Search

Novel host plants are incorporated into the diets of phytophagous insects when females oviposit and juveniles feed and survive on them. A change in diet, however, can have morphological consequences. We recently found a population of the leaf-footed cactus bug, Narnia femorata (Hemiptera: Coreidae), a historical cactus specialist, living and feeding on Cirsium thistle. We also found adults breeding and males using their enlarged hind legs (i.e., weapons) in male-male combat on thistle. When we compared this thistle population with a population feeding on cactus, we found that both populations had similar body and weapon sizes as well as weapon composition. However, the population living on thistle had longer mouthparts than the population found on cactus, although this difference only occurred at larger body sizes. This difference in adult mouthpart size is likely a result of the juvenile rearing environment (i.e., thistle or cactus). However, genetic differences may also affect this trait. Our results provide some interesting avenues for future research (e.g., a reciprocal transplant experiment) in a species with a recent host range expansion., Competing Interests: None., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

The structured professional judgement (SPJ) approach was initially developed to support risk assessment and management decisions. The approach is now being adapted and applied to admission assessments for adult secure services. This systematic review aims to summarise the evidence for the effectiveness and acceptability of the SPJ approach in admission assessments of this kind. A comprehensive electronic search strategy was used to identify studies indexed in PubMed, PsycInfo, Medline and Cochrane Library (January 2007 -January 2024). Two search strategies included terms (and synonyms) for psychiatric patients (quantitative) or clinicians and clinicians' experiences (qualitative), structured professional judgement, admission, and secure services. Twelve quantitative articles (published 2007-2020) were identified. SPJ-informed guidance included were the DUNDRUM-1, DUNDRUM-2, DUNDRUM-3, DUNDRUM-4, and the HCR-20. While findings were variable, the overall pattern indicated that ratings suggestive of more problems were associated with increased likelihood of admission or movement to higher security levels. There is emerging evidence for the use of SPJ guidance to support admission decision-making. Specifically, it should be used as an adjunct to existing decision-making processes rather than as a replacement for those processes. Further research, both quantitative and qualitative, across a wider range of settings and populations is recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bowden 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.)

The ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology, and variant interpretation. This VCEP made specifications for the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines for the ataxia telangiectasia mutated (ATM) gene according to the ClinGen protocol. These gene-specific rules for ATM were modified from the ACMG/AMP guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar, and re-evaluation with the VCEP's ATM-specific rules resulted in four that were classified as benign, one as likely pathogenic, and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 of the 33 pilot variants were not VUS, leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM., Competing Interests: Declaration of interests M.J.A. was a paid employee of Invitae. M.E.R., T.B., T.P., and C.C.Y. were paid employees of Ambry Genetics. L.Z. was a paid employee of Natera. S.H. was a paid employee of GeneDx., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The ENIGMA research consortium develops and applies methods to determine clinical significance of variants in hereditary breast and ovarian cancer genes. An ENIGMA BRCA1/2 classification sub-group, formed in 2015 as a ClinGen external expert panel, evolved into a ClinGen internal Variant Curation Expert Panel (VCEP) to align with Food and Drug Administration recognized processes for ClinVar contributions. The VCEP reviewed American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) classification criteria for relevance to interpreting BRCA1 and BRCA2 variants. Statistical methods were used to calibrate evidence strength for different data types. Pilot specifications were tested on 40 variants and documentation revised for clarity and ease of use. The original criterion descriptions for 13 evidence codes were considered non-applicable or overlapping with other criteria. Scenario of use was extended or re-purposed for eight codes. Extensive analysis and/or data review informed specification descriptions and weights for all codes. Specifications were applied to pilot variants with pre-existing ClinVar classification as follows: 13 uncertain significance or conflicting, 14 pathogenic and/or likely pathogenic, and 13 benign and/or likely benign. Review resolved classification for 11/13 uncertain significance or conflicting variants and retained or improved confidence in classification for the remaining variants. Alignment of pre-existing ENIGMA research classification processes with ACMG/AMP classification guidelines highlighted several gaps in the research processes and the baseline ACMG/AMP criteria. Calibration of evidence strength was key to justify utility and strength of different data types for gene-specific application. The gene-specific criteria demonstrated value for improving ACMG/AMP-aligned classification of BRCA1 and BRCA2 variants., Competing Interests: Declaration of interests M.A. was a paid employee of Invitae. R.C.C. and R.O. are paid employees of Color Health. M.E.R., T.P., and R.K. are paid employees of Ambry Genetics. A.R.M. and M.J.V. received funds from AstraZeneca for contribution to sponsored quality assessments and variant interpretation of BRCA1 and BRCA2 VUS (funds paid to the institution)., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections., Methods: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed., Results: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004)., Conclusions: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: The authors do not declare conflicts of interest related to the submitted manuscript. The funder of the study (Scynexis) had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The acquisition or reactivation of Epstein-Barr virus (EBV) after allogeneic Hematopoietic Stem Cell Transplant (HSCT) can be associated with complications including the development of post-transplant lymphoproliferative disorder (PTLD), which is associated with significant morbidity and mortality. A number of risk factors for PTLD have been defined, including T-cell depletion, and approaches to monitoring EBV, especially in high-risk patients, with the use of preemptive therapy upon viral activation have been described. Newer therapies for the preemption or treatment of PTLD, such as EBV-specific cytotoxic T-cells, hold promise. Further studies to help define risks, diagnosis, and treatment of EBV-related complications are needed in this at-risk population.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2 nd most accurate model measured by WIS in 2021-22 and the 5 th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Cardiothoracic surgical trainees perceive a need for more instruction and exposure to robotic-assisted thoracoscopic surgery during their training. We sought to assess use and trainee exposure to robotic surgery in thoracic residency programs to identify areas for improvement., Methods: A voluntary electronic survey of 10 questions was distributed to surgeons working in all thoracic surgery residency programs in the United States. The survey asked respondents to provide the size of the residency, the availability and use of robots, and the trainee's adoption of robotic surgery in their practice after graduation. Multivariable logistic regression was performed., Results: Of a total of 76 cardiothoracic surgery training programs, surgeons from 69 training programs (90.8%) completed the survey. Most pulmonary lobectomy was performed using robotic surgery (55%). Approximately half of the training programs (35 of 69) have a formal robotic curriculum for the residents. Of 121 thoracic track trainees, 118 (97.5%) performed robotic surgery as part of their practice, whereas 62 of 110 (56.4%) cardiothoracic track and 16 of 158 (10.1%) cardiac track trainees performed robotic surgery. In a multivariate analysis, the adoption of robotic surgery was associated with having an established robotic training curriculum (odds ratio, 5.82; 95% CI, 1.32-35.7) and a larger training program (odds ratio, 3.78; 95% CI, 1.34-10.6)., Conclusions: A disparity exists in robotic surgical training among the training programs. A standardized curriculum and formal case requirements may be needed to ensure optimal preparation for future graduates., Competing Interests: Disclosures Samuel Kim reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees and with Intuitive Foundation that includes: speaking. Brian Mitzman reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees. Natalie Lui reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees; and with Centese that includes: research support. Natalie S. Lui and Samuel S. Kim disclose research support from the Intuitive Foundation. Stephen Yang reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees. Manu Sancheti reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees. Desmond D’Souza reports a relationship with Intuitive Surgical Inc that includes: speaking and lecture fees. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A detailed understanding of the binding of serum proteins to small ( d core <10 nm) nanoparticles (NPs) is essential for the mediation of protein corona formation in next generation nanotherapeutics. While a number of studies have investigated the details of protein adsorption on large functionalized NPs, small NPs (with a particle surface area comparable in size to the protein) have not received extensive study. This study determined the affinity constant ( K a values at 25 °C for MHA, MEEE, and MPTMA-AuNPs were 5.2 ± 0.2 × 10 K a for BSA, indicating that electrostatic interactions are likely not the primary driving force in binding of BSA to these small AuNPs. K a values at 25 °C for MHA, MEEE, and MPTMA-AuNPs were 5.2 ± 0.2 × 10 7 , 3.7 ± 0.2 × 10 7 , and 3.3 ± 0.16 × 10 7 M -1 in water, respectively. Fluorescence quenching titrations performed in 100 mM NaCl resulted in lower K a values for the charged AuNPs, while the K a value for the MEEE-AuNPs remained unchanged. Measurement of the hydrodynamic diameter ( D h ) by dynamic light scattering (DLS) suggests that adsorption of 1-2 BSA molecules is sufficient to saturate the AuNP surface. DLS and negative-stain TEM images indicate that, despite the lower observed K a values, the binding of MPTMA-AuNPs to BSA likely induces significant protein misfolding and may lead to extensive BSA aggregation at specific BSA:AuNP molar ratios.

