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A gene cluster responsible for the degradation of nicotinic acid (NA) in Bacillus niacini has recently been identified, and the structures and functions of the resulting enzymes are currently being evaluated to establish pathway intermediates. One of the genes within this cluster encodes a flavin monooxygenase (BnFMO) that is hypothesized to catalyze a hydroxylation reaction. Kinetic analyses of the recombinantly purified BnFMO suggest that this enzyme catalyzes the hydroxylation of 2,6-dihydroxynicotinic acid (2,6-DHNA) or 2,6-dihydroxypyridine (2,6-DHP), which is formed spontaneously by the decarboxylation of 2,6-DHNA. To understand the details of this hydroxylation reaction, we determined the structure of BnFMO using a multimodel approach combining protein X-ray crystallography and cryo-electron microscopy (cryo-EM). A liganded BnFMO cryo-EM structure was obtained in the presence of 2,6-DHP, allowing us to make predictions about potential catalytic residues. The structural data demonstrate that BnFMO is trimeric, which is unusual for Class A flavin monooxygenases. In both the electron density and coulomb potential maps, a region at the trimeric interface was observed that was consistent with and modeled as lipid molecules. High-resolution mass spectral analysis suggests that there is a mixture of phosphatidylethanolamine and phosphatidylglycerol lipids present. Together, these data provide insights into the molecular details of the central hydroxylation reaction unique to the aerobic degradation of NA in Bacillus niacini .

Background: Firearm suicides constitute a major public health issue. Policies that enhance economic security and decrease community-level poverty may be effective strategies for reducing risk of firearm suicide. This study examined the association between state minimum wage and firearm suicide., Methods: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualised using the modified Kaitz Index and a continuous variable centred on the federal minimum wage. State-level suicide counts were obtained from 2000 to 2020 multiple-cause-of-death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm suicides, stratifying by demographic groups. Analyses were conducted in 2023., Results: A one percentage point increase in a state's modified Kaitz Index was associated with a 0.3% (95% CI -0.6% to -0.0%) decrease in firearm suicides within a state. A US$1.00 increase in a state's minimum wage above the federal minimum wage was associated with a 1.4% (95% CI -2.1% to -0.6%) decrease in firearm suicides. When stratified by quartile of firearm ownership, the modified Kaitz Index was associated with decreases in firearm suicides most consistently in the two lowest quartiles., Conclusion: Increasing a state's minimum wage may be a policy option to consider as part of a comprehensive approach to reducing firearm suicides. These findings expand the evidence base for how economic policies may be leveraged to reduce firearm suicides., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

LGBTQ+ patients comprise one of the fastest-growing user demographics in fertility care, yet they remain underrepresented in fertility research, practice, and discourse. Existing studies have revealed significant systemic barriers, including cisheteronormativity, discrimination, and gaps in clinical expertise. In this article, we present a checklist of measures clinics can take to improve LGBTQ+ inclusion in fertility care, co-created with members of the LGBTQ+ community. This checklist focuses on three key areas: cultural competence, clinical considerations, and online presence. The cultural competence criteria encompass inclusive communication practices, a broad understanding of LGBTQ+ healthcare needs, and knowledge of treatment options suitable for LGBTQ+ individuals. Clinical considerations include awareness of alternative examination and gamete collection techniques for transgender and non-binary patients, the existence of specific clinical pathways for LGBTQ+ patients, and sensitivity to the psychological aspects of fertility care unique to this demographic. The online presence criteria evaluate provider websites for the use of inclusive language and the availability of LGBTQ+-relevant information. The checklist was used as the foundation for an audit of fertility care providers across the UK in early 2024. Our audit identified a widespread lack of LGBTQ+ inclusion, particularly for transgender and non-binary patients, highlighting deficiencies in clinical knowledge and cultural competence. Our work calls attention to the need for further work to understand the barriers to inclusive and competent LGBTQ+ fertility care from both healthcare provider and patient perspectives.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.

The bacterial pathogen Staphylococcus aureus employs a thick cell wall for protection against physical and chemical insults. This wall requires continuous maintenance to ensure strength and barrier integrity, but also to permit bacterial growth and division. The main cell wall component is peptidoglycan. Accordingly, the bacteria produce so-called peptidoglycan hydrolases (PGHs) that cleave glycan strands to facilitate growth, cell wall remodelling, separation of divided cells and release of exported proteins into the extracellular milieu. A special class of PGHs contains so-called 'cysteine, histidine-dependent amidohydrolase/peptidase' (CHAP) domains. In the present study, we profiled the roles of 11 CHAP PGHs encoded by the core genome of S. aureus USA300 LAC. Mutant strains lacking individual CHAP PGHs were analysed for growth, cell morphology, autolysis, and invasion and replication inside human lung epithelial cells. The results show that several investigated CHAP PGHs contribute to different extents to extracellular and intracellular growth and replication of S. aureus, septation of dividing cells, daughter cell separation once the division process is completed, autolysis and biofilm formation. In particular, the CHAP PGHs Sle1 and SAUSA300_2253 control intracellular staphylococcal replication and the resistance to β-lactam antibiotics like oxacillin. This makes the S. aureus PGHs in general, and the Sle1 and SAUSA300_2253 proteins in particular, attractive targets for future prophylactic or therapeutic anti-staphylococcal interventions. Alternatively, these cell surface-exposed enzymes, or particular domains of these enzymes, could be applied in innovative anti-staphylococcal therapies., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: To explore the attitudes, facilitators and barriers in providing oral care for inpatients with dysphagia post-stroke as perceived by healthcare professionals., Background: Dysphagia is a common complication of stroke and is associated with a higher incidence of aspiration pneumonia, malnutrition and dehydration. In the acute phase of stroke recovery, a dental professional is not usually part of the multidisciplinary team caring for the patient and oral care is the responsibility of the healthcare professionals in the stroke unit. There is a lack of high-quality evidence to demonstrate the most effective method of providing oral care for patients with dysphagia post-stroke., Materials and Methods: This was a single-site study conducted with healthcare professionals working in the Stroke Unit of Cork University Hospital in Ireland, using focus groups and a qualitative thematic analysis approach., Results: A total of three focus groups were conducted in the Stroke Unit with 17 healthcare professionals. The focus groups included representation from all healthcare professional groups providing direct clinical care to patients on the Stroke Unit including geriatric medicine, dietetics, speech and language therapy, healthcare assistance, nursing, occupational therapy and physiotherapy. A qualitative thematic analysis was carried out and seven overarching themes emerged from the data. Three themes related to facilitators to providing oral care for this patient group: (i) a focus on oral care in both policy and practice, (ii) expanding professional roles in the provision of oral care, (iii) perceived importance of oral care in recovery and rehabilitation. Four themes related to barriers to the provision of oral care for this patient group: (i) lack of confidence and concerns related to the perceived risk for patients with dysphagia, (ii) unique challenges of patient and stroke-related factors, (iii) lack of resources and time and (iv) perceived importance of oral care in recovery and its relative importance with competing demands., Conclusion: Members of the stroke multidisciplinary team believe that they all have a part to play in the delivery of oral care for patients with dysphagia post-stroke. Opportunities exist for the development of multidisciplinary interventions to improve the oral cavity assessment and oral care provided in the Stroke Unit., (© 2023 The Authors. Gerodontology published by Gerodontology Association and John Wiley & Sons Ltd.)

