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Antibiotic resistance poses a significant public health challenge, with biogas digestate, a byproduct of anaerobic digestion (AD), presenting potential risks when applied as a biofertilizer. Understanding the actual resistance levels in digestate is crucial for its safe application. While many studies have investigated antibiotic resistance in AD processes using culture-independent molecular methods, these approaches are limited by their reliance on reference databases and inability to account for gene expression, leading to potential inaccuracies in resistance assessment. This study addresses these limitations by combining culture-independent whole-genome sequencing (WGS) with culture-dependent phenotypic testing to provide a more accurate understanding of antibiotic resistance in digestate. We investigated the phenotypic and genotypic resistance profiles of 18 antibiotic-resistant bacteria (ARB) isolated from digestates produced from food waste and animal manure. Resistance was assessed using WGS and Estrip testing across 12 antibiotics from multiple classes. This is the first study to directly compare phenotypic and genotypic resistance in bacteria isolated from digestate, revealing significant discrepancies between the two methods. Approximately 30 % of resistance levels were misinterpreted when relying solely on culture-independent methods, with both over- and underestimation observed. These findings highlight the necessity of integrating both methods for reliable resistance assessments. Additionally, our WGS analysis indicated low potential for transferability of detected ARGs among the isolated ARB, suggesting a limited risk of environmental dissemination. This study provides new insights into antibiotic resistance in digestate and underscores the importance of integrating methodological approaches to achieve accurate evaluations of resistance risks., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: He Sun reports financial support was provided by China Scholarship Council. 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: Pelvic dysfunction, including urinary incontinence, significantly impacts the quality of life of affected women, diminishing their freedom and dignity. In many African countries, challenges such as limited funding, competing health priorities and cultural stigma on pelvic health further restrict access to care. This information gap may hinder the effective design and implementation of interventions aimed at improving urogynaecological healthcare delivery. The objective of this study was to estimate the urogynaecological workload, the availability of tools to investigate and treat urinary incontinence in women, and to understand the challenges faced by providers of urogynaecological healthcare in 10 African countries., Methods: A cross-sectional online survey of urogynaecological service providers., Results: Forty-seven responses were analysed, revealing that 40% of gynaecological consultations addressed urogynaecological concerns, with 60% related to prolapse, 40% to bladder issues, 7.5% to bowel problems and 5% to sexual dysfunction. Among bladder issues, 35% involved obstetric fistulas, 22.5% stress urinary incontinence, 12.5% mixed urinary incontinence and 10% overactive bladder. Identified resource gaps included insufficient numbers and training of providers, limited access to diagnostic tools such as urodynamics equipment, and inadequate availability of neuromodulation and advanced surgical options. Key challenges in healthcare delivery were lack of patient awareness and inadequate funding, especially in public-sector facilities., Conclusion: Gaps exist in the access and delivery of urogynaecological healthcare to patients with pelvic floor dysfunction in sub-Saharan Africa. Specific areas of focus should include patient education and capacity building, including human resources, access to affordable screening and diagnostic tools and technologies, and investment in affordable management options., Competing Interests: Declarations. Ethical/Institutional Review Board (IRB) Approval: Ethical approval was not sought as the study involved a survey of professionals and did not include any individual patient information. Informed consent was obtained at the outset of the survey. Participation was entirely voluntary, and all participants were provided with information about the purpose of the study to inform their consent and participation. Conflicts of Interest: None., (© 2025. The International Urogynecological Association.)

