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Objective/hypothesis: To compare the systemic changes following two office-based procedures-subepithelial vocal fold steroid injections (VFSI) and vocal fold augmentation (VFA), and to characterize the magnitude and chronicity of the effects observed., Study Design: Prospective, controlled before-after comparative study., Methods: Patients prospectively underwent VFSI with 0.8-2 mg of dexamethasone or VFA. Serum cortisol, white cell count (WCC), and C-reactive protein (CRP) were measured at day 0 (pre-procedure), 1 and 7. Salivary cortisol was measured at baseline and daily for 7 days post-procedure., Results: Fourteen patients underwent VFSI and 36 VFA. At baseline serum cortisol measured 304.6 ± 116.6 nmol/L and fell significantly to 48.1 ± 41.8 nmol/L 1 day following dexamethasone injection (p = 0.001) and recovered by day 7 to 303.7 ± 78.7 nmol/L. Salivary cortisol demonstrated a similar pattern with significant recovery demonstrated by day 3 (p = 0.001). White cell counts were affected by the systemic absorption of exogenous steroid and normalized by day 7. Patients who underwent VFA demonstrated no significant change in their serum or salivary cortisol and no significant change in their WCC. No significant changes in CRP or patient's physiological parameters were observed in either procedure., Conclusion: Our findings demonstrate systemic absorption of dexamethasone following VFSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression which normalizes day 3 post-procedurally., Level of Evidence: 3 Laryngoscope, 135:801-808, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

This study provides an in-depth qualitative exploration of Aboriginal peoples' experiences with seeking help for gambling-related issues in the Northern Territory (NT), Australia. Through semi-structured interviews with 29 participants, including regular and occasional gamblers as well as those affected by others' gambling, the research highlights key barriers to seeking formal help. These barriers included the normalisation of gambling within Aboriginal communities, denial of gambling problems, feelings of shame, privacy concerns, and a lack of trust in mainstream services. Additionally, past negative experiences with services, fear of judgment, and logistical challenges, such as long waiting times and transportation difficulties in remote areas, contributed to the low uptake of professional services. Instead, informal support from family and friends was occasionally sought, reflecting the collectivist nature of Aboriginal cultures. Participants also reported employing self-help strategies and offered practical suggestions for minimising gambling harm. This research underscores the complexity of gambling behaviours within Aboriginal communities and the cultural, social, and systemic factors that deter access to formal support services. It calls for the integration of Indigenous knowledge and practices into gambling prevention and intervention programs, which may improve the relevance and effectiveness of these strategies. By addressing both cultural norms and access barriers, such targeted approaches may reduce the need for reactive interventions and better support the health and wellbeing of Aboriginal people affected by gambling in the NT. To improve relevant policies and practices, we also consider these findings to contribute to the broader Indigenous-specific gambling prevention evidence-base contexts nationally and globally., Competing Interests: Declarations. Ethics Approval: The study was conducted in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. Ethics approval to conduct this study was obtained from the Central Australian Human Research Ethics Committee (CA-20-3747) and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (2020–3728). All participants provided consent to participate in the study – verbal for telephone interviews and written for face-to-face interviews. Consent to Participate: “I agree to participate in this study and understand the purposes and procedures of the study (including audio-recording of the interview) and any risks relating to my participation in the study”. Consent for Publication: Not applicable. Competing Interests: All authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s).)

Background: Acute bronchiolitis (AB) is the most common lower respiratory tract infection in infants. Clinician diagnosis and management vary due to limited objective assessment tools. Point-of-care lung ultrasound (LUS) offers a promising diagnostic and prognostic tool in the emergency department (ED), however, the time to perform LUS is of concern in the emergency setting., Methods: Infants ≤ 12 months diagnosed with AB in the emergency department were enrolled. Two LUS techniques were performed sequentially: a 12-segment "lawnmower" approach and a posterior paravertebral "waterfall" technique. LUS were scored (0-36 for lawnmower; 0-6 for waterfall). Respiratory support (RS) was categorized into three levels: no RS (room air), low RS (wall O2 or heated high flow nasal cannula < 1L/kg), and high RS (heated high flow nasal cannula ≥ 1L/kg or positive pressure). Clinical data, including RS at 12 and 24 h, maximum RS, disposition, and length of stay, were extracted via chart review and compared to mean LUS scores for each technique. Calculated areas under the curve (AUC) were compared using the Youden Index (J)., Results: 82 infants were enrolled. The mean waterfall scanning time was 1.65 min (SD 0.55) compared to the lawnmower's 7.65 min (SD 1.45). The difference between mean LUS scores for the waterfall technique was statistically significant for all disposition comparisons and nearly all RS comparisons. While the lawnmower AUC was greater than the waterfall AUC for all RS and disposition comparisons, the Youden Index (J) was statistically significantly different for only two of the eight comparisons., Conclusion: The posterior-only LUS technique is faster than the lawnmower technique, provides comparable information for disposition, and has a stronger association with LOS, but is less associated with RS. The waterfall technique may be a suitable alternative to more time-intensive, thorough techniques., Competing Interests: Declarations. Ethics approval and consent to participate: Institutional Review Board approval for the University of Texas Southwestern was obtained. Written informed consent by the legal guardian was obtained for each participant. Consent for publication: Consent for individual person’s data was obtained, specifically, the images of the child used to demonstrate the technique. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA)., Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data. Agreement was defined as ≥ 2/3 clinical experts with a rating of ≤ -1 or ≥ 1, and high confidence agreement as ≤ -2 or ≥ 2. The association of clinical features and both global assessments was tested with modified Poisson regression models., Results: Two hundred seventy-two of 303 cases (89.8%) achieved agreement with clinical data alone. Adding imaging data affected agreement in 38.9% (118/303) and directionality of agreement in 23.4% (71/303). Agreement was facilitated in 26/31 cases and lost in 21/272 cases. Of those 71 cases that changed directionality, 33 changed from axial disease being absent to present and 38 from present to absent. The final model had an area under the receiver-operating characteristic (AUROC) curve of 0.93 and 3 factors were independently associated with expert agreement (HLA-B27: relative risk [RR] 1.41, 95% CI 1.14-1.74; pain improvement with activity: RR 1.27, 95% CI 1.05-1.54; and bone marrow edema on MRI: RR 4.08, 95% CI 2.91-5.73)., Conclusion: The addition of imaging data affected directionality and improved high confidence agreement of expert assessment of axial disease. These results underscore the integral role of MRI in the determination of axial disease in JSpA.

