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Introduction: Individuals with headache choose over-the-counter (OTC) medications to relieve pain and associated symptoms. This real-world evidence study investigated the effect of three OTC headache treatments on headache intensity and the associated impairment of cognitive and functional parameters in headache sufferers in Germany, Brazil, and Japan., Methods: This prospective, multinational, observational eDiary-based study included adults experiencing headache for ≥ 6 months, with ≥ 2 headache episodes per month requiring treatment and using one of the three OTC headache treatments (Germany: ibuprofen 400 mg + caffeine 100 mg; Brazil: dipyrone 1 g; Japan: ibuprofen 100 mg + caffeine 40 mg). The primary endpoint was change in headache intensity (11-point numeric rating scale [NRS]) from baseline (headache onset) to 2 h post-treatment. Secondary endpoints were association between NRS scores for headache intensity and for cognitive and functional parameters and change in these parameters from baseline to 2 h post-treatment., Results: Of the 32,623 individuals screened, 1239 were enrolled in the study, with 607 having their first headache episode treated using one of the OTC treatments. Baseline demographics and characteristics were similar across the cohorts. At 2 h post-treatment, headache intensity significantly improved, with the mean change from baseline being 3.4 (3.1, 3.7, 95% confidence interval), 4.2 (3.9, 4.5), and 3.0 (2.7, 3.3) for German, Brazilian, and Japanese cohorts, respectively. Improvement was observed in all cognitive and functional parameters. The NRS score for headache intensity significantly predicted NRS scores of all cognitive and functional parameters (P < 0.0001)., Conclusions: The study shows that headache intensity significantly affects cognitive and functional aspects, as well as overall quality of life, for sufferers globally. It confirms the effectiveness of OTC medications and suggests using headache intensity as a self-assessment tool for symptom severity, highlighting the need for new parameters in the OTC domain to improve public health benefits., Competing Interests: Declarations. Conflict of Interest: Peter J. Goadsby reports, over the last 36 months, personal fees from Sanofi; grant from Kallyope, and personal fees from Aeon Biopharma, AbbVie, Aurene, CoolTech LLC, Dr Reddy’s, Eli Lilly and Company, Linpharma, Lundbeck, Pfizer, PureTech Health LLC, Satsuma, ShiraTronics, Teva Pharmaceuticals, Tremeau, and Vial; personal fees for advice from Gerson Lehrman Group, Guidepoint, SAI Med Partners, and Vector Metric; fees for educational materials from CME Outfitters; and publishing royalties or fees from Massachusetts Medical Society, Oxford University Press, UptoDate, and Wolters Kluwer. Peter J. Goadsby is an Editorial Board member of Pain and Therapy. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Andrew Stewart has received honoraria for advisory boards and educational talks from Allergan/AbbVie, AllergoSan, Eli Lilly, Lundbeck, Novartis, Sanofi, and Teva. Mamoru Shibata has no competing interests. Mario Fernando Prieto Peres has received personal fees from Ache, Allergan/AbbVie, Eli Lilly, Eurofarma, Libbs, Lundbeck, Novartis, Pfizer, Sanofi, and Teva, and has received research support from Allergan/AbbVie, Eli Lilly, Eurofarma, Janssen-Cilag, Libbs, Natura, Novartis, and Teva. Mary Kay Margolis is a former employee of PPD, part of Thermo Fisher Scientific, which provides consulting and other research services to pharmaceutical, device, government, and non-government organizations. As a PPD employee, she worked with a variety of companies and organizations and was expressly prohibited from receiving any payment or honoraria directly from these organizations for services rendered. Chris Colby is an employee of PPD, part of Thermo Fisher Scientific. Valentine Polivka is an employee of the AIXIAL Group, an ALTEN company, which provides statistical consulting and research services to Sanofi, and has no other competing interests. Luminita Constantin, Caroline Amand, and Andrew Stewart are currently employees of Sanofi and may hold shares and/or stock options in the company. Ethical Approval: The study (21062-01) was submitted and approved by the US Institutional Review Board (IRB): Ethical and Independent (E&I) Review Services, which is now known as Salus IRB. The study was approved by local ethics committees in Germany, Brazil, and Japan. All participants provided informed consent electronically before initiation of data collection., (© 2025. The Author(s).)

Objective: People with osteoarthritis (OA) commonly experience flares. Whether COVID-19 vaccination triggers OA flares is unknown., Design: Adults with OA enrolled in a COVID-19 Rheumatology Registry were invited to participate in a case-crossover study. Vaccine data were ascertained from self-report and electronic health records (EHR). OA was identified using coding algorithms and validated via EHR. Participants reported flare and non-flare periods. Vaccine exposures in the 2-, 7-, and 14-day "lookback windows" prior to OA flares were compared to vaccine exposures during similar non-flare ("control") periods., Results: 279 participants had validated OA, and 136 (49%) contributed at least one flare and one control period. Mean age was 68 years [SD ±8], 82% female, 87% White, 62% knee OA, 56% hip OA, 37% hand/wrist OA and 60% had >= one anatomic location of OA. 525 COVID-19 vaccine doses were recorded, and participants reported 374 OA flares: 30% were mild, 55% were moderate, and 14% were severe. OA flares were not associated with COVID-19 vaccination 2 or 7 days prior (odds ratios [OR] 0.69 [95% confidence interval (CI): 0.28, 1.66], OR 0.54 [95% CI: 0.27, 1.07], respectively). In the 14-day lookback window, fewer flares occurred after vaccination (OR 0.57 [95% CI: 0.34, 0.97], p=0.039). Analyses stratified on sex, age, knee or hand OA, vaccine brand, and dose showed no increased association between COVID-19 vaccination and OA flares., Conclusion: The lack of positive association between COVID-19 vaccination and OA flare in any primary or secondary analysis provides reassurance regarding the use of COVID-19 vaccines in people with OA., Competing Interests: Declaration of competing interest In the past three years, Vivian P. Bykerk has served as a consultant for Pfizer and BMS. Her institution has received a grant to study immune cell subsets in RA. Dr. Mandl receives royalties from Wolters Kluwer and receives financial support from the American College of Physicians., (Copyright © 2025. Published by Elsevier Ltd.)

Introduction: Florida remains a high-incidence, high-prevalence setting for HIV. Long-acting (LA) antiretroviral therapies (ART) could improve HIV-related outcomes and reduce transmission. This study identifies preferred LA ART characteristics and classes of preference among people with HIV (PWH) in Florida., Methods: The Florida Cohort enrolls adult PWH from six counties. In February 2023, a best-worst scaling discrete choice experiment (BWDCE) was added which included 12 tasks with three alternatives and an opt-out (i.e., their current regimen). Six attributes were included: treatment type (e.g., shot), long-term effects, side effects, location (e.g., at home), effectiveness, and frequency. A Hierarchical Bayes model was used to estimate level utilities, attribute importance was calculated, and a latent class model was run in Sawtooth Software., Results: Overall, 208 PWH participated (60% aged 50+, 49% non-Hispanic Black, 54% male). Treatment type had the greatest impact on preference [27.2% (95%CI 25.1-29.3)], followed by frequency [23.4% (95%CI 21.6-25.2)], and long-term effects [19.0% (95%CI 17.8-20.3)]. Within treatment type, LA pills were preferred over other options, including their current regimen. Less frequent administration was preferred, but only yearly administration was preferred over their current regimen. Within long-term effects, participants preferred no increase in risk. Two classes were identified where one class (27% of participants) preferred their current regimen and the other (73% of participants) preferred an alternative, placing greater importance on frequency., Conclusion: PWH preferred LA pills and less frequent administration, so future ART development could focus on options with these traits. Further exploration of user preference classes is needed., Competing Interests: The authors report no conflicts of interest related to this work., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Posttraumatic stress disorder (PTSD) and eating disorders (EDs) frequently co-occur, with PTSD potentially worsening ED treatment outcomes. Integrated and concurrent interventions that treat both conditions together have been recommended, but no best practices exist. This case series of nine patients provides preliminary data on Written Exposure Therapy (WET), a brief, low-resource PTSD intervention, delivered concurrently with inpatient or day hospital ED treatment. Results showed reductions in PTSD symptoms, with most patients experiencing clinically significant improvements. Changes in ED symptoms varied, but no patients experienced deterioration. These findings suggest WET is a promising, efficient method for treating PTSD alongside ED treatment, supporting the need for clinical trials to assess its acceptability and efficacy for ED-PTSD.