Background and Aims: The single nucleotide polymorphisms (SNPs) in SLC30A8 gene have been recognized as contributing to type 2 diabetes (T2D) susceptibility and colorectal cancer. This study aims to predict the structural stability, and functional impacts on variations in non-synonymous SNPs (nsSNPs) in the human SLC30A8 gene using various computational techniques., Materials and Methods: Several in silico tools, including SIFT, Predict-SNP, SNPs&GO, MAPP, SNAP2, PhD-SNP, PANTHER, PolyPhen-1,PolyPhen-2, I-Mutant 2.0, and MUpro, have been used in our study., Results: After data analysis, out of 336 missenses, the eight nsSNPs, namely R138Q, I141N, W136G, I349N, L303R, E140A, W306C, and L308Q, were discovered by ConSurf to be in highly conserved regions, which could affect the stability of their proteins. Project HOPE determines any significant molecular effects on the structure and function of eight mutated proteins and the three-dimensional (3D) structures of these proteins. The two pharmacologically significant compounds, Luzonoid B and Roseoside demonstrate strong binding affinity to the mutant proteins, and they are more efficient in inhibiting them than the typical SLC30A8 protein using Autodock Vina and Chimera. Increased binding affinity to mutant SLC30A8 proteins has been determined not to influence drug resistance. Ultimately, the Kaplan-Meier plotter study revealed that alterations in SLC30A8 gene expression notably affect the survival rates of patients with various cancer types., Conclusion: Finally, the study found eight highly deleterious missense nsSNPs in the SLC30A8 gene that can be helpful for further proteomic and genomic studies for T2D and colorectal cancer diagnosis. These findings also pave the way for personalized treatments using biomarkers and more effective healthcare strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aims: The main objective of the current study is to investigate the pathways and therapeutic targets linked to stevioside in the management of T2D using computational approaches., Methods: We collected RNA-seq datasets from NCBI, then employed GREIN to retrieve differentially expressed genes (DEGs). Computer-assisted techniques DAVID, STRING and NetworkAnalyst were used to explore common significant pathways and therapeutic targets associated with T2D and stevioside. Molecular docking and dynamics simulations were conducted to validate the interaction between stevioside and therapeutic targets., Results: Gene ontology and KEGG analysis revealed that prostaglandin synthesis, IL-17 signaling, inflammatory response, and interleukin signaling were potential pathways targeted by stevioside in T2D. Protein-protein interactions (PPI) analysis identified six common hub proteins (PPARG, PTGS2, CXCL8, CCL2, PTPRC, and EDN1). Molecular docking results showed best binding of stevioside to PPARG (-8 kcal/mol) and PTGS2 (-10.1 kcal/mol). Finally, 100 ns molecular dynamics demonstrated that the binding stability between stevioside and target protein (PPARG and PTGS2) falls within the acceptable range., Conclusions: This study reveals that stevioside exhibits significant potential in controlling T2D by targeting key pathways and stably binding to PPARG and PTGS2. Further research is necessary to confirm and expand upon these significant computational results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Cystic Fibrosis is a multi-system disease, arising from a mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR). There is a lack of information regarding oral disease levels among people with cystic fibrosis. As part of an ongoing study assessing oral health in adults with cystic fibrosis at XXXXXXXXXX, a systematic review of available literature was conducted to ascertain the caries experience of people with cystic fibrosis. The objective was to systematically present and evaluate the literature comparing caries experience between people with cystic fibrosis and people without cystic fibrosis., Methods: Five online databases were searched; Embase, Scopus, Web of Science Core Collection, Medline Ebsco and Cochrane Library. Studies that reported caries experience in people with cystic fibrosis were included in this review., Results: The initial search identified 1199 publications from online databases. Twenty-one studies were included for qualitative analysis. Fourteen studies reported a lower caries experience in children with CF compared to children without CF, five studies reported a higher caries experience in adults with CF, and two studies found inconclusive evidence regarding the association between caries experience and CF status. All studies had a risk of bias that may influence results., Conclusion: Despite a lack of complete unanimity between all studies, there is a general trend that children with cystic fibrosis have a lower caries experience than their healthy counterparts, whereas adults with cystic fibrosis have a higher caries experience. The review highlights the need for further studies involving adults with cystic fibrosis as the majority of studies primarily consist of paediatric populations., Clinical Significance: Dental practitioners should be aware that adults with cystic fibrosis have higher caries experience. Tailored approaches to dental care specific to cystic fibrosis individuals should be developed., Competing Interests: Declaration of competing interest I Dr Fiona O'Leary the corresponding author confirm on behalf of all authors that there have been no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. There was no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: National Personal Health Records (PHRs) have been proposed to improve the transfer of medication-related information during transition of care. Objective: To evaluate the concordance between the medications captured in the Australian national PHR, My Health Record (MyHR), and the pharmacist obtained best possible medication history (BPMH) for patients upon hospital admission. Method: This prospective observational study used a convenience sample of hospital patients. For newly admitted patients, the investigating pharmacist obtained a BPMH and then compared it to the medication list captured in MyHR. Upon comparison, the medications were categorised into either complete match, partial match or mismatch. Medications with a complete or partial match were grouped together. Medications with deviations were then assessed for risk based on their potential consequence, and reported descriptively. A multivariable logistic regression was conducted to assess the factors associated with a drug being mismatched. Results: A total of 82 patients were recruited, with a cumulative total of 1,207 medications documented. Of the 1,207 medications, 714 (59.2%) medications were documented as a complete/partial match. The remaining 493 (40.8%) medications were mismatched. Of the 493 mismatched medications, 442 (89.7%) were deemed low-risk deviations and 51 (10.3%) were deemed high-risk. A medication was more likely to be mismatched, rather than completely/partially matched, if it was a regular non-prescription medication, or "when-required" prescription medication, or "when required" non-prescription medication, or if it was administered parenterally. Conclusion: National PHRs may be a secondary source to either confirm a patient's medication history or be used as a starting point for a BPMH., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Tomato ( Solanum lycopersicon L.) is one of the most widely consumed and produced vegetable crops worldwide. It offers numerous health benefits due to its rich content of many therapeutic elements such as vitamins, carotenoids, and phenolic compounds. Biotic stressors such as bacteria, viruses, fungi, nematodes, and insects cause severe yield losses as well as decreasing fruit quality. Conventional breeding strategies have succeeded in developing resistant genotypes, but these approaches require significant time and effort. The advent of state-of-the-art genome editing technologies, particularly CRISPR/Cas9, provides a rapid and straightforward method for developing high-quality biotic stress-resistant tomato lines. The advantage of genome editing over other approaches is the ability to make precise, minute adjustments without leaving foreign DNA inside the transformed plant. The tomato genome has been precisely modified via CRISPR/Cas9 to induce resistance genes or knock out susceptibility genes, resulting in lines resistant to common bacterial, fungal, and viral diseases. This review provides the recent advances and application of CRISPR/Cas9 in developing tomato lines with resistance to biotic stress.