Background: Letermovir is approved for primary prophylaxis of cytomegalovirus (CMV) in high-risk kidney transplant recipients. However, many experts suggest the drug be reserved as a second-line agent when valganciclovir is not tolerated or fails., Objective: The purpose of this study was to describe the feasibility of a de novo letermovir prophylactic approach for CMV high-risk and seropositive abdominal solid organ transplant patients., Methods: Retrospective review of abdominal transplant recipients who required CMV prophylaxis between June 6, 2023, and June 6, 2024. The purpose was to evaluate feasibility of universal letermovir prophylaxis and prophylaxis success., Results: 278 patients required CMV prophylaxis and 207 obtained letermovir (74% success). Mean time from transplant to drug approval was 10.5 ± 27 days. Mean out of pocket patient cost was $10.19 ± $36.06 per 28-day supply of letermovir and $55.69 ± $311.48 per 30-day supply of valganciclovir ( P = 0.0419). For patients who obtained letermovir, 107 (52%) required prior authorization; 32 (16%) required insurance appeal after denial of prior authorization. Forty-two patients (20%) used Merck copay assistance program while 23 (11%) used the Merck Access patient assistance program to obtain drug. There were no episodes of prophylaxis failure due to breakthrough replication necessitating termination., Conclusion and Relevance: De novo use of letermovir for CMV primary prophylaxis after abdominal transplant was found to be feasible with a high rate of success in obtaining the drug in a timely manner posttransplant and without significant out-of-pocket cost to the patient., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MRJ—speaker, research funding: Merck. JLD, HLK, CMS, JAS JPR, DAM, JSO—nothing to disclose.

Background: Since older adults spend significant time in their neighborhood environment, environmental factors such as neighborhood socioeconomic disadvantage, high racial segregation, low healthy food availability, low access to recreation, and minimal social engagement may have adverse effects on cognitive function and increase susceptibility to dementia. DNA methylation, which is associated with neighborhood characteristics as well as cognitive function and white matter hyperintensity (WMH), may act as a mediator between neighborhood characteristics and neurocognitive outcomes., Methods: In this study, we examined whether DNA methylation in peripheral blood leukocytes mediates the relationship between neighborhood characteristics and cognitive function (N = 542) or WMH (N = 466) in older African American (AA) participants without preliminary evidence of dementia from the Genetic Epidemiology Network of Arteriopathy (GENOA)., Results: For a 1-mile buffer around a participant's residence, each additional fast food destination or unfavorable food store with alcohol per square mile was nominally associated with a 0.05 (95%CI: 0.01, 0.09) and a 0.04 (0.00, 0.08) second improvement in visual conceptual tracking score, respectively. Also, each additional alcohol drinking place per square mile was nominally associated with a 0.62 (0.05, 1.19) word increase in delayed recall score, indicating better memory function (all p < 0.05). Neighborhood characteristics were not associated with WMH. We did not find evidence that DNA methylation mediates the observed associations between neighborhood characteristics and cognitive function., Conclusions: The presence of fast food destinations and unfavorable food stores with alcohol was associated cognitive measures, possibly due to greater social interaction provided in these venues. However, replication of these findings is necessary. Further examination of the potential pathways between the neighborhood environment and cognitive function/WMH may allow the development of potential behavioral, infrastructural, and pharmaceutical interventions to facilitate aging in place and healthy brain aging in older adults, especially in marginal populations that are most at risk., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Health Sciences and Behavioral Sciences Institutional Review Board at the University of Michigan (HUM00113791). Written informed consent was obtained from all participants. Consent for publication: All authors have read and agreed to the published version of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Identifying robust integrated pest management (IPM) strategies requires the testing of multiple factors at the same time and assessing their combined effects e.g., on disease control. This makes field-based experiments large, resource intensive and expensive. Hence, there are limits to the number of treatment combinations that can be practically tested under field conditions. Taguchi approach to design of experiments (DOE) or the Taguchi approach is commonly employed to enhance the quality of industrial products. It uses smaller experiments than classical DOE but its applicability to late blight research, and agricultural research, has not been widely evaluated., Results: Two existing datasets, following the same protocol and investigating the effectiveness of different IPM treatments to control late blight, caused by Phytophthora infestans, on potato, were used to test the Taguchi approach. Disease severity was quantified as area under the disease progress curve (AUDPC). The method could accurately predict the performance of a cultivar and fungicide-based integrated disease management strategy from a small dataset and identified cultivar as a key factor for disease control. Linear regression demonstrated a strong and statistically significant relationship between AUDPC values collected during the original experiments and the predicted disease severity values generated using the Taguchi method., Conclusions: The Taguchi approach can accurately predict disease severity, with predicted values similar to those collected during the original experiments. Moreover, associated analyses identified the most effective treatment combinations and the factors that exert the greatest influence on disease control. The relevance of this approach when designing and interpreting IPM strategies is discussed. © 2025 Society of Chemical Industry., (© 2025 Society of Chemical Industry.)

ObjectiveKidney failure increases people's risk of cardiovascular disease, sometimes requiring cardiac surgery. The aim of this study was to estimate the risk of cardiac surgery for adults with treated kidney failure in comparison with the general population in Australia.MethodsWe performed a population-based retrospective cohort study by linking data between the Australia and New Zealand Dialysis and Transplant Registry and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database, for 2010-2019. Age-sex-standardised surgery risk relative to the general population was estimated for adults receiving long-term dialysis and kidney transplant recipients, and subpopulations defined by procedure type, comorbidity, clinical status and dialysis-related factors.ResultsAmong 1541 adults receiving treatment for kidney failure at the time of cardiac surgery in 2010-2019, the prevalence of comorbidity and risk factors was usually highest in those receiving dialysis, followed by transplant recipients and the general population (n=113,126). For all major cardiac surgical procedure types, the incidence of surgery for adults receiving dialysis and transplant recipients exceeded that for the general population (e.g. isolated coronary artery bypass grafting relative rates 15.3 [95% CI 13.7-17.0] and 2.0 [1.6-2.6] respectively). Relative incidence was especially high for the dialysis cohorts with insulin-treated diabetes and those with body mass index <25kg/m2.ConclusionsAdults with treated kidney failure had a higher risk of cardiac surgery than the general population in Australia in 2010-2019, especially when associated with diabetes. Data linkage between clinical quality registries enabled estimation of the extent of cardiac surgical burden.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones., Competing Interests: Declaration of interests L.M.R. and S.S.R. are consultants for the TOPMed Administrative Coordinating Center (through Westat). A.G.B. is on the scientific advisory board of TenSixteen Bio unrelated to the present work. P.L.A. serves on the board of Geno.Me, Inc. V.G.S. serves as an advisor and/or has equity in Branch Biosciences, Ensoma, and Cellarity, all unrelated to the present work. E.J., M.D.K., and A.E.L. are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The discipline of ecology and evolutionary biology (EEB) has long grappled with issues of inclusivity and representation, particularly for individuals with systematically excluded and marginalized backgrounds or identities. For example, significant representation disparities still persist that disproportionately affect women and gender minorities; Black, Indigenous, and People of Color (BIPOC); individuals with disabilities; and people who are LGBTQIA+. Recent calls for action have urged the EEB community to directly address issues of representation, inclusion, justice, and equity. One aspect of this endeavor is to examine the use of EEB's discipline-specific language and terminology, which may have the potential to perpetuate unjust systems and isolate marginalized groups. Through a mixed-methods survey, we examined how members of the EEB community perceive discipline-specific terminology, including how they believe it can be harmful and which terms they identified as problematic. Of the 795 survey respondents, we found that almost half agreed that there are harmful terms in EEB and that many individuals from marginalized groups responded that they have been harmed by such terminology. Most of the terms identified as harmful relate to race, ethnicity, and immigration; sex and gender; geopolitical hierarchies; and historical violence. Our findings suggest there is an urgent need for EEB to confront and critically reassess its discipline-specific terminology. By identifying harmful terms and their impacts, our study represents a crucial first step toward dismantling deeply rooted exclusionary structures in EEB. We encourage individuals, communities, and institutions to use these findings to reevaluate language used in disciplinary research, teaching and mentoring, manuscripts, and professional societies. Rectifying current harms in EEB will help promote a more just and inclusive discipline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Rice 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.)