Objective: This study tests the effectiveness of leader- and provider-level implementation strategies to implement evidence-based interventions (EBIs) in 2 of the service systems caring for autistic children. The TEAMS Leadership Institute (TLI) targets implementation leadership and climate, and TEAMS Individualized Provider Strategy (TIPS) targets provider motivation and engagement., Method: A cluster randomized hybrid type 3 implementation-effectiveness trial tested the effects of the implementations strategies when paired with AIM HI (An Individualized Mental Health Intervention for Autism) in mental health programs (study 1) and CPRT (Classroom Pivotal Response Teaching) in classrooms (study 2). The combined sample included 65 programs/districts across 4 training cohorts (2018-2019 to 2020-2021). Organizations were randomized to receive a leader-level strategy, provider strategy, both strategies, or neither strategy (EBI provider training only). Leader and provider participants were recruited from enrolled programs/districts, and child participants were recruited from providers' caseloads or classrooms. Data from a total of 387 providers (mean age = 36.39 years; 91% female participants; 30% Latino/a/x participants) and 385 children (mean age = 9.13 years; 84% male participants; 60% Latino/a/x participants) were analyzed. Outcomes were assessed over 6 months. Provider outcome measures included provider EBI certification and observed EBI fidelity. Clinical outcome measures included the Eyberg Child Behavior Inventory (ECBI) (study 1) and the Pervasive Developmental Disorder Behavior Inventory (PDD-BI) (study 2). Outcomes were analyzed using intent-to-treat models., Results: There was no significant effect of TLI on EBI Certification. TLI was associated with significantly higher EBI fidelity compared to non-TLI (B = 0.37, p = .04). Moreover, a statistically significant TLIX1Time interaction was found for child outcome T scores (B = -10.47, p = .03), with a significant reduction in T-scores across time only for those in the TLI condition. There were no significant effects of TIPS on any outcomes., Conclusion: Findings support the effectiveness of leader-focused strategies to promote implementation and clinical outcomes of autism EBIs in multiple public service systems and for multiple EBIs., Clinical Trial Registration Information: Translating Evidence-based Interventions for ASD: Multi-Level Implementation Strategy (TEAMS); https://clinicaltrials.gov/; NCT03380078., (Copyright © 2025 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: There are no evidence based guidelines for clinicians to follow in advising pediatric patients with traumatic brain injury (TBI) on return to play (RTP)., Objective: To understand practice patterns of experts in pediatric traumatic brain injury (TBI) in relation to how they assess severity of TBI and guide return to play (RTP) decisions with their patients who sustain complicated mild, moderate, or severe TBI., Design: Cross-sectional web-based survey., Setting: Not applicable., Participants: Thirty experts (defined by attesting to their clinical management of children with TBI and demonstrating a history of publication in the area of pediatric TBI including mild TBI) represented by physical medicine and rehabilitation, neurology, neurosurgery, sports medicine, and neuropsychology. Fifty-five candidates were invited, 37 responded (67% response rate), and 30 were eligible to participate., Interventions: Not applicable., Main Outcome Measure(s): Ratings of agreement as to the relative importance of a variety of factors used to assess initial severity of injury as well as to measure recovery. RTP timelines were measured for different scenarios (adjusted by level of risk of activity returned to and the severity of initial injury sustained). Finally, ratings of agreement with various factors that could influence their RTP decision making as well as a free text option., Results: Recommendations on RTP timing varied significantly based on risk of activity returned to for all levels of TBI severity (p < .05). There was large variability of RTP timeline for any given level of injury severity. There was no significant association between medical specialty and RTP recommendations. Experts also noted a variety of factors which may inform their RTP decision making, many with high agreement., Conclusions: These results can inform clinicians who care for these patients in their own RTP decision making. The description of these RTP trends, in combination with the variability seen in both severity determination and recovery assessment, highlight the importance of further study of outcomes related to RTP and the eventual development of standardized guidelines for this patient population., (© 2025 The Author(s). PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

When studying the impact of policy interventions or natural experiments on air pollution, such as new environmental policies or the opening or closing of an industrial facility, careful statistical analysis is needed to separate causal changes from other confounding factors. Using COVID-19 lockdowns as a case study, we present a comprehensive framework for estimating and validating causal changes from such perturbations. We propose using flexible machine learning-based comparative interrupted time series (CITS) models for estimating such a causal effect. We outline the assumptions required to identify causal effects, showing that many common methods rely on strong assumptions that are relaxed by machine learning models. For empirical validation, we also propose a simple diagnostic criterion, guarding against false effects in baseline years when there was no intervention. The framework is applied to study the impact of COVID-19 lockdowns on atmospheric nitrogen dioxide (NO2) levels in the eastern United States. The machine learning approaches guard against false effects better than common methods and suggest decreases in NO2 levels in 4 US cities (Boston, Massachusetts; New York, New York; Baltimore, Maryland; and Washington, DC) during the pandemic lockdowns. The study showcases the importance of our validation framework in selecting a suitable method and the utility of a machine learning-based CITS model for studying causal changes in air pollution time series. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

One in three people with Alzheimer's or other dementias lives alone, without a spouse/partner or nearby children (i.e., is aging solo), yet most dementia caregiving research has focused solely on spouses or children. This study examined the experiences of friends, neighbors, siblings, and others providing unpaid care for someone with dementia. We conducted semi-structured interviews with 14 caregivers (100% female; age 54-85, mean 71; 93% white, 7% black; 29% friend, 29% sibling or in-law, 21% neighbor, 21% church congregant). Participants balanced three priorities: the person living with dementia's quality of life, the person's safety and well-being, and the caregiver's resources. Caregivers described tensions when these priorities conflicted, such as the person with dementia's goal to live alone versus risks to their physical safety. These findings and future research can inform policies and programs to support non-family dementia caregiving., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Millions of children are diagnosed with a traumatic brain injury (TBI) each year, most being mild TBI (mTBI). The effect of mTBIs on academic performance is of significant importance. We investigate mTBI's impact on parent-reported academic outcomes in school-aged pediatric participants., Methods: This cross-sectional survey study queried parents (N = 285) regarding letter grade performance and the presence or absence of academic accommodations before and after an mTBI, including complicated mTBI (c-mTBI, or mTBI with radiographic abnormality)., Results: We found a parent-reported decline in letter grades following c-mTBI (p < .001), with no significant change following uncomplicated mTBIs. Degree and length of recovery were also associated with grade changes (p < .05). Those with no academic accommodations prior to the injury showed significant decreases in grades after injury regardless of post-injury accommodation status (p < .05)., Implications of School Health Policy, Practice, and Equity: This study underscores the need for an improved framework of support to maximize academic performance of children following mTBI, especially in those with a c-mTBI and still recovering from their injury., Conclusion: Our study identifies children who are at risk for adverse academic outcomes following mTBI. We encourage efforts to better support school nurses in this effort, including improved communication between health care teams and school teams., (© 2024 The Author(s). Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

