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Introduction: Quality improvement (QI) methods play a critical role in ensuring that patients receive high-quality and timely care. Healthcare systems should use valid and reliable measures to inform QI efforts. Mental health settings including substance use disorder (SUD) residential programs have been slow to develop and incorporate quality measurement into routine practice. Unplanned discharge is of particular concern because this event is associated with harm including suicide. Healthcare systems require criteria that they can use to operationalize unplanned discharge as a quality measure in SUD residential programs., Methods: The study included all discharges from the Department of Veterans Affairs (VA) residential SUD programs between 2018 and 2022. The study calculated crude and adjusted rates of irregular discharge. The study used the first two years of observation (2018-2019) in a logistic regression model to determine the parameter estimates for three important covariates, age, risk for homelessness, and principal diagnosis. The study tested permutations of bin size (N) and days (D) per bin to identify a single set of parameters to enable small and large facilities to have sufficient power to detect out-of-control processes (i.e., significant worsening or improvement in rates). Aligned with standard nomenclature, the study calculated the control limits based on three standard deviations (SD). Values that fell above or below three SD were statistically significant., Results: The cohort included 56 facilities (26,361 discharges). Irregular discharge was associated with younger age (18-40 years) and a principal diagnosis of a drug use disorder. Testing parameter values of 100 discharges (N) over 120 days (D) would yield enough power to detect modest relative changes to the irregular discharge rate for small and large facilities while testing frequently enough to make the evaluations temporally relevant. Because secular trends such as staff changes over time will impact results, the quality control method should allow for real-time feedback to those most proximal to the event., Conclusions: The study created a set of parameters and a methodology that residential SUD programs can use to operationalize unplanned discharge locally. These data could assist programs in conducting QI work to address unplanned discharge and related harms., 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., (Published by Elsevier Inc.)

Objectives: Mammographic breast arterial calcification (BAC) is an emerging imaging biomarker of cardiovascular disease (CVD) risk in women. The purpose of this study was to assess if breast radiation therapy (RT) exposure impacts the screening utility of this imaging biomarker., Methods: This cross-sectional study included women ages 40-75 years who underwent index screening mammography between January 1, 2011 and December 31, 2012. Chart review was performed to extract data on the breast cancer RT exposure and CVD risk factors. Mammograms were reviewed for the presence of BAC. Multivariate logistic regression was used to examine breast RT exposure and BAC, with adjustment for age, body mass index, smoking status, hypertension, Type 2 diabetes, statin medication use, and antihypertensive medication use., Results: Of the 1155 women included in this analysis, 222 (19.2%) had mammographic evidence of BAC, 122 (10.6%) had a history of RT exposure, and 39 (32%) women with RT exposure had mammographic BAC. Women with breast RT exposure had higher odds of BAC compared to women without (odds ratio: 2.18, 95% CI: 1.43, 3.28; P-value = .0008). However, this association became non-significant after multivariable adjustment, with the maximally adjusted model demonstrating an odds ratio of 1.52 (95% CI: 0.95, 2.40; P-value = .07)., Conclusions: Our findings suggest that breast RT exposure does not impact the prevalence of mammographic BAC. Therefore, it does not affect its utility as an imaging biomarker of CVD risk., Advances in Knowledge: This is the first observational study addressing the knowledge gap pertaining to the influence of breast RT exposure on BAC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins., 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.

Abstract: The presence of multiple cutaneous vascular lesions in infancy can signal the possibility of visceral involvement. Dermatopathologists must appreciate how the differential diagnosis includes entities that have distinct therapeutic and prognostic implications. Fortunately, these rare entities can be distinguished histopathologically with the help of clinicopathologic correlation and immunohistochemistry. In this article, we discuss congenital disseminated pyogenic granuloma, multifocal infantile hemangioma, and multifocal lymphangioendotheliomatosis with thrombocytopenia. Subtle morphologic and immunophenotypic features permit their distinction, which in turn is important for identifying extracutaneous manifestations and effective treatments. We present a case of a 3-week-old infant with congenital disseminated pyogenic granuloma involving the skin and the liver whose lesions regressed without therapeutic intervention over 6 months of close follow-up. We review the literature on these rare, overlapping entities and present an approach to resolving the differential diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Traumatic injury in children, particularly adolescents, is both frequently and costly. In this study, we directly examined children's causal attributions for the recent traumas and asked them to propose prevention strategies of their own. We predict that children who attribute their injuries to their own actions, rather than an external force such as luck, will be more likely to develop strategies to avoid trauma in the future., Methods: All children aged 10 -18 years who presented to a Level 1 pediatric trauma center at an urban children's hospital over a ten-month period were identified and presented with a series of structured interview questions. They were asked to describe the cause of their injuries, whether they believed them to be avoidable, and what strategies, if any, they thought might have prevented their trauma., Results: 46 children with an average age of 13.4 years were surveyed and the responses of 44 children were analyzed. Most injuries resulted from sports (24) or motor vehicle accidents (14). The remaining injuries were due to burns (4) and falls (2). Twelve (27%) children believed that their own behavior was to blame for their injuries. 32 children ascribed their injuries to circumstances outside of their control with the majority (30, 94%) viewing themselves as "unlucky." Children who accepted fault for injury and children who thought their accident was avoidable were more likely to be able to formulate a strategy for preventing future injury. Children who thought their accident was avoidable were also more likely to accept fault for it., Conclusion: Children surveyed denied their own culpability and preferred to attribute their injuries to bad luck. Moreover, children who believed themselves to be simply unlucky were less able than others to propose strategies that might prevent further injury., Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Informed consent: Informed consent was obtained from all participants in accordance with applicable guidelines governing research involving human subjects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The two widely available evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD) are cognitive processing therapy and prolonged exposure. Although the U.S. Department of Veterans Affairs (VA) has invested in intensive clinical training to provide these first-line treatments, most military veterans do not receive these therapies. Prior research indicates that patient interest and motivation depend on how patients are educated, and differences in how information is presented shape their decision-making. To our knowledge, no studies have addressed how clinicians "pitch" EBPs for PTSD and examined whether certain approaches are more effective than others. We recorded and thematically analyzed 25 treatment planning sessions across 10 VA sites in the United States to better understand how providers talk to patients about treatment options. Five themes were identified: using rich description, integrating various forms of questioning to engage the patient, sharing prior patient success stories, using inviting and direct language, and tailoring therapy talk to fit patient needs. Providers learning to offer EBPs can use these strategies to serve as a "menu" of options that will allow them to present EBPs in a way that appeals to a particular patient., (© ([0‐9]+) International Society for Traumatic Stress Studies.)

Splenic biopsies for cytology remain challenging due to the inherent difficulty in obtaining adequate samples and the paucity of literature on rare entities arising in the spleen. Among these, are tumors arising from blood vessels, lymphomas and rarely, mesenchymal dendritic cell neoplasms. An important but rarely considered entity primarily arising in the spleen is Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS). EBV+ IFDCS is an indolent neoplasm with useful cytomorphologic and distinct biologic characteristics that can be evaluated on fine-needle aspiration (FNA) cytology and small biopsies. In this report, we present a challenging case with the final diagnosis facilitated by cytomorphology and diagnostic markers in an ambiguous initial presentation., (© 2024 Wiley Periodicals LLC.)

