Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n=67) were sequenced for clarithromycin and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples that amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C the most common mutation, 90%. While prevalence of metronidazole resistance-associated mutations was higher, 93.9%, mutations were more variable, with D95N the most common, followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider the resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed.

Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.

The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy.1 Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.

Gonorrhea is a major global public health problem with emergence of multiple drug-resistant strains with no effective vaccine. This retrospective cohort study aimed to estimate the effectiveness of the New Zealand meningococcal B vaccine against gonorrhea associated hospitalization. The cohort consisted of individuals born 1984-1999 residing in New Zealand, therefore eligible for meningococcal B vaccination during 2004-2008. Administrative datasets of demographics, customs, hospitalization, education, income tax and immunization, were linked using the national Integrated Data Infrastructure. The primary outcome was hospitalization with a primary diagnosis of gonorrhea. Cox’s proportional hazards models were applied with a Firth correction for rare outcomes to generate estimates of hazard ratios. Vaccine effectiveness estimates were calculated as 1-Hazard Ratio expressed as percent. There were 1,143,897 eligible cohort members, with 135 missing information on gender, 16,245 missing ethnicity and/or 197,502 missing deprivation hence 935,496 were included in the analysis. After adjustment for gender, ethnicity and deprivation, vaccine effectiveness (MeNZB™) against hospitalization caused by gonorrhea was estimated to be 24% (95% CI 1-42%). In conclusion, vaccination with MeNZB™ significantly reduced the rate of hospitalization from gonorrhea. This supports prior research indicating possible cross protection of this vaccine against gonorrhea acquisition and disease in the outpatient setting.

Background: In Arizona Helicobacter pylori prevalence of infection among Navajo adults is about 62% and gastric cancer incidence rate is 3-4 times higher than that of the non-Hispanic White population. Aim: The aim of this study was to estimate the prevalence of specific H. pylori virulence factors (cagA and vacA) among Navajo patients undergoing and their association with gastric disease. Methods: Virulence genes, cagA and vacA, in H. pylori were investigated in gastric biopsies from 96 Navajo patients over age 18 who were undergoing esophagogastroduodenoscopy. Biopsies from the antrum and fundus were used for molecular characterization to determine cagA type and number of EPIYA motifs and presence of alleles in the signal (s) and medium (m) regions of the vacA gene. Results: H. pylori infection was found in 22.9% of the biopsy samples. The cagA gene amplified in 57.6% of samples and showed a predominant “Western cagA” type, with the EPIYA-ABC motif (45.4%), most prevalent. The vacA allele s1bm1 was the most prevalent (54.5%). Conclusions: H. pylori genotypes were predominantly cagA Western-type and ABC EPIYA motifs. The vacA s1bm1 genotype was the most prevalent and seemed to be associated with gastritis. American Indian/Alaska Native populations are at higher risk for gastric cancer. It is important to identify genotypes of H. pylori and virulence factors involved in the high prevalence of H. pylori and associated disease among the Navajo population.

Background: Portable oxygen concentrators (POCs) have shown efficacy in delivering adequate oxygen for various patient scenarios; however, there is a lack of research on POCs’ efficacy across different respiratory rates specifically among COPD patients. Methods: This bench study was conducted using the IngMar Medical Active Servo Lung 5000 attached to flexible tubing, which simulated an adult patient’s nares. An oxygen analyzer (Maxtec Handi+) was connected to the tubing 6 inches below the nares to estimate the inspired oxygen concentration at the adult trachea. A standard nasal cannula was placed in the simulated patient nares, which was also attached to each POC. The IngMar Lung was programmed to simulate a COPD patient at the following respiratory rates: 15, 20, 30, and 40 breaths/min. POC devices were then compared to an oxygen wall outlet and a standard oxygen concentrator (non-portable CAIRE device). The POCs included the CAIRE FreeStyle Comfort (with Autosat), CAIRE FreeStyle Comfort (without Autosat), Inogen G4, Inogen G5, Phillips SimplyGo Mini, GCE Zen-O lite, Drive Medical iGo2, and Kingon POCs. Descriptive statistics and ANOVAs were computed to determine statistically significant differences between POCS and control devices (wall oxygen and standalone oxygen concentrator). Results: Across most respiratory rate scenarios, the wall oxygen and standalone oxygen concentrator (control group) resulted higher oxygen measurements compared to the POCs. Among the POCs on setting 2, the highest oxygen measurement for 15, 30, and 40 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity 5 (24.43%, 24.81%, and 25.0%, respectively). On setting 2, the 20 breaths/min highest oxygen measurement was the Inogen G4 (24.43%). For setting 5, the highest oxygen measurement for 15 breaths/min and 40 breaths/min was the CAIRE FreeStyle Comfort without AutoSat (31.56% and 26.13%, respectively), while the highest oxygen measurement for 20 breaths/min was the Inogen G5 (30.26%), and the highest oxygen measurement for 30 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity level 5 (27.89%). Conclusions: The oxygen administered through the wall and the standalone CAIRE oxygen concentrator all delivered higher oxygen levels compared to the POCs (with the exception of the 40 breaths/min scenario on setting 2). However, among the POCs, the CAIRE Freestyle Comfort with AutoSat, CAIRE Freestyle Comfort without AutoSat, and the Inogen G4 all performed the best among the various breathing rate scenarios.

Tunable hydrogels have gained significant attention in the bioengineering field due to their designer preparation approach. Towards this end, gelatine stands out as a promising candidate owing to the desirable attributes, such as biocompatibility, ability to support cell adhesion and proliferation, biodegradability, along with being cost-effective. This study presents the preparation of a robust gelatine hydrogel employing sacran dialdehyde (SDA) as a natural crosslinker. The resulting SDA-crosslinked gelatine hydrogels (GSDA) display an optimal compressive stress of 0.15 MPa at 50% strain, five times higher as compared to pure gelatine hydrogel. As SDA crosslinking concentration is increased, swelling capacity of GSDA declines. Probing further with FTIR spectroscopy and SEM at the micron-scale unveiled a dual-crosslinking mechanism within the hydrogels. This mechanism encompasses both short- and long-range covalent crosslinking, along with thermo-reversible physical crosslinking, resulting in a significant enhancement of the load-bearing capacity of the fabricated hydrogels.

Beta-glucan-stimulated mammalian macrophages show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity. Our study aimed to explore training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with β-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with β-glucan microparticulates (M-βG), LPS, recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analysed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of CSF1R and the activation markers CD40 and MHC-II was higher on macrophages that were trained with a combination of M-βG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with β-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have potential to improve health and vaccination strategies within the poultry sector.

