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Group therapy has evolved as a powerful therapeutic approach, facilitating mutual support, interpersonal learning, and personal growth among members. However, the complexity of studying communication dynamics, emotional expressions, and group interactions between multiple members and often coleaders is a frequent barrier to advancing group therapy research and practice. Fortunately, advances in machine learning technologies, for example, natural language processing (NLP), make it possible to study these complex verbal and behavioral interactions within a small group. Additionally, these technologies may serve to provide leaders and members with important and actionable feedback about group therapy sessions, possibly enhancing the utility of feedback-informed care in group therapy. As such, this study sought to provide a proof of concept for applying NLP technologies to automatically assess alliance ratings from participant utterances in two community-based online support groups for weight stigma. We compared traditional machine learning approaches with advanced transformer-based language models, including variants pretrained on mental health and psychotherapy data. Results indicated that several models detected relationships between participant utterances and alliance, with the best performing model achieving an area under the receiver operating characteristic curve of 0.654. Logistic regression analysis identified specific utterances associated with high and low alliance ratings, providing interpretable insights into group dynamics. While acknowledging limitations such as small sample size and the specific context of weight stigma groups, this study provides insights into the potential of NLP in augmenting feedback-informed group therapy. Implications for real-time process monitoring and future directions for enhancing model performance in diverse group therapy settings are discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Purpose: Patients with dementia symptoms often struggle to limit movements during PET examinations, necessitating motion compensation in brain PET imaging to ensure the high image quality needed for diagnostic accuracy. This study validates a data-driven motion-compensated (MoCo) PET brain image reconstruction algorithm that corrects head motion by integrating the detected motion frames and their associated rigid body transformations into the iterative image reconstruction. Validation was conducted using phantom scans, healthy volunteers, and clinical patients using four radiotracers with distinct tracer activity distributions., Methods: We conducted technical validation experiments of the algorithm using Hoffman brain phantom scans during a series of controlled movements, followed by two blinded reader studies assessing image quality between standard images and MoCo images in 38 clinical patients receiving dementia scans with [ 18 F]Fluorodeoxyglucose, [ 18 F]N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)-nortropane, [ 18 F]flutemetamol, and a research group comprising 25 elderly subjects scanned with [ 18 F]fluoroethoxybenzovesamicol., Results: The Hoffman brain phantom study demonstrated the algorithm's capability to detect and correct for even minimal movements, 1-mm translations and 1⁰ rotations, applied to the phantom. Within the clinical cohort, where standard images were deemed suboptimal or non-diagnostic, all MoCo images were classified as having acceptable diagnostic quality. In the research cohort, MoCo images consistently matched or surpassed the standard image quality even in cases with minimal head movement, and the MoCo algorithm never led to degraded image quality., Conclusion: The PET brain MoCo reconstruction algorithm was robust and worked well for four different tracers with markedly different uptake patterns. Moco images markedly improved the image quality for patients who were unable to lie still during a PET examination and obviated the need for any repeat scans. Thus, the method was clinically feasible and has the potential for improving diagnostic accuracy., Competing Interests: Declarations. Ethics approval: The research study was conducted according to the Declaration of Helsinki and approved by the Regional Ethics Committee (project number 1-10-72-270-19). Consent to participate: Informed consent was obtained from all individual participants included in the research study. Consent to publish: Publication consent was obtained from all research study participants. Competing interests: The authors JJ, IH and SZ are full-time employees of Siemens Medical Solutions USA, Inc. ABR is a full-time employee of Siemens Healthcare A/S Denmark. No other potential conflicts of interest relevant to this article have been reported., (© 2025. The Author(s).)

Background: American Indians (AI) experience disparities in cancer outcomes. Little is known about the quality of end-of-life (EOL) care in AI patients with cancer., Methods: We retrospectively analyzed EOL care for North Carolina patients who died (decedents) diagnosed with any cancer (2003-2018) using the Cancer Information and Population Health Resource. Measures of EOL care quality were informed by existing literature and included in-hospital death, hospice use and other healthcare utilization within the last 30 days of life. Associations between race/ethnicity and EOL outcomes were evaluated to estimate adjusted risk ratios (aRRs). Because within group heterogeneity can influence health outcomes and intervention effectiveness, we also evaluated associations among AI individuals only., Results: We identified 163,285 (1,769 AI and 161,516 White) decedents. The majority (60%) of AIs lived in a geographic area characterized by non-federally recognized tribes. AI decedents had greater proportions of rural residence than White decedents (54.5% AI vs 30.4% White) and dual Medicaid/Medicare enrollment (37.4% AI vs 17.7% White). Compared with White decedents, AI decedents had increased hospital admission (aRR, 1.10, 95% confidence interval [CI], 1.06-1.15), ICU admission (aRR, 1.21; 95% CI, 1.11-1.32), and >1 ED visit (aRR, 1.31; 95% CI, 1.20-1.44) in the last 30 days of life. We observed significant within-group variation in EOL care quality among AI patients., Conclusions: Structural barriers to care and rurality may contribute to lower quality EOL care among AI decendents, when compared with White patients. High-quality, culturally appropriate EOL care will require a better understanding of care decision-making and access., (© The Author(s) 2025. Published by Oxford University Press. 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.)

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer., Patients and Methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer., Results: More than 2,500 patients were screened for target expression. In the multiarm study, 738 (45%) of 1,638 tested patients were HLA-A*02-positive. NY-ESO-1 and LAGE-1a testing was positive in 12% (62/525) and 4% (15/348) of tested patients, respectively. Forty-one patients positive for HLA-A*02 and antigen expression were screened in the single-arm study. Overall, 43 patients underwent leukapheresis and 18 received lete-cel across studies. Lete-cel demonstrated a manageable safety profile. No fatal treatment-related serious adverse events (AE) were reported in either study. Cytopenias and cytokine release syndrome were the most common treatment-emergent AEs. Combining pembrolizumab with lete-cel did not seem to increase toxicity over lete-cel alone. Limited antitumor activity was observed; one of 18 patients had a durable response persisting for 18 months. Pharmacokinetic data showed similar T-cell expansion in all patients., Conclusions: Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Antitumor activity was observed in a limited number of patients., (©2024 The Authors; Published by the American Association for Cancer Research.)

Aims: The Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma., Methods: With representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting's process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries. Supported by major orthopaedic oncology organizations, the meeting used a modified Delphi process to develop consensus statements through online questionnaires, thematic groupings, narrative reviews, and anonymous pre-meeting polling., Results: Strong (> 80%) consensus was achieved on 19 out of 21 statements, reflecting agreement among delegates. Key areas of consensus included the role of radiology in diagnosis and surveillance, the management of locally recurrent disease, and the treatment of dedifferentiated chondrosarcoma. Notably, there was agreement that routine chemotherapy has no role in chondrosarcoma treatment, and radiological surveillance is safe for intraosseous chondrosarcomas. Despite the overall consensus, areas of controversy remain, particularly regarding the treatment of atypical cartilage tumours and surgical margins. These unresolved issues underscore the need for further research and collaboration within the orthopaedic oncology community., Conclusion: BOOM represents the largest global consensus meeting in orthopaedic oncology, providing valuable guidance for clinicians managing chondrosarcoma worldwide. The consensus statements offer a reference for clinical practice, highlight key research priorities, and aim to improve patient outcomes on a global scale., Competing Interests: L. M. Jeys reports royalties or licenses from Implantcast, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Implantcast, Zimmer Biomet, and Stryker, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study. G. V. Morris reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study. E. Botello reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Zimmer Biomet, all of which are unrelated to this study. R. A. Boyle reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and support for attending meetings and/or travel from Zimmer Biomet, unrelated to this study. M. T. Houdek reports consulting fees from Link Orthopedics and Stryker, unrelated to this study. A. Puri is a member of the editorial board of The Bone & Joint Journal. P. Ruggieri reports consulting fees from Exactech and royalties or licenses from Stryker, unrelated to this study. M. Laitinen reports support for attending meetings and/or travel from Tree-Step, unrelated to this study., (© 2025 Jeys et al.)

