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In the last decades, many publicly available large fundus image datasets have been collected for diabetic retinopathy, glaucoma, and age-related macular degeneration, and a few other frequent pathologies. These publicly available datasets were used to develop a computer-aided disease diagnosis system by training deep learning models to detect these frequent pathologies. One challenge limiting the adoption of a such system by the ophthalmologist is, computer-aided disease diagnosis system ignores sight-threatening rare pathologies such as central retinal artery occlusion or anterior ischemic optic neuropathy and others that ophthalmologists currently detect. Aiming to advance the state-of-the-art in automatic ocular disease classification of frequent diseases along with the rare pathologies, a grand challenge on "Retinal Image Analysis for multi-Disease Detection" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2021). This paper, reports the challenge organization, dataset, top-performing participants solutions, evaluation measures, and results based on a new "Retinal Fundus Multi-disease Image Dataset" (RFMiD). There were two principal sub-challenges: disease screening (i.e. presence versus absence of pathology - a binary classification problem) and disease/pathology classification (a 28-class multi-label classification problem). It received a positive response from the scientific community with 74 submissions by individuals/teams that effectively entered in this challenge. The top-performing methodologies utilized a blend of data-preprocessing, data augmentation, pre-trained model, and model ensembling. This multi-disease (frequent and rare pathologies) detection will enable the development of generalizable models for screening the retina, unlike the previous efforts that focused on the detection of specific diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Epstein-Barr virus meningoencephalitis is a rare central nervous system infection that lacks standardized treatment. Immunocompetent and immunosuppressed individuals with this condition frequently have poor prognostic outcomes, making the need to identify therapeutic interventions high. Here, we report 2 pediatric cases of severe Epstein-Barr virus meningoencephalitis, both unresponsive to immunoglobulin and corticosteroid therapy, who demonstrated rapid clinical recovery following rituximab administration. Prognostic outcomes revealed marked improvements in symptoms, neurologic function, and quality of life. Rituximab may offer therapeutic potential in severe and refractory Epstein-Barr virus meningoencephalitis through the medication's target of Epstein-Barr virus harboring B cells. This report emphasizes the need for timely evaluation and consideration of rituximab therapy in immunocompetent pediatric patients with Epstein-Barr virus meningoencephalitis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Validated computerized assessments for cognitive functioning are crucial for older individuals and those at risk of cognitive decline. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) exhibits good construct validity but requires validation in diverse populations and for adults aged 85+. This study uses data from the Assessing Reliable Measurement in Alzheimer's Disease and cognitive Aging study to explore differences in the factor structure of the NIHTB-CB for adults 85 and older, Black participants versus White participants, and those diagnosed as amnestic Mild Cognitive Impairment (aMCI) vs cognitively normal (CN)., Method: Subtests from the NACC UDS-3 and NIHTB-CB were administered to 503 community-dwelling Black and White adults ages 55-99 (367 CN; 136 aMCI). Confirmatory factor analyses were used to investigate the original factor structure of NIHTB-CB that forms the basis for NIHTB-CD Index factor scores., Results: Factor analyses for all participants and some participant subsets (aMCI, White, 85+) substantiated the two anticipated factors (Fluid and Crystallized). However, while Black aMCI participants had the expected two-factor structure, for Black CN participants, the List Sorting Working Memory and Picture Sequence tests loaded on the Crystallized factor., Conclusions: Findings provide psychometric support for the NIHTB-CB. Differences in factor structure between Black CN individuals and Black aMCI individuals suggest potential instability across levels of cognitive impairment. Future research should explore changes in NIHTB-CB across diagnoses in different populations.

Despite the challenges associated with periprocedural imaging, transcatheter tricuspid valve interventions have shown important impact on outcomes. A comprehensive understanding of the anatomy of the right heart and surrounding structures is crucial. One way to optimize these interventions is by identifying the optimal fluoroscopic viewing angles along the S-curve of the tricuspid valve. Integration of chamber views using multimodality imaging (multislice computed tomography, fluoroscopy, and echocardiography) may increase operator confidence and reduce procedural duration, radiation exposure, contrast volume, and complication rates., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Urinary tract infections (UTIs) are one of the most commonly reported infections in Belgian nursing home residents. In older adults, UTI diagnosis and management is complex, often leading to over-diagnosis and irrational antimicrobial use, stressing the need for a guideline approach., Objectives and Methods: A consensus statement on the prevention, diagnosis and treatment of UTIs in older adults residing in nursing homes was developed in a collaborative effort between the Flemish Hospital Outbreak Support Teams, the Flemish Agency for Care and Health, the Association of the Flemish Coordinating and Advising General Practitioners, the Belgian Association of Urology, the Belgian Society for Gerontology and Geriatrics and PhD researchers based on a combination of clinical expertise, (inter)national guidelines and peer-reviewed studies., Results: Optimizing fluid intake, appropriate toilet behaviour and posture, mobilization and local estrogen therapy in women are of proven value in UTI prevention, whereas the use of cranberry and probiotics is not to be advocated. The importance of avoiding bladder catheterization is stressed. In older nursing home residents, the diagnosis of UTIs remains challenging, mostly due to atypical systemic symptoms. A consensus diagnostic algorithm for UTI among residents with and without a urinary catheter was developed, including the presence of suggestive clinical symptoms and a positive urine culture. Urine dipsticks have a high negative but a low positive predictive value. C-reactive protein point-of-care testing is not recommended. Asymptomatic bacteriuria should not be screened for, in order to avoid unnecessary triggers for treatment. In cystitis, nitrofurantoin is the primary choice for treatment, with fosfomycin as an alternative; in prostatitis and uncomplicated pyelonephritis a fluoroquinolone is the advocated empirical antimicrobial.

Objective: This study aimed to describe the demand for, supply of, and clinic processes associated with behavioral health care delivery in the Military Health System and to examine the clinic-level factors associated with receipt of a minimally adequate dosage of psychotherapy., Methods: This retrospective study used administrative behavioral health data from eight military treatment facilities (N=25,433 patients; N=241,028 encounters) that were participating in a larger implementation study of evidence-based psychotherapy for posttraumatic stress disorder. Minimally adequate dosage of psychotherapy was defined in two ways: at least three sessions within a 90-day period and at least six sessions within a 90-day period. The authors then used a path model to examine clinic-level factors hypothesized to predict psychotherapy dosage, including care demand, supply, and processes., Results: Patients had an average of 2.5 psychotherapy appointments per quarter. Wait times for intake, between intake and the first psychotherapy session, and between follow-up sessions all averaged 17 days or longer. Path modeling showed that a higher patient-to-encounter ratio was associated with a longer wait time between follow-up psychotherapy appointments. In turn, a longer wait time between appointments was associated with a lower probability of receiving an adequate dosage of psychotherapy. However, a greater proportion of care delivered in groups was associated with a greater probability of receiving at least six sessions of psychotherapy., Conclusions: Receipt of a minimally adequate dosage of psychotherapy in the Military Health System is hindered by clinic staffing and workflows that increase wait times between follow-up psychotherapy appointments., Competing Interests: Dr. McLean reports receiving royalties from the American Psychological Association and an honorarium from the Association for Behavioral and Cognitive Therapies. Dr. Peterson reports research funding from the Bob Woodruff Foundation and Texas Veterans and Family Alliance. Dr. Riggs reports ownership of stock in Johnson & Johnson and ownership of a health-related mutual fund. The other authors report no financial relationships with commercial interests.