Abstract: Background: The birthrate of Black preterm (BPT) infant is 65% higher than White preterm (WPT) infants with BPT mortality 2.3 times higher. The incidence of culture positive sepsis is as high as 41% in preterms. This study aimed to examine infections and mortality in BPTs and WPTs. Methods: We enrolled 362 preterms born < 32 weeks gestational age (GA) between 2019-2023 in 5 neonatal intensive care unit (NICU)s to study onset of infections, and dispositions; RedCap data were analyzed for descriptive statistics. Results: 226 BPTs (63.5%) and 107 WPTs (30.8%) enrolled, with 29 other than White or Black, 50.5% female, mean GA of 27.67 weeks and 986.74 grams birthweight. Of 426 suspected infections evaluated in enrolled infants, there were 7 infants with early onset sepsis (EOS) and 39 infants with late onset sepsis (LOS). The incidence of EOS was 1.9% overall, 2.2% in BPTs vs 0.9% in WPTs. LOS incidence was 10.8% overall, 11.9% in BPTs and 9.3% in WPTs. Both BPT and WPT infants had ~ 8% gram-positive LOS events and 3% gram-negative LOS events; however, 82% of all gram-negative LOS episodes occurred in BPTs. There were 27 urinary tract infections and 78% were in BPTs. Two cerebral spinal fluid cultures were positive in BPTs. Necrotizing enterocolitis was diagnosed in 5.8% of the sample, with an incidence of 6.1% in BPTs versus 4.7% in WPTs. Death occurred in 6.0% of the enrolled infants with the rate of death being slightly higher in BPTs (7.0%) versus WPTs (5.6%). Conclusions: BPTs had a higher rate of positive cultures, double the gram-negative infections, a much higher rate of urinary tract infec-tions and a higher rate of mortality than their WPT counterparts. This study emphasizes higher risk of morbidity and mortality for BPTs.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L) and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post procedure (P &lt; 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10-20 min (0.05 &lt; P &lt; 0.01), 20-30 min (P &lt; 0.05) and 40-50 min (0.05 &lt; P &lt; 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 &lt; P &lt; 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10-20 min (0.05 &lt; P &lt; 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0-10 min (0.05 &lt; P &lt; 0.01), and 10-40 min (P &lt; 0.05). Analgesic benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer lasting analgesia. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post procedure to establish efficacy.

In 2021, the American Association of Colleges of Nursing (AACN) added “the impact of climate change on environmental and population health” into The Essentials: Core Competencies for Professional Nursing Education. Presently, little guidance exists for nursing faculty new to climate education. The year prior, the Nurses Climate Challenge (NCC) - a campaign to educate 50,000 health professionals about health impacts of climate change - launched the School of Nursing Commitment through a series of focus groups and collaborative content development. With an aim of increasing access to knowledge and tools to support education about the health impacts of climate change, the NCC Commitment partners with nursing schools and provides a community of practice. Partner schools use NCC resources in courses and report the number of students educated. Within three years, 61 nursing schools in 30 states joined the Commitment. Participants included academic health centers, research institutions, multi-state schools, and small private colleges, and programs ranged from AD to PhD. Faculty 1) integrated resources into didactic and clinical settings such as population or organ-system content, leadership, and policy and 2) used resources to support assignments. In four years, faculty reported educating over 37,700 students using NCC resources in 439 educational sessions. The Commitment may be valuable for faculty fulfilling AACN Essentials by bringing climate change to the classroom, community, and bedside. Furthermore, the Commitment may be a replicable model for health professional education and inspiring action on climate change.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.

Highly macroporous thin films of WO₃ were fabricated on transparent conductive substrates by application of a polymeric organic paste loaded with an amine/tungstate complex. After spin-coating and annealing at 550^oC, the resulting yellow films are found to be comprised of channeled array of clustered nanoparticles. These channels are confirmed by scanning electron microscopy to extend through the entire length of the coating. The high porosity of the material enables the insertion of a co-catalyst into the internal structure of the film. These internally functionalized composites demonstrate good photosensitivity and stability in neutral electrolyte.

The effects of toxic air in the form of air pollution are known to harm women’s health. New data has shown that air pollution has effects on maternal anemia. Yet the effects of particulate matter 2.5 (PM_2.5) on hemoglobin among reproductive maternal (15-49 years) has been understudied. In this population-based study, we study the region-specific associations between prevalence of hemoglobin among reproductive women and PM_2.5 in 43 countries of Africa from 2000-2019. Using generalized linear regression models, we found that after adjusting for key covariates, PM_2.5 had a slight negative association with hemoglobin among reproductive women. Other studies are needed in other low-income settings to expand our findings.

This research discusses the business model challenges faced by cag aggregator platform models in developing countries. Technology-based platforms have been disrupting traditional businesses and rewriting the rules of the game. Ola cabs has been instrumental in shaping the Indian platform business landscape in a big way. Using case methodology the author analyses the situation and business model to present the salient features of Ola’s model. However, this paper also puts the spotlight on the inherent challenges in this model and warns the need for continuous business model innovation and service quality.

The Internet of Things (IoT) technology and devices constitute an exciting field in computer science that is rapidly emerging worldwide. IoT devices function by connecting real-world objects to the internet, resulting in a higher number of interconnected devices than ever witnessed in history. Through internet connectivity, these devices can be utilized in various ways, such as monitoring and tracking. Their prevalence is increasing exponentially, coinciding with advancements in wireless networking technologies. The internet’s enhanced connectivity has played a vital role in fostering the proliferation of IoT devices. Presently, almost any everyday object can be network-connected. The demand for automation and efficiency has also been a contributing factor to the advancements in this technology. This paper aims to review the emergence of IoT devices, analyze their common applications, and explore the future prospects in this promising field of computer science. The examined applications encompass healthcare, agriculture, and smart cities. Although IoT technology exhibits similar deployment trends, this paper will explore different fields to discern the subtle nuances that exist among them. IoT technology can be applied to nearly any domain, and each use case has unique requirements. To comprehend the future of IoT, it is essential to comprehend the driving forces behind its advancements in various industries. By gaining a better understanding of the emergence of IoT devices, readers will develop insights into the factors that have propelled their growth and the conditions that led to technological advancements. Moreover, a comprehensive understanding of the prevalent methodologies will enable readers to distinguish between current practices and future methods. Given the rapid rate at which IoT technology is advancing, this paper aims to provide researchers with an understanding of the factors that have brought us to this point and the ongoing efforts to shape the future of IoT.