We describe a proof of concept for a new microbial identification technique using Direct Frequency Infrared (DFIR) multispectral imaging. This approach combines Quantum Cascade Laser (QCL) light sources with a microbolometer array in a lensless configuration to capture detailed multispectral images of microbial colonies. These optical fingerprints blend both morphological and spectral information, without the need for staining or colony picking. A proof-of-concept database was acquired, comprising 10 strains from 8 species across 4 distinct genera. In total, 2253 microbial colonies were imaged at 9 different mid-infrared wavelengths. Machine learning classification correctly identified up to 94.4% ± 1.6 of colonies fingerprints, efficiently discriminating even closely related strains. Reducing the number of wavelengths to 4 maintained high classification performance, demonstrating the method's robustness. The resulting system is faster and simpler than existing FTIR imaging systems, making it a promising tool for microbial identification., (© 2025 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Purpose: Hepatoscope® is an ultraportable ultrasound system with 50 Hz two-dimensional transient elastography (2DTE) for liver stiffness measurement (LSM). It provides a quality index (QI) for individual stiffness values that is based on imaging features. This study evaluated the 2DTE intra- and inter-user repeatability in patients with chronic liver diseases (CLD) for novice and expert operators across various QI conditions. We compared the performances with other imaging and non-imaging elastography techniques., Methods: This investigation was a prospective cross-sectional single-center study. One hundred CLD patients underwent LSMs with vibration-controlled transient elastography (VCTE™), two-dimensional shear wave elastography (2DSWE) and 2DTE. Expert and novice operators each performed two consecutive exams with 2DTE, blinded to any output. Intra-class correlation coefficient for intra-, and inter-user repeatability were calculated as well as applicability for various QI conditions, and Spearman's correlations against VCTE and 2DSWE were assessed., Results: Computing LSM as the median of 10 stiffness values with a QI>85 % yielded the best compromise between reliability and applicability. In this setting, expert and inter-operator repeatability showed significant improvement over the condition with no QI threshold (ICC = 0.81 and 0.79, respectively) and 95 % applicability. Novice repeatability was excellent with a more restrictive QI (ICC = 0.80). LSM with 2DTE demonstrated strong and moderate correlation with VCTE and 2DSWE (r = 0.63 and 0.55, respectively)., Conclusion: Hepatoscope 2DTE provides a promising and reliable alternative for non-invasive liver stiffness assessment in patients with CLD. The application of the image-based QI enhances LSM reliability and consistency across novice and expert operators., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Juliette Foucher reports financial support, administrative support, equipment, drugs, or supplies, and statistical analysis were provided by E-Scopics. Cindy Serdjebi reports financial support was provided by E-Scopics. Adrien Besson reports financial support was provided by E-Scopics. Adele DELAMARRE reports financial support, administrative support, equipment, drugs, or supplies, and statistical analysis were provided by E-Scopics. Joel GAY reports financial support was provided by E-Scopics. Claude COHEN-BACRIE reports financial support was provided by E-Scopics. Cindy Serdjebi reports a relationship with E-Scopics that includes: employment. Adrien BESSON reports a relationship with E-Scopics that includes: employment and equity or stocks. Juliette FOUCHER reports a relationship with E-Scopics that includes: funding grants. Adele DELAMARRE reports a relationship with E-Scopics that includes: funding grants. Joel GAY reports a relationship with E-Scopics that includes: employment and equity or stocks. Claude COHEN-BACRIE reports a relationship with E-Scopics that includes: employment and equity or stocks. Adrien BESSON has patent #SONDE DE MESURE DE PROPRIETES VISCOELASTIQUES D'UN MILIEU WO 2022/084,502 issued to Assignee. Claude COHEN-BACRIE has patent #SONDE DE MESURE DE PROPRIETES VISCOELASTIQUES D'UN MILIEU WO 2022/084,502 pending to Assignee. Adrien BESSON has patent #PROCEDE D'ANALYSE D'UN MILIEU PERMETTANT DE REDUIRE LES EFFETS D'ARTEFACTS DUS A DES DEFORMATION STATIQUES DANS LE MILIEU WO 2024/068,949 issued to Assignee. Claude Cohen-Bacrie has patent #PROCEDE D'ANALYSE D'UN MILIEU PERMETTANT DE REDUIRE LES EFFETS D'ARTEFACTS DUS A DES DEFORMATION STATIQUES DANS LE MILIEU WO 2024/068,949 issued to Assignee. If there are other authors, they 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 © 2025 Elsevier Masson SAS. All rights reserved.)

Background: The knowledge and proficiency of primary care practitioners (PCPs) in diagnosing and managing irritable bowel syndrome (IBS) remain generally low and variable internationally. This variability is partly due to a lack of familiarity with the Rome Foundation diagnostic criteria and treatment guidelines for this condition., Methods: We conducted an electronic survey of PCPs in the United States and nine European countries to assess their understanding of IBS pathophysiology; the use of Rome IV criteria in diagnosis, knowledge of and frequency in prescribing various recommended treatments; and the likelihood of referring patients with suspected IBS to subspecialists., Results: Most PCPs in the United States and Europe perceive IBS as a diagnosis of exclusion rather than a definitive diagnosis. They also believe IBS is underdiagnosed in primary care and challenging to diagnose confidently. The majority of PCPs consider diet as a crucial component of IBS management. Notably, US PCPs reported greater confidence than their European counterparts in recommending dietary interventions such as increased dietary fiber, a low FODMAP diet, and gluten restriction. Conversely, both groups exhibited moderate to high confidence in recommending over-the-counter treatments. European PCPs showed greater confidence in treating IBS with antispasmodics and secretagogues, while US PCPs expressed greater confidence in prescribing neuromodulators. Additionally, US PCPs were more likely to refer patients with suspected IBS to a gastroenterologist, whereas both US and European PCPs showed similar referral patterns to dietitians and referred very few patients to mental health providers. Both US and European PCPs reported that IBS is moderately to extremely difficult to treat effectively and emphasized the importance of a strong and longitudinal doctor-patient relationship in managing the condition., Conclusion: Despite the Rome Foundation recommendations and criteria to support a positive diagnosis of IBS, most PCPs still rely on exclusionary investigations such as endoscopy and a serologic workup, while a significant percentage suggest referring patients to gastroenterologists., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objectives: Patients with rheumatoid arthritis (RA) are more likely to develop work disability than the general population. We investigated whether individuals younger than 65 years of age who had both RA and new-onset work disability were at higher risk of CVD compared to similarly aged individuals with RA who did not develop disability. We identified the factors that best explained the excess risk., Methods: This was a retrospective cohort study using data from the CorEvitas RA registry. Patients younger than 65 with RA were included. Exposure was new-onset work disability, and comparator was consistently working individuals. Cohorts were age- and sex-matched. Demographics, medications, and disease specific factors were collected for all patients. Incidence rates (IR) for cardiovascular events were calculated using Poisson regression and explanatory multivariable models were built using Cox proportional hazard ratios (HR) to determine the factors that explained the excess CVD risk., Results: Age and sex-adjusted IR was 5.40 per 1,000 person-years in the new-onset work disability group compared to 2.17 per 1,000 person-years in the working group. Work disability associated with CVD with HR = 2.32 (95 % CI 1.52, 3.53) in the age- and sex-adjusted model. Multivariate models accounting for functional status, education, medications, and traditional CVD risk factors could not fully explain the excess risk for CVD in newly work disabled patients with RA: HR = 1.78 (1.09, 2.91)., Conclusions: Patients younger than 65 with RA and new-onset work disability are at significantly increased risk for incident CVD compared to working peers. The excess CVD risk remained unexplained after accounting for multiple variables, possibly due to variables we cannot fully account for, such as social determinants of health and allostatic load., Competing Interests: Declaration of competing interest The authors declare the following interests: JRC received research support and consulting fees from Abbvie, Amgen, Aqtual, Bendcare, BMS, CorEvitas, FASTER, GSK, Janssen, Labcorp, Lilly, Novartis, Pfizer, Revero, Sanofi, Scipher, Setpoint, TNacity Blue Ocean, UCB JRC is supported by P30AR072583. KK receives salary support from the Corrona Research Foundation. JK received consulting fees from Rheum Now and Lilly. GWR received consulting fees from the Corrona Research Foundation and CorEvitas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: JG and HRK are named as inventors on PCT patent application #15/878,640, entitled Genotype-guided dosing of opioid agonists, filed Jan 24, 2018 and issued on Jan 26, 2021 as US Patent No. 10 900 082. MB is a paid member of the scientific advisory board for Nucleus Genomics.

Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC., Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients., Results: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients., Conclusions: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To distinguish the patterns of inner ear changes between meningogenic and otogenic routes in meningitis cases. Our hypothesis is that pinpointing distinct patterns linked to each route could aid in the development of diagnostic strategies and targeted therapies., Methods: Temporal bones (TBs) from patients with a history of meningitis and histopathological evidence of labyrinthitis were divided into two groups (otogenic and meningogenic). Inner ear histopathological examination was performed to identify qualitative and semi-quantitative changes. This assessment encompassed inflammation patterns, indications of early ossification, hair cell loss, and alterations in the lateral wall, round window membrane, cochlear aqueduct and vestibular aqueduct., Results: Thirty-six TBs were included in the study (otogenic, 21; meningogenic, 15). Generalized labyrinthitis was more common in otogenic cases (100% vs. 53%, p < 0.001). Early signs of cochlear ossification were exclusively observed in otogenic cases (9 TBs). The spiral ligament of otogenic cases has shown a uniform loss of fibrocytes across all cochlear turns, while meningogenic cases showed more severe loss in the apical turn. Otogenic cases exhibited a higher prevalence of severe inflammation of the cochlear aqueduct and endolymphatic sac. Meningogenic cases showed more severe loss of vestibular hair cells in the otolithic organs., Conclusion: Otogenic cases displayed a higher prevalence of changes in the spiral ligament and signs of early ossification, whereas meningogenic cases were associated with a higher degree of vestibular damage. Our findings emphasize the importance of considering the infection route and its implications for timely diagnosis and development of pathology-oriented treatment strategies., Level of Evidence: NA Laryngoscope, 135:864-872, 2025., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The rising prevalence of Alzheimer's disease (AD) and related dementia worldwide underscores the urgent need for effective interventions, particularly for managing neuropsychiatric symptoms (NPS) such as sleep disturbance. This review explores the emerging role of Dual Orexin Receptor Antagonists (DORA) in addressing sleep disturbance in patients with Alzheimer's disease dementia., Methods: A comprehensive literature search identified four relevant publications between 2014 and 2024, detailing the use of DORA medications, including suvorexant and lemborexant, in patients with Alzheimer's disease., Results: Findings suggest that suvorexant may improve total sleep time (TST), wakefulness after sleep onset (WASO), and sleep efficiency (SE) in Alzheimer's patients with insomnia. Lemborexant demonstrated potential in improving circadian rhythm parameters, particularly in patients with irregular sleep-wake rhythm disorder (ISWRD). Safety profiles of DORA medications appeared favorable, with mild to moderate adverse events reported. However, concerns over potential adverse events, such as falls, underscore the need for careful monitoring., Conclusion: While the evidence suggests promise for DORA medications in addressing sleep disturbance in Alzheimer's disease, limitations in study populations and duration highlight the need for further investigation. Future clinical trials should aim for broader inclusion criteria, encompassing diverse dementia subtypes and severity levels, to enhance generalizability. Additionally, longer-term trials are essential to assess the sustained efficacy and safety of DORA interventions in this vulnerable population., Competing Interests: DISCLOSURES The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension., Approach and Results: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value., Conclusions: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Intent inferral on a hand orthosis for stroke patients is challenging due to the difficulty of data collection. Additionally, EMG signals exhibit significant variations across different conditions, sessions, and subjects, making it hard for classifiers to generalize. Traditional approaches require a large labeled dataset from the new condition, session, or subject to train intent classifiers; however, this data collection process is burdensome and time-consuming. In this paper, we propose ChatEMG, an autoregressive generative model that can generate synthetic EMG signals conditioned on prompts (i.e., a given sequence of EMG signals). ChatEMG enables us to collect only a small dataset from the new condition, session, or subject and expand it with synthetic samples conditioned on prompts from this new context. ChatEMG leverages a vast repository of previous data via generative training while still remaining context-specific via prompting. Our experiments show that these synthetic samples are classifier-agnostic and can improve intent inferral accuracy for different types of classifiers. We demonstrate that our complete approach can be integrated into a single patient session, including the use of the classifier for functional orthosis-assisted tasks. To the best of our knowledge, this is the first time an intent classifier trained partially on synthetic data has been deployed for functional control of an orthosis by a stroke survivor.

Most cancer screening data report on Black participants without distinguishing nativity, limiting our understanding of the needs of distinct groups within the African diaspora. The purpose of this pilot study was to assess demographic characteristics and perceptions of the benefits of and barriers to mammography among African immigrant women in New York City (NYC). Forty-two women who were 40 years or older, born in Africa, and English and/or French-speaking were recruited from African immigrant communities in NYC to complete a survey. Eighty percent of our sample aged 50 to 73 was adherent to the 2016 USPSTF mammography screening guideline. The most frequently endorsed benefits were that mammography will help find breast cancer early, could help find a breast lump before it is big enough to feel, and that if found early, breast cancer could be successfully treated. The most endorsed barriers were that having a mammogram is painful and that lack of insurance or being treated rudely at the mammogram center would keep participants from having a mammogram. Chi-square analyses assessed relationships between demographic characteristics and perceptions about mammography and revealed that endorsement of barriers to screening (e.g., health issues, transportation problems, pain, and time associated with mammography) varied by educational attainment. Findings suggest that future interventions should be multi-level and (1) support patients in accessing screening via resource sharing, (2) address other commonly cited barriers such as fear of pain during the procedure, and (3) support anti-racist healthcare environments especially in terms of treatment by providers., Competing Interests: Declarations. Ethics Approval: This pilot study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai (protocol code STUDY-19–00114, initially approved 11/26/2019). Consent to Participate: Informed consent was obtained from all individual participants included in the pilot study. Competing Interests: The authors declare no competing interests., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background: Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery., Methods: In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models., Results: The primary composite occurred in 4725 (13.2%) patients in VISION and 1903 (20.6%) in POISE-2; in both studies cardiac events had a strong, graded association with lower preoperative eGFR that was attenuated by older age (P interaction <0.001 for VISION; P interaction =0.008 for POISE-2). For eGFR of 30 compared with 90 ml min -1 1.73 m -2 , relative risk was 1.49 (95% confidence interval 1.26-1.78) at age 80 yr but 4.50 (2.84-7.13) at age 50 yr in female patients in VISION. This differed modestly (but not meaningfully) in men in VISION (P interaction =0.02) but not in POISE-2 (P interaction =0.79). eGFR contributed the most predictive information and mean net benefit of all predictors in both studies, most C-statistic in VISION, and third most C-statistic in POISE-2., Conclusions: Continuous preoperative eGFR is among the best cardiac risk predictors in noncardiac surgery of the large set examined. Along with its interaction with age, preoperative eGFR would improve risk calculators., Clinical Trial Registration: ClinicalTrials.gov NCT00512109 (VISION) and NCT01082874 (POISE-2)., Competing Interests: Declarations of interest Roche Diagnostics provided troponin T assays and financial support for the VISION study. Bayer Pharma provided the aspirin used in the POISE-2 study, and Boehringer Ingelheim provided the clonidine and financial support for the POISE-2 study. Dr Devereaux reports grants from Roche Diagnostics and Abbott Diagnostics during the conduct of the study, and grants from Roche, Octopharma, Philips Healthcare, Stryker, Covidien, and Boehringer Ingelheim outside the submitted work. Dr Meyhoff is founder of a start-up company, WARD24/7 ApS, with the aim of pursuing the regulatory and commercial activities of the WARD-project (Wireless Assessment of Respiratory and circulatory Distress, a project developing a clinical support system for continuous wireless monitoring of vital signs) and has filed a patent for ‘Wireless Assessment of Respiratory and circulatory Distress (WARD), EP 21184712.4 and EP 21205557.8’. Dr Borges reports grants from Roche Diagnostics outside the scope of this work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Oral potentially malignant disorders (OPMDs) occur in up to 4%-5% of the population, of which oral leukoplakia (OL) is the most common subtype. Predicting high-risk OL remains a challenge. Early diagnosis and effective treatment are thought to be of paramount importance to improve outcomes., Methods: We searched PubMed and Clinicaltrials.gov data for updates in the clinical management of OL from 2015 to current., Results: Recent publication of large cohorts of patients with OL aids in counseling patients regarding risk of malignant transformation. Management for OL includes surveillance, excision, and laser surgery, as well as local and systemic approaches to chemoprevention. Several new entities show promise regarding candidate biomarkers, chemoprevention agents, and diagnostic adjuncts, though all require further validation., Conclusion: This update serves to further inform clinical management of OL and provide impetus for future investigations., Trial Registration: NCT00099021, NCT00951379, NCT05727761, NCT05727761., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objective: This cross-sectional study demonstrates the differences in the dimensions of musculoskeletal (MSK) pain between participants with mental distress and/or insomnia among general population with MSK pain within the past 12 months., Methods: Participants of Northern Finland Birth Cohort 1966 (NFBC1966) were studied (n = 4316). They were divided into groups based on their mental distress and insomnia status (co-occurring mental distress and insomnia [CMI], isolated mental distress [M] and insomnia [I], and absence of both [AMI]). The AMI group was used as a reference for the main analyses. The dimensions of MSK pain included frequency, bothersomeness (Numerical Rating Scale [NRS] 0-10), intensity of pain (NRS), and number of pain sites (1-8). Multinomial and general linear regression analyses were used to study the associations, and adjustments were made for sex, education, number of somatic diseases, and physical activity., Results: The CMI group was associated with more severe pain in every dimension when contrasted to all other groups (daily pain adjusted OR 5.08, 95 % CI 3.43-7.51; bothersomeness adjusted β 1.7, 95 % CI 1.5-2.0; intensity adjusted β 1.4, 95 % CI 1.2-1.7; number of pain sites adjusted β 1.2, 95 % CI 1.0-1.4). Compared to AMI, I and M groups also had relationships with all pain dimensions, but with lower magnitude compared to the CMI group., Conclusions: The results suggest that insomnia and mental distress co-exist with more severe MSK pain, and when co-occurring, MSK pain severity tends to increase. Therefore, contemplating insomnia and mental distress are important to consider when comprehensively evaluating MSK pain symptoms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. NFBC1966 46y follow-up study received financial support from the University of Oulu Grant no. 24000692, Oulu University Hospital Grant no. 24301140, ERDF European Regional Development Fund Grant no. 539/2010 A31592. The funders played no role in the study design, data collection or interpretation, nor in the decision to submit the study for publication. The authors did not receive any external funding., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Right ventricular (RV) dysfunction (RVD) after orthotopic heart transplantation (OHT) is a common cause of morbidity and mortality. Impella RP Flex was recently approved for RV support as a temporary mechanical circulatory device. We present the first case of its use in managing RVD in a patient after OHT. Here, a 40 year old male patient with familial dilated cardiomyopathy and factor V Leiden mutation presented with Society for Cardiovascular Angiography & Interventions (SCAI) stage B cardiogenic shock. Hemodynamics at admission were indicative of need for intra-aortic balloon pump (IABP) support. Hemodynamics improved and patient underwent OHT. Postoperative day (POD) 1, IABP support was changed to 1:2 and eventually removed. Hemodynamics deteriorated quickly, requiring pharmacologic RV support and diuresis, but refractory RV failure persisted. Impella RP Flex was chosen due to the patient's small size and was placed via the right internal jugular vein on POD 12. The procedure was well tolerated, with the patient ambulatory the following day (POD 13). Impella was removed on POD 25 after 13 days of support. Patient achieved normal kidney, intrinsic rhythm improved sinus rhythm, and ultimately discharged on POD 50. Impella RP flex has emerged as a promising future indication as single or biventricular support postcardiac transplantation., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

