Single Cell RNA-sequencing of BCG naïve and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM-mediated immune-suppressive pathway.

Unlabelled: Non-muscle invasive bladder cancer (NMIBC) represents 70-80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guérin (BCG) remains a cornerstone treatment for intermediate-and high-risk NMIBC to prevent disease recurrence and progression. However, many patients experience recurrence after induction BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing on freshly collected NMIBC samples, distinguishing between those naïve to BCG treatment and those that recurred post-BCG treatment.

A Forgotten Encounter: A Case of Amebic Liver Abscess Mimicking Hepatic Malignancy in a Non-endemic Region.

Amebic liver abscess (ALA), caused by , is prevalent in endemic regions such as Central/South America, Southeast Asia/India, and Africa but is considered rare in North America. Symptoms of infection typically emerge eight to 20 weeks after exposure in endemic areas. We present the case of a 58-year-old woman who developed right-sided abdominal pain, weakness, fever, and significant weight loss.

Exploring the utility of snRNA-seq in profiling human bladder tissue: A comprehensive comparison with scRNA-seq.

Single cell sequencing technologies have revolutionized our understanding of biology by mapping cell diversity and gene expression in healthy and diseased tissues. While single-cell RNA sequencing (scRNA-seq) has been widely used, interest in single-nucleus RNA sequencing (snRNA-seq) is growing due to its benefits, including the ability to analyze archival tissues and capture rare cell types that are challenging to dissociate. However, comparative studies across tissues have yielded mixed results, with some reporting enhanced cell type retention using snRNA-seq while others finding cell type identification to be challenging in snRNA-seq data.

Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract.

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials And Methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021.

Benign Prostatic Hyperplasia Knowledge Deficits Among Male Urology Patients.

Objective: To measure patient knowledge about Benign prostatic hyperplasia (BPH) and identify factors associated with knowledge deficiencies among those newly presenting to our urology clinic.

Methods: Adult men presenting as new patients to our institution's urology clinic, regardless of chief complaint, were invited to complete a 26-item multiple choice questionnaire to assess basic knowledge about BPH, related symptomatology, and treatment options prior to their initial consultation. Responses were correlated to demographic variables using Analysis of Variance (ANOVA) and multivariable linear modeling.

Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models.

Single-cell RNA sequencing analysis identifies acute changes in the tumor microenvironment induced by interferon α gene therapy in a murine bladder cancer model.

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Bladder-preserving radiation therapy for patients with locally advanced and node-positive bladder cancer.

Purpose: Trimodality therapy for muscle-invasive bladder cancer (MIBC) yields similar oncologic outcomes compared to radical cystectomy in appropriately selected patients; however, data regarding locally advanced MIBC (LA-MIBC) is limited. We explored our experience with LA-MIBC undergoing radiation therapy (RT).

Methods: We retrospectively identified 30 patients from an institutional prospectively collated database with non-metastatic, LA-MIBC.

Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.

Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month.

An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer.

Purpose: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response.

Standardization of the evaluation and surveillance of patients with BCG unresponsive high grade non-muscle invasive bladder cancer clinical trials.

There are multiple ongoing and planned clinical trials that are evaluating novel therapies to treat patients with BCG-unresponsive high grade nonmuscle invasive bladder cancer (NMIBC). Importantly, there is considerable variation in surveillance strategies between these clinical trials, specifically with regards to the use of advanced imaging, enhanced cystoscopy, and mandatory biopsies, which could impact landmark efficacy assessments of investigational agents. To present guideline recommendations for the standardization of cystoscopic evaluation, surveillance, and efficacy assessments for patients with BCG-unresponsive NMIBC participating in clinical trials.

Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial.

Background: Alcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported.

Methods: This was a secondary analysis of the HOLIDAY Trial.

Oncologic outcomes of intravesical therapy in the management of nonmuscle invasive bladder cancer with variant histology.

Purpose: There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center.

Materials And Methods: A retrospective review of an IRB-approved bladder cancer database was performed.

Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy.

Introduction: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH.

Patients And Methods: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included.

Comparison of non-laser and laser transvenous lead extraction: a systematic review and meta-analysis.

Aims: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis.

Heat shock induces alternative polyadenylation through dynamic DNA methylation-regulated chromatin looping.

Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CTCF binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms.

Physiologic tension of the abdominal wall.

Background: Tension-free abdominal closure is a primary tenet of laparotomy. But this concept neglects the baseline tension of the abdominal wall. Ideally, abdominal closure should be tailored to restore native physiologic tension.

An evolutionarily nascent architecture underlying the formation and emergence of biomolecular condensates.

Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular condensates is thought to rely on collective interactions between many components, it is unclear how the collective interactions required for their formation emerge during evolution. Here, we show that the structure and evolution of a recently emerged biomolecular condensate, the nucleolar fibrillar center (FC), is explained by a single self-assembling scaffold, TCOF1.

Synergistic Combination of Visual Features in Vision-Taste Crossmodal Correspondences.

There has been a rapid recent growth in academic attempts to summarise, understand, and predict the taste profile matching complex images that incorporate multiple visual design features. While there is now ample research to document the patterns of vision-taste correspondences involving individual visual features (such as colour and shape curvilinearity in isolation), little is known about the taste associations that may be primed when multiple visual features are presented simultaneously. This narrative historical review therefore presents an overview of the research that has examined, or provided insights into, the interaction of graphic elements in taste correspondences involving colour, shape attributes, texture, and other visual features.

Oncological Outcomes for Patients with European Association of Urology Very High-risk Non-muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin or Early Radical Cystectomy.

Background: European Urology Association (EAU) guidelines recommend immediate radical cystectomy (early RC) for patients with very high-risk (VHR) non-muscle invasive bladder cancer (NMIBC), with bacillus Calmette-Guérin (BCG) recommended only for those who refuse or are unfit for RC.

Objective: To describe oncological outcomes following BCG or early RC in a contemporary cohort of patients with VHR NMIBC (EAU criteria).

Design, Setting, And Participants: Patients diagnosed