Introduction: Sleep Apnea (SA) is a common sleep disorder that increases postoperative morbidity. There is limited research on how SA influences outcomes following operative fixation of ankle fractures. Therefore, the aim of this study was to determine whether patients who undergo surgical fixation for bimalleolar ankle fractures have higher rates of medical complications and health care expenditures., Methods: A retrospective review from January 1, 2005 to March 31, 2014 was conducted using the parts A and B Medicare Data from PearlDiver database. Patients with and without SA on the day of the primary open reduction and internal fixation (ORIF) of their bimalleolar ankle fractures were queried using the International Classification of Diseases, Ninth Revision codes. Welch's t -tests were used to compare costs of care. A multivariate binomial logistic regression model was used to calculate the odds ratio (OR) of adverse events. A P-value <.001 was considered statistically significant., Results: There were 20 560 patients (SA = 3150; comparison cohort = 17 410) who underwent ORIF for bimalleolar ankle fractures during the study period. Sleep apnea patients were found to have significantly higher rates and odds of 90-day medical complications (21.42% vs 7.47%, OR: 3.11, P < .0001) and 90-day costs of care ($7213.12 vs $5415.79, P < .0001)., Conclusion: This research demonstrates an increased risk of postoperative medical complications and health care costs among patients with SA undergoing ORIF for bimalleolar ankle fractures., Level of Evidence: Therapeutic, Level IV: Retrospective., 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.

Objectives: To determine whether limited English proficiency (LEP) is associated with likelihood of prior audiogram and hearing aid use among US adults with hearing loss., Methods: This cross-sectional study of four merged National Health and Nutrition Examination Survey (NHANES) cycles included 12,636 adults with subjective (self-reported) or objective (audiometric) hearing loss. Subjects were classified as LEP if they completed the NHANES survey in a language other than English, or with the help of an interpreter. Likelihood of audiogram among participants with subjective and objective hearing loss, and likelihood of hearing aid use among participants with objective hearing loss were assessed using unadjusted and adjusted logistic regression., Results: Individuals with LEP were less likely to have undergone audiogram among subjects with subjective (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.67-0.77), and objective (OR 0.70, 95% CI 0.65-0.74) hearing loss. The association persisted for those with subjective hearing loss (OR 0.79, 95% CI 0.72-0.86), and objective hearing loss (OR 0.81, 95% CI 0.73-0.89) after adjusting for relevant covariates. Individuals with LEP were less likely to use hearing aids (OR 0.88, 95% CI 0.84-0.93). This association disappeared (OR 0.99, 95% CI 0.95-1.04) after adjustment., Conclusion: LEP is associated with lower utilization of hearing healthcare services. This may be due to the complex interplay of socioeconomic and language disparities, which may act as barriers to hearing healthcare utilization. Individuals with LEP should be prioritized when designing interventions to improve accessibility to hearing healthcare., Level of Evidence: 3 Laryngoscope, 134:5122-5130, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Alcohol withdrawal is a common reason for admission to acute care hospitals. Prescription of medications for alcohol-use disorder (AUD) and close outpatient follow-up are commonly recommended, but few studies report their effects on postdischarge outcomes., Objectives: The objective of this study is to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence., Methods: This retrospective cohort study evaluated veterans admitted for alcohol withdrawal to medical services at 19 Veteran Health Administration hospitals between October 1, 2018 and September 30, 2019. Factors associated with all-cause 30-day readmission and 6-month abstinence were examined using logistic regression., Results: Of the 594 patients included in this study, 296 (50.7%) were prescribed medications for AUD at discharge and 459 (78.5%) were discharged with follow-up appointments, including 251 (42.8%) with a substance-use clinic appointment, 191 (32.9%) with a substance-use program appointment, and 73 (12.5%) discharged to a residential program. All-cause 30-day readmission occurred for 150 patients (25.5%) and 103 (17.8%) remained abstinent at 6 months. Medications for AUD and outpatient discharge appointments were not associated with readmission or abstinence. Discharge to residential treatment program was associated with reduced 30-day readmission (adjusted odds ratio [AOR]: 0.39, 95% confidence interval [95% CI]: 0.18-0.82) and improved abstinence (AOR: 2.50, 95% CI: 1.33-4.73)., Conclusions: Readmission and return to heavy drinking are common for patients discharged for alcohol withdrawal. Medications for AUD were not associated with improved outcomes. The only intervention at the time of discharge that improved outcomes was discharge to residential treatment program, which was associated with decreased readmission and improved abstinence., (Published 2024. This article is a US Government work and is in the public domain in the USA.)

In everyday life, humans perform sequences of tasks. These tasks may be disrupted in people with obsessive-compulsive disorder (OCD). Symptoms, such as compulsions, can be considered sequential and often cause repetitions of tasks that disrupt daily living (e.g., checking the stove while cooking). Motor sequences have been used to study behavioral deficits in OCD. However, not all sequences are motor sequences. Some are more "abstract" in that they are composed of a series of tasks (e.g., chopping and stirring) rather than being dependent on individual actions or stimuli. These abstract task sequences require cognitive control mechanisms for their execution. Although theory has proposed deficits in these sequences in OCD as well, they have not been directly investigated. We tested the hypotheses that OCD participants exhibit deficits in the control mechanisms specific to abstract task sequences and more general flexible behavior (measured with task switching within the sequences), relative to health controls (HCs) and clinical controls (participants with anxiety disorders [ANX]). A total of 112 participants completed abstract task sequences consisting of simple categorization tasks. Surprisingly, participants with OCD did not perform worse than HCs or ANX. However, ANX participants showed impairments specific to sequential control that did not extend to more general flexible control. Thus, we showed a novel behavioral dissociation between OCD and ANX specific to abstract task sequential control. These results also implicate deficits in specific frontal sequential control neural circuitry in ANX and not in OCD, where implicit sequential deficits may more closely align with striatal circuits., (© 2024. The Psychonomic Society, Inc.)

Organizational ethics-defined as the alignment of an institution's practices with its mission, vision, and values-is a growing field in health care not well characterized in empirical literature. To capture the scope and context of organizational ethics work in United States healthcare institutions, we conducted a nationwide convenience survey of ethicists regarding the scope of organizational ethics work, common challenges faced, and the organizational context in which this work is done. In this article, we report substantial variability in the structure of organizational ethics programs and the settings in which it is conducted. Notable findings included disagreement about the activities that comprise organizational ethics and a lack of common metrics used to assess organizational ethics activities. A frequently cited barrier to full engagement in these activities was poor institution-wide understanding about the role and function of organizational ethics resources. These data suggest a tension in the trajectory of organizational ethics' professionalization: while some variability is appropriate to the field's relative youth, inadequate attention to definitions of organizational ethics practice and metrics for success can impede discussions about appropriate institutional support, leadership context, and training for practitioners., Competing Interests: Declarations. Conflict of Interest: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ovarian cancer (OvCa) is a leading cause of mortality among gynecological malignancies and usually manifests as intraperitoneal spheroids that generate metastases, ascites, and an immunosuppressive tumor microenvironment. In this study, we explore the immunomodulatory properties of cowpea mosaic virus (CPMV) as an adjuvant immunotherapeutic agent using an in vitro model of OvCa peritoneal spheroids. Previous findings highlighted the potent efficacy of intratumoral CPMV against OvCa in mouse tumor models. Leveraging the precision control over material deposition and cell patterning afforded by digital-light-processing (DLP) based bioprinting, we constructed OvCa-macrophage spheroids to mimic peritoneal spheroids using gelatin methacrylate (GelMA), a collagen-derived photopolymerizable biomaterial to mimic the extracellular matrix. Following CPMV treatment, bioprinted spheroids exhibited inhibited OvCa progression mediated by macrophage activation. Our analysis indicates that CPMV regulates and activates macrophage to both induce OvCa cell killing and restore normal cell-cell junctions. This study deepened our understanding of the mechanism of CPMV intratumoral immunotherapy in the setting of OvCa. This study also highlights the potential of studying immunotherapies using high throughput tissue models via DLP bioprinting., Competing Interests: Declaration of competing interest Nicole F. Steinmetz reports a relationship with Mosaic ImmunoEnginering Inc. that includes: equity or stocks. Steven N. Fiering reports a relationship with Mosaic ImmunoEnginering Inc. that includes: equity or stocks. Nicole F. Steinmetz reports a relationship with Pokometz Scientific LLC that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

CXCL13 is a chemokine which is upregulated within the CNS in multiple sclerosis, Lyme neuroborreliosis, and other inflammatory diseases and is increasingly clinically useful as a biomarker. This review provides background for understanding its function in the immune system and its relationship to ectopic lymphoid follicles. Also reviewed are its utility in multiple sclerosis and Lyme neuroborreliosis and potential problems in its measurement. CXCL13 has the potential to be an exceptionally useful biomarker in a range of inflammatory diseases.

Background: Most individuals who come under the care of large healthcare systems will have experienced at least one traumatic incident in their lifetime that may continue to influence their mental and physical health, disease management, and engagement with treatment and medical professionals. Histories of trauma are especially common in patients with gastrointestinal (GI) illness. Trauma reactions can arise in GI settings, but healthcare providers may not recognize these reactions or know how to respond effectively., Aims: We aimed to increase awareness and understanding of the relationship between trauma and GI symptoms, trauma reactions in a healthcare setting, strategies for responding to patients in emotional distress, and opportunities to reduce risk of retraumatization in a GI setting., Methods: Within a larger initiative to enhance behavioral healthcare access and engagement in a GI setting, patient and stakeholder interviews were conducted, and a needs assessment survey was administered. Interview and survey findings informed development of innovative solutions to the identified need for improved trauma services and resources using an iterative, team-based approach., Results: Programs and resources were developed and implemented to increase recognition of the impact of trauma, improve responses to trauma reactions during encounters with patients (e.g., clinical and procedure visits, telephone calls), and provide support to patients receiving GI care., Conclusions: Trauma-focused programming specific to the needs of patients with GI conditions is desired by patients, providers, and staff. Education, intervention, and support initiatives have potential to increase awareness of the effects of trauma and enhance experience of healthcare., Competing Interests: Declarations. Conflicts of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Concerns persist about the potential impact of prenatal exposure to bisphenols (BP) and their replacement analogues on childhood asthma and allergies. Previous studies on single and small cohorts had limited statistical power, few investigated analogues BPF and BPS, and even fewer examined atopic outcomes. Our objective was to assess whether prenatal exposures to individual environmental bisphenols (BPA, BPF, BPS) influence risk of childhood asthma, allergic rhinitis, and atopic dermatitis. Data from the U.S. Environmental Influences on Child Health Outcomes (ECHO) consortium were harmonized on measures of prenatal urinary BPA, BPF and BPS and asthma and allergic rhinitis (ages 5-9 years) and atopic dermatitis (up to age 3 years) from 1905 mother-child pairs that were collected between 1998 and 2017. Across the 2012 federal ban of BPA from certain infant products, median BPA levels decreased from 1.11 ng/ml to 0.86 ng/ml; median BPF levels decreased from 0.51 ng/ml to 0.39 ng/ml; and median BPS levels increased from 0.23 ng/ml to 0.31 ng/ml (dilution adjusted; p < 0.001 for all three median comparisons). Prenatal measures of BPA, BPF, and BPS were unrelated to the risk of childhood asthma, allergic rhinitis, or atopic dermatitis in the total population. Modest sex-dependent effects were observed: only among girls, second tertile levels of BPF was associated with a reduced odds of asthma (odds ratio (OR) 0.27, 95% confidence interval (CI) 0.08, 0.93); a continuous index of prenatal BPS was associated with reduced odds of atopic dermatitis (OR 0.64, 95% CI 0.44, 0.93). The ongoing and changing patterns of exposure to bisphenols in the U.S. population require further study with additional attention to time windows of exposure and co-occurring social determinants of health, to continue to inform current policies and evaluate the importance of limiting exposure to BPA and its analogues on childhood asthma, allergic rhinitis, and atopic dermatitis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Scott Weiss reports financial support was provided by National Institutes of Health. Scott Weiss reports financial support was provided by UptoDate Inc. Rachel L. Miller reports financial support was provided by National Institutes of Health. Yuyan Wang reports financial support was provided by National Institutes of Health. Jenny Aalborg reports financial support was provided by National Institutes of Health. Akram N. Alshawabkeh reports financial support was provided by National Institutes of Health. Deborah H. Bennett reports financial support was provided by National Institutes of Health. Carrie V. Breton reports financial support was provided by National Institutes of Health. Jessie P. Buckley reports financial support was provided by National Institutes of Health. Dana Dabelea reports financial support was provided by National Institutes of Health. Anne L. Dunlop reports financial support was provided by National Institutes of Health. Assiamira Ferrara reports financial support was provided by National Institutes of Health. Griffith Gao reports financial support was provided by National Institutes of Health. Abigail Gaylord reports financial support was provided by National Institutes of Health. Diane R. Gold reports financial support was provided by National Institutes of Health. Tina Hartert reports financial support was provided by National Institutes of Health. Irva Hertz-Picciotto reports financial support was provided by National Institutes of Health. Lori A. Hoepner reports financial support was provided by National Institutes of Health. Margaret Karagas reports financial support was provided by National Institutes of Health. Catherine J. Karr reports financial support was provided by National Institutes of Health. Rachel S. Kelly reports financial support was provided by National Institutes of Health. Camilo Khatchikian reports financial support was provided by National Institute of Health. Mengling Liu reports financial support was provided by National Institutes of Health. John D. Meeker reports financial support was provided by National Institutes of Health. Thomas G. OConnor reports financial support was provided by National Institutes of Health. Alicia K. Peterson reports financial support was provided by National Institutes of Health. Sheela Sathyanarayana reports financial support was provided by National Institutes of Health. Joanne Sordillo reports financial support was provided by National Institutes of Health. Leonardo Trasande reports financial support was provided by National Institutes of Health. Yeyi Zhu reports financial support was provided by National Institutes of Health. Rachel L. Miller reports a relationship with UptoDate Inc that includes: consulting or advisory. Scott Weiss is on the Board of Histolix a digital pathology company. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Studies conducted in the US indicate that exposure to trauma, and stigma related to weight are environmental factors associated with the development of disordered eating. Few studies have explored psychosocial and contextual factors surrounding disordered eating in Latin American populations. This study examined everyday discrimination, verbal weight-related abuse, adverse childhood experiences, and disordered eating across individuals seeking versus not seeking weight loss treatment in Peru., Method: Participants (N = 420) were recruited via social media and a weight management clinic in Peru. Participants completed disordered eating, everyday discrimination, verbal weight-related abuse, and adverse childhood experiences measures., Results: The weight loss treatment seeking group showed greater disordered eating behaviors (dietary restraint) and cognitions (body dissatisfaction, overvaluation of shape/weight) compared to the non-weight loss treatment seeking group. Increased experiences of everyday discrimination, adverse childhood experiences, and verbal weight-related abuse were associated with greater levels of disordered eating behaviors and cognitions in both samples. Weight loss treatment seeking status was not a moderator of the relationships among disordered eating behaviors and cognitions, and everyday discrimination., Discussion: Results suggest discrimination, adverse childhood experiences, and verbal weight-related abuse are associated with eating pathology, and more disordered eating and behaviors are seen in individuals seeking or engaged in weight loss treatment. Findings highlight the importance of evaluating eating pathology for individuals reporting, or at high risk for discrimination, childhood trauma or weight-related abuse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A growing evidence base suggests that the integration of museum-based activities into health professions education can contribute to learner resilience and wellbeing, promote capacity for patient-centered care, and encourage equity in learning environments. However, the styles and methods for implementing museum-based programs vary widely across different institutions. This retrospective leverages the lessons learned from 5 years of experience implementing museum-based programs at one large academic institution to examine the various operational and logistical considerations in implementing a museum-based program for health professions learners. These efforts are intended to support the Association of American Medical Colleges and National Academies of Sciences, Engineering, and Medicine's aims to formally integrate the arts and humanities into health professions education. We structure our recommendations under the subheadings of program form, audience, function, and evaluation, with hopes of providing medical educators with starting guidelines that are broadly adoptable across different institutions., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

While deep learning (DL) offers the compelling ability to detect details beyond human vision, its black-box nature makes it prone to misinterpretation. A key problem is algorithmic shortcutting, where DL models inform their predictions with patterns in the data that are easy to detect algorithmically but potentially misleading. Shortcutting makes it trivial to create models with surprisingly accurate predictions that lack all face validity. This case study shows how easily shortcut learning happens, its danger, how complex it can be, and how hard it is to counter. We use simple ResNet18 convolutional neural networks (CNN) to train models to do two things they should not be able to do: predict which patients avoid consuming refried beans or beer purely by examining their knee X-rays (AUC of 0.63 for refried beans and 0.73 for beer). We then show how these models' abilities are tied to several confounding and latent variables in the image. Moreover, the image features the models use to shortcut cannot merely be removed or adjusted through pre-processing. The end result is that we must raise the threshold for evaluating research using CNNs to proclaim new medical attributes that are present in medical images., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: AI is big and moving fast into healthcare, creating opportunities and risks. However, current approaches to governance focus on high-level principles rather than tailored recommendations for specific domains like consumer health. This gap risks unintended consequences from generic guidelines misapplied across contexts and from providing answers before agreeing on the questions., Objective: Our objective is to explore pragmatic multi-stakeholder approaches to govern consumer-facing health AI. The aims are to (1) establish an approach tailored for consumer health AI governance and (2) identify key constraints and desirable model characteristics., Methods: This paper synthesizes insights informed by a 4-month multidisciplinary expert consensus process with nearly 200 participants. The deliberations provided guidance for the development of the proposed governance models in consumer health AI., Results: (1) A Shared View of Consensus: A process for consumer health AI governance should limit the scope and incorporate multi-stakeholder perspectives centered on patient needs. Desirable model characteristics include adaptability, patient empowerment, and transparency. (2) Recommended Collaborative Process: A pathway for effective governance should begin by forming a Health AI Consumer Consortium (HAIC 2 ) representing patients and aligning incentives across stakeholders., Conclusions: While examples focus on the United States healthcare system, core themes around incorporating consumer voices, enabling transparency, and balancing innovation with thoughtful oversight while avoiding overambitious scope will have relevance globally. As consumer AI spreads worldwide, the multi-stakeholder alignment and patient empowerment principles proposed here may offer productive ways to ensure AI for consumers is safe, effective, equitable, and trustworthy (SEET)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven Labkoff is an employee of Quantori, LLC. Eileen Koski is employed by IBM and owns stock. Kiran Dattani is an employee of Google Cloud Healthcare and Life Sciences. Monica Lopez-Gonzalez is an employee of Cognitive Insights for Artificial Intelligence. Views in this paper are of the authors and not of their employers. The authors had no other conflicts or competing interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown. Using HSV-1 with intact and ablated gE-mediated IgG Fc binding, and Fc-engineered antibodies with modified ability to interact with gE/gI, we investigated the role of the vFcR in viral pathogenesis and mAb-mediated protection from nHSV. The gD-specific human mAb HSV8 modified to lack binding to gE exhibited enhanced neutralization and in vivo protection compared to its native IgG1 form. This improved protection by the engineered mAbs was dependent on the presence of the vFcR. Human IgG3 allotypes lacking vFcR binding also exhibited enhanced antiviral activity in vivo , suggesting that vaccines that robustly induce IgG3 responses could show enhanced protection. suggesting the value of vaccination strategies that robustly induce this subclass. Lastly, analysis of longitudinal responses to acute primary genital infection in humans raised the possibility that unlike most viruses, HSV may exhibited slow induction of IgG3. In summary, this study demonstrates that mAbs lacking the ability to interact with the vFcR can exhibit improved protection from HSV-offering new prospects for antibody-based interventions., Competing Interests: Competing Interests: I.M.B., D.A.L., and M.E.A. report a patent, WO2020077119A1, for the use of HSV-specific mAbs as method for the treatment for nHSV infections. CJ reports consulting for GSK, Pfizer, and Assembly Biosciences and research funding from GSK and Moderna unrelated to this work. MEA reports consulting for Seromyx Systems and research funding from Moderna unrelated to this work.

Importance: Leaders of healthcare organizations play a key role in developing, prioritizing, and implementing plans to adopt new evidence-based practices. This study examined whether a letter with peer comparison data and social norms messaging impacted healthcare leaders' decision to access a website with resources to support evidence-based practice adoption., Methods: Pragmatic, parallel-group, randomized controlled trial completed from December 2019 -June 2020. We randomized 2,387 healthcare leaders from health systems, hospitals, and physician practices in the United States, who had previously responded to our national survey of healthcare organizations, in a 1:1 allocation ratio to receive one of two cover letter versions via postal mail (all) and email (for the 60.6% with an email address), accompanying a report with their survey results. The "nudge" letter included messaging that highlighted how an organization's results compared to peers using text, color, and icons. Both nudge and control letters included links to a resource website. We interviewed 14 participants to understand how the letter and report impacted behaviors., Results: Twenty-two of 1,194 leaders (1.8%) sent the nudge letter accessed online resources, compared to 17 of 1193 (1.4%) sent the control letter (p = 0.424). Nine of the 14 interviewed leaders stated that viewing the letter (regardless of version) and accompanying report influenced their decision to take a subsequent action other than accessing the website. Seven leaders forwarded the report or discussed the results with colleagues; two leaders stated that receiving the letter and report resulted in a concrete practice change., Conclusions: Receiving cover letters with a behavioral nudge did not increase the likelihood that organizational leaders accessed a resource website. Qualitative results suggested that the survey report's peer comparison data may have been a motivator for prioritizing and delegating implementation activities, but leaders themselves did not access our online resources., Competing Interests: The authors have read the journal’s policy and have the following competing interests: The statements, findings, conclusions, views, and opinions contained and expressed in this article are based in part on data obtained under license from IQVIA information services (OneKey subscription information services 2010-2017, IQVIA incorporated all rights reserved). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Trend estimates from national surveys over the last 20 years have suggested converging rates of alcohol use over time between adult men and women. However, limited research has utilized an intersectional lens to examine how sociodemographic characteristics influence gender differences in these trends., Methods: The current study used data from the National Survey on Drug Use and Health (NSDUH) to examine whether gender intersected with race/ethnicity, age, education level, marital status, employment status, household income, and urbanicity on temporal trends (2009-2019) in alcohol use disorder (AUD). Logistic regression and linear trend analyses were conducted to examine interaction effects of sociodemographic variables and changes in rates of AUD over time in males and females., Results: We observed decreasing rates of AUD over time in males and females, with larger declines in males (p=0.01; OR=0.96 in males vs. OR=0.98 in females). We identified subpopulations of females that demonstrated little or no reductions during this timeframe (2009-2019), which varied by race/ethnicity, age, marital status, employment, and income but not by education or urbanicity. In adults aged 49 years and younger (overall p=0.02; ages 18-25 OR=0.92 in males vs. 0.96 in females, ages 26-29 OR=0.97 in males vs. OR=0.99 in females), and in those employed (overall p=0.05; OR=0.96 in males vs. OR=0.99 in females), women demonstrated smaller declines in comparison to men. Additionally, women who reported that they were Black (p=0.006; OR=0.94 in males vs. OR=1 in females), single (p=0.009; OR=0.94 in males vs. 0.96 in females) or earning between $20,000 and $49,000 (p=0.012; OR=0.96 in males vs. 0.98 in females), had smaller or no declines in AUD in compared to men with the same demographic characteristic., Conclusions: Our findings provide support for converging rates of AUD between genders and newly identify subpopulations of females that may be at heightened risk., Competing Interests: Declaration of Competing Interest The authors have no financial or personal conflicts of interest to share., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This study aims to report otologic manifestations in a cohort of patients with aspirin exacerbated respiratory disease (AERD) to determine if severity of sinonasal inflammation is associated with presence of otologic sequalae (OS)., Methods: All AERD patients treated at a tertiary care center between 2009 and 2016 were included in analysis. Demographics, history of hearing loss, Lund-Mackay (LMK) scores, number of previous sinus procedures, CT findings, and pure tone averages (PTA) were compared between patients with and without OS using chi-square test, Fisher's exact test, and Wilcoxon rank sum test., Results: Of 255 AERD patients, 58.4% were female with a mean age of 48.9 (SD: 13.4) years. The majority (52.2%) had otologic manifestations, most commonly: otitis media requiring antibiotics (n = 89, 34.9%), peripheral vertigo (n = 59, 23.1%), and middle ear effusion (n = 44, 17.3%). A total of 74 patients (29.0%) had hearing loss. PTA ranged from 13.3 to 61.7 dB for the cohort, with no significant difference between those with and without OS. There was no significant difference in LMK in both groups. Patients with OS had a significantly greater number of sinus procedures than those without OS (median = 2.4 and 1.8 respectively; P  = .01)., Conclusions: Otologic manifestations are common in patients with AERD. While there was an increased number of sinonasal surgeries performed in the patients with OS, there was no correlation between sinonasal inflammation, and the presence of OS as measured by LMK score or PTA. Otologic signs and symptoms should be considered in patients with AERD to help mitigate patient morbidity., Level of Evidence: III., 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.

Intra-individual variability (IIV) quantifies an individual's scatter in performances across a test battery (dispersion) or across reaction times within a single task (consistency). No studies have meta-analyzed the cross-sectional IIV literature in those with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). An additional aim of this meta-analysis was to examine IIV in APOE ε4 + healthy control (HC) samples. A systematic search strategy was applied to six databases (Academic Search Complete, PsycINFO, MEDLINE, CINAHL Complete, ERIC, and ProQuest Dissertations & Theses) to identify studies comparing the extent of dispersion- and consistency-based cognitive IIV between clinical (MCI, AD) and HC samples. Thirty-five studies met the inclusion criteria for our random-effects cross-sectional meta-analysis. Hedges' g was used to aggregate between-group effect sizes, with higher positive values indicating clinical > HC IIV. Meta-regression and subgroup-analyses were conducted to evaluate continuous and categorical moderator variables, respectively. Omnibus models yielded analogous moderate-strength, albeit heterogeneous, effects for dispersion and consistency (g = 0.65). Clinical severity was a robust moderator of dispersion (MCI = 0.47, AD = 1.16) and consistency (MCI = 0.51, AD = 1.31) effects. Supplemental analysis of APOE ε4 status in HCs revealed a nonsignificant trend of elevated overall (i.e., dispersion + consistency) IIV in APOE ε4 + vs. APOE ε4 - HC samples (g = 0.24). Cognitive IIV is sensitive to the presence of AD-related genetic risk as well as neurocognitive impairment across the neurocognitive disorder severity spectrum, with a graded-pattern of HC < MCI < AD samples., Competing Interests: Declarations. Ethical Approval: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Human milk contains human milk oligosaccharides (HMOs) and microRNAs (miRNAs), which are key bioactive components. HMOs are indigestible carbohydrates that impact infant growth and development. miRNAs are small, non-coding RNAs that regulate post-transcriptional gene expression. miRNAs are abundant in human milk and can be contained in extracellular vesicles (EVs). There is evidence that miRNAs are synthesized in the mammary epithelium and may influence mammary gland development and milk synthesis. However, the relationships between miRNAs and HMOs have yet to be fully characterized., Methods: This study examined the associations between 210 human milk EV-miRNAs and 19 HMOs in a cohort of 98 Latina mothers. HMO measures included summary measures and concentrations of 19 HMOs. Relationships between EV-miRNAs and HMOs were examined using principal components analysis and associations between individual EV-miRNAs and HMOs were assessed., Results: Overall patterns of EV-miRNA levels, summarized using principal components, were associated with HMO summary measures and concentrations. Levels of individual EV-miRNAs were associated with HMO summary measures and individual concentrations of 2'FL, 3FL, 3'SL, 6'SL, FLNH, LNFP I, and LNH., Discussion: Results from this study suggest that human milk EV-miRNAs are associated with the concentration of HMOs, which may have important effects on infant growth and development., Competing Interests: MG receives book royalties and is a scientific advisor for Yumi. LB is a co-inventor on patent applications related to the use of HMOs in preventing necrotizing enterocolitis and other inflammatory diseases. 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 Holzhausen, Patterson, Wong, Kim, Kupsco, Howe, Bode, Goran and Alderete.)

Intracellular membrane fusion is catalyzed by SNAREs, Rab GTPases, SM proteins, tethers, Sec18/NSF and Sec17/SNAP. Membrane fusion has been reconstituted with purified vacuolar proteins and lipids to address 3 salient questions: whether ATP hydrolysis by Sec18 affects its promotion of fusion, whether fusion promotion by Sec17 and Sec18 is only seen with mutant SNAREs or can also be seen with wild-type SNAREs, and whether Sec17 and Sec18 only promote fusion when they work together or whether they can each work separately. Fusion is driven by two engines, completion of SNARE zippering (which does not need Sec17/Sec18) and Sec17/Sec18-mediated fusion (needing SNAREs but not the energy from their complete zippering). Sec17 is required to rescue fusion that is blocked by incomplete zippering, though optimal rescue also needs the ATPase Sec18. ATP is an essential Sec18 ligand, but at limiting Sec17 levels Sec18 ATP hydrolysis also drives release of Sec17 without concomitant trans -SNARE complex disassembly. At higher (physiological) Sec17 levels, or without ATP hydrolysis, fusion prevails over Sec17 release. Stiff 16:0, 18:1 fatty acyl chain lipids provide an alternative route to suppressing fusion, with entirely wild-type SNAREs and without impediment to zippering. In this case, Sec17 and Sec18 restore comparable fusion with either ATP or a nonhydrolyzable analog. Fusion blocked by impaired zippering can be restored by concentrated Sec17 alone (but not by Sec18), while fusion inhibited by stiff fatty acyl chains is partially restored by Sec18 alone (but not by Sec17). With distinct fusion impediments, Sec18 and Sec17 have both shared roles and independent roles in promoting fusion.

Background: Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool., Methods: To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2-5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs., Results: PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received 4 IPV doses. Across the 3 PV serotypes, both nasal (Spearman ρ ≥ 0.87, P ≤ .0003 for all) and adenoid (Spearman ρ ≥ 0.57, P ≤ .05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization., Conclusions: Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Poorly differentiated chordoma is an exceedingly rare, aggressive subtype of chordoma. These tumors typically arise in the axial skeleton of young patients, most commonly the skull base, followed by the cervical spine. Herein, we present a 60-year-old patient with longstanding knee pain and nondiagnostic imaging, initially thought to be due to osteoarthritis. No discrete mass-forming lesion was identified by radiology. Synovial histology at the time of arthroplasty revealed a multinodular proliferation of epithelioid-to-histiocytoid cells with a moderate amount of eosinophilic-to-clear, vacuolated cytoplasm. Scattered cells with high-grade nuclear atypia were present. A diagnosis of metastatic carcinoma was considered due to immunohistochemical positivity for keratin and GATA3. However, a diagnosis of epithelioid sarcoma was rendered based on clinical context, morphology, and loss of immunohistochemical expression for SMARCB1 (INI1). However, upon re-review of the tumor, brachyury was retrospectively added to the immunohistochemistry panel and showed strong positivity, thus prompting amendment of the initial diagnosis of epithelioid sarcoma to extra-axial poorly differentiated chordoma. Given the rarity of this diagnosis, molecular testing was performed which revealed a unique SMARCB1 molecular profile with a single-nucleotide variant in addition to the commonly reported loss of chromosome 22q. This report of an ultra-rare sarcoma in an uncommon anatomic site highlights multiple potential pitfalls in the diagnosis of poorly differentiated chordoma, emphasizes the importance of brachyury immunohistochemistry in rendering a correct interpretation, and underscores an opportunity for further molecular analysis to better define the molecular profile of this entity., 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.

Protein Ser/Thr phosphatase PP1 is always associated with one or two regulatory subunits or RIPPOs. One of the earliest evolved RIPPOs is PPP1R2, also known as Inhibitor-2. Since its discovery nearly 5 decades ago, PPP1R2 has been variously described as an inhibitor, activator or (metal) chaperone of PP1, but it is still unknown how PPP1R2 affects the function of PP1 in intact cells. Here, using specific research tools, we demonstrate that PPP1R2 stabilises a subgroup of PP1 holoenzymes, exemplified by PP1:RepoMan, thereby promoting the dephosphorylation of their substrates. Mechanistically, the recruitment of PPP1R2 disrupts an inhibitory, fuzzy interaction between the C-terminal tail and catalytic domain of PP1, and generates an additional C-terminal RepoMan-interaction site. The resulting holoenzyme is further stabilized by a direct PPP1R2:RepoMan interaction, which renders it refractory to competitive disruption by RIPPOs that do not interact with PPP1R2. Our data demonstrate that PPP1R2 modulates the function of PP1 by altering the balance between holoenzymes through stabilisation of specific subunit interactions., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

As a model organism in the study of immunity to infection, Toxoplasma gondii has been instrumental in establishing key principles of host anti-microbial defense and its regulation. Here, we employed an attenuated uracil auxotroph strain of Type I Toxoplasma designated OMP to further untangle the early immune response to this parasitic pathogen. Experiments using αβ T cell-deficient Tcrb -/- mice unexpectedly revealed that an intact αβ T lymphocyte compartment was essential to survive infection with OMP. Subsequent antibody depletion and knockout mouse experiments demonstrated contributions from CD4 + T cells in resistance. Using transgenic knockout mice, we found only a partial requirement for IFN-γ and a lack of requirement for Toll-like receptor (TLR) adaptor MyD88 in resistance. In contrast to other studies on + , the ability to survive OMP infection did not require IL-12p40. Surprisingly, T cell-dependent IL-10 was found to be critical for survival, and deficiency of this cytokine triggered an abnormally high systemic inflammatory response. We also found that parasite molecule GRA24, a dense granule protein that triggers TLR-independent IL-12 production, acts as a virulence factor contributing to death of OMP-infected Toxoplasma , the ability to survive OMP infection did not require IL-12p40. Surprisingly, T cell-dependent IL-10 was found to be critical for survival, and deficiency of this cytokine triggered an abnormally high systemic inflammatory response. We also found that parasite molecule GRA24, a dense granule protein that triggers TLR-independent IL-12 production, acts as a virulence factor contributing to death of OMP-infected Tcrb -/- mice via monoclonal depletion of IL-12p40, suggesting that GRA24-induced IL-12 underlies the fatal immunopathology observed. Collectively, our studies provide insight into a novel and rapidly arising T lymphocyte-dependent anti-inflammatory response to IL-10 which operates independently of MyD88 and IL-12 and that depends on the function of parasite-dense granule protein GRA24.IMPORTANCEAs a model infectious microbe and an important human pathogen, the apicomplexan -/- mice. Furthermore, resistance against OMP was restored in Tcrb strain emerges as a virulent parasite in the absence of an intact T cell compartment. Both CD4 -/- mice via monoclonal depletion of IL-12p40, suggesting that GRA24-induced IL-12 underlies the fatal immunopathology observed. Collectively, our studies provide insight into a novel and rapidly arising T lymphocyte-dependent anti-inflammatory response to T. gondii T lymphocytes are required for optimal protection, in line with previous findings in other models of Toxoplasma gondii infection. Nevertheless, several novel aspects of the response were identified in our study. Protection occurs independently of IL-12 and MyD88 and only partially requires IFN-γ. This is noteworthy particularly because the cytokines IL-12 and IFN-γ have previously been regarded as essential for protective immunity to Toxoplasma . Instead, we identified the anti-inflammatory effects of T cell-dependent IL-10 as the critical factor enabling host survival. The parasite dense granule protein GRA24, a host-directed mitogen-activated protein kinase activator, was identified as a major virulence factor in T cell-deficient hosts. Collectively, our results provide new and unexpected insights into host resistance to + and CD8 + T lymphocytes are required for optimal protection, in line with previous findings in other models of Toxoplasma infection. Nevertheless, several novel aspects of the response were identified in our study. Protection occurs independently of IL-12 and MyD88 and only partially requires IFN-γ. This is noteworthy particularly because the cytokines IL-12 and IFN-γ have previously been regarded as essential for protective immunity to T. gondii . Instead, we identified the anti-inflammatory effects of T cell-dependent IL-10 as the critical factor enabling host survival. The parasite dense granule protein GRA24, a host-directed mitogen-activated protein kinase activator, was identified as a major virulence factor in T cell-deficient hosts. Collectively, our results provide new and unexpected insights into host resistance to Toxoplasma ., Competing Interests: The authors declare no conflict of interest.

The opportunistic pathogen Pseudomonas aeruginosa infects the airways of people with cystic fibrosis (CF) and produces a virulence factor Cif that is associated with worse outcomes. Cif is an epoxide hydrolase that reduces cell-surface abundance of the cystic fibrosis transmembrane conductance regulator (CFTR) and sabotages pro-resolving signals. Its expression is regulated by a divergently transcribed TetR family transcriptional repressor. CifR represents the first reported epoxide-sensing bacterial transcriptional regulator, but neither its interaction with cognate operator sequences nor the mechanism of activation has been investigated. Using biochemical and structural approaches, we uncovered the molecular mechanisms controlling this complex virulence operon. We present here the first molecular structures of CifR alone and in complex with operator DNA, resolved in a single crystal lattice. Significant conformational changes between these two structures suggest how CifR regulates the expression of the virulence gene cif. Interactions between the N-terminal extension of CifR with the DNA minor groove of the operator play a significant role in the operator recognition of CifR. We also determined that cysteine residue Cys107 is critical for epoxide sensing and DNA release. These results offer new insights into the stereochemical regulation of an epoxide-based virulence circuit in a critically important clinical pathogen., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

What Was the Educational Challenge?: Representation gaps in medical education publishing are widely recognized and may be attributed to epistemic injustice, defined as 'wrong done to someone in their capacity as a knower.' Although peer review is meant to ensure 'rigor,' some quality assurance practices can inadvertently silence entire populations and impede understanding of a field's foundational concepts., What Was the Proposed Solution?: To honor our journal's commitment to equitable knowledge production, a diversity, equity, and inclusion working group at Teaching and Learning in Medicine (TLM) reimagined rigor to include striving for a 'more equitable, diverse, and inclusive research system.', How Was the Proposed Solution Implemented?: We implemented structural peer review reform at TLM by adapting Hogan et al.'s Dimensionality and R4P framework for health equity, prioritizing change in our communication with contributors., What Lessons Learned Are Relevant to a Wider Audience?: Since implementation, our journal has received feedback expressing appreciation for humanity and personal connection in our peer review, and we have observed increased publications from geographically marginalized authors. We believe our outcomes result from respecting marginalized authors' authority to pursue their own interests, concerns, and successes with respect to knowledge production., What Are the Next Steps?: We believe our approach can be adopted by other peer-reviewed journals. We invite application and critique of our framework to advance community development in creating relevant, accessible, and equitable knowledge production for all people.

Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that PBD BM alone is not enough for stable binding between CENP-U and Plk1 highlighting the complexity of the interaction which warrants further investigation. An important interactor for Plk1 during mitosis is the checkpoint protein BubR1. Plk1 bound to BubR1 via PBD interaction with pT620 phosphorylates BubR1 S676/T680 to promote BubR1-PP2A/B56 interaction. The BubR1-PP2A/B56 complex counteracts the destablizing effect on kinetochore-microtubule attachments by mitotic kinases to promote mitotic progression. Here we show that Plk1 phosphorylates T600/T608 on BubR1 and the double phosphorylation is critical for BubR1-Plk1 interaction. A similar mechanism for Plk1-Bub1 interaction also exists indicating a general principle for Plk1 kinetochore recruitment through self-priming. Mechanistically preventing BubR1 T600/T608 phosphorylation impairs chromosome congression and checkpoint silencing by reducing Plk1 and PP2A/B56 binding to BubR1. Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression., (© 2024. The Author(s).)

Importance: There is limited evidence guiding surgeons in how much mesh to resect when treating mesh complications., Objective: The aim of the study was to compare rates of recurrent prolapse after mesh excisional surgical procedures for prolapse mesh complications., Study Design: This multicenter, retrospective cohort study included patients, identified by Current Procedural Terminology codes, who were treated surgically for prolapse mesh complications at 8 institutions between 2010 and 2019. Excisional surgical procedures were categorized as major (total vaginal, extravaginal, and total mesh excisions) or minor (partial vaginal excisions and mesh revisions). The primary outcome was prolapse recurrence 1 year after mesh excision surgery. Secondary outcomes included long-term prolapse recurrence. Prolapse recurrence was evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression., Results: Two hundred sixty-one patients met inclusion criteria with 188 (72%) undergoing minor and 73 (28%) major excisions, with a median follow-up time of 1.0 years. Groups differed in parity, location of implant surgery, and number of vaginal compartments involved in excision. Within the first year, major excisions had a higher prolapse recurrence rate (8.7%) than minor excisions (2.9%), P < 0.05. Adjusting for mesh implant type, the hazard ratio for pelvic organ prolapse was 6.1 in the major compared to minor excision. In the entire study period, prolapse recurrence was 33.8% and did not differ between groups., Conclusions: Patients undergoing major excision surgical procedures may have higher rates of prolapse at 1 year compared to those undergoing minor excisions. However, in long-term follow-up, recurrence rates were not different. Our findings may aid surgeons in expectation setting prior to excisional procedures., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Context.—: Quality communication between clinicians and pathologists is required for optimal cancer care. The College of American Pathologists provides anatomic site-specific cancer protocols that facilitate synoptic reporting for efficient communication, contributing to accuracy and completeness of cancer staging., Objective.—: To evaluate synoptic cancer pathology reporting across the Department of Veterans Affairs (VA), the largest integrated health system in the United States, for 4 common cancers: melanoma and colon, bladder, and kidney cancer., Design.—: For each cancer type, we investigated at least 200 biopsy and 200 resection reports from 2019 to 2021. In each report, we determined whether a synoptic format was used. The reports were selected using random sampling across all VA health care facilities. We also identified a set of core elements that were underdocumented., Results.—: Among 1618 pathology reports, 778 (48%; 95% CI, 46%-50%) were synoptic reports. Synoptic reporting was much more common among resections (621 of 811; 77%; 95% CI, 74%-79%) than among biopsies (157 of 807; 19%; 95% CI, 17%-22%). It was most common in colorectal resections (200 of 206; 97%; 95% CI, 94%-99%) and least common in colon biopsy reports (1 of 200; 0.5%; 95% CI, 0%-3%). Core elements that were underdocumented included procedure and regional lymph nodes for resections of bladder and kidney cancer and of melanoma., Conclusions.—: Synoptic reporting was used about three-quarters of the time for resections and about 1 in 5 times for biopsies. Future work should develop implementation strategies to improve synoptic reporting, especially for biopsy specimens and core elements that were relatively underdocumented., (© 2024 College of American Pathologists.)

The advanced glycation end products (AGEs) Webinar was co-hosted by Diabetes Technology Society and Kitalys Institute on August 8, 2024, with the goal of reviewing progress made in the measurement and use of AGEs in clinical practice. Meeting topics included (1) AGEs as predictors of diabetic nephropathy (DKD), (2) hemoglobin glycation index (HGI) and the glycation gap (GG), (3) formation and structure of AGEs, (4) AGEs as a risk factor of cardiovascular disease (CVD), and (5) approaches to limit or prevent AGE formation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.N.H. is a consultant for Liom.ATA is a consultant for Liom.DCK is a consultant for Afon, Embecta, Glucotrack, Lifecare, Novo, Samsung, Synchneuro, and Thirdwayv.GAF is an advisor for 180 Life Sciences, 89bio, Adocia, Abbott, AdipoPharma, Aerami, Amolyt, Carthera, Catalyst, Cohen Global, CMC Magnetics, Diasome, Eleos, Entera Bio, Enterin, Glyscend, Hagar, Hogan Lovells, IM Therapeutics, Innoneo, Intarcia, Levicure, Lilly Asia Ventures, Lumos, Mars Symbioscience, Melior, metaLead Therapeutics, Microbiotix, MMD, Modular Medical, New Amsterdam, Northwestern, NuSirt, NuVox, Oramed, Pano, Pasithea, PhylloPharma, Pleiogenix, Recordati, Regor, Remodeless, Renaissance, RenovoRx, Rivus, RxMP, Sera Biopharma, Seraxis, Serpin, SFC Fluidics, Skinject, SROne, Stalicla, Surf Bio, TIXiMED, Veroscience, Verthermia, WaveBreak, Zealand Pharma, and Zucara.PB is co-founder and Chief Scientific Officer at Journey Biosciences.SC has nothing to disclose.AMS holds patents and patent applications with the NYU Grossman School of Medicine for small molecule antagonists of RAGE–DIAPH1.AP has received grant funding (to the institution) from Applied Therapeutics, Gilead Sciences, Ultromics, Myovista, and Roche; has served as a consultant for and/or received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc., Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Sarfez Therapeutics, Edwards Lifesciences, Merck, Bayer, Novo Nordisk, Alleviant, Axon Therapies, and has received nonfinancial support from Pfizer and Merck. AP is also a consultant for Palomarin Inc with stocks compensation and has received research support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01), the National Institute on Minority Health and Disparities (R01MD017529), and the National Institute of Heart, Lung, and Blood Institute (R21HL169708).PK is one of the patent holders of GLYLO, a supplement licensed to Juvify Bio by the Buck Institute. PK is also the founder of Juvify Bio.

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research., Competing Interests: Conflict of interest: Y.C.G. Lee receives drainage kits without charge for participants of a clinical trial he leads. J.S. Reisenauer has a research grant with Intuitive Surgical and is an educational consultant for Vergent, Isola, Medview and Imvaria, outside the submitted work. M.M. DeCamp is an educational consultant for PulmonX and is on the scientific advisory board for Pleural Dynamics. D.J. Feller-Kopman is an educational consultant for AstraZeneca, Noah Medical and Boston Scientific, outside the submitted work. H. Grosu has a sponsored research agreement with Known Medicine. J.F.B. Chick is an educational consultant and speaker for Inari Medical, Guerbet, C. R. Bard, Argon Medical Devices, Boston Scientific, NXT Biomedical and AiDoc, outside the submitted work. F. Maldonado received research funding from Medtronic and personal consulting fees from J&J and Intuitive, outside of the submitted work. The remaining authors do not have any disclosures or conflicts of interest to report., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: To evaluate and compare the readability and quality of patient information generated by Chat-Generative Pre-Trained Transformer-3.5 (ChatGPT) and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) using validated instruments including Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease, DISCERN, and Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P)., Methods: ENTHealth.org and ChatGPT-3.5 were queried for patient information on laryngology topics. ChatGPT-3.5 was queried twice for a given topic to evaluate for reliability. This generated three de-identified text documents for each topic: one from AAO-HNS and two from ChatGPT (ChatGPT Output 1, ChatGPT Output 2). Grade level and reading ease were compared between the three sources using a one-way analysis of variance and Tukey's post hoc test. Independent t-tests were used to compare DISCERN and PEMAT understandability and actionability scores between AAO-HNS and ChatGPT Output 1., Results: Material generated from ChatGPT Output 1 and ChatGPT Output 2 were at least two reading grade levels higher than that of material from AAO-HNS (p < 0.001). Regarding reading ease, ChatGPT Output 1 and ChatGPT Output 2 documents had significantly lower mean scores compared to AAO-HNS (p < 0.001). Moreover, ChatGPT Output 1 material on vocal cord paralysis had a lower PEMAT-P understandability compared to that of AAO-HNS material (p > 0.05)., Conclusion: Patient information on the ENTHealth.org website for select laryngology topics was, on average, of a lower grade level and higher reading ease compared to that produced by ChatGPT, but interestingly with largely no difference in the quality of information provided., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Oxysterols are metabolites of cholesterol that regulate the homeostasis of cholesterol, fatty acids, and glucose. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation. We previously reported that circulating 27-hydroxycholesterol (27-OHC), an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, in addition to 27-OHC, we report on four other circulating oxysterols: 25-hydroxycholesterol, 24(S)-hydroxycholesterol, 7ɑ-hydroxycholesterol, and 4β-hydroxycholesterol. Oxysterol concentrations were measured using liquid chromatography/mass spectrometry from fasting plasma collected at baseline from 1,246 participants of the Vitamin D/Calcium Polyp Prevention Study, a multicenter adenoma chemoprevention trial. To evaluate multiple oxysterols simultaneously, we used both log-linear regression and Bayesian kernel machine regression models developed for analyses of complex mixtures adjusted for potential confounding factors. Higher circulating 7ɑ-hydroxycholesterol was associated with higher adenoma risk (Bayesian kernel machine regression-based multivariable-adjusted risk ratios (RR; for the 75th vs. 25th percentile, 1.22; 95% credible interval, CI, 1.04-1.42). In contrast, higher circulating 4β-hydroxycholesterol was associated with lower risk of these polyps (RR, 0.84; 95% CI, 0.71-0.99). The positive association with advanced adenoma risk that we previously reported for circulating 27-OHC persisted when controlling for other oxysterols (RR, 1.26; 95% CI, 0.98-1.62), including among those with advanced adenomas at baseline (RR, 1.75; 95% CI, 1.01-3.06). Prevention Relevance: Circulating concentrations of multiple oxysterols measured at the time of an initial colorectal adenoma diagnosis may be risk factors for subsequent incidence of these lesions. Novel colorectal cancer prevention strategies may target oxysterol formation., (©2024 American Association for Cancer Research.)

Phenomenon. The language of medicine (i.e., biomedical discourse) represents queerness as pathological, yet it is this same discourse medical education researchers use to resist that narrative. To be truly inclusive, we must examine and disrupt the biomedical discourse we use. The purpose of this study is to disrupt oppressive biomedical discourses by examining the language and structures medical educators use in their publications about queerness in relation to physicians and physician trainees. Approach. We searched PubMed, Web of Science, CINAHL, PsycINFO, and ERIC in October 2021 and again in June 2023 using a combination of controlled vocabulary (select terms designated by a database to enhance and reduce ambiguity in search) and keywords to identify articles related to sexuality, gender, identity, diversity and medical professionals. Searches were limited to articles published from 2013 to the present to align with the passage of The Respect for Marriage Act. Articles were included if they focused on the experiences and paths of physicians and physician trainees identifying with or embodying queerness, were authored by individuals based in the United States, and presented empirical studies. We excluded articles only discussing attitudes of cisgender heterosexual individuals about queerness. Two authors independently screened all articles for inclusion. We then used narrative techniques to "re-story" included articles into summaries, which we analyzed with four guiding questions, using queer theory as a sensitizing concept. Finally, we sought recurrent patterns in these summaries. Findings. We identified 2206 articles of which 23 were included. We found that biomedical discourse often: characterized individuals associated with queerness as a single homogenous group rather than as individuals with a breadth of identities and experiences; implied queer vulnerability without naming-and making responsible-the causes or agents of this vulnerability; and relied minimally on actual intervention, instead speculating on potential changes without attempting to enact them. Reflections. Authors each reflect on these findings from their positionalities, discussing: disrupting essentializing categories like "LGBT"; addressing harm through allyship around queerness; editorial responsibility to disrupt structures supporting oppressive biomedical discourse; the importance of program evaluation and interventions; and shifting the focus of medical education research toward queerness using QuantCrit theory.

Researchers in ubiquitous computing have long promised that passive sensing will revolutionize mental health measurement by detecting individuals in a population experiencing a mental health disorder or specific symptoms. Recent work suggests that detection tools do not generalize well when trained and tested in more heterogeneous samples. In this work, we contribute a narrative review and findings from two studies with 41 mental health clinicians to understand these generalization challenges. Our findings motivate research on actionable sensing, as an alternative to detection research, studying how passive sensing can augment traditional mental health measures to support actions in clinical care. Specifically, we identify how passive sensing can support clinical actions by revealing patients' presenting problems for treatment and identifying targets for behavior change and symptom reduction, but passive data requires additional contextual information to be appropriately interpreted and used in care. We conclude by suggesting research at the intersection of actionable sensing and mental healthcare, to align technical research in ubiquitous computing with clinical actions and needs.