As recently as the 1980s, it was not uncommon for paediatric surgeons to operate on infants without anaesthesia. Today, the same omission would be considered criminal malpractice, and there is an increased concern with the possibility of consciousness in the earliest stage of human infancy. This concern reflects a more general trend that has characterised science since the early 1990s of taking consciousness seriously. While this attitude shift has opened minds towards the possibility that our earliest experiences predate our first memories, convincing demonstrations of infant consciousness remain challenging given that infants cannot report on their experiences. Furthermore, while many behavioural and neural markers of consciousness that do not rely on language have been validated in adults, no one specific marker can be confidently translated to infancy. For this reason, we have proposed the 'cluster-based' approach, in which a consensus of evidence across many markers, all pointing towards the same developmental period, could be used to argue convincingly for the presence of consciousness. CONCLUSION: We review the most promising markers for early consciousness, arguing that consciousness is likely to be in place by 5 months of age if not earlier., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Characterizing HIV clustering rates and their trends over time can improve understanding a local epidemic and enhance its control., Methods: Leveraging an academic-public health partnership in Rhode Island, we explored longitudinal dynamics of statewide clustering rates among key populations from 1991 to 2023. Partial HIV-1 pol sequences were grouped by year of HIV-1 diagnosis. Molecular clusters were identified in cumulative annual phylogenies. Overall clustering rates, and clustering rates of newly diagnosed and prevalent infections, and of specific sociodemographic characteristics of key populations over time were determined. Mann-Kendall statistics were used to estimate clustering rate trends and relationships among groups., Results: By the end of 2023, 2630 individuals with sequences represented the statewide epidemic in Rhode Island. Overall clustering rates increased from 7% in 1991 to 46% in 2023, correlating with cumulative sequence increase. Clustering rates of newly diagnosed and prevalent infections significantly increased over time, higher in newly diagnosed individuals since the early 2000s. Increases were also observed among groups defined by gender, age, transmission risks, race, mental illness, HIV-1 subtypes, and country of birth, with some crossovers and divergence patterns over time., Conclusion: Exploring dynamics of HIV clustering rates over three decades in a statewide HIV-1 epidemic expanded its characterization and provided insight into its evolving changes. These dynamics may indicate a gradual shift towards a more concentrated and localized HIV-1 epidemic, highlighting important opportunities for targeted interventions to effectively prevent new HIV transmissions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Durable biventricular support may be necessary to bridge patients with end-stage biventricular failure to heart transplantation. This study compares waitlist and post-transplant outcomes between patients supported with continuous flow, durable biventricular assist devices (BiVAD), and total artificial heart (TAH)., Methods: Using the UNOS registry, we analyzed adult (≥18 years old), first-time transplant candidates with TAH or BiVAD at the time of listing or transplantation from 10/1/2010-10/31/2020, with follow-up through 3/31/2022. Multivariable proportional subdistribution hazards models and cause-specific Cox proportional hazards models were used to compare death/deterioration or heart transplantation on the waitlist between cohorts. Kaplan-Meier and multivariable Cox proportional hazards model were used to evaluate one-year post-transplant survival and evaluate difference in outcomes based on annual transplant center volume., Results: The waitlist cohort included a total of 228 patients (25% BiVAD). Waitlist outcomes between device types were similar. The transplanted cohort included a total of 352 patients (25% BiVAD). There was a trend towards worse one-year post-transplant survival in patients bridged with TAH versus BiVAD (log-rank p-value = 0.072) that persisted after adjusting for age, gender, policy, and removing dual-organ recipients (HR 1.94 (0.94, 3.98) p-value = 0.07). There was a difference in one-year post-transplant survival amongst TAH-bridged patients when stratified by annual transplant center volume (log-rank p-value = 0.013). One-year post-transplant survival between TAH-supported patients from high annual transplant volume centers and BiVAD-supported patients was similar (p-value = 0.815)., Conclusions: BiVAD and TAH are reasonable support strategies with TAH implantation at high-volume transplant centers (51+ transplants/year) having similar 1-year post-transplant survival to BiVAD-supported patients., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objective: The authors aimed to increase measurement-based care in an outpatient academic psychiatry service., Methods: The Measurement-Assisted Care program (MAC) was implemented as a clinical quality-improvement effort that included 4,665 unique patients and 176 clinicians over 12 months. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), PTSD Checklist for DSM-5, and Brief Inventory of Thriving were automatically included in the patient electronic check-in process for new visits; the PHQ-9 and GAD-7 were included for return visits. Patient responses were automatically routed to clinicians' electronic health record inboxes and documentation templates. MAC was rolled out in two phases, and clinicians were surveyed about their use of MAC data 3-6 months after the start of the program., Results: After implementation of MAC, PHQ-9 completion rates increased from 5% to 66% of visits for phase 1 and from 5% to 60% for phase 2. Post-MAC completion rates were higher for telehealth (70%) than for in-person (40%) visits. More than 90% of clinicians reported that MAC was useful with at least one of their three most recent patients, and 51% reported that it was useful with all three of their three most recent patients. Clinician adoption was high, with 78% reporting that they use MAC data to guide care., Conclusions: MAC increased the completion rate of patient-reported outcome measures, especially for telehealth visits. Clinicians reported that they frequently use and discuss MAC data with patients, implying that technology-supported workflows can help systems with high telehealth utilization capture and use patient-reported outcomes., Competing Interests: Dr. Raffel has received payments for her contributions to articles published through UpToDate. Dr. Nagle-Yang has received honoraria for continuing medical education presentations through Physicians’ Education Resource, the Annenberg Center for Health Sciences, and Postpartum Support International. Ms. Schwenk receives consulting fees from the Fairbanks Native Association. Dr. Dempsey has a contract to conduct a pilot implementation of Babyscripts, a digital-based platform for postpartum mental health education and symptom monitoring. She has received grant funding from Health Rhythms and has received speaker honoraria from the National Perinatal Association, Cornell School of Medicine, and Dell Medical School at the University of Texas at Austin. The other authors report no financial relationships with commercial interests.