Importance: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Quantifying the contribution of major potentially modifiable risk factors to the burden of MCC may inform prevention efforts., Objective: To estimate the population attributable fraction of MCC cases in the US that were attributable to major immunosuppressing conditions (eg, HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation [UVR] exposure, and Merkel cell polyomavirus [MCPyV])., Design, Setting, and Participants: This epidemiological assessment combined data from population-based registries and case series and included cases of MCC that were diagnosed from January 2001 to December 2019 diagnosed in people with HIV, solid organ transplant recipients, and patients with CLL who were identified through population-based cancer registries and linkages with HIV and transplant registries. UVR-based on cloud-adjusted daily ambient UVR irradiance was merged with cancer registry data on the county of residence at diagnosis. Studies reporting the prevalence of MCPyV in MCC specimens collected in the US were combined via a meta-analysis., Exposures: HIV, solid organ transplant, CLL, UVR, and MCPyV., Main Outcomes and Measures: Population attributable fraction of MCC cases attributable to major risk factors., Results: A total of 38 020 MCCs were diagnosed in the US among xx patients (14 325 [38%] female individuals; 1586 [4%] Hispanic, 561 [1%] non-Hispanic Black, and 35 171 [93%] non-Hispanic White individuals). Compared with the general US population, MCC incidence was elevated among people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75). Due to the rarity of these conditions, only 0.2% (95% CI, 0.1%-0.3%) of MCC cases were attributable to HIV, 1.5% (95% CI, 1.4%-1.7%) to solid organ transplant, and 0.8% (95% CI, 0.5%-1.3%) to CLL. Compared with individuals of racial and ethnic minority groups, MCC incidence was elevated among non-Hispanic White individuals at lower and higher ambient UVR exposure levels (incidence rate ratios: 4.05 and 4.91, respectively, for MCC on the head and neck). Overall, 65.1% (95% CI, 63.6%-66.7%) of MCCs were attributable to UVR. Based on a meta-analysis of 19 case series, 63.8% (95% CI, 54.5%-70.9%) of MCCs were attributable to MCPyV. Studies were identified from a MEDLINE search performed on October 12, 2023., Conclusions and Relevance: The results of this study suggest that most MCC cases in the US were attributable to ambient UVR exposure or MCPyV, with a small fraction due to immunosuppressive conditions. Efforts to lower MCC incidence could focus on limiting UVR exposure.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed. This implementation survey examined the associations of sociodemographic background, substance use, and sexual risk behaviors with willingness to use daily oral and long-acting injectable (LAI) PrEP among substance using men who have sex with men (SU-MSM). Participants were 225 SU-MSM recruited from sexually transmitted infection (STI) clinics, syringe services programs (SSPs), and substance use treatment programs (SUTPs) in eight Southern U.S. cities. Rates of willingness were high for both daily oral PrEP (78%) and LAI PrEP (66%). In multivariable analyses, distinct factors were associated with willingness towards each. For daily oral PrEP, greater willingness was associated with condomless anal sex, less frequent non-injection opioid use, prior PrEP awareness, and past use of PrEP. For LAI PrEP, greater willingness was associated with Black race, identifying as gay, being single, and higher injection drug use frequency. Lower willingness to use LAI PrEP was associated with higher non-injection opioid use frequency. Findings about willingness to use LAI PrEP, as a relatively newer modality, and greater willingness among Black SU-MSM as a disproportionately HIV-impacted population, are especially important. These findings argue for the necessity to enhance PrEP promotion efforts that distinguish between oral and LAI PrEP and that are specifically tailored to major SU-MSM subgroups in the Southern U.S., Competing Interests: Declarations. Ethical approval: The University of Washington Human Subjects Division determined that this study (STUDY00007617) was exempt from federal human subjects regulations, including the requirement for a full IRB review approval and continuing review. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Surprise Question (SQ) - Would you be surprised if this patient died within the next 6 months? - is a validated tool for mortality prediction. The Mount Sinai Cardiac Intensive Care Unit (CICU) incorporated the SQ into a novel EHR workflow to identify patients who would benefit from early initiation of Palliative Care (PC)., Methods: Implementation of the SQ proceeded in two steps. During the feasibility pilot (December 2021-March 2022), providers answered the SQ using an EXCEL spreadsheet for all CICU patients, without changing other workflows. In April 2022, the CICU launched a new workflow-column built into the Epic patient-list dashboard with the SQ as the backbone. For patients with SQ answers of "NO," providers were prompted to facilitate and document a goals of care (GOC) conversation. We conducted a retrospective, observational, quasi-experimental study of all admissions to the CICU with SQ = NO between December 2021-September 2022. Clinical data was obtained via EHR query and chart review. We compared the frequency and timing of GOC conversations and the likelihood of redirected GOC (defined as code status change and/or hospice discharge) during the 3-month pilot versus the 6-month implementation period., Results: 195 admissions were included: median [IQR] age 72.0 [61.0, 84.0] years; LOS > 5 days 43.6%; CICU mortality 17.9%. These clinical characteristics were comparable between the pilot (N = 57) and implementation (N = 138) periods. However, ICU interventions (i.e. mechanical ventilation, renal replacement therapy) were more common among the pilot cohort (52.6% vs. 33.3%, p = .015). For the primary outcomes, compared to the pilot period, there was a significantly higher frequency of GOC conversations (61.4% vs. 81.2%, p = .004) and GOC conversations < 2 days from CICU admission (40.4% vs. 61.6%, p = .007) in the intervention period. There was no difference in the likelihood of redirected GOC towards comfort or no escalation (28.1% vs. 21.0%, p = .288)., Conclusion: We facilitated earlier GOC conversations directed to critically ill patients with high mortality risk by integrating the SQ into the EHR., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the Mount Sinai School of Medicine (STUDY-22-00741), in accordance with Mount Sinai’s Federal Wide Assurances (FWA#00005656, FWA#00005651) to the Department of Health and Human Services. The need for written informed consent to participate was waived by the Institutional Review Board of the Mount Sinai School of Medicine due to the retrospective nature of the study. The study was conducted in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct "dark microglia" linked to pathological synapse loss. In AD models, microglial ISR activation exacerbates neurodegenerative pathologies and synapse loss while its inhibition ameliorates them. Mechanistically, we present evidence that ISR activation promotes the secretion of toxic lipids by microglia, impairing neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR or lipid synthesis mitigates synapse loss in AD models. Our results demonstrate that microglial ISR activation represents a neurodegenerative phenotype, which may be sustained, at least in part, by the secretion of toxic lipids., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lead (Pb 2+ ) and hexavalent chromium (Cr 6+ ) are highly toxic pollutants with no safe exposure levels, posing significant health risks globally, especially in developing countries. Current detection methods for these metals are often complex and inaccessible, highlighting the urgent need for innovative approaches. In this study, we present a rapid, cost-effective colorimetric assay utilizing ascorbic acid-capped gold nanoparticles (AuNPs) for the selective detection of Pb 2+ and Cr 3+/6+ ions at levels recommended by regulatory bodies such as the WHO and EPA. The synthesis of our AuNPs was achieved by reducing gold(III) chloride with ascorbic acid, resulting in stable, negatively charged nanoparticles, as characterized by dynamic light scattering, UV-vis spectroscopy and high-resolution transmission electron microscopy. Our method demonstrated high sensitivity, with limits of detection (LOD) of 5.4 ± 0.25 ppb for Pb 2+ , and 6.3 ± 0.23 ppb for Cr 6+ , confirming specificity towards these ions in various water samples. The assay's efficacy was validated in real-world applications, including testing drinking water from multiple sources and assessing the performance of filtration systems. This straightforward assay offers a promising tool for monitoring water quality, enhancing public health initiatives and accessibility to critical environmental testing.