In mammals, the oviduct (or the Fallopian tube in humans) can be divided into the infundibulum (responsible for oocyte pick-up), ampulla (site of fertilization), isthmus (where preimplantation embryos develop), and uterotubal junction (where embryos transit to the uterus). The oviductal fluid, as well as extracellular vesicles produced from the oviductal epithelial cells, referred to as oEVs, have been shown to improve the fertilization process, prevent polyspermy, and aid in embryo development. oEVs contain molecular cargos (such as miRNAs, mRNAs, proteins, and lipids) that can be delivered and fuse to recipient cells. oEVs produced from the ampulla appear to be functionally distinct from those produced from the isthmus. In multiple species including mice, cats, dogs, pigs, and cows, oEVs can be incorporated into the oocytes, sperm, and embryos. In this review, we show the positive impact of oEVs on gamete function as well as blastocyst development and how they may improve embryo quality in in vitro conditions in an assisted reproductive technology setting for rodents, domestic animals, farm animals, and humans.

The objective of this study was to identify the factors determining a company’s corporate governance related to climate change. We analyzed the effect of various sustainability corporate governance variables on the disclosure level of climate change governance. These variables included facts such as having a dedicated sustainability executive and board committee, the mediating effect of female representation on the board of directors, number of reporting years according to TCFD, membership in a sustainability index, MSCI ESG rating, the existence of a corporate climate transition plan, a mention of the UN Global Compact and GRI, company location, as well as company size and profitability. By adopting a multi-theoretical framework that included stakeholder theory as well the legitimacy and agency theory, the underlying research study used a sample of 100 of the largest global companies by market capitalization and their reporting for the year 2020. Based on 1,400 observations for fiscal year 2020 and using correlation analysis, univariate and linear multiple regressions, we find a positive association between having a climate transition plan in place, being a leader in sustainability according to MSCI ratings, and being a DJSI constituent and the propensity to disclose information on governance for climate change. In addition, we find a company with a dedicated sustainability executive show an increased tendency to be transparent on climate governance issues. Furthermore, having a company location in a developed country is significantly and positively associated with climate change governance. Surprisingly, gender diversity in the corporate board or having a sustainability board committee did not show any significant correlation between a higher climate change governance level. The same was true for companies being active in either the extractive or non-extractive sector. Companies referring to the Global Reporting Initiative (GRI) or UN Global Compact also did not score higher in climate change governance. Neither did corporate profitability or size play a significant role. Our results are robust to variations and provide valuable insights for researchers, academics, executives, practitioners as well as regulators. As more and more companies are shifting towards a climate change reporting framework, it is of paramount importance that we are able to determine the contributing variables that lead to effective climate change corporate governance. Our results are inconsistent with stakeholder theory and are strongly suggesting that a diversified board and the existence of a sustainability committee that meets often/sufficiently may not necessarily lead to a higher level of transparency/quality regarding climate change. While more research is needed, knowing that a dedicated sustainability executive as well as having a climate plan in place can make a difference in climate change reporting, can be very beneficial to many corporate stakeholders. Given the current urgent climate change situation and the crucial role that corporation play in it, dedicated sustainability positions and committees need to be established. The findings could be useful for managers as well as governmental standards setter and regulators who are interested in improving corporate practices dealing with climate change. This study applies STATA software with various regression models to empirically test the relationship between CG and other variables and corporate climate change reporting.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

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

The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

Abattoir workers are liable to zoonotic infections from animals and animal products, pri-marily to diseases with asymptomatic and chronic clinical manifestations in animals such as brucellosis. No published reports exist on the seroprevalence of brucellosis in abattoir workers in South Africa. Therefore, this cross-sectional study was conducted to estimate the occurrence and risk factors for Brucella exposure in abattoir workers in Gauteng Province. A total of 103 abattoir workers and managers from six abattoirs, where brucellosis-positive slaughtered cattle and sheep were previously detected, were interviewed, and tested with serological assays using the Rose Bengal test (RBT), BrucellaCapt, and IgG-ELISA. A pre-tested questionnaire was administered to consenting respondents to obtain infor-mation on risk factors for brucellosis. Of the 103 respondents tested, the distribution of fe-male and male workers was 16 (15.5%) and 87 (84.5%), respectively. The seroprevalence for exposure to brucellosis was 21/103 (20.4%, 95%CI: 13.1-29.5) using a combination of RBT, BrucellaCapt, or IgG-ELISA. For test-specific results, seroprevalences by RBT, BrucellaCapt, and IgG-ELISA were 13/103 (12.6%, 95%CI: 6.9-20.6), 9/103 (8.74%, 95%CI: 4.1-15.9) and 18/103 (17.5%, 95%CI: 10.7-26.2), respectively. Low-throughput abattoirs were identified as associated risk as 29.3% of workers were seropositive compared to 12.7% of workers in high-throughput abattoirs, which highlights that direct contact at abattoirs poses higher risk to workers than indirect and direct contact outside abattoirs. This study confirmed the occurrence of Brucella spp. antibodies among abattoir workers in South Africa, possibly due to occupational exposure to Brucella spp. and highlight the occupational hazard to workers. Furthermore, findings underscore that abattoir facilities can serve as points for active and passive surveillance for indicators of diseases of public health importance. We recommend periodic implementation of brucellosis testing of abattoir workers country-wide to establish baseline data for informing appropriate preventive practices and reduce the potential burden of infection rate among these high-risk workers.

Robin sequence is a congenital anomaly characterized by a triad of features that include micrognathia, glossoptosis, and airway obstruction. This comprehensive historical review maps the evolution of approaches and appliances for its treatment from the past until current modern possibilities of interdisciplinary combination of modern engineering, medicine, materials, and computer science combined approach with emphasis to design appliances inspired by nature - individual human anatomy. Current biomimetic designs are clinically applied resulting in appliances that are more efficient, comfortable, sustainable, and safer than legacy traditional designs. Review maps the treatment modalities that have been used for patients with Robin sequence over the years. Early management of Robin sequence focused primarily on airway maintenance and feeding support, while current management strategies involve both nonsurgical and surgical interventions and biomimetic biocompatible personalized appliances. The goal of this paper was to provide a review of the evolution of management strategies for patients with Robin sequence that led to the current interdisciplinary biomimetic approaches impacting the future of Robin Sequence treatment with biomimetics at the forefront.

The use of Smart Antenna Systems (SAS) in pervasive environments such the Mobile Ad hoc Networks (MANET) has been promoted as the best choice to improve Spatial Division Multiple Access (SDMA) and throughput. Although directional communications are expected to provide great advantages in terms of network performance, directional MAC (Medium Access Control) protocols introduce several issues. One of the most known problems in this context is represented by the fact that, attempting to solve or at least mitigate the problems introduced by these kinds of antennas especially at MAC layer, a large amount of energy consumption is achieved ; for example, due to excessive retransmissions introduced by very frequently issue such as deafness and handoff. The expedients proposed in order to reduce these drawbacks attempting to limit beamforming time of nodes in cooperation with a Round-Robin scheduling, can grant high performance in terms of fairness and throughput. However the overall energy consumption in the network is not efficent due to the static approach. In view of this, we propose an Adaptive Beamforming Time with Round-Robin MAC providing for a dynamic assignment of the beamforming time with the purpose to limit the waste of energy of nodes.

