the surface properties depend on loading speed and temperature. Different peeling speeds result in different adherence strength of an interface between the gripper and the substrate. This feature is mechanically characterized and the viscoelastic behavior of the stamp is examined. Based on this experimental characterization, an empirical model is proposed. Furthermore, a discussion of the applicability and limitation of the elastomeric gripper is given.

Abstract: Doppler renal resistive index (RRI) has been used for several decades as a potential indi-cator for renal disease and progression. In recent years, RRI has emerged as a useful prognostic indicator for a range of co-morbidities in patients who are acutely unwell and as a potential marker for sub-clinical acute kidney injury (AKI) and post procedural AKI risk. Despite this, the clinical and theoretical determinants of RRI are poorly understood and remain contentious. Method: A narrative review of studies exploring the theoretical, experimental, and clinical evidence for factors affecting RRI. No date restrictions were set. Findings: Both experimental and clinical data confirm that RRI is markedly affected by a range of systemic and renal determinants and is influenced closely by the underlying risk factors and sys-temic vascular changes that lead to progressive renal damage. Discussion: This paper provides an overview of the key haemodynamic determinants of renal re-sistive index and aims to clarify their relative importance. With reference to a simplified theoretical model, evidence from experimental and clinical studies is reviewed. Pathophysiological factors and patient characteristics that influence RRI are explored to provide a better understanding of why RRI values change in the presence of common or complex pathologies. Conclusion: By gaining a better understanding of the complex systemic and renal factors that influ-ence RRI, ultrasound users will be better prepared to understand and interpret changes in RRI across a range of patient presentations.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

How to align leg segments between the four groups of arthropods (insects, crustaceans, myriapods, and chelicerates) has tantalized researchers for over a century. By comparing the loss-of-function phenotypes of leg patterning genes in diverged arthropod taxa, including a crustacean, insects, and spiders, we show that all arthropod legs can be aligned in a one-to-one fashion. We propose a model wherein insects incorporated two proximal leg segments into the body wall, which moved the ancestral leg lobe (exite) up onto the back to later form wings. For myriapods and chelicerates with seven leg segments, it appears that one proximal leg segment was incorporated into the body wall. According to this model, the chelicerate exopod and the crustacean exopod emerge from different leg segments, and are therefore proposed to have arisen independently. A framework for how to align arthropod appendages now opens up a powerful system for studying the origins of novel structures, the plasticity of developmental fields, and convergent evolution.

A long-standing problem in the understanding of deep-water turbidite reservoirs relates to how the three-dimensional evolution of deep-water channel systems evolve in response to channel filling on spatio-temporal scales, and how depositional environments affect channel architecture. The 3-D structure and temporal evolution of late Miocene deep-water channel complexes in the southern Taranaki Basin, New Zealand is investigated, and the geometry, distribution and stacking patterns of the channel complexes are analyzed. Two recently acquired 3-D seismic datasets, the Pipeline-3D (proximal) and Hector-3D (distal) are analyzed. These surveys provide detailed imaging of late Miocene deep-water channel systems, allowing for the assessment of the intricate geometry and seismic geomorphology of the systems. Seismic attributes resolve the channel bodies and the associated architectural elements. Spectral decomposition, amplitude curvature, and coherence attributes reveal NW-trending straight to low-sinuosity channels and less prominent NE-trending high-sinuosity feeder channels. Stratal slices across the seismic datasets better characterize the architectural elements. The mapped turbidite systems transition from low-sinuosity to meandering high-sinuosity patterns, likely caused by a change in the shelf-slope gradient due to localized structural relief. Stacking facies patterns within the channel systems reveal the temporal variation from a depositional environment characterized by sediment bypass to vertically aggrading channel systems.

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

Green innovation has become an important combination of high-quality economic growth and sustainable development of ecological environment. In this paper, the super-efficiency network SBM model is used to measure the two-stage green innovation efficiency of industrial science and technology R&D and achievement transformation in 30 provinces and cities from 2009 to 2019, and exploratory Data Analysis (ESDA) and spatial econometric model are used to investigate the spatial-temporal evolution characteristics and influencing factors of green innovation efficiency. The results show that: firstly, the overall efficiency of industrial green innovation is low, and the efficiency of scientific research and development and achievement transformation has experienced three stages of "upward-declining-revitalized period". The low efficiency of achievement transformation is an important factor hiding the improvement of the efficiency of industrial green innovation. Secondly, The industrial green innovation efficiency gradually increases from northwest to southeast, forming a centralized "line" and "block" distribution. The high efficiency area is still concentrated in the eastern coastal region, and the balanced development trend is obvious in the central and western regions. Finally, openness has a positive impact on the two-stage green innovation efficiency; Industrial structure and government investment in science and technology have a positive impact on the efficiency of science and technology research and development, but have no significant effect on the efficiency of achievement transformation. Enterprise size has a positive effect on achievement transformation efficiency, but has no significant effect on R&D efficiency. Environmental regulation has a positive impact on R&D efficiency and a negative impact on achievement transformation efficiency.

An iconic feature of insects is the apparent lack of legs on the abdomen, which is believed to be due to the repression of the leg-patterning gene Distalless (Dll) by abdominal Hox genes. However, in contrast to these molecular observations, it is not widely appreciated that the embryos of most insect groups do in fact form paired protrusions on most abdominal segments that appear to be homologous to the thoracic legs. However, these degenerate before hatching to form the abdominal body wall. To resolve this discordance between molecular and morphological observations, the expression patterns of pannier and araucan, genes known to distinguish proximal leg segments in all arthropods, are examined in embryos of the flour beetle Tribolium castaneum. In Tribolium embryos, all pregenital abdominal segments develop leg-like paired protrusions, and the stripes of pannier and araucan expression that delineate the proximal leg segments of the thorax are also expressed in the same configuration around these abdominal protrusions. This suggests that insect abdominal legs are homologous to only the proximal portion of the thoracic legs, which in insect adults forms the body wall (lateral tergum and pleura). These cryptic, truncated abdominal legs – likely inherited from their crustacean ancestors – appear to be an important wellspring for new functions in insects, such as caterpillar prolegs, gills, and structures for camouflage¹⁶ and aposematic warning.

The role of natural factors mainly solar eleven-year cycle variability, and volcanic eruptions on two major modes of climate variability the North Atlantic Oscillation (NAO) and El Niño Southern Oscillation (ENSO) are studied for around last 150 years period. The NAO is the primary factor to regulate Central England Temperature (CET) during winter throughout the period, though NAO is impacted differently by other factors in various time periods. Solar variability indicates a strong positive influence on NAO during 1978-1997, though suggests opposite in earlier period. Solar NAO lag relationship is also shown sensitive to the chosen times of reference and thus points towards the previously proposed mechanism/ relationship related to the sun and NAO. The ENSO is influenced strongly by solar variability and volcanic eruptions in certain periods. This study observes a strong negative association between the sun and ENSO before the 1950s, which is even opposite during the second half of 20th century. The period 1978-1997, when two strong eruptions coincided with active years of strong solar cycles, the ENSO, and volcano suggested a stronger association, and we discussed the important role played by ENSO. That period showed warming in central tropical Pacific while cooling in the North Atlantic with reference to the later period (1999-2017) and also from chosen earlier period. Here we show that the mean atmospheric state is important for understanding the connection between solar variability, the NAO and ENSO and associated mechanism. It presents a critical analysis to improve knowledge about major modes of variability and their role in climate. We also discussed the importance of detecting the robust signal of natural variability, mainly the sun.

Under the development mode of deep blending of emerging technologies, major projects are important for enhancing China's comprehensive national strength and independent innovation capability. Based on the social benefits of major projects, and considering the influence of reputation factors, an evolutionary game model composed of a general contractor and subcontractor of major projects is established. This paper studies the influence of various factors including the income distribution coefficient of collaborative innovation, and MATLAB simulation software is analyzed the influence of factors on an evolutionary path. The results show that a reasonable income distribution coefficient can promote the game behavior of both parties to the direction of active collaborative innovation; The reduction of innovation cost and the improvement of spillover technology absorption capacity can make innovation subjects tend to choose active collaborative innovation strategies. In addition, reputation loss above a specific threshold can effectively inhibit free-riding behavior and encourage innovation subjects to choose active collaborative innovation strategies. The research results provide reference for promoting major projects' technology innovation.