The animal gut acts as a potent reservoir for spreading and maintaining conjugative plasmids that confer antimicrobial resistance (AMR), fitness, and virulence attributes. Interventions that inhibit the continued emergence and expansion of AMR and virulent strains in agricultural and clinical environments are greatly desired. This study aims to determine the presence and efficacy of short-chain fatty acids (SCFA) inhibitory effects on the conjugal transfer of AMR plasmids. In vitro broth conjugations were conducted between donor Escherichia coli strains carrying AMP plasmids and the plasmid-less Escherichia coli HS-4 recipient strain. Conjugations were supplemented with ddH 2 O or SCFAs at 1, 0.1, 0.01, or 0.001 molar final concentration. The addition of SCFAs completely inhibited plasmid transfer at 1 and 0.1 molar and significantly ( p  < 0.05) reduced transfer at 0.01 molar, regardless of SCFA tested. In explant models for the chicken ceca, either ddH 2 O or a final concentration of 0.025 M SCFAs were supplemented to the explants infected with donor and recipient E. coli . In every SCFA tested, significant decreases in transconjugant populations compared to ddH 2 O-treated control samples were observed with minimal effects on donor and recipient populations. Finally, significant reductions in transconjugants for plasmids of each incompatibility type (IncP1ε, IncFIβ, and IncI1) tested were detected. This study demonstrates for the first time the broad inhibition ability of SCFAs on bacterial plasmid transfer and eliminates AMR with minimal effect on bacteria. Implementing interventions that increase the concentrations of SCFAs in the gut may be a viable method to reduce the risk, incidence, and rate of AMR emergence in agricultural and human environments., Competing Interests: LCO and MM are listed as inventors on a pending patent covering research presented in this paper. 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 Ott and Mellata.)

Introduction: There is an increasing incidence of hip and pelvic fractures with an ageing population. Accurate and timely diagnosis is important in the emergency setting. While magnetic resonance imaging (MRI) is the gold standard, it is a limited resource. Dual energy CT (DECT) is comparable to MRI in detection of bone marrow oedema. Our hospital was the first centre in our country to introduce DECT for occult pelvic fractures. We aimed to describe its utility in occult pelvic fractures since commencement., Methods: Retrospective study of consecutive pelvic bone CT (conventional or DECT) performed to look for an occult fracture over a 10-month period. Sensitivity and specificity calculated based on clinical and imaging follow-up. ROC study performed where three observers visually interpreted pelvic radiographs, conventional CT and DECT and scored their confidence for an acute fracture from 1 to 5. The null hypothesis was that DECT would not improve observer performance compared with conventional CT., Results: DECT studies were performed on 178 patients of whom 84 (47%) had acute fractures. Sensitivity on audit was 99% and specificity was 100%. ROC analysis showed that, for all observers, the area under curve increased from radiograph to conventional CT to DECT. The difference between conventional CT and DECT was statistically significant for all observers where metal implants were not present., Conclusion: DECT improves accuracy compared to conventional CT in the diagnosis of occult pelvic fractures and should be used for this indication when available., (© 2024 Royal Australian and New Zealand College of Radiologists.)