Background: To date, HIV molecular epidemiology (HIV ME) has been primarily used to identify clusters of related infections (cluster detection and response [CDR]) and then address interventions to these clusters. Community groups have raised concern regarding CDR regarding privacy and ethical concerns. Here we demonstrate how an alternative approach to HIV ME can provide public health benefit., Methods: A limited dataset for Miami-Dade County provided by the Florida Department of Public Health was curated and annotated by neighborhood health district (NBHD) and genetic linkage (using a genetic distance threshold of ≤ 0.5%) and phylodynamic analyses were performed. Phylodynamic analyses were used to infer viral transmissions into Miami-Dade County, and between NBHDs within the county., Results: 7274 HIV sequences from unique persons collected between 1/1/2015 and 12/31/2021 were analyzed, including 50% of the 7894 new diagnoses during this period. The proportion of sequences in local clusters increased over time. Higher ratios of local introductions, compared to viral egress (i.e., source of local clusters in other NBHDs) were observed in three NBHDs in North Miami [range 1.9-2.5], suggesting earlier diagnosis, but high numbers of susceptible persons not on pre-exposure prophylaxis. South Dade/Homestead had a low ratio (0.3) of local introductions compared to egress, suggesting later diagnosis and less durable suppression., Conclusions: Phylodynamic and genetic linkage analyses can highlight populations and geographic regions that might benefit more from particular types of HIV prevention interventions. These findings will need to be explored by evaluating the impact of scaling up interventions informed by these analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Methods: The authors performed a computerized search using PubMed, Embase, and Google Scholar. The search terms used were "chemotherapy AND surgery", "immunotherapy AND surgery", "radiotherapy AND surgery", "nutrition AND surgery", "(oculoplastic OR orbit OR eyelid OR lacrimal OR puncta) AND (chemotherapy OR immunotherapy OR radiotherapy)", "(facial OR facial plastic OR oculoplastic) AND (chemotherapy OR immunotherapy OR radiotherapy)", "(cancer OR malignancy) AND surgery", "(cancer OR malignancy) AND (surgery OR surgical) complications", "wound healing AND (cancer OR malignancy)", "infection AND (cancer OR malignancy)", "(bleeding OR blood loss) AND (cancer OR malignancy) AND surgery", "(chemotherapy OR immunotherapy OR radiotherapy) AND wound healing", "(chemotherapy OR immunotherapy OR radiotherapy) AND (bleeding OR blood loss)", "(chemotherapy OR immunotherapy OR radiotherapy) AND infection"., Results: A total of 89 articles, published from 1993 to 2023 in the English language or with English translations were included. Articles published earlier than 2000 were cited for foundational knowledge. References cited in the identified articles were also used to gather further data for the review., Conclusions and Relevance: Patients who are being treated for cancer or are undergoing current treatment for cancer require special considerations. Systemic therapies and radiotherapy impact the physiology of patients and the integrity of tissue in ways that significantly impact surgical interventions. It is imperative for the oculofacial plastic surgeon to have a complete understanding on how a previous or current diagnosis of cancer can influence surgical outcomes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To examine inpatient COVID-19-related outcomes among patients with and without diabetes alone or with a history of established heart failure (HF) or established atherosclerotic cardiovascular disease (ASCVD)., Design: Observational study; longitudinal analysis of registry data., Setting: Hospitals in the USA reporting to the American Heart Association (AHA) COVID-19 Registry from January 2020 to May 2021., Participants: 20 796 individuals with diabetes (11 244 men; mean age 64.2) and 30 798 without diabetes (15 980 men; mean age 59.0) hospitalised for COVID-19 in the USA., Primary and Secondary Outcome Measures: Primary outcome measures were all-cause mortality, inpatient major adverse cardiovascular events (MACE) and/or inpatient mechanical ventilation. Secondary outcome measures included the association with diabetes and these outcomes among those with and without pre-existing ASCVD and HF and the association with insulin use and these outcomes in patients hospitalised for COVID-19., Results: After adjustment for relevant covariates diabetes increased the risk of mortality (HR 1.12, 95% CI: 1.03 to 1.21), MACE (HR 1.32, 95% CI: 1.17 to 1.48) and mechanical ventilation (HR 1.33, 95% CI: 1.26 to 1.42). Among patients with established ASCVD or HF, diabetes did not modify the risk of adverse outcomes. There was a significant difference in the risk of mortality between patients taking insulin compared with those who were not (HR 1.32, 95% CI: 1.01 to 1.26); however, there was no difference in the risk of MACE or mechanical ventilation., Conclusions: Diabetes was associated with a higher risk of in-hospital all-cause mortality, MACE and need for mechanical ventilation in patients hospitalised for COVID-19. Diabetes was independently associated with adverse outcomes, particularly among those without pre-existing cardiovascular disease., Competing Interests: Competing interests: FP reports research support (to Emory University) from Insulet, Dexcom, Novo Nordisk, Tandem and Ideal Medical Technologies and consulting for Dexcom and Medscape. UG, LTV, AG, AQ, CA and SD have no interests to declare., (© 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.)

With the rise in demand for mental health services and the changed landscape of post-COVID-19 therapy delivery, examining both therapy modality (e.g., individual, group) and delivery methods (e.g., in-person, remote) has become increasingly important. While empirical evidence generally supports equivalency of outcomes across modalities and delivery methods, there is less evidence regarding comparative preferences and perceptions of these variables. To begin to answer these questions, we surveyed a random sample of 777 university students at a large, western university. Congruent with the previous literature, results suggest that there is a strong preference for in-person individual therapy, in spite of the increased experience with teletherapy. We also found a strong reluctance to engage with group therapy. Demographic factors predicting modality and delivery preferences indicated that being older and a woman were associated with increased likelihood to prefer individual therapy (both in-person and teletherapy), and lower class standing was associated with a stronger preference for group therapy. The only symptoms predictor for preferences included higher levels of social anxiety being associated with a higher preference for online self-help. While those who had previously engaged in a particular type of therapy were typically two to three times more likely to prefer it in the future, those who had attended in-person group therapy were over five times more likely to prefer it in the future. Finally, perceptions of past experiences with in-person therapy were significantly more positive than experiences with teletherapy. We discuss the implications of these findings for future research and practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose: Increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) highlights a desire for screening with liver ultrasound normalized local variance (NLV). We aimed to assess variations in NLV values measured at different sampling depths and discuss common technical considerations in measuring liver NLV., Methods: We retrospectively measured liver NLVs at variable depths on ultrasound images pre-recorded in 116 participants who underwent liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and ultrasound to screen for MASLD. Liver NLVs were measured and differences at variable depths were tested using one-way analysis of variance (ANOVA) and multiple paired comparisons using post hoc Tukey honestly significant difference (HSD), Scheffé, Bonferroni, and Holm multiple comparisons. Diagnostic performance of NLV values were analyzed by area under the receiver operating characteristic (AUROC) curve., Results: The NLV measured at a depth of 10 cm significantly differed from those measured near the liver capsule and at depths of 6 cm and 8 cm (p < 0.001) from the skin. There was no significant difference in NLV value in other paired groups (p > 0.05). The difference in the area under AUROCs for NLVs measured at variable depths was not significant (p > 0.05)., Conclusions: The best diagnostic performance of liver NLV was measured at depth of 8 cm from the skin, although NLV measured at variable depth showed similar diagnostic performance for assessing ≥ mild hepatic steatosis. The study results provide a reference that can be used in the development of standardized scanning protocols and technical considerations in measuring liver NLV., Competing Interests: Declaration of competing interest We hereby declare that this research is entirely our own work and that any additional sources of information have been duly cited. We also declare that it has not been previously published in any other journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to profile modified Radiographic Union Scale for Tibia (mRUST) scores over time in distal femur fractures treated with intramedullary nails and identify predictors of radiographic union timing and delayed progression., Design: Multicenter retrospective cohort study., Setting: Ten Level I Trauma Centers., Patient Selection Criteria: The inclusion criteria were patients with distal femur fractures (OTA/AO 33A and 33 C) treated with intramedullary nails, with a minimum follow-up of 1 year or until radiographic union or reoperation. The exclusion criteria were fractures treated with combination nail-plate constructs, pathologic fractures, and patients younger than 18 years old., Outcome Measures and Comparisons: The primary outcome was the mRUST score at 3, 6, and 12 months postoperatively. Receiver operating characteristic curve analysis identified the optimal 3-month mRUST score predicting reoperation. Multivariable models were used to identify predictors of radiographic union timing and delayed progression., Results: The study included 155 fractures in 152 patients, with a mean patient age of 51 and a mean follow-up of 17 months. A 3-month mRUST score of ≤8 predicted reoperation with a PPV of 25% and a NPV of 99%. The timing of radiographic union was associated with tobacco use (1.2 months later; P = 0.04), open fracture (1.4 months later; P = 0.04), and the use of topical antibiotics (2.1 months longer; 95% CI, 0.33-3.84; P = 0.02); however, topical antibiotics were at high risk of being confounded by injury severity. Delayed progression to fracture healing, wherein the most rapid radiographic healing occurs more than 3 months postoperatively, was predicted by chronic kidney disease ( P < 0.01)., Conclusions: A 3-month mRUST score >8 suggests a very high likelihood of avoiding reoperation for nonunion. Tobacco use and open fractures were associated with a longer time to radiographic union. Chronic kidney disease is associated with a delayed radiographic progression, suggesting a need for adjusted expectations and management strategies in these patients., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bladder cancer patients unable to receive cystectomy or who choose to pursue organ-sparing approach are managed with definitive (chemo)radiotherapy. However, this standard of care has not evolved in decades and disease recurrence and survival outcomes remain poor. Identifying novel therapies to combine with radiotherapy (RT) is therefore paramount to improve overall patient outcomes and survival. One approach is to find cellular mechanisms that can be targeted to increase the radiosensitivity of bladder cancer. The stress-activated kinase directly downstream from p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase activated protein kinase 2 (MAPKAPK2 or MK2), has been shown to enhance cancer-mediated inflammation, mesenchymal gene expression, and in vivo tumor growth. Here we examined the impact that MK2 knockdown (KD) has on bladder cancer cell radiosensitivity., Methods: We utilized short hairpin RNA (shRNA) KD of MK2 using lentiviral transfection in the bladder cancer cell lines, T24 and HTB9. We compared the growth of KD cells to wild type using colony formation assays, proliferation assays and cell counts to determine differences in cell growth. Apoptosis was examined by annexin-based flow cytometry and western blots. Flow cytometry was also used for cell cycle analysis., Results: KD clones showed a greater than 90% inhibition of MK2 expression as determined by western blot. Clonogenic assays exhibited an increase in radiosensitivity among the MK2 KD bladder cancer cells. These data were supported with proliferation assays that displayed a greater reduction in cell number following RT in MK2 KD bladder cancer cells. Annexin V binding in bladder cancer cells suggested increased apoptosis in MK2 KD cells. This was confirmed by comparing the amount of cleaved caspase products for the caspases 3 and 8 to scrambled control (SCR), and the release of cytochrome C into the cytosol. Both cell types showed disruptions in the cell cycle but at different points in the cycle., Conclusion: These results show that MK2 controls irradiation-induced apoptosis in bladder cancer cells., Competing Interests: None to declare., (Copyright 2024, Morgan et al.)

