Citations

Abstract As an intrinsically mechanosensitive organ, the lung experiences a range of mechanical forces. Chronic obstructive pulmonary disease (COPD) involves abnormal macroscopic cellular and extracellular matrix (ECM) changes that impact mechanical properties of the lung. Mechanosensitive Piezo1/2 channels are expressed in the lung including on airway smooth muscle cells (ASM) that mediate cellular responses to stretch and ECM biomechanics. The expression and roles of Piezos in COPD lung ASM are not known. We hypothesized that Piezo expression and activation are altered in COPD lung ASM influencing ECM regulation. Distribution of Piezo proteins in ASM and epithelium of small airways of COPD stage II and IV vs. non-COPD controls was assessed using immunohistochemistry and ImageJ (n=10-17/group). Isolated ASM cells from control (n=6) vs. COPD stage II and IV patients (n=3 each stage) were exposed to stretch or the Piezo1 agonist Yoda1 followed by measurement of ECM gene and protein expression. Less Piezo2 staining was observed in COPD IV patients compared to controls, with lesser area and intensity of staining in the epithelial layer, and lower intensity of staining in ASM and small airways as a whole. Fura-2-based imaging of ASM Ca 2+ showed lower influx after Yoda1 exposure in COPD II compared to control and COPD IV. Gene expression of Piezo1 increased upon stretching in controls but not in COPD ASM, while Piezo2 protein expression decreased with stretching in all groups. Yoda1 treatment resulted in decreased collagen1 , fibulin1 and periostin gene and collagen 1 and periostin protein expression in ASM. Overall, these results support a role for Piezo activation in abnormal ECM-ASM cell crosstalk in COPD.

Abstract Spatial transcriptomics has been widely applied to study the spatial distribution of cell types, cell states, and specific gene expression in tissue samples. However, we show that there is a prevalent transcript leakage problem in spatial transcriptomics data, where transcripts expressed by a cell diffuse to its neighborhood and are recurrently detected in the nearby cells. By analyzing published data sets, we show that this problem is general across data produced from different tissues and different species using different imaging-based and sequencing-based spatial transcriptomics platforms. It affects both upstream tasks such as expression quantification as well as downstream tasks such as cell-type annotation and detection of spatially-dependent gene expression. To tackle the transcript leakage problem, we propose a reference-free Bayesian model-based method, DeLeakage, which cleans up the data much more effectively than existing denoising methods. DeLeakage also improves cell-type annotation and avoids false detection of spatially dependent expression.

Transitions from inpatient rehabilitation to home critically affect patient recovery and caregiver well-being. Social determinants of health (SDoH) shape these outcomes yet remain underexamined in rehabilitation settings. The objective of this study was to examine the prevalence of SDoH on patient and caregiver experiences during the first 30 days following discharge from a multi-site inpatient rehabilitation facility in the southeastern United States and explore patterns of patient satisfaction and caregiver burden that can influence care transitions. A prospective cross-sectional descriptive study surveyed 61 patients and 50 caregivers using validated instruments assessing SDoH, communication, discharge preparedness, and caregiver burden. Social isolation, affecting 18% of patients and 10% of caregivers, was the most prevalent challenge. Additional challenges include health literacy and transportation barriers. Caregivers experienced substantial burden: 60% decline in social activities, 50% decreased energy, and 40.9% negative physical health effects. However, 58.1% reported strengthened patient relationships. This study identifies the importance of care continuity and SDoHs after inpatient rehabilitation. Interdisciplinary interventions focused on these key challenges are essential for improving outcomes.

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using FFPE tissues from 159 patients with DLBCL, and identified 746 cancer genes at or proximal to the rearrangement breakpoints with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis for genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

Purpose To assess if hospitals with high physician employment differ in risk-standardized mortality and readmission rates. Design/methodology/approach A cross-sectional evaluation of data from the 2021 Hospital Readmission Reduction program, Hospital Value-Based Purchasing Program, American Hospital Association and Area Health Resource Files was utilized. A binary variable was created to identify hospitals with ≤ 50% or >50% employed physicians. Dependent variables included 30-day mortality and readmission rates for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia (PN), and chronic obstructive pulmonary disease (COPD) hospitalizations. Propensity score matching was utilized to compare hospitals. The final matched cohort compared 200 hospitals in each group ( ≤ 50% physicians and > 50% physicians). Findings After matching, hospitals with > 50% physician employment were associated with improved mortality scores for AMI (−0.36, 95% CI: −0.58, −0.14), COPD (−0.38, 95% CI: −0.63, −0.14), and PN (−0.71, 95% CI: −1.15, −0.27). No significant differences were noted for CHF mortality or readmission rates. Originality/value There has been a growth in hospitals employing physician in the United States. This work demonstrates that hospitals with higher physician employment levels are associated with lower mortality scores. This likely reflects a broader organizational phenotype characterized by alignment, scale and clinical integration rather than physician employment as an isolated strategy. Further research should examine organizational features to better disentangle the structure and combination of organizational characteristics underlying these associations.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Importance Hypopigmented mycosis fungoides (HMF) is uncommon in adults, and data on clinicopathologic features and long-term outcomes remain sparse. Objective To investigate the clinicopathologic features and outcomes of adults with HMF in a large multicenter cohort. Design, Setting, and Participants This retrospective multicenter cohort study conducted from January 2011 to October 2023 at 6 US tertiary referral centers and included adults (18 years or older at diagnosis) with biopsy-confirmed HMF and hypopigmentation documented at diagnosis, with a median (range) follow-up of 39 (1-347) months. Data were analyzed from February to December 2025. Exposures Clinical variant, immunophenotype predominance, and polymerase chain reaction–based T-cell receptor ( TCR ) gene rearrangement in peripheral blood and/or skin. Main Outcomes and Measures Best overall response, defined as complete response, partial response, stable disease, or progressive disease, and progression to a higher stage. Results The cohort included 224 adults with HMF (median [range] age, 44 [18-74] years), of whom 164 (73%) were women (60 men [27%]), 5 (2%) were Asian individuals, 1 (0.4%) was a Hispanic/Latino individual, 1 (0.4%) was a Middle Eastern individual, 19 (8%) were White individuals, and 186 (83%) were Black individuals; 219 (98%) presented with early-stage disease. Most had hypopigmented lesions only (159 [71%]), whereas 65 (29%) exhibited mixed-variant mycosis fungoides; outcomes were similar between groups. Among 141 patients with available immunophenotyping, 88 (63%) had CD8-positive predominance. Among 207 treated patients, most (179 [90%]) received skin-directed therapy alone. Among 198 evaluable patients, the best overall response was complete response for 52 (26%), partial response for 101 (51%), stable disease for 34 (17%), and progressive disease for 11 (6%). Over a median (range) follow-up of 39 (1-347) months, 14 of 224 patients (6%) experienced progression to a higher stage, including 5 of 219 patients (2%) with early-stage disease at baseline who experienced progression to advanced-stage disease. Peripheral blood TCR monoclonality was detected in 23 of 85 tested patients (27%) and was associated with poorer treatment response but not with disease progression. Conclusions and Relevance The finding of this cohort study suggest that adult HMF demonstrated a generally indolent course, with favorable response to skin-directed therapy, irrespective of immunophenotype or mixed-variant presentation. Peripheral blood TCR monoclonality was associated with lower treatment response but not disease progression.