Objective: Psychiatric comorbidities are frequent in people with epilepsy (PWE) or psychogenic nonepileptic seizures (PNES), and the use of validated screening instruments to identify respective symptoms is recommended. Our aim was to investigate the recommendations resulting from routine screening for depression, anxiety and suicidality with the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Generalized Anxiety Disorder Scale (GAD-7) in the outpatient clinic of a tertiary epilepsy center., Methods: We retrospectively analyzed NDDI-E and GAD-7 scores (German versions) of 264 outpatients at a tertiary epilepsy center and extracted recommendations regarding psychopathology from the outpatient letters., Results: The screening revealed a likely major depression (NDDI-E ≥17) in 15.2% of PWE (without PNES, 30/197) and an NDDI-E score ≥17 in 51.2% of patients with PNES ± epilepsy (21/41), moderate to severe symptoms of generalized anxiety (GAD-7 ≥10) in 20.3% of PWE (40/197) and 56.1% of patients with PNES (23/41), and a high risk of suicidality (NDDI-E item 4 ≥3) in 8.1% of PWE (16/197) and in 24.4% of patients with PNES (10/41). The most frequently given recommendations regarding depression or anxiety were a psychiatric/psychotherapeutic treatment for PWE and an admission to the psychotherapy ward of the epilepsy center for patients with PNES. No evidence for active suicidal tendencies was found in any of the patients with a positive screening for suicidality., Conclusion: Routine screening with NDDI-E and GAD-7 for depression, anxiety and suicidality is efficient and feasible and leads to individual recommendations for further assessment and treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CB has received support from and/or has served as a paid consultant for Angelini, Jazz Pharmaceuticals, Johnson & Johnson, Marinus and Xenon Pharma. The other 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 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Introduction and Hypothesis: Evidence on health system challenges mostly relate to high-income countries. Lack of context-specific knowledge, educational opportunities, and access to resources among pelvic health care providers could be barriers to effective implementation of pelvic health services in South Africa. The aim of this study was to determine the patient and therapist profile, and the educational and resource needs of pelvic health physiotherapists in South Africa., Methods: Ninety-five pelvic health physiotherapists, recruited over 6 months, participated in a cross-sectional study during 2022-2023. Participants completed a REDCap survey covering the stipulated domains. Frequencies, percentages, and Chi-squared tests were used for data analysis., Results: The majority were employed in the private sector (n = 72; 75.8%) and had undergraduate training in pelvic health (n = 86; 89.5%); mostly in pre- and postnatal care (n = 69; 72.6%). Urinary incontinence was the most frequently seen condition (n = 81; 85.3%). Conditions were seen very seldom (n = 46; 48.4%) and most participants treated < 5 patients per month (n = 75; 78.9%), did not have patient educational material available (n = 58; 61.1%), preferred hard-copy formats (63.8%, n = 60), whereas 94.7% (n = 90) felt that there is a lack of patient resources. Participants (n = 66; 69.5%) indicated a need for educational opportunities for clinicians., Conclusions: This study highlights the contextualising of educational and resource needs in mid- to low-income countries, such as South Africa, which might be contrary to common beliefs and practices., Competing Interests: Declarations. Ethics Statement: The cross-sectional study was approved by the Human Research Ethics Committee (Medical) of the University of the Witwatersrand (M180712). Conflicts of Interest: None., (© 2025. The Author(s).)

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6500 SARS-CoV-2 Alpha genomes (B.1.1.7) across 7 months within Thuringia while collecting patients' isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are subclusters. Mobile service data can indicate these clusters' spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept was successfully implemented as a proof-of-concept for a mobility-guided sampling strategy in response to the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance., Competing Interests: RS, MP, CF, AK, CH, MH, ML, MJ, MM, PD, RS, MH, DK, CB No competing interests declared, (© 2024, Spott et al.)

Background: Predicting the clinical trajectory of individual patients with implantable cardioverter-defibrillators (ICDs) is essential to inform clinical care. Machine learning approaches can potentially overcome the limitations of conventional statistical methods and provide more accurate, personalized risk estimates., Objectives: The authors sought to develop and externally validate a novel machine learning algorithm for predicting all-cause mortality and/or heart failure (HF) hospitalization in ICD patients with and without cardiac resynchronization therapy (CRT) using variables that are readily available to treating clinicians. We also sought to identify key factors that separate patients along a continuum of risk., Methods: Random forest for survival, longitudinal, and multivariate (RF-SLAM) data analysis was applied to predict 3-month and 1-year risks for all-cause mortality and a composite outcome of death/HF hospitalization during the first 5 years of device implant. Models were trained using a nationwide cohort from the Veterans Health Administration. Three models were sequentially tested, and external validation was performed in a separate nonveteran clinical registry., Results: The training and validation cohorts included 12,043 patients (age 67.5 ± 9.4 years) and 1,394 patients (age 66.3 ± 11.9 years), respectively. Median follow-up was 3.3 years for the training cohort and 3.6 years for validation cohort. The most accurate models for both outcomes