Introduction: Fresh frozen plasma (FFP) transfusion in the intensive care unit (ICU) is commonly used to treat coagulopathy and bleeding in cardiac surgery, despite suggestion that it may increase the risk of morbidity and mortality through mechanisms such as fluid overload and infection., Methods: We retrospectively studied consecutive adults undergoing cardiac surgery from the Medical Information Mart for Intensive Care III and IV databases. We applied propensity score matching to investigate the independent association of within-ICU FFP transfusion with mortality and other key clinical outcomes., Results: Of our 12,043 adults who met inclusion criteria, 1585 (13.2%) received perioperative FFP with a median of 2.48 units per recipient (interquartile range [IQR]: 2.04, 4.33) at a median time of 1.83 h (IQR: 0.75, 3.75) after ICU admission. After propensity matching of 952 FFP recipients to 952 controls, we found no significant association between FFP use and hospital mortality (odds ratio (OR): 1.58; 99% confidence interval (CI): 0.57, 3.71), suspected infection (OR: 0.72; 99% CI: 0.49, 1.08), or acute kidney injury (OR: 1.23; 99% CI: 0.91, 1.67). However, FFP was associated with increased days in hospital (adjusted mean difference (AMD): 1.28; 99% CI: 0.27, 2.41; p = .0050), days in intensive care (AMD: 1.28; 99% CI: 0.27, 2.28; p = .0011), and chest tube output in millilitres up to 8 h after transfusion (AMD: 92.98; 99% CI: 52.22, 133.74; p < .0001)., Conclusions: After propensity matching, FFP transfusion was not associated with increased hospital mortality, but was associated with increased length of stay and no decrease in bleeding in the early post-transfusion period., 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.

Instruments attached to animals ('biologgers') have facilitated extensive discoveries about the patterns, causes, and consequences of animal behavior. Here, we present examples of how biologging can deepen our fundamental understanding of ecosystems and our applied understanding of global change impacts by enabling tests of ecological theory. Applying the iterative process of science to biologging has enabled a diverse set of insights, including social and experiential learning in long-distance migrants, state-dependent risk aversion in foraging predators, and resource abundance driving movement across taxa. Now, biologging is poised to tackle questions and refine ecological theories at increasing levels of complexity by integrating measurements from numerous individuals, merging datasets from multiple species and their environments, and spanning disciplines, including physiology, behavior and demography., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Issue Addressed: This scoping review aims to explore the size and scope of the body of literature relating to Aboriginal and Torres Strait Islander male health and wellbeing programs and describe key program elements., Methods: This review considered unpublished and published literature from electronic peer-reviewed databases and grey literature sources. Included articles must refer to an Aboriginal and Torres Strait Islander male health and wellbeing program. Descriptive data synthesised, and seven key program elements were analysed: (1) Origin of Design, (2) Governance, (3) Leads/Facilitators, (4) Funding, (5) Length and Frequency, (6) Outcomes and Measures, and (7) Monitoring and Evaluation., Results: The review identified 54 programs described in 49 publications that were published between 1998 and 2022. Only 20 publications were peer-reviewed articles. Most programs (n = 44) were instigated, co-designed or adapted by Aboriginal and Torres Strait Islander people to suit cultural and community needs. Reporting on key program elements varied, with only n = 25 of the included publications reporting governance systems., Conclusions: This work is the first to synthesise the literature and describe the key elements of Aboriginal and Torres Strait Islander male health and wellbeing programs. Relatively few publications were found describing programs designed specifically for this population group. SO WHAT?: While the descriptive findings of the programs and their key elements in this review can assist health promotion and primary care practitioners, further investment and research are required to strengthen the evidence base and achieve the best health and wellbeing outcomes for Aboriginal and Torres Strait Islander males., (© 2024 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Cough and itch are protective mechanisms in the body. Cough occurs as a reflex motor response to foreign body inhalation, while itch is a sensation that similarly evokes a scratch response to remove irritants from the skin. Both cough and itch can last for sustained periods, leading to debilitating chronic disorders that negatively impact quality of life. Understanding the parallels and differences between chronic cough and chronic itch may be paramount to developing novel therapeutic approaches. In this article, we identify connections in the mechanisms contributing to the complex cough and scratch reflexes and summarize potential shared therapeutic targets. An online search was performed using various search engines, including PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov from 1983 to 2024. Articles were assessed for quality, and those relevant to the objective were analyzed and summarized. The literature demonstrated similarities in the triggers, peripheral and central nervous system processing, feedback mechanisms, immunologic mediators, and receptors involved in the cough and itch responses, with the neuronal sensitization processes exhibiting the greatest parallels between cough and itch. Given the substantial impact on quality of life, novel therapies targeting similar neuroimmune pathways may apply to both itch and cough and provide new avenues for enhancing their management., Competing Interests: Disclosure statement Disclosure of potential conflicts of interest: J. A. Smith has received funding or grants from Medical Research Council, Wellcome, National Institute for Health and Care Research Manchester Biomedical Research Centre and National Institute for Health and Care Research Manchester Clinical Research Facility, Merck Inc, and Bellus Health; and has received fees for consulting from Bayer Bellus Health, Nocion Therapeutics, Merck, Trevi Therapeutics, Shionogi, Bayer, Merck, Algernon, AstraZeneca, Boehringer Ingelheim, Cheisi, GSK, and Vitalograph. G Yosipovitch has received funding or grants from Sanofi, Regeneron Pharmaceuticals Inc, Pfizer, Escient Health, Novartis, Eli Lilly, Celldex, and Kiniksa Pharmaceuticals; has participated on a Data Safety Monitoring/Advisory Board for Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharamaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and Trevi Therapeutics; received consulting support from AbbVie, Arcutis, Escient Health, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals Inc, Sanofi, Trevi Therapeutics, Vifor, Kamari, Kiniksa, and GSK; and holds patents including Topical Acetaminophen Formulations for Itch Relief. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies identified corrosion between the modular tibial components of total knee arthroplasty devices. However, gaps persist. Compared to the hip, damage modes that occur within taper junctions in the knee remain poorly understood. In this study, we investigated corrosion on total knee arthroplasty components with titanium-titanium junctions. We asked the following question: under typical in vivo cyclic loading conditions, will the same alloy damage modes from total knee arthroplasty devices resemble those documented in the hip?, Methods: A total of 50 paired titanium alloy tibial baseplates and stems were collected and semiquantitatively analyzed using Goldberg corrosion scoring. To characterize damage, a subsection of moderately and severely corroded components was sectioned and imaged using scanning electron and digital optical microscopy., Results: Of the 100 device components, 95% showed visual evidence of corrosion. The initial contact area between the stem and bore generally occurred 3 mm from the stem taper base. Scanning electron microscopy revealed 4 damage modes, including oxide film formation, crevice corrosion, selective dissolution, and pitting., Conclusions: Each of the damage modes identified in modular titanium-titanium tibial junctions was previously reported by total hip arthroplasty retrieval studies. Cumulatively, our results suggest that mechanically assisted crevice corrosion promoted this damage in vivo., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria amongst youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria., Methods: This was a retrospective cross-sectional sample of youth diagnosed with juvenile SpA who met the axJSpA classification criteria. Demographics, clinical manifestations, and physician and patient-reported outcomes were abstracted from medical records. MRI scans underwent central imaging review by at least 2 central raters. Differences between groups were compared using Wilcoxon signed-rank test or chi-square, as appropriate., Results: Of 158 patients that met axJSpA criteria, 107 (68%) met the PRINTO provisional criteria for enthesitis/spondylitis-related arthritis. Forty-one (26%) did not fulfill any of the 3 major PRINTO criteria due to lack of peripheral disease manifestations. Demographics, prevalence of inflammatory or structural lesions on MRI, family history of SpA, and duration of pain were not statistically different between those who did and did not meet PRINTO criteria. Those who fulfilled the PRINTO criteria had significantly more peripheral arthritis, enthesitis, and HLA-B27 positivity but reported less sacral/buttock pain., Conclusions: Phenotypic differences of children with axJSpA between those who were and were not classified by the PRINTO criteria were primarily due to peripheral disease manifestations and HLA-B27 positivity. Modification of the PRINTO provisional criteria may facilitate capture of youth with primarily axial disease., (This article is protected by copyright. All rights reserved.)