Designing and implementing processing procedures for producing safe complementary foods in dynamic and unregulated food systems where common food staples are frequently contaminated with mycotoxins is challenging. This paper presents lessons about minimizing aflatoxins (AF) in groundnut flour and AF and/or fumonisins (FUM) in maize and groundnut pre-blended flour for complementary feeding in the context of a dietary research intervention in rural Tanzania. The flours were processed in collaboration with Halisi Products Limited (Halisi), a medium scale enterprise with experience in milling cereal-based flours in Arusha, Tanzania. Using a hazard analysis critical control point (HACCP) approach for quality assurance, two critical control points (CCPs) for AF in processing the pre-blended flour were identified: 1) screening maize before procurement, and 2) blending during the processing of each constituent flour. Blending of maize flour was also identified as a CCP for FUM. Visual inspection during screening and sorting were identified as important control measures for reducing AF, but these steps did not meet the criteria for a CCP due to lack of objective measurement and verifiable standards for AF. The HACCP approach enabled the production of low AF (<5 μg/kg) and FUM (<2 μg/g) flours with low rejection rates for the final products. The paper presents practical lessons that could be of value to a range of commercial processors in similar low- and middle-income contexts who are keen on improving food quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: To evaluate the prediction accuracy of various intraocular lens (IOL) power calculation formulas on American Society of Cataract and Refractive Surgery (ASCRS) calculator and Barrett True-K total keratometry (TK) in eyes with previous laser refractive surgery for myopia., Methods: This retrospective study included eyes with history of myopic laser refractive surgery, which have undergone clear or cataractous lens extraction by phacoemulsification followed by IOL implantation. Those who underwent uneventful crystalline lens extraction were included. Eyes with any complication of refractive surgery or those with eventful lens extraction procedure and those who were lost to follow-up were excluded. Formulas compared were Wang-Koch-Maloney, Shammas, Haigis-L, Barrett True-K no-history formula, ASCRS average power, ASCRS maximum power on the ASCRS post-refractive calculator and the IOLMaster 700 Barrett True-K TK. Prediction error was calculated as the difference between the implanted IOL power and the predicted power by various formulae available on ASCRS online calculator., Results: Forty post-myopic laser-refractive surgery eyes of 26 patients were included. Friedman's test revealed that Shammas formula, Barrett True-K, and ASCRS maximum power were significantly different from all other formulas (P < 0.00001 for each). Median absolute error (MedAE) was the least for Shammas and Barrett True-K TK formulas (0.28 [0.14, 0.36] and 0.28 [0.21, 0.39], respectively) and the highest for Wang-Koch-Maloney (1.29 [0.97, 1.61]). Shammas formula had the least variance (0.14), while Wang-Koch-Maloney formula had the maximum variance (2.66)., Conclusion: In post-myopic laser refractive surgery eyes, Shammas formula and Barrett True-K TK no-history formula on ASCRS calculator are more accurate in predicting IOL powers., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Humans have moved domestic animals around the globe for thousands of years. These have occasionally established feral populations in nature, often with devastating ecological consequences. To understand how natural selection shapes re-adaptation into the wild, we investigated one of the most successful colonizers in history, the European rabbit. By sequencing the genomes of 297 rabbits across three continents, we show that introduced populations exhibit a mixed wild-domestic ancestry. We show that alleles that increased in frequency during domestication were preferentially selected against in novel natural environments. Interestingly, causative mutations for common domestication traits sometimes segregate at considerable frequencies if associated with less drastic phenotypes (for example, coat colour dilution), whereas mutations that are probably strongly maladaptive in nature are absent. Whereas natural selection largely targeted different genomic regions in each introduced population, some of the strongest signals of parallelism overlap genes associated with neuronal or brain function. This limited parallelism is probably explained by extensive standing genetic variation resulting from domestication together with the complex mixed ancestry of introduced populations. Our findings shed light on the selective and molecular mechanisms that enable domestic animals to re-adapt to the wild and provide important insights for the mitigation and management of invasive populations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Logically, regulation of blood glucose should reverse dysfunction, but the Epidemiology of Diabetes Interventions and Complications study found strict control ineffective. However, it is possible that strict control may prevent DBD if initiated before symptoms appear. We examine the effect of early glucose control on development of DBD in the female diabetic Akita mouse (Type 1) and test the potential of inhibiting/deleting NLRP3 as adjunct therapy to glucose control., Materials and Methods: Female Akita mice were bred NLRP3 +/+ or NLRP3 -/- . At 6 weeks of age, diabetics received either no glucose control or insulin pellets (s.c., Linshin) designed to poorly or strictly control blood glucose. At Week 15, blood glucose (glucometer), the extravasation potential of bladder (an indirect measurement of inflammation) and bladder function (urodynamics) were assessed., Results: Blood glucose of diabetics was reduced in poorly controlled and strongly reduced in strictly controlled groups. Levels were not affected by deletion of NLRP3. Evans blue dye extravasation correlated with glucose control and was eliminated in the NLRP3 -/-  groups. Urodynamics found markers of overactivity in diabetics which was improved in the poorly controlled group and eliminated in the strictly controlled group. In the NLRP3 -/-  mice, no bladder dysfunction developed, regardless of glucose control., Conclusions: Early-initiated strict glycemic control and NLRP3 elimination can effectively prevent DBD, suggesting hyperglycemia acts through NLRP3-induced inflammation to trigger DBD., (© 2024 Wiley Periodicals LLC.)