Rice blast is the most harmful disease caused by Magnaporthe oryzae, leading to yield loss. The aim of the work is to improve resistance of rice to blast by introducing and pyramiding genes using conventional breeding technique and modern MAS analysis. Pyramiding is the combination of several resistance genes in one genotype, in this case it improves the resistance of rice to pathogens. MAS analysis revealed that 3 out of 4 studied domestic high-yielding rice cultivars (Bakanasski, Aisaule and Aru) contain 1 blast resistance gene (Pi-2). It was discovered 7 pyramidal lines with the introduction of a combination of 2 blast resistance genes (Pi-1 and Pi-ta) into 6 hybrids and 3 genes (Pi-1, Pi-33 and Pi-ta) into 1 line. Phytopathological test of local cultivars and pyramidal lines of rice showed that 3 out of 7 pyramidal lines have moderate resistance: 2 lines (F2 Bakanasski/7667 (var. vulgaris Koern.) and F2 Aisaule/7664 (var. italica Alef.)), containing 2 resistance genes (Pi-1 and Pi-ta) and 1 line – F2 Aisaule/7689 (var. zeravschanica Brsch.), carrying 3 genes (Pi-1, Pi-33 and Pi-ta), while the local cultivars Bakanasski, Aisaule and Aru are susceptible. As a result, the blast resistance of rice was improved by creating pyramidal lines. Pyramided lines can be used for germplasm exchange and in rice breeding programs to improve blast resistance in rice.

Industrial green technology innovation has become an important content in achieving high-quality economic growth and comprehensively practicing the new development concept in the new era. This paper measures the efficiency of industrial green technology innovation and regional differences based on Chinese provincial panel data from 2005 to 2018, using a combination of the super-efficient SBM model for considering undesirable outputs and the Dagum Gini coefficient method, and discusses and analyses the factors influencing of the industrial green technology innovation efficiency by constructing a spatial econometric model. The results show that: firstly, the industrial green technology innovation efficiency in China shows a relatively stable development trend, going through three stages: " stationary period", " recession period " and "growth period ". However, the efficiency gap between different regions is obvious, specifically in the eastern > central > western regions of China, and the industrial green technology efficiency innovation in the central and western regions is lower than the national average. Secondly, regional differences in the efficiency of industrial green technology innovation in China are evident but tend to narrow overall, with the main reason for the overall difference being regional differences. In terms of intra-regional variation, variation within the eastern region is relatively stable, variation within the central region is relatively low and shows an inverted 'U' shaped trend, and variation within the western region is high and shows a fluctuating downward trend. Thirdly, the firm size, government support, openness to the outside world, environmental regulations and education levels contribute to the efficiency of industrial green technology innovation. In addition, the industrial structure hinders the efficiency of industrial green technology innovation, and each influencing factor has different degrees of spatial spillover effects.

Major (exo)planetary and satellite bodies seem to concentrate at intermediate areas of the radial 1 distributions of all the objects orbiting in each (sub)system. We show that angular-momentum transport during secular evolution of (exo)planets and satellites necessarily results in the observed intermediate accumulation of the massive objects. We quantify the ‘middle’ as the mean of mean motions (orbital angular velocities) when three or more massive objects are involved. Radial evolution of the orbits is expected to be halted when the survivors settle near mean-motion resonances and angular-momentum transfer between them ceases (gravitational Landau damping). This dynamical behavior is opposite in direction to what has been theorized for viscous and magnetized accretion disks, in which gas spreads out and away from either side of any conceivable intermediate area. We present angular momentum transfer simulations in few-body systems, and we calculate the tidal dissipation timescales and the physical properties of the mean tidal field in planetary and satellite (sub)systems.

The greater U.S. Midwest is on the leading edge of tick and tick-borne disease (TBD) expansion, with tick and TBD encroachment into Illinois occurring from both the northern and the southern regions. To assess historical and future habitat suitability of four ticks of medical concern within the state, we fit individual and mean-weighted ensemble species distribution models for Ixodes scapularis, Amblyomma americanum, Dermacentor variabilis, and a newly invading species, Amblyomma maculatum using a variety of landscape and mean climate variables for the periods of 1970-2000, 2041-2060, and 2061-2080. Ensemble model projections for the historical climate were consistent with known distributions of each species but predicted the habitat suitability of A. maculatum to be much greater throughout Illinois than what known distributions demonstrate. Presence of forest and wetlands were the most important landcover classes predicting occurrence of all tick species. As the climate warmed, the expected distribution of all species became strongly responsive to precipitation and temperature variables, particularly precipitation of the warmest quarter and mean diurnal range, as well as proximity to forest cover and water sources. The suitable habitat all species was predicted to shrink in the 2050 climate scenario, and then increase more broadly statewide in the 2070 scenario, but at reduced likelihoods. Predicting where ticks may invade and concentrate as the climate changes will be important to anticipate, prevent, and treat TBD in Illinois.

Deuterium is a heavy nonradioactive isotope of hydrogen, having a neutron as well as a proton, making it twice as heavy. It is a natural element, present at 156 parts per million in seawater. The ATPase pumps in the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage the pumps, producing a stutter that can cause reactive oxygen release and inefficiencies in ATP synthesis. Cellular metabolism incorporates several novel mechanisms to assure low deuterium content in the mitochondria and other organelles. Nicotinamide adenine dinucleotide (NAD) is a major carrier of deuterium depleted (deupleted) protons to supply the mitochondria. Many enzymes, especially flavoproteins, are able to use proton tunneling to fractionate out deuterium. In this paper, we argue that the amino acid proline is able to trap and sequester deuterium, and that peptidyl prolyl isomerases (PPIases) play a central role in facilitating deuterium trapping in proline-rich proteins, most notably collagen. The endothelial glycocalyx also sequesters deuterium in gelled water lining the blood vessels, creating a battery and promoting low deuterium in the circulation. Excess deuterium promotes cancer growth, and cancer cells release large quantities of lactate via aerobic glycolysis to help reverse deuterium overload, systemically.

A fundamental question in biology is whether phenotypes can be predicted by ecological or genomic rules. At least five cases of convergent evolution of the crab-like body plan (with a wide and flattened shape, and a bent abdomen) are known in decapod crustaceans, and have, for over 140 years, been known as ‘carcinization’. The repeated loss of this body plan has been identified as ‘decarcinization’. In reviewing the field, we offer phylogenetic strategies to include poorly known groups, and direct evidence from fossils, that will resolve the history of crab evolution and the degree of phenotypic variation within crabs. Proposed ecological advantages of the crab body are summarized into a hypothesis of phenotypic integration suggesting correlated evolution of the carapace shape and abdomen. Our premise provides fertile ground for future studies of the genomic and developmental basis, and the predictability, of the crab-like body form.

Universities can do more to deliver against the Sustainable Development Goals (SDGs), working with faculty, staff and students as well as their wider stakeholder community and alumni body. They play a critical role in helping shape new ways for the world, educating global citizens and delivering knowledge and innovation into society – universities can be engines of societal transformation. Here, using a case study approach, different ways of strategizing sustainability in a university setting are explored with an example from the UK, Europe and USA. The first case is a public UK university that adopted enterprise and sustainability as its academic mission to secure differentiation in a disrupted and increasingly marketized global higher education sector which then became a source of inspiration for change in regional businesses and the local community. The second case study is a business sector-led sustainability-driven transformation working with a private university in Bulgaria to catalyze economic regeneration and social innovation. Finally, the case of Harvard’s Office for Sustainability engagement program is given to show how this approach connects faculty and students with institutional sustainability plans and external partners. Each case is a living lab, positioning sustainability as an intentional strategy. Leadership at all levels, and by students, was key to success in acting with purpose. Partnerships within and with universities can help accelerate delivery of the SDGs, with higher education making a fuller contribution to sustaining the economic, cultural and intellectual well-being of our global communities.

The well-being and sociability of individuals have always been part of modernity. The development of new technologies that meet these aspirations is receiving increasing attention. Thus, strengthening the desired objectives of these tools and minimizing their undesirable side effects is the subject of a growing commitment. The present contribution aims, in this context, to evaluate and analyze the desired and undesirable effects of the interaction of electromagnetic fields with living tissues in general. This involves routines reinforcing expected functions as well as those controlling and protecting against undesirable effects. First, the interactions of electromagnetic fields with tissues are analyzed, involving their thermal biological effects of desired and undesired exposures. The roles of blood and sap fluids in bio-affected tissues are then analyzed. Secondly, the governing electromagnetic, bio-heat equations, and their coupled solution are studied. Third, the thermal behavior of tissues and the exposure adverse effects are examined. Next, monitoring and defending of the effects of exposures are discussed. This contribution illustrates and discusses mathematical modeling routines based on a generalized interaction of electromagnetic fields with living tissues.

Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

Care coordination (CC) for children with special healthcare needs and medical complexity (CSHCN-CMC) is challenging, and medication management is especially difficult for providers, parents/caregivers, and patients alike. While numerous strategies for CC have been suggested and implemented, barriers to medication optimization remain. The report describes the creation of a pediatric clinical pharmacotherapy practice, related standard operating procedures to assure consistent application of screening tools and care provision through comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy delegation, monitoring, and modification. The methodology of a prospective case series is also presented to highlight drug therapy problems and their resolution in CSHCN-CMC. Future opportunities to expand the practice for engagement in population health management as well as prior authorization activities on behalf of physicians will be discussed.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

We analyze a time-delayed SIQR model that considers the transportation-related infections and entry-exit screening. This model aims to determine the measures for preventing and controlling major emergent infectious diseases and the associated costs. We calculate the basic reproduction number (R0), apply the linearization method, and construct an appropriate Lyapunov function to determine the stability of the disease-free equilibrium in the local and global. We collect COVID-19 infection data from two regions in the United States in 2020 for data fitting, obtain a set of optimal parameter values, and show that the model is suitable for simulating the outbreak and spread of emerging infectious diseases. We find that transportation-related infections increase the basic reproduction number, enhancing the impact on disease spread. Entry-exit screening effectively suppress the spread of disease by reducing the basic reproduction number. Furthermore, we investigate the influence of the incubation period on disease and find that a shorter incubation period results in a shorter duration but a larger scale of infection, and the peaks are reduced. We conduct a sensitivity analysis of the R0 and propose three measures to prevent the spread of new infectious diseases based on the most sensitive parameters: wearing masks, implementing urban closures, and administering medication to sick but not yet hospitalized patients promptly. In the case of COVID-19, we use Pontryagin’s minimum principle to get time-varying control measures to control the spread of the outbreak. Optimal control effectively controls the development and deterioration of the disease. Finally, several control measures are compared through cost-effectiveness analysis, and the results show that wearing masks is the most cost-effective measure. Our study provides some practical guidance for controlling the spread of major emerging infectious diseases.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

O estudo apresenta uma afirmação e explicação de que ocorrem progressões numéricas maiores e menores que dependem da representação contida no espaço físico. Em casos gerais, números maiores são múltiplos e números menores são simples, porque vários números contêm mais números em muitos espaços físicos do que números simples. Em casos específicos, dependem da afirmação do que é a representação específica, podendo ocorrer realidades diferentes de casos gerais. Além disso, a teoria explica a mudança no número de números primos.

(1) Background: OCT imaging has been used to assess enamel demineralization in dental research but is not yet developed enough to qualify as a diagnostic technique in clinics. The current capabilities of most commercial acquisition software allow for visual and qualitative assessment. There is a need for a fast and verified batch-processing algorithm for segmenting and analyzing the de-mineralized enamel. This study suggests a GUI MATLAB algorithm for processing and quantitative analysis of the demineralized enamel. (2) Methods: A group of artificially demineralized human enamels was in vitro scanned under the OCT, and ROI frames were extracted. By using a selected intensity threshold colormap, inter- (Ie) and intra- (Ia) prismatic demineralization can be segmented. A set of quantitative measurements for average demineralized depth, average line profile, and integrated reflectivity can be obtained for an accurate assessment. Real and simulated OCT frames were used for algorithm verification. (3) Results: A strong correlation between automated and known Excel measurements for the average demineralization depth was found (R² > 0.97). (4) Conclusions: OCT image segmentation and quantification of the enamel demoralization zones are possible. The algorithm can assess the future development of a real-time assessment of dental diagnostics using an oral probe OCT.

This study investigated the content of macro- and microelements in the lower reaches of the Ob River (Western Siberia). Seasonal sampling was performed over a four-year period (2020-2023) during the main hydrological seasons (winter low water, spring-summer floods, and early fall low water) at three river stations. Suspended and dissolved fractions were separated by filtration through 0.45-micron nitrocellulose filters. The results revealed significant seasonal variations in the elemental content of the Ob River water, associated with changes in catchment inputs, physical and chemical conditions of the aquatic environment, and the amount and composition of incoming suspended sediment. During high water flow events in the Ob River, the concentration of suspended solids increased substantially. These included significant quantities of sparingly soluble hydrolysates such as Al, Ti, Zr, Ga. During the winter period when the Ob River was ice-covered, a 2- to 3-fold rise was observed in the concentration of Na, Mg, Ca, K, Si, Mn. Having accounted for these seasonal variations in water chemistry, we were able to refine our estimates of elemental export to the Arctic Ocean. Compared to estimates from previous studies, we observed with 2.3-fold higher dissolved loads of Mn, 2.1-fold for Zn, 1.6-fold for Fe, and 1.4-fold for Pb.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

In order to assess the human exposure risks from the release of contaminants from water pipes made of polyvinyl chloride (PVC), experiments were carried out by subjecting the PVC pipe material to burning and leaching conditions followed by analysis of the emission and leachate samples. The emissions of burning pipes were analyzed by both infrared spectrometry and gas chromatography-mass spectrometry (GC-MS). The emission results indicate the presence of chlorinated components including chlorine dioxide, methyl chloride, methylene chloride, allyl chloride, vinyl chloride, ethyl chloride, 1-chlorobutane, tetrachloroethylene, chlorobenzene, and hydrogen chloride were detected in the emissions of burning PVC pipes. Furthermore, the concentrations of benzene, 1,3-butadiene, methyl methacrylate, carbon monoxide, acrolein, and formaldehyde were found at levels capable of affecting human health adversely. The analysis of PVC pipe leachates using GC-MS shows that there are 40-60 tentatively identified compounds, mostly long-chain hydrocarbons such as tetradecane, hexadecane, octadecane, and docosane, were released when the burned PVC materials were soaked in deionized water for one week. Quantitative analysis shows that 2-butoxyethanol, 2-ethyl-1-hexanol, and diethyl phthalate were found in the burned PVC polymer at the average levels of 2.7, 14.0, and 3.1 micrograms per gram (g/g) of pipe material. This study has significant implications for understanding the benzene contamination of drinking water in the aftermath of wildfires that burned polymer pipes in California.

Acute myeloid leukemia (AML) is a hematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterized as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukemias. Furthermore gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.

Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cogni-tive Behaviour Therapy (ICBT) can reduce barriers to care for broad cross sections of the population. How-ever, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are underrepresented in clinical trials of psychological interventions. To address this research gap, we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the effectiveness, satisfaction, and engagement in the adapted ICBT by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) drawn from a previous non-adapted version of the ICBT program. Inntent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and de-pression symptoms among PDEGs. Large within-group pre-to-post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT program reported high overall satisfaction, 90.9 % reported increased confidence in managing symptoms, and 70.7% of participants completed the ma-jority of the psychoeducational lessons in the ICBT program. No statistically significant differences in clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

Omics technologies, viz., genomics, transcriptomics, proteomics, metabolomics, and phenomics, are becoming an integral part of virtually every commercial cereal breeding program because they provide substantial dividends per unit time in both pre-breeding and breeding phases. Continuous advances in cereal-omics promise—in combination with time efficiency—the cost benefits. In this review, we provide a comprehensive overview of the established cereal-omics methods in five major cereals, viz., rice, sorghum, maize, barley, and bread wheat. We cover the evolution of technologies in each omics section independently and concentrate on their use to improve economically important agronomic as well as biotic and abiotic stress-related traits. Advancements in the (1) identification, mapping, and sequencing of molecular/structural variants, (2) high-density transcriptomics data to study gene expression patterns, (3) global and targeted proteome profiling to study protein structure and interaction, (4) metabolomic profiling to quantify organ level small-density metabolites and their composition, and (5) high-resolution high-throughput image-based phenomics approaches are surveyed in this review.

The study aimed to evaluate for the first time the degree of contamination of soil and crops with major and trace elements (Cd, Co, Cr, Cu, Ni, Pb, Zn, F, Na, Mg, Si, P, Cl, Fe, Al) in agricultural lands situated in the Lower Danube Basin, Galati and Braila counties (SE Romania), impacted by the steel industry. Soil samples from two depths (0–5 cm and 5–30 cm), as well as leaves and seeds of wheat, corn, and sunflower, were collected from 11 different sites. Along with elemental and mineralogical analysis, performed by HR-CS AAS, PIGE, SEM-EDX and ATR-FTIR, the soil pH, texture, organic matter, electric conductivity and CaCO3 content were investigated. The results showed that the levels of Cr (83.270–383.100 mg kg-1), Cu (17.110–68.151 mg kg-1), Ni (30.157–55.656 mg kg-1), and F (319–544 mg kg-1) in soil exceeded the Romanian regulations for sensitive use of the land. The pollution indices (Igeo, EF, PI, PERI) indicate that the soil is moderate to highly contaminated with Cr, Ni and Cu, while CSI and mERMQ indices suggested a relatively low risk for metal contamination. The concentrations of elements in plant tissues and bioaccumulation factors (BFs) show the soil-plant relation and health risk, but also the elemental selectivity of vegetal compartments. Thus, the results showed that wheat plants tend to exclude the bioaccumulation of certain elements in their tissues, while for Zn and Cu, the bioaccumulation pattern is different. In the case of corn, most BFs were below 1, indicating limited phytoaccumulation capacity. However, exceptions were observed for Cd, Zn, and Cu. Sunflower BFs indicate higher bioconcentration of Cu, Cd, and Zn in both the leaves and seeds compared to other elements. Chromium (Cr) contributes to non-carcinogenic dermal contact and ingestion hazards, with children being more susceptible to the adverse effects of this contaminant.

