Citations

Abstract Uterine leiomyosarcoma (ULMS) is an orphan disease that frequently recurs and metastasizes, with patients undergoing multiple lines of chemotherapy due to lack of effective therapeutic targets. To address this gap, we used single-cell RNA sequencing and spatial transcriptomic analysis to comprehensively profile ULMS. We uncovered multiple states of tumor cells, including tumor cells with mesenchyme-like features, ischemic tumor cells defined by a MYC program, inflammatory tumor cells with active interferon signaling, and stem cell-like hormone receptor-positive cells. The inferred spatial correlates of these tumor cell states demonstrated unique localization patterns. By correlating these signatures to bulk RNA sequencing data, we demonstrate the relevance of these findings to clinical outcomes. Finally, using the single-cell integration and drug response prediction algorithm (scIDUC), we propose drug predictions that may target specific tumor states. Our findings suggest new avenues for further exploration of individualized and multifaceted therapeutic strategies to treat ULMS.

Background: Emerging neuromodulation approaches, including epidural electrical stimulation (EES), offer hope for restoration of function following chronic spinal cord injury (SCI). However, integrating neuromodulation therapies into clinical procedures is challenging due to the unique needs of the SCI population. Objectives: The purpose of this study was to understand the experiences of participants during a first-in-human trial of perilesional EES aimed at restoring sensorimotor function. Methods: We report participants’ experiences by describing their clinical care, experiences during experimental neuromodulation sessions, and perspectives on the utility of a perilesional EES system. Three participants with chronic thoracic SCI participated in semistructured interviews after completing a 14-day inpatient experimental protocol, which included stimulation mapping, lower extremity motor control experiments, and treadmill stepping. Interview data were analyzed using an applied thematic analysis approach. Nine key themes addressed 4 major topic areas: clinical experiences, experiences during laboratory experiments, experiences as a research participant, and perceived value of perilesional EES. Results: All participants noted the potential for EES to enhance functional recovery, though their postoperative experiences related to clinical care, postoperative pain, and disruptions to routine care differed. Insights gained from qualitative analyses highlighted challenges and opportunities for improving postsurgical care and refining application of EES technology. Further, these results inform recommendations for neuromodulation trials in the SCI community to help mitigate postoperative complications and improve study participant experiences. Conclusion: Key recommendations include being proactive regarding potential postsurgical complications, educating clinical staff regarding common SCI comorbidities, and customizing experimental protocols to align with the priorities and clinical needs of each participant.

Unilateral yellow discoloration of the eye, commonly referred to as scleral icterus, is an uncommon clinical finding; there are only 14 cases of persistent unilateral scleral icterus documented in the literature. Here, the authors describe a patient with Gilbert’s syndrome who presented with left-sided conjunctival and scleral icterus presumed secondary to poor vascular outflow following surgical and radiation treatment of squamous cell carcinoma of the left ear with parotid and cervical lymph node involvement. The current case describes a unique physical finding, reviews the pathophysiology of conjunctival and scleral icterus, and reviews the current literature on this topic.

Foundation models can streamline imaging workflows, improve diagnostic accuracy, enable personalized treatment, and, via integrated generative artificial intelligence, create synthetic images to augment scarce real-world data; however, successful adoption requires explainability, trust, and workflow integration.

ABSTRACT Background While radiofrequency ablation (RFA) and cryoablation (CBA) are established treatments for atrial fibrillation (AF), pulsed field ablation (PFA) offers potential benefits. This study compares PFA's procedural outcomes with RFA and CBA. Methods A PRISMA‐guided systematic review searched PubMed, Cochrane, Embase, and Scopus through September 2024. Studies comparing PFA to RFA or CBA in paroxysmal and persistent AF were included. Results From 1413 titles, 28 studies (7944 patients, 4–13 months follow‐up) met inclusion criteria. PFA showed lower recurrence versus RFA (RR = 0.85, p < 0.05) and CBA (RR = 0.81, p < 0.01). Procedure times were shorter versus RFA (‐46.39 min, p < 0.01) and CBA (‐9.26 min, p < 0.01). PFA had fewer complications than CBA (RR = 0.45, p < 0.01) and thermal ablation (RR = 0.55, p < 0.01), with similar rates to RFA (RR = 0.81, p = 0.25). Fluoroscopy times were higher. Conclusion Promising results with PFA suggest it as a viable alternative to thermal ablation.

ABSTRACT The genomic sequences of seven phages isolated from municipal sewage in Rochester, Minnesota, USA, using Klebsiella pneumoniae strains ( bla KPC carriers) as hosts are reported. These phages are lytic and belong to the Ackermannviridae, Drexlerviridae , and Zobellviridae families. No known antimicrobial resistance or virulence genes were found within their genomes.

The role of circulating tumor DNA (ctDNA) in gastroesophageal adenocarcinoma (GEA) has expanded in recent years. In resectable disease, postoperative ctDNA is able to detect patients at highest risk of recurrence months before scans. Tumor-informed assays provide the best sensitivity and emerging methylation assays are useful when tissue is scarce. In metastatic GEA, baseline ctDNA burden correlates with prognosis, and a decrease in ctDNA level after treatment initiation reflects therapeutic response. It can also uncover actionable targets, including ERBB2, FGFR2, and MSI-H, and detect resistance that can arise after starting treatment. Limitations include variable assay performance, low shedding in some tumors, clonal hematopoiesis confounding, and a lack of randomized data showing that ctDNA-guided changes improve outcomes. Ongoing trials are testing MRD-guided escalation/de-escalation and ctDNA-directed biomarker therapy. In this review, we evaluate the role of ctDNA in GEA cancers over recent years.

Objectives Heritable connective tissue disorders (HCTDs), including hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobile spectrum disorder (HSD), have complex clinical manifestations, but the prevalence of left common iliac vein (LCIV) compression in these groups is not well known. This study aimed to compare the prevalence of significant LCIV compression in patients with hEDS, HSD, and healthy controls. Methods This retrospective, IRB-approved, single-center study analyzed 109 patients (25 hEDS, 64 HSD, 20 controls) who underwent contrast-enhanced abdominal and pelvic CT imaging from 2020 to 2023. LCIV compression was measured on axial CT, with >50% luminal narrowing defined as significant. Statistical analyses included chi-square tests, odds ratios, and t -tests. Interrater reliability was evaluated using intraclass correlation coefficients. Results Significant LCIV compression occurred in 68.0% of hEDS, 65.6% of HSD, and 35.0% of controls ( p = 0.034). Both hEDS ( p = 0.027) and HSD ( p = 0.015) groups had significantly higher compression rates than controls, with no statistically significant difference between the two clinical groups ( p = 0.831). Odds of compression were nearly fourfold greater in hEDS (OR 3.95) and HSD (OR 3.54) compared to controls. Conclusion LCIV compression is significantly more prevalent in patients with hEDS and HSD than in healthy controls, warranting further investigation of its clinical significance.