The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology and variant interpretation. This VCEP made specifications for ACMG/AMP guidelines for the ataxia telangiectasia mutated ( ATM ) gene according to the Food and Drug Administration (FDA)-approved ClinGen protocol. These gene-specific rules for ATM were modified from the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar and reevaluation with the VCEP's ATM -specific rules resulted in four that were classified as benign, one as likely pathogenic and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 the 33 pilot variants were not VUS leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM ., Competing Interests: Declaration of Interests MA and SN were a paid employee of Invitae. MER, TB, TP, CCY, and were paid employees of Ambry Genetics. LZ was a paid employee of Natera. SH was a paid employee of GeneDx.

Chronic stress undermines psychological and physiological health. We tested three remotely delivered stress management interventions among clergy, accounting for intervention preferences. United Methodist clergy in North Carolina enrolled in a partially randomized, preference-based waitlist control trial. The interventions were: mindfulness-based stress reduction (MBSR), Daily Examen prayer practice, and Stress Proofing (stress inoculation plus breathing skills). Co-primary outcomes were symptoms of stress (Calgary Symptoms of Stress Inventory) and 48-hour ambulatory heart rate variability (HRV) at 12 weeks compared to waitlist control. Survey data were collected at 0, 12, and 24 weeks and 48-hour ambulatory HRV at 0 and 12 weeks. The 255 participants were 91% White and 48% female. Forty-nine participants (22%) without a preference were randomly assigned between the three interventions (n = 40) and waitlist control (n = 9). Two hundred six participants (78%) with a preference were randomly assigned to waitlist control (n = 62) or their preferred intervention (n = 144). Compared to waitlist control, MBSR [mean difference (MD) = -0.30, 95% CI: -0.41, -0.20; P < .001] and Stress Proofing (MD = -0.27, 95% CI: -0.40, -0.14; P < .001) participants had lower stress symptoms at 12 weeks; Daily Examen participants did not until 24 weeks (MD = -0.24, 95% CI: -0.41, -0.08). MBSR participants demonstrated improvement in HRV at 12 weeks (MD = +3.32 ms; 95% CI: 0.21, 6.44; P = .036). MBSR demonstrated robust improvement in self-reported and objective physical correlates of stress; Stress Proofing and Daily Examen resulted in improvements in self-reported correlates of stress. These brief practices were sustainable and beneficial for United Methodist clergy during the heightened stressors of the COVID pandemic. ClinicalTrials.gov identifier: NCT04625777., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

We examined associations between prenatal fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM 2.5 exposure modestly increased risk of current asthma (RR adj  = 1.15, 95% CI: 0.88-1.51); canalicular PM 2.5 exposure modestly increased risk of asthma with recent exacerbation (RR adj  = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (OR adj  = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O 3 , but not NO 2 , and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Extracorporeal life support (ECLS) serves as a rescue therapy for patients with congenital diaphragmatic hernia (CDH) and severe cardiopulmonary failure, and only half of these patients survive to discharge. This costly intervention has a significant complication risk and is reserved for patients with the most severe disease physiology refractory to maximal cardiopulmonary support. Some contraindications to ECLS do exist such as coagulopathy, lethal chromosomal or congenital anomaly, very preterm birth, or very low birth weight, but many of these limits are being evaluated through further research. Consensus guidelines from the past decade vary in recommendations for ECLS use in patients with CDH but this therapy appears to have a survival benefit in the most severe subset of patients. Improved outcomes have been observed for patients treated at high-volume centers. This review details the evolving literature surrounding management paradigms for timing of CDH repair for patients receiving preoperative ECLS. Most recent data support early repair following cannulation to avoid non-repair which is uniformly fatal in this population. Longer ECLS runs are associated with decreased survival, and patient physiology should guide ECLS weaning and eventual decannulation rather than limiting patients to arbitrary run lengths. Standardization of care across centers is a major focus to limit unnecessary costs and improve short-term and long-term outcomes for these complex patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the US, yersinosis was understood to predominantly occur in winter and among Black or African American infants and Asian children. Increased use of culture-independent diagnostic tests (CIDTs) has led to marked increases in yersinosis diagnoses., Methods: We describe differences in the epidemiology of yersiniosis diagnosed by CIDT versus culture in 10 US sites, and identify determinants of health associated with diagnostic method., Results: Annual reported incidence increased from 0.3/100 000 in 2010 to 1.3/100 000 in 2021, particularly among adults ≥18 years, regardless of race and ethnicity, and during summer months. The proportion of CIDT-diagnosed infections increased from 3% in 2012 to 89% in 2021. An ill person's demographic characteristics and location of residence had a significant impact on their odds of being diagnosed by CIDT., Conclusions: Improved detection due to increased CIDT use has altered our understanding of yersinosis epidemiology, however differential access to CIDTs may still affect our understanding of yersinosis., Competing Interests: Potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1 + ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants., Competing Interests: Declaration of interests E.J.B. and S.G.G. are scientific cofounders at Tellus Therapeutics—a startup company developing therapies for neonatal brain injury. There is no intellectual property associated with this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing epithelial tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth. Our model incorporates probabilistic rules governing cell growth, division, and elimination, also taking into account their feedback with tissue mechanics. In particular, cell growth is suppressed and apoptosis is enhanced in regions of high cell density. With these rules and model parameters calibrated using experimental data for epithelial monolayers, we predict how tissue confinement influences cell size and proliferation dynamics and how single-cell physical properties influence the spatiotemporal patterns of tissue growth. In this model, mechanical feedback between tissue confinement and cell growth leads to enhanced cell proliferation at tissue boundaries, whereas cell growth in the bulk is arrested, recapitulating experimental observations in epithelial tissues. By tuning cellular elasticity and contact inhibition of proliferation we can regulate the emergent patterns of cell proliferation, ranging from uniform growth at low contact inhibition to localized growth at higher contact inhibition. We show that the cell size threshold at G1/S transition governs the homeostatic cell density and tissue turnover rate, whereas the mechanical state of the tissue governs the dynamics of tissue growth. In particular, we find that the cellular parameters affecting tissue pressure play a significant role in determining the overall growth rate. Our computational study thus underscores the impact of cell mechanical properties on the spatiotemporal patterns of cell proliferation in growing epithelial tissues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine the clinical results of carpal tunnel release using ultrasound guidance (CTR-US) at a minimum of 2 years postprocedure., Methods: The study consisted of 102 patients (162 hands) treated with CTR-US by the same physician between June 2017 and October 2020 for whom minimum 2-year follow-up data were available. Questionnaires were sent to gather long-term information, with additional phone calls for clarification if needed. Outcomes included Boston Carpal Tunnel Questionnaire symptom severity (BCTQ-SSS) and functional status (BCTQ-FSS) scores; Quick Disabilities of the Arm, Shoulder, and Hand ( Quick DASH) scores; global satisfaction scores; and subsequent surgeries., Results: The 102 patients included 68 females and 34 males with a mean age of 56.9 years at the time of surgery. Fifty-five (53.9%) patients had simultaneous bilateral procedures, 42 (41.2%) had unilateral procedures, and 5 (4.9%) had staged bilateral procedures. Significant improvements in BCTQ-SSS, BCTQ-FSS, and Quick DASH scores persisted at a mean final follow-up of 46 months (range 2-6 years). At final follow-up, 91.2% of patients reported satisfaction with the procedure. No outcomes were significantly different between those treated with simultaneous bilateral versus unilateral procedures. No revision surgeries were reported., Conclusions: CTR-US is a safe and effective procedure that results in significant improvements that persist up to 6 years postprocedure. Long-term results of simultaneous bilateral and unilateral procedures are similar., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: No benefits in any form have been received or will be received related directly to this article., (© 2024 The Authors.)