Purpose: This study examined the use of behavioral design strategies to improve healthier food sales., Design: A quasi-experimental, one-group, repeated measures design examined changes in food sales following behavioral design adjustments., Setting: United States military base hospital dining facility., Subjects: U.S. military service members, retirees, and civilian employees., Intervention: Behavioral design changes included placement, layout, messaging, default healthy bundling, a stoplight rating system, strategic positioning of healthy items on menu boards, and an increase in healthier snacks., Measures: Food sales were assessed by point-of-sales data., Analysis: T-tests examined total sales of each food adjusted weekly between baseline and intervention and intervention and post-intervention. 16 food items targeted by the intervention were examined. Weekly food sales were calculated for the 18-week baseline, 18-week intervention, and 9-week post-intervention. Further, analysis estimated negative binomial models for food item sales., Results: The hospital dining facility served 600 to 900 meals per day. Weekly foods sales decreased during the intervention for desserts, cooked starches, hummus, and yogurt ( P < 0.01). Sales increased during the intervention for fruit cups, cooked vegetables, vegetable and turkey burgers, grilled chicken, packaged salads, French fries, hamburgers, and hot dogs ( P < 0.02)., Conclusion: This study demonstrates that a mixture of behavioral design strategies can be operationalized with reasonable fidelity and can lead to increases in the sales of some healthy foods in military worksites., 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.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine., Competing Interests: Declaration of interests JA received research support from Pfizer, Janssen, and Merck; has been a speaker for BMS, AbbVie, and Janssen; and reports consultancy with Janssen, Pfizer, AbbVie, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb Roivant, and Adiso. JB received grants to institution from Bausch, Grifols, Mallinckrodt, Cosmo, and Sequana and received personal fees for acting as has consultant for Merz and Novo Nordisk. PDC was co-founder of The Akkermansia Company and Enterosys. WMdV was co-founder and shareholder of The Akkermansia Company (Belgium), Caelus Pharmaceuticals (Netherlands) and Alba Health (Copenhagen-Stockholm). EE is a scientific cofounder of DayTwo and BiomX and is an advisor to Purposebio, Aposense, Zoe, and MyGutly. FG has received personal fees for acting as speaker and consultant from Biocodex, Danone, BioGaia, Menarini, and Sanofi. CLH received lecture honoraria from Baxter, Janssen, BMS, and Tillotts. SK received research support from Rebioitx/Ferring, Vedanta, Finch, Seres, and Pfizer and served as consultant for ProbioTech, Takeda, and Rise. OK is a co-founder of Shela Accurate Diagnosis (Israel). JKu received travel support and speaker fees from Ferring, AbbVie, KRKA, Takeda, Janssen, Pfizer, and Ipsen. RL received research funding from Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, and McKusker Charitable Foundation and is an advisory board member for AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda. PM received speaker honoraria from Aboca, Alfasigma, Allergosan, Bayer, Biocodex, and Menarini and is a member of the advisory board of Aboca, Alfasigma, Allergosan, Bayer, Biocodex, and Menarini. JM has received consultancy fees from Cultech and EnterioBioti. SCN received personal fees for acting as speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; receives patent royalties through her affiliated institutions and is named inventors of patent applications held by The Chinese University of Hong Kong and Microbiota I-Center that cover the therapeutic and diagnostic use of microbiome; received research grants through her affiliated institutions from Olympus, Ferring, and AbbVie; is a founder member and shareholder of GenieBiome; and has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie. SPa reports consultancy for Vedanta Biosciences and received personal fees for acting as speaker and for acting as advisory board member for AbbVie, Dr Falk Pharma, Ferring, Janssen, and Takeda. FRP received personal fees for acting as speaker or consultant for AbbVie, Gilead, Roche, Astra Zeneca, Ipsen MSD, Eisai, Kedrion, Bayer, and Alfasigma and is an advisory board member of AbbVie, Gilead, Roche, Astra Zeneca, Ipsen MSD, Eisai, Kedrion, Bayer, and Alfasigma. MRS received personal fees for acting as speaker or advisory board member for Hemofarm, Abela Pharm, and ADOC Pharma. HS reports lecture fee, board membership, or consultancy from Amgen, Fresenius, Ipsen, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, and AbbVie; has stocks from Enterome bioscience; and is co-founder of Exeliom Biosciences. HTu is a named inventor of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. RKW received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico, and Ferring; received speaker's fees from MSD, AbbVie, and Janssen Pharmaceuticals; and acted as consultant for Takeda Pharmaceuticals. GZ is named inventor on a patent (EP2955232A1) and received personal fee as member of the scientific advisory board of Alpha Biomics. FZ conceived the concept of GenFMTer and trasnendoscopic enteral tubing and the devices related to them (FMT Medical) and is an advisory board participant for Ferring and Seres. NS reports consultancy or SAB contracts with Zoe, Roche, Ysopia, and Freya, and Alia Therapeutics; speaker fees by Illumina; and is cofounder of PreBiomics. AG reports personal fees for consultancy for Eisai, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie Board MRGE, and Sanofi; personal fees for acting as a speaker for Takeda, AbbVie, and Sandoz; and personal fees for acting on advisory boards for VSL3 and Eisai. GC has received personal fees for acting as advisor for Ferring Therapeutics. GI has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics, Illumina, and Tillotts Pharma and for acting as consultant or advisor for Ferring Therapeutics, Giuliani, Metagenics, and Tillotts Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Antimicrobial resistance is considered a global One Health threat. Controlling selection pressure by reducing antibiotic use in livestock is a significant component of the response to this threat. The science concerning use and resistance is complicated and affected by time from antibiotic exposure, changing bacterial fitness, and varies by drug and pathogen. From May 2020 through October 2023, we collected intestinal (substandard and sick pigs) and fecal swab (healthy pig) samples at breed-to-wean (BTW) and wean-to-market (WTM) swine production sites and isolated E. coli bacteria. Antibiotic susceptibility testing was performed on these isolates to determine minimum inhibitory concentrations (MIC) for ceftiofur and enrofloxacin. Monthly antibiotic purchase data were used to calculate the active milligrams of drug purchased and these were divided by the kilograms of pigs produced from a farm site to provide a mass-adjusted proxy metric for farm-level antibiotic use. The relationship between use and MIC was then evaluated using a variety of multivariable statistical models. Across multiple modeling approaches, both farm type (i.e., BTW versus WTM) and farm-level antibiotic use maintained statistically significant relationships relative to E. coli MIC values for each respective drug. Use of ceftiofur and enrofloxacin can lead to increased MIC values among E. coli over time. The reasons for antibiotic purchases were not tracked as part of this project. Future work should evaluate the age of the individual pig and the time from last treatment when sampling these animals to separate out the group from individual-level effects of antibiotic use., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by National Pork Board. All authors reports financial support was provided by Foundation for Food and Agriculture Research. Laura Ruesch, Marlee Braun, Karyn Havas, Roy Edler, Joel Nerem, Scott Dee, Taylor Spronk reports financial support was provided by United States Department of Agriculture. Karyn A Havas, Roy Edler, Joel Nerem, Scott Dee, Taylor Spronk reports a relationship with Pipestone managed sow farms and independent family farmers that includes: consulting or advisory and employment. Authors from Pipestone Research and Pipestone Veterinary Services provide veterinary and research support to the farmers’ pigs that were sampled as part of the study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Specific information about the dispersion of Culex quinquefasciatus from Dschang in western Cameroon is scarce, and evidence-based interventions are needed. Common use of larvicides and adulticides conduct to the development of vectors resistance which can lead to deep biological changes, including fitness costs. We assessed the profile of insecticide resistance in field populations of Cx. quiquefasciatus and its potential fitness cost in a lineage selected for deltamethrin and permethrin resistance in the laboratory for two generations. The resistance intensity of the Cx. quinquefasciatus population was moderated when the population was exposed to deltamethrin at 10 × . Preexposure to PBO led to the restoration of full susceptibility to both deltamethrin and permethrin. Compared with that of the control group, female fecundity rates, egg hatchability, and pupation rates were significantly lower in the insecticide exposed groups. Larval development time and adults emergence rates were comparable between insecticide-exposed groups and the control. Insecticide-exposed adults lived longer than control adults did. Our findings suggest that the mechanisms selected for pyrethroid resistance are associated with negative impacts on different life-trait parameters and support the hypothesis that insecticide resistance is related to a high fitness cost., Competing Interests: Declarations. Ethics approval: All procedures performed in the study were in accordance with the local research ethics committee Statement for Use of Animals in Research. The ethical principles established by the Regional Ethics Committee for Human Health Research and Use of Laboratory Animals were followed. The research protocol was approved by the Ethics Committee on Animal Use (ethical clearance N° 2020/22/836/CE/CNERSH/SP). Consent for publication: Not applicable. Consent to participate: All authors confirm their participation in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Motivation: Spatial transcriptomics is a state-of-art technique that allows researchers to study gene expression patterns in tissues over the spatial domain. As a result of technical limitations, the majority of spatial transcriptomics techniques provide bulk data for each sequencing spot. Consequently, in order to obtain high-resolution spatial transcriptomics data, performing deconvolution becomes essential. Most existing deconvolution methods rely on reference data (e.g., single-cell data), which may not be available in real applications. Current reference-free methods encounter limitations due to their dependence on distribution assumptions, reliance on marker genes, or the absence of leveraging histology and spatial information. Consequently, there is a critical need for the development of highly flexible, robust, and user-friendly reference-free deconvolution methods capable of unifying or leveraging case-specific information in the analysis of spatial transcriptomics data., Results: We propose a novel reference-free method based on regularized non-negative matrix factorization (NMF), named Flexible Analysis of Spatial Transcriptomics (FAST), that can effectively incorporate gene expression data, spatial, and histology information into a unified deconvolution framework. Compared to existing methods, FAST imposes fewer distribution assumptions, utilizes the spatial structure information of tissues, and encourages interpretable factorization results. These features enable greater flexibility and accuracy, making FAST an effective tool for deciphering the complex cell-type composition of tissues and advancing our understanding of various biological processes and diseases. Extensive simulation studies have shown that FAST outperforms other existing reference-free methods. In real data applications, FAST is able to uncover the underlying tissue structures and identify the corresponding marker genes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s).)