Multijunction photovoltaics (PVs) are gaining prominence owing to their superior capability of achieving power conversion efficiencies (PCEs) beyond the radiative limit of single-junction cells 1-8 , where improving narrow bandgap tin-lead perovskites is critical for thin-film devices 9 . With a focus on understanding the chemistry of tin-lead perovskite precursor solutions, we herein find that Sn(II) species dominate interactions with precursors and additives and uncover the exclusive role of carboxylic acid in regulating solution colloidal properties and film crystallisation, and ammonium in improving film optoelectronic properties. Materials that combine these two function groups, amino acid salts, considerably improve the semiconducting quality and homogeneity of perovskite films, surpassing the effect of the individual functional groups when introduced as part of separate molecules. Our enhanced tin-lead perovskite layer allows us to fabricate solar cells with PCEs of 23.9, 29.7 (certified 29.26%), and 28.7% for single-, double-, and triple-junction devices, respectively. Our 1-cm 2 triple-junction devices show PCEs of 28.4% (certified 27.28%). Encapsulated triple-junction cells maintain 80% of their initial efficiencies after 860 h maximum power point tracking in ambient. We further fabricate quadruple-junction devices and obtain PCEs of 27.9% with the highest open-circuit voltage of 4.94 V. This work establishes a new benchmark for multijunction PVs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective(s): This study was designed to assess the relative association between adjunctive fresh frozen plasma (FFP) or adjunctive cryoprecipitate and morbidity and mortality in cardiac surgery patients receiving platelets for perioperative bleeding., Design: Retrospective cohort study using inverse probability of treatment weighting with entropy balancing., Setting: Multi-institutional study of 58 centers using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database from January 1, 2005, to December 31, 2021., Participants: Cardiac surgery patients who received platelets for perioperative bleeding., Interventions: Adjunctive FFP versus adjunctive cryoprecipitate transfusion in the perioperative period., Measurements and Main Results: A total of 12,889 platelet-transfused patients were assessed. Of these, 8,764 received adjunctive FFP and 4,125 received adjunctive cryoprecipitate, with cryoprecipitate increasing over time relative to FFP. After entropy balancing, compared with adjunctive cryoprecipitate, adjunctive FFP transfusion was associated with increased operative mortality (relative risk [RR]: 1.49, 95% confidence interval [CI]: 1.24, 1.79, p < 0.001); 1-year mortality (RR: 1.37, 95% CI: 1.13, 1.66, p = 0.001); increased risk of acute kidney injury (RR: 1.16, 95% CI: 1.02, 1.33, p = 0.024); all-cause infection (RR: 1.14, 95% CI: 1.02, 1.29, p = 0.026), and intensive care length of stay in days (adjusted mean difference: 8.02, 95% CI: 1.72, 14.33, p = 0.013)., Conclusions: In cardiac surgery patients receiving platelets for perioperative bleeding, adjunctive FFP was independently associated with greater morbidity and mortality compared with adjunctive cryoprecipitate. These hypothesis-generating findings warrant further prospective investigation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup. We define a metric called "expected PRS" (ePRS), the expected value of a PRS based on one's global or local admixture patterns. We further define the "residual PRS" (rPRS), measuring the deviation of the PRS from the ePRS. Simulation studies confirm that it suffices to adjust for ePRS to obtain nearly unbiased estimates of the PRS-outcome association without further adjusting for PCs. Using the TOPMed dataset, the estimated effect size of the rPRS adjusting for the ePRS is similar to the estimated effect of the PRS adjusting for genetic PCs. Similarly, we applied the ePRS framework to six cardiovascular-related traits in the All of Us dataset, and the results are consistent with those from the TOPMed analysis. The ePRS framework can protect from population stratification in association analysis and provide an equitable strategy to quantify genetic risk across diverse populations., Competing Interests: Competing interests BP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. LMR and SSR are consultants to the TOPMed Administrative Coordinating Center (through Westat®).

Background: The decision to continue aspirin before elective coronary artery bypass graft surgery remains contentious because of competing thrombotic and bleeding risks. We performed a contemporary systematic review and meta-analysis to compare outcomes between patients undergoing coronary artery bypass grafting who stopped and continued aspirin before surgery., Methods: PubMed, MEDLINE, and CENTRAL databases were searched from inception to 4 October 2023 for randomized controlled trials comparing patients undergoing coronary artery bypass grafting who continued preoperative aspirin with those who discontinued before surgery. Studies with cointervention arms and multivariable-adjusted or propensity matched observational studies were excluded. Summary odds ratios were calculated using a random effects model for dichotomous and continuous variables. Subgroup and sensitivity analyses were conducted in order to explore sources of heterogeneity., Results: Fifteen eligible randomized controlled trials were included with a total of 6,188 patients. Patients who continued aspirin demonstrated no significant difference in all-cause mortality (odds ratio, 1.37; confidence interval, 0.81-2.33), perioperative myocardial infarction (odds ratio, 0.81; confidence interval, 0.55-1.18), and postoperative blood loss (mean difference, 66.12 mL; confidence interval, -1.45 to 133.69). No significant difference was observed between low-dose and greater doses of aspirin. There was minimal heterogeneity amongst included studies (I 2  = 0%, P = .97, I 2  = 33%, P = .13, and I 2 = 76, P = .06, respectively). Studies were of low methodologic quality according to Cochrane Risk of Bias for Randomized Trials., Conclusions: This largest to-date systematic review and meta-analysis found no significant difference for risk of all-cause mortality, perioperative myocardial infarction, and postoperative bleeding between patients continuing and stopping aspirin before coronary artery bypass grafting., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Broad discussion is needed to chart a path forward.