Abstract: Mass participation events include endurance events (e.g., marathon, triathlon) and/or competitive tournaments (e.g., baseball, tennis, football (soccer) tournaments). Event management requires medical administrative and participant care planning. Medical management provides safety advice and care at the event that accounts for large numbers of participants, anticipated injury and illness, variable environment, repeated games or matches, and mixed age groups of varying athletic ability. This document does not pertain to the care of the spectator., (Copyright © 2023 by the American College of Sports Medicine.)

Abstract: Mass participation events include endurance events (e.g., marathon, triathlon) and/or competitive tournaments (e.g., baseball, tennis, football (soccer) tournaments). Event management requires medical administrative and participant care planning. Medical management provides safety advice and care at the event that accounts for large numbers of participants, anticipated injury and illness, variable environment, repeated games or matches, and mixed age groups of varying athletic ability. This document does not pertain to the care of the spectator., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Nontyphoidal Salmonella causes an estimated 1.35 million US infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death., Methods: We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004 to 2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all 5 agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source., Results: Twenty percent of isolates (1105/5549) had any resistance, and 16% (469/2969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs 28%, P = .01) or have length-of-stay ≥3 days (20% vs 16%, P = .01). Deaths were rare but more common among those with any than no resistance (1.0% vs 0.4%, P = .01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04-1.46) remained significantly associated with hospitalization., Conclusions: We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (eg, strain virulence, strain source, host factors) may be important., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background and Aim: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium., Methods: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression., Results: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant., Conclusions: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls., (© 2024. The Author(s).)

Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp., including against frequently multidrug-resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance end points as a marker of success., Competing Interests: Potential conflicts of interest. R.B. has participated in educational activities (lectures, webinars) for Gilead and Teva and advisory boards for MSD and GSK. T.B. has participated in advisory boards for and received speaker fees from Gilead, Pfizer, and Mundipharma and received research funding from MSD, Gilead, and Pfizer. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Modifiable risk factors account for a substantial proportion of Alzheimer's disease (AD) cases and we currently have a discrete AT(N) biomarker profile for AD biomarkers: amyloid (A), p-tau (T), and neurodegeneration (N). Here, we investigated how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD., Methods: Participants from the European Prevention of Alzheimer's Dementia (EPAD) study underwent clinical assessments, brain magnetic resonance imaging, and cerebrospinal fluid collection and analysis. Generalized additive models (GAMs) with penalized regression splines were modeled in the AD Workbench on the NTKApp., Results: A total of 1,434 participants were included (56% women, 39% APOE ε4+) with an average age of 65.5 (± 7.2) years. We found that modifiable risk factors of less education ( t = 3.9, p < 0.001), less exercise ( t = 2.1, p = 0.034), traumatic brain injury ( t = -2.1, p = 0.036), and higher body mass index ( t = -4.5, p < 0.001) were all significantly associated with higher AD biomarker burden., Discussion: This cross-sectional study provides further support for modifiable risk factors displaying neuroprotective associations with the characteristic AT(N) biomarkers of AD., Competing Interests: MC is a full-time employee of Roche Diagnostics International Ltd, Rotkreuz, Switzerland and holds shares in F. Hoffman-La Roche. CL is a full-time employee of Roche Diagnostics GmbH, Penzberg, Germany. ELECSYS is a trademark of Roche. The remaining 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 Roccati, Bindoff, Collins, Eastgate, Borchard, Alty, King, Vickers, Carboni and Logan.)