The purpose of this study is to investigate the effect of academic advising on changing or maintaining majors in university degrees. It is also a goal of the study to determine which semester of the course study is most likely or less likely witness the change of major and whether advising contributes to that change. Through this correlational study, the researchers explored students’ perceptions about the academic advising they received and the relationship of its absence on students’ major change. The participants were 1725 undergraduate students from all year levels. One survey is used to collect the data for this study: Influences on Choice of Major Survey. Based on the findings, it is found that university advisors have a very poor effect on students' decisions to select their majors as 45.6% of the 1725 participants indicate NO influence of advising in their survey answers. Whereas career advancement opportunities, students' interests, and job opportunities indicate a strong effect on their majors’ selections as they score the highest means of 3.76, 3.73, 3.64 respectively. In addition, findings show that students are most likely changing their majors in their second year and specifically in the second semester. Second year major change scored 36.9% in the second semester and 30.9% in the first semester. More importantly, results indicate that there is a positive significant correlation between college advisor and change major in the second year (p = 0.000). It is to researchers understanding based on the findings that when students receive enough academic advising in the first year of study and continues steadily to the next year, the possibilities of students changing their majors decreases greatly.

This qualitative research study is a part of a larger research project exploring the experiences of young caregivers aged 5-26 years and their families navigating the COVID-19 pandemic between 2020 to 2023. Data was collected from 14 young caregivers who participated in baseline interviews. The central research question guiding this study: What was, is, and will be the impact of changing public health restrictions on young caregivers and their families during the pandemic and pandemic recovery? Seven themes emerged through analysis: 1) Navigating Care During the Height of Public Health Restrictions, 2) Neighbourhood and Built Environment During the Pandemic, 3) Perceptions Towards COVID and Public Health Restrictions/Efforts, 4) The Impact of Public Health Restrictions on Relationships, 5) Mental Health Challenges of Being a Young Caregiver During a Pandemic, 6) Navigating Formal Services and Supports and 7) Recommendations from Young Caregivers. The findings from this empirical research suggest that young caregivers found it easier to navigate their caregiving responsibilities when public health restrictions and work-from-home mandates were initially implemented, however, this later changed due to challenges in finding respite from caregiving, maintaining social connections with friends, creating personal space at home, and finding adequate replacements of programs once offered in-person.

The aim of the study is to obtain a more complete picture of the blood plasma melatonin concentration in the donkey species. To this purpose sampling and statistical processing were carried out in such a way that allowed to establish the annual and daily rhythm. Based on human observations, according to the hypothesis of the authors, the blood plasma melatonin concentration of pregnant individuals rises during late gestational period, before parturition. To confirm this, the melatonin concentration of pregnant and non-pregnant mares was monitored and compared. In regard to the circannual rhythm, the significantly lowest midnight melatonin value (27.67 pg/ml) is typical for the summer solstice. Under consideration of circadian changes, a significantly strongest melatonin production (45.16 pg/ml) can be observed on the night of the winter solstice (p < 0.001). Considering the gestational age, the blood plasma melatonin concentration (around 38 pg/ml) does not change as pregnancy progresses (p = 0.136). The results obtained in the study population of the domestic ass usefully expand the little knowledge previously gathered about the development of blood plasma melatonin concentration of this species.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

This empirical research is part of a larger project beginning in 2020 and ongoing until 2023 exploring the impact of the COVID-19 pandemic on young caregivers aged 5-25 years and their families in Canada. Utilizing the social determinants of health as a conceptual framework, this case study emphasizes the voices of professionals offering services to young caregiver clients during the pandemic, and explores their perspectives on the impact of the pandemic on young caregivers and their families. Across three (3) different organizations offering programs and services to young caregiver clients in Ontario, six (6) individual interviews were conducted with directors/program managers and four (4) group interviews were conducted with thirteen (13) staff members who worked directly with young caregivers and their families. Nineteen (19) service providers participated in total. The results of this study highlight five (5) primary themes that emerged through data analysis: i) the role of service providers, ii) the impact of the COVID-19 pandemic on organizations and service providers supporting young caregivers and their families, iii) barriers for service users, iv) helpful resources for service providers and organizations, and v) resources needed/preferred by service providers and organization. The pandemic significantly impacted young caregivers and their families, as reported by professionals, and organizations working with young caregivers and their families were tasked with addressing increased service demands and adapting service delivery to follow public health guidelines.

T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) of histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis with high-field Fourier transform ion cyclotron resonance MS (FTICR-MS) can detect species missed by bottom-up approaches. We used high-resolution reversed-phase liquid chromatography (RPLC) FTICR-MS, alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. First online RPLC separation sorted histone families then weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative PTM identifications were assigned by matching peptide masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for Histone-intact protein PTM mapping (HiPTMap) and to quantify PTMs on core histones purified from CD8+ T cells directly isolated ex vivo post-influenza infection. Activation significantly reduced PTMs in vivo following influenza infection, histone maps changed as T cells migrated to infections, and T cells responding to secondary heterologous infections had significantly more PTMs enhancing transcriptional activation. Thus, HiPTMap identifies and quantifies PTMs on CD8+ T cell histones and determines their combinations in T cell states.

Objectives: The promising specific growth regulators are employed tissue culture of the bamboo species. The specific natural hardening mixture supports the acclimatization and adaptation of the protected cultivation. The bamboo species contribute to the carbon sequestration and stabilization of the environment. Findings: The growth regulator 2, 4-D encourages callus induction and growth regulators NAA + TDZ, BAP + Kinetin + Gelrite, BAP + Kinetin + Coconut water + myo-inositol, NAA and TDZ impose plant regeneration in the Bambusa species. The growth regulator of 2,4-D, 2,4-D + Kinetin, 2,4-D + BA, 2,4-D + BAP and 2,4-D + NAA + BAP produces callus induction in the Dendrocalamus species. The growth regulator of TDZ, BA and IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA has facilitated shoot regeneration in the Dendrocalamus species with the specific period. The growth regulator of BA and TDZ; BAP + TDZ, IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA develops root regeneration with unambiguous time in the Dendrocalamus species. The growth regulator of BAP and Kinetin + BAP imposes shoot regeneration and IBA and IBA + Coumarin + sucrose conducts root regeneration in the edible bamboo. The natural hardening materials of cocopeat, vermicompost, perlite, cow dung, FYM, compost, soil & garden soil and humus soil, perlite, and FYM recommend in the acclimatization and adaptation of the Bambusa species and Dendrocalamus species respectively. Novelty: The standard growth regulators and hardening mixtures impose tissue culture, acclimatization and adaptation in the bamboo species. The bamboo species involves in managing carbon sequestration, biogeochemical cycle and the environment.

