Recent ucsf_postprints items

From 4Ms to 5 domains: ensuring new CMS Age-Friendly hospital measure improves care for older adults

Fri, 28 Aug 2026 00:00:00 +0000

In 2024, the Centers for Medicare and Medicaid Services (CMS) added a novel Age-Friendly Hospital Inpatient Quality Reporting (IQR) Measure, composed of 10 attestation statements in 5 domains. The measure is designed to improve care for older adults through promoting care processes and structural capabilities drawn from evidence-based standards included in the 4Ms Framework (What Matters, Medication, Mentation, and Mobility) and operationalized in 3 programs: Geriatric Surgery Verification, Geriatric Emergency Department Accreditation, and the Institute for Healthcare Improvement's Age-Friendly Health System recognition. We highlight synergies and gaps between these programs and the CMS Age-Friendly IQR measure to guide hospital efforts as they prepare for their first attestation in 2026. In addition, we make recommendations to CMS to improve measure validity through better specifications that ensure meaningful impact on care for older adults and to reduce associated reporting...

Dietary tryptophan mitigates lung ischemia-reperfusion injury in association with increased indole-3-propionate and aryl hydrocarbon receptor signaling

Fri, 28 Aug 2026 00:00:00 +0000

Background

Lung ischemia-reperfusion (IR) injury drives early morbidity after lung transplantation and cardiothoracic surgery, yet targeted preventive therapies are lacking. The gut-lung axis and microbiota-derived tryptophan metabolites, including indole-3-propionate (IPA), may regulate pulmonary immunity and inflammation. We investigated whether a tryptophan-rich (Trp-Rich) diet attenuates sterile lung IR injury by increasing microbiota-derived indole metabolites and reprogramming alveolar macrophage (AM) inflammatory responses.

Methods

C57BL/6 mice receiving isocaloric tryptophan-standard (Trp-Std) or tryptophan-rich (Trp-Rich) diets underwent lung IR injury. Oxygen saturation, lung cytokines, and aryl hydrocarbon receptor (AhR) signaling readouts were evaluated. Gut microbiota was profiled by 16S rRNA sequencing, and targeted metabolomics quantified tryptophan metabolites in feces, portal vein (PV) plasma, and lung tissue. To further assess inflammatory priming...

Barriers and facilitators to implementing a brief tobacco cessation intervention during vaccine administration in community pharmacies: A mixed-methods study

Fri, 28 Aug 2026 00:00:00 +0000

OBJECTIVE: This study describes the implementation of a brief tobacco cessation intervention (Ask, Advise, Refer: AAR) into routine vaccination workflows. METHODS: Using a convergent mixed methods approach, data were collected from 10 community pharmacies in (independent, hospital outpatient, and chain locations) via electronic documentation during vaccine administration and semi-structured interviews with pharmacy staff. The Consolidated Framework for Implementation Research served as a framework to guide qualitative interview coding and analyses, and quantitative data were analyzed descriptively. Findings were triangulated following the analyses. RESULTS: Pharmacy staff members (14 pharmacists, 3 pharmacy technicians) participated in interviews and electronic intervention documentation was submitted by 8 of the 10 pharmacies. Participants found the AAR intervention to be appropriate, feasible, and compatible with existing vaccination workflows. Seven of the 10 pharmacies included...

The CODEX action incubator: a consensus-driven approach to identify and implement diagnostic excellence measures in the context of artificial intelligence

Fri, 28 Aug 2026 00:00:00 +0000

Diagnostic errors are a substantial source of patient harm. As artificial intelligence (AI) integrates into clinical workflows, opportunities are emerging to assess their impacts on diagnostic excellence (DxEx). The Coordinating Center for Diagnostic Excellence (CODEX) at the University of California San Francisco established the Action Incubator to translate research advances in DxEx into tangible strategies for improving diagnosis. The September 2025 in-person inaugural Action Incubator convened 30 multidisciplinary stakeholders representing health systems, patient advocacy, industry, and policy groups. Through structured discussions and breakout sessions, participants identified AI scribes as a near-term, scalable use case for evaluating AI's impact on diagnosis not only because of their widespread adoption, but - as supported by cognitive load theory - because of their potential to reduce cognitive burden and allow clinicians to focus more on diagnosis....

Advancing Toward Clinical Deployment of AI-Generated Discharge Summaries—Beyond the Bench

Fri, 28 Aug 2026 00:00:00 +0000

Advancing Toward Clinical Deployment of AI-Generated Discharge Summaries—Beyond the Bench

Impacts of land use and fallowing on coccidioidomycosis incidence in California: A population-based longitudinal study

Fri, 28 Aug 2026 00:00:00 +0000

Coccidioidomycosis (Valley fever) is a growing public health concern in the western U.S., with California reporting more than an eightfold rise in cases over the past two decades. As climate change, groundwater regulation, and prolonged drought drive major agricultural land-use shifts in the state, including widespread retirement of cultivated lands (i.e., fallowing), understanding their effects on this soil-borne fungal infection is critical. We linked 65,657 confirmed, geolocated cases (2008-2021) to high-resolution maps distinguishing natural vegetation, crop types, and fallowed fields to quantify how land use and land cover were associated with disease rates. Flexible statistical models showed that natural land covers, shrubland, barren ground, and grassland, were associated with higher incidence. Some agricultural uses (grain/hay, field crops, corn, and cotton) were associated with higher incidence, whereas others (orchards, rice, and truck crops/berries) were associated...

Building Tobacco Treatment Capacity and Sustainability: A Qualitative Study on Implementation of Community Pharmacy Technicians as Community Health Workers

Fri, 28 Aug 2026 00:00:00 +0000

Community pharmacies are increasingly providing health care services like tobacco treatment and disease-related management but need sustainable models for implementation. As several state Medicaid programs reimburse for community health worker (CHW) services, one promising model is to have pharmacy technicians engage with patients as designated CHWs. This qualitative study interviewed staff in seven California pharmacies about their experience with and perspectives on implementing community pharmacy technicians as CHWs. Guided by implementation science frameworks, data were hand-coded and analyzed iteratively using thematic analysis. Relative advantage and compatibility of CHWs was high across all pharmacies. Pharmacy culture aligned with CHW values, and CHW integration helped formalize the work that pharmacy staff were already doing. Challenges included the complexity of billing and obtaining payment for services provided. Despite these barriers, pharmacies successfully integrated...

Patient Outcomes Associated With a Composite Measure of 4Ms Care Adherence in the Inpatient Setting.

Fri, 28 Aug 2026 00:00:00 +0000

Background

The 4Ms (what matters, medication, mentation, and mobility) is a widely adopted age-friendly care framework. However, there is no evidence on inpatient 4Ms adherence thresholds associated with improved outcomes.

Methods

In a retrospective cross-sectional analysis, we measured encounter-level adherence to the 4Ms for inpatients 65+ at the University of California San Francisco between January 1, 2021 and December 31, 2024. Outcomes included 30-day unplanned readmissions, 30-day emergency department (ED) visits, length of stay (LOS), and community admissions discharged to a facility. Using fixed effects regression models, we estimated the effect on outcomes of adherence to 100% of 4Ms assessments (what matters, medication, mentation, and mobility screening) plus 25%, 50%, and 75% of shifts with full adherence to 4Ms Act Ons (actions, such as de-prescribing high-risk medications, ambulating). We conducted subgroup analyses by age and medical versus surgical...

Recurrent acquisition of nuclease-protease pairs in antiviral immunity

Fri, 28 Aug 2026 00:00:00 +0000

Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed that the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Two distinct immune systems, Hachiman and AVAST (antiviral adenosine triphosphatase/nucleoside triphosphatase of the STAND superfamily, Avs), use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease (canu) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pronucleases and their activating proteases within different...

SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease

Thu, 27 Aug 2026 00:00:00 +0000

The Hirschsprung disease (HSCR) is a complex congenital disorder, arising from abnormalities in enteric nervous system (ENS) development. There is a gender disparity among the patients, with the male to female ratio as high as 5 : 1. Loss-of-function mutations of HSCR genes and haploinsufficiency of their gene products are the primary pathogenic mechanisms for disease development. Recent studies identified over half of the HSCR disease susceptibility genes as targets for the sex-determining factor SRY, suggesting that this Y-encoded transcription factor could be involved in sexual dimorphism in HSCR. Among the SRY targets, the tyrosine kinase receptor RET represents the most important disease gene, whose mutations account for half of the familial and up to one-third of the sporadic forms of HSCR. RET is regulated by a distal and a proximal enhancer at its promoter, in which PAX3 and NKX2-1 are the resident transcription factors respectively. We show that the SRY-box 10 (SOX10)...

Ten simple rules for effective use of generative AI for code development in environmental science

Thu, 27 Aug 2026 00:00:00 +0000

Ten simple rules for effective use of generative AI for code development in environmental science

IN MEMORIAM - Irwin Feinberg, MD

Thu, 27 Aug 2026 00:00:00 +0000

IN MEMORIAM - Irwin Feinberg, MD

The 2019 Ming K. Jeang awards for excellence in Cell & Bioscience

Thu, 27 Aug 2026 00:00:00 +0000

Two articles published by the research groups led by You-Shuo Liu of the Central South University, Changsha, Hunan, and Min Fang of the Huazhong University of Science and Technology, Wuhan, China have been selected as the recipients of the 2019 Ming K. Jeang Award for Excellence in Cell & Bioscience.

Changes in Outpatient and Telehealth Visits Among Undocumented Patients.

Thu, 27 Aug 2026 00:00:00 +0000

Importance

Anti-immigration policies in 2025 may influence outpatient care and telehealth among immigrant communities. Understanding visit patterns is essential for health systems leaders to prepare for shifts in health care use and ensure preventive care.

Objective

To compare outpatient in-person and telehealth visit completion rates among patients classified as likely undocumented and those likely with legal status, before and after 2025 federal immigration policy changes.

Design, setting, and participants

This cross-sectional study analyzed electronic health record data from outpatient encounters in a public safety-net system. Documentation status was approximated using non-English primary language without a Social Security number (SSN) to classify patients with likely undocumented status and using English primary language with SSN for patients likely with legal status. Analyses compared visits from January to June 2024 and January to June 2025.