Injuries to the central nervous system, such as stroke and traumatic spinal cord injury, result in an aggregate scar that both limits tissue degeneration and inhibits tissue regeneration. The aggregate scar includes chondroitin sulfate proteoglycans (CSPGs), which impede cell migration and axonal outgrowth. Chondroitinase ABC (ChASE) is a potent yet fragile enzyme that degrades CSPGs, and thus may enable tissue regeneration. ChASE37, with 37-point mutations to the native enzyme, has been shown to be more stable than ChASE, but its efficacy has never been tested. To answer this question, we investigated the efficacy of ChASE37 first in vitro using human cell-based assays and then in vivo in a rodent model of stroke. We demonstrated ChASE37 degradation of CSPGs in vitro and the consequent cell adhesion and axonal sprouting now possible using human induced pluripotent stem cell (hiPSC)-derived neurons. To enable prolonged release of ChASE37 to injured tissue, we expressed it as a fusion protein with a Src homology 3 (SH3) domain and modified an injectable, carboxymethylcellulose (CMC) hydrogel with SH3-binding peptides (CMC-bp) using inverse electron-demand Diels-Alder chemistry. We injected this affinity release CMC-bp/SH3-ChASE37 hydrogel epicortically to endothelin-1 stroke-injured rats and confirmed bioactivity via degradation of CSPGs and axonal sprouting in and around the lesion. With CSPG degradation shown both in vitro by greater cell interaction and in vivo with local delivery from a sustained release formulation, we lay the foundation to test the potential of ChASE37 and its delivery by local affinity release for tissue regeneration after stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Macrophage and osteoclast proliferation, differentiation and survival are regulated by colony-stimulating factor 1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 and Csf1r mutations has been attributed to the loss of osteoclasts and deficiency in bone resorption. Here, we demonstrate that homozygous Csf1r mutation in rat leads to delayed postnatal skeletal ossification associated with substantial loss of osteal macrophages in addition to osteoclasts. Osteosclerosis and site-specific skeletal abnormalities were reversed by intraperitoneal transfer of wild-type bone marrow cells (bone marrow cell transfer, BMT) at weaning. Following BMT, IBA1+ macrophages were detected before TRAP+ osteoclasts at sites of ossification restoration. These observations extend evidence that osteal macrophages independently contribute to bone anabolism and are required for normal postnatal bone growth and morphogenesis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Forensic investigation of DNA samples from multiple contributors has become commonplace. These complex analyses use statistical frameworks accounting for multiple levels of uncertainty in allelic contributions from different individuals, particularly for samples containing few molecules of DNA. These methods have been thoroughly tested along some axes of variation, but less attention has been paid to accuracy across human genetic variation. Here, we quantify the accuracy of DNA mixture analysis over 83 human groups. We find higher false inclusion rates for mixtures with more contributors and for groups with lower genetic diversity. Even for three-contributor mixtures where two contributors are known and the reference group is correctly specified, false inclusion rates are 1e-5 or higher for 36 out of 83 groups. This means that, depending on multiple testing, some false inclusions may be expected. These false positives could be lessened with more selective and conservative use of DNA mixture analysis., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Transcatheter tricuspid valve intervention (TTVI) has been increasingly adopted in recent years for the treatment of patients with tricuspid regurgitation (TR). However, no dedicated risk stratification has been established for patients undergoing TTVI., Objectives: The aim of the present study was to propose a dedicated risk score for patients affected by severe TR undergoing TTVI., Methods: The score was derived from the TRIVALVE (International Multisite Transcatheter Tricuspid Valve Therapies Registry; NCT03416166) registry, according to data availability. A stepwise model approach was used on predictor variables to develop a scoring system for predicting 12-month mortality or rehospitalization using multivariable logistic regression. Internal discrimination, calibration, and validation were assessed using receiver-operating characteristic curve analysis and bootstrapping with 1,000 resamples., Results: A total of 483 patients were included in the study, with an overall 12-month mortality or rehospitalization rate of 19% (n = 94). The final risk score, ranging from 0 to 4.5, included the following 5 parameters (adjusted for age and gender): 1) atrial fibrillation at baseline; 2) glomerular filtration rate <30 mL/min; 3) elevated gamma-glutamyl transferase/bilirubin levels; 4) signs of right heart failure; and 5) left ventricular ejection fraction <50%. The bias-corrected area under the receiver-operating characteristic curve was 68% (95% CI: 62%-75%). A cutoff value of 2.5 demonstrated sensitivity of 65.4% and specificity of 60.5% for the outcome., Conclusions: The present study proposes a dedicated risk score for patients undergoing TTVI, providing an additional and simple tool for heart teams to select the best therapy for patients affected by severe TR., Competing Interests: Funding Support and Author Disclosures Dr Russo has received a fellowship training grant from the European Association of Percutaneous Cardiovascular Interventions, sponsored by Edwards Lifesciences. Dr Adamo has received personal fees from Abbott Vascular, Medtronic, and Novartis. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; has stock options with NaviGate; and is chief scientific officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Andreas is a proctor, consultant, and speaker for Edwards Lifesciences, Abbott, Medtronic, Boston Scientific, and Zoll; and has received institutional research grants from Edwards Lifesciences, Abbott, Medtronic, and LSI Solutions. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences. Dr Estevez-Loureiro is a consultant for Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr Nickenig has received honoraria for lectures or advisory board membership from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Schofer is a consultant for Edwards Lifesciences. Dr Sievert has received study honoraria to the institution, travel expenses, and consulting fees from 4tech Cardio, Abbott, Ablative Solutions, Adona Medical, Akura Medical, Ancora Heart, Append Medical, Axon, Bavaria Medizin Technologie, Bioventrix, Boston Scientific, Cardiac Dimensions, Cardiac Success, Cardimed, Cardionovum, CeloNova Biosciences, Contego, Coramaze, CroíValve, CSL Behring, CVRx, Dinova, Edwards Lifesciences, EndoBar, Endologix, EndoMatic, Esperion Therapeutics, Hangzhou Nuomao Medtech, Holistick Medical, InterShunt Technologies, Intervene, K2, Laminar, Life Tech Care, Magenta, Maquet Getinge Group, Metavention, Mitralix, Mokita, Neurotronic, NXT Biomedical, Occlutech, Recor, Renal Guard, Shifamed, Terumo, Trisol, Vascular Dynamics, Vectorious Medtech, Venus, Venock, Vivasure Medical, Vvital Biomed, and WhiteSwell. Dr Tang has served as a physician proctor for Medtronic; has served as a consultant for Medtronic, Abbott Structural Heart, and NeoChord; has served on the transcatheter aortic valve replacement advisory board for Abbott Structural Heart; and has served on the physician advisory board for JenaValve. Dr von Bardeleben has served for trials and as a principal investigator for Abbott, Edwards Lifesciences, and Medtronic. Dr Windecker has received research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, Cardiovalve, CorFlow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an advisory board member and/or a member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, with payments to the institution but no personal payments; and is a member of the steering or executive committee groups of several investigator-initiated trials that receive funding from industry, without impact on his personal remuneration. Dr Enriquez-Sarano is a consultant for Edwards Lifesciences, ChemImage, Cryolife, and HighLife. Dr Maisano is a consultant for Abbott Vascular, Medtronic, Edwards Lifesciences, Perifect, Xeltis, Transseptal Solutions, Magenta, and Cardiovalve; has received grant support from Abbott Vascular, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo; has received royalties from Edwards Lifesciences and 4Tech; and is a cofounder and shareholder of Transseptal Solutions, 4Tech, Cardiovalve, Magenta, Perifect, Coregard and SwissVortex. Dr Taramasso has received consultancy fees from Abbott Vascular, Edwards Lifesciences, 4Tech, Boston Scientific, CoreMedic, Mitraltech, and SwissVortex (outside the submitted work). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Global policy and guidelines for low back pain (LBP) management promote physical activity and self-management yet adherence is poor and a decline in outcomes is common following discharge from treatment. Health coaching is effective at improving exercise adherence, self-efficacy, and social support in individuals with chronic conditions, and may be an acceptable, cost-effective way to support people in the community following discharge from treatment for LBP., Aim: This qualitative study aimed to understand which aspects of a community over-the-phone health-coaching program, were liked and disliked by patients as well as their perceived outcomes of the service after being discharged from LBP treatment., Methods: A purposive sampling approach was used to recruit 12 participants with chronic LBP, from a large randomised controlled trial, who were randomly allocated to receive a health coaching program from the Get Healthy Service ® in Australia. Semi-structured interviews were conducted, and a general inductive thematic analysis approach was taken., Results: The main themes uncovered regarding the intervention included the positive and negative aspects of the health coaching service and the relationship between the participant and health coach. Specifically, the participants spoke of the importance of the health coach, the value of goal setting, the quality of the advice received, the benefits of feeling supported, the format of the coaching service, and LBP-specific knowledge. They also reported the health coach and the coaching relationship to be the primary factors influencing the program outcomes and the qualities of the coaching relationship they valued most were connection, communication, care, and competence. The sub-themes uncovered regarding the outcomes of the intervention included positive impacts (a greater capacity to cope, increased confidence, increased motivation and increased satisfaction) and negative impacts (receiving no personal benefit)., Clinical Implications: In an environment where self-management and self-care are becoming increasingly important, understanding the patient's experience as part of a coaching program is likely to lead to improved quality of health coaching care, more tailored service delivery and potentially more effective and cost-effective community-based care for individuals with chronic LBP in the community after being discharged from treatment., Trial Registration: The GBTH trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000889954) on 10/9/2020. Ethical approval was prospectively granted by the Western Sydney Local Health District Human Research and Ethics Committee (2020/ETH00115). Written informed consent was obtained from all participants. The relevant sponsor has reviewed the study protocol and consent form., (© 2024. The Author(s).)