Background: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV and solid organ transplant recipients, 2 immunosuppressed populations, may help identify novel etiologic relationships with infectious agents., Methods: We used 2 linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified according to site and histology codes. Standardized incidence ratios were used to compare risk in people with HIV and solid organ transplant recipients with the general population. For selected cancer entities, incidence rate ratios were calculated for indicators of immunosuppression within each population., Results: We identified 38 047 cancer cases in solid organ transplant recipients and 53 592 in people with HIV, yielding overall standardized incidence ratios of 1.66 (95% confidence interval [CI] = 1.65 to 1.68) and 1.49 (95% CI = 1.47 to 1.50), respectively. A total of 43 cancer entities met selection criteria, including conjunctival squamous cell carcinoma (people with HIV standardized incidence ratio = 7.1, 95% CI = 5.5 to 9.2; solid organ transplant recipients standardized incidence ratio = 9.4, 95% CI = 6.8 to 12.6). Sebaceous adenocarcinoma was elevated in solid organ transplant recipients (standardized incidence ratio = 16.2, 95% CI = 14.0 to 18.6) and, among solid organ transplant recipients, associated with greater risk in lung and heart transplant recipients compared with recipients of other organs (incidence rate ratio = 2.3, 95% CI = 1.7 to 3.2). Salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma showed elevated risk in solid organ transplant recipients (standardized incidence ratio = 3.9,  4.7, and  3.2, respectively) but not in people with HIV. However, risks for these cancers were elevated following an AIDS diagnosis among people with HIV (incidence rate ratio = 2.4, 4.3, and  2.0, respectively)., Conclusions: Elevated standardized incidence ratios among solid organ transplant recipients and people with HIV, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival squamous cell carcinoma, sebaceous adenocarcinoma, salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma., (Published by Oxford University Press 2024.)

Introduction: Dorsiflexion weakness, or footdrop, is a well-described sequela of high-energy acetabular and pelvic trauma, but little data exists describing the factors related to neurologic recovery and the timeline therein. An improved understanding of these factors would facilitate prognostication, patient education, and treatment decision-making. The aim of this study was to compare neurologic recovery between acetabular and pelvic fractures, delineate factors associated with recovery, and determine the expected timeline of recovery., Methods: A retrospective chart review was conducted at a level 1 tertiary referral center from 2000 to 2021 using CPT codes and keyword search functions to identify adult patients with neurologic injury in the setting of operative acetabular and/or pelvic ring trauma. Patients were included if they had documented, graded weakness not clearly explained by a concomitant injury (extremity or spine) following a pelvic/acetabular injury. Patients were followed to a minimum of 6 months follow-up or to neurologic recovery. Primary outcomes were the presence of motor recovery and time to initial and maximum recovery. The contributions of injury type and initial neurologic status were analyzed using logistic regression for impact on neurologic recovery., Results: We identified 121 patients with neurologic injury and resultant footdrop in the setting of an operative pelvic ring or acetabular fracture. From this cohort, 58 patients (47.9 %) demonstrated some degree of neurologic recovery in follow-up. There was no difference in recovery when comparing injury type (pelvis vs. acetabulum). Any motor function (including flicker) at time of initial evaluation was predictive of recovery (OR 6.18, [2.00 - 19.14]; p = 0.002). Initial neurologic function also correlated with more rapid recovery in comparison to patients with initial absent neurologic function both in time to initial recovery (56 days vs 107 days; p = 0.016) and time to maximum recovery (153 days vs 241 days; p = 0.027)., Conclusions: These results highlight the relatively poor prognosis for neurologic recovery in operative pelvic and acetabular injuries. Any initial neurologic function is predictive of likelihood of neurologic recovery and correlates with a more expedient neurologic recovery. Ultimately, this enables providers to better educate patients and facilitates decisions regarding further intervention., Competing Interests: Declaration of competing interest Colby C. Wollenman:none Cade Morris: none Ridge Maxson: none Claudia Davidson: none Jacquelyn S. Pennings: 3Spine – personal fees Steamboat Orthopaedics – personal fees Steamboat Orthopaedics – personal fees Phillip M. Mitchell: none The relationship, financial and otherwise, between Jacquelyn Pennings and the listed entities does not represent a conflict of interest regarding the subject matter of the paper entitled Recovery after Neurologic Injury in Operative Acetabular and Pelvic Fractures: Defining the Natural History of Foot Drop. As such, there are no other conflicts of interest which would impact the subject matter of this article in any way., (Copyright © 2024. Published by Elsevier Ltd.)

Stiff systems of ordinary differential equations (ODEs) are pervasive in many science and engineering fields, yet standard neural ODE approaches struggle to learn them. This limitation is the main barrier to the widespread adoption of neural ODEs. In this paper, we propose an approach based on single-step implicit schemes to enable neural ODEs to handle stiffness and demonstrate that our implicit neural ODE method can learn stiff dynamics. This work addresses a key limitation in current neural ODE methods, paving the way for their use in a wider range of scientific problems., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: A significant portion of youth sustain a concussion every year, with around 30% experiencing persistent post-concussion symptoms (PPCS). Research has shown exercising just below the exertion level that provokes symptoms can lead to more rapid recovery. However, youth often struggle to adhere to exercise recommendations following concussion., Methods: We conducted structured qualitative interviews ( n  = 32) with concussed youth and their parents to examine factors influencing motivation to engage in exercise post-concussion. Questions were framed through the lens of Self-Determination Theory (SDT) and Thematic Analysis was used to code and analyze transcripts., Results: Four primary factors appeared to motivate youth to exercise after receiving a concussion: 1) social support, 2) accountability, 3) goal setting, and 4) structure. Utilizing the lens of SDT, one could theorize that including social support and accountability helped fulfill the need of relatedness, setting goals helped fulfill the need of autonomy, and providing program structure helped fulfill the need for competence., Conclusions: Our results suggest that Self-Determination Theory may be a useful frame for examining exercise adherence post-concussion. Incorporating social support, accountability, goal setting and structure could increase the effectiveness of exercise prescription post-concussion and should be the focus of further study.