Main...

Top Ten Tips Palliative Care Clinicians Should Know About Trauma-Informed Care

Thu, 27 Aug 2026 00:00:00 +0000

Trauma is a personal stress response to experiences perceived as harmful or life-threatening, and has ongoing impacts on illness and health. Exposure to trauma is increasingly prevalent, and the risk of medical trauma or re-traumatization is heightened for people living with serious illness. Trauma not only impacts health outcomes, but can also interfere with decision-making and worsen symptom burden at the end of life. Thus, it is critical that palliative care clinicians in all professions be skilled at providing high-quality trauma-informed care (TIC). TIC seeks to provide more holistic and equitable care through better understanding of how a person's life situation impacts behavior, reactions, behavior, responses, or relationships. A clinician using a trauma-informed lens asks, "What has happened to this person?" instead of, "What is wrong with this person?" A "universal precautions" approach is recommended, encouraging broad acknowledgment of possible trauma and recognition...

Comparison between the new Xpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) Ultra assay and Xpert MTB/RIF for diagnosis of extra-pulmonary tuberculosis in a tertiary care center.

Thu, 27 Aug 2026 00:00:00 +0000

Tuberculosis remains a significant global health challenge, with the re-emergence of Mycobacterium tuberculosis (MTB) posing serious concerns, especially in its extra-pulmonary forms. Rapid and accurate diagnosis is crucial for effective management. This study evaluates the performance of the Xpert MTB/RIF Ultra assay compared with the Xpert MTB/RIF and traditional microscopy (Ziehl-Neelsen stain) in diagnosing extra-pulmonary tuberculosis (EPTB) in a tertiary care center in northern India. A total of 100 samples collected from September 2024 to February 2025 underwent testing using these methods. Our findings indicate that the Xpert MTB/RIF Ultra assay demonstrated superior sensitivity and reliability compared with the Xpert MTB/RIF, whereas microscopy was the least effective. This study is the first of its kind in India, highlighting the enhanced diagnostic capabilities of the Xpert MTB/RIF Ultra assay for EPTB.

Importance

This is the first study to come out of...

The human testis-specific protein Y-linked (TSPY) is a male-specific cancer-testis antigen capable of eliciting significant immune responses and elimination of positive tumor cells in hepatocellular carcinoma

Thu, 27 Aug 2026 00:00:00 +0000

The testis-specific protein Y-linked (TSPY) is a male-specific cancer-testis antigen specifically expressed in germ cells of the testis under normal conditions and various cancers, particularly in hepatocellular carcinoma (HCC), under oncogenic conditions. It binds to cyclin B and exacerbates the cyclin B-CDK1 phosphorylation of factors important for mitotic/meiotic divisions. To determine if such TSPY proliferative actions could contribute to various male-biases in liver cancer, TSPY transgene was expressed in an oncogene-induced preclinical mouse model of HCC, using the hydrodynamic tail vein injection strategy. The results showed that TSPY expression suppressed tumor cell growth at early stage but could evolve to resume oncogenic progression at late stage in this mouse model. Transcriptome and bioinformatic analyses demonstrated that significant immune and inflammatory responses were activated in early stage of the cancer, resulting in elimination of positive tumor cells. Significant...

The Phenotype List String Grammar for Enhanced Protein and Antigen Reporting in the Immunogenetic Context

Thu, 27 Aug 2026 00:00:00 +0000

Standardised data representation is fundamental to the integrity, interoperability and reproducibility of immunogenetics and histocompatibility testing. While well-established standards such as the genotype list (GL) String, histoimmunogenetics markup language (HML) and minimum information for reporting next-generation sequence genotyping exist for encoding HLA genotyping results, no equivalent syntax currently exists for describing phenotype- or antigen-level information that underlies antibody testing and immunological risk assessment. We introduce the phenotype list (PL) String grammar and the phenotype list string code (PLSC) syntax, structured, machine-readable grammars designed to represent antigen- and protein-level data across three contexts: (1) the HLA phenotype composition of assay reagents, (2) test results derived from those reagents and (3) clinical interpretations of HLA antibody specificities. PL String extends the hierarchical logic of the GL String grammar, while...

Steroids and Cross-Linking for Ulcer Treatment

Thu, 27 Aug 2026 00:00:00 +0000

Importance: Adjunctive topical corticosteroids and/or corneal cross-linking (CXL) have the potential to improve outcomes in bacterial keratitis. Objective: To determine the benefit of adjunctive topical difluprednate and CXL with riboflavin in addition to topical antibiotics. Design, Setting, and Participants: This was a National Institutes of Health (NIH)-funded, sham, placebo-controlled trial randomizing participants to topical moxifloxacin, 0.5%, plus topical placebo plus sham CXL, vs topical moxifloxacin, 0.5%, plus difluprednate, 0.05%, plus sham CXL, vs topical moxifloxacin, 0.5%, plus difluprednate, 0.05%, plus CXL. Between September 2020 and October 2023, participants in clinics at the Aravind Eye Hospitals in India and Bascom Palmer Eye Institute, University of Miami, in Miami, Florida, were screened for inclusion. Included participants had smear- and/or culture-positive bacterial corneal ulcers with Snellen visual acuity of 20/40 or worse. Main Outcomes and Measures:...

A multiplex, prime editing framework for identifying drug resistance variants at scale

Thu, 27 Aug 2026 00:00:00 +0000

CRISPR-based genome editing has revolutionized functional genomics, enabling thousands of perturbations to be concurrently assayed in single experiments. However, for methods such as saturation genome editing (SGE), which aims to generate and assay libraries of point mutations, a challenge is that only one region (e.g., one exon) is studied per experiment. Here, we describe prime-SGE, a prime editing-based framework in which libraries of specific point mutations are installed into genes throughout the genome and then functionally assessed by sequencing of prime editing guide RNAs (pegRNAs) rather than the mutations themselves. We apply prime-SGE in two cell lines to assay thousands of point mutations in eight oncogenes for their ability to confer drug resistance to four tyrosine kinase inhibitors. Our prime-SGE strategy, combined with ongoing improvements in prime editing efficiency, opens the door to efficient positive selection screens of large numbers of point mutations at...

Expert consensus on intracranial vessel wall MRI in cerebrovascular disease: Society for Magnetic Resonance Angiography recommendations

Thu, 27 Aug 2026 00:00:00 +0000

In recent years, the clinical interest and research evidence of intracranial vessel wall MR imaging (iVWI) in vasculopathy lesion detection and characterization have made the technique a mainstay of patient care. Employing techniques with sufficient blood signal suppression (black blood) allows for direct visualization of lesions in the vessel wall itself, and facilitates the detection, evaluation, diagnosis, and differentiation of various cerebrovascular diseases. Clinical applications have extended rapidly to include multiple indications and pathologies, but the level of evidence and confidence varies for each of these indications and needs to be stratified and updated. On the other hand, a recent academic survey emphasized the need for additional technical and educational support in the neuroradiology community. The aim of this article is to provide expert consensus from the Society for Magnetic Resonance Angiography (SMRA) working group members for current clinical practice...

Pharmacokinetics, lineage identity, and trafficking of ex vivo expanded polyclonal regulatory T cells in a prospective randomized clinical trial of kidney transplant recipients with allograft inflammation

Thu, 27 Aug 2026 00:00:00 +0000

Regulatory T cells (Tregs) can reverse inflammation in animal models. We conducted a randomized controlled clinical trial of Treg therapy in kidney transplant recipients with subclinical graft inflammation (NCT02711826). The primary endpoint was the change in graft inflammation on a follow-up biopsy 6 months after Treg infusion. The trial accrued 8 control group participants and 7 polyclonal Treg group participants; the latter received 400 × 10⁶ to 1 × 10⁹ polyclonally expanded Tregs without adverse events. Graft inflammation decreased substantially in both groups at 6 months; however, the degree of change was not significantly different between the groups. The peak of infused Tregs in circulation correlated positively with the pre-existing circulating CD4⁺ T cell numbers, suggesting that Treg engraftment was limited by the size of the endogenous CD4⁺ T cell compartment. Infused Tregs were detected in 14-day postinfusion biopsies, albeit...

The TSPY gene and the loss of Y chromosome predisposition to cancers

Thu, 27 Aug 2026 00:00:00 +0000

Mosaic loss of Y chromosome is a common genetic phenomenon in elderly men. It predisposes affected individuals to cancers, suggesting that genes on this male-specific chromosome contribute to the well-being of men. Currently, the putative gene(s) responsible for such cancer predisposition when lost is/are currently unknown. A recent study identified the testis-specific protein Y-encoded (TSPY) gene possesses significant immunogenicity, capable of eliciting significant immune responses against and eliminating positive tumor cells in a mouse model of liver cancer. TSPY is a male-specific cancer-testis antigen expressed in a wide variety of cancers but not normal somatic cells. It is an ampliconic gene constituting a majority (~ 42%) of all protein-coding genes on the human Y chromosome. TSPY is hypothesized to be a guardian gene for man, protecting man from cancer development. Its high copy-number of conserved functional units ensures that it is intrinsically activated in early/progenitor...

Clinical Diagnosis—Is There Any Other Type?

Thu, 27 Aug 2026 00:00:00 +0000

Clinical Diagnosis—Is There Any Other Type?

Effects of improved water, sanitation, handwashing, and nutrition on early childhood IgG immune repertoire development against Shigella and enteroinvasive Escherichia coli (EIEC).

Thu, 27 Aug 2026 00:00:00 +0000

We studied the effects of a combined water, sanitation, handwashing, and nutritional supplementation (WSH + N) intervention on Shigella/EIEC IgG immune development among Bangladeshi children enrolled in a cluster-randomized trial. We used a bacterial display assay to measure IgG-specific binding to Shigella/EIEC Ipa proteins (IpaA, IpaB, IpaC, IpaD, and IpaH) from a substudy of 120 children (60 intervention, 60 control) at median ages 3, 14, and 28 months. We found that the WSH + N intervention did not impact IgG seroprevalence (56% vs 53%, P = 0.6) or IgG epitope repertoire development (P = 0.15-0.97), but there were distinct age-based patterns of IgG linear epitopes and motifs charting the development of the immune repertoire. Samples from before age 6 months, reflecting predominantly maternal IgG, had higher epitope breadth and magnitude compared with samples from older ages. A modeling analysis of maternal-child IgG dynamics suggests that peak susceptibility...