Background: Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.4 years)., Results: A total of 50, 46, 7, and 12 CpG sites across the epigenome mediated the total effects of stress on body mass index, waist circumference, high-density lipoprotein cholesterol, and C-reactive protein, respectively. When reducing the dimensionality of the CpG mediators to their top 10 uncorrelated principal components (PC), the cumulative effect of the PCs explained between 35.8 and 46.3% of these associations., Conclusions: A subset of the mediating CpG sites were associated with the expression of genes enriched in pathways related to cytokine binding and receptor activity, as well as neuron development. Findings from this study help to elucidate the underlying mechanisms through which DNA methylation partially mediates the relationship between psychosocial stress and cardiometabolic risk factors., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Michigan Health Sciences and Behavioral Sciences Institutional Review Board (HUM00139262, 11/20/2017). Written informed consent was obtained from all participants in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Vitrimer is a new, exciting class of sustainable polymers with healing abilities due to their dynamic covalent adaptive networks. However, a limited choice of constituent molecules restricts their property space and potential applications. To overcome this challenge, an innovative approach coupling molecular dynamics (MD) simulations and a novel graph variational autoencoder (VAE) model for inverse design of vitrimer chemistries with desired glass transition temperature (T g ) is presented. The first diverse vitrimer dataset of one million chemistries is curated and T g for 8,424 of them is calculated by high-throughput MD simulations calibrated by a Gaussian process model. The proposed VAE employs dual graph encoders and a latent dimension overlapping scheme which allows for individual representation of multi-component vitrimers. High accuracy and efficiency of the framework are demonstrated by discovering novel vitrimers with desirable T g beyond the training regime. To validate the effectiveness of the framework in experiments, vitrimer chemistries are generated with a target T g = 323 K. By incorporating chemical intuition, a novel vitrimer with T g of 311-317 K is synthesized, experimentally demonstrating healability and flowability. The proposed framework offers an exciting tool for polymer chemists to design and synthesize novel, sustainable polymers for various applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: Children with epilepsy may have significant mental health needs with detrimental impact on quality of life, and families often request support and intervention. This paper explores the change experienced by parents of young people with epilepsy and mental health difficulties receiving an integrated mental health intervention., Methods: A qualitative study was conducted within a randomised controlled trial evaluating the Mental Health Intervention for Children with Epilepsy (MICE) psychological therapy in addition to usual care. Twenty-four families receiving the intervention were interviewed twice, at baseline and at six months, about their experience with their child's mental and physical health, and therapy. Transcripts were analysed inductively, idiographically and longitudinally using a combination of Interpretative Phenomenological Analysis (IPA) and Framework Analysis (FA). This combination allows us to begin our analysis with the detailed analysis of cases and then move to an appropriately higher level of generalization across the corpus., Results: Analysis shows changes in how the parents report their experience of their child's difficulties between baseline and 6-month interviews. While parents tended to show some understanding of epilepsy and its effects on their child in the first interview, comparisons with the second interview show enhanced understanding along with improvements in their relationship with their child, and feelings about themselves as parents. These findings were particularly relevant for parents of children with autism spectrum disorders and/or intellectual disability., Study Limitations: Not all families were able to benefit equally from the therapy, with some declining to participate or being lost to follow up and mothers being more forthcoming than fathers to take part in the research. It would have been interesting to also interview families 12 months post-baseline to gain insight on the longer-term impacts of the intervention., Conclusions: The qualitative findings presented here offer new insights into parental experiences of living with and attempting to assist a child with a complex condition. We would also hope the study will be helpful to researchers and clinicians working with a range of illnesses which impact families., Competing Interests: Declaration of competing interest Bruce Chorpita is a co-founder and member of PracticeWise, which owns the MATCH-ADTC protocol on which the Mental Health Intervention for Children with Epilepsy programme is based. PracticeWise was paid for training and consulting during the trial setup phase and provided supervision of the study supervisors to ensure integrity of treatment implementation. Bruce Chorpita did not interact with participants or study therapists and was not involved in the analysis. The other authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Correlative species distribution modeling (SDM) is an important tool to predict distributions of invasive species. A unique challenge of implementing SDMs in aridland stream networks is identifying which streams are perennial and which of those offer suitable habitat for obligate aquatic species. Here, we map perennial streams and habitat suitability of invasive virile crayfish (Faxonius virilis) in the Lower Colorado River Basin (LCRB) in the southwestern USA, and quantify drivers of uncertainty in these projections. First, we surveyed F. virilis at 122 stream sites in May-July of 2021, 2022, and 2023. We then implemented an ensemble of SDMs fit using combinations of randomly drawn sites, categories of environmental covariates measured at different spatial scales, survey years, and statistical algorithms. Next, we used open-source street view images from May-July of 2022 and 2023 to assess dry-wet status at 326 road-stream intersections and the same ensemble framework to map perennial stream reaches. Lastly, we quantified drivers of variation in predictive accuracy and mapped habitat suitability across replicates. Median true skill statistic (TSS) across F. virilis replicates was 0.613 and habitat suitability was highest in mountain ecoregions and lowest in desert ecoregions. Of the 130,847 stream km in the LCRB, we estimate 29,078 km (22.2 %) have wetted channels during the May-June dry season and median 50.3 % of these perennial streams provide suitable habitat for F. virilis. The statistical algorithm was the strongest driver of TSS variation across replicates, whereas the spatial scale at which covariates were measured was the strongest driver of variation in mapped habitat suitability across replicates. We confirm the widespread invasion of F. virilis throughout the LCRB, particularly in perennial mountain streams. The modest predictive accuracy highlights the generalistic niche of F. virilis. Overall, we demonstrate that spatiotemporally comprehensive datasets combined with ensemble modeling can guide management at regional extents., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Provo.X nebulisation system is comparable to the obsolete KoKo dosimeter for measuring cough responses to capsaicin and is an acceptable device for use in future cough challenge studies https://bit.ly/45P1X8V., Competing Interests: Conflicts of interest: The VitaloJAK algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties which may be shared with the clinical division in which J.A. Smith works. The other authors have nothing to disclose., (Copyright ©The authors 2024.)

The relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts. We identified 412 CpGs (FDR p < 0.05) associated with mtDNA heteroplasmy. Higher levels of heteroplasmy burden were associated with lower nDNA methylation levels at most significant CpGs. Functional inference analyses of genes annotated to heteroplasmy-associated CpGs emphasized mitochondrial functions and showed enrichment in cardiometabolic conditions and traits. We developed CpG-scores based on heteroplasmy-count associated CpGs (MHC-CpG scores) using elastic net Cox regression in a training cohort. A one-unit higher level of the standardized MHC-CpG scores were associated with 1.26-fold higher hazard of all-cause mortality (95% CI: 1.14, 1.39) and 1.09-fold higher hazard of CVD (95% CI: 1.01-1.17) in the meta-analysis of testing cohorts, adjusting for age, sex, and smoking. These findings shed light on the relationship between mtDNA heteroplasmy and DNA methylation, and the role of heteroplasmy-associated CpGs as biomarkers in predicting all-cause mortality and cardiovascular disease.