Purpose: We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities., Methods: In this first-in-human, phase I, dose escalation and expansion clinical trial, patients with relapsed or refractory large B-cell lymphoma received 19(T2)28z-1XX CAR T cells at four dose levels (DLs), ranging from 25 to 200 × 10 6 ., Results: Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 × 10 6 was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow-up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome rates were low at 4% and 7%, respectively. 1XX CAR T-cell products contain a higher proportion of CD8 T cells with memory features, and CAR T-cell persistence has been detected beyond 1-2 years in patients with ongoing remission., Conclusion: The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.

Background: Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, whole-exome sequencing (WES) studies of AUD are hampered by the lack of available samples., Methods: We analyzed WES data of 4,530 samples from the Yale-Penn cohort and 469,835 samples from the UK Biobank (UKB), which represents an unprecedented resource for exploring the contribution of coding variants in AUD. After quality controls, 2,039 European-ancestry (EUR: 1,420 cases) and 1,750 African-ancestry samples (AFR: 1,142 cases) from Yale-Penn, and 415,617 EUR samples (12,861‬ cases), 6,142 AFR samples (130 cases) and 4,607 South Asian (SAS) samples (130 cases) from UKB were included in the analyses., Results: We confirmed the well-known functional variant rs1229984 in ADH1B (P=4.88×10 -31 ) and several other variants in ADH1C. Gene-based collapsing tests considering the high allelic heterogeneity revealed the previously unreported genes, CNST (P=1.19×10 -6 ) attributable to rare variants with allele frequency < 0.001, and IFIT5 (P=3.74×10 -6 ) driven by the burden of both common and rare loss-of-function and missense variants., Conclusions: This study extends our understanding of the genetic architecture of AUD, by providing insights into the contribution of rare coding variants, separately and convergently with common variants in AUD., (Copyright © 2025. Published by Elsevier Inc.)

Equine Erythroparvovirus 1 is a parvovirus that was identified in the blood of four horses in the United States. Here, we report one genome from a horse in New York State. This genome may represent a new species within the genus Erythroparvovirus .

Background: The Oswestry Disability Index (ODI) is a well-validated and widely used patient-reported outcome instrument to evaluate lumbar spinal stenosis (LSS) patients' treatment outcomes. The objective of the present study was to determine long the average interval between 2 preoperative measurements can be before a clinically significant difference of 10 points or more might appear., Methods: This was a retrospective observational study utilizing prospectively collected data from a single university hospital database, which was compatible with the national registry. One hundred and four surgically treated LSS patients were included in this observational study using systematic sampling. The preoperative ODI score was obtained at 2 timepoints. The 2-month mark as a potential turning point was of special interest, as the registry in question excludes preoperative data as outdated if the data are older than 2 months. Possible time dependence of the change in ODI scores was explored using a linear mixed-effects model with ODI as the dependent variable and interval length, sex, age, body mass index (BMI), and the presence of a concomitant disease as fixed effects., Results: The mean ODI score was 41.7 points (SD = 16.0) at the first and 41.1 points (SD = 15.5) at the second measurement. Mean time between the ODI scores was 74 days (range 8-361). On average, ODI changed by 9.17 points (SD = 7.16) between the 2 measurements, increasing for 48 patients, remaining unchanged for 9 patients, and decreasing for 47 patients. The arithmetic mean of the changes was -0.60 points and the median was 0.00 points. The estimated change in the population mean was -0.0005 points/day (95% CI [-0.022, 0.022], P = 0.97), meaning that we have strong evidence that the change in the mean is not clinically significant for up to 15 months (95% CI between ±10 points). Furthermore, no evidence was found that age, sex, BMI, or concomitant diseases were associated with the change of ODI score over time. Furthermore, the probability to observe a clinically significant change in a patient did not depend on the number of days between the 2 measurements (OR 1.003, 95% CI [0.997, 1.010], P = 0.30). Variance in ODI change did not grow over time., Conclusions: The probability of observing a clinically significant differences does not depend on the length of the observation interval, and ODI scores can be considered equally reliable for a significantly longer time than 2 months, even up to 1 year., Clinical Relevance: Preoperative ODI scores do not lose reliability up to 1 year in patients undergoing operatively treatment for LSS., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2025 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

The opioid crisis has disproportionately affected U.S. veterans, leading the Veterans Health Administration to implement opioid prescribing guidelines. Veterans who receive care from both VA and non-VA providers-known as dual-system users-have an increased risk of Opioid Use Disorder (OUD). The interaction between dual-system use and demographic and clinical factors, however, has not been previously explored. We conducted a retrospective study of 856,299 patient instances from the Washington DC and Baltimore VA Medical Centers (2012-2019), using a deep neural network (DNN) and explainable Artificial Intelligence to examine the impact of dual-system use on OUD and how demographic and clinical factors interact with it. Of the cohort, 146,688(17%) had OUD, determined through Natural Language Processing of clinical notes and ICD-9/10 diagnoses. The DNN model, with a 78% area under the curve, confirmed that dual-system use is a risk factor for OUD, along with prior opioid use or other substance use. Interestingly, a history of other drug use interacted negatively with dual-system use regarding OUD risk. In contrast, older age was associated with a lower risk of OUD but interacted positively with dual-system use. These findings suggest that within the dual-system users, patients with certain risk profiles warrant special attention., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Institution Review Boards for the Washington DC VA. Medical Center and West Haven VA., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included. Of those, 93.8% were on ART (95% CI 93.3-94.2) and 76.7% were VS (95% CI 75.8-77.6). In 2022, we tested the tool in the RESPOND Cohort for all countries with more than 100 participants under follow-up in 2019. We included 26,426 HIV positive persons from clinics in 27 countries, 97.8% (95% CI 97.6-98.0) were on ART and 91.5% were VS (95% CI 91.2-91.8%). There was good agreement between the RESPOND country estimates of ART and VS and the estimations using a random sample calculated in ESTIHIV. With ESTIHIV, clinics can produce a reliable estimate in figures for reporting and for monitoring the effectiveness of care in their clinics., Competing Interests: AM has received personal honoraria, travel support, and lecture fees from Gilead and ViiV, and consultancy fees from Eiland and Bonnin, all outside the submitted work. JG is an employee at Gilead Sciences. HG is an employee at ViiV Healthcare. For the remaining authors none were declared., (Copyright: © 2025 Raben 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.)