The basic pattern of MHC variation in fish, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical, is similar in fish and mammals. Nevertheless, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I genes tend to be much higher than in mammals; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. The present study is a review and discussion of the fish MHC situation.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

In Bangladesh, climate change is a major concern because of its geophysical location and climate dependent agriculture. As sessile organisms, crops plants have to face difficulties often in this environmentally vulnerable country. Therefore, this study examines the seasonal trend of two climatic parameters viz. temperature (maximum and minimum) and rainfall over a period of 1983 to 2013. Besides, this study provides insight into the relationship between climatic parameters and crop yield of two major crops viz. rice and wheat during 1997-2013. To assess the relationship of climatic parameters with time and yield using Pearson correlation analysis, time series data used at an aggregate level. SPSS software utilized for this analysis. The cropping seasons such as rice growing seasons Aus (summer rice), Aman (autumn rice) and Boro (winter rice) exhibited a significant increase in maximum and minimum temperature. Rainfall found to have a decreasing trend for all the seasons. This study also revealed that the climatic parameters had significant effects on rice yield, but these results varied among three rice crops. Maximum temperature had positive effects on all rice yields, especially on Aus and Aman. Minimum temperature had a negative effect on Aman rice yield but a positive effect on Aus rice yield. Wheat yield negatively associated with temperature. Rainfall exhibited negative relation with both rice and wheat yield.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Cows produce saliva in very large quantities to lubricate and facilitate food processing. Estimates indicate an amount of 50-150 liter per day. Human saliva has previously been found to contain numerous antibacterial components, such as lysozyme, histatins, members of the S-100 family and lactoferrin to limit pathogen colonization. Cows are dependent of a complex microbial community in their digestive system for food digestion. We wondered how this would influence the content of their saliva. We therefore sampled saliva from five humans and both nose secretions and saliva from six cows and separated the saliva on SDS-PAGE gradient gels and analyzed the major protein bands by LC-MS/MS. The cow saliva was found to be dominated by a few major proteins only, the carbonic anhydrase 6, a pH stabilizing enzyme, and the short palate, lung and nasal epithelium carcinoma-associated protein 2A (SPLUNC2A), also named bovine salivary protein 30kDa (BSP30). This latter protein has been proposed to play a role in local antibacterial response by binding bacterial lipopolysaccharide (LPS) and inhibit bacterial growth, but may instead according to more recent data instead have primarily surfactant activity. Numerous peptide fragments of mucin-5B were also detected in the MS analysis. However, mucins stain poorly by the gel staining solution and they are large and have difficult to enter regular gels why their presence easily are overseen. Interestingly, no major band on gel was detected representing any of the antibacterial proteins indicating that cows may produce them at very low levels not to harm the microbial flora of their digestive system. The nose secretions of the cows primarily contained the odorant protein, a protein thought to be involved in enhancing the sensing of smell by the olfactory receptors to enhance the possibility to quickly sense potential poisonous food components. High levels of secretory IgA was also found in one sample of cow mouth drippings indicating a strong upregulation during an infection. The human saliva we more complex containing both secretory IgA, amylase, carbonic anhydrase 6, lysozyme, histatins and a number of other less abundant proteins.

An empirical investigation was carried out to study the relationship between the soil characteristics, including the Nitrogen (N), Phosphorus (P), Potassium (K), potential of Hydrogen (pH), Electrical conductivity (EC), Sulfur (S,), Zinc (Zn), Iron (Fe), Copper (Cu), Manganese (Mn) and Boron (B) using principal component analysis (PCA), Factor Analysis (FA), and Canonical Correlation analysis (CCA) for data reduction multivariate techniques. The first five main components accounted for 24.22%, 18.52%, 16.1%, 9.97%, and 9.27% of sample variances, respectively. All five principal components (PCs) accounted for 78.07% of the sample variance. The soil characteristics viz., P and K have highly dominated the first PC; the soil characteristics N and pH have dominated the second PC; K, EC, and Cu have dominated the third PC; Fe, Mn, and pH have dominated in the fourth PC; whereas the parameter Cu dominated the fifth PC. The first factor showed a strong negative loading on S and a strong favorable loading on Cu; P, K, and EC have substantial positive loadings in the second factor. Significant positive loadings on Mn, Fe, Cu, pH, N, and K are present in the third component. The fourth factor had a significantly positive pH, Fe, N, P, K, and B loadings. Fe, P, and B have much weight in the fifth factor. The soil characteristics viz., N, Zn, pH, K, Fe, and Mn have dominated the first PC; the soil characteristics B, P, S, Zn, and Fe have dominated the second PC; B and P have dominated the third PC whereas the only character Cu dominated the fourth PC. Cu and OC have much weight in the fourth factor. The canonical redundancies for dependent and independent sets are 12% and 17%, respectively. The Stewart-Love canonical redundancy index is 70.58%, which means that the first linear combination of the X-set explains 70.58% of the total variance in the Y-set.

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

Mucormycosis (previously called zygomycosis or phycomycosis), an aggressive, life-threatening infection is further aggravating the human health-impact of the devastating COVID-19 pandemic. Additionally, a great deal of mostly misleading discussion is focused also on the aggravation of the COVID-19 accrued impacts due to the white and yellow fungal diseases. In addition to the knowledge of important risk factors, modes of spread, pathogenesis and host defences, a critical discussion on the botanical insights into the main causative agents of mucormycosis in the current context is very imperative. Given above, in this paper: (i) general background of the mucormycosis and COVID-19 is briefly presented; (ii) overview of fungi is presented, the major beneficial and harmful fungi are highlighted; and also the major ways of fungal infections such as mycosis, mycotoxicosis, and mycetismus are enlightened; (iii) the major causative agents of mucormycosis are critically discussed; (iv) the systematic position, occurrence, structure, and the major modes of reproduction are summarized for Rhizopus sp. and Mucor sp., the major causative agents of mucormycosis; (v) the other causative agents of mucormycosis includes Cunninghamella bertholletiae, Apophysomyces elegans, Lichtheimia (Absidia), Saksenaea, and Rhizomucor pusillus are briefly introduced; (vi) facts related with the infection-misnomers based on fungi colour are also highlighted; and lastly, (vii) the major take-home message and clues for future research on the subject are listed.

Identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly targeted strategies designed to improve the outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3, is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD), present in 30%-35% of AML patients at diagnosis. An established driver mutation and marker of poor prognosis, the FLT3 tyrosine kinase has emerged as an attractive therapeutic target, and thus has encouraged the development of FLT3 tyrosine kinase inhibitors (TKIs). However, the therapeutic benefit of FLT3 inhibition, particularly as monotherapy, frequently results in the development of treatment resistance and disease relapse. Commonly, FLT3 inhibitor resistance is induced by the emergence of secondary lesions in the FLT3 gene, particularly in the second tyrosine kinase domain at residue Asp835 (D835) to form a ‘dual mutation’ (ITD-D835). Individual FLT3-ITD and FLT3-TKD mutations influence independent signaling cascades however, currently little is known which divergent signaling pathways are controlled by each of these FLT3 specific mutations, particularly in the context of patients harboring dual ITD-D835 mutations. This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways regulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise for development of more durable and personalized therapeutic approaches targeting mutant FLT3, to improve the treatment of AML.

This study estimates the effects of double long memory and structural breaks on the persistence level of six major cryptocurrency markets. We apply the Bai and Perron’s structural break test, Inclán and Tiao’s iterated cumulative sum of squares (ICSS) algorithm, and the fractionally integrated generalized autoregressive conditional heteroscedasticity (FIGARCH) model with different distributions. The results show that long memory and structural breaks characterize the conditional volatility of cryptocurrency markets and confirm our hypothesis that ignoring structural breaks leads to an underestimation of the persistence of volatility modelling. The ARFIMA-FIGARCH model with structural breaks and a skewed Student–t distribution fits the cryptocurrency market’s price dynamics well.

In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

The COVID-19 pandemic has had a significant impact on every individual in the United States. The launch of the COVID-19 vaccines is estimated to have averted millions of deaths and reduced over 18 million COVID-19 related hospitalizations. In September 2023, the updated 2023-2024 COVID-19 vaccine that include a monovalent component that corresponding to the omicron variant XBB.1.5 reflecting the predominant circulating variant at the time of strain selection, was approved and was recommended for use in all people ≥ 6 months of age. Despite this recommendation, the US uptake of the updated COVID vaccines over the 2023-2024 season has been far from optimal, placing many people at unnecessary risk of severe COVID-19 outcomes. This paper provides an overview of the current state of COVID-19 in 2023-2024, and barriers to vaccine uptake. With the continued evolution of the virus, the potential for more virulent variants and the lower public acceptance of vaccination, the potential barriers that contributed to low vaccine uptake are explored, as well as to provide solutions for improving COVID-19 protection for future seasons.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

The integration of commodities into stock exchanges marked a pivotal moment in the analysis of price dynamics. Commodities, essential for both daily sustenance and industrial processes, encompass hard commodities like metals and energy, alongside soft commodities such as agricultural produce. This paper investigates the implications of commodity price volatility on commercial and financial landscapes, recognizing its profound impact on global economies. This study employs a meticulous methodology, delineated into four stages: identification, control, and final selection of academic articles, culminating in their tabulation. Methodologically, a literature review serves as the primary tool for data acquisition, with a focus on existing scientific knowledge to bridge gaps and propose avenues for further inquiry. Drawing from reliable sources, including Google Scholar and Science Direct, the research navigates through a wealth of scholarly discourse on commodity market dynamics. By analyzing trends in academic publications, particularly focusing on the interplay between volatility spillover and gold, this paper provides insights into the evolution of research paradigms over time. Ultimately, this paper not only synthesizes existing knowledge but also identifies lacunae for future investigation, thereby contributing to a deeper understanding of the complexities surrounding commodity markets and their ramifications on global economies.