Switchgrass is a potential crop for bioenergy or carbon capture schemes, but further yield improvements through selective breeding are needed to encourage commercialization. To identify promising switchgrass germplasm for future breeding efforts, we conducted multi-site and multi-trait genomic prediction with a diversity panel of 630 genotypes from 4 switchgrass subpopulations (Gulf, Midwest, Coastal, and Texas), which were measured for spaced plant biomass yield across 10 sites. Our study focused on the use of genomic prediction to share information among traits and environments. Specifically, we evaluated the predictive ability of cross-validation (CV) schemes using only genetic data and the training set, (cross validation 1: CV1), a subset of the sites (cross validation 2: CV2), and/or with two yield surrogates (flowering time and fall plant height). We found that genotype-by-environment interactions were largely due to the north-south distribution of sites. The genetic correlations between yield surrogates and biomass yield were generally positive (mean height r=0.85; mean flowering time r=0.45) and did not vary due to subpopulation or growing region (North, Middle, South). Genomic prediction models had cross-validation predictive abilities of -0.02 for individuals using only genetic data (CV1) but 0.55, 0.69, 0.76, 0.81, and 0.84 for individuals with biomass performance data from one, two, three, four and five sites included in the training data (CV2), respectively. To simulate a resource-limited breeding program, we determined the predictive ability of models provided with: one site observation of flowering time (0.39), one site observation of flowering time and fall height (0.51), one site observation of fall height (0.52), one site observation of biomass (0.55), and five site observations of biomass yield (0.84). The ability to share information at a regional scale is very encouraging but further research is required to accurately translate spaced plant biomass to commercial-scale sward biomass performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Technology-facilitated child sexual abuse (TF-CSA), or child sexual abuse that occurs online or through electronic communication, is a preventable public health problem that can be addressed within youth-serving organizations (YSOs). This study is a review of a purposive sample of organizational policies and practices designed to prevent TF-CSA collected from 13 national and local YSOs in the United States. Documents were coded to identify practices to prevent TF-CSA related to YSO activities or YSO staff, volunteers, or participants. Qualitative analysis indicated that YSOs included seven common practices to prevent TF-CSA in their documents. These practices included transparent electronic communication between youth and YSO staff; codes of conduct and online behavior agreements related to youth; monitoring the YSO's online presence; parental controls for youth online activity; safety behaviors for online activity for staff, parents, and youth; parent and youth trainings for youth online engagement and prevention of TF-CSA; and practices to address staff policy violations. Most prevention practices documented by YSOs identified in this study are consistent with emerging literature on TF-CSA prevention. Key gaps include protections for youth from groups inequitably burdened by TF-CSA and evaluation of the implementation and effectiveness of practices in preventing TF-CSA across settings and populations.

Background: Children in households experiencing poverty are disproportionately exposed to maltreatment. Income support policies have been associated with reductions in child abuse and neglect. The advance child tax credit (CTC) payments may reduce child maltreatment by improving the economic security of some families. No national studies have examined the association between advance CTC payments and child abuse and neglect. This study examines the association between the advance CTC payments and child abuse and neglect-related contacts to the Childhelp National Child Abuse Hotline., Methods: A time series study of contacts to the Childhelp National Child Abuse Hotline between January 2019 and December 2022 was used to examine the association between the payments and hotline contacts. An interrupted time series (ITS) exploiting the variation in the advance CTC payments was estimated using fixed effects., Results: The CTC advance payments were associated with an immediate 13.8% (95% CI -17.5% to -10.0%) decrease in contacts to the hotline in the ITS model. Following the expiration of the advance CTC payments, there was a significant and gradual 0.1% (95% CI +0.0% to +0.2%) daily increase in contacts. Sensitivity analyses found significant reductions in contacts following each payment, however, the reductions were associated with the last three of the six total payments., Conclusion: These findings suggest the advance CTC payments may reduce child abuse and neglect-related hotline contacts and continue to build the evidence base for associations between income-support policies and reductions in child abuse and neglect., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

How organisms respond to environmental stress is a key topic in evolutionary biology. This study focused on the genomic evolution of Laburnicola rhizohalophila, a dark-septate endophytic fungus from roots of a halophyte. Chromosome-level assemblies were generated from five representative isolates from structured subpopulations. The data revealed significant genomic plasticity resulting from chromosomal polymorphisms created by fusion and fission events, known as dysploidy. Analyses of genomic features, phylogenomics, and macrosynteny have provided clear evidence for the origin of intraspecific diploid-like hybrids. Notably, one diploid phenotype stood out as an outlier and exhibited a conditional fitness advantage when exposed to a range of abiotic stresses compared with its parents. By comparing the gene expression patterns in each hybrid parent triad under the four growth conditions, the mechanisms underlying growth vigor were corroborated through an analysis of transgressively upregulated genes enriched in membrane glycerolipid biosynthesis and transmembrane transporter activity. In vitro assays suggested increased membrane integrity and lipid accumulation, as well as decreased malondialdehyde production under optimal salt conditions (0.3 M NaCl) in the hybrid. These attributes have been implicated in salinity tolerance. This study supports the notion that hybridization-induced genome doubling leads to the emergence of phenotypic innovations in an extremophilic endophyte., (© 2024. The Author(s).)

We examined the associations of vegetarianism with metabolic biomarkers using traditional and genetic epidemiology. First, we addressed inconsistencies in self-reported vegetarianism among UK Biobank participants by utilizing data from two dietary surveys to find a cohort of strict European vegetarians (N = 2,312). Vegetarians were matched 1:4 with nonvegetarians for non-genetic association analyses, revealing significant effects of vegetarianism in 15 of 30 biomarkers. Cholesterol measures plus vitamin D were significantly lower in vegetarians, while triglycerides were higher. A genome-wide association study revealed no genome-wide significant (GWS; 5×10-8) associations with vegetarian behavior. We performed genome-wide gene-vegetarianism interaction analyses for the biomarkers, and detected a GWS interaction impacting calcium at rs72952628 (P = 4.47×10-8). rs72952628 is in MMAA, a B12 metabolic pathway gene; B12 has major deficiency potential in vegetarians. Gene-based interaction tests revealed two significant genes, RNF168 in testosterone (P = 1.45×10-6) and DOCK4 in estimated glomerular filtration rate (eGFR) (P = 6.76×10-7), which have previously been associated with testicular and renal traits, respectively. These nutrigenetic findings indicate genotype can modify the associations between vegetarianism and health outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Francis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia-responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia-selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Competing Interests: We declare no competing interests.