Rationale: The measurement of cough frequency is widely used in clinical trials, typically expressed as the number of explosive cough sounds per hour. However, this measure does not capture the clustering of coughs into bouts. Coughing bouts contribute to perceived cough severity and the physical complications of coughing, but an agreed standard definition of cough bouts is lacking. The objectives of the present study were to explore the impact of different definitions of cough bouts on the parameters generated, their relationships with reported cough severity and influence of age and gender in refractory chronic cough (RCC)., Methods: We analysed 24-h acoustic recordings and concurrent cough severity visual analogue scales from 91 RCC patients (62% female, median (interquartile range) age 60.0 (54-67.0) years). A custom-built algorithm calculated cough bouts, defined by the intervals between explosive cough sounds. Bouts defined by inter-cough intervals from ≤0.5 to ≤10 s (0.5 s increments) were explored, and parameters including number of bouts, median/maximum bout length and total bout duration calculated., Measurements and Main Results: Using inter-cough intervals of >3 s to define cough bouts made little difference to cough bout parameters. Correlations between cough severity and bout parameters were weak but most likely to be significant when single coughs were removed. Cough-free time/total time spent coughing tended to have more influence on cough severity than the average cough bout length, irrespective of the interval used., Conclusion: These analyses favour definitions of cough bouts utilising inter-cough intervals of ≤3 s and the exclusion of single coughs from cough bout analysis., Competing Interests: Conflict of interest: K. McGuinness invented the VitaloJAK filtering algorithm that has been licensed by Manchester University NHS Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties that may be shared with K. McGuinness as the inventor and the clinical division in which J.A. Smith works. The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n  = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel ( CADM3 , NALCN, NLRC5, ZNF792 , and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level ( p  < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5 , NOD2 , and AIM2 . Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.

Background and Aim: Colorectal cancer (CRC) is the fourth leading cause of cancer death globally. CRC surveillance is a common indication for colonoscopy, representing a considerable burden for endoscopy services. Accurate identification of high-risk patients who would benefit from more intensive surveillance, as well as low-risk patients suitable for less frequent follow-up, could improve the effectiveness of surveillance protocols and resource use. Our aim was to identify and critically appraise published risk models for the occurrence of metachronous advanced colorectal neoplasia (ACN), defined here as CRC or advanced adenomas detected during surveillance colonoscopy., Methods: We searched PubMed and EMBASE for primary research studies reporting the development and/or validation of multivariable models that predict metachronous ACN risk. Screening of studies for inclusion, data extraction, and risk of bias assessment were conducted by two researchers independently., Results: We identified nine studies describing nine risk models. Six models were internally validated and two were externally validated. No model underwent both internal and external validation. Good model discrimination (concordance index > 0.7) was reported for two models during internal validation and for one model during external validation. Calibration was acceptable when assessed (n = 4). Methodological limitations and a high risk of bias were observed for all studies., Conclusions: Several published models predicting metachronous ACN risk showed some promise. However, adherence to methodological standards was limited, and only two models were externally validated. Head-to-head comparisons of existing models using populations independent from model development cohorts should be prioritized to identify models suitable for use in clinical practice., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes., Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP., Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01)., Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA., (© 2023. The Author(s).)

Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress ( n  = 2,689) from the Health and Retirement Study (mean age = 70.4 years), assessing DNA methylation (Illumina Infinium HumanMethylationEPIC Beadchip) at 789,656 CpG sites. For identified CpG sites, we conducted a formal mediation analysis to examine whether smoking, alcohol use, physical activity, and body mass index (BMI) mediate the relationship between stress and DNA methylation. Nine CpG sites were associated with psychosocial stress (all p  < 9E-07; FDR q < 0.10). Additionally, health behaviours and/or BMI mediated 9.4% to 21.8% of the relationship between stress and methylation at eight of the nine CpGs. Several of the identified CpGs were in or near genes associated with cardiometabolic traits, psychosocial disorders, inflammation, and smoking. These findings support our hypothesis that psychosocial stress is associated with DNA methylation across the epigenome. Furthermore, specific health behaviours mediate only a modest percentage of this relationship, providing evidence that other mechanisms may link stress and DNA methylation.

Objective: The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA)., Methods: This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort., Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians, which collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included the following: imaging of active inflammation, imaging of structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% confidence interval [CI] 91.4%-99.7%), sensitivity of 64.3% (95% CI 54.9%-73.1%), and area under the receiver operating characteristic curve of 0.81 (95% CI 0.76%-0.86%)., Conclusion: The new AxJSpA classification criteria require an entry criterion and a physician diagnosis of juvenile SpA and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies., (© 2024 American College of Rheumatology.)

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGPs, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high-molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for 4 wk restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants. Restoration of the glycocalyx with DSGP was accompanied by improved flow-mediated dilation (FMD) and reduced arterial stiffness in isolated mesenteric arteries. Further corroborating these findings, the treatment of cultured endothelial cells with that same mixture of glycocalyx precursors promoted glycocalyx growth. Next, as an initial step to investigate the translatability of these findings, we conducted a pilot ( n = 22) double-blinded randomized placebo-controlled clinical trial to assess the effects of DSGP (3,712.5 mg/day) for 8 wk on endothelial glycocalyx integrity and indices of vascular function, including FMD, in Veterans with T2D. Contrary to the hypothesis, DSGP neither enhanced endothelial glycocalyx integrity nor improved vascular function indices relative to placebo. Together, these findings conceptually support the notion that restoration of the endothelial glycocalyx can lead to improvements in vascular function in a mouse model of T2D; however, DSGP as a therapeutic strategy to enhance vascular function in individuals with T2D does not appear to be efficacious. NEW & NOTEWORTHY Endothelial glycocalyx degradation in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to vascular dysfunction. The findings of this study support the notion that restoration of the endothelial glycocalyx using a dietary supplementation of glycocalyx precursors can lead to improvements in vascular function in diabetic mice. However, the utilized dietary supplement as a therapeutic strategy to enhance vascular function in individuals with T2D is not efficacious.

Background: Evidence for the effectiveness and cost-savings of workplace wellness programs (WWPs) is varied, likely due to the variability in program design, as not all WWPs meet the five-point criteria of a "comprehensive WWP" set by the U.S. Centers for Disease Control and Prevention. A 2019 study of changes in cardiovascular disease (CVD) risk for those enrolled in a comprehensive WWP found that nearly half of enrolled employees with moderate to high CVD risk improved their risk compared to the initial predictions. This study extends those findings by evaluating the cost-savings and return on investment (ROI) resulting from participants' CVD risk reduction from the employer's perspective., Method: Cost-savings related to CVD risk were extrapolated using two studies that provided associated cost-savings for individuals participating in a WWP. Utilizing reference groups used in previous studies, we calculated cost-savings per 1% reduction in CVD risk using our population's specific CVD risk and our program-specific costs. The cost-savings were annualized per person within each risk category., Results: Across all risk categories, cost-savings were USD 1224 per individual or USD 4.90 ROI for every USD 1 spent. Those at risk had a higher ROI per USD 1.00 spent (USD 35.4 and USD 19.2 for males and females, respectively) than those with minimal risk. However, even those with minimal risk showed a positive ROI (USD 0.3 and USD 5.0 for males and females, respectively)., Conclusions/application to Practice: Investment in WWPs should prioritize programs that include all five elements of the standards established by the U.S Centers for Disease Control and Prevention. Well-designed and comprehensive WWPs can effectively impact employee health and lead to a positive ROI and cost-savings for employers.