The changes in the properties of three biological events, that occur with cerebral aging, are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by mitochondria in such transition of these three important processes toward more deleterious variants as brain aging proceeds. 1. The immune system. The shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. 2. Reactive oxygen species are important intracellular signaling systems. Also, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted and persistent generation of pro-oxidant free radicals (oxidative stress). 3. The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffuse. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

Major depressive disorder (MDD) is a highly prevalent, debilitating disorder with a high rate of treatment resistance. One strategy to improve treatment outcomes is to identify patient-specific, pre-intervention factors that can predict treatment success. Neurophysiological measures such as electroencephalography (EEG), which measures the brain’s electrical activity from sensors on the scalp, offer one promising approach for predicting treatment response for psychiatric illnesses, including MDD. In this study, a secondary data analysis was conducted on the publicly available Two Decades-Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. Specifically, hierarchical regression modeling was used to predict treatment response from baseline demographics, symptom severity, and resting-state EEG features in 119 MDD patients receiving repetitive transcranial magnetic stimulation (rTMS). Across models, both age and baseline symptom severity, assessed by the Beck’s Depression Inventory, were significant predictors of rTMS treatment response, with older individuals and more severe depression scores associated with decreased odds of a positive treatment response. EEG measures contributed predictive power to these models; however, these improvements in outcome predictability only trended towards statistical significance (p~0.07 in multiple models). These findings provide confirmation of previous demographic and clinical predictors, while pointing to EEG metrics that may provide predictive information in future studies.

Transporter proteins, P-glycoprotein (P-gp) and P4ATPase-CDC50, are responsible for the transport of Miltefosine drug across cell membrane of a protozoan parasite Leishmania major. Mutations or change in activity of these proteins may lead to emergence of resistance in the parasite. Owing to the structural and functional importance of these transporter proteins, in this ppaper, we have tried to decipher the evolutionary divergence of these Miltefosine transporter proteins across different forms of life including Protists, Fungi, Plants and Animals. We retrieved 96, 207, and 189 sequences of P-gp, P4ATPase and CDC50 proteins respectively, across diverse variety of organisms for the conserved analysis. Phylogenetic trees were constructed for these three transporter proteins based on Bayesian posterior probability inference. The evolutionary analysis concluded that these proteins remain highly conserved throughout the species diversity but still substantial differences in the proteins for host (Homo sapiens) and parasite (L. major) were observed which have led in targeting these Miltefosine transporter proteins in a parasite specific manner.

Background: Dietary quality and the consumption of antioxidant-rich foods has been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: compared to the placebo, nutritional supplementation was associated with larger improvements in episodic memory, a self-report measure of everyday memory, increased plasma brain-derived neurotrophic factor, decreased plasma malondialdehyde, and increased skin carotenoid concentrations. However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

The predominant management approach for municipal solid waste (MSW) remains disposal, given significant increases in generation and disposal rates of MSW in recent decades. In addition to the well-documented carbon emissions from disposal sites, these sites accumulate numerous elements, the masses of which are substantial globally yet inadequately quantified. The unique combinations of waste constituents, elements, diverse environments, and confined spaces in disposal sites create distinct biogeochemical conditions, setting them apart from any other infrastructure or geological feature on Earth. This review first presents a global summary of the cumulative masses and disposal rates of MSW constituents and associated elements. The five dominant transformation and transport processes influencing disposed elements are examined: biochemical degradation, physicochemical transformation, gas migration, leachate migration, and solid spillage. The magnitudes and rates of the processes corresponding to major disposed elements, including carbon, nitrogen, sulfur, chlorine, and several metals, are systematically summarized. We examine and quantify the potential environmental impacts and health risks associated with element transformation and transport. We also explore the existing knowledge and techniques for resource recovery and site remediation of disposal sites. The distilled compilation of measurements and insights herein serves as a valuable primer for researchers, practitioners, and decision-makers involved in MSW management.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

In 2002, the Higher Learning Commission, a regional accrediting agency in the US, placed the community college in this study on academic probation for several criteria and many residents of the community believed that closing doors was the best option for addressing these concerns. This study is designed to ascertain data from external stakeholders of the community college regarding their current perceived value of the community college and suggestions about moving from the present to the future. The main question of the study is: What are external stakeholders’ perceptions of the value of the college to the service area? This qualitative approach is used consisting of interviews, focus groups, surveys, and document review to triangulate stakeholder perspectives. Participants included 176 high school seniors from different counties, four counselors, and four focus groups. The findings from the data are presented in this study are planned to be used by community college officials to incorporate into their strategic plans. They showed that the college needs to consider the value that it brings to the service area including economic benefits, specifically community support; accessibility; and cost of tuition.

Anthracnose and root rot are major foliar and root diseases of strawberry, respectively that cause most yield and quality losses. Anthracnose is caused by multiple species belonging to Colletotrichum spp complex. This disease alone can causeup to 70% yield loss in North America. Colletotrichum spp. cause several disease symptoms on strawberries, including root, fruit, and crown rot, lesions on petioles and runners, and irregular black spots on the leaf. In many cases, a lower level of infection on foliage remains non-symptomatic (quiescent), posing a challenge to growers as these plants can be a significant source of inoculum for the fruiting field. Reliable detection methods for quiescent infection should play an important role in preventing infected plants' entry into the production system or guiding growers to take appropriate preventative measures to control the disease. The selection of highly effective fungicides and including them in a schedule to prevent the development of fungicide resistance in fungal populations will remain an area of continued research. Disease management methods should entail sensitive molecular testing of suspected fungal isolates for resistance, rotation of products, and monitoring of quiescent infections in transplant materials. Testing and the inclusion of non-chemical methods such as biologicals and biorational treatments especially for soilborne pathogens will also be necessary to make disease management economically feasible and sustainable.

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders worldwide. Among the symptoms of MDD, sleep disturbance such as insomnia is prominent and the first reason patients may seek professional help. However, the underlying pathophysiology of this comorbidity is still elusive. Recently, genome-wide association studies (GWAS) have begun to unveil the genetic background of several psychiatric disorders, including MDD and insomnia. Identifying the shared genomic risk loci between comorbid psychiatric disorders could be a valuable strategy to understand their comorbidity. This study seeks to identify the shared genes and biological pathways between MDD and insomnia based on their shared genetic variants. First, we performed a meta-analysis based on the GWAS summary statistics of MDD and insomnia obtained from Psychiatric Genomics Consortium and UK Biobank, respectively. Next, we associated shared genetic variants to genes using two gene mapping strategies: (a) positional mapping based on genomic proximity and (b) expression quantitative trait loci (eQTL) mapping based on gene expression linkage across multiple tissues. As a result, a total of 719 shared genes were identified. Over half (51%) of them are protein-coding genes. Functional enrichment analysis shows that the most enriched biological pathways are related to epigenetic modification, sensory perception, and immunologic signatures. We also identified druggable targets using a network approach. Together these results may provide insights into understanding the genetic predisposition and underlying biological pathways of comorbid MDD and insomnia symptoms.

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a novel ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition sup-presses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to pre-vent ovarian cancer recurrence and has potential for clinical translation.

Choosing a college major is a crucial issue for twelfth-grade students. Many students feel confused and influenced by their surroundings when making this decision. This can have negative consequences if it does not align with the students interests and talents. This research proposes a web application as a solution, providing introductory information for each major. We employed a design and developement approach to create an application that assists prospective students in identifying majors based on their interests. The primary objective is to alleviate students discomfort during their studies, which often leads to decreased performance. With this application, students can avoid selecting majors solely due to peer pressure or parental coercion.

Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.