Over the past 50 years, intensive short-term dynamic psychotherapy (ISTDP) has been developed, implemented, and evaluated with respect to the treatment of a broad spectrum of complex, chronic, and treatment-resistant conditions. This therapy was developed specifically to treat a range of patients, including those who are highly defensive, those who experience the repression of emotions, and those who have cognitive-perceptual disruptions along with primitive defenses. These three groups of patients are characterized by patterns of attachment trauma and deficits related to neglect. Among the many categories of mental illness with these features that ISTDP can treat, personality disorders, treatment-resistant depression, and somatic symptoms have been the most frequently studied. In this article, the authors provide an overview of the ISTDP treatment method with regard to complex, chronic, and treatment-resistant conditions and summarize evidence for its effectiveness for diverse patient populations. On the basis of the available evidence, ISTDP warrants consideration as a tool for the management of diverse populations who have chronic and complex conditions and have not responded to other treatments., Competing Interests: The authors report no financial relationships with commercial interests. Holly A. Swartz, M.D., Editor of the journal, was the decision editor during peer review.

Evidence-based treatment of chronic pain requires a multidisciplinary approach grounded in the biopsychosocial model. Implementing this approach within health systems relies on its acceptance by both healthcare providers and patients. While pioneering multidisciplinary pain clinics can serve as a model for implementation, a systematic effort is needed to share knowledge effectively and broadly. In the current paper we provide an overview of the knowledge translation initiatives undertaken at our Transitional Pain Service (TPS) at Toronto General Hospital, a state-of-the-art multidisciplinary pain program established in 2014 for patients at risk of developing chronic pain after surgery. The TPS team strives to enhance acceptance of this model of care among patients and providers, facilitate the establishment of similar clinics, and promote patient understanding of the integrated multidisciplinary pain care approach. Guided by the Knowledge to Action (KTA) framework, knowledge translation activities undertaken by our TPS team include clinician training, resources and outreach activities for providers, and patient education. Resource development was preceded by consultation and needs assessment among patients and providers and feedback from both groups was incorporated as part of the development process. The tailored resources were disseminated via the TPS clinic website and monitoring of online usage enables continuous evaluation of engagement. Barriers to engagement with the resources were examined through patient surveys and staff interviews. Based on these activities, we offer insights gained by our team throughout the knowledge translation process and provide recommendations for other clinical teams who wish to undertake similar initiatives., Competing Interests: Declarations. Ethics approval and consent to participate: The activities described in this project were approved by the Quality Improvement Review Committee (QIRC) at the University Health Network (UHN), including protocols and informational consent (QI ID#: 21–0310). QIRC determined that the project falls outside the scope of research requiring Research Ethics Board (REB) review, as described in the Canadian Tri‐Council Policy Statement V.2. This determination was subsequently reviewed and confirmed by a UHN REB Chair. The need for signed consent to participate was deemed unnecessary as part of the approval by QIRC (QI ID#: 21–0310) and in accordance with Canadian Tri‐Council Policy Statement V.2. An informational consent letter was provided instead to all participants, which outlined the objective of the project, privacy and confidentiality, and contact information for the project team and QIRC. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The Extractables and Leachables Safety Information Exchange (ELSIE) Consortium added to the sensitization potency analysis of Parris et al. (2023) by including the Product Quality Research Institute (PQRI) extractable and leachable dataset (Johnson et al., 2024; Product Quality Research Institute, 2021). This analysis of the comprehensive E&L dataset showed 5% of chemicals (20/407) had experimental results demonstrating or were predicted to be potent (strong or extreme) sensitizers, supporting the previous conclusion, that potent sensitizers are of low prevalence and are not routinely observed as leachables in pharmaceutical products. By accounting for prevalence of sensitization in the overall E&L dataset, the probability of any potential leachable being more potent than the less than lifetime ICH M7 (10, 20, and 120 μg/day for human exposure of >1-10 years, >1-12 months, and <1 month repectively) and non-mutagenic ELSIE threshold values (35, 110, and 180 μg/day for human exposures of >10 years to lifetime, >1-10 years, and ≤1 year respectively) (Masuda-Herrera et al., 2022) was considered. The M7 and ELSIE thresholds are anticipated to provide ≥95% coverage of induction of sensitization, supporting the use of these thresholds to set the Safety Concern Threshold (SCT)., Competing Interests: Declaration of Competing Competing Interest The authors have nothing to declare., (Copyright © 2025. Published by Elsevier Inc.)

In response to increased illicit use of synthetic opioids, various μ-receptor antagonist formulations, with varied pharmacological characteristics, have been and are being developed. To understand how pharmacologic characteristics such as absorption rate and clearance rate affect reversal in treating community opioid overdose, we used our previously published translational opioid model. We adapted this model with in vitro receptor binding data and clinical pharmacokinetic data of three intranasal nalmefene formulations along with an intranasal naloxone formulation to study the reversal of fentanyl and carfentanil-induced respiratory depression in chronic opioid users. Nalmefene has a longer plasma half-life and slower unbinding from the μ-receptor compared to naloxone. For a more rapid reversal of acute overdose-induced respiratory depression, a fast-absorbing antagonist formulation may be of greater utility than a slow-absorbing one containing the same dosage of the antagonist. For preventing renarcotization caused by a long opioid exposure, a slow-clearing antagonist with slow unbinding from the receptor may be of value. While a more potent antagonist with a longer half-life may have the potential to facilitate recovery from respiratory depression for overdose with synthetic opioids, such interventions may also lead to longer and more pronounced withdrawal. This emphasizes the need for a nuanced consideration of several facets while choosing a μ-receptor antagonist, dose, and formulation to treat community opioid overdose cases., (Published 2025. This article is a U.S. Government work and is in the public domain in the USA.)

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measure the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments show that N-terminal domain mutations affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP but also provides insights into its evolutionary constraints., Competing Interests: Declaration of interests N.C.W. consults for HeliXon., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Objectives: Reversal of warfarin-induced anticoagulation using prothrombin complex concentrate (PCC4) is more rapidly achieved than with traditional methods, such as fresh frozen plasma (FFP). In many rural facilities, the availability of both FFP and PCC4 has been limited. A tertiary hospital instituted a program to provide PCC4 to rural sites using an air transport team and pharmacy exchange. We hypothesized that increasing accessibility of PCC4 would shorten time to INR reversal., Methods: This was a retrospective study with the primary outcome being time to INR reversal (INR ≤ 1.6) and time to PCC4 administration from outside hospital admission. Active warfarin prescription, transfer to a tertiary facility, and administration of anticoagulation reversal between January 2013 and December 2020 were required for inclusion. Patients were grouped by dates before and after implementation of the program in August 2016. Linear regressions were performed to determine the effect of the variable and INR reversal methods on the time to INR reversal as well as the time to PCC4 administration. Time-to-event analysis was used to analyze the primary outcome between comparison groups. p values of less than 0.05 were considered significant., Results: Chart review identified 189 patients: 56 within the pre-implementation group and 133 within the post-implementation group. Statistics were compared between these two groups. The post-implementation group had a shorter time to INR reversal (median 9.97 h) compared with the pre-implementation group (median 14.58 h, p  = 0.00004). Time to PCC4 administration was also significantly decreased ( p  = 0.023). No statistically significant differences were found for hospital survival or 30-day mortality., Conclusion: In rural hospitals, increasing availability of PCC4 using air medical transport along with a medication exchange program significantly reduces time to PCC4 administration in warfarin anticoagulated patients.