Chitosan-based bioplastics are attractive biodegradable alternatives to petroleum-derived plastics. However, optimizing the properties of chitosan materials to fit a particular application or obtain a desired property is not a trivial feat. Here, we report the tunability of glycerol-plasticized chitosan films with the addition of boric acid. In combination, glycerol and boric acid form neutral complexes that alter the hydrogen-bonding face of the plasticizer and ultimately limit glycerol's ability to plasticize chitosan. Thus, we found that chitosan films containing glycerol-boric acid complexes were less flexible, had increased thermal transition temperatures, and showed more uniform morphologies. Structural, thermal, mechanical and morphological characterization was performed using ATR-FTIR, TGA and DSC, DMA, and SEM respectively. Molecular-level interactions of the neutral boron complexes and D-glucosamine, the repeat unit of chitosan, were also investigated used NMR and ATR-FTIR. The results of this work demonstrate the necessity of specific hydrogen-bonding interactions between the plasticizer and the polymer for effective plasticization, an important insight into the plasticization mechanism of chitosan films. Furthermore, the formation of complexes with glycerol is a novel and convenient method for tuning the physical properties of chitosan films., 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 B.V. All rights reserved.)

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins. ZCCHC17 knockdown results in widespread RNA-splicing changes that significantly overlap with splicing changes found in AD brain tissue, with synaptic genes commonly affected. ZCCHC17 expression correlates with cognitive resilience in AD patients, and we uncover an APOE4-dependent negative correlation of ZCCHC17 expression with tangle burden. Furthermore, a majority of ZCCHC17 interactors also co-IP with known tau interactors, and we find a significant overlap between alternatively spliced genes in ZCCHC17 knockdown and tau overexpression neurons. These results demonstrate ZCCHC17's role in neuronal RNA processing and its interaction with pathology and cognitive resilience in AD, and suggest that the maintenance of ZCCHC17 function may be a therapeutic strategy for preserving cognitive function in the setting of AD pathology., (Copyright © 2024 the authors.)

Background: Ozone (O 3 ) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O 3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups., Methods: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O 3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV 1 ) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O 3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization., Results: In our sample (n = 648), O 3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O 3 exposure were observed with either FEV 1 (β = 0.12, 95% CI: -0.04, 0.29) or FVC (β = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O 3 ., Conclusions: In this sample with low O 3 concentrations, we did not observe adverse associations between O 3 exposures averaged from birth to age 8 and lung function in middle childhood., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non-small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments. Herein, we found that phosphorylation of MIG6, encoded by the ERRFI1 gene, was downregulated by ALK/ROS1 inhibitors as were mRNA levels, thus potentiating EGFR activity to support cell survival as an adaptive resistance mechanism. MIG6 downregulation was sustained following chronic exposure to ALK/ROS1 inhibitors to support the establishment of acquired resistance. A higher ratio of EGFR to MIG6 expression was found in ALK TKI-treated and ALK TKI-resistant tumors and correlated with the poor responsiveness to ALK/ROS1 inhibition in patient-derived cell lines. Furthermore, we identified and validated a MIG6 EGFR-binding domain truncation mutation in mediating resistance to ROS1 inhibitors but sensitivity to EGFR inhibitors. A MIG6 deletion was also found in a patient after progressing to ROS1 inhibition. Collectively, this study identifies MIG6 as a novel regulator for EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibitors and suggests EGFR to MIG6 ratios and MIG6-damaging alterations as biomarkers to predict responsiveness to ALK/ROS1 and EGFR inhibitors., (©2023 The Authors; Published by the American Association for Cancer Research.)

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups., 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.

Background: Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies., Methods: Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George's Hospital, London, UK, during the first UK pandemic wave (1 st March-10 th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection., Results: Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1-2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4-7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26-1.18)., Conclusions: Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19., (© 2023. The Author(s).)

Background: The vast majority of patients with ROS1 positive non-small cell lung cancer (NSCLC) derive clinical benefit from currently approved ROS1 therapies, including crizotinib and entrectinib. However, a small proportion of patients treated with ROS1 inhibitors fail to derive any clinical benefit and demonstrate rapid disease progression. The biological mechanisms underpinning intrinsic resistance remain poorly understood for oncogene-driven cancers., Methods: We generated a patient-derived cell line, CUTO33, from a ROS1 therapy naive patient with CD74-ROS1+ NSCLC, who ultimately did not respond to a ROS1 inhibitor. We evaluated a panel of ROS1+ patient-derived NSCLC cell lines and used cell-based assays to determine the mechanism of intrinsic resistance to ROS1 therapy., Results: The CUTO33 cell line expressed the CD74-ROS1 gene fusion at the RNA and protein level. The ROS1 fusion protein was phosphorylated at baseline consistent with the known intrinsic activity of this oncogene. ROS1 phosphorylation could be inhibited using a wide array of ROS1 inhibitors, however these inhibitors did not block cell proliferation, confirming intrinsic resistance in this model and consistent with the patient's lack of response to a ROS1 inhibitor. CUTO33 expressed high levels of AXL, which has been associated with drug resistance. Combination of an AXL inhibitor or AXL knockdown with a ROS1 inhibitor partially reversed resistance., Conclusions: In summary, we demonstrate that AXL overexpression is a mechanism of intrinsic resistance to ROS1 inhibitors., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approval by the FDA, tianeptine has been distributed online and at small retail locations. The term "gas station drugs" refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as "Zaza" and "Tianna Red." It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances., (© 2023. The Author(s).)