Perovskite solar cells (PSCs) offer an efficient, inexpensive alternative to current photovoltaic technologies, with the potential for manufacture via high-throughput coating methods. However, challenges for commercial-scale solution-processing of metal-halide perovskites include the use of harmful solvents, the expense of maintaining controlled atmospheric conditions, and the inherent instabilities of PSCs under operation. Here, we address these challenges by introducing a high volatility, low toxicity, biorenewable solvent system to fabricate a range of 2D perovskites, which we use as highly effective precursor phases for subsequent transformation to α-formamidinium lead triiodide (α-FAPbI 3 ), fully processed under ambient conditions. PSCs utilising our α-FAPbI 3 reproducibly show remarkable stability under illumination and elevated temperature (ISOS-L-2) and "damp heat" (ISOS-D-3) stressing, surpassing other state-of-the-art perovskite compositions. We determine that this enhancement is a consequence of the 2D precursor phase crystallisation route, which simultaneously avoids retention of residual low-volatility solvents (such as DMF and DMSO) and reduces the rate of degradation of FA + in the material. Our findings highlight both the critical role of the initial crystallisation process in determining the operational stability of perovskite materials, and that neat FA + -based perovskites can be competitively stable despite the inherent metastability of the α-phase., Competing Interests: Competing interests: H.J.S. is a co-founder and Chief Scientific Officer of Oxford PV Ltd., a company industrialising perovskite PV. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: Adolescence is a crucial period for establishing healthy behaviours that can reduce the risk of noncommunicable diseases. However, limited data exist on the clustering of health-related behaviours, in adolescents from low- and middle-income countries (LMICs). This study examined how diet and physical activity behaviours cluster and how they are influenced by home and school area-level deprivation., Methods: The study surveyed 527 adolescents in Yaoundé (Cameroon), Kingston (Jamaica), and Cape Town (South Africa) and grouped them into three categories according to the socioeconomic status (SES) of their homes and school areas (low-low, low-high, and high-high). A k-median algorithm defined three clusters and measured dietary attributes including Dietary Habit Score (DHS), Healthy Food Score (HFS), Nutritional Knowledge Questionnaire (NKQ), moderate-to-vigorous physical activity (MVPA), and sedentary time using validated questionnaires. The clusters were ranked based on their physical activity levels and compared them within each city using statistical tests., Results: The scores on the NKQ and HFS indicated a poor level of both nutritional knowledge and healthy food consumption across sites. Cluster analysis revealed a consistent pattern of high screen time clustering with lower (less healthy) dietary scores across sites. This pattern was consistent regardless of SES in Kingston, and SES and school socioeconomic areas in Cape Town and Yaoundé., Conclusion: An inverse clustering of sedentary behaviour duration and eating habits remained consistent across different strata for at least two sites, suggesting that interventions to reduce sedentary time could have a ripple effect on multiple NCD risk factors in adolescence., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Centre Regional Ethics Committee of the Human Health Research (CE No. 1836 CRERSHC/2020) in Yaoundé) and relevant education departments such as the school district administration and principals of selected schools. This study was conducted in accordance with the Declaration of Helsinki and the Association for Adolescent Health Research Guidelines [73] Written. Informed assent was obtained from all adolescents (aged < 18 years), and written informed consent was obtained from their parents or caregivers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Cough severity represents an important endpoint to assess the impact of therapies for patients with refractory chronic cough (RCC)., Objective: To develop a new patient-reported outcome measure addressing cough severity in patients with RCC., Methods: Phase 1 (item generation): A systematic survey, focus groups, and expert consultation generated 51 items. Phase 2 (item reduction): From a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The MCSQ included items reported to occur most frequently and that had the highest importance scores. Patient feedback on the MCSQ led to elimination of redundant items. Another 100 patients completed the MCSQ, from which we performed an exploratory factor analysis and a Rasch analysis to further refine items on the MCSQ., Results: Phase 2 led to selection of 15 items from the initial 51. Patient feedback on the 15 items led to elimination of 5 redundant items. An exploratory factor analysis of the 10-item MCSQ led to selection of two domains, elimination of one item that demonstrated cross-loading, and another that had high inter-item correlations. A Rasch analysis of the 8-item MCSQ confirmed that the response options functioned in a logically progressive manner and that no items exhibited differential item functioning. The final 8-item MCSQ has a one-week recall period and includes two domains (intensity and frequency). The 8-item MCSQ had high internal consistency (Cronbach's alpha, 0.89), proved able to distinguish different levels of cough severity (Pearson separation index, 0.89), and demonstrated high cross-sectional convergent validity (Pearson's correlation, 0.76 [95% CI 0.66 to 0.83]) with the 100-mm cough severity visual analogue scale., Conclusion: Initial evidence supports the validity of the MCSQ, an 8-item instrument measuring cough severity in patients with RCC. Future studies should evaluate its properties in measuring change over time., (Copyright ©The authors 2024.)

Abstract: Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program (n = 32 572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 131 340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, 4 are driven by common variants of small effect with reported minor allele frequency (MAF) at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor 2 conditionally distinct, noncoding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA) contains 7 distinct signals, including 1 novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR = 0.180; MAFEUR = 0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

Objective: This study aimed to quantify public acceptability and anticipated uptake with risk stratification incorporated at three points on the bowel cancer screening pathway, compared with current screening in England., Methods: We conducted an online population-based survey of 1,203 UK adults in 2024. The main outcome measures were overall acceptability of three strategies where risk stratification is introduced at 1) the point of eligibility, 2) the referral threshold and 3) the screening interval, compared with the current programme (screening as usual), and the acceptability of high- and low-risk screening practices at each point. Other outcomes included anticipated uptake of screening and the acceptability of data collection methods., Results: Acceptability of risk-stratified eligibility and referral thresholds was significantly greater than for screening as usual ( p  < 0.001). There was no difference for stratified intervals. At all three points, more intense screening for those at high-risk was more acceptable and less intense screening for those at low-risk less acceptable when compared with screening as usual ( p  < 0.0001). The anticipated likelihood of taking up screening was also significantly higher if at high-risk and significantly lower if at low-risk, compared with screening as usual for all strategies ( p  < 0.0001)., Conclusions: Participants expressed strong acceptability for risk-stratified bowel cancer screening, particularly for risk-stratified eligibility and thresholds for referral. However, acceptability for less intense screening for those at low-risk was lower than for the current programme and may negatively impact uptake. This suggests that the design and framing of risk groups requires careful consideration and communication with the public., Patient and Public Contribution: Three members of the public contributed through online correspondence to the development of the survey and participant-facing documents., 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. Published by Elsevier Inc.)