We bring a strength-based and socially-oriented lens to behaviors observed in profound autism. Social deficits are a defining characteristic of autism. Yet humans’ biological drive for social connection is sufficiently strong that is should be observable, in some form at least, in individuals with autism. We describe a case that validates this view. Mahad is a 20-year-old Pakistani-American male, with intellectual disability, and minimal verbal abilities. Mahad has an intense interest in food and the steps involved in food preparation. He employs and capitalizes on his family’s meal routines to ensure continual social attention from his mother. When not immersed in food, Mahad uses his limited capacities to pursue the additional biological needs of exploring his environment, seeking information, and developing his cognitive abilities.

In the rapidly evolving landscape of wireless communication, each successive generation of networks has achieved significant technological leaps, profoundly transforming the way we connect and interact. From the analog simplicity of 1G to the digital prowess of 5G, the journey of mobile networks has been marked by constant innovation and escalating demands for faster, more reliable, and more efficient communication systems. As 5G becomes a global reality, laying the foundation for an interconnected world, the quest for even more advanced networks leads us to the threshold of the sixth-generation (6G) era. This paper presents a hierarchical exploration of 6G networks, poised at the forefront of the next revolution in mobile wireless technology. This study delves into the technological advancements that underpin the need for 6G, examining its key features, benefits, and the key enabling technologies. We dissect the intricacies of cutting-edge innovations like terahertz communication, ultra-massive MIMO, artificial intelligence (AI), machine learning, quantum communication, and re-configurable intelligent surfaces. Through a meticulous analysis, we evaluate the strengths, weaknesses, and state-of-the-art research in these areas, offering a wider view of the current progress and potential applications of 6G networks. Central to our discussion is the transformative role of AI in shaping the future of 6G networks. By integrating AI and machine learning, 6G networks are expected to offer unprecedented capabilities, from enhanced mobile broadband to groundbreaking applications in areas like smart cities and autonomous systems. This integration heralds a new era of intelligent, self-optimizing networks that promise to redefine the parameters of connectivity and digital interaction. This paper also addresses critical challenges in the deployment of 6G, from technological hurdles to regulatory concerns, providing a holistic assessment of potential barriers. By highlighting the interplay between 6G and AI technologies, this study not only maps out the current landscape but also lights the path forward in this rapidly evolving domain. This paper aims to be a cornerstone resource, providing essential insights, addressing unresolved research questions, and stimulating further investigation into the multifaceted realm of 6G networks. By highlighting the synergy between 6G and AI(Artificial Intelligence) technologies, we aim to illuminate the path forward in this rapidly evolving field.

The increasing demand for energy, driven by technological advances, population growth, and economic expansion, has intensified the focus on efficient energy management. Tri-generation systems, such as Combined Cooling, Heating, and Power (CCHP) systems, are of particular interest due to their efficiency and sustainability. Integrating renewable energy sources like solar power with traditional fossil fuels further optimizes CCHP systems. This study presents a novel method for enhancing CCHP system efficiency by identifying optimal design parameters and assisting decision-makers in selecting the best geometric configurations. A mathematical programming model using the Harris Hawks optimizer was developed to maximize net power and exergy efficiency while minimizing CO2 emissions in a solar-assisted CCHP system. The optimization resulted in 100 Pareto optimal solutions, offering various choices for performance improvement. This method achieved higher net power output, satisfactory exergy efficiency, and lower CO2 emissions compared to similar studies. The study shows that maximum net power and exergy efficiency, with reduced CO2 emissions, can be achieved with a system having a low compression ratio and low combustion chamber inlet temperature. The proposed approach surpassed the response surface method, achieving at least a 4.2% reduction in CO2 emissions and improved exergy values.

Honey has been employed for the treatment of wounds and diseases for ancient time, thanks to its antimicrobial and curative properties. This study aims to present the biochemical characteristics, including the amount of sugar, total phenols, phenolic chemicals, antioxidant properties, and antibacterial activities of a specific type of French honey (Sologne summer forest) in comparison with a manuka honey. According to our findings, the Manuka honey tested has 23% fewer polyphenols total than Sologne summer forest honey. The results showed that the Sologne summer honey had a different polyphenols profile than Manuka honey with specific polyphenol like p- Hydroxybenzoic acid. Additionally, the antioxidant activity of the two honeys is comparable (9 μmole Trolox.g-1 honey). Furthermore, the antibacterial activity of the two honeys is comparable against Pseudomonas aeruginosa and Staphylococcus aureus. Our research indicates for the first time that there are significant nutritional and biological potentials for a French honey from the Sologne summer forest.

We aimed to evaluate the safety of maternal Tdap we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 grams at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8,299 infants were born to 8,178 mothers exposed to Tdap (12%), primarily between 28-38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap and stillbirth, infant Apgar score at 5 minutes after birth, microcephaly, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

Infrared (IR) thermography is a powerful tool to measure temperature with a high space and time resolution. A particular interesting application of this technology is in the field of catalysis, where new insights to highly dynamic surface reactions are possible. This paper presents guidelines for the development of a reactor cell that can aid in the efficient exploitation of infrared thermography for the investigation of catalytic and other surface reactions. Firstly, the necessary properties of the catalytic reactor are described. In fact, special equipment must be developed to ensure the realization of true operando conditions in the IR thermography experiments. Here, we provide the guidelines to assemble a chemical reactor with an IR transmitting window through which the reaction can be studied with the infrared camera. Secondly, we analyze the requirements towards the catalytic system to be directly observable by IR thermography. This includes the need for a catalyst that provides a sufficiently high heat production (or absorption) rate. We present selected examples of catalytic reactions that can be monitored by IR thermography and showing the potential of the technology in revealing transient and steady state chemical phenomena.

Horizontal transfer of transposons (HTT) is an important source of genomic evolution in eukaryotes. The HTT dynamics is well characterized in eukaryotes including insects however, but there is a huge gap of knowledge about HTT regarding many eukaryotes’ species. In this study we analyzed the events of the HTT between Rhus gall aphids (Hemiptera) and other insects. We analyzed the Mariner-like transposable elements (MLEs) belongs to Rhus gall aphids for the possible HT events. The MLEs have patchy distribution and have high similarity over the entire length of element with insects MLEs from different orders. We selected representative sequences from the Rhus gall MLEs and identified five events of HT between MLEs of Rhus gall aphids and other insects from five different orders. We also found multiple HTT events among the MLEs of insects from the five orders which demonstrate that these Mariner elements have been involved in recurrent HT between these six order of insects. Our current study closed the knowledge gap of HTT and reported the events between Rhus gall aphids and other insects for the first time. We believe that this study about HTT events will help to understand the evolution and spread of transposable elements in the genomes of Rhus gall aphids.