Purpose of Review: Our aim is to review recent literature on antibiotic use in patients with neutropenia., Recent Findings: Prophylactic antibiotics are associated with risks and have limited mortality benefit. While early antibiotic use in febrile neutropenia (FN) is critical, early de-escalation or discontinuation may be safe in many patients., Summary: With an increasing understanding of potential risks and benefits of use and improved risk assessment, paradigms of antibiotic use in neutropenic patients are changing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The job-demand-control-support model indicates that clergy are at high risk for chronic stress and adverse health outcomes. A multi-group pre-test-post-test design was used to evaluate the feasibility, acceptability, and range of outcome effect sizes for four potentially stress-reducing interventions: stress inoculation training, mindfulness-based stress reduction (MBSR), the Daily Examen, and Centering Prayer. All United Methodist clergy in North Carolina were eligible and recruited via email to attend their preferred intervention. Surveys at 0, 3, and 12 weeks assessed symptoms of stress, anxiety, and perceived stress reactivity. Heart rate variability (HRV) was assessed at baseline and 12 weeks using 24 h ambulatory heart rate monitoring data. A subset of participants completed in-depth interviews and reported skill practice using daily text messages. Standardized mean differences with 95% and 75% confidence intervals were calculated for the change observed in each intervention from baseline to 3 and 12 weeks post-baseline to determine the range of effect sizes likely to be observed in a definitive trial. 71 clergy participated in an intervention. The daily percentage of participants engaging in stress management practices ranged from 47% (MBSR) to 69% (Examen). Results suggest that participation in Daily Examen, stress inoculation, or MBSR interventions could plausibly result in improvement in stress and anxiety at 12 weeks with small-to-large effect sizes. Small effect sizes on change in HRV were plausible for MBSR and Centering Prayer from baseline to 12 weeks. All four interventions were feasible and acceptable, although Centering Prayer had lower enrollment and mixed results., (© 2023. The Author(s).)

Sterile processing department (SPD) technicians are responsible for providing properly reprocessed surgical instruments for procedures. They use utility (ie, tap) water for precleaning, cleaning, and disinfection; and critical (ie, treated to remove impurities) water for the final rinse and steam sterilization. Water maintenance personnel should work with SPD personnel to ensure that the facility's water supply meets the quality parameters for hardness, pH, conductivity, chlorides, bacteria, and endotoxins. Inadequate water quality and quantity can affect SPD technicians' ability to reprocess instruments correctly and may result in pathogen transmission. When water quality concerns arise, SPD personnel should notify perioperative personnel. Health care facilities should have a water management program to address both normal and abnormal water operations and an emergency water supply plan. Pandemics, geopolitical conflicts, and natural disasters may disrupt water supplies. Proactive planning for water shortages should help facility leaders respond quickly and effectively when shortages occur., (© AORN, Inc, 2023.)

Introduction: Gut microbes like segmented filamentous bacteria (SFB) play a key role in gut maturation during early life, as demonstrated in humans and mice. Our previous study demonstrated oral inoculation of ileum-spores containing SFB to chickens after hatch increases early SFB gut colonization, which increases immune maturation and resistance to bacteria, like Salmonella , as tested in vitro ; however, more studies are needed for treatment optimization and in vivo testing. The objectives of this study were to (1) test a treatment that includes both spores and filamentous SFB, (2) validate antimicrobial ability of the treatment in layer hens in vivo, and (3) elucidate its molecular mechanism., Methods: One-day-old specific pathogen-free layers ( n  = 12 per group) were orally treated with either PBS (CON) or SFB-based treatment (SFB). At 4 days post-inoculation (DPI), both CON and SFB groups were orally challenged with Salmonella Typhimurium. Total Enterobacteriaceae and Salmonella were examined by plating and enumeration in feces at 7,10 and 14 dpi; and in the ileum, cecum, and spleen at 16 dpi in euthanized birds. The presence and levels of SFB were determined from ilea scrapings via microscopy and qPCR, respectively. Relative gene expression of host-derived antimicrobial peptides and cytokines in the distal ileum was determined by RT-qPCR., Results: At 10 and 14 dpi, a significant decrease in total Enterobacteriaceae was observed in the feces of the SFB group. At necropsy, the level of SFB was significantly higher in the SFB group than in the CON group, while a significant decrease in total Enterobacteriaceae and Salmonella was observed in the ceca of the SFB group. RT-qPCR revealed increased expression of β -defensin 14, and cytokines IL-10 and IFNγ., Discussion: The introduction of SFB at hatch as a prophylactic treatment may benefit commercial partners as well as consumers by reducing the incidence of Enterobacteriaceae in food animals. Reduction of these bacteria in animals would, in turn, increase animal health, productivity, and safety for consumers. Studies to optimize the treatment for poultry industry applications are ongoing in our lab., 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., (Copyright © 2023 Meinen-Jochum, Ott and Mellata.)

Farmers are continually looking for new, reliable, objective, and non-invasive methods for evaluating the conditions of ewes. Live weight (LW) and body condition score (BCS) are used by farmers as a basis to determine the condition of the animal. Body composition is an important aspect of monitoring animal condition. The body composition is the amount of fat, muscle, and bone; knowing the amount of each is important because the information can be used for better strategic management interventions. Experiments were conducted to establish the relationship between body composition and body parameters at key life stages (weaning and pre-mating), using measurements automatically determined by an image processing application for 88 Coopworth ewes. Computerized tomography technology was used to determine the body composition. Multivariate linear regression (MLR), artificial neural network (ANN), and regression tree (RT) statistical analysis methods were used to develop a relationship between the body parameters and the body composition. A subset of data was used to validate the predicted model. The results showed a correlation between fat, muscle, and bone determined by CT and the fat, muscle, and bone weight estimated by the live weight and body parameters calculated using the image processing application, with r 2 values of 0.90 for fat, 0.72 for muscle, and 0.50 for bone using ANN. From these results, farmers can utilize these measurements to enhance nutritional and management practices.