Expression of the Y-Encoded TSPY is Associated with Progression of Prostate Cancer

Thu, 27 Aug 2026 00:00:00 +0000

TSPY is a Y-encoded gene that is expressed in normal testicular germ cells and various cancer types including germ cell tumor, melanoma, hepatocellular carcinoma, and prostate cancer. Currently, the correlation between TSPY expression and oncogenic development has not been established, particularly in somatic cancers. To establish such correlation, we analyzed the expression of TSPY, in reference to its interactive oncoprotein, EEF1A, tumor biomarker, AMACR, and normal basal cell biomarker, p63, in 41 cases of clinical prostate cancers (CPCa), 17 cases of latent prostate cancers (LPCa), and 19 cases of non-cancerous prostate (control) by immunohistochemistry. Our results show that TSPY was detected more frequently (78%) in the clinical prostate cancer specimens than those of latent prostate cancer (47%) and control (50%). In the latent cancer group, the levels of TSPY expression could be correlated with increasing Gleason grades. TSPY expression was detected in seven out of nine...

Reconstructing pathogen-specific antibody binding epitopes and age-dependent immune signatures from proteomic-scale peptide libraries.

Thu, 27 Aug 2026 00:00:00 +0000

High-density peptide arrays are useful for mapping linear antibody epitopes and resolution of antibody specificity in a single-assay platform. Here, we used peptide library screening to evaluate magnitude and breadth of humoral responses to enteric pathogens in the context of public health interventions. We characterized the epitope landscape to known immunogenic proteins to several viruses, bacteria, and parasites and used that to infer immunological profiles at age 3, 14, and 28 months. The peptide libraries detected immune signatures better for viruses compared with bacteria and parasites and captured distinct dynamics of protein-level variation in immune signatures over time. We found limited sensitivity for bacterial and protozoan pathogens whose humoral responses may depend more on conformational or natively modified epitopes than linear-peptide binding. Unbiased peptide libraries have potential utility for broad analysis of antibody responses in integrated serosurveillance,...

Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer

Thu, 27 Aug 2026 00:00:00 +0000

BackgroundThe human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors and various somatic cancers, such as prostate and liver cancer, and melanoma. The TgTSPY9 transgenic mouse line harbors a 8.2-kb human TSPY structural gene, which is tandemly integrated in the mouse Y chromosome, and expressed in a similar pattern as that of the endogenous gene in the human genome. This mouse model of human TSPY gene offers an opportunity to examine its behavior and potential contribution in various mouse models of human diseases, such as human cancers. We had investigated the expression of such TSPY-transgene in the LADY mouse model of prostate cancer, harboring a SV40 T antigen gene directed by a rat probasin promoter; and compared the expression pattern with those...

Reirradiation for recurrent head and neck squamous cell carcinoma: international expert consensus recommendations endorsed by the Reirradiation Collaborative Group, the European Society for Radiotherapy and Oncology Reirradiation Focus Group, and the American Society for Radiation Oncology

Thu, 27 Aug 2026 00:00:00 +0000

Reirradiation can be considered for some patients with recurrent or second primary head and neck squamous cell carcinoma arising within previously irradiated regions, a clinical scenario associated with few therapeutic options. The increasing use of modern conformal radiotherapy techniques, including intensity-modulated radiotherapy, proton therapy, and stereotactic body radiotherapy, has expanded the feasibility of reirradiation in clinical practice. However, evidence remains heterogeneous, and clinical choices are challenged by substantial variability in patient presentation, previous treatments, and toxicity risk. This international expert consensus statement aims to provide pragmatic guidance across key domains, including patient selection, imaging, target delineation, treatment planning, dose accumulation, and toxicity management. Developed through a structured expert consensus process with formal agreement assessment, this document reflects current expert practice. By offering...

The Daily Grind

Thu, 27 Aug 2026 00:00:00 +0000

A 56-year-old woman was hospitalized with gait instability. Eight weeks earlier, she had noticed ascending symmetric sensations of painful “pins and needles” that had begun in her feet; she later h...

Prevalence of falls in a pooled US cohort of adults with systemic lupus erythematosus: a nested cross-sectional study.

Thu, 27 Aug 2026 00:00:00 +0000

Objective

Epidemiologic data on falls in the population with systemic lupus erythematosus (SLE) remain sparse. We estimated the prevalence and correlates of falls among adults with SLE and compared SLE prevalence estimates with those in the general US population.

Methods

We assessed falls in a nested cross-sectional study within two pooled population-based SLE cohorts in California (3/2025-2/2026) and Georgia (10/2019-5/2022). Stratified prevalence was assessed with marginal estimates from logistic regression models with falls as the outcome. Age-standardised and sex-standardised estimates in SLE were compared with 2023 US population estimates (ages ≥45 only).

Results

In this pooled SLE cohort (N=780; mean age, 47.9; 91.9% women; 14.5% Asian, 51.7% black, 13.2% Hispanic), 26.0% reported any fall in the prior year; among these, 59.1% reported falling two times or more and 31.0% reported associated injuries. General factors (oldest vs youngest age (37.4% vs...

The Writing on the Wall: An Exercise in Clinical Reasoning

Thu, 27 Aug 2026 00:00:00 +0000

The Writing on the Wall: An Exercise in Clinical Reasoning

IN MEMORIAM - Irwin Feinberg, MD

Thu, 27 Aug 2026 00:00:00 +0000

IN MEMORIAM - Irwin Feinberg, MD

Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy

Thu, 27 Aug 2026 00:00:00 +0000

Regulatory T cell (Treg) therapy is an emerging platform for controlling immune overactivation. Persistence of infused Tregs is limited by insufficient IL-2, which is essential for Treg survival and function. IL-2 activates many immune cells, imposing a challenge for the selective provision of IL-2 to infused Tregs. In this study, we found that infusions of orthogonal (ortho) IL-2 failed to enhance Tregs expressing a corresponding orthoIL-2 receptor (IL-2R) in a mouse model of autoimmune diabetes. Engineering Tregs with an orthoIL-2 tethered to its receptor achieved selective autocrine signaling; increased CD25, CTLA-4, and Foxp3 expression; supported Treg persistence without exogenous IL-2 in vivo; and improved the efficacy of Treg prevention of autoimmune diabetes. Inserting the tethered orthoIL-2 construct into the Foxp3 locus enabled Treg-specific self-reinforced expression through the activation of the Foxp3 locus by increased IL-2 signaling. Together, these results illustrate...

Seasonally varying effects of improved water, sanitation and handwashing interventions on Giardia infection in Bangladesh

Thu, 27 Aug 2026 00:00:00 +0000

Abstract Background Giardia is the most common enteric parasite among children in low-resource settings, causing diarrhoea and leading to prolonged infection or asymptomatic carriage. We assessed whether the effect of water, sanitation and handwashing (WSH) interventions on Giardia infection among rural Bangladeshi children varies with seasonal conditions. Methods We conducted a secondary analysis of the WASH Benefits Bangladesh cluster-randomized trial, with 450 clusters assigned to four arms in a 2x2 factorial design (WSH: WSH, WSH+Nutrition; no WSH: Control, Nutrition). Giardia infection was measured by multiplex real-time PCR in stool samples after two years of intervention. Effects were estimated by marginal treatment and assessed for heterogeneity by season when Giardia was measured. We also assessed heterogeneity by cumulative exposure to dry and monsoon seasons from birth to measurement age to estimate cumulative seasonal exposure history. Results Giardia prevalence,...

Gonadoblastoma locus and the TSPY gene on the human Y chromosome

Thu, 27 Aug 2026 00:00:00 +0000

The gonadoblastoma (GBY) locus is the only oncogenic locus on the human Y chromosome. It is postulated to serve a normal function in the testis, but could exert oncogenic effects in dysgenetic gonads of individuals with intersex and/or dysfunctional testicular phenotypes. Recent studies establish the testis-specific protein Y-encoded (TSPY) gene to be the putative gene for GBY. TSPY serves normal functions in male stem germ cell proliferation and differentiation, but is ectopically expressed in early and late stages of gonadoblastomas, testicular carcinoma in situ (the premalignant precursor for all testicular germ cell tumors), seminomas, and selected nonseminomas. Aberrant TSPY expression stimulates protein synthetic activities, accelerates cell proliferation, and promotes tumorigenicity in athymic mice. TSPY binds to type B cyclins, enhances an activated cyclin B-CDK1 kinase activity, and propels a rapid G(2)/M transition in the cell cycle. TSPY also counteracts the normal...

Congenital Genitourinary Anomaly Identification and Referral in Rural Nepal: A Qualitative Study on the Perspective of Female Community Health Volunteers

Thu, 27 Aug 2026 00:00:00 +0000

Background and aims

Delayed presentation of congenital anomalies is common in Nepal, highlighting the importance of timely diagnosis. Female community health volunteers (FCHVs), who are integral to health care delivery in communities, may offer an opportunity for early identification and referral of these anomalies. This study explored the perceptions, willingness, and motivations of FCHVs in Nepal regarding their potential role in the identification of congenital external genitourinary (GU) anomalies.

Methods

Twelve FCHVs from Devdaha municipality, Rupandehi district, Nepal, participated in a focus group discussion (FGD). FCHVs were purposively sampled to ensure diversity in geographic setting (urban/rural), age, and years of experience. A semi-structured FGD guide was used to explore knowledge, attitudes, perceived community acceptance, and recommendations for future training. Data was analyzed using inductive thematic analysis following Braun and Clarke's framework.

Results

Five...

Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes

Thu, 27 Aug 2026 00:00:00 +0000

BACKGROUND: Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk-benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. METHODS AND FINDINGS: We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole...

Development and validation of machine learning models to predict risk of undiagnosed dementia using healthcare claims and electronic health record data.