Ectomycorrhizal symbiosis, which involves mutually beneficial interactions between soil fungi and tree roots, is essential for promoting tree growth. To establish this symbiotic relationship, fungal symbionts must initiate and sustain mutualistic interactions with host plants while avoiding host defense responses. This study investigated the role of reactive oxygen species (ROS) generated by fungal NADPH oxidase (Nox) in the development of Laccaria bicolor/Populus tremula × alba symbiosis. Our findings revealed that L. bicolor LbNox expression was significantly higher in ectomycorrhizal roots than in free-living mycelia. RNAi was used to silence LbNox, which resulted in decreased ROS signaling, limited formation of the Hartig net, and a lower mycorrhizal formation rate. Using Y2H library screening, BiFC and Co-IP, we demonstrated an interaction between the mitogen-activated protein kinase LbSakA and LbNoxR. LbSakA-mediated phosphorylation of LbNoxR at T409, T477 and T480 positively modulates LbNox activity, ROS accumulation and upregulation of symbiosis-related genes involved in dampening host defense reactions. These results demonstrate that regulation of fungal ROS metabolism is critical for maintaining the mutualistic interaction between L. bicolor and P. tremula × alba. Our findings also highlight a novel and complex regulatory mechanism governing the development of symbiosis, involving both transcriptional and posttranslational regulation of gene networks., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

The widespread use of polyamides such as nylons has led to the accumulation of nylon waste, which is particularly resistant to decomposition due to the intrinsic stability of the amide bond. New methods are required for the true recycling of these waste materials by depolymerization. Enzymes that are capable of hydrolyzing polyamides have been proposed as biocatalysts that may be suitable for this application. NylC is an enzyme that can mediate the hydrolysis of aminohexanoic acid oligomers, and to some extent, bulk polymers. However, current assays to characterize the activity of this enzyme require long reaction times and/or rely on secondary reactions to quantify hydrolysis. Herein, we have designed structurally-optimized small molecule chromogenic esters that serve as substrate analogues for monitoring NylC acyltransferase activity in a continuous manner. This assay can be performed in minutes at room temperature, and the substrate N-acetyl-GABA-pNP ester (k cat  = 0.37 s -1 , K M  = 256 μM) shows selectivity for NylC in complex biological media. We also demonstrate that activity towards this substrate analogue correlates with amide hydrolysis, which is the primary activity of this enzyme. Furthermore, our screening of substrate analogues provides insight into the substrate specificity of NylC, which is relevant to biocatalytic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Radiotherapy trial quality assurance (RT QA) is crucial for ensuring the safe and reliable delivery of radiotherapy trials, and minimizing inter-institutional variations. While previous studies focused on outlining and planning quality assurance (QA), this work explores the process of Image-Guided Radiotherapy (IGRT), and adaptive radiotherapy. This study presents findings from during-accrual QA in the RAIDER trial, evaluating concordance between online and offline plan selections for bladder cancer participants undergoing adaptive radiotherapy. RAIDER had two seamless stages; stage 1 assessed adherence to dose constraints of dose escalated radiotherapy (DART) and stage 2 assessed safety. The RT QA programme was updated from stage 1 to stage 2., Materials and Methods: Data from all participants in the adaptive arms (standard dose adaptive radiotherapy (SART) and DART) of the trial was requested (33 centres across the UK, Australia and New Zealand). Data collection spanned September 2015 to December 2022 and included the plans selected online, on Cone-Beam Computed Tomography (CBCT) data. Concordance with the plans selected offline by the independent RT QA central reviewer was evaluated., Results: Analysable data was received for 72 participants, giving a total of 884 CBCTs. The overall concordance rate was 83% (723/884). From stage 1 to stage 2 the concordance in the plans selected improved from 75% (369/495) to 91% (354/389)., Conclusion: During-accrual IGRT QA positively influenced plan selection concordance, highlighting the need for ongoing support when introducing a new technique. Overall, it contributes to advancing the understanding and implementation of QA measures in adaptive radiotherapy trials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Huddart reports grants received by their institution from Cancer Research UK, MSD and Roche, consultation fees from Janssen, Bristol Myers Squibb, Astellas, Roche and Nektar Pharmaceuticals, payment or honoraria from Roche, Bristol Myers Squibb and Merck, support for attending meetings and/or travel from MSD, Roche and Janssen, participation on a data safety monitoring board or advisory board for Biontech, Gilead and Merck and leadership or fiduciary role at Cancer Centre London, Parkside. Shaista Hafeez reports grants from NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, non-financial support from Elekta (Stockholm, Sweden), personal fees and non-financial support from Roche, non-financial support from Merck Sharp & Dohme (MSD), outside the submitted work. EH reports non-financial support (study drug supplies) received by their institution from Astra-Zeneca and Bayer, outside the submitted work. EH also reports grants received by their institution from Cancer Research UK (within scope of submitted work and outside the submitted work) and Prostate Cancer UK (outside submitted work). Amanda Webster, Michael Francis, Hannah Gribble, Clare Griffin, Vibeke N Hansen, Rebecca Lewis, Helen McNair and Elizabeth Miles have no conflicts to declare, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction., Methods: Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice., Results: Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan's blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks., Conclusions: Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model., (© 2024. The Author(s).)

Objective:  This study aimed to identify factors associated with refractory severe hypertension that does not resolve after an initial dose of antihypertensive medication in patients with preeclampsia., Study Design:  This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Inclusion criteria were patients with preeclampsia who developed severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications for acute severe hypertension. We defined refractory severe hypertension as a systolic blood pressure of ≥160 mm Hg or a diastolic blood pressure of ≥110 mm Hg that did not improve after receiving the initial treatment. To evaluate for factors associated with refractory severe hypertension, we developed multivariable modified Poisson regression using all variables with p -value <0.1 on bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs)., Results:  Of 850, 386 (45.4%) had refractory severe hypertension and 464 (54.6%) responded to the initial antihypertensive medications. Factors associated with refractory severe hypertension included higher body mass index (BMI), chronic hypertension, and higher systolic pressure. Every 5 kg/m 2 increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02-1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04-1.17). Chronic hypertension was associated with a 25% increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.01-1.56) in the diastolic pressure model., Conclusion:  Refractory severe hypertension was associated with elevated BMI, chronic hypertension, and higher systolic blood pressure., Key Points: · Risk factors for refractory severe hypertension are not well-known.. · Almost half of the patients had refractory severe hypertension.. · Higher BMI, chronic hypertension, and higher systolic pressure were the risk factors.. · These patients would require closer follow-up and prompt response to vital signs.., Competing Interests: None declared., (Thieme. All rights reserved.)