Herein, we report a selective photooxidation of commodity postconsumer polyolefins to produce polymers with in-chain ketones. The reaction does not involve the use of catalyst, metals, or expensive oxidants, and selectively introduces ketone functional groups. Under mild and operationally simple conditions, yields up to 1.23 mol % of in-chain ketones were achieved. Installation of in-chain ketones resulted in materials with improved adhesion of the materials and miscibility of mixed plastics relative to the unfunctionalized plastics. The introduction of ketone groups into the polymer backbone allows these materials to react with diamines, forming dynamic covalent polyolefin networks. This strategy allows for the upcycling of mixed plastic waste into reprocessable materials with enhanced performance properties compared to polyolefin blends. Mechanistic studies support the involvement of photoexcited nitroaromatics in consecutive hydrogen and oxygen atom transfer reactions., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Household well water can be degraded by contaminants from the land's surface, but private well owners lack means to protect the source water from neighboring disturbances. Rural residents of southwestern Wisconsin, USA, rely on private well water, and the combination of land use and fractured carbonate bedrock makes groundwater vulnerable to contamination. To identify the extent, sources, and risk factors of private well contamination, randomly selected wells sampled during two-day periods in fall (n = 301) and spring (n = 529) were analyzed for nitrate and indicator bacteria, and a subset (n = 138) was sampled across four seasonal events for analysis of pathogens and microbial source tracking markers by quantitative polymerase chain reaction. Risk factors representing land use, hydrology, geology, and well construction were analyzed for associations with contamination in multivariable models. The importance of risk factors varied by contaminant, illustrating the multifaceted nature of rural groundwater quality. Nitrate contamination was associated with agricultural land use, and wells with casings that extended below a shale aquitard accessed less contaminated water than those drawing water from above it. Human fecal microbes were detected in 64 wells (46%), and rainfall was the key risk factor for contamination, indicating that wastewater from septic systems was available to contaminate wells when transport conditions were favorable. Manure microbes from cattle/ruminants and pigs were detected in 33 and 13 wells, respectively, and concentrations increased with the hectarage of cultivated land near wells. Pathogen genes for viruses, bacteria, and protozoa were detected in 66 wells (48%), including more detections of zoonotic than human-specific pathogens, and human Bacteroides, an indicator of wastewater, was an equivocal predictor of pathogen presence in private wells. Characterizing important elements of the setting, like geology, and identifying sources and risk factors for contaminants can inform landscape-level policies to protect groundwater quality., 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 © 2025. Published by Elsevier Ltd.)

Human Metapneumovirus (HMPV) is a re-emerging respiratory pathogen causing significant morbidity and mortality, particularly among young children, the elderly, and immunocompromised individuals. First identified in 2001, HMPV has since been recognised as a leading cause of acute respiratory tract infections (ARTIs) worldwide. Its transmission occurs through droplets, direct contact, and surface contamination, with crowded spaces and healthcare facilities serving as key environmental amplifiers. HMPV's clinical manifestations, ranging from mild cold-like symptoms to severe pneumonia, often overlap with those of other respiratory pathogens like RSV and COVID-19, complicating timely diagnosis and management. Despite advancements in molecular diagnostics, the limited accessibility of these tools in low-resource settings presents a challenge. Preventive measures, such as hygiene practices and physical distancing, remain critical, as no approved vaccines or targeted antiviral therapies are currently available. However, promising innovations, including AI-guided vaccine design and portable diagnostic tools, highlight the potential for future breakthroughs. This article highlights the urgent need for enhanced surveillance, scalable diagnostics, and intensified research into vaccines and therapeutic strategies. By addressing these gaps, HMPV's global burden can be significantly mitigated, improving outcomes for high-risk populations, and strengthening preparedness against respiratory virus outbreaks.

Small molecules like PLX5622 for microglia depletion and Tamoxifen for inducible Cre recombination are commonly used in mouse research. Traditional application methods, such as chow or oral gavage and injections, have limitations, including uncontrolled dosage and risk of injury. To address this issue, we have developed an alternative oral drug delivery system using a gel-based rodent maintenance diet that allows for controlled consumption and adjustment of dosage and is suitable for water-insoluble small molecules. We tested DietGel ® 93M (93M) infused with PLX5622 (0.8 mg/g and 2.0 mg/g) in the Cx3cr1 gfp/+ retinal microglia reporter mouse and Tamoxifen-infused 93M (0.3125 mg/g) in the Rlbp1-Cre ERT2 ; Rosa ai14 mouse with an inducible tdTomato reporter in retinal Müller glia. Mice were single-caged and received daily batches of PLX5622-infused 93M over 14 days or Tamoxifen-infused 93M for one or three days followed by a 14-day observation period. Longitudinal scanning laser ophthalmoscopy in vivo and fixed tissue imaging were used to track GFP and tdTomato expression. Following evaluation of a suitable 93M consumption rate (g/d) to sustain body weight, the PLX5622-93M diet at both concentrations showed a 94% microglia depletion rate at 3 days and >99% after one and two weeks. The Tamoxifen-93M diet confirmed suitability for inducible Cre recombination, with significant treatment-time dependent efficacy and a positive correlation between total Tamoxifen dose and tdTomato expression. This study demonstrates that a diet gel-based drug delivery system offers a controllable and less invasive alternative to current drug application methods for PLX5622 and Tamoxifen.

Spinocerebellar ataxia type 3 (SCA3) is a rare inherited neurodegenerative disease caused by the expansion of a polyglutamine repeat in the protease ataxin-3 (Atx3). Despite extensive knowledge of the downstream pathophysiology, no disease-modifying therapies are currently available to halt disease progression. The accumulation of protein inclusions enriched in the polyQ-expanded Atx3 in neurons suggests that inhibiting its self-assembly may yield targeted therapeutic approaches. Here it is shown that a supramolecular tweezer, CLR01, binds to a lysine residue on a positively charged surface patch of the Atx3 catalytic Josephin domain. At this site, the binding of CLR01 decreases the conformational fluctuations of the distal flexible hairpin. This results in reduced exposure of the nearby aggregation-prone region, which overlaps with the substrate ubiquitin binding site and primes Atx3 self-assembly, ultimately delaying Atx3 amyloid fibril formation and reducing the secondary nucleation rate, a process linked to fibril proliferation and toxicity. These effects translate into the reversal of synapse loss in a SCA3 cultured cortical neuron model, an improved locomotor function in a C. elegans SCA3 model, and a delay in disease onset, accompanied by reduced severity of motor symptoms in a SCA3 mouse model. This study provides critical insights into Atx3 self-assembly, revealing a novel allosteric site for designing CLR01-inspired therapies targeting pathological aggregation pathways while sparing essential functional sites. These findings emphasize that targeting allosteric sites in amyloid-forming proteins may offer unique opportunities to develop safe therapeutic strategies for various protein misfolding disorders.

Objective: To determine common domains across existing musculoskeletal COSs. Secondary aims were to assess the development quality of existing musculoskeletal COSs and whether development quality and patient participation was associated with domain selection., Study Design and Setting: A systematic review of musculoskeletal COSs. We searched six databases from inception until December 2023. Studies were included if they reported on the development of a COS in adults with musculoskeletal conditions for any type of intervention. Quality was assessed using the Core Outcome Set-Standards for Development recommendations. Data extracted included scope of the COS, health condition, interventions, and outcome domains. We defined a common core domain when present in >66% of all COSs. Analyses were performed using descriptive statistics., Results: We included 51 studies reporting on 40 COSs, 25 were developed for research settings only, 5 for clinical settings only and 10 for both. We identified 310 domains consisting of 255 mandatory/compulsory/not specified, 45 important, and 10 for further research. Pain (90%) and physical function (88%) were common core domains. COS development quality varied (range: 4 to 11 recommendations met); six COS met all standards. Domain definitions were provided in 13 COSs, 27 included patients or representatives in their development process, while 9 met all recommendations for the consensus process. COSs involving patients were of higher quality (median: 9 vs 5 for those not involving patients)., Conclusion: Pain and physical function core domains should be considered for inclusion in all new musculoskeletal COSs. Developers should follow COS development recommendations and include patients or their representatives., (Copyright © 2025. Published by Elsevier Inc.)