Thu, 27 Aug 2026 00:00:00 +0000

BackgroundApproximately half of people living with Alzheimer's disease and related dementias are undiagnosed.ObjectiveTo develop and validate algorithms that predict risk of undiagnosed dementia using electronic health record (EHR) and/or healthcare claims data.MethodsStudy participants were adult patients aged 65 years or older without evidence of dementia (diagnosis/medication) at baseline in two U.S. data sources: 1) Medicare claims (2010 to 2021); 2) EHR and claims from a primary care network (2016 to 2023). We applied coefficients from an existing, validated EHR-based algorithm to predictors defined using Medicare claims and used machine learning to develop new EHR- and claims-based predictive models. We assessed model discrimination using c-statistics.ResultsStudy participants included 8,374,400 Medicare beneficiaries (mean [SD] age, 76 [7] years; 57% female) and 29,983 primary care patients (age: 75 [6] years; 56% female). Model discrimination was good when applying EHR-based...

GTV Expert Opinion: The Past Is Part of the Prescription: Spatially Aware Cumulative Dose Assessment for Complex Reirradiation

Thu, 27 Aug 2026 00:00:00 +0000

GTV Expert Opinion: The Past Is Part of the Prescription: Spatially Aware Cumulative Dose Assessment for Complex Reirradiation

Role of the Y-located putative gonadoblastoma gene in human spermatogenesis

Thu, 27 Aug 2026 00:00:00 +0000

The gonadoblastoma locus on the human Y chromosome (GBY) is postulated to serve normal functions in spermatogenesis, but could exert oncogenic properties in predisposing susceptible germ cells to tumorigenesis in incompatible niches such as streaked gonads in XY sex reversed patients or dysfunctional testis in males. The testis-specific protein Y-linked (TSPY) repeat gene has recently been demonstrated to be the putative gene for GBY, based on its location on the GBY critical region, expression patterns in early and late stages of gonadoblastoma and ability to induce gonadoblastoma-like structures in the ovaries of transgenic female mice. Over-expression of TSPY accelerates G(2)/M progression in the cell cycle by enhancing the mitotic cyclin B-CDK1 kinase activities. Currently the normal functions of TSPY in spermatogenesis are uncertain. Expression studies of TSPY, and its X-homologue, TSPX, in normal human testis suggest that TSPY is co-expressed with cyclin B1 in spermatogonia...

The Sex-Determining Factors SRY and SOX9 Regulate Similar Target Genes and Promote Testis Cord Formation during Testicular Differentiation

Thu, 27 Aug 2026 00:00:00 +0000

Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/β-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates...

The potential contributions of a Y-located protooncogene and its X homologue in sexual dimorphisms in hepatocellular carcinoma

Thu, 27 Aug 2026 00:00:00 +0000

There is a significant sex disparity favoring males among hepatocellular carcinoma (HCC) patients. Although various risk factors have been identified, the exact etiology of such sexual dimorphism(s) in HCC is uncertain. Previous studies showed that overexpression of the Y-located protooncogene, testis-specific protein Y encoded (TSPY), promotes cell proliferation and oncogenesis whereas its X-located homologue, TSPYhomologue X (TSPX), retards cell cycle and oncogenic progression. Furthermore, TSPX promotes proteasomal degradation of hepatitis B virus-encoded X oncoprotein and hence could serve as a tumor suppressor in virus-associated HCC. Using immunohistochemistry and reverse-transcription polymerase chain reaction analysis, we had examined the expression of TSPY and TSPX with reference to other established biomarkers in HCC and related liver cancers. Our results demonstrated that 55 (19.2%) of 287 male cases were TSPY positive in immunohistochemistry of tissue arrays, and 15...

The human and mouse sex-determining SRY genes repress the Rspol/β-catenin signaling

Thu, 27 Aug 2026 00:00:00 +0000

The sex-determining region Y (SRY) is the gene on the Y chromosome responsible for switching on male sex determination during mammalian embryogenesis. In its absence, ovaries develop in the embryo. Hence, ovarian determination and differentiation is considered to be a default, or passive, developmental pathway. Recently this classical paradigm of sex determination has been challenged with the discovery of the R-spondin 1 (RSPO1) as an active ovarian determinant. Mutations of RSPO1 cause a female-to-male sex reversal. RSPO1 synergizes with WNT4 in activating an ovarian development in the bipotential gonad via the canonical Wnt signaling. Early studies showed that SRY represses such Wnt signaling, but also generated discrepancies on whether only mouse Sry is capable of inhibiting such Wnt signaling and whether both human and mouse SRY proteins are able to interact with beta-catenin, the intracellular messenger responsible for executing the Wnt signals. Our studies show that both...

Personalized modeling of stress and blood pressure reactivity using mobile health data

Thu, 27 Aug 2026 00:00:00 +0000

Psychological stress is a key driver of short-term blood pressure (BP) elevations and cardiovascular risk, yet its moment-to-moment impact in daily life remains difficult to predict. In this longitudinal observational study, we collected multimodal data from 20 adults with self-reported hypertension, including continuous wearable-derived heart rate and activity, ecological momentary assessment (EMA) stress ratings, and ambulatory BP measurements in free-living conditions. The dataset comprised 3694 EMA responses and 3812 BP measurements collected over approximately four weeks per participant (mean 24.1 ± 8.5 days). We evaluated whether participant-specific (“personalized”) models outperform a single pooled population model. Two prediction tasks were examined: (i) prediction of near-term BP elevations from wearable signals and stress EMA responses and (ii) prediction of self-reported stress from wearable signals and BP. Across both tasks, personalized models consistently improved...

Caller Volume and Gestational Length at an Abortion Fund After Dobbs

Thu, 27 Aug 2026 00:00:00 +0000

Importance: Since the Supreme Court's 2022 decision in Dobbs v Jackson Women's Health Organization, state legislatures have enacted laws severely restricting abortion. Facility case studies have reported post-Dobbs increases in patient volume and gestational length at abortion. Objective: To understand changes from before to after the Dobbs decision in the overall volume of callers and gestational length of their pregnancies at a large, regional abortion fund. Design, Setting, and Participants: This cross-sectional study used data from monthly caller records (June 2016-June 2024) from the District of Columbia Abortion Fund (DCAF) using interrupted time series analyses with segmented regression. DCAF serves the Washington, DC, area, which is unique in its absence of gestational restrictions, service availability, and proximity to states with post-Dobbs restrictions. Data were analyzed from November 2024 through August 2025. Exposure: Time in months, with change points and discontinuities...

End-of-Life Education in Action: Evaluating Simulation-Based Palliative Care Training for Emergency Medicine Residents

Thu, 27 Aug 2026 00:00:00 +0000

Introduction: This simulation-based curriculum aimed to improve emergency medicine residents' confidence and knowledge in applying palliative care principles in end-of-life scenarios in the emergency department. Methods: Residents participated in 4 simulation cases: (1) an elderly patient on hospice presenting with altered mental status, whose surrogate requests full intervention despite physician orders for life-sustaining treatment (POLST) indicating do not resuscitate/do not intubate and comfort-focused goals; (2) a patient with advanced dementia and hypotension, with a 2-year-old POLST indicating "Full Code," requiring reassessment of goals of care; (3) a 3-year-old in cardiac arrest after drowning with no return of spontaneous circulation; and (4) a previously healthy 12-month-old found apneic and cyanotic with persistent arrest despite prolonged resuscitation. All cases and debriefs were performed in succession and completed in 1 hour. Critical actions included leading goals-of-care...

Antimicrobial Resistance Gene Profiles in Integron-Positive and Integron-Negative Third-Generation Cephalosporin-Resistant E. coli from Human and Animal Sources

Wed, 26 Aug 2026 00:00:00 +0000

Background/Objectives: Integrons are genetic platforms that allow bacteria to acquire antimicrobial resistance (AMR) genes, making them a focal point for many AMR studies and surveillance programs. This study investigated how the prevalence of integrons (intI and attI genes) in third-generation cephalosporin-resistant E. coli (3GCR-Ec) varied across three different sources (i.e., healthy children, domestic animals and urinary tract infections). The study aimed to determine how different classes of AMR genes vary among 3GCR-Ec with integrons present versus those where integrons are absent. Methods: We analyzed 3GCR-Ec isolates collected from semirural parishes of Eastern Quito, Ecuador, that included: (1) 3GCR-Ec from healthy children (n = 946), (2) 3GCR-Ec from domestic animal species (n = 673), and 3GCR-Ec from patients with urinary tract infections (UTIs) (n = 138). Genomic analyses were performed for all 1757 sequences...

LGBTQ+ Realities in the Biological Sciences.

Wed, 26 Aug 2026 00:00:00 +0000

While scientific environments have been described as unwelcoming to the LGBTQ+ community, and fields such as physics have systematically documented these challenges, the climate in biology-specific workplaces has not exclusively been assessed. We conducted the largest survey to date of LGBTQ+ biologists to examine how their sense of belonging and perception of climate in the biology workplace and professional societies compare to that of their straight and cis peers. In 2023, we surveyed 1419 biologists across five professional societies, with 486 identifying as LGBTQ+. Trans and gender non-conforming (TGNC) biologists reported lower belonging and morale within the workplace, professional societies, and the biology community compared with cis, straight biologists. They also reported being less comfortable with the climate of various professional biology environments. While LGBTQ+ biologists report that their workplaces are moderately inclusive, over 20% of all LGBTQ+ biologists...

Do Virtual Environments Close the Gender Gap in Participation in Question-and-Answer Sessions at Academic Conferences? In Search of Moderation by Conference Format

Wed, 26 Aug 2026 00:00:00 +0000

Consistent with power and status differences between men and women in society, men tend to participate more than women do in question-and-answer (Q&A) sessions at in-person academic conferences. This gap in participation in scientific discourse may perpetuate the status quo. The current research examines whether this gender gap in participation in Q&A sessions extends to virtual conferences, which have become more prevalent during the COVID-19 pandemic. Due to shifts in conference formats to enable asynchronous, anonymous, and/or simultaneous participation, we examined whether virtual conferences are more inclusive, and mitigate the gender gap in Q&A participation. Across four virtual conferences that varied in gender representation and Q&A structured format, men continued to take a disproportionate amount of time and space in Q&A sessions. Disproportionate participation did not significantly vary between in-person and virtual formats and did not systematically...

Single-library chromosome-scale diploid assemblies of vole genomes resolve a species-specific duplication implicated in pair bonding.