Dercas nina Mell 1913 (Pieridae) is a little-studied butterfly species endemic to China that flies primarily in the forest canopy. Genome skimming by Illumina sequencing allowed assembly of 146,702 reads for complete 1471.3-fold mean coverage of the circular 15,264 bp mitogenome from D. nina consisting of 82.1% AT nucleotides. A gene order typical of butterflies was recovered consisting of 13 protein-coding genes, 22 tRNAs, two rRNAs, and a predicted control region. The Dercas nina COX1 open reading frame begins with atypical start codon CGA. Six protein-coding genes ( COX1 , COX2 , ND2 , ND3 , ND4 , ND5 ) with single-nucleotide (T) stop codons, and two protein-coding genes ( ATP6 , ATP8 ) with two-nucleotide (TA) stop codons encoded in the DNA were inferred to be completed by adenine nucleotides from the Poly-A tail of the mRNA. Bayesian's phylogenetic reconstruction places the D. nina and D. lycorias mitogenomes as sister clades. Dercas mitogenomes were sister to those from genus Colias in the monophyletic subfamily Coliadinae. The mitogenome phylogeny is consistent with previous molecular phylogenetic hypotheses based on other markers, but differs somewhat from a morphology-based hypothesis that suggested that Dercas was more closely related to genus Gonepteryx . This may falsify the hypothesis or may instead reflect mitochondrial-nuclear phylogenetic discordance., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Tissue-resident memory T (T RM ) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T RM cell fate remains poorly understood. Here, we show that whereas skin T RM cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T RM cells in the small intestine. We found that RA was required for the long-term maintenance of intestinal T RM populations, in part by impeding their retrograde migration. Moreover, enhanced RA signaling modulated T RM cell phenotype and function, a phenomenon mirrored in mice with increased microbial diversity. Together, our findings reveal RA as a fundamental component of the host-environment interaction that directs immunosurveillance in tissues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cancer risk among people with HIV (PWH) has declined over time as a result of antiretroviral therapy, but it is unclear whether all racial/ethnic groups and transmission risk groups have experienced equal declines., Methods: We used data on PWH aged ≥20 years old from the HIV/AIDS Cancer Match Study during 2001-2019. We used Poisson regression to assess time trends in incidence rates for each cancer site by racial/ethnicity and risk group, adjusting for age, registry, and sex. We also estimated adjusted rate ratios across racial and ethnic and risk groups in 2001-2004 and 2015-2019., Results: Trends in age-standardized rates differed across Black, White and Hispanic PWH, and across risk groups for some cancers. For example, liver cancer rates declined 23% per 5-year period among White PWH, 11% in Black PWH and 18% in Hispanic PWH. Anal cancer rates declined among men who have sex with men, were stable among people who inject drugs, and increased among other risk groups Between 2001-2004 and 2015-2019, relative difference in cancer incidence rates by race/ethnicity increased for HL and liver cancer but decreased for NHL; by risk group, relative differences increased for NHL and liver cancer, and decreased for HL, lung and anal cancers., Conclusions: Among PWH in the US, during 2001-2019, HL, lung, liver, and cervical cancer rate trends were different across racial/ethnic groups. HL, lung, anal, and liver cancer rates trends were different across risk groups. Future work should examine underlying causes of the differences in trends., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Objective: To investigate the extent of extraskeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI)., Study Design: This cross-sectional study utilized the Kids' Inpatient Database as a part of the Healthcare Cost and Utilization Project to investigate inpatient hospital outcomes and management in patients with OI from 1997 through 2016. Data regarding hospital characteristics, cost of treatment, inpatient outcomes, and procedures were collected and analyzed., Results: There were 7291 admissions that listed OI as a diagnosis in the Kids' Inpatient Database from 1997 through 2016. Unexpectedly, more than one-third of all admissions in these children with OI presented with an extraskeletal manifestation. The rate of major complications was 3.85%. The rate of minor complications was 19.4%, most commonly respiratory problems. The mortality rate was 18.2% in the neonatal period and 1.0% in all other admissions. Total charges of hospital stay increased over the years., Conclusions: We identified a striking prevalence of extraskeletal manifestations in OI along with inpatient outcomes and complications associated with OI, of which respiratory complications were predominant. We observed a significant financial burden for patients with OI and identified additional risks for financial crisis, in addition to disparities in care identified among socioeconomic groups. These data contribute to a more holistic understanding of OI from diagnosis to management., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Studies show metformin use before and during SARS-CoV-2 infection reduces severe COVID-19 and postacute sequelae of SARS-CoV-2 (PASC) in adults. Our objective was to describe the incidence of PASC and possible associations with prevalent metformin use in adults with type 2 diabetes mellitus (T2DM)., Research Design and Methods: This is a retrospective cohort analysis using the National COVID Cohort Collaborative (N3C) and Patient-Centered Clinical Research Network (PCORnet) electronic health record (EHR) databases with an active comparator design that examined metformin-exposed individuals versus nonmetformin-exposed individuals who were taking other diabetes medications. T2DM was defined by HbA1c ≥6.5 or T2DM EHR diagnosis code. The outcome was death or PASC within 6 months, defined by EHR code or computable phenotype., Results: In the N3C, the hazard ratio (HR) for death or PASC with a U09.9 diagnosis code (PASC-U09.0) was 0.79 (95% CI 0.71-0.88; P < 0.001), and for death or N3C computable phenotype PASC (PASC-N3C) was 0.85 (95% CI 0.78-0.92; P < 0.001). In PCORnet, the HR for death or PASC-U09.9 was 0.87 (95% CI 0.66-1.14; P = 0.08), and for death or PCORnet computable phenotype PASC (PASC-PCORnet) was 1.04 (95% CI 0.97-1.11; P = 0.58). Incident PASC by diagnosis code was 1.6% metformin vs. 2.0% comparator in the N3C, and 2.1% metformin vs. 2.5% comparator in PCORnet. By computable phenotype, incidence was 4.8% metformin and 5.2% comparator in the N3C and 24.7% metformin vs. 26.1% comparator in PCORnet., Conclusions: Prevalent metformin use is associated with a slightly lower incidence of death or PASC after SARS-CoV-2 infection. PASC incidence by computable phenotype is higher than by EHR code, especially in PCORnet. These data are consistent with other observational analyses showing prevalent metformin is associated with favorable outcomes after SARS-CoV-2 infection in adults with T2DM., (© 2024 by the American Diabetes Association.)