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

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

Air sampling using vortex air samplers combined with species specific amplification of pathogen DNA, was carried out over two years in four or five locations in the Salinas Valley of California. The resulting time series data for the abundance of pathogen DNA trapped per day displayed complex dynamics with features of both deterministic (chaotic) and stochastic dynamics. Methods of nonlinear time series analysis developed for the reconstruction of low dimensional attractors provided new insights into the complexity of the pathogen abundance data, but also indicated that practicality may limit the capacity for definitively classifying the dynamics of air borne plant pathogen inoculum. Over the two years of the study five location/year combinations were classified as having stochastic linear dynamics and four were not. Calculation of entropy values for either the number of pathogen DNA copies or for a binary string indicating the pathogen abundance data were increasing or not, revealed (1) some robust differences in the dynamics between seasons that were not obvious in the time series data themselves, and also (2) that the series were almost all at their theoretical maximum entropy value when considered from the simple perspective of whether instantaneous change along the sequence is positive or not.

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

Mycoviruses are widespread across the major taxa of fungi including yeasts. Mycoviruses in the yeast fungus Geotrichum candidum are not well studied with three G. candidum-associated viral species characterized to date, all of which belong to the Totiviridae genus Totivirus. In this study, we report the molecular characteristics of another two totiviruses co-infecting isolate Gc6 of G. candidum. The two totiviruses were tentatively named Geotrichum candidum totivirus 2 (GcTV2-Gc6) and GcTV4-Gc6). Both viruses have typical genome organization of totiviruses comprising two ORFs encoding capsid protein (CP) and RNA-dependent RNA polymerase (RdRp) at the N and C termini, respectively. Genomes of GcTV2-Gc6 and GcTV4-Gc6 are 4592 and 4530 bp long, respectively. Both viruses contain the -1 frameshifting elements and their proteins could be expressed as a single fusion protein. GcTV2-Gc6 is closely related to a totivirus isolated from the same host whereas GcTV4-Gc6 is related to insect-associated totiviruses. The phylogenetic analysis indicated that GcTV2-Gc6 and GcTV4-Gc6 belong to two different sister clades, I-A and I-B, respectively. It is interesting that all viruses identified from G. candidum belong to the genus Totivirus. It is possible that the RNA interference (RNAi) mechanism is not active to suppress totivirus accumulation in isolate Gc6.

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

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

Emerging risk factors for childhood (<5 years) anemia cases in low-income countries have not been limited to COVID-19 and the spread of infectious diseases, hidden hunger, and other economic factors. Yet the effects of climatic factors, such as ambient temperatures, on child anemia have been in its infancy. In this population-based study, we study the region-specific associations between child anemia and ambient temperatures in 43 countries of Africa from 2000-2019. Using generalized linear regression models, we found that after adjusting for key covariates, the risk that temperatures pose on child anemia varies across the four African regions (Western, Eastern, Central, and Southern). This suggests that ambient temperatures have varying effects on child anemia by region. Other studies are needed in other low-income settings to expand our findings.

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

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system. Model estimates of nuclear war casualties employed ESRI's ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency's WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency's (DTRA's) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory's LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kiloton (kt) detonations and a single 1 megaton (1000kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims.

The ultimate aim of dynamic load balancing in cloud computing systems is to maximise the efficiency with which resources are utilised and workloads are distributed. Given that load balancing is a multi-objective process and that response time is a priority, the Harris hawk optimisation (HHO) algorithm was developed as a unique solution for dynamic load balancing. Based on burden distribution and resource utilisation, the HHO algorithm is responsible for dynamically assigning workloads to virtual machines (VMs). Through iterative interactions and position updates, the hawks investigate the solution space, determine the optimal method for dividing the work, and adapt to the ever-changing conditions of the workload. The HHO algorithm has been demonstrated to be effective and efficient in the management of dynamic load balancing via a series of experimental evaluations and comparisons with other load-balancing approaches. These discoveries have led to quicker response times and more efficient resource utilisation. Utilising the collaborative search behaviour of hawks, this technique provides a solution that is both practicable and effective for addressing load balancing concerns in dynamic scenarios.

Visible light photography diagnostic images are coloured ex vivo medical images popularly used in Dermatology and Endoscopy for diagnosis and monitoring. The need to protect the integrity of these images as well as associated patient data calls for techniques such as image steganography and watermarking. This research explores and compares the effect of watermarking on the YIQ and YCbCr colour transforms used in processing digital coloured images and video in recent times. Using a new spread spectrum watermarking algorithm, it was found that YIQ has better distortion performance than YCbCr in the order of 3dB while YCbCr had lower BER for accurate watermark retrieval and tamper detection in the order of 1.3 x 10-3.

Product counterfeiting is an on-going problem in supply chains and retail environments, Recently an anti-counterfeiting protocol to address this issue via cost-effective use of auto-identification technologies such as radio-frequency identification (RFID) was proposed by researchers.Yet the use case of re-selling the same product was not been fully addressed which might cause serious problem for the exciting and proposed schemes and transactions. This paper proposes an extended RFID-based anti-counterfeiting to address the use case of the original buyer reselling the same item to a second buyer. The extended scheme will be followed by a formal security analysis to show that the proposed protocol satisfies the requirements of security correctness and is resistant to compromise through security attacks.

A developed six-port reflectometry (SPR) system was integrated to measure the relative permittivity of tumor and normal breast tissue for medical diagnostic purpose. In order to obtain an accurate and precise measurement, the calibration process was done to the SPR using the well-known three-standard technique. Next, the studied dielectric probe was connected to the calibrated measurement-port of the SPR. The open end of the probe aperture was dibbed into the normal and tumor synthetic breast tissue samples to measure the synthetic breast tissues dielectric constant, ɛrʹ, and loss factor, ɛrʺ in the frequency range of 1.5 GHz to 3.3 GHz. Finally, the comparative studies were conducted between commercial VNA with Keysight 85070E dielectric probe and the studied SPR-probe system based on the measured magnitude of the reflection coefficient, phase shift, dielectric constant, and loss factor of the synthetic breast samples. The maximum absolute errors of the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor were found to be 0.01, 1.07°, 1.12, and 0.75, respectively. It was ascertained that the predicted dielectric constant, ɛrʹ, is able to differentiate between normal, (ɛrʹ &lt; 50) and tumor, (ɛrʹ &gt; 50) breast tissues.