Wed, 26 Aug 2026 00:00:00 +0000

Comparing prairie voles (Microtus ochrogaster), a species that forms lasting pair bonds and exhibits biparental care, with meadow voles (Microtus pennsylvanicus), a non-monogamous species showing maternal care only, provides a framework to examine the genomic basis of behavioral divergence over short evolutionary time. Here, we develop a simplified assembly approach combining PacBio HiFi and CiFi sequencing in a single library and run, producing high-quality contiguous chromosome-scale diploid prairie and meadow vole genomes (2.3 Gbp). Comparative analysis reveals substantial differences, including near-complete Y chromosome divergence and a prairie-vole-specific duplication of Avpr1a, a vasopressin receptor gene implicated in social bonding and autism in humans. These extensive genomic changes suggest rapid chromosome evolution as a driver of the dramatic Microtus radiation, generating ∼60 vole species in >2 million years. This single-library approach facilitates a simplified...

A Cross-Sectional Study of COVID-19 Impacts on Faculty in Academic Health Care: Lessons Learned to Help Navigate the Current National Institutes of Health Financial Crisis

Mon, 24 Aug 2026 00:00:00 +0000

Background: COVID-19 significantly disrupted academic health care, with evidence suggesting disproportionate impacts on women versus men faculty. Understanding these gender-based differences can inform institutional policies to support equity, a priority amid the current climate, where reduced research funding and limitations to health care access are reshaping the scientific and clinical landscape. Objective: To examine gender differences in pandemic-related professional impacts, caregiving responsibilities, institutional supportive services, and mitigation strategies among faculty at a large academic health care center during COVID-19. Methods: All eligible faculty ( N = 1448) were invited to complete an anonymous survey about their experiences during the first year of the pandemic. Gender differences were examined using chi-square and independent-samples t tests. Results: Of 824 respondents (57% response rate), 768 were included in the analyses. Women faculty were significantly...

Adaptive optical correction for in vivo two-photon fluorescence microscopy with neural fields

Fri, 21 Aug 2026 00:00:00 +0000

Adaptive optics restore ideal imaging performance in complex samples by measuring and correcting optical aberrations but often require custom-built microscopes with carefully aligned wavefront sensing/shaping devices and can be susceptible to sample motion. Here we describe NeAT, a computational framework using neural fields for adaptive optics two-photon fluorescence microscopy. NeAT estimates wavefront aberration and recovers sample structure from a 3D image stack without requiring external datasets for training. Incorporating motion correction in learning and correcting conjugation errors commonly found in commercial microscopes, NeAT is designed for deployment in biological laboratories for in vivo imaging. We validate NeAT’s performance using a custom-built microscope with a wavefront sensor under varying signal-to-noise ratios, aberration and motion conditions. With a commercial microscope, we demonstrate real-time aberration correction for in vivo morphological and functional...

Radiologically Relevant Clinical History Summarization with Large Language Models: A Multireader Performance Study.

Thu, 20 Aug 2026 00:00:00 +0000

Background Clinical histories accompanying imaging orders guide protocol selection and diagnostic focus. However, they are often incomplete, potentially compromising diagnostic accuracy and workflow efficiency. Purpose To evaluate whether large language models (LLMs) can improve the clinical utility of provided imaging indications by leveraging clinical notes. Materials and Methods This retrospective study curated a dataset from deidentified electronic health records at the University of California San Francisco (January 2012 to August 2024), consisting of radiology reports with paired referring clinician-provided and radiologist-curated indications linked to clinical notes. The dataset was stratified across five body systems and five pathophysiologic categories to derive LLM selection and reader study internal test sets. For the reader study, 20 radiologists with 2-25 years of experience compared indications from the referring clinician, radiologist, and best-performing LLMs....

Field Evaluation of Do-It-Yourself Air Filtration Solutions for Evaporative Coolers to Reduce Ambient Particle Infiltration in Homes in Wildfire-Affected Communities

Wed, 19 Aug 2026 00:00:00 +0000

Evaporative coolers (ECs) introduce outdoor air pollutants indoors when operating. This study evaluates the potential of do-it-yourself (DIY) air filtration solutions for ECs to cost-effectively reduce the infiltration of ambient fine particulate matter (PM_2.5) in homes with ECs using measurements in 48 homes in wildfire-affected agricultural communities in California. All homes received one portable air cleaner (PAC); 25 homes also received DIY filters (mostly MERV 13) attached to their ECs. PurpleAir monitors measured indoor and outdoor PM_2.5 concentrations. PAC operation was monitored in all of the homes. EC usage was monitored in some homes and predicted using relative humidity dynamics in all homes. Conditional analyses between EC likely on and off conditions were used to evaluate the impacts of DIY EC filters on ambient PM_2.5 infiltration, including during several wildfire-affected days. Median levels of ambient PM_2.5 infiltration...

A belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication

Wed, 19 Aug 2026 00:00:00 +0000

Fast-acting botulinum neurotoxins (BoNTs) are highly desirable for both medical and aesthetic indications, but the underlying mechanism for the differing onset of BoNTs’ action remains unknown. Here, we demonstrate that the “belt” of BoNTs, a largely unstructured loop wrapping around their catalytic light chain (LC), is key to onset of intoxication. The more flexible BoNT/E belt promotes quicker LC translocation into the neuronal cytosol, leading to faster onset of action compared to BoNT/A. Furthermore, we discover a “belt-buckle” checkpoint that regulates this process. By loosening the BoNT/A belt-buckle via protein engineering, we enhance its sensitivity to acidic pH, leading to an accelerated onset of action. Conversely, locking the belt-buckle with an antibody neutralizes BoNT/A. Our findings open avenues for developing fast-acting BoNTs and effective countermeasures.

Exploring Barriers to Crisis Support: Considerations for the Design of Automated Digital Safety Planning Interventions

Sun, 16 Aug 2026 00:00:00 +0000

Suicidal ideation is common among young adults in the United States and represents an important mental health concern. However, formal mental health care utilization remains limited due to attitudinal and structural barriers. Digital mental health interventions (DMHIs) offer a promising approach to help-seeking, especially for young adults who prefer self-managing their symptoms. Text messaging-based safety planning interventions can be a scalable approach to seeking help that can mitigate many structural barriers for young adults. We conducted two online focus groups (n = 15 each) to understand what prevents young adults from seeking help for their suicidal thoughts and what might prevent them from engaging with a fully automated text messaging-based safety planning intervention. Participants reported barriers to help seeking both within and outside crisis states. Outside crisis states, the major barriers to help seeking include an unwillingness to burden others, inability to...

Pre-Health Students Can Extend the Kidney Transplant Navigator Workforce to Help Patients Search for Living Donors

Fri, 14 Aug 2026 00:00:00 +0000

Purpose: The disparity between kidney donor supply and demand remains a critical challenge, with living donor kidney transplantation playing a key role in addressing the organ shortage. Most patients need support in searching for living donors. At our academic medical center, since 2021 the kidney transplant team is deploying pre-health students as kidney transplant navigator interns. Eighty percent of students in the program are from underrepresented populations, thereby extending the cultural and linguistic competency of the workforce. Accordingly, students focus on helping patients from underserved populations. Methods: We identified the number of consecutive patients seeing 6 participating nephrologists for evaluation appointments between 8/27/23 and 11/20/24. We assessed how many of these received support from a student navigator, how many found living donors, and how many received transplants. For an exploratory comparison, we assessed how many patients receiving usual care...

A Hybrid Compliant–Tendon Laparoscopic Instrument for Distal Articulation and Grasping: Design and Experimental Validation

Fri, 14 Aug 2026 00:00:00 +0000

BACKGROUND: Conventional laparoscopic instruments provide limited dexterity in confined anatomical environments, whereas existing articulated designs rely on complex rigid joints or motorised actuation, increasing mechanical complexity and limiting miniaturisation. METHODS: A hybrid compliant-tendon laparoscopic instrument was developed to integrate articulated distal motion and active grasping within a 5 mm form factor. The compliant segment was fabricated from super-elastic Nitinol, and grasping was achieved using a tendon-pulley mechanism. The system was evaluated using nonlinear finite element analysis and experimental testing, including digital image correlation and benchtop force measurements. RESULTS: The mechanism achieved up to 75° articulation with mean model errors below 8%. The grasper produced a maximum force of 13.2 ± 0.47 N and maintained performance across articulation angles. Pull-out tests confirmed stable interaction with soft-tissue analogues. CONCLUSIONS:...

Implementing the Guiding an Improved Dementia Experience (GUIDE) Model within UCSF Care at Home

Fri, 14 Aug 2026 00:00:00 +0000

https://ucsf.app.box.com/s/m0ubpopvnaswniggpy4edakfza8tdat3

Helping Veterans Access Sleep Care Virtually: How Patient Support Corps Students Extend the TeleSleep Workforce at VA

Fri, 14 Aug 2026 00:00:00 +0000

ABSTRACT: Objective: The Veterans Health Administration (VA) uses e-screening surveys to request information from Veterans before appointments, and VA Video Connect (VVC) readiness calls to ensure that Veterans can attend appointments virtually. Providers and staff face challenges in working with Veterans to complete e-screenings and VVC readiness calls. For example, in 2023, VA’s Sleep Clinical Resource Hub completed 20% of e-screenings. Team leaders therefore asked UCSF’s Patient Support Corps (PSC) to deploy student interns who could help with e-screenings and VVC readiness calls. PSC is a four-year co-op internship where pre-health college students earn academic credit while gaining experience and serving patients. Eighty percent of PSC students are from underrepresented populations, thereby extending the cultural and linguistic competency of the workforce. Study Design: In March 2024, PSC signed a Trainee Qualifications and Credentials Verification Letter with VA, designating...

Reducing Backlog in Behavioral Health Access With Student Interns

Fri, 14 Aug 2026 00:00:00 +0000

https://ucsf.app.box.com/s/x4kt8vyxd03hefqfy856cw8vww580620

Student Interns Increase Completion of Health Risk AssessmentsAmong Medicare Patients with Upcoming Annual Wellness Visits at UCSF

Fri, 14 Aug 2026 00:00:00 +0000

https://ucsf.app.box.com/s/ex5cvp6xwq2ewob19pyn5hqm3ef4wl4d

Quality of Life in Patients With p16+ Oropharyngeal Cancer Receiving Accelerated Radiation Therapy With Either Cisplatin or Cetuximab in the NRG/RTOG 1016 Randomized Controlled Trial.