included baseline demographics entered at the time of ICD implant (age, sex, CRT therapy) and time-varying ICD data with area under the receiver-operating characteristic curve for predicting death at 3 months (0.91; 95% CI: 0.87-0.94) and 1 year (0.80; 95% CI: 0.78-0.82); death/HF hospitalization at 3 months (0.81; 95% CI: 0.79-0.83) and 1 year (0.71; 95% CI: 0.70-0.72). Models demonstrated high discrimination and good calibration in the validation cohort. Additionally, time-varying physiologic data from ICDs, especially daily physical activity, had substantial importance in predicting outcomes., Conclusions: The RF-SLAM algorithm accurately predicted all-cause mortality and death/HF hospitalization at 3 months and 1 year during the first 5 years of device implant, demonstrating good internal and external validity. Prospective studies and randomized trials are needed to evaluate model performance in other populations and settings and to determine its impact on patient outcomes., Competing Interests: Funding Support and Author Disclosures Data for this study was provided by Medtronic. However, Medtronic was not involved in the study design, analysis and interpretation of data, nor writing or publishing this study. Dr Rosman was sponsored by a grant from the National Heart, Lung, and Blood Institute (K23HL141644); has received research grants from Boston Scientific; has served on an advisory board for Biotronik; and has received consultancy fees from Pfizer and Biotronik. Drs Rosman and Wang are the inventors of the technology/ML software evaluated in this paper (U.S. Provisional Patent Application 63/684,842). Dr Gehi has received research funding from the Bristol Myers Squibb Foundation; and has received consultancy/speaker honoraria from Zoll Medical, Abbott, and iRhythm. Dr Lampert has served on an advisory board for Medtronic; and has received research funding and honoraria from Abbott (both completed 5/22). Dr Sears has received honoraria/consulting fees from Medtronic, Abbott, Zoll Medical, Milestone Pharmaceutical, Thryve, and Tenaya. Dr Sears has received research grants from CVRx, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; the U.S. Department of Health and Human Services; or the U.S. Department of Veterans Affairs., (Copyright © 2025 American College of Cardiology Foundation. All rights reserved.)

Background: DNA methylation (DNAm) data from human samples has been leveraged to develop "epigenetic clock" algorithms that predict age and other aging-related phenotypes. Some DNAm clocks were trained using DNAm obtained from blood cells, while other clocks were trained using data from diverse tissue/cell types. To assess how DNAm clocks perform across non-blood tissue types, we applied DNAm algorithms to DNAm data generated from 9 different human tissue types., Methods: We generated array-based DNAm measurements for 973 samples from deceased tissue donors from the GTEx (Genotype Tissue Expression) project representing nine distinct tissue types: lung, colon, prostate, ovary, breast, kidney, testis, skeletal muscle, and whole blood. For all samples, we generated DNAm clock estimates for 8 epigenetic clocks and characterized these tissue-specific clock estimates in terms of their distributions, correlations with chronological age, correlations of clock estimates between tissue types, and association with participant characteristics., Results: For each clock, the mean DNAm age estimate varied substantially across tissue types, and the mean values for the different clocks varied substantially within tissue types. For most clocks, the correlation with chronological age varied across tissue types, with blood often showing the strongest correlation. Each clock showed strong correlation across tissues, with some evidence of some residual correlation after adjusting for chronological age. In lung tissue, smoking generally had a positive association with epigenetic age., Conclusions: This work demonstrates how differences in epigenetic aging among tissue types leads to clear differences in DNAm clock characteristics across tissue types. Tissue or cell-type specific epigenetic clocks are needed to optimize predictive performance of DNAm clocks in non-blood tissues and cell types.

Introduction: Cochlear implant (CI) users differ greatly in their rehabilitation outcomes, including speech understanding in noise. This variability may be related to brain changes associated with intact senses recruiting cortical areas from stimulation-deprived senses. Numerous studies have demonstrated such cross-modal reorganization in individuals with untreated hearing loss. How it is affected by regular use of hearing devices remains unclear, however. To shed light on this, the current study measured cortical responses reflecting comprehension abilities in experienced CI users and normal-hearing controls., Methods: Using multichannel electroencephalography, we tested CI users who had used their devices for at least 12 months and closely matched controls (N = 2 × 13). Cortical responses reflecting comprehension abilities - the N400 and late positive complex (LPC) components - were evoked using congruent and incongruent digit-triplet stimuli. The participants' task was to assess digit-triplet congruency by means of timed button presses. All measurements were performed in speech-shaped noise 15 dB above individually measured speech recognition thresholds. Three stimulus presentation modes were used: auditory-only, visual-only, and visual-then-auditory., Results: The analyses revealed no group differences in the N400 and LPC responses. In terms of response times, the CI users were slower and differentially affected by the three stimulus presentation modes relative to the controls., Conclusion: Compared to normal-hearing controls, experienced CI users may need more time to comprehend speech in noise. Response times can serve as a proxy for speech comprehension by CI users., (© 2024 S. Karger AG, Basel.)