Previous work suggests that synergistic activity among motor elements implicated in force production tasks underlies enhanced performance stability associated with visual feedback. A hallmark of synergistic activity is reciprocal compensation, that is, covariation in the states of motor elements that stabilizes critical performance variables. The present study examined if characteristics of reciprocal compensation are indicators of individuals' capacity to respond adaptively to variations in the resolution of visual feedback about criterion performance. Twenty healthy adults (19.25 ± 1.25 years; 15 females and five males) pressed two sensors with their index fingers to produce a total target force equivalent to 20% of their maximal voluntary contraction under nine conditions that differed in the spatial resolution of real-time feedback about their performance. By combining within-trial uncontrolled manifold and sample entropy analyses, we quantified the amount and degree of irregularity (i.e., non-repetitiveness) of reciprocal compensations over time. We found a U-shaped relationship between performance stability and gain. Importantly, this relationship was moderated by the degree of irregularity of reciprocal compensation. Lower irregularity in reciprocal compensation patterns was related to individuals' capacity to maintain (or minimize losses in) performance under changes in feedback resolution. Results invite future investigation into how interindividual variations in reciprocal compensation patterns relate to differences in control strategies supporting adaptive responses in complex, visually guided motor tasks.

Background: The standard diagnosis of Ascaris lumbricoides and other soil-transmitted helminth (STH) infections relies on the detection of worm eggs by copromicroscopy. However, this method is dependent on worm patency and shows only limited accuracy in low-intensity infection settings. We aimed to decipher the diagnostic accuracy of different antibodies using various Ascaris antigens in reference to copromicroscopy and quantitative PCR (qPCR), four months after national STH preventative chemotherapy among school children in western Kenya., Methodology: STH infection status of 390 school children was evaluated via copromicroscopy (Kato-Katz and mini-FLOTAC) and qPCR. In parallel, Ascaris-specific antibody profiles against larval and adult worm lysates, and adult worm excretory-secretory (ES) products were determined by enzyme-linked immunosorbent assay. Antibody cross-reactivity was evaluated using the closely related zoonotic roundworm species Toxocara cati and Toxocara canis. The diagnostic accuracy of each antibody was evaluated using receiver operating curve analysis and the correspondent area under the curve (AUC)., Principal Findings: Ascaris was the predominant helminth infection with an overall prevalence of 14.9% (58/390). The sensitivity of mini-FLOTAC and Kato-Katz for Ascaris diagnosis reached only 53.5% and 63.8%, respectively compared to qPCR. Although being more sensitive, qPCR values correlated with microscopic egg counts (R = -0.71, P<0.001), in contrast to antibody levels. Strikingly, IgG antibodies recognizing the ES products of adult Ascaris worms reliably diagnosed active Ascaris infection as determined by qPCR and microscopy, with IgG1 displaying the highest accuracy (AUC = 0.83, 95% CI: 0.75-0.91)., Conclusion: IgG1 antibody responses against adult Ascaris-ES products hold a promising potential for complementing the standard fecal and molecular techniques employed for monitoring Ascaris infections. This is of particular importance in the context of deworming programs as the antibody diagnostic accuracy was independent of egg counts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mugo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Secure firearm storage might help reduce access by children and other unauthorized users and the related risk for injury or death. Information about state-specific prevalence of firearm storage practices can be used to develop secure storage messages and programs; however, such information is often unavailable. Data from the Behavioral Risk Factor Surveillance System, by respondent characteristics, were used to estimate prevalence of keeping firearms in or around the home and related storage practices for eight states that administered the firearm safety module in 2021 or 2022. Overall, 18.4% (California) to 50.6% (Alaska) of respondents reported that a firearm was kept in or around their home. Among those with a firearm in or around the home, 19.5% (Minnesota) to 43.8% (North Carolina) reported that a firearm was stored loaded. Across all eight states, approximately one half of those with a loaded firearm stored at least one loaded firearm unlocked. Among respondents with a child and a loaded firearm in the home, 25.2% (Ohio) to 41.4% (Alaska) reported that a loaded firearm was stored unlocked. Variability in firearm storage practices highlights the importance of local data and suggests opportunities to tailor prevention efforts to specific population groups to reduce risk for firearm handling by children without adult supervision, and other unauthorized persons., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Classically, ATM is known for its role in sensing double-strand DNA breaks, and subsequently signaling for their repair. Non-canonical roles of ATM include transcriptional silencing, ferroptosis, autophagy and angiogenesis. Angiogenesis mediated by ATM signaling has been shown to be VEGF-independent via p38 signaling. Independently, p38 signaling has been shown to upregulate metalloproteinase expression, including MMP-2 and MMP-9, though it is unclear if this is linked to ATM. Here, we demonstrate ATM regulates aminopeptidase-N (CD13/APN/ANPEP) at the protein level. Positive correlation was seen between ATM activity and CD13 protein expression using both "wildtype" (WT) and knockout (KO) ataxia telangiectasia (AT) cells through western blotting; with the same effect shown when treating neuroblastoma cancer cell line SH-SY5Y, as well as AT-WT cells, with ATM inhibitor (ATMi; KU55933). However, qPCR along with publically available RNAseq data from Hu et al. (J. Clin. Invest., 2021, 131, e139333), demonstrated no change in mRNA levels of CD13, suggesting that ATM regulates CD13 levels via controlling protein degradation. This is further supported by the observation that incubation with proteasome inhibitors led to restoration of CD13 protein levels in cells treated with ATMi. Migration assays showed ATM and CD13 inhibition impairs migration, with no additional effect observed when combined. This suggests an epistatic effect, and that both proteins may be acting in the same signaling pathway that influences cell migration. This work indicates a novel functional interaction between ATM and CD13, suggesting ATM may negatively regulate the degradation of CD13, and subsequently cell migration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Stevenson, Page, Dowson, ElBadry, Barnieh, Falconer and El-Khamisy.)

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II., Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism., Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II., (© 2024. The Author(s).)