Purpose: The purpose of this study was to evaluate longitudinal changes in choroidal vascular characteristics in childhood, and their relationship with eye growth and refractive error., Methods: Analysis of high-resolution optical coherence tomography (OCT) scans, collected over an 18-month period as part of the Role of Outdoor Activity in Myopia (ROAM) study, was conducted in 101 children (41 myopic, 60 non-myopic, age 10-15 years). OCT images were automatically analyzed and binarized using a deep learning software tool. The output was then used to compute changes in macular choroidal vascularity index (CVI), choroidal luminal, and stromal thickness over 18-months. Associations of these variables with refractive error and axial length were analyzed., Results: CVI decreased significantly, whereas luminal and stromal thickness increased significantly over 18 months (all P < 0.001). The magnitude of change was approximately double in stromal tissue compared to luminal tissue (luminal β = 2.6 µm/year; 95% confidence interval [CI] = -1.0 to 4.1 µm/year; stromal β = 5.2 µm/year; 95% CI = 4.0, 6.5 µm/year). A significant interaction between baseline axial length and change in CVI over time (P = 0.047) was observed, with a greater CVI reduction in those with shorter axial lengths. Significant associations were observed between the change in CVI, luminal thickness, stromal thickness, and change in axial length over time (all P < 0.05)., Conclusions: Faster axial eye growth was associated with smaller reductions in CVI, and less increase in choroidal luminal and stromal thickness. The changes in choroidal vascularity, particularly in the stromal component, may thus be a marker for eye growth., Translational Relevance: This knowledge of the longitudinal changes in choroidal vascularity in childhood and their relationship with eye growth may assist clinicians in the future to better predict eye growth and myopia progression in childhood.

Introduction: Emotional functioning in older adults is influenced by normal aging and cognitive impairment, likely heterogeneous across positive versus negative aspects of emotional functioning. Little is known about positive emotional experiences at the early stages of cognitive impairment. Methods: We assessed different aspects of emotional functioning among 448 participants aged 65+ (Normal Control (NC) = 276, Mild Cognitive Impairment (MCI) = 103, and mild dementia of the Alzheimer type (mild DAT) = 69) and tested moderators. Results: Compared to NC, older adults with MCI and mild DAT have maintained many positive aspects of emotional functioning, despite higher levels of negative affect, sadness, and loneliness. Among the oldest-old, the mild DAT group experienced higher fear and lower self-efficacy. Discussion: Older adults at early stages of cognitive impairment can experience positive aspects of emotional functioning, such as positive affect, purpose, and life satisfaction, all of which are important buildable psychological resources for coping., 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.

Phosphaturic mesenchymal tumor (PMT) is a rare tumor causing bone complications and myopathy. Histologically, PMT displays a mix of spindled cells, osteoclast-like giant cells, basophilic matrix, and flocculent or "grungy" calcification. Here we describe a case of PMT in the right hip and proximal femur, initially suspected to be multiple myeloma, presenting with osteolytic lesions and elevated alkaline phosphatase. Tests for malignancy were negative, but a subsequent biopsy confirmed PMT. The patient underwent hip biopsy, femur resection, and hemiarthroplasty, with follow-up MRI recommended., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

In recent years there has been increased interest in identifying biological signatures of food consumption for use as biomarkers. Traditional metabolomics-based biomarker discovery approaches rely on multivariate statistics which cannot differentiate between host- and food-derived compounds, thus novel approaches to biomarker discovery are required to advance the field. To this aim, we have developed a new method that combines global untargeted stable isotope traced metabolomics and a machine learning approach to identify biological signatures of cruciferous vegetable consumption. Participants consumed a single serving of broccoli ( n  = 16), alfalfa sprouts ( n  = 16) or collard greens ( n  = 26) which contained either control unlabeled metabolites, or that were grown in the presence of deuterium-labeled water to intrinsically label metabolites. Mass spectrometry analysis indicated 133 metabolites in broccoli sprouts and 139 metabolites in the alfalfa sprouts were labeled with deuterium isotopes. Urine and plasma were collected and analyzed using untargeted metabolomics on an AB SCIEX TripleTOF 5,600 mass spectrometer. Global untargeted stable isotope tracing was completed using openly available software and a novel random forest machine learning based classifier. Among participants who consumed labeled broccoli sprouts or collard greens, 13 deuterium-incorporated metabolomic features were detected in urine representing 8 urine metabolites. Plasma was analyzed among collard green consumers and 11 labeled features were detected representing 5 plasma metabolites. These deuterium-labeled metabolites represent potential biological signatures of cruciferous vegetables consumption. Isoleucine, indole-3-acetic acid-N-O-glucuronide, dihydrosinapic acid were annotated as labeled compounds but other labeled metabolites could not be annotated. This work presents a novel framework for identifying biological signatures of food consumption for biomarker discovery. Additionally, this work presents novel applications of metabolomics and machine learning in the life sciences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bouranis, Ren, Beaver, Choi, Wong, He, Traber, Kelly, Booth, Stevens, Fern and Ho.)