Objectives: This review aims to explore potential associations between immunological biomarkers and phonotraumatic vocal fold lesions., Study Design: Scoping review., Methods: Ovid MEDLINE, CINAHL, PubMed, Proquest Theses and Dissertations, Scopus, and Web of Science were searched using the terms "vocal fold" and "inflammatory marker" initially, and later "development" and "phonotraumatic lesion." Papers were included for review if they were published in the last 20 years in English language, used human cell lines or biological samples, and outcomes were measured objectively using immunological biomarkers., Results: In total, 4107 papers were identified for screening. The automation tools EndNote and Covidence removed 1257 duplicates. A further 2687 papers were excluded by reviewers at the title and abstract screening stage. The remaining 62 papers underwent full-text screening and 28 publications were ultimately included in the review., Conclusions: Research concerning the possible association between immunological biomarkers and phonotraumatic lesions is still in its early stages, largely due to difficulty obtaining biological vocal fold samples in a safe and noninvasive manner, and challenges in identifying laboratory techniques that are sensitive enough to detect concentrations of biomarkers in small volumes of vocal fold samples. Signaling molecules are likely the most promising biomarkers to investigate the role of voice use patterns in the development of phonotraumatic lesions due to relatively rapid shifts in response to host conditions. Future research would benefit from control of potential systemic contributions to laryngeal manifestations of inflammation., 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 Inc. All rights reserved.)

Background: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. The primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. The secondary aim was to evaluate efficiency, value, and impact of the novel trial design., Methods: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across seven hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone 1 mg/kg or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (more than 48 h), sepsis, renal failure, myocardial infarction, stroke, and death., Results: Of 2,562 patients assessed for eligibility, 1,951 were randomized (median age, 63 yr; 80% male). The median number of home days was 23.0 (interquartile range, 20.1 to 24.1) in the no dexamethasone group and 23.1 (interquartile range, 20.1 to 24.6) in the dexamethasone group (median difference, 0.1; 95% CI, -0.3 to 0.5; P = 0.66). The rates of prolonged mechanical ventilation (risk ratio, 0.72; 95% CI, 0.48 to 1.08), sepsis (risk ratio, 1.02; 95% CI, 0.57 to 1.82), renal failure (risk ratio, 0.94; 95% CI, 0.80 to 1.12), myocardial infarction (risk ratio, 1.20; 95% CI, 0.30 to 4.82), stroke (risk ratio, 1.06; 95% CI, 0.54 to 2.08), and death (risk ratio, 0.72; 95% CI, 0.22 to 2.35) were comparable between groups (all P > 0.10). Dexamethasone reduced intensive care unit stay (median, 29 h; interquartile range, 22 to 50 h vs. median, 43 h; interquartile range, 24 to 72 h; P = 0.004). The authors' novel trial design was highly efficient (89.3% enrollment)., Conclusions: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

In many low- and middle-income countries, school children consume untreated water that has been pumped into storage tanks. The water is often of poor quality and consumption can cause gastrointestinal illnesses resulting in missed school days, growth stunting, and cognitive impairment. This study deployed a silver-ceramic technology (MadiDrop) to disinfect drinking water in school storage tanks. While silver ionization is effective at the household scale, relatively little research has been conducted on its effectiveness at the community scale. To address this gap, we assessed disinfection via MadiDrop at three schools that serve vulnerable populations in rural India. Tank inflow and treated outflow samples were tested for total coliforms (TCs) and Escherichia coli (EC). TC was significantly reduced overall and in two of three intervention tanks. Compared to the baseline, reductions in TC were significant in all three tanks and overall, while EC reductions were significant overall and in two of three tanks. TC reduction was negatively correlated with silver concentration and tank residence time, and silver concentrations were maintained below the drinking water quality guideline. While the intervention could be considered successful, several barriers and caveats are provided as are study limitations and areas for future research., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits copying, adaptation and redistribution, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).)

The microfossil record contains abundant, diverse, and well-preserved fossils spanning multiple trophic levels from primary producers to apex predators. In addition, microfossils often constitute and are preserved in high abundances alongside continuous high-resolution geochemical proxy records. These characteristics mean that microfossils can provide valuable context for understanding the modern climate and biodiversity crises by allowing for the interrogation of spatiotemporal scales well beyond what is available in neo-ecological research. Here, we formalize a research framework of "micropaleoecology," which builds on a holistic understanding of global change from the environment to ecosystem level. Location: Global. Time period: Neoproterozoic-Phanerozoic. Taxa studied: Fossilizing organisms/molecules. Our framework seeks to integrate geochemical proxy records with microfossil records and metrics, and draws on mechanistic models and systems-level statistical analyses to integrate disparate records. Using multiple proxies and mechanistic mathematical frameworks extends analysis beyond traditional correlation-based studies of paleoecological associations and builds a greater understanding of past ecosystem dynamics. The goal of micropaleoecology is to investigate how environmental changes impact the component and emergent properties of ecosystems through the integration of multi-trophic level body fossil records (primarily using microfossils, and incorporating additional macrofossil data where possible) with contemporaneous environmental (biogeochemical, geochemical, and sedimentological) records. Micropaleoecology, with its focus on integrating ecological metrics within the context of paleontological records, facilitates a deeper understanding of the response of ecosystems across time and space to better prepare for a future Earth under threat from anthropogenic climate change., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: There is evidence that engaging in research is directly associated with better performance. If this relationship is to be strengthened, it is necessary to understand the mechanisms that might underlie that relationship., Aim: To explore the perspectives of staff and wider stakeholders about mechanisms by which research activity may impact on the performance of general practices., Design & Setting: Qualitative study using semi-structured interviews with general practice professionals and wider stakeholders in England., Method: Individual interviews with 41 purposively sampled staff in 'research-ready' or 'research-active' general practices, and 21 other stakeholders. Interviews were independently coded by three researchers using a framework approach., Results: Participants described potential 'direct' and 'indirect' impacts on their work. 'Direct' impacts included improved knowledge and skills that could change practice work (for example, additional records searches for particular conditions); bringing in additional resources (for example, access to investigations or staff); and improving relationships with patients. 'Indirect' impacts included job satisfaction (for example, perception of practice as a centre of excellence and innovation, and the variety afforded by research activity reducing burnout); and staff recruitment (increasing the attractiveness of the practice as a place to work). Responders identified few negative impacts., Conclusion: Staff and stakeholders identified a range of potential impacts of research activity on practice performance, with impacts on their working lives most salient. Negative impacts were not generally raised. Nevertheless, responders generally discussed potential impacts rather than providing specific examples of those impacts. This may reflect the type of research activity conducted in general practice, often led by external collaborators., (Copyright © 2024, The Authors.)

Background: Epigenome-wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits., Results: We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p < 0.0001). We examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with BP levels, i.e., a one-unit increase in ERS was associated with 0.74 mm Hg (p = 0.002) higher SBP and 0.50 mm Hg (p = 0.0006) higher DBP, but not with HTN. Longitudinal analyses in FHS (n = 3260) and five independent external cohorts (n = 4021) showed that the baseline ERS was not associated with a change in BP over time or with incident HTN., Conclusions: Our findings demonstrate that the ERS has potential clinical utility in assessing lifestyle factors related to cardiovascular risk, especially when self-reported behavioral data (e.g., alcohol consumption) are unreliable or unavailable., (© 2024. The Author(s).)