This study reports rapid hydrolysis, acylation, and lipolysis with lipase B from Candida antarctica (CalB) and nanofructosome encapsulated CalB (CalB@NF) enzymes immobilized on silica-coated magnetic nanoparticles (Si-MNPs). Enzymatic hydrolysis was confirmed for conversion to p-nitrophenol (p-NP, λex=400 nm) from p-nitrophenyl butyrate (p-NPB, λex=270 nm), and various catalytic parameters such as Km, Vmax, and Kcat were calculated from Michaelis-Menten and Lineweaver-Burk plot. Efficiency of enzymatic hydrolysis was in the order of CalB > Si-MNPs@CalB > CalB@NF > Si-MNPs@CalB@NF, and reusability was much better with the enzyme immobilized on Si-MNPs than with the native enzyme. Enzymatic acylation was confirmed by the formation of benzyl benzoate (λex=229 nm) from benzoic anhydride (λex=240 nm), and efficiency exceeded 99% in all samples. Finally, enzymatic lipolysis was confirmed by the decomposition of olive oil to fatty acid such as oleic acid (λex=230 nm) using thin-layer chromatography (TLC), column chromatography, and proton nuclear magnetic resonance (1H -NMR). The lipases immobilized on Si-MNPs have the advantage of good thermal stability and reusability and are thus applicable to a wide range of industries.

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

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

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

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

The offshore oil and gas working environment is an inherently dangerous one, with risks posed to physical safety on a daily basis. One neglected field of research is the added psychosocial stressors present in this environment. This research examined the experiences of offshore oil and gas workers through one-on-one online interviews which were recorded and transcribed. Transcripts were analysed through qualitative software NVivo, which generated themes and patterns for the responses given to questions which were developed through a focus group. The results of the analysis showed that multiple psychosocial stressors are present for this population, such as fear of speaking up, unsatisfactory company-provided facilities, work-life interference, work status, micromanaging, gender harassment and bullying. In addition, interviews identified that production and time pressures along with fatigue can influence accidents and mistakes. Climate factors also cause discomfort, however these are managed according to best practice by organisations. Due to the timing of the study, COVID-19 was a significant stressor for some, but not all, employees. In conclusion, offshore oil and gas workers face multiple stressors in a dangerous environment that may lead to devastating consequences.

Diffusion bonding is often used on pre-machined parts to generate internal cavities, e.g. for cooling injection molding tools close to the mold cavity. Only then, the workpieces are finished to their final dimensions. In the case of micro-process devices, however, it is essential to precisely control the deformation, as otherwise uncontrollable pressure losses will occur with channel cross-sections in the sub-millimeter range. Post-processing is not possible. The most important process parameters for diffusion bonding are temperature, dwell time and contact pressure, with the bonding temperature and contact pressure acting in opposite directions and showing a strong non-linear dependence on deformation. In addition, the deformation is influenced by a number of other factors such as the absolute size of the cross-section and the aspect ratio of the parts, the dimensions and distribution of the internal cross sections and the overall percentage of the cross-section to be bonded. In micro process engineering, small material cross-sections in the range of the materials microstructure can facilitate additional deformation mechanisms such as grain boundary sliding, which are not relevant at all for larger structures. For parts consisting of multiple layers, tolerances in thickness and roughness of multiple surfaces must be levelled, contributing to the percentaged deformation. This makes it difficult, especially in micro process engineering and in single or small series production, to determine suitable joining parameters in advance, which on the one hand do not cause unforeseen large deformations, but on the other hand reliably produce highly vacuum-tight components. Hence, a definition of a fixed percentaged deformation does not work for all kinds of components. This makes it difficult to specify parameters for surely obtain high-vacuum tight parts. For successful diffusion bonding, atoms must diffuse over the bonding planes, forming a monolithic part in which the original layers are no longer visible. Only then, mechanical properties identical to those of the base material, which has been subjected to identical heat treatment, can be achieved. In this paper, the impacts of different material cross section widths as well as of the aspect ratio on deformation were investigated. By accident, it was found that also accuracy of the temperature measurement may have a serious impact in terms of deformation.

COVID-19 outbreak started in the Chinese city of Wuhan and spread around the globe in months due to its high contagious level. Hence, this disease posed a great challenge to researchers and mathematicians. Numerous mathematical models have been suggested to visualize the spreading speed and trends of this pandemic. In this paper, a comparison of a widely established and accepted method, the Susceptible-Exposed-Infected-Quarantined-Recovered-Death-Insusceptible (SEIQRDP) model with a newly-proposed fractional-order SEIQRDP is studied. Densely populated Countries of Asia (Pakistan, India, and Bangladesh) have been chosen as data sets and both algorithms have been applied to their data. The same comparison technique has also been used on the data of two polar countries, New Zealand and Russia, that validated our findings. Error comparison of both algorithms has been recorded in a tabulated form which shows multi-fold erroneous trends over WHO data of selected countries.

The production of recombinant enzymes, mainly used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to produce recombinant α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500 respectively, using the pBE-S shuttle vector, and to characterize them. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their own signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700-750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. The SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which was in accordance with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 amylase was significantly reduced when exiting the producer cells. Ca2+ had no significant activating effect on the activities of Amy1974 amylase and Amy3500 amylase, likely due to its tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45-70°C, with a maximum at 65°C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards cyclodextrins. The Amy1974 amylase converts starch to dextrins of varying lengths, whereas Amy3500 almost entirely converts starch into glucose.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin-system (RAS) is critically involved in their pathophysiology and is counterbalanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin-system (KKS). Considerable research interest with respect to COVID-19 treatment is, thus, currently directed towards the components of these systems. In an earlier study, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and partially excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized (HoP) COVID-19 patients and a sub-group of covalescent patients, while in the majority of the probands recovering from the disease these values had returned to normal. The data had been obtained using bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE, and they were supplemented by serum proteomics of the same patient cohort. We hypothesized that the data could be indicative of Long COVID, which had not been fully appreciated at the time of our study.; (2) Methods: The data were re-evaluated in the light of Long COVID. The recent literature on the RAS in COVID-19, antihypertensiva, and Long COVID was briefly reviewed.; (3) Results: While the levels of the BK serum degradation products should return to normal concentrations during convalescence, this was not true for some patients. This could be due to persisting liver problems, because CPN is synthesized there, but also to a dysregulated RAS. This was not reflected in the levels of selected RAS/KKS serum proteins like angiotensinogen (AGT), although AGT correlated with disease severity in HoP. However, standard tests in routine patient care in Long COVID often come back normal, and it may be that BK degradation is specific in some pathophysiologies. Moreover, the HoP group was sub-divided based on the serum protein profiles and COVID-19 severity.; (4) Conclusions: We point out two insights: 1) Sensitive technology such as omics methods might provide unexpected significant differences within the pre-defined patient groups of a clinical study. Those can only be explored, if the cohorts are large enough and properly matched with respect to the parameters known beforehand (e.g., age, gender, co-morbidities). 2) Results of the BK-reporter serum protease activity assay could be indicative of persisting liver problems and/or potentially of Long COVID. Clinical studies are required to test this hypothesis.