Environmental mixtures, which reflect joint exposure to multiple environmental agents, are a major focus of environmental health and risk assessment research. Advancements in latent variable modeling and psychometrics can be used to address contemporary questions in environmental mixtures research. In particular, latent variable models can quantify an individual's cumulative exposure burden to mixtures and identify hidden subpopulations with distinct exposure patterns. Here, we first provide a review of measurement approaches from the psychometrics field, including structural equation modeling and latent class/profile analysis, and discuss their prior environmental epidemiologic applications. Then, we discuss additional, underutilized opportunities to leverage the strengths of psychometric approaches. This includes using item response theory to create a common scale for comparing exposure burden scores across studies; facilitating data harmonization through the use of anchors. We also discuss studying fairness or appropriateness of measurement models to quantify exposure burden across diverse populations, through the use of mixture item response theory and through evaluation of measurement invariance and differential item functioning. Multi-dimensional models to quantify correlated exposure burden sub-scores, and methods to adjust for imprecision of chemical exposure data, are also discussed. We show that there is great potential to address pressing environmental epidemiology and exposure science questions using latent variable methods., Competing Interests: Conflict of interest The authors have no conflict of interest to declare.

The shift from film to PACS in reading rooms, coupled with escalating case volumes, exposes radiologists to the issues of the modern computer workstation including computer work posture and work-related musculoskeletal disorders (WMSD). Common WMSDs affecting the neck and upper extremities include cervical myofascial pain, shoulder tendonitis, lateral epicondylitis, carpal tunnel syndrome, and cubital tunnel syndrome. This review examines each pathology along with its pathogenesis, clinical features, physical exam findings, and potential risk factors. Furthermore, a comprehensive 11-part physical therapy regimen that is both prophylactic and therapeutic is illustrated and described in detail. One of the objectives of this review is to advocate for the inclusion of a physical therapy regimen in the working routine of diagnostic radiologists to prevent WMSDs. A brief daily commitment to this regimen can help radiologists remain healthy and productive in order to deliver optimal patient care throughout their careers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sustainable urban transformation requires comprehensive knowledge about the built environment, including people's perceptions, use of sites, and wishes. Qualitative interviews are conducted to understand better people's opinions about a specific topic or location. This study explores the automatization of the interview coding process by investigating how state-of-the-art natural language processing techniques classify sentiment and semantic orientation from interviews transcribed in Swedish. For the sentiment analysis, the Swedish bidirectional encoder representations from transformers (BERT) model KB-BERT was used to perform a multi-class classification task on a text sentence level into three different classes: positive, negative, and neutral. Named entity recognition (NER) and string search were used for the semantic analysis to perform multi-label classification to match domain-related topics to the sentence. The models were trained and evaluated on partially annotated datasets. The results demonstrate that the implemented deep learning techniques are a possible and promising solution to achieve the stated goal., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

In adults, viral load and disease severity can differ by SARS-CoV-2 variant, patterns less understood in children. We evaluated symptomatology, cycle threshold (Ct) values, and SARS-CoV-2 variants among 2,299 pediatric SARS-CoV-2 patients (0-21 years of age) in Colorado, USA, to determine whether children infected with Delta or Omicron had different symptom severity or Ct values than during earlier variants. Children infected during the Delta and Omicron periods had lower Ct values than those infected during pre-Delta, and children <1 year of age had lower Ct values than older children. Hospitalized symptomatic children had lower Ct values than asymptomatic patients. Compared with pre-Delta, more children infected during Delta and Omicron were symptomatic (75.4% pre-Delta, 95.3% Delta, 99.5% Omicron), admitted to intensive care (18.8% pre-Delta, 39.5% Delta, 22.9% Omicron), or received oxygen support (42.0% pre-Delta, 66.3% Delta, 62.3% Omicron). Our data reinforce the need to include children, especially younger children, in pathogen surveillance efforts.

Objective: To examine the effectiveness of a specially designed video-based exercise program in promoting physical and balance performance in people with intellectual disability., Methods: This study was a multicenter controlled trial. Participants with intellectual disability were divided into exercise group and control group by cluster sampling. The participants in the exercise group received 1 h exercise training sessions twice a week for 8 weeks, and the controls continued their usual care without exercise training. The exercises were specially designed to match the physical ability level of the participants classified as high and low, and a third group called "special" was designed for those wheelchair-bound persons with limited mobility. Elements of light-tempo music and animation were introduced in the videos to motivate the participants. Recording the exercises in video format makes it easier for the class instructors and participants to perform the exercises together, and ensure consistency across different exercise groups conducted in different centers. Each participant underwent the pre- and post-intervention assessment including 30-s chair stand repetitions, five-time chair stand duration, 4-m comfortable walk time, standing static balance level, 6-min walk test, and short physical performance battery score. These variables were compared within each group at pre- and post-intervention stages, and they were also compared between the two groups., Results: A total of 180 participants were enrolled in 16 subcenters, including 160 participants in the exercise group and 20 participants in the control group. After 8 weeks of exercise training, there were significant improvements in their physical performance including 30-s chair stand repetitions and five-time chair stand duration, 4-m comfortable walk time and also 6-min walk test, within the exercise group (all P  < 0.05). Approximately 39% of the participants in the exercise group also showed significant improvement in standing static balance level. No significant differences were found when compared with the control group participants who did not have any regular exercise participation., Conclusion: A specially designed video-based exercise program has demonstrated some positive effects on physical and balance performance after 8 weeks of training among adults with intellectual disability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kwan, Szeto, Ho, Wu, Wong, Ho, Lau, Wong, Kwok and Cheung.)

Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions., (© 2024 Wiley Periodicals LLC.)

Tracking has been criticized for relegating disadvantaged students to lower track courses in which students encounter a greater lack of instructional support. While an end to tracks through detracking is a possible solution, there are concerns that detracking will create more heterogeneous classrooms, making it harder for teachers to provide adequate support to their students. Using the 2015 PISA dataset, this study conducts a causal inferential analysis to understand the differences in student perceptions of teaching in tracked and untracked environments. The results provide evidence that students' needs, with respect to adaptation of instruction and provision of individualized feedback and support, are being met to the same extent on average in tracked and untracked science classes, suggesting that teachers may not necessarily have a harder time meeting the needs of students in untracked classes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample., Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms., Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone., Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom., Competing Interests: On behalf of DR, VP, and PD, the Monell Chemical Senses Center and Temple University have been awarded patent protection (US patent no 11,337,640) and this patent has been licensed to Ahersla Health, Inc. DR, VP, and PD may benefit financially through their institution’s patent policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hunter, Zola, Ho, Kallen, Adjei-Danquah, Achenbach, Smith, Gershon, Reed, Schalet, Parma and Dalton.)