To examine whether complementary and integrative health approaches mitigate opioid prescriptions for pain and whether the relationship differs by post-dramatic stress disorder (PTSD) diagnosis, we followed 1,993,455 Veterans with musculoskeletal disorders during 2005-2017 using Veterans Healthcare Administration electronic health records. Complementary and integrative health (CIH) approaches were defined as ≥ 1 primary care visits for meditation, Yoga, and acupuncture etc using natural language processing. Opioid prescriptions were ascertained from pharmacy dispensing records. A propensity score was estimated and used to match one control Veteran to each CIH recipient. Over the 2-year follow-up period after the index diagnosis, 140,902 (7.1 %) Veterans received ≥ 1 modalities. Among the matched analytic sample (272,296 Veterans), the likelihood of dispensing opioid prescriptions was significantly lower for Veterans in the CIH group than their controls [adjusted hazard ratio (aHR), 0.45 (95 % Confidence Intervals (CI): 0.44-0.46)]. The association did not differ between Veterans with [aHR: 0.46 (95 % CI: 0.45-0.47)] and without [aHR: 0.44 (95 % CI: 0.43-0.45)] PTSD. In sensitivity analyses, the exposure group had 3.82 (95 % CI: 3.76-3.87) months longer restricted mean survival time to opioid initiation, 2 % (95 % CI: 4 %-1 %) lower morphine equivalent and 17 % lower total days' supply (95 % CI: 18 %-16 %). The relationship remains significant but was attenuated after eliminating waiting time for the exposure group (aHR, 0.63 (95 % CI: 0.62-0.64)). These observations suggest that CIH approaches may help reduce opioid prescriptions for Veterans with musculoskeletal disorders and related pain. The impact of the timing of receiving such approaches warrants further investigation. PERSPECTIVE: This article presents a quasi-experimental investigation into potential benefit of complementary and integrative health approaches (CIH) on de-prescribing opioids. The findings may potentially help clinicians who are seeking non-pharmacological alternative options to manage patient pain and opioid dependence"., Competing Interests: Declaration of Competing Interest The authors have no financial interests/personal relationships which may be considered as potential competing interests to declare., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Nearly 20% of US cancer survivors develop cardiovascular disease (CVD) from cardiotoxic cancer treatments. Patients and providers may consider alternative treatments to lower cardiotoxicity risk, but these may be less effective at preventing relapse/recurrence, presenting a difficult tradeoff., Aims: This study explored survivors' cancer treatment decision-making when weighing this tradeoff., Methods: Using adjusted multivariable logistic regression, we examined 443 US survivors' risk perceptions (deliberative, affective, and intuitive) about cancer and CVD and associations of these with their selection between two hypothetical cancer treatments: Treatment A: 5% chance of cancer recurrence and 10% chance of CVD; Treatment B: 10% chance of recurrence and 5% chance of CVD. We explored the effects of delay discounting by randomizing to a condition describing cancer recurrence/CVD as either immediate or delayed., Results: More survivors (Mage = 48, range = 18-93; M = 10.8 years post-diagnosis) selected Treatment A than Treatment B (72% v. 28%). Timing of onset was not associated with treatment selection. Greater affective risk perception (worry) about cancer was associated with increased odds of choosing Treatment A, whereas greater CVD worry was associated with decreased odds (OR-cancer = 1.33, p = 0.006; OR-CVD = 0.72, p = 0.007). Neither deliberative nor experiential risk perceptions were associated with treatment choice., Conclusions: Survivors were more likely to select the treatment that minimized recurrence rather than CVD-regardless of the timing of onset. Treatment decision was linked to both cancer- and CVD-related worry but not deliberative or experiential risk perceptions. During treatment discussions, clinicians should open conversations about the risks of treatment-associated cardiotoxicity, the probabilities, and patients' relative worries about cancer and cardiotoxicity., (Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Psycho‐Oncology published by John Wiley & Sons Ltd.)