Background: Overhead athletes are particularly susceptible to elbow valgus extension overload syndrome and development of pathologic changes in the posteromedial elbow. Though arthroscopic débridement/osteophyte resection is frequently performed, few studies have analyzed the outcomes of this procedure and none have specifically addressed professional level athletes., Hypothesis: We hypothesized that following posteromedial elbow débridement, Major League Baseball (MLB) pitchers would exhibit a higher rate of ulnar collateral ligament (UCL) reconstruction than baseline incidence in the existing literature, along with a decline in pitching performance., Methods: Using publicly accessible websites, MLB athletes undergoing posteromedial elbow débridement from 2007 to 2022 were identified. Demographic information, procedure details, return to play (RTP) information, return to the disabled/injured list (DL/IL), subsequent UCL reconstruction, and pitching statistics were analyzed. Pitching performance metrics included earned runs average, walks plus hits per innings pitched, innings pitched, and fastball velocity., Results: A total of 39 MLB players, including 26 pitchers, were included. Within the first three seasons after surgery, 82.1% (n = 32) of players returned to play at the MLB level at a mean time of 176.1 ± 69 days. Pitchers exhibited a RTP rate of 76.9% (n = 20) at 175.8 ± 16 days. A total of 38.5% (n = 10) of pitchers returned to the DL/IL for elbow-related issues within three seasons. Subsequent UCL reconstruction was seen only in pitchers, with a frequency of 19.2% (n = 5). No statistically significant differences between single season preoperative/postoperative pitching metrics were identified. A small but significant (P < .05) decrease in fastball velocity (94.4 vs. 92.84; P = .02) was observed over a three-season comparison., Conclusion: Contrary to our hypothesis, this study demonstrates that posteromedial elbow débridement is a viable surgery in MLB athletes, with RTP rate of 82.1% and no increase in rate of UCL reconstruction. Furthermore, there was no significant difference in single season preoperative and postoperative statistical pitching performance. However, over three years postoperatively, there was a 38.5% rate of return to the DL/IL for ongoing elbow ailment and a significant decrease in pitch velocity, raising some concern over the longevity of postoperative improvements., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pragmatic measures of evidence-based practice (EBP) implementation can support and evaluate implementation efforts. We examined the predictive validity of therapist reports of EBP strategy delivery for children's mental health outcomes. Data were obtained from 1,380 sessions with 248 children delivered by 76 therapists in two county systems. Children (M age =11.8 years, SD = 3.7) presented with internalizing (52%), externalizing (27%), trauma (16%), and other (5%) concerns. Therapists reported their delivery of EBP strategies on a revised version of the EBP Concordant Care Assessment (ECCA; Brookman-Frazee, et al., Administration and Policy in Mental Health and Mental Health Services Research, 48, 155-170, 2021) that included 25 content (e.g., parenting, cognitive behavioral) and 12 technique strategies (e.g., modeling, practice/role-play). On average, 5.6 ECCA session reports (SD = 2.3) were obtained for each client, and caregivers reported symptoms on the Brief Problem Checklist (Chorpita, et al., Journal of Consulting and Clinical Psychology, 78(4), 526-536, 2010) at baseline, weekly over two months, and again at four months. Multilevel models examined whether the mean extensiveness of each EBP strategy predicted trajectories of child outcomes. More individual technique (6 of 12) than content strategies (1 of 25) were associated with outcome trajectories. For techniques, more extensive use of Performance Feedback and Live Coaching and less extensive use of Addressing Barriers were associated with greater declines in total symptoms, and more extensive use of Establishing/Reviewing Goals, Tracking/Reviewing Progress, and Assigning/Reviewing Homework was associated with declines in externalizing symptoms. For content, more extensive use of Cognitive Restructuring was associated with declines in total symptoms. In addition, higher average extensiveness ratings of the top content strategy across sessions was associated with greater declines in total and externalizing symptoms. Therapist-reported delivery of some EBP strategies showed evidence of predictive validity and may hold utility in indexing quality of care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study was to: (1) confirm the factor structure of a therapist-report measure of adaptations to an autism evidence-based intervention (EBI), (2) identify predictors of adaptation types, and (3) examine associations of adaptation types with observed therapist fidelity. Participants included a subset of therapists (N = 70; 31.4% Hispanic), autistic children (N = 79; ages 5-13 years; 57.0% Hispanic), and their caregivers (N = 77; 54.5% Hispanic), who participated in the training condition of a community effectiveness trial of An Individualized Mental Health Intervention for Autism (AIM HI). Families reported demographics and completed assessments of child functioning and caregiver strain at baseline. Therapists submitted video recordings of psychotherapy sessions during EBI training, which were later coded for fidelity by independent raters. Therapists completed the Adaptations to Evidence-Based Practices Scale at the end of the 6-month training period. Multi-level confirmatory factor analysis yielded two adaptation types consistent with prior research: Augmenting and Reducing/Reordering adaptations. In multi-level models, higher Augmenting adaptations were associated with lower child cognitive functioning (B= -0.01, p < .05), higher child autism characteristics (B = 0.01, p < .05), and Non-Hispanic White caregiver ethnicity (B = - 0.17, p < .01). Higher Reducing/Reordering adaptations were associated with Non-Hispanic White caregiver race/ethnicity only (B = - 0.33, p < .01). There were no significant associations between therapist-reported adaptations and observed fidelity. This study further supports Augmenting and Reducing/Reordering as distinct subtypes of adaptations with unique predictors. Therapists likely adapt AIM HI to tailor the EBI to individual client needs and do so in ways that do not appear to interfere with fidelity. Trial Registration ClinicalTrials.gov identifier NCT02416323., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Symbolic regression with polynomial neural networks and polynomial neural ordinary differential equations (ODEs) are two recent and powerful approaches for equation recovery of many science and engineering problems. However, these methods provide point estimates for the model parameters and are currently unable to accommodate noisy data. We address this challenge by developing and validating the following Bayesian inference methods: the Laplace approximation, Markov Chain Monte Carlo (MCMC) sampling methods, and variational inference. We have found the Laplace approximation to be the best method for this class of problems. Our work can be easily extended to the broader class of symbolic neural networks to which the polynomial neural network belongs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fronk 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.)

Objective: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs)., Design: In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another antiretroviral drug to their regimen., Methods: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a nonlinear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use-related variables., Results: The median BMI gain in 4 194 patients over 3 years was + 1.9 kg/m 2 [interquartile range (IQR) 0.1-4.1]. Most patients were black (55%) and men (77%). Multivariable modeling from 20 528 BMI measurements revealed that the type of ART accounted for just 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain but no differences were observed between INSTIs, PIs, and rilpivirine, or between TAF and abacavir., Conclusion: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population., Methods: We performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors., Results: Participants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine., Conclusion: Our results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Youth have been increasingly struggling with their mental health, leading to an unprecedented rise in emergency room visits and inpatient psychiatric admissions. It is prudent for mental health providers to be familiar with all services within a continuum of care that can address the early phases of a crisis, allowing youth to remain in the community while being treated. The system of care (SOC) approach has demonstrated positive effects in mitigating the need for hospital-based services. There is a call among experts to integrate SOC concepts during inpatient psychiatric admissions to promote youth remaining within a community after discharge., Competing Interests: Disclosure The authors have no disclosures or conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study examined the heterogeneity of early literacy profiles of English learners and non-English learners. Utilizing a latent profile analysis, the degree to which distinct learner profiles emerged was examined using code-based and language-based measures administered in the beginning of first grade. Participants included 11,803 English learners and 34,129 non-English learners. Three early literacy profiles emerged for English learners while four profiles emerged for non-English learners. Both sets of profiles can be identified based on the severity of students' difficulties with component skills rather than the specificity of their difficulties. Resulting profiles in both samples were then utilized to predict performance on a measure of broad reading comprehension administered at the end of first and second grade. Results indicated that the profile that was associated with the greatest success on the later measures of reading comprehension for both samples included the strongest performance on measures of both code-related and language-related skills. Results highlight the heterogeneity of early literacy skills within the English learner and non-English learner populations and demonstrate the importance of designing instruction that addresses the severity of a student's skill deficit.

Introduction: Congenital pulmonary airway malformations (CPAM), intra- and extralobar bronchopulmonary sequestrations (iBPS/eBPS), CPAM-BPS hybrid lesions (HL), congenital lobar emphysema (CLE), bronchial atresia (BA), and foregut duplication cysts (FDC), collectively referred to as congenital thoracic lesions (CTL), are mostly solitary. Patients with multiple CTL are rare, and reports on such cases are scarce. To address this dearth, we analyzed a large multifocal CTL patient cohort., Methods: Retrospective chart review of patients born between September 1, 2013, and March 31, 2023, who underwent surgery for a CTL at our tertiary center. Patients with radiological and surgical diagnosis of multifocal CTL, defined as ≥2 CTL present in more than one lobe were included to record pre-, peri-, and postnatal patient characteristics., Results: Among 701 CTL patients, 74 (10.5%) had multiple CTL. CTL multifocality was prenatally recognized correctly in 8 (12.9%) patients. Most multiple CTL were right-sided, unilateral multilobar lesions (n = 33, 44%). Bilateral CTL were found in 9 (12.1%) patients. CPAM-CPAM lesions were the most prevalent CTL types (n = 36, 49%). Genetic syndromes were confirmed in 3 (4%) and additional congenital anomalies in 9 (12.9%) patients, 5 of those had multiple congenital anomalies. Of 49 (65%) patients with multilobar CTL, 25 (51%) underwent bilobectomy and 24 (49%) lung-sparing surgery. Length of stay was similar. Mortality was 5.4%., Conclusion: We report on the largest patient cohort with multiple CTL to date. Multiple CTL occurred in 1/10 patients with CTL, and only 12.9% were recognized prenatally. Lung-sparing surgery can be considered. Multiple additional congenital anomalies and genetic syndromes may be more common and genetic testing should be considered. Overall, outcomes in this patient population are favorable., (© 2024 S. Karger AG, Basel.)