Background: Data on the prognostic role of the TRI-SCORE in patients undergoing transcatheter tricuspid valve intervention (TTVI) are limited., Objectives: The aim of this study was to evaluate the performance of the TRI-SCORE in predicting outcomes of patients undergoing TTVI., Methods: TriValve (Transcatheter Tricuspid Valve Therapies) is a large multicenter multinational registry including patients undergoing TTVI. The TRI-SCORE is a risk model recently proposed to predict in-hospital mortality after tricuspid valve surgery. The TriValve population was stratified based on the TRI-SCORE tertiles. The outcomes of interest were all-cause death and all-cause death or heart failure hospitalization. Procedural complications and changes in NYHA functional class were also reported., Results: Among the 634 patients included, 223 patients (35.2%) had a TRI-SCORE between 0 and 5, 221 (34.8%) had 6 or 7, and 190 (30%) had ≥8 points. Postprocedural blood transfusion, acute kidney injury, new atrial fibrillation, and in-hospital mortality were more frequent in the highest TRI-SCORE tertile. Postprocedure length of stay increased with a TRI-SCORE increase. A TRI-SCORE ≥8 was associated with an increased risk of 30-day all-cause mortality and all-cause mortality and the composite endpoint assessed at a median follow-up of 186 days (OR: 3.00; 95% CI: 1.38-6.55; HR: 2.17; 95% CI: 1.78-4.13; HR: 2.08, 95% CI: 1.57-2.74, respectively) even after adjustment for procedural success and EuroSCORE II or Society of Thoracic Surgeons Predicted Risk of Mortality. The NYHA functional class improved across all TRI-SCORE values., Conclusions: In the TriValve registry, the TRI-SCORE has a suboptimal performance in predicting clinical outcomes. However, a TRISCORE ≥8 is associated with an increased risk of clinical events and a lack of prognostic benefit after successful TTVI., Competing Interests: Funding Support and Author Disclosures Dr Adamo has received speaker honoraria from Abbott. Dr Russo has received a fellowship training grant from the EAPCI sponsored by Edwards Lifesciences. Dr Badano is on the Speaker Bureau of GE Healthcare, Philips Medical Systems, and EsaOte SpA; is currently serving on the Clinical Event Committee of Edwards Lifesciences; and is the director of the echocardiography core laboratory at the Istituto Auxologico Italiano, IRCCS for multiple industry-sponsored trials for which he receives no direct industry compensation. Dr Andreas is a proctor/consultant/speaker for Edwards Lifesciences, Abbott, Medtronic, Boston Scientific, Zoll; and has received institutional research grants from Edwards Lifesciences, Abbott, Medtronic, and LSI. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences. Dr Estevez-Loureiro is a consultant for Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr Gavazzoni is a proctor for Abbott. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; has stock options with Navigate; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials for which she receives no direct industry compensation. Dr Nickenig has received honoraria for lectures or advisory boards from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Schofer is a consultant for Edwards Lifesciences. Dr Sievert has received study honoraria to institution, travel expenses, and consulting fees from 4tech Cardio, Abbott, Ablative Solutions, Adona Medical, Akura Medical, Ancora Heart, Append Medical, Axon, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Cardiac Dimensions, Cardiac Success, Cardimed, Cardionovum, Celonova, Contego, Coramaze, Croivalve, CSL Behring LLC, CVRx, Dinova, Edwards Lifesciences, Endobar, Endologix, Endomatic, Esperion Therapeutics, Inc, Hangzhou Nuomao Medtech, Holistick Medical, Intershunt, Intervene, K2, Laminar, Lifetech, Magenta, Maquet Getinge Group, Metavention, Mitralix, Mokita, Neurotronic, NXT Biomedical, Occlutech, Recor, Renal Guard, Shifamed, Terumo, Trisol, Vascular Dynamics, Vectorious Medtech, Venus, Venock, Vivasure Medical, Vvital Biomed, and Whiteswell. Dr Tang has served as a physician proctor for Medtronic; has served as a consultant for Medtronic, Abbott Structural Heart, and NeoChord; has served on the TAVR Advisory Board for Abbott Structural Heart; and has served on the Physician Advisory Board for JenaValve. Dr von Bardeleben has served for trials and principal investigator for Abbott, Edwards Lifesciences, and Medtronic. Dr Windecker has received research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an Advisory Board member and/or member of the Steering/Executive Group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis with payments to the institution but no personal payments; and is a member of the Steering/Executive Committee Group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Maisano is a consultant for Abbott Vascular, Medtronic, Edwards Lifesciences, Perifect, Xeltis, Transseptal Solutions, Magenta, and Cardiovalve; has received grant support from Abbott Vascular, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo; has received royalties from Edwards Lifesciences and 4Tech; and is cofounder/shareholder of Transseptal Solutions, 4Tech, Cardiovalve, Magenta, Perifect, Coregard, and SwissVortex. Dr Metra has received consulting fees from Abbott Vascular, Actelion, Amgen, AstraZeneca, Bayer, Edwards Therapeutics, Livanova, Servier, Vifor Pharma, and WindTree Therapeutics. Dr Taramasso has received consultancy fees from Abbott Vascular, Edwards Lifesciences, 4Tech, Boston Scientific, CoreMedic, Mitraltech, and SwissVortex outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We applied a novel hierarchical Bayesian weighted quantile sum (HBWQS) regression to combine data across 3 study sites to examine associations between prenatal exposure to metals and cognitive functioning in childhood. Data from 326 mother-child dyads enrolled in an ongoing cohort study, the Programming of Intergenerational Stress Mechanisms (PRISM) Study, based in New York, New York (recruitment in 2013-2020) and Boston, Massachusetts (recruitment 2011-2013), and the First Thousand Days of Life (FTDL) cohort study (recruitment 2012-2019), based in northern Virginia, were used. Arsenic, cadmium, manganese, lead, and antimony were measured in urine collected during pregnancy. Cognitive functioning was assessed in children aged 3-11 years using the National Institutes of Health Toolbox Cognition Battery. The HBWQS regression showed a negative association between the urinary metal mixture and the Cognition Early Childhood Composite Score in the PRISM New York City (β = -3.67, 95% credible interval (CrI): -7.61, -0.01) and FTDL (β = -3.76, 95% CrI: -7.66, -0.24) samples, with a similar trend in the PRISM Boston sample (β = -3.24, 95% CrI: -6.77, 0.144). We did not detect these associations in traditionally pooled models. HBWQS regression allowed us to account for site heterogeneity and detect associations between prenatal metal-mixture exposure and cognitive outcomes in childhood. Given the ubiquity of metals exposure, interventions aimed at reducing prenatal exposure may improve cognitive outcomes in children. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: In low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors., Methods: Opportunistic outreach screenings using finger prick HBsAg tests were performed at civic integration programmes between 11/2017 and 09/2022. If an individual tested positive, an appointment was given immediately at the outpatient hepatology clinic for follow-up and confirmation of HBsAg positivity in blood. Dedicated personnel contacted these individuals to motivate them for further LTC, which was defined as being assessed by a hepatologist, a blood test and an abdominal ultrasound., Results: A total of 677 people from different ethnicities (Asian, Middle Eastern and African) were serologically screened using POCT. The observed positivity for HBsAg was 3.4 % (95% CI 2.17-5.05, 23/677). Apart from ethnicity and male sex, none of the surveyed HBV risk factors were associated with HBsAg seropositivity. All HBsAg positive individuals were linked to care and assessed by a hepatologist, despite the COVID-19 pandemic increase in time to follow-up of 82 days (95% CI 51-112 days) vs. 24 days (95% CI 5-43 days, p = 0.008)).Among HBV-infected patients, 31.8% (7/22), 100 % (22/22) and 26.1% (6/23) met the criteria for treatment indication, intrafamilial transmission risk and need for hepatocellular carcinoma surveillance, respectively., Conclusion: The proportion of HBsAg seropositivity in ethnic minorities was 3.4%. POCT and commitment of dedicated personnel can overcome previously identified barriers resulting in a 100% LTC., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Vanwolleghem is supported by a senior clinical investigator grant from the Research Foundation Flanders (grant number 18B2821 N). Part of these studies have been supported by grants from the Flemish Government (Centrum Medische Innovatie Vlaanderen-Hepatotrope Organismen, 2015), Gilead Sciences (Gilead BELUX Fellowship 2017) and Abbvie., (© 2024 The Authors.)