Background: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time., Methods: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance., Results: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin ( P < .001) and from 2.6% to 3.3% for erythromycin ( P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1)., Conclusions: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) framework for classifying variants uses six evidence categories related to the splicing potential of variants: PVS1, PS3, PP3, BS3, BP4, and BP7. However, the lack of guidance on how to apply such codes has contributed to variation in the specifications developed by different Clinical Genome Resource (ClinGen) Variant Curation Expert Panels. The ClinGen Sequence Variant Interpretation Splicing Subgroup was established to refine recommendations for applying ACMG/AMP codes relating to splicing data and computational predictions. We utilized empirically derived splicing evidence to (1) determine the evidence weighting of splicing-related data and appropriate criteria code selection for general use, (2) outline a process for integrating splicing-related considerations when developing a gene-specific PVS1 decision tree, and (3) exemplify methodology to calibrate splice prediction tools. We propose repurposing the PVS1&#95;Strength code to capture splicing assay data that provide experimental evidence for variants resulting in RNA transcript(s) with loss of function. Conversely, BP7 may be used to capture RNA results demonstrating no splicing impact for intronic and synonymous variants. We propose that the PS3/BS3 codes are applied only for well-established assays that measure functional impact not directly captured by RNA-splicing assays. We recommend the application of PS1 based on similarity of predicted RNA-splicing effects for a variant under assessment in comparison with a known pathogenic variant. The recommendations and approaches for consideration and evaluation of RNA-assay evidence described aim to help standardize variant pathogenicity classification processes when interpreting splicing-based evidence., Competing Interests: Declaration of interests A.L., L.M.V., S.H., H.Z., R.K., D.B.-B., A.C., A.T., and T.P. are employed by fee-for-service laboratories performing clinical sequencing services., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

The U.S. COVID-19 Forecast Hub aggregates forecasts of the short-term burden of COVID-19 in the United States from many contributing teams. We study methods for building an ensemble that combines forecasts from these teams. These experiments have informed the ensemble methods used by the Hub. To be most useful to policymakers, ensemble forecasts must have stable performance in the presence of two key characteristics of the component forecasts: (1) occasional misalignment with the reported data, and (2) instability in the relative performance of component forecasters over time. Our results indicate that in the presence of these challenges, an untrained and robust approach to ensembling using an equally weighted median of all component forecasts is a good choice to support public health decision-makers. In settings where some contributing forecasters have a stable record of good performance, trained ensembles that give those forecasters higher weight can also be helpful., 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., (© 2022 The Authors.)

Objective(s): Letermovir (LET), a novel antiviral, has largely supplanted more traditional preemptive therapy (PET) for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplant (allo-HCT) patients. Use of LET demonstrated efficacy against placebo in phase III randomized controlled trials, but is considerably more expensive than PET. This review aimed to evaluate the real-world effectiveness of LET in preventing clinically significant CMV infection (csCMVi) for allo-HCT recipients and related outcomes., Design: A systematic literature review was performed using an a priori protocol using PubMed, Scopus, and ClinicalTrials.gov from January 2010 to October 2021., Setting and Participants: Studies were included if they met the following criteria: LET compared with PET, CMV-related outcomes, patients aged 18 years or older, and English language-only articles. Descriptive statistics were used to summarize study characteristics and outcomes., Outcome Measures: CMV viremia, csCMVi, CMV end-organ disease, graft-versus-host-disease, all-cause mortality., Results: A total of 233 abstracts were screened, with 30 included in this review. Randomized trials demonstrated efficacy of LET prophylaxis in preventing csCMVi. Observational studies demonstrated varying degrees of effectiveness of LET prophylaxis compared with use of PET alone. All studies with a comparator group resulted in lower rates of csCMVi for patients using LET. Included studies varied widely by CMV viral load threshold cutoff and CMV test units, limiting synthesis of results owing to high heterogeneity., Conclusion: LET reduces risk of csCMVi, but lack of standardized clinical definitions on how to evaluate csCMVi and related outcomes largely prevent synthesis of results. Clinicians must consider this limitation in the context of evaluating the effectiveness of LET to other antiviral therapies, especially for patients at risk of late-onset CMV. Future studies should focus on prospective data collection through registries and concordance of diagnostic definitions to mitigate study heterogeneity., (Copyright © 2023 American Pharmacists Association®. All rights reserved.)

Background: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year., Methods: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models., Results: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma., Conclusion: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Each year, infections from major foodborne pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalizations, and 1,350 deaths in the United States (1). To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites. During 2020-2021, FoodNet detected decreases in many infections that were due to behavioral modifications, public health interventions, and changes in health care-seeking and testing practices during the COVID-19 pandemic. This report presents preliminary estimates of pathogen-specific annual incidences during 2022, compared with average annual incidences during 2016-2018, the reference period for the U.S. Department of Health and Human Services' Healthy People 2030 targets (2). Many pandemic interventions ended by 2022, resulting in a resumption of outbreaks, international travel, and other factors leading to enteric infections. During 2022, annual incidences of illnesses caused by the pathogens Campylobacter, Salmonella, Shigella, and Listeria were similar to average annual incidences during 2016-2018; however, incidences of Shiga toxin-producing Escherichia coli (STEC), Yersinia, Vibrio, and Cyclospora illnesses were higher. Increasing culture-independent diagnostic test (CIDT) usage likely contributed to increased detection by identifying infections that would have remained undetected before widespread CIDT usage. Reducing pathogen contamination during poultry slaughter and processing of leafy greens requires collaboration among food growers and processors, retail stores, restaurants, and regulators., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Elaine Scallan Walter reports consulting fees for a peer review of a Salmonella risk profile for the U.S. Department of Agriculture Food Safety and Inspection Service via RTI International during 2022. No other potential conflicts of interest were disclosed.