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antimicrobials are molecules that prevent the formation of microorganisms such as bacteria, viruses, fungi, and parasites. The necessity to detect antimicrobial peptides (AMPs) using machine learning and deep learning arises from the need for efficiency to accelerate the discovery of AMPs, and contribute to developing effective antimicrobial therapies, especially in the face of increasing antibiotic resistance. This study introduced AMP-RNNpro based on Recurrent Neural Network (RNN), an innovative model for detecting AMPs, which was designed with eight feature encoding methods that are selected according to four criteria: amino acid compositional, grouped amino acid compositional, autocorrelation, and pseudo-amino acid compositional to represent the protein sequences for efficient identification of AMPs. In our framework, two-stage predictions have been conducted. Initially, this study analyzed 33 models on these feature extractions. Then, we selected the best six models from these models using rigorous performance metrics. In the second stage, probabilistic features have been generated from the selected six models in each feature encoding and they are aggregated to be fed into our final meta-model called AMP-RNNpro. This study also introduced 20 features with SHAP, which are crucial in the drug development fields, where we discover AAC, ASDC, and CKSAAGP features are highly impactful for detection and drug discovery. Our proposed framework, AMP-RNNpro excels in the identification of novel Amps with 97.15% accuracy, 96.48% sensitivity, and 97.87% specificity. We built a user-friendly website for demonstrating the accurate prediction of AMPs based on the proposed approach which can be accessed at http://13.126.159.30/ ., (© 2024. The Author(s).)

Introduction: Maxillary reconstruction is often a challenging task for the surgeons because of the complex anatomy. However, with the advances in virtual surgical planning (VSP) and 3D printing technology there is a new avenue for the surgeons which offers a suitable alternative to conventional flap-based reconstructions., Patients and Methods: In this article, we have described 4 case scenarios which were managed with the help of VSP and additive manufacturing technology for complex maxillary reconstruction procedures. Use of the technologies aided the clinician in achieving optimal outcomes with regards to form, function and esthetics., Discussion: Virtual surgical planning (VSP) has gained a lot of impetus in past 1 decade. These aides the surgeon in determining the extent of disease and also carry out the treatment planning. In addition to VSP, the concept of additive manufacturing provides a viable alternative to the conventional reconstruction modalities for maxillary defect rehabilitation. Increased accuracy, rehabilitation of normal anatomical configuration, appropriate dental rehabilitation, decreased intra-operative time and post-operative complications are some of the advantages. In addition, patient-specific implants eliminate the need for a separate donor site. Apart from the treatment of pathologies, they also can be used for reconstruction of post-traumatic defect, where endosteal implant placement is not possible., Conclusion: These modalities show promising results for reconstruction of complex maxillary defects., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2023.)

Introduction: Recent research has indicated an association between both poverty and income inequality and firearm homicides. Increased minimum wages may serve as a strategy for reducing firearm violence by increasing economic security among workers earning low wages and reducing the number of families living in poverty. This study aimed to examine the association between state minimum wage and firearm homicides in the U.S. between 2000 and 2020., Methods: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualized using the Kaitz Index. State-level homicide counts were obtained from 2000 to 2020 multiple-cause-of death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm homicides, stratifying by demographic groups. Analyses were conducted in 2023., Results: A 1% point increase in a state's Kaitz Index was associated with a 1.3% (95% CI: -2.1% to -0.5%) decrease in a state's firearm homicide rate. When interacted with quartile of firearm ownership, the Kaitz Index was associated with decreases in firearm homicide in all except the lowest quartile. These findings were largely consistent across stratifications., Conclusions: Changing a state's minimum wage, whereby a full-time minimum wage worker's salary is closer to a state's median income, may be an option for reducing firearm homicides., (Published by Elsevier Inc.)

Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs., Competing Interests: Competing interests: D.R.L. consults and has equity interest in Vedanta, Immunai, Imidomics, Sonoma Biotherapeutics and Pfizer Pharmaceuticals. M.A.F. is a co-founder of Kelonia and Revolution Medicines, a member of the scientific advisory boards of the Chan Zuckerberg Initiative, Stand Up to Cancer, NGM Biopharmaceuticals, and TCG Labs/Soleil Labs, and an innovation partner at The Column Group. The remaining authors have no conflict of interest.

Ecosystems that offer carbon sequestration by leaching bicarbonate to groundwater are valuable natural capital. One region that may offer this service is the west coast of South Africa. Over 20 % is covered by soil mounds ("heuweltjies") up to 40 m diameter, 2 m high, inhabited by the southern harvester termite Microhodotermes viator and enriched in soil organic and inorganic carbon and soluble minerals. We aimed to generate radiogenic and stable isotope data for soils and groundwater in a region where these data are absent, to 1) verify the atmosphere-soil-groundwater link, and 2) resolve the timing and pattern of calcite dissolution and water infiltration in the landscape. Results show that soil and groundwater sulfate have the same marine aerosol source. Episodic calcite dissolution in mound centers, which increased during periods of global cooling, has been set against background input of marine aerosols since before the Last Glacial according to radiocarbon ( 14 C) ages. Our data push back soil organic carbon 14 C ages of inhabited termite mounds to 13-19 ka (kiloannum, thousand years before present), nest carbonate 14 C ages to 33 ka, and mound soil carbonate 14 C ages to 34 ka, making these the oldest active termite features ever dated. These ages are consistent with soil organic carbon and carbonate 14 C ages of regional, non-mound, coastal petrocalcic horizons formed by accumulation of carbonate leached from their overlying aeolian dune fields. Harvesting activities of termites inject younger organic material around nests >1 m deep, leading to continuous renewal of important soil carbon reservoirs at depth. Termite bioturbation increases the system's ability to dissolve carbonate. The central, bioturbated part of the mounds have greater infiltration depths and greater calcite dissolution, whereas surrounding soils experienced more surface runoff. Calcareous termite mounds offer a mechanism to sequester CO 2 through dissolution and leaching of soil carbonate-bicarbonate to groundwater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the limits of spatiotemporal carrier dynamics, especially in III-V semiconductors, is key to designing ultrafast and ultrasmall optoelectronic components. However, identifying such limits and the properties controlling them has been elusive. Here, using scanning ultrafast electron microscopy, in bulk n-GaAs and p-InAs, we simultaneously measure picosecond carrier dynamics along with three related quantities: subsurface band bending, above-surface vacuum potentials, and surface trap densities. We make two unexpected observations. First, we uncover a negative-time contrast in secondary electrons resulting from an interplay among these quantities. Second, despite dopant concentrations and surface state densities differing by many orders of magnitude between the two materials, their carrier dynamics, measured by photoexcited band bending and filling of surface states, occur at a seemingly common timescale of about 100 ps. This observation may indicate fundamental kinetic limits tied to a multitude of material and surface properties of optoelectronic III-V semiconductors and highlights the need for techniques that simultaneously measure electro-optical kinetic properties.