Timely detection of cognitive impairment (CI) is critical for the wellbeing of elderly individuals. The MyCog assessment employs two validated iPad-based measures from the NIH Toolbox ® for Assessment of Neurological and Behavioral Function (NIH Toolbox). These measures assess pivotal cognitive domains: Picture Sequence Memory (PSM) for episodic memory and Dimensional Change Card Sort Test (DCCS) for cognitive flexibility. The study involved 86 patients and explored diverse machine learning models to enhance CI prediction. This encompassed traditional classifiers and neural-network-based methods. After 100 bootstrap replications, the Random Forest model stood out, delivering compelling results: precision at 0.803, recall at 0.758, accuracy at 0.902, F1 at 0.742, and specificity at 0.951. Notably, the model incorporated a composite score derived from a 2-parameter higher order item response theory (HOIRT) model that integrated DCCS and PSM assessments. The study's pivotal finding underscores the inadequacy of relying solely on a fixed composite score cutoff point. Instead, it advocates for machine learning models that incorporate HOIRT-derived scores and encompass relevant features such as age. Such an approach promises more effective predictive models for CI, thus advancing early detection and intervention among the elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yao, Shono, Nowinski, Dworak, Kaat, Chen, Lovett, Ho, Curtis, Wolf, Gershon and Benavente.)

Introduction: Many regions in the world are using the population health approach and require a means to measure the health of their population of interest. Population health frameworks provide a theoretical grounding for conceptualization of population health and therefore a logical basis for selection of indicators. The aim of this scoping review was to provide an overview and summary of the characteristics of existing population health frameworks that have been used to conceptualize the measurement of population health., Methods: We used the Population, Concept and Context (PCC) framework to define eligibility criteria of frameworks. We were interested in frameworks applicable for general populations, that contained components of measurement of health with or without its antecedents and applied at the population level or used a population health approach. Eligible reports of eligible frameworks should include at least domains and subdomains, purpose, or indicators. We searched 5 databases (Pubmed, EMBASE, Web of Science, NYAM Grey Literature Report, and OpenGrey), governmental and organizational sites on Google and websites of selected organizations using keywords from the PCC framework. Characteristics of the frameworks were summarized descriptively and narratively., Results: Fifty-seven frameworks were included. The majority originated from the US (46%), Europe (23%) and Canada (19%). Apart from 1 framework developed for rural populations and 2 for indigenous populations, the rest were for general urban populations. The numbers of domains, subdomains and indicators were highly variable. Health status and social determinants of health were the most common domains across all frameworks. Different frameworks had different priorities and therefore focus on different domains., Conclusion: Key domains common across frameworks other than health status were social determinants of health, health behaviours and healthcare system performance. The results in this review serve as a useful resource for governments and healthcare organizations for informing their population health measurement efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan 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.)

Purpose: Despite proven benefits, few cancer patients exercise during chemotherapy. The American College of Sports Medicine's Exercise is Medicine® (EIM) initiative describes a model to integrate exercise into oncology care, based upon assessing patients' ability to exercise safely, advising on exercise benefits, and referring patients to exercise. We developed and tested a strategy to implement EIM in a community-based oncology clinic, to assess-advise-refer 20 patients undergoing chemotherapy to a 3-month online exercise class, and measured implementation outcomes., Methods: Using a community-based provider participation in research (CBPPR) model, researchers and staff co-designed and tested a 4-level implementation strategy, with a goal of assessing-advising-referring 20 cancer patients to exercise. Surveys and interviews were conducted with 12 (100%) staff at baseline and post-implementation on acceptability/appropriateness/feasibility, perceptions of individual implementation roles, and organizational strengths/conditions. Data were analyzed using correlations, t-tests, and content analysis., Results: The proposed strategy was revised in collaboration with staff who requested assistance for recruitment and data collection. EIM was successfully implemented with 41 (92%) patients assessed, 37 (90%) advised, and 22 (60%) referred to exercise classes. Barriers to implementation were staff shortages and time constraints; facilitators included research team supports. Staff's perceived organizational strengths were positively correlated with exercise promotion acceptability, appropriateness, and feasibility. There were no statistically significant changes in implementation outcomes (acceptability/appropriateness/feasibility) post-implementation., Conclusions: Using a collaborative model, EIM was successfully implemented in a community oncology clinic; however, the clinic required significant support from the research team. Adaptations to the EIM process may be required to improve implementation outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Scope: The glucosinolate glucoraphanin from broccoli is converted to sulforaphane (SFN) or sulforaphane-nitrile (SFN-NIT) by plant enzymes or the gut microbiome. Human feeding studies typically observe high inter-individual variation in absorption and excretion of SFN, however, the source of this variation is not fully known. To address this, a human feeding trial to comprehensively evaluate inter-individual variation in the absorption and excretion of all known SFN metabolites in urine, plasma, and stool, and tested the hypothesis that gut microbiome composition influences inter-individual variation in total SFN excretion has been conducted., Methods and Results: Participants (n = 55) consumed a single serving of broccoli or alfalfa sprouts and plasma, stool, and total urine are collected over 72 h for quantification of SFN metabolites and gut microbiome profiling using 16S gene sequencing. SFN-NIT excretion is markedly slower than SFN excretion (72 h vs 24 h). Members of genus Bifidobacterium, Dorea, and Ruminococcus torques are positively associated with SFN metabolite excretion while members of genus Alistipes and Blautia has a negative association., Conclusion: This is the first report of SFN-NIT metabolite levels in human plasma, urine, and stool following consumption of broccoli sprouts. The results help explain factors driving inter-individual variation in SFN metabolism and are relevant for precision nutrition., (© 2023 Wiley-VCH GmbH.)

Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases, including 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). The OGG1 protein contains a C2H2 zinc (Zn) finger DNA binding domain. However, the impact of dietary Zn deficiency on OGG1 catalytic activity has not been extensively studied. Zn is a common nutrient of concern with increasing age, and the prevalence of oxidative DNA damage is also concurrently increased during aging. Thus, understanding the potential regulation of OGG1 activity by Zn is clinically relevant. The present study investigates the impact of a range of Zn statuses, varying from severe Zn deficiency to exogenous Zn-supplementation, in the context of young and aged animals to determine the impact of dietary Zn-status on OGG1 activity and oxidative DNA damage in mice. Our findings suggest that nutritional Zn deficiency impairs OGG1 activity and function, without altering gene expression, and that aging further exacerbates these effects. These results have important implications for nutritional management of Zn during aging to mitigate age-associated DNA damage., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Initiating and maintaining physical activity is particularly difficult for at-risk groups such as those with chronic low back pain (LBP)., Objective: This study aimed to assess whether there is a relationship between perceived social support (e.g., emotional and physical support) in individuals recently discharged from treatment for chronic LBP and the number of exercise sessions and total amount of exercise they perform over a 6-month period. This study also aimed to investigate a possible mediation effect of exercise self-efficacy on the relationship between perceived social support and exercise adherence (number of exercise sessions and total amount of exercise)., Methods: This prognostic study employed a secondary analysis of data collected for The Buddy Study; Data was collected through online weekly diaries over a 6-month period. Poisson regression analyses were used to quantify the relationship between social support at baseline and total number of exercise sessions, and total amount of exercise performed (frequency and duration) in the 6-month follow-up period. Where a relationship was observed, the Stata SEM command was used for the mediation analysis., Results: A positive relationship was found between participants' perceived levels of social support at baseline and the total number of exercise sessions they performed (IRR = 1.56, 95%CI: 1.18 to 2.06) and the total amount of exercise they performed (IRR = 1.57, 95%CI: 1.05 to 2.35) during the 6-month follow-up period. No mediating relationship was found between exercise self-efficacy at 3-months and the total number of exercise sessions performed (β 3.96, 95% CI: -4.91 to 12.84), or the total amount of exercise performed (β 243.96, 95% CI: -258.08 to 746.01)., Conclusion: Social support is potentially an important aspect of exercise adherence, following discharge from treatment, for those with chronic LBP. People's self-efficacy to exercise does not appear to mediate this relationship. Harnessing social support following physiotherapy treatment may increase exercise adherence and may therefore improve long term outcomes for those with chronic LBP.