Background: More than 75 common variant loci account for only a portion of the heritability for Alzheimer's disease (AD). A more complete understanding of the genetic basis of AD can be deduced by exploring associations with AD-related endophenotypes., Methods: We conducted genome-wide scans for cognitive domain performance using harmonized and co-calibrated scores derived by confirmatory factor analyses for executive function, language, and memory. We analyzed 103,796 longitudinal observations from 23,066 members of community-based (FHS, ACT, and ROSMAP) and clinic-based (ADRCs and ADNI) cohorts using generalized linear mixed models including terms for SNP, age, SNP × age interaction, sex, education, and five ancestry principal components. Significance was determined based on a joint test of the SNP's main effect and interaction with age. Results across datasets were combined using inverse-variance meta-analysis. Genome-wide tests of pleiotropy for each domain pair as the outcome were performed using PLACO software., Results: Individual domain and pleiotropy analyses revealed genome-wide significant (GWS) associations with five established loci for AD and AD-related disorders (BIN1, CR1, GRN, MS4A6A, and APOE) and eight novel loci. ULK2 was associated with executive function in the community-based cohorts (rs157405, P = 2.19 × 10 -9 ). GWS associations for language were identified with CDK14 in the clinic-based cohorts (rs705353, P = 1.73 × 10 -8 ) and LINC02712 in the total sample (rs145012974, P = 3.66 × 10 -8 ). GRN (rs5848, P = 4.21 × 10 -8 ) and PURG (rs117523305, P = 1.73 × 10 -8 ) were associated with memory in the total and community-based cohorts, respectively. GWS pleiotropy was observed for language and memory with LOC107984373 (rs73005629, P = 3.12 × 10 -8 ) in the clinic-based cohorts, and with NCALD (rs56162098, P = 1.23 × 10 -9 ) and PTPRD (rs145989094, P = 8.34 × 10 -9 ) in the community-based cohorts. GWS pleiotropy was also found for executive function and memory with OSGIN1 (rs12447050, P = 4.09 × 10 -8 ) and PTPRD (rs145989094, P = 3.85 × 10 -8 ) in the community-based cohorts. Functional studies have previously linked AD to ULK2, NCALD, and PTPRD., Conclusion: Our results provide some insight into biological pathways underlying processes leading to domain-specific cognitive impairment and AD, as well as a conduit toward a syndrome-specific precision medicine approach to AD. Increasing the number of participants with harmonized cognitive domain scores will enhance the discovery of additional genetic factors of cognitive decline leading to AD and related dementias., (© 2023. The Author(s).)

Background: Prior literature has associated preoperative corticosteroid shoulder injection (CSI) with infection following shoulder surgery. A recent study found an equally elevated risk of total knee arthroplasty infection with preoperative injection of either CSI or hyaluronic acid. The implication is that violation of a joint prior to surgery, even in the absence of corticosteroid, may pose an elevated risk of infection following orthopedic surgery. The aim of the present study was to determine whether violation of the shoulder joint for magnetic resonance arthrogram (MRA) poses an elevated risk of infection following shoulder arthroscopy, and to compare this risk to that introduced by preoperative CSI., Methods: A national, all-payer database was queried to identify patients undergoing shoulder arthroscopy between January 2015 and October 2020. Patients were stratified into the following groups: (1) no CSI or MRA within 6 months of surgery (n = 5000), (2) CSI within 2 weeks of surgery (n = 1055), (3) CSI between 2 and 4 weeks prior to surgery (n = 2575), (4) MRA within 2 weeks of surgery (n = 414), and (5) MRA between 2 and 4 weeks prior to surgery (n = 1138). Postoperative infection (septic shoulder or surgical site infection) was analyzed at 90 days, 1 year, and 2 years, postoperatively. Multivariable logistic regression analysis controlled for differences among groups., Results: MRA within 2 weeks prior to shoulder surgery was associated with an increased risk of infection at 1 year (odds ratio [OR], 2.17; P = .007), while MRA 2-4 weeks preceding surgery was not associated with an increased risk of postoperative infection at any time point. By comparison, CSI within 2 weeks prior to surgery was associated with an increased risk of postoperative infection at 90 days (OR, 1.72; P = .022), 1 year (OR, 1.65; P = .005), and 2 years (OR, 1.63; P = .002) following surgery. Similarly, CSI 2-4 weeks prior to surgery was associated with an increased risk of postoperative infection at 90 days (OR, 1.83; P < .001), 1 year (OR, 1.62; P < .001), and 2 years (OR, 1.79; P < .001)., Conclusion: Preoperative CSI within 4 weeks of shoulder arthroscopy elevates the risk of postoperative infection. Needle arthrotomy for shoulder MRA elevates the risk of infection in a more limited fashion. Avoidance of MRA within 2 weeks of shoulder arthroscopy may mitigate postoperative infection risk. Additionally, the association between preoperative CSI and postoperative infection may be more attributed to medication profile than to needle arthrotomy., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Bioengineered corneal tissue is a promising therapeutic modality for the treatment of corneal blindness as a substitute for cadaveric graft tissue. In this study, we fabricated a collagen gel using ultraviolet-A (UV-A) light and riboflavin as a photosensitizer (PhotoCol-RB) as an in situ -forming matrix to fill corneal wounds and create a cohesive interface between the crosslinked gel and adjacent collagen. The PhotoCol-RB gels supported corneal epithelialization and exhibited higher transparency compared to physically crosslinked collagen. We showed that different riboflavin concentrations yielded gels with different mechanical and biological properties. In vitro experiments using human corneal epithelial cells (hCECs) showed that hCECs are able to proliferate on the gel and express corneal cell markers such as cytokeratin 12 (CK12) and tight junctions (ZO-1). Using an ex vivo burst assay, we also showed that the PhotoCol-RB gels are able to seal corneal perforations. Ex vivo organ culture of the gels filling lamellar keratectomy wounds showed that the epithelium that regenerated over the PhotoCol-RB gels formed a multilayer compared to just a double layer for those that grew over physically cross-linked collagen. These gels can be formed either in situ directly on the wound site to conform to the geometry of a defect, or can be preformed and then applied to the corneal wound. Our results indicate that PhotoCol-RB gels merit further investigation as a way to stabilize and repair deep and perforating corneal wounds.