Fri, 14 Aug 2026 00:00:00 +0000

Purpose

NRG/RTOG 1016 was a phase III randomized noninferiority de-escalation trial comparing cetuximab versus cisplatin, concurrent with accelerated radiation 70 Gy/6 weeks, in p16+ oropharyngeal cancer. Quality of life (QOL) was a secondary endpoint.

Methods and materials

Eligible/consenting patients among the first 400 entered completed the EORTC QLQ-C30/H&N35 at baseline, end of treatment, 3, 6, and 12 months posttreatment, to provide 90% power to detect an effect size of 0.5 in the between-arm change in QOL scores from baseline to 6 months. We report completion, responsiveness, and patterns over time across domains between arms, considering a difference of >10 points as clinically significant.

Results

Consent to the QOL substudy was 91%, with analyzable data in 375 patients. No significant differences in patient/tumor characteristics were found by QOL participation status. Completion at the 5 timepoints did not differ by arm (intensity modulated...

Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial

Thu, 13 Aug 2026 00:00:00 +0000

BACKGROUND AND HYPOTHESIS: Psychiatric medications contribute to high rates of metabolic dysfunction in psychotic disorders. Ketogenic diets reduce metabolic syndrome, have anticonvulsant effects in epilepsy, and may improve symptoms of schizophrenia and bipolar disorder. We report the first randomized controlled trial to assess effects of ketogenic diets on metabolism, psychiatric symptoms, and cognition in people with schizophrenia-spectrum and bipolar-1 disorders. STUDY METHODS: Participants were randomized to a ketogenic diet (KETO; n = 28) or diet-as-usual (DAU; n = 30) for 1 month. Partway through the trial, a KETO extension was offered to both groups, resulting in a sub-group who completed the diet for 4 months (n = 25). We assessed changes in metabolic health, clinical symptoms, and cognition after 1 month (KETO versus DAU) and after 4 months (KETO versus baseline). STUDY RESULTS: KETO participants' daily ketone levels surpassed the standard ketosis...

Neuropathic pain through the perspective of microglia–neuron interactions: a translational review for clinicians

Thu, 13 Aug 2026 00:00:00 +0000

BACKGROUND/IMPORTANCE: Neuropathic pain affects up to 10% of the population and is often refractory to current treatments. Growing evidence implicates neuroimmune interactions, particularly microglia, in the pathophysiology, but their role is underappreciated in clinical practice. OBJECTIVE: To summarize current evidence for microglial contributions to neuropathic pain, emphasizing microglia-neuron interactions and translational implications for clinicians. EVIDENCE REVIEW: This narrative review synthesizes preclinical and emerging human data (postmortem histopathology, glial-signal positron emission tomography (PET) imaging, dorsal root ganglion transcriptomics) to examine microglial contributions to pain initiation, maintenance and resolution, sex differences and therapeutic implications. FINDINGS: Preclinical evidence demonstrates that microglia are necessary and sufficient for pain initiation. Nerve injury engages central sensitization through colony-stimulating factor 1 (CSF1)-CSF1...

Improving Food Security in the Context of a Stagnating Federal Minimum Wage

Thu, 13 Aug 2026 00:00:00 +0000

Improving Food Security in the Context of a Stagnating Federal Minimum Wage

Mapping the space of dementia with EEG in stained glass

Thu, 13 Aug 2026 00:00:00 +0000

Dementia conditions, including Alzheimer's disease, are progressive disorders for which effective treatments remain under development. Accordingly, interventions that improve quality of life are an important focus of patients, caregivers, and providers, including traditional art forms like painting and sculpture. In this Perspective article, we discuss the use light as a unique form of art to create transformative spaces that stimulate the senses and potentially support wellbeing. We outline an art-science collaborative initiative in which the patients themselves contribute, including through the recording and conversion their EEG brainwave activity to 2D time-frequency spectrogram representations. These representations are transferred to the ancient art of stained glass and installed into the patient's own home. This intervention creates a novel dynamic environment of illumination and colour saturation, derived from the patient and in sync with ever-changing solar and climate...

1022 Novel cannabinoid agonist for treatment of prurigo nodularis and itch

Thu, 13 Aug 2026 00:00:00 +0000

1022 Novel cannabinoid agonist for treatment of prurigo nodularis and itch

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Thu, 13 Aug 2026 00:00:00 +0000

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal...

A framework for integrating health‐related social needs education into electronic health record clinical pathways

Thu, 13 Aug 2026 00:00:00 +0000

Health-related social needs (HRSN) significantly influence patient outcomes, yet they are rarely integrated into point-of-care decision-making. We developed a process to embed HRSN-informed and HRSN-targeted care recommendations directly into three electronic health record-integrated high-use clinical pathways-cirrhosis, diabetes, and congestive heart failure-at a tertiary academic medical center and affiliated community hospitals. This pilot process leveraged literature review, community input, interdisciplinary collaboration, and targeted specialist feedback to produce concrete, actionable guidance for providers. Our approach can be adapted by other health systems to address social needs within established clinical workflows.

Social Media Perspectives on Over‐The‐Counter Hearing Aids: Sentiment and Thematic Analysis of Twitter (X) Data

Thu, 13 Aug 2026 00:00:00 +0000

Objective: To assess public perspective on over-the-counter (OTC) hearing aids through social media data. Methods: Twitter (X)'s Application Program Interface was utilized to collect English-language tweets mentioning OTC hearing aids between January 2019 and October 2022. Sentiment analysis was conducted using the Valence Aware Dictionary and Sentiment Reasoner, categorizing tweets as positive, neutral, or negative. Main outcomes and measures were average compound sentiment scores. Joinpoint analysis was used to evaluate changes in sentiment scores over time. Two independent raters categorized account type and tweets into categories determined by thematic analysis. Results: A total of 8912 tweets were included. The tweets were categorized as Economy, Political, Logistics, Information, and Other based on thematic analysis. Overall mean (SD) compound sentiment score (range: -1 to +1) was weakly positive at 0.15 (0.40). The total number of tweets increased significantly after August...

A mixed methods evaluation of 99DOTS digital adherence technology uptake among adolescents treated for pulmonary tuberculosis in Uganda

Thu, 13 Aug 2026 00:00:00 +0000

Background: Adolescents are at risk of poor adherence to tuberculosis (TB) treatment and subsequently worse treatment outcomes. Digital adherence technologies, including the mobile phone-based 99DOTS platform, can support TB treatment, but there is limited data on their use among adolescents. We evaluated factors associated with uptake of 99DOTS among adolescents with TB. Methods: We conducted an explanatory sequential mixed methods study that utilized quantitative data from adolescents collected at 30 health facilities in Uganda, in-depth and key informant interviews with adolescents diagnosed for TB who were offered 99DOTS, and healthcare workers at participating facilities. Findings were further mapped onto the Capability, Opportunity, Motivation, and Behavior model. Results: Overall, 299/410 (73 %) adolescents were enrolled in 99DOTS. Older adolescents 15-19 years old were more likely to enroll in 99DOTS than younger adolescents 10-14 years [aPR= 1.88, 95 % CI: (1.54-2.33)]....

The Resolution of Abdominal Pain: an Ominous Sign of Mesenteric Ischemia

Thu, 13 Aug 2026 00:00:00 +0000

The Resolution of Abdominal Pain: an Ominous Sign of Mesenteric Ischemia

Dental, Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC): An infrastructure for accelerating regenerative therapies from discovery to clinical impact

Thu, 13 Aug 2026 00:00:00 +0000

Translating scientific discoveries in tissue engineering and regenerative medicine (TE/RM) into clinically adopted therapies is hindered by fragmented development pipelines, regulatory and manufacturing challenges, and limited funding. Despite substantial investment by the U.S. National Institutes of Health (NIH), few NIH-funded TE/RM projects achieve commercialization or regulatory approval by the US Food and Drug Administration. The gap between academic innovation and clinical implementation is particularly evident in the dental, oral, and craniofacial (DOC) domain, where market and reimbursement constraints further restrict translation. To address these barriers, the National Institute of Dental and Craniofacial Research established the Dental, Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC), comprising two nationwide Resource Centers tasked with guiding promising technologies from universities and small businesses through preclinical validation toward clinical...

The impact of ethical implications intertwined with tuberculosis household contact investigation: A qualitative study

Thu, 13 Aug 2026 00:00:00 +0000

BACKGROUND: Household contact investigation (HCI) is an effective and widely used approach to identify persons with tuberculosis (TB) disease and infection globally. Despite widespread recommendations for the use of HCI, there remains poor understanding of the impact on and value of contact investigation for participants. Further, how HCI as a practice impacts psychosocial factors, including stigma and possible unintended disclosure of illness among persons with TB, their families, and communities, is largely unknown. METHODS: This exploratory qualitative study nested within a randomized trial (ClinicalTrials.gov: NCT04520113, 17 August 2020) was conducted in South Africa to understand the impacts of HCI on index patients living with TB and their household contact persons in two rural districts in the Limpopo province (Vhembe and Capricorn) and Soshanguve, a peri-urban township in Gauteng province. People with TB and household members of people with TB were recruited to participate...

Hippocampal formation–cortical high-fidelity memory networks in healthy older adults during the mnemonic discrimination task

Thu, 13 Aug 2026 00:00:00 +0000

Fidelity of detailed information retrieved from long-term memory (LTM) declines in aging due to changes affecting learning and remembering processes. Such behavioral deficits correspond with functional alterations in the hippocampal formation. However, it is unclear whether age-related decline in high-fidelity retrieval alters functional connections between hippocampal and cortical regions. Twenty-two cognitively intact older adults (69.4 ± 4.4 years) completed mnemonic discrimination tasks during fMRI indicating, whether previously encoded targets, lures, or novel objects were old or new. Participants’ high-fidelity memory, measured by the lure discrimination index (the proportion of “new” responses to lures minus the proportion of “old” responses to novel objects), was 0.45 ± 0.04 – lower than previously reported scores in young adults. High-fidelity LTM in older adults engaged a hippocampal formation region in the left entorhinal cortex with trial-wise beta-series connections...