Background: Amyloid-beta (Aβ) plaque is a neuropathological hallmark of Alzheimer's disease (AD). As anti-amyloid monoclonal antibodies enter the market, predicting brain amyloid status is critical to determine treatment eligibility., Objective: To predict brain amyloid status utilizing machine learning approaches in the Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA) study., Design: ARMADA is a multisite study that implemented the National Institute of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in older adults with different cognitive ability levels (normal, mild cognitive impairment, early-stage dementia of the AD type)., Setting: Participants across various sites were involved in the ARMADA study for validating the NIHTB., Participants: 199 ARMADA participants had either PET or CSF information (mean age 76.3 ± 7.7, 51.3% women, 42.3% some or complete college education, 50.3% graduate education, 88.9% White, 33.2% with positive AD biomarkers)., Measurements: We used cognition, emotion, motor, sensation scores from NIHTB, and demographics to predict amyloid status measured by PET or CSF. We applied LASSO and random forest models and used the area under the receiver operating curve (AUROC) to evaluate the ability to identify amyloid positivity., Results: The random forest model reached AUROC of 0.74 with higher specificity than sensitivity (AUROC 95% CI:0.73 - 0.76, Sensitivity 0.50, Specificity 0.88) on the held-out test set; higher than the LASSO model (0.68 (95% CI:0.68 - 0.69)). The 10 features with the highest importance from the random forest model are: picture sequence memory, cognition total composite, cognition fluid composite, list sorting working memory, words-in-noise test (hearing), pattern comparison processing speed, odor identification, 2-minutes-walk endurance, 4-meter walk gait speed, and picture vocabulary. Overall, our model revealed the validity of measurements in cognition, motor, and sensation domains, in associating with AD biomarkers., Conclusion: Our results support the utilization of the NIH toolbox as an efficient and standardizable AD biomarker measurement that is better at identifying amyloid negative (i.e., high specificity) than positive cases (i.e., low sensitivity)., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

Xanthohumol (XN), a polyphenol found in the hop plant ( Humulus lupulus ), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo . We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

Background and Aims: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes., Methods: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year., Results: Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure., Conclusions: In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Functional or secondary tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs. VSTR) are lacking. The aim of this study was to assess characteristics and outcomes of patients with ASTR versus VSTR undergoing T-TEER., Methods and Results: Patients with STR undergoing T-TEER were selected from the Transcatheter Tricuspid Valve Therapies (TriValve) registry. ASTR was defined by (i) left ventricular ejection fraction ≥50%, (ii) atrial fibrillation, and (iii) systolic pulmonary artery pressure <50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key endpoints included procedural success and survival at follow-up. A total of 298 patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs. 83% for ASTR vs. VSTR, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12-month follow-up, survival was significantly higher in the ASTR versus VSTR cohort (91% vs. 72%, log-rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75)., Conclusions: In a real-world, multicentre registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-month follow-up, ASTR showed better survival than VSTR., (© 2023 European Society of Cardiology.)

Introduction: Biomarkers are needed to identify patients with metastatic renal cell carcinoma (mRCC) most likely to benefit from immune checkpoint inhibitors. We examined associations between radiographically assessed body composition (BC) variables and body mass index (BMI) with clinical outcomes for patients with mRCC receiving first-line ipilimumab + nivolumab (ipi/nivo)., Patients and Methods: We retrospectively reviewed all patients with mRCC treated with first-line ipi/nivo at one institution before June 1, 2021 with an analyzable baseline computed tomography (CT) scan. BC variables (skeletal muscle index [SMI], subcutaneous adipose tissue index [SATI], and visceral adipose tissue index [VATI]) were measured using baseline CT scans. Relationships between BC variables and clinical outcomes were examined using Cox proportional hazard regression models., Results: Ninety-nine patients were analyzed (74% male, 64% overweight/obese, 75% low SMI). Controlling for age, IMDC risk, and sex (for BMI analyses), high vs. low SMI (HR=2.433, CI: 1.397-4.238, P=.0017), high vs. low SATI (HR=1.641, CI: 1.023-2.632, P=.0398), and obese BMI (≥ 30 kg/m 2 ) vs. normal/overweight BMI (<30 kg/m 2 ) (HR=1.859, CI: 1.156-2.989, P=.0105) were significantly associated with progression-free survival (PFS). Median overall survival (OS) for low SMI patients was higher (42.74 months, CI: 26.84, NR) than median OS for high SMI patients (27.01 months, CI: 15.28, NR) (adjusted HR=1.728, CI: 0.909-3.285, P=.0952). No BC variables were significantly associated with OS or objective response rate., Conclusions: Low SMI and low SATI were associated with significantly better PFS for patients with mRCC receiving first-line ipi/nivo. Radiographic BC variables may be useful prognostic biomarkers in this setting., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Populations in crisis!A global overview of health challenges and policy efforts within the scope of current nutrition issues, from persistent forms of undernutrition, including micronutrient deficiency, to diet-related chronic diseases. Nutrition science has evolved from a therapeutic and prevention emphasis to include a focus on diets and food systems. Working and consensus definitions are needed, as well as guidance related to healthy diets and the emerging issues that require further research and consensus building. Between nutrient deficiency and chronic disease, nutrition has evolved from focusing exclusively on the extremes of overt nutrient deficiency and chronic disease prevention, to equipping bodies with the ability to cope with physiologic, metabolic, and psychological stress. Just what is 'optimal nutrition', is that a valid public health goal, and what terminology is being provided by the nutrition science community? Nutrition research on 'healthspan', resilience, and intrinsic capacity may provide evidence to support optimal nutrition. Finally, experts provide views on ongoing challenges of achieving consensus or acceptance of the various definitions and interventions for health promotion, and how these can inform government health policies.Nutrition topics that receive particular focus in these proceedings include choline, NAD-replenishment in neurodegenerative diseases, and xanthophyll carotenoids. Choline is a crucial nutrient essential for cellular metabolism, requiring consumption from foods or supplements due to inadequate endogenous synthesis. Maternal choline intake is vital for fetal and infant development to prevent neural tube defects. Neurodegenerative diseases pose a growing health challenge, lacking effective therapies. Nutrition, including NAD-replenishing nutrients, might aid prevention. Emerging research indicates xanthophyll carotenoids enhance vision and cognition, potentially impacting age-related diseases., (© 2023. The Author(s).)

Background: Chronic diseases often accumulate with musculoskeletal (MSK) pain. However, less evidence is available on idiosyncratic patterns of chronic diseases and their relationships with the severity of MSK pain in general MSK pain populations., Material and Methods: Questionnaire-based data on physician-diagnosed chronic diseases, MSK pain and its dimensions (frequency, intensity, bothersomeness, and the number of pain sites), and confounders were collected from the Northern Finland Birth Cohort 1966 at the age of 46. Latent Class Analysis (LCA) was used to identify chronic disease clusters among individuals who reported any MSK pain within the previous year ( n  = 6105). The associations between chronic disease clusters, pain dimensions, and severe MSK pain, which was defined as prolonged (over 30 d within the preceding year), bothersome (Numerical Rating Scale >5), and multisite (two or more pain sites) pain, were analyzed using logistic regression and general linear regression models, adjusted for sex and educational level (n for the full sample = 4768)., Results: LCA resulted in three clusters: Metabolic (10.8% of the full sample), Psychiatric (2.9%), and Relatively Healthy (86.3%). Compared to the Relatively Healthy cluster, the Metabolic and Psychiatric clusters had higher odds for daily pain and higher mean pain intensity, bothersomeness, and the number of pain sites. Similarly, the odds for severe MSK pain were up to 75% (95% confidence interval: 44%-113%) and 155% (81%-259%) higher in the Metabolic and Psychiatric clusters, respectively, after adjustments for sex and educational level., Conclusions: Distinct patterns of chronic disease accumulation can be identified in the general MSK pain population. It seems that mental and metabolic health are at interplay with severe MSK pain. These findings suggest a potential need to screen for psychiatric and metabolic entities of health when treating working-aged people with MSK pain.Key messagesThis large study on middle-aged people with musculoskeletal pain aimed to examine the idiosyncratic patterns of chronic diseases and their relationships with the severity of musculoskeletal pain. Latent class cluster analysis identified three chronic disease clusters: Psychiatric , Metabolic , and Relatively Healthy . People with accumulated mental ( Psychiatric cluster) or metabolic diseases ( Metabolic cluster) experienced more severe pain than people who were relatively healthy ( Relatively Healthy cluster). These findings suggest a potential need to screen for psychiatric and metabolic entities of health when treating working-aged people with MSK pain.