In recent years, marine, freshwater and terrestrial pollution with microplastics has been discussed extensively, whereas atmospheric microplastic transport has been largely overlooked. Here, we present the first global simulation of atmospheric transport of microplastic particles produced by road traffic (TWPs – tire wear particles and BWPs – brake wear particles), a major source that can be quantified relatively well. We find a high transport efficiency of these particles to remote regions, such as the Arctic Ocean (14%). About 34% of the emitted coarse TWPs and 30% of the emitted coarse BWPs (100 kt yr^-1 and 40 kt yr^-1 respectively) were deposited in the World Ocean. These amounts are of similar magnitude as the total estimated terrestrial and riverine transport of TWPs and fibres to the ocean (64 kt yr^-1). Atmospheric transport of microplastics is thus an underestimated threat to global terrestrial and marine ecosystems and affects air quality on a global scale, especially considering that other large but highly uncertain emissions of microplastics to the atmosphere exist. High latitudes and the Arctic are highlighted as an important receptor of mid-latitude emissions of road microplastics, which may imply a future climatic risk, considering their affinity to absorb solar radiation and accelerate melting.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), lung histology and transcriptomes of six weeks old male rats with PH induced by: 1) hypoxia (HO), 2) administration of monocrotaline (CM) or 3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed especially in HM group, indicate metabolic shift towards aerobic glycolysis.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Executive functioning is a key component involved in many of the processes necessary for effective weight management behavior change (e.g., setting goals). Cognitive behavioral therapy (CBT) and third-wave CBT (e.g., mindfulness) are considered first-line treatments for obesity, but it is unknown to what extent they can improve or sustain executive functioning. This pilot randomized controlled trial examined if a CBT-based generalized weight management intervention would affect executive functioning and executive function-related brain activity in individuals with obesity or overweight. Participants were randomized to an intervention condition (N=24) that received the Noom Weight program or to a control group (N=26) receiving weekly educational newsletters. EEG measurements were taken during Flanker, Stroop, and N-back tasks at baseline and months 1 through 4. After 4 months, the intervention condition evidenced greater accuracy over time and, to some extent, neural markers of executive function (error-related negativity and beta and gamma band powers) compared to the control group on the Flanker and Stroop tasks. The intervention condition also lost more weight than controls (-7.1 pounds vs. +1.0 pounds). Given mixed evidence on whether CBT-based interventions can change markers of executive function, this study contributes preliminary evidence that a multicomponent CBT-based weight management intervention (i.e., that provide both support for weight management and is based on CBT) can help individuals sustain executive function compared to controls.

Trees in residential landscapes provide many benefits, but can injure persons and damage property when they fail. In hurricane-prone regions like Florida, USA, the regular occurrence of hurricanes has provided an opportunity to assess factors that influence the likelihood of wind-induced tree failure and develop species failure profiles. We assessed open-grown trees in Naples, Florida, following the passage of Hurricane Irma in September 2017 to determine the effect of relevant factors on the degree of damage sustained by individual trees. Of 4,034 assessed individuals (n = 15 species), 74% sustained no damage, 4% sustained only minor damage (i.e., minimal corrective pruning needed), 6% sustained significant damage (i.e., major corrective pruning needed), and 15% were whole tree failures (i.e., overturned trees or trees requiring removal). The proportion of individuals in each damage category varied among species, stem diameter at 1.4 m above ground, and the presence of utility lines, which was a proxy for maintenance. We compared our results with the findings of seven previous hurricanes in the region to explore species’ resilience in hurricanes.

Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel Salmonella typhimurium (ST) vector expressing the bacterial collagenase Streptomyces omiyaensis trypsin (SOT), a serine protease known to hydrolyze collagens I and IV, which are predominantly found in PDAC. Utilizing aggressive models of PDAC, we show that ST-SOT selectively degrades intratumoral collagen leading to enhancement of immune checkpoint blockade (ICB) therapy in tumor-bearing mice. Ultimately, we found that ST-SOT treatment significantly modifies the intratumoral immune landscape to generate a microenvironment more conducive to ICB.

In this paper we review dynamics and roughness of bonds in proteins on example of albumin, that is important from the physiological point of view. We have performed computer simulations of albumin chain. Statistics were collected by performing many simulations realizations for each experimental setting. We concentrate on hydrogen bonds, cation-π and π- π interactions and NP contacts. Histograms of hydrogen bonds length are positively skewed in contrary to histograms of interactions and HP contacts that are negatively skewed. Scaling exponents of power spectra of energies of bonds / interactions /contacts are in range -0.2 to -0.5 and significantly differ between various hydrogen bonds or interactions. Varying scaling of such spectra can be used to classify between distinct bonds or contacts. Concerning particular amino-acids, largest amount of HBO H20 bonds are between Glutamate (GLU) amino-acids and water particle, while large amount of HBO bonds are formed with Lysine (LYS). For HP contacts the mayor role plays Phenylalanine (PHE) and Leucine (LEU) amino-acids. From decay curves HBO H2O bonds decays in fastest rate, while HBO bonds and HP contacts at slowest rate. We present as well decay curves of bonds formed by particular amino-acids, that gives interesting results.

Background: This study, conducted in October 2017 at two Canadian universities, aimed to explore the relationships between gender expression, protective coping strategies, alcohol saliency, and high-risk alcohol use. Methods: Validated scales were employed to assess these variables using survey data. Multivariate analyses were conducted to investigate the associations between these factors and high-risk drinking. Results: The study revealed significant associations between high-risk drinking and androgynous gender roles (OR=1.58, 95% CI: 1.19-2.10) as well as among self-reported males (OR=2.21; 95% CI: 1.77-2.75). Additionally, protective behavioral strategies were inversely related to high-risk drinking (OR=0.95; 95% CI: 0.94-0.96), while higher alcohol saliency exhibited a positive correlation with high-risk drinking (OR=1.12; 95% CI: 1.11-1.14). Conclusions: These findings underscore the importance of considering gender, alcohol saliency beliefs, and protective behavioral strategies in the development and refinement of interventions aimed at reducing high-risk alcohol use on Canadian campuses.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d >0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d <0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Background: Stoma closure is a widely performed surgical procedure, with 6295 undertaken in England in 2018 alone. This procedure is associated with significant complications; incisional hernias are the most severe, occurring in 30% of patients. Complications place considerable financial burden on the NHS; hernia costs are estimated at GBP 114 million annually. As recent evidence (ROCSS, 2020) found that prophylactic meshes significantly reduce rates of incisional hernias following stoma closure surgery, an evaluation of this intervention vs. standard procedure is essential. Methods: A cost-utility analysis (CUA) was conducted using data from the ROCSS prospective multi-centre trial, which followed 790 patients, randomly assigned to mesh closure (n=394) and standard closure (n=396). Quality of life was assessed using mean EQ-5D-5L scores from the trial, and costs in GBP using UK-based sources over a 2-year time horizon. Results: The CUA yielded an incremental cost-effectiveness ratio (ICER) of GBP 128,356.25 per QALY. Additionally, two univariate sensitivity analyses were performed to test the robustness of the model. Conclusion: The results demonstrate an increased benefit with mesh prophylaxis, but at an increased cost. Although the intervention is cost-ineffective and greater than the ICER threshold of GBP 30,000/QALY (NICE), further investigation into mesh prophylaxis for at risk population groups is needed.

Objective: To describe the proportion of patients undergoing major abdominal surgery who develop postoperative hypothermia, and the variables associated with its occurrence. Material and Methods: We conducted a prospective cohort study in a tertiary care referral hospital in Mexico City to describe the incidence of perioperative hypothermia and factors associated with postoperative hypothermia. A repeated measures ANOVA model was used to compare preoperative, intraoperative, and postoperative temperatures. Potential variables associated with hypothermia were evaluated with a logistic regression analysis. Results: A total of 110 patients were included in the analysis. Of them, 61% (n=67) were women. The mean age was 56.7 years (SD: 16.3, range: 75). The most frequently involved organ on which surgery was performed was kidney or urinary tract (21.8%), followed by large bowel (14.5%) and exploratory laparotomy (14.5%). The incidence of postoperative hypothermia in patients undergoing major abdominal surgery was 57.3%, while preoperative and intraoperative hypothermia occurred in 55.5% and 79.1%, respectively. Age over 60 years was the only variable associated with postoperative hypothermia after multivariable adjustment for sex, age, and time surgery (OR=18.4, 95% CI:3.79-89.6, p<0.0001). Conclusion: Increasing age was the only variable associated with postoperative hypothermia in patients undergoing major abdominal surgery.

Nepal is one of the most seismically active regions in the world, as highlighted by the recent devastating 2015, Mw7.8 Gorkha earthquake and a robust assessment of seismic hazard is paramount for the design of earthquake-resistant structures. In this study we present a new probabilistic seismic hazard assessment (PSHA) model for Nepal. We considered data and findings from recent scientific publications, which allowed us to develop a unified homogenized seismicity catalogue, propose alternative Seismic Source Characterization (SSC) models including up-to-date parameters of major thrust faults like Main Frontal Thrust – MFT and Main Boundary Thrust – MBT, while also considering existing SSC models and various hazard modelling strategies within a logic tree framework. The sensitivity analyses show the hazard levels are generally higher for SSC models integrating the major thrust faults, followed by homogenous volume sources and smoothed seismicity approach. The hazard maps covering entire Nepal is presented as well as the Uniform Hazard Spectra (UHS) for 5 selected locations (Kathmandu, Pokhara, Biratnagar, Nepalganj and Dipayal) at return periods of 475- and 2,475-years considering Vs,30=760 m/s. The results obtained are generally consistent with most recent studies. However, a notable variability in hazard levels and several discrepancies with respect to the Nepal Building Code NBC105: 2020 [1] and Global Hazard Model, GEM [2] are noted and possible causes are discussed.