Nature provides plenty of good examples for simple and very efficient joint assemblies. One example is the enormously flexible cervical spine of American barn owls, which consists of 14 cervical vertebrae. Each pair of vertebrae produces a comparatively small individual movement in order to provide a large overall movement of the entire cervical spine. The biomimetic replication of such joints is difficult due to the delicate and geometric unrestricted joint shapes as well as the muscles that have to be mimicked. Using X-ray as well as micro computed tomography images and with the utilisation of additive manufacturing, it is possible to produce the owl neck vertebrae in scaled-up form, to analyse them and then to transfer them into technically usable joint assemblies. The muscle substitution of these joints is realised by smart materials actuators in the form of shape memory alloy wire actuators. This actuator technology is outstanding for its muscle-like movement and for its enormous energy density [1,2]. The disadvantage of this wire actuator technology is the low rate of contraction, which means that a large length of wire has to be installed to generate adequate movement. For this reason, the actuator wires are integrated into additively manufactured carrier components to mimic the biological joints. This results in joint designs that compensate for the disadvantages of the small contraction of the actuators by intelligently installing large wire lengths on comparatively small installation spaces, while also providing a sufficient force output. With the help of a test rig, the developed technical joint variants are examined and evaluated. This demonstrates the technical applicability of this bionic joints.

Aquaporins (AQPs) are water channels widely distributed in living organisms and involved in many pathophysiologies as well as in cell volume regulations (CVR). In the present study, based on the structural homology existing between mineralocorticoids receptors (MR), glucocorticoids receptors (GR), cholesterol consensus motif (CCM) and the extra-cellular vestibules of AQPs, we investigated the binding of corticosteroids on AQP family through in silico molecular dynamics simulations of AQP2 interactions with cortisol. We propose for the first time a putative AQPs corticosteroids binding site (ACBS) and discussed its conservation through structural alignment. Corticosteroids can mediate non-genomic effects, nonetheless, the transduction pathways involved are still misunderstood. Moreover, a growing body of evidence is pointing out toward the existence of a novel membrane receptor mediating part of these rapid corticosteroids effects. Our results suggest that the naturally produced glucocorticoid cortisol inhibits channel water permeability. Based on these results, we propose a detailed description of a putative underlying molecular mechanism. In this process, we also bring new insights on the regulatory function of AQPs extra-cellular loops and on the role of ions in tuning the water permeability. Altogether, this work brings new insights into corticosteroids non-genomic effects through the proposition of AQPs as membrane receptor of this family of regulatory molecules. This original result is the starting point for future investigations to define more in depth and in vivo the validity of this functional model.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

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

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

This research is aimed at evaluating two different scenarios, firstly, appraising the impacts of employing the concepts of Total Quality Management (TQM) to the construction projects in Saudi Arabia. The results of the study were obtained through utilization of a descriptive analytical approach, where 300 questionnaires were distributed to engineering firms and companies with a response rate of 200 questionnaires, hence achieving the study sample for this research. The data gathered was analyzed by applying the Statistical Package for Social Science (SPSS) program and calculating the Relative importance index (RII) and the mean values. From the research conducted, the outcomes showed that the management’s ability to commit using TQM while applying BIM obtained a relative importance of (0.717), while the relative importance for the management’s ability to commit using TQM without the application of BIM is (0.552). The results showed that construction projects in Saudi Arabia still sustain setbacks from applying TQM concepts and suffer from the lack of administrative, scientific and technical applications. In a second scenario, a hybridized support vector regression (SVR) Harris-hawks optimization (HHO) (i.e., SVR-HHO) were used to predict the TQM. The performance accuracy of the models was checked through three different evaluation metrics namely; mean square error (MSE), correlation co-efficient (CC) and Nash-Sutcliffe efficiency (NSE). the hybridized emerging SVR-HHO outperformed the other two data driven approaches in both the training and testing stages based on the employed evaluation metrics. Overall, the obtained results showed that both the machine learning and metaheuristic approaches were capable of predicting TQM.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of &gt;95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

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

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p&lt;0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Thermal treatment in Australia is gaining interest due to legislative changes, waste reduction goals, and the need to address contaminants risks in biosolids used for agriculture. The resulting biochar product has the potential to be beneficially recycled as a soil amendment. On-farm management practices were reviewed to identify barriers that need to be overcome to increase recycling and examine the role of pyrolysis and gasification in effectively improving the quality and safety of biochar. Key findings revealed: (1) thermal treatment can effectively eliminate persistent organic pollutants, microplastics and pathogens, and (2) more than 90% of the total heavy metals content in biosolids become immobilized when these are converted to biochar, thus reducing their bioavailability following land application. While reported research on the short-term effects of biosolids-derived biochar suggested promising agronomic results, there is dearth of information on long-term effects. Other knowledge gaps include optimisation of land application rates, understanding of rate of breakdown and fate of contaminants in soil and water, heavy metal mobility in soil and bioaccumulation or transfer to the food chain. Improved understanding of nutrients and contaminants dynamics in soils receiving biosolids-derived biochar is a pre-requisite for their safe use in Australian agriculture, and therefore it is highlighted as priority area for future research.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

The opportunities and potential of Artificial Intelligence (AI) in Environmental Assessment (EA) are often mentioned. However, do we in the EA field understand the implications of what is happening in other biological sciences, and are we preparing for the changes that are coming? This interdisciplinary letter focuses on AI-driven developments in biodiversity data and analysis as a starting point for stimulating discussion about what AI means in practice for the field of EA. We highlight implications for training, transformation of practice and decision making as first steps in a research agenda.

Childhood obesity is one of the most prevalent public health challenges in the United States and although rates are declining overall, rates among children living in underserved neighborhoods are increasing. This five-year intervention project seeks to empower teachers (n=92) to invest in their own health and then to integrate nutrition concepts into core subjects’ lessons in elementary schools. The professional development sessions reflect the concepts in the Whole Child, Whole School, Whole Community model. Results indicate that teachers who attended professional development sessions were more likely to implement nutrition lessons in the classroom (r = 0.54, p&lt;0.01) and students demonstrated a significant increase in nutrition knowledge (p &lt; .001, df = 2, F = 9.66). Investing in school-based programs that ensure teacher well-being and professional development can yield positive benefits for both teachers and students.