Arsenic occurs naturally in the environment and humans can be exposed through food, drinking water and inhalation of air-borne particles. Arsenic exposure is associated with cardiovascular, pulmonary, renal, immunologic, and developmental toxicities as well as carcinogenesis. Arsenic displays dose-depen toxicities in target organs or tissues with elevated levels of arsenic. Zinc is an essential micronutrient with proposed protective benefits due to its antioxidant properties, integration into zinc-containing proteins and zinc-related immune signaling. In this study, we tested levels of arsenic and zinc in plasma, kidney, liver, and spleen as model tissues after chronic (42-day) treatment with either arsenite, zinc, or in combination. Arsenite exposure had minimal impact on tissue zinc levels with the exception of the kidney. Conversely, zinc supplementation of arsenite-exposed mice reduced the amount of arsenic detected in all tissues tested. Expression of transporters associated with zinc or arsenic influx and efflux were evaluated under each treatment condition. Significant effects of arsenite exposure on zinc transporter expression displayed tissue selectivity for liver and kidney, and was restricted to Zip10 and Zip14, respectively. Arsenite also interacted with zinc co-exposure for Zip10 expression in liver tissue. Pairwise comparisons show neither arsenite nor zinc supplementation alone significantly altered expression of transporters utilized by arsenic. However, significant interactions between arsenite and zinc were evident for Aqp7 and Mrp1 in a tissue selective manner. These findings illustrate interactions between arsenite and zinc leading to changes in tissue metal level and suggest a potential mechanism by which zinc may offer protection from arsenic toxicities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erica Dashner-Titus reports financial support was provided by National Institutes of Health. Laurie Hudson reports financial support was provided by National Institutes of Health. Emily Ho reports financial support was provided by National Institutes of Health. Sandra Alvarez reports financial support was provided by National Institutes of Health. Laurie Hudson reports financial support was provided by United States Environmental Protection Agency. Carmen Wong reports financial support was provided by National Institutes of Health. Karen Simmons reports financial support was provided by National Institutes of Health. Emily Ho reports financial support was provided by Oregon Agricultural Experimental Station. Carmen Wong reports financial support was provided by Oregon Agricultural Experimental Station. Laurie Hudson reports a relationship with National Institutes of Health that includes: funding grants. L.H. is a guest editor for the special issue for which we are submitting., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.

Background: There are no guidelines for anesthesia or staff support needed during rigid bronchoscopy (RB). Identifying current practice patterns for RB pertinent to anesthesia, multidisciplinary teams, and algorithms of intra and post-procedural care may inform best practice recommendations., Methods: Thirty-three-question survey created obtaining practice patterns for RB, disseminated via email to the members of the American Association of Bronchology and Interventional Pulmonology and the American College of Chest Physicians Interventional Chest Diagnostic Procedures Network., Results: One hundred seventy-five clinicians participated. Presence of a dedicated interventional pulmonology (IP) suite correlated with having a dedicated multidisciplinary RB team ( P =0.0001) and predicted higher likelihood of implementing team-based algorithms for managing complications (39.4% vs. 23.5%, P =0.024). A dedicated anesthesiology team was associated with the increased use of high-frequency jet ventilation ( P =0.0033), higher likelihood of laryngeal mask airway use post-RB extubation ( P =0.0249), and perceived lower rates of postprocedural anesthesia adverse effects ( P =0.0170). Although total intravenous anesthesia was the most used technique during RB (94.29%), significant variability in the modes of ventilation and administration of muscle relaxants was reported. Higher comfort levels in performing RB are reported for both anesthesiologists ( P =0.0074) and interventional pulmonologists ( P =0.05) with the presence of dedicated anesthesia and RB supportive teams, respectively., Conclusion: Interventional bronchoscopists value dedicated services supporting RB. Multidisciplinary dedicated RB teams are more likely to implement protocols guiding management of intraprocedural complications. There are no preferred modes of ventilation during RB. These findings may guide future research on RB practices., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The role of advanced diagnostic bronchoscopy (ADB) for assessing atypical respiratory infections is unclear. The purpose of this study was to ascertain: (I) the diagnostic utility of ADB-tissue sampling in patients with focal thoracic lesions due to atypical respiratory infections; (II) how multimodal bronchoscopic sampling and testing enhance diagnosis in a Coccidioides -endemic region., Methods: A retrospective observational cohort study analyzing all ADBs performed over a 10-year period in patients with focal thoracic lesions diagnosed with a non-malignant disorder. Only cases which procured lower respiratory tract secretion and tissue samples by ADB, and had both cytohistology and culture results available were included., Results: Among 403 subjects with non-malignant disease, 136 (33.7%) were diagnosed with atypical respiratory infections, with ADB contributing a diagnosis in 119 (87.5%) of these. Coccidioidal disease was independently associated with a cytohistologic diagnosis [odds ratio =7.64, 95% confidence interval (CI): 2.51-23.26; P<0.001]. Mycobacteria were more effectively identified by culture (overall yield of 8.4%, vs. 2.7% by cytohistology; P<0.001). Among subjects for which both respiratory secretion and tissue sampling were dual-tested with culture and cytology/cytohistology, adding ADB-guided transbronchial needle aspiration and/or forceps biopsy (TBNA/TBFB) to bronchoalveolar lavage and/or bronchial washings (BAL/BW) more than doubled the yield for dimorphic fungi, from 7.1% to 15.1% (increase of 8.0%, 95% CI: 5.2-11.9%). For lung lesions, adding tissue culture to dual TBNA/TBFB cytohistology-tested lung samples doubled the proportion diagnosed with atypical infection over using TBNA-cytohistology alone (increase of 15.8%, 95% CI: 10.4-23.1%). Adding lymph node to lung sampling increased the proportion diagnosed with coccidioidomycosis by 8.8% (95% CI: 4.8-15%). Among subjects with atypical respiratory infections, major ADB-related complications occurred in 1.5%., Conclusions: ADB is useful for diagnosing atypical respiratory infections manifesting as focal thoracic lesions. A multimodal approach to both sampling and testing enhances yield, while maintaining a favorable procedure safety profile. Cytohistology testing and nodal sampling are beneficial for pulmonary coccidioidomycosis, and culture for mycobacterial disease. The approach to ADB-sampling should be adjusted according to clinical context and regional infection patterns., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-83/coif). AAC has received consulting and speaker fees from Intuitive Surgical, Inc. BF has received speaker fees from Insmed, Inc. and consulting fees from Intuitive Surgical, Inc., and STERIS Life Sciences. EH has received consulting fees from Biodesix Inc., Intuitive Surgical, Inc., and Olympus Corp. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)