We present our experience with the implantation of flow diverter stents (FDSs) for the management of intern carotid artery (ICA) dissections in tortuous tonsillar loop segments. 16 patients (10 women, 62.5%; mean age 39±8 years; median baseline NIHSS 13; median ASPECTS 8.5) with acute ischemic stroke due to ICA dissection in a tortuous tonsillar loop segment, with/without large intracranial vessel thrombotic occlusion, from 6/2015−2/2022 were included in this retrospective study under a waiver of informed consent. An FDS device was deployed from the petrous ICA toward the upper cervical ICA, completely covering the tonsillar loop. Stentriever-assisted thrombectomy was performed when indicated. A dual antiplatelet regimen was used during and after the procedure. Thrombocyte inhibition levels were evaluated before, during, and after the intervention. The ICA occlusion/near occlusion was successfully recanalized in all 16 patients with postangioplasty residual stenosis of 34±14% (range 0−50%). Stent-assisted embolectomy was performed in 15/16 patients (93.7%), achieving revascularization (TICI 2b−3) in all. There were no procedural complications and no intraprocedural embolic events; one asymptomatic petechial hemorrhage was detected. At 3-month follow-up, mRS 0−2 was seen in all patients. This report provides pilot data for a subsequent study on the use of flow diverter stents for ischemic cerebrovascular conditions. Our encouraging preliminary results await confirmation from further experience and prospective randomized studies.

The diversification of life-histories is mediated by cooperation, innovations of biological information, modularity, and heterochrony in developmental processes. These processes are defined, contextualized, and exemplified, studying the evolution of coloniality (i.e. life-history involving modularization of the multicellular individual) in the family of benthic tunicates Styelidae. This study proposes that in these colonial tunicates there is an inter-generational division of labor, where one generation is feeding, a second is developing by morphogenetic processes, and a third is aging by programmed cell death and phagocytosis. The communication system developed in these colonies is mediated, by changes in proportion, location, and gene expression of specialized blood cells. Colonial life-history in animals is related to the reduction of individual size; development of extra-corporeal tissues to interconnect zooids; the inter-generational division of labor; and the reduction of zooid’s individuality. Processes analogous with the widely accepted major evolutionary transitions (METs), suggesting that coloniality could be studied as a MET. The understanding of colonial life-histories could provide information about key mechanisms for life diversification.

In response to escalating global concerns regarding climate change, nations worldwide have been undertaking structural adjustments in their energy sectors to promote diversification and decarbonization. This study conducts a comparative analysis of the policies and measures adopted by major economies, including the United States, the United Kingdom, Japan, Germany, and France, focusing on climate change, energy structural adjustments, and carbon emission reduction. By analyzing recent carbon emission and highlighting achievements in renewable energy promotion, green industry development, industrial restructuring, and energy production decarbonization, this study aims to provide valuable insights and formulate strategies for constructing an innovative energy system that ensures economic and social development while facilitating rapid growth and wide applications of low-carbon energy sources.

Mycobacterium tuberculosis (Mtb) the causative agent of human tuberculosis (TB) is one of the most successfully adapted-human pathogens. Human-to-human transmission occurs at high rates through aerosols containing bacteria, but the pathogen evolved prior to the establishment of crowded populations. Mtb has developed a particular strategy to ensure persistence in the host until an opportunity for transmission arise. It has refined its lifestyle to obviate the need for virulence factors such as capsules, flagella, pilli, or toxins to circumvent mucosal barriers. Instead, the pathogen uses host macrophages, where it establishes intracellular niches, for its migration into the lung parenchyma and other tissues and for the induction of long-lived latency in granulomas. Finally, at the end of the infection cycle Mtb induces necrotic cell death of macrophages to escape to extracellular milieu and instructs a strong inflammatory response required for progression from latency to disease and transmission. Common to all these events is ESAT-6, one of the major virulence factors secreted by the pathogen. This review highlights the recent advances in understanding the role of ESAT-6 in hijacking macrophage function to establish a successful infection and transmission and its use as a target for the development of diagnostic tools, and vaccines.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

Technological advances in tea production are critical to meet global demands for tea consumption. To illuminate differences in the scientific and commercial relevance of research programs between major tea-related research organizations around the world, we conducted a bibliometric analysis comparing the scientific outputs, including peer-reviewed publications and patents, of six major research organizations published between January 01, 2008 and July 11, 2020. For this competitive ranking analysis, we examined a number of papers, research topics, academic influence, capacity for development, capacity for collaboration, and capacity for technological innovation. Among the six research organizations, Anhui Agricultural University (in China) had the most publications, while the Chinese Academy of Agricultural Sciences, Tea Research Institute showed a higher capacity for development. The Council for Scientific and Industrial Research (in India) and the University of Shizuoka (Japan) both showed high academic influence, while the University of Shizuoka, Tea Research Association Tocklai and National Agriculture and Food Research Organization (Japan) showed a high capacity for collaboration. The Chinese Academy of Agricultural Sciences, Tea Research Institute applied for the most patents, while the Council for Scientific and Industrial Research applied for the most international patents.

Study of fungal antibiotics in their competitive interactions with arthropods may lead to development novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained by various methods showed a wide range of biological activity, including entomotoxic properties. Analysis of their composition and bioactivity allowed to reveal several known mycotoxins and unidentified compounds that may be involved in entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with LT50 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited growth of G. mellonella larvae and caused mortality of Acheta domesticus imagines (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact-intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing the 12 and 40% of mortality at a concentration of 1 mg/mL. TeA was cytotoxic to Sf9 cell line (IC50 25 µg/mL). Thus, model insect G. mellonella and cell line Sf9 could be used for a further toxicological characterization of TeA.

Tick-borne tularemia was first described in 1924. Nearly 100 years later, questions remain about the tick vector(s) that pose(s) the greatest risk for transmitting Francisella tularensis (Ft), the causative agent of tularemia. Additionally, few studies have identified genes/proteins required for Ft to infect, persist, and replicate in ticks. To answer questions about vector competence and Ft transmission by ticks, we infected Dermacentor variabilis (Dv), Amblyomma americanum (Aa), and Haemaphysalis longicornis (Hl; invasive species from Asia) ticks with Ft, finding that although Aa ticks initially become infected with 1-log higher Ft, Ft replicated more robustly in Dv ticks, and did not persist in Hl ticks. In transmission studies, both Dv and Aa ticks efficiently infected naïve mice, causing disease in 57% and 46% of those mice, respectively. We identified a putative Ft chitinase, FTL1793, generated a FTL1793 mutant, and found that FTL1793 was deficient in tick infection, persistence, and replication in ticks. Recombinant FTL1793 exhibited chitinase activity in vitro, suggesting that this chitinase may provide an alternative energy source for Ft in ticks. Taken together, Dv ticks appear to pose a greater risk for harboring and transmitting tularemia and FTL1793 plays a major role in promoting tick infections by Ft.

A recent manuscript (Zhou, P. et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin”, Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7) from Wuhan Institute of Virology claimed the identification of a bat coronavirus, RaTG13, which showed 96.2% genome homology with SARS-CoV-2. In this paper, we raise the puzzling observations surrounding the identification, characterization, unique genome features of this RaTG13 strain, as well as its 100% nucleotide identity in partial RdRp gene with another bat coronavirus strain BtCoV/4991. And the paper presented premature hypothesis of potential bat origin of SARS-CoV-2 while RaTG13 strain was not successfully isolated. We also present the concerns on the methodology, data quality and experiment procedures described in this paper. We call for the authors to provide additional data, to share related samples to be verified and further characterized by other scientists.

Beta thalassemia major (β-TM) disorder characterized by the lack, or severe reduction in the production of hemoglobin β-globin chains. The standard protocol for the management of β-TM is blood transfusion and iron chelation therapy to reduce the iron overload state. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin (HEPC) and erythroferrone (ERFE) levels and iron status parameters (ISPs) in Iraqi patients with β-TM. ISPs and hormones were measured in sixty patients and compared with thirty healthy controls. The results indicated significant changes in different iron status parameters, while ferritin (FRT) with the ~11 fold increase showed the most change. Significant reduction in HEPC and increase in ERFE levels were detected in patients as compared to the control group, while no direct correlation was identified with the other measured ISPs. Receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE+FRT has a full diagnostic ability for β-TM. In conclusion, our finding indicated the correlation between different ISPs, FRT as the leading predictor of iron overload and tow main iron regulatory hormones.

Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.