Building a Global Research Network for Fair, Accountable, Interpretable, and Responsible AI in Emergency Care: Protocol for a FAIR-EC Study.

Thu, 13 Aug 2026 00:00:00 +0000

Background

The current landscape of emergency care (EC) is marked by high demand, leading to issues such as emergency department boarding, overcrowding, and subsequent delays that impact the quality and safety of patient care. Integrating data science into EC can enhance decision-making with predictive, preventative, personalized, and participatory approaches. However, gaps in adherence to fairness, accountability, interpretability, and responsibility are evident, particularly due to barriers to data-sharing, which often result in a lack of transparency and robust oversight in these applications.

Objective

The FAIR-EC (Fair, Accountable, Interpretable, and Responsible-Emergency Care) collaboration adapts the existing Fair, Accountable, Interpretable, and Responsible principles to address emerging challenges as data science integrates with EC. This initiative aims to transform EC by establishing ethical artificial intelligence standards specifically tailored for...

Modification of pre-operative order set to reduce PACU stay times for outpatient benign gynecological surgery

Thu, 13 Aug 2026 00:00:00 +0000

A quality improvement project was implemented at a single medical center's outpatient benign gynecological surgery division to address prolonged post anesthesia care unit (PACU) stays (defined as greater than 120 minutes). Initial barrier analysis within the department identified gabapentin use in the perioperative setting as a possible contributor. The intervention removed the default pre-op order set of 600 mg gabapentin. One-year post-intervention (baseline n = 281, intervention n = 573) it was observed that the average PACU stay time for benign gynecological surgeries was reduced from an average of ~183 to ~159 minutes marking a 12.6% reduction in PACU stay time (p < 0.0001). Gabapentin use decreased from 92.17% to 1.25% with no change in pain scores. After the intervention, there was no longer a statistically significant difference in PACU stay times by age. This intervention successfully decreased PACU stay times, highlighting pathways to advance individualized, age-conscious...

Modified Anti-PstS1 Bi-specific antibodies unlock potent protection against tuberculosis

Thu, 13 Aug 2026 00:00:00 +0000

The role of antibodies in the host response against Mycobacterium tuberculosis (M. tb) bacteria is still poorly understood. We previously isolated two monoclonal antibodies (mAbs), p4-36 and p4-163, from an M. tb infected donor that target two non-overlapping epitopes on PstS1, a subunit of the M. tb phosphate transporter. Although these antibodies reduced lung bacterial burden in mice (30-40% reduction in CFU), their efficacy remained modest for therapeutic application. Here, we employed a rational antibody engineering approach to further enhance their anti-M. tb potency. Affinity maturation of p4-163 yielded p4-163LR, a variant with superior binding to PstS1 and improved recognition of live, attenuated M. tb. Surprisingly, p4-163LR alone did not confer enhanced protection against virulent M. tb in vivo. However, the generation of a bispecific antibody combining p4-36 and p4-163LR (Bi-S 36/163LR) significantly improved bacterial binding and antibody-dependent cellular phagocytosis...

Integrated Pest Management Intervention in Child Care Centers Improves Knowledge, Pest Control, and Practices

Wed, 12 Aug 2026 00:00:00 +0000

INTRODUCTION: To reduce young children's exposure to pests and pesticides, an integrated pest management (IPM) intervention was provided for child care center staff. METHODS: The 7-month IPM education and consultation intervention was conducted by trained nurse child care health consultants in 44 child care centers in California. IPM knowledge surveys were completed by child care staff, objective IPM assessments were completed by research assistants pre- and postintervention, and activity logs were completed by the nurses. RESULTS: There were significant increases in IPM knowledge for the child care staff who attended workshops. There were reductions in the prevalence of pests and increases in IPM practices at the postintervention compared with the preintervention time point. The nurses consulted an average of 5.4 hours per center. DISCUSSION: A nurse-led IPM intervention in child care centers can reduce exposure to harmful substances for young children attending child care...

An Interactive Narrative Intervention to Increase Adolescents' Knowledge and Self-Efficacy to Reduce Alcohol Use: Pre-Post Study.

Wed, 12 Aug 2026 00:00:00 +0000

BACKGROUND: Accidents and injuries are the leading causes of preventable death among adolescents and are often related to substance use. About 60% of US high school students have tried alcohol and 22% report current alcohol use. Preventing and reducing adolescent alcohol use would contribute to substantial health benefits and prevent major health morbidity and mortality. Advances in interactive narrative learning technologies hold promise for designing games for health that effectively deliver age-appropriate and personalized behavior change interventions. The Interactive Narrative System for Patient-Individualized Reflective Exploration (INSPIRE) is designed to serve as an extension to clinical preventive care, engaging adolescents in a theoretically grounded alcohol prevention intervention by leveraging the dual mechanisms of interactive narrative and 3D game technologies. OBJECTIVE: This pre-post study aims to examine the impact of INSPIRE on adolescents' self-efficacy to avoid...

Early Release - Adeno-Associated Virus Type 2 and Human Adenovirus Species F Type 41 Co-infection Associated with Acute Severe Hepatitis in Children, California, USA - Volume 32, Number 7—July 2026 - Emerging Infectious Diseases journal - CDC

Wed, 12 Aug 2026 00:00:00 +0000

Since late 2021, clusters of acute severe hepatitis of unknown etiology in previously healthy children, including some requiring liver transplantation, have been reported worldwide. Co-infection with adeno-associated virus type 2 (AAV2) and human adenovirus species F type 41 (HAdV-F41) has been identified in most cases. Global incidence peaked in 2022, and pediatric liver failure involving co-infection with AAV2 and HAdV-F41 has remained rare in recent years. We report 2 cases of pediatric liver failure associated with AAV2 and HAdV-F41 in California, USA, in March 2024 and January 2025. The patients had high adenovirus loads (393,000 and 480,000 copies/mL), extended adenovirus viremia (2 and 3.5 months), and high AAV2 viral loads (1.3 and 1.0 × 10⁶ copies/mL). One patient required liver transplantation; both patients recovered. Our findings underscore the need for heightened physician awareness and expanded surveillance to identify and characterize new cases, improve...

Training Global Leaders in Perioperative Equity: An Evaluation of the CHESA Fellowship

Tue, 11 Aug 2026 00:00:00 +0000

BACKGROUND: Few programs exist to train learners in advancing equity in perioperative care. In response, the UCSF Center for Health Equity in Surgery and Anesthesia (CHESA) launched the CHESA Fellowship in 2021. This 18-month, non-ACGME fellowship uses asynchronous modules, expert-led seminars, mentored research, and community building to equip fellows with the skills to advance perioperative equity worldwide. METHODS: This report describes the fellowship's structure and evaluates its early impact on alumni career development. We conducted a mixed-methods fellowship evaluation comprising alumni and end-of-year surveys, focus groups, and a list of fellow-authored publications. Surveys assessed skill development, scholarly output, and satisfaction with curriculum elements. Qualitative data from focus groups were coded to highlight fellows' experiences and identify areas for improvement. RESULTS: Since 2021, CHESA has trained 80 fellows across 18 countries and 12 specialties; 71.3%...

Transcriptome-Wide Cox Regression Identifies Candidate Survival-Associated Genes in Newly Diagnosed Acute Myeloid Leukemia

Sat, 8 Aug 2026 00:00:00 +0000

Acute myeloid leukemia (AML) exhibits substantial biological heterogeneity that is not fully captured by current prognostic systems. We aimed to identify transcriptome-wide gene expression markers associated with overall survival in newly diagnosed AML patients. Gene expression and clinical data from 399 newly diagnosed AML patients in the OHSU cohort were obtained via cBioPortal. Cox proportional hazards regression was performed independently for 22,836 genes to evaluate associations with overall survival. Analyses were restricted to genes with sufficient observations, and Bonferroni correction was applied to account for multiple testing. A total of 46 genes were significantly associated with overall survival after multiple testing correction. Higher expression of FAM213A (hazard ratio [HR] 1.240) and TJP2 (HR 1.439) was associated with increased mortality risk, whereas higher expression of PJA2 (HR 0.381), MICALL2 (HR 0.779), and LTK (HR...

Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts

Wed, 5 Aug 2026 00:00:00 +0000

Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to capture and quantify the transcriptomic profile of a single cell at a specific timepoint. Among the computational techniques used to predict cellular trajectories, RNA velocity has emerged as a predominant tool for modeling transcriptional dynamics. RNA velocity leverages the mRNA maturation process to generate velocity vectors that predict the likely future state of a cell, offering insights into cellular differentiation, aging, and disease progression. Although this technique has shown promise across biological fields, the performance accuracy varies depending on the RNA velocity method and dataset. We established a comparative pipeline and analyzed the performance of five RNA velocity methods on three datasets based on local consistency, method agreement, identification of driver genes, and robustness to sequencing depth. This benchmark provides a resource for scientists...

Fathers’ Presence Makes a Difference During Children’s Evening Meals

Tue, 4 Aug 2026 00:00:00 +0000

This observational study used descriptive analysis to improve understanding of the relationship between fathers’ presence or absence, the occurrence of mothers’ feeding practices, and child eating behaviors at evening meals. Participants were 141 Mexican-origin families with children aged 8 to 10 years. We coded behavioral observations of video-recorded meals. Three parental feeding practices were established a priori : (1) pressure to eat, (2) restriction of amount of food, and (3) positive involvement in child’s meals. Additionally, we identified child eating behaviors and food eaten. Fewer mothers engaged in certain types of positive involvement in child’s meals when fathers were present at the meals, compared to when fathers were absent. Regarding child eating behaviors, when fathers were present, more children engaged in positive talk about food, compared to when fathers were absent. Additionally, when fathers were present, more children ate grains and fewer ate fruit, compared...

Rostral ventral medulla circuits regulate both the sensory and affective dimensions of neuropathic pain: a commentary on Dogrul et al.

Mon, 3 Aug 2026 00:00:00 +0000

Rostral ventral medulla circuits regulate both the sensory and affective dimensions of neuropathic pain: a commentary on Dogrul et al.