Study Design: Multicenter, international prospective study., Objective: This study investigated the clinical outcome up to 2 years after multi-level spinal deformity surgery in the elderly by reporting the minimal clinically important difference (MCID) of EuroQol 5-dimensions (EQ-5D), EQ-VAS, and residential status., Methods: As an ancillary study of 219 patients ≥60 years with spinal deformity undergoing primary instrumented fusion surgery of ≥5 levels, this study focuses on EQ-5D (3-L) as the primary outcome and EQ-VAS and residential status as secondary outcomes. Data on EQ-5D were compared between pre-operatively and postoperatively at 10 weeks, 12 months, and 24 months. An anchor-based approach was used to calculate the MCID., Results: The EQ-5D index and EQ-VAS, respectively, improved significantly at each time point compared to pre-operatively (from .53 (SD .21) and 55.6 (SD 23.0) pre-operatively to .64 (SD .18) and 65.8 (SD 18.7) at 10 weeks, .74 (SD .18) and 72.7 (SD 18.1) at 12 months, and .73 (SD .20) and 70.4 (SD 20.4) at 24 months). 217 (99.1%) patients lived at home pre-operatively, while 186 (88.6%), 184 (98.4%), and 172 (100%) did so at 10 weeks, 12 months, and 24 months, respectively. Our calculated MCID for the EQ-5D index at 1 year was .22 (95% CI .15-.29)., Conclusions: The EQ-5D index significantly increased at each time point over 24 months after ≥5 level spinal deformity surgery in elderly patients. The MCID of the EQ-5D-3 L was .22. Patients living at home pre-operatively can expect to be able to live at home 2 years postoperatively., 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.

Venous thromboembolism (VTE), comprising pulmonary embolism and deep vein thrombosis, is one of the most common complications after knee arthroscopy. Sequelae of VTE include VTE recurrence, postthrombotic syndrome, and potential for loss of limb or life. Given the increasing volume of knee arthroscopy procedures worldwide and the considerable morbidity and mortality associated with VTE, it is important to prevent, diagnose, and treat VTEs efficiently and effectively. Risk factors such as history of VTE, family history of VTE, genetic coagulopathy, oral contraceptive use, cancer history, and old age increase the risk of postoperative VTE and warrant consideration of prophylaxis. Diagnosis and treatment should be initiated rapidly in the setting of concerning symptoms and positive imaging diagnosis, respectively. The purpose of this review was to provide a framework to individualized VTE risk, weigh prophylaxis options, expedite diagnostic pathways, and implement outpatient treatment algorithms., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Prior reviews have highlighted that nature exposure was a valuable coping strategy enhancing mental health during the COVID-19 pandemic. However, no existing reviews have determined the quality of evidence and risk of bias of the empirical studies supporting this claim. To address this gap, we employed a Navigation Guide systematic review and meta-analysis approach to investigate associations between nature exposure and mental health during the pandemic. Searches in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo retrieved relevant articles published between January 1, 2020, and March 4, 2024. We used the Navigation Guide methodology to assess the risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments to evaluate the overall quality of evidence. Our search retrieved 113 studies that met the inclusion criteria and reported diverse types of exposure, including nature availability, nature visit frequency, green space accessibility, and green space type, alongside associations with 12 mental health outcomes. Meta-analyses found access to gardens was associated with lower odds of depression [(Pooled odds ratio [OR] = 0.71, 95%CI = 0.61, 0.82), I 2  = 0%, n = 3] and anxiety [(Pooled OR = 0.73, 95%CI = 0.63, 0.84), I 2  = 0%, n = 3]. Increased time in green spaces was associated with lower level of stress [(Pooled Corr = -0.11, 95%CI = -0.17, -0.05), I 2  = 0%, n = 2]. Higher frequency of visits to nature was associated with improved mental well-being [(Pooled standardized beta = 0.10, 95%CI = 0.07, 0.14), I 2  = 0%, n = 2] and general mental health [(Pooled standardized beta = 0.11, 95%CI = 0.03-0.38), I 2  = 82%, n = 2]. However, the number of pooled studies was small and the overall quality of evidence was "very low" for all outcomes, and high levels of bias were observed (26% of studies had high, 71% probably high). Nonetheless, given the trends in the results, nature-based solutions emphasizing exposure to gardens and green spaces near the home may have promoted psychological resilience during this public health crisis., 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 Ltd. All rights reserved.)

Myotonic dystrophy type 1 is an autosomal dominant condition due to a CTG repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. This multisystem disorder affects multiple organ systems. Hypogonadism in males affected by myotonic dystrophy is commonly reported; however, the effect on female hypogonadism remains controversial. A 19-year-old female was referred to our genetics clinic due to primary amenorrhea without any family history of similar symptoms. Initial genetics evaluation identified a variant of uncertain significance in IGSF10, c.2210T>C (p.Phe737Ser). Follow-up genetic evaluation via whole genome sequencing identified at least 100 CTG repeats in the DMPK gene, thus resulting in the diagnosis of myotonic dystrophy type 1. The patient remains otherwise asymptomatic from myotonic dystrophy. This is the first report that demonstrates primary amenorrhea as a possible presenting feature of myotonic dystrophy type 1, thus providing evidence supporting female hypogonadism in myotonic dystrophy type 1., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

This study examined six reading intervention teachers' implementation of the SPELL-Links to Reading and Writing intervention with students in Grades 2 and 3. The purpose was to explore the extent to which teachers who received a one-day training session without ongoing coaching support were able to implement the intervention with fidelity. It also aimed to better understand the determinants (i.e., barriers and facilitators) of teachers' implementation and their perceptions related to the importance, feasibility, and effectiveness of the intervention. Data from four sources (implementation logs, implementation observations, interviews, and surveys) were collected and analyzed. Participating teachers did not implement the intervention at the intended dosage of 4 days per week, but they did demonstrate high adherence and quality on average. Several barriers to implementation were identified, including intervention training, intervention content and structure, compatibility with existing practices, and alignment with goals. Notable facilitators of implementation were teacher capability and peer support. Teachers had varying perceptions of the intervention, with neutral satisfaction on average. These findings indicate a need for further research on determinants of intervention implementation as they may be crucial in supporting teachers' implementation fidelity., (© 2024. The Author(s).)

Palladin is an actin binding protein that accelerates actin polymerization and is linked to metastasis of several types of cancer. Previously, three lysine residues in an immunoglobulin-like domain of palladin have been identified as essential for actin binding. However, it is still unknown where palladin binds to F-actin. Evidence that palladin binds to the sides of actin filaments to facilitate branching is supported by our previous study showing that palladin was able to compensate for Arp2/3 in the formation of Listeria actin comet tails. Here, we used chemical crosslinking to covalently link palladin and F-actin residues based on spatial proximity. Samples were then enzymatically digested, separated by liquid chromatography, and analyzed by tandem mass spectrometry. Peptides containing the crosslinks and specific residues involved were then identified for input to HADDOCK docking server to model the most likely binding conformation. Small angle X-ray scattering was used to provide further insight into palladin flexibility and the binding interface, and NMR spectra identified potential interactions between palladin's Ig domains. Our final structural model of the F-actin:palladin complex revealed how palladin interacts with and stabilizes F-actin at the interface between two actin monomers. Three actin residues that were identified in this study also appear commonly in the actin binding interface with other proteins such as myotilin, myosin, and tropomodulin. An accurate structural representation of the complex between palladin and actin extends our understanding of palladin's role in promoting cancer metastasis through regulation of actin dynamics., Significance: In this study we have combined various advanced structural biology techniques to provide the first comprehensive model of the palladin-actin complex. Considering palladin's role in cancer cell metastasis, this structure could be useful in screening and developing chemotherapeutic agents that target this interaction and prevent cancer cell metastasis.

Hypochlorous acid (HOCl) is crucial for pathogen defense, but an imbalance in HOCl levels can lead to tissue damage and inflammation. Existing HOCl indicators employ an oxidation approach, which may not truly reveal the chlorinative stress environment. We designed a suite of indicators with a new chlorination-based mechanism, termed HOClSense dyes, to resolve HOCl in sub-cellular compartments. HOClSense dyes allow the visualization of HOCl with both switch-on and switch-off detection modes with diverse emission colors, as well as a unique redshift in emission. HOClSense features a minimalistic design with impressive sensing performance in terms of HOCl selectivity, and our design also facilitates functionalization through click chemistry for resolving subcellular HOCl. As a proof of concept, we targeted plasma membrane and lysosomes with HOClSense for subcellular HOCl mapping. With utilizing HOClSense, we discovered the STING pathway-induced HOCl production and the abnormal HOCl production in Niemann-Pick diseases. To the best of our knowledge, this is the first chlorination-based HOCl indicator series for resolving subcellular HOCl., Competing Interests: Declaration of interests The authors declare no competing financial interests.