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

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

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

Background: pathophysiological changes like low cardiac output (LCO) impact pharmacokinetics, but its extent may be different throughout pediatrics compared to adults. Physiologically based pharmacokinetic (PBPK) modelling enables further exploration. Methods: A validated propofol model was used to simulate the impact of LCO on propofol clearance across age groups using the PBPK platform, Simcyp® (version 19). The hepatic and renal extraction ratio of propofol was then determined in all age groups. Subsequently, dose explorations were conducted under LCO conditions, targeting a 3 µg/mL (80-125%) propofol concentration range. Results: Both hepatic and renal extraction ratios increased from neonates, infants, children to adolescents and adults. The relative change in clearance following CO reductions increased with age, with the least impact of LCO in neonates. The predicted concentration remained within the 3 µg/mL (80-125%) range under normal CO and LCO (up to 30%) conditions in all age groups. When CO was reduced by 40-50%, a dose reduction of 15% is warranted in neonates, infants and children, 25% in adolescents and adults. Conclusions: PBPK driven, the impact of reduced CO on propofol clearance is predicted to be age-dependent, proportionally greater in adults. Consequently, age group specific dose reductions for propofol are required in LCO conditions.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

In tropical Africa, forests and savannas are the two most widespread biomes and potentially represent alternative stable states with divergent species composition. A classic, but untested, hypothesis posited by White (1983) suggests that the transition zones between forests and savannas contain a floristically impoverished assemblage with few representatives from each biome. Further, the evolutionary dimension of diversity has received limited attention, despite its importance for understanding the biogeographic history of biomes. Here, we quantify species richness and several measures of evolutionary diversity in 1° grid cells, using c. 300K occurrence records of trees and shrubs combined with biome affiliation data for 3,125 species. We find that assemblages in transition zones hold fewer woody species than assemblages in forest and savanna zones, as posited by White. However, transition zones hold more phylogenetic diversity than expected given their species richness, whether one considers forest and savanna assemblages separately or together. We also show that the Congo basin forest has low levels of phylogenetic diversity given the number of species and highlight south-eastern African savannas as a centre of savanna woody species richness and phylogenetic diversity. Regions with high phylogenetic diversity given the number of both forest and savanna species were centred around the Dahomey Gap and Cameroon, mainly in transition zones. Overall, our study shows that even if floristically impoverished, transition zones lead to unexpectedly high evolutionary diversity, suggesting they are important centres of evolutionary innovation and diversification.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

With metal oxide semiconductors being a promising candidate for accurate indoor air quality assessments, multiple drawbacks of the gas sensors prevent their widespread use. Examples include poor selectivity, instability over time, and sensor poisoning. Complex calibration methods and advanced operation modes can solve some of those drawbacks. However, this leads to long calibration times, which are unsuitable for mass production. In recent years, multiple attempts to solve calibration transfer have been made with the help of direct standardization, orthogonal signal correction, and many more methods. Besides those, a new promising approach is transfer learning from deep learning. This article will compare different calibration transfer methods, including direct standardization, piecewise direct standardization, transfer learning for deep learning models, and global model building. The machine learning methods to calibrate the initial models for calibration transfer are feature extraction, selection, and regression (established methods) and a custom convolutional neural network TCOCNN. It is shown that transfer learning can outperform the other calibration transfer methods regarding the root mean squared error, especially if the initial model is built with multiple sensors. It was possible to reduce the number of calibration samples by up to 99.3 % (from 10 days to approximately 2 hours) and still achieve an RMSE for acetone of around 18 ppb (15 ppb with extended individual calibration) if six different sensors were used for building the initial model. Furthermore, it was shown that the other calibration transfer methods (direct standardization and piecewise direct standardization) also work reasonably well for both machine learning approaches, primarily when multiple sensors are used for the initial model.

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated if immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations can be overcome by immunization with VVX001 (i.e., Alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by ELISA and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by CFSE staining and subsequent FACS analysis. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the NTCP attachment site. IgG reactivity to sub-viral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusion: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

This paper aims to outline the effectiveness of modern universal gate quantum computers when utilizing different configurations to solve the B-SAT(Boolean Satisfiability) problem. The quantum computing experiments are performed using Grover’s Search algorithm to find a valid solution. The experiments are performed under different variations to demonstrate their effects on the results. Changing the number of shots, qubit mapping, and using a different quantum processor are all among the experimental variables. The study also branches into a dedicated experiment highlighting a peculiar behavior that IBM quantum processors exhibit when running circuits with a certain number of shots.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of critical limb ischaemia (CLI) patients undergoing lower limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018-02/2020), 106 CLI-patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020-07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%) and hospitalised patients decreased. Patients treated in <=14/5 days after referral significantly increased to 64/63%. Kaplan-Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target lesion revascularisation decreased during COVID-19. 1-year mortality was significantly worse in hospitalised as compared to day cases (14% vs 43%) at similar wound healing rates (83% vs 84%). The most frequent known-causes-of-death were infectious disease (64%) and cardiovascular (21%) was less frequent. Despite COVID-19 restriction a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLI should be treated more aggressively and earlier.

This research aims to understand the vision and the reaction of the population towards tourism and holidays during this period of the COVID-19 pandemic. It investigates also the tourist needs of the Algerian population after the closure of international borders. Methods: The data were collected using mixed quantitative and qualitative methods through a questionnaire applied to 203 people in different regions of Algeria (a North African country) from 1st June to 13 July 2020. Results: The needs of Algerian tourists are characterized by a great need for leisure to relieve psychological stress caused by COVID-19 (M = 25.33) among the study sample (p <0.05). The results also show an average need to rationalize the costs of tourist services (M = 5.26) according to the respondents (p <0.01). This is in addition to the great need (M = 7.75) among respondents (p <0.05) of the awareness that the tourism sector can contribute to the economic recovery in Algeria after the confinement period. About 75.86% of respondents demand the cleanliness of tourist sites, while 69.95% recommend improving safety because of the size of tourist sites in the Algerian territory and also measures related to social distancing. The results show that 53.69% of respondents preferred the month of August to go on vacation, 29.06% chose the month of September, and 17.25% would prefer the months of October, November and December since they expect a reduction in the risks of the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has affected the tourism needs of the Algerian population, which has become increasingly aware of the consequences of the pandemic in relation to their health and on the country's economy. These results can help the authorities of the tourism sector to better understand and identify the tourism needs of this population in the current period and after the COVID-19 pandemic.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Policing duties may inherently be dangerous due to stab, blunt trauma and ballistic threats. The addition of individual light armour vests (ILAVs) has been suggested as a means to protect officers. However, the addition of the extra load of the ILAV may affect officer ability to conduct occupational tasks. The purpose of this study was to determine if wearing any of 3 different ILAVs (ILAV A, ILAV B, & ILAV C) affected occupational task performance when compared to that in normal station wear. A prospective, within-subjects repeated measures design was employed, using a counterbalanced randomization in which each ILAV was worn for an entire day while officers completed a variety of occupationally relevant tasks. These tasks included a victim drag, car exit and 5 meter sprint, step down and marksmanship task. Results showed that performance in each task did not vary between any of the ILAV or normal station wear conditions. There was less variability in the marksmanship task with ILAV B, however. The results suggest that none of the ILAVs used in this study were heavy enough to significantly affect task performance in the assessed tasks when compared to wearing normal station wear.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.