Background: Chronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa., Methods: Between November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment., Results: Of 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, p<0.001) among participants with chronic myocardial injury than those with undetectable cTnT values., Conclusion: In Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Julian Hertz’s institution, Duke University School of Medicine, received a research grant from Roche Diagnostics. Zak Loring’s institution, Duke University School of Medicine, received grant support from Huxley Medical and Boston Scientific for unrelated research projects in which he serves as an investigator. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Rahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mycorrhizal symbioses between plants and fungi are vital for the soil structure, nutrient cycling, plant diversity, and ecosystem sustainability. More than 250 000 plant species are associated with mycorrhizal fungi. Recent advances in genomics and related approaches have revolutionized our understanding of the biology and ecology of mycorrhizal associations. The genomes of 250+ mycorrhizal fungi have been released and hundreds of genes that play pivotal roles in regulating symbiosis development and metabolism have been characterized. rDNA metabarcoding and metatranscriptomics provide novel insights into the ecological cues driving mycorrhizal communities and functions expressed by these associations, linking genes to ecological traits such as nutrient acquisition and soil organic matter decomposition. Here, we review genomic studies that have revealed genes involved in nutrient uptake and symbiosis development, and discuss adaptations that are fundamental to the evolution of mycorrhizal lifestyles. We also evaluated the ecosystem services provided by mycorrhizal networks and discuss how mycorrhizal symbioses hold promise for sustainable agriculture and forestry by enhancing nutrient acquisition and stress tolerance. Overall, unraveling the intricate dynamics of mycorrhizal symbioses is paramount for promoting ecological sustainability and addressing current pressing environmental concerns. This review ends with major frontiers for further research., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated the potential of Ki-67 index as a surrogate of tumor grade. We also compared the predictability of mitoses and Ki-67 index for overall survival (OS). Ninety-six PEM samples from 85 patients were identified from the surgical pathology file during 2000-2021 at our institution, and all glass slides were reviewed by 2 pulmonary pathologists to confirm the diagnosis and assign the tumor grade. Digital image analysis (DIA) was done for Ki-67 index. The agreement on tumor grading between 2 reviewers was moderate (kappa value = 0.47). The correlation between mitotic count (average count by 2 reviewers) and Ki-67 index was 0.65. The areas under the curve for predicting tumor grade by mitotic score and Ki-67 index were 0.84 and 0.74 (reviewer 1) and 0.85 and 0.81 (reviewer 2), respectively. High Ki-67 index and mitoses were significantly associated with poor OS ( P =0.03 and 0.0005, using 30% and 10/2 mm 2 as cutoffs, respectively). In conclusion, Ki-67 index by DIA was associated with tumor grade as well as mitotic count, and its predictability for OS was comparable to that of mitotic score, thus being a potential surrogate for tumor grade., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To determine the contributions of different durations of hypoxia to NLRP3 inflammasome activation in urothelial cells and how ischemic changes in bladder tissues is an important chemical que that leads to pathological changes seen in BOO., Methods: A rat urothelial cell line (MYP3) was exposed to either a short duration (2 h) or long duration (6 h) of enzyme-induced hypoxia. Following exposure to a short duration of hypoxia, NO and ATP concentrations were measured from supernatant media and caspase-1 levels were measured from cell lysates. In a separate experiment, cells were fixed following hypoxia exposure and immunostained for HIF-1α stabilization., Results: Although short exposure of low oxygen conditions resulted in a hypoxic response in MYP3 cells, as indicated by HIF-1α stabilization and increased NO activity, NLRP3 inflammasome activation was not observed as caspase-1 activity remained unchanged. However, exposure of MYP3 cells to a longer duration of hypoxia resulted in an increase in intracellular caspase-1 activity. Furthermore, treatment with antioxidant (GSH) or TXNIP inhibitor (verapamil) attenuated the hypoxia-induced increase in caspase-1 levels indicating that hypoxia primarily drives inflammation through a ROS-mediated TXNIP/NLRP3 pathway., Conclusion: We conclude that hypoxia induced bladder damage requires a duration that is more likely related to elevated storage pressures/hypoxia, seen in later stages of BOO, as compared to shorter duration pressure elevation/hypoxia that is encountered in normal micturition cycles or early in the BOO pathology where storage pressures are still normal., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Severe maternal morbidity (SMM) has disproportionate frequencies among racial minorities and those of socioeconomic disadvantage, with people of Black race consistently having the highest proportion. Neighborhood level deprivation has been associated with maternal morbidity and mortality, including adverse pregnancy outcomes. We sought to explore the relationship between neighborhood socioeconomic disadvantage and SMM and describe how neighborhood context impacts the relationship between race and SMM., Study Design: We performed a retrospective cohort analysis of all delivery admissions in a single health care network from 2015 to 2019. Area deprivation index (ADI) was used to represent neighborhood socioeconomic disadvantage and is a composite index of neighborhood that spans income, education, household characteristics, and housing. The index ranges from 1 to 100 with higher values indicating higher disadvantage. Logistic regression assessed the relationship between ADI and SMM and estimated the effect that ADI has on the relationship between race and SMM., Results: Of the 63,208 birthing persons in our cohort, the unadjusted incidence of SMM was 2.2%. ADI was significantly associated with SMM, with higher values conferring higher risk for SMM ( p  < 0.001). The absolute risk of SMM increased roughly by 1.0% from the lowest to highest ADI value. Those of Black race had the highest unadjusted incidence of SMM compared with the referent group (3.4 vs. 2.0%) and highest median ADI (92; interquartile range [IQR]: 20). In the multivariable model, in which the primary exposure was race and ADI was adjusted for, Black race had a 1.7 times odds SMM when compared with White race (95% confidence interval [CI]: 1.5-1.9). This association was attenuated to 1.5 adjusted odds when controlling for ADI (95% CI: 1.3-1.7). Risk attenuation for SMM was not seen in other race categories., Conclusion: Neighborhood context contributes to SMM but does not explain the majority of racial disparities., Key Points: · Neighborhood context is associated with SMM, with higher disadvantage conferring higher risk.. · Compared with White race, all other races had higher rates of SMM, with Black race having the highest.. · Accounting for neighborhood modestly attenuates the magnitude of association of Black race with SMM.. · Neighborhood context contributes to health outcomes but does not explain the majority of disparities.., Competing Interests: H.N.S. reports grants from the NIH, CDC, and Gates Foundations, royalties or licenses from Uptodate, consulting fees from Organon, and is a founder of Naima Health LLC., (Thieme. All rights reserved.)