It all began in Issaquah 50 years ago

Mon, 3 Aug 2026 00:00:00 +0000

ABSTRACT: "Somehow scientists still pursue the same questions, if now on higher levels of theoretical abstraction rooted in deeper layers of empirical evidence… To paraphrase an old philosophy joke, science is more like it is today than it has ever been. In other words, science remains as challenging as ever to human inquiry. And the need to communicate its progress… remains as essential now as then." - Tom Siegfried, Science News 2021In fact, essential questions about pain have not changed since IASP's creation in Issaquah: what causes it and how can we treat it? Are we any closer to answering these questions, or have we just widened the gap between bench and bedside? The technology used to answer questions about pain mechanisms has certainly changed, whether the focus is on sensory neurons, spinal cord circuitry, descending controls or cortical pain processing. In this paper, we will describe how transgenics, transcriptomics, optogenetics, calcium imaging, fMRI, neuroimmunology...

A Randomized, Controlled Study of a Rural Sanitation Behavior Change Program in Madhya Pradesh, India

Mon, 3 Aug 2026 00:00:00 +0000

Poor sanitation and open defecation are thought to be a major cause of diarrhea and intestinal parasite infections among young children. In 1999, India launched the Total Sanitation Campaign with the goal of achieving universal toilet coverage in rural India by 2012. This paper reports on a cluster-randomized, controlled trial that was conducted in 80 rural villages in Madhya Pradesh to measure the effect of the program on toilet access, sanitation behavior, and child health outcomes. The study analyzed a random sample of 3,039 households and 5,206 children under five years of age. Field staff collected baseline measures of sanitation conditions, behavior, and child health, and re-visited households 21 months later. The analysis finds that implementation of the program activities was slower than the original timeline (only 35 percent of villages were triggered more than six months before the follow-up survey). Nevertheless, the Total Sanitation Campaign successfully increased...

Blood Flow Restriction Therapy Stimulates Intercellular Mitochondria Transfer and Improves Muscle Regeneration and Shoulder Function in a Murine Rotator Cuff Injury Model

Mon, 3 Aug 2026 00:00:00 +0000

BACKGROUND: Rotator cuff (RC) tears are among the most common causes of shoulder dysfunction in sports medicine. Muscle atrophy and degeneration are important risk factors for RC tendon retearing and suboptimal recovery of shoulder function after tendon repair. Although blood flow restriction (BFR) can stimulate muscle regeneration after lower extremity trauma and anterior cruciate ligament reconstruction, the mechanisms that underlie BFR remain unknown, and its application to RC tears has not yet been explored. HYPOTHESIS: The authors hypothesized that BFR induces transfer of mitochondria from intramuscular fibro-adipogenic progenitors (FAPs) to myocytes, enhances muscle regeneration, and improves shoulder function after RC injury. STUDY DESIGN: Controlled laboratory study. METHODS: To assess mitochondrial transfer after BFR, the authors used Prrx1-Cre/MitoTag reporter mice, in which FAP mitochondria are labeled. Mice underwent unilateral forelimb BFR, and supraspinatus (SS)...

Differential contribution of α2δ auxiliary subunits of voltage-gated calcium channels in mouse models of pain and itch

Mon, 3 Aug 2026 00:00:00 +0000

Voltage-gated calcium channels (VGCCs) are multimeric proteins composed of alpha 1, β and γ subunits, as well as one of four auxiliary α2δ subunits. Although there is considerable preclinical and clinical evidence for a contribution of VGCCs to nociceptive processing, notably the gabapentin-targeted α2δ-1 subunit, unclear is the extent to which other α2δ subunits contribute to baseline or injury-altered pain and itch processing. Here, we investigated the anatomical and behavioral consequences of deleting α2δ-2, α2δ-3 or α2δ-4 in the mouse and report that selectively ablating each α2δ subunit leads to different, and in some cases, opposite effects on behavioral indices of pain and itch. Specifically, deleting α2δ2 resulted in mechanical and heat hypersensitivity, and an increase in spinal cord microglial immunoreactivity, but reduced scratching (presumptive) itch in response to a pruritogen. In contrast, ablation of α2δ3 led to thermal hyposensitivity, but no change in mechanical...

A bad break: mechanisms and assessment of acute and chronic pain after bone fracture

Mon, 3 Aug 2026 00:00:00 +0000

ABSTRACT: Pain is one of the primary indicators of a bone fracture and serves both a functional and practical role in guiding recovery. However, fracture pain can persist long after the fracture itself has clinically healed. The neural and molecular mechanisms that drive acute pain postfracture, and how these mechanisms are pathologically usurped to trap patients into persistent, debilitating, and often difficult to treat, chronic pain, are not well understood. The aim of this review is to provide insight into the risk factors for pain persistence after fracture, review the physiological and pathophysiological mechanisms of fracture pain, and critically evaluate the literature around fracture pain assessment techniques/models. Taken together, the concepts covered herein will provide a strong foundation to support the development of more effective treatments to better alleviate postfracture pain.

Meningeal regulatory T cells inhibit nociception in female mice

Mon, 3 Aug 2026 00:00:00 +0000

T cells have emerged as orchestrators of pain amplification, but the mechanism by which T cells control pain processing is unresolved. We found that regulatory T cells (T_reg cells) could inhibit nociception through a mechanism that was not dependent on their ability to regulate immune activation and tissue repair. Site-specific depletion or expansion of meningeal T_reg cells (mT_reg cells) in mice led to female-specific and sex hormone-dependent modulation of mechanical sensitivity. Specifically, mT_reg cells produced the endogenous opioid enkephalin that exerted an antinociceptive action through the delta opioid receptor expressed by MrgprD⁺ sensory neurons. Although enkephalin restrains nociceptive processing, it was dispensable for T_reg cell-mediated immunosuppression. Thus, our findings uncovered a sexually dimorphic immunological circuit that restrains nociception, establishing T_reg cells as sentinels...

Long-term optical imaging of the spinal cord in awake behaving mice

Mon, 3 Aug 2026 00:00:00 +0000

Advances in optical imaging and fluorescent biosensors enable study of the spatiotemporal and long-term neural dynamics in the brain of awake animals. However, methodological difficulties and fibrosis limit similar advances in the spinal cord. Here, to overcome these obstacles, we combined in vivo application of fluoropolymer membranes that inhibit fibrosis, a redesigned implantable spinal imaging chamber and improved motion correction methods that together permit imaging of the spinal cord in awake behaving mice, for months to over a year. We demonstrated a robust ability to monitor axons, identified a spinal cord somatotopic map, performed months-long imaging in freely moving mice, conducted Ca2+ imaging of neural dynamics in behaving mice responding to pain-provoking stimuli and observed persistent microglial changes after nerve injury. The ability to couple in vivo imaging and behavior at the spinal cord level will drive insights not previously possible at a key location for...

Cincuenta años de investigación sobre el dolor y avances clínicos: aspectos destacados y tendencias clave

Mon, 3 Aug 2026 00:00:00 +0000

Este artículo destaca los avances en la investigación preclínica en ciencias básicas del dolor, la investigación clínica y la investigación psicológica que se han producido durante los 50 años transcurridos desde que se fundó la Asociación Internacional para el Estudio del Dolor. Presenta hallazgos importantes y tendencias clave en estas 3 áreas de la ciencia del dolor: investigación preclínica en ciencias básicas, investigación clínica e investigación psicológica. This article highlights advances in basic science preclinical pain research, clinical research, and psychological research occurring over the 50 years since the International Association for the Study of Pain was founded. It presents important findings and key trends in these 3 areas of pain science: basic science preclinical research, clinical research, and psychological research.

Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results

Mon, 3 Aug 2026 00:00:00 +0000

Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently...

OR23-06 Sensory neuronal ACVR1-mediated neuroimmune contribution to neuropathic pain and heterotopic ossification in fibrodysplasia ossificans progressiva

Mon, 3 Aug 2026 00:00:00 +0000

Abstract

Disclosure: X. Yu: None. J. Braz: None. L. Lam: None. K. Bhardwaji: None. K. Jin: None. H. Yuan: None. D. Mohsenin: None. E. Yu: None. J. Weinrich: None. B. Ahanonu: None. A. Basbaum: None. E.C. Hsiao: None.

Heterotopic ossification (HO), a pathological bone formation within muscle and connective tissues, is acquired following orthopedic surgery, severe burns, combat wounds, and traumatic injury of the central nervous system. Neither HO nor its associated pain has effective treatments, and the underlying mechanisms remain unclear. However, insight has come from studies of an hereditary HO subset, namely Fibrodysplasia Ossificans Progressiva (FOP), in which 97% of patients carry an arginine²⁰⁶ to histidine gain-of-function point mutation (R206H) in the BMP type I receptor (ACVR1). We previously reported that adult FOP patients have baseline nociceptive hypersensitivity to both heat and mechanical stimuli in the absence of an inflammatory flareup or...

Poster 3: Is Muscle Fatty Infiltration a Hidden Cause of Pain After Rotator Cuff Tears? Insights From a Preclinical Study

Mon, 3 Aug 2026 00:00:00 +0000

Objectives:

Chronic rotator cuff tear (RCT) presents a significant pain burden leading to substantial functional impairment. Despite advances in treatment, pain management remains a critical aspect of quality of life. Up to 20% of patients are on opioids for RCT-related pain and continue use even after surgery; however, they pose substantial risks due to their potential for addiction and adverse effects. Thus, understanding the underlying neurologic pain pathways associated with chronic RCTs is essential for developing effective therapeutic strategies. The objective of this study was to demonstrate the presence of sensory neuron injury and neuropathic pain after RCT through in a mouse model and determine the effectiveness of various classes of pain medications, such as nonsteroid anti-inflammatory drugs (NSAIDs), gabapentin, and opioids. Further, due to the overall degenerative effects of muscle fatty infiltration (FI), we also sought to investigate the relationship of rotator...

International Association for the Study of Pain publications over the 50-year span

Mon, 3 Aug 2026 00:00:00 +0000

ABSTRACT: The International Association for the Study of Pain (IASP) has a 50-year history of publishing educational and research materials, ranging from traditional print format books, journals, and other informational formats to online and electronic formats. Here we provide a historical overview of IASP publications and reflections from the perspective of 5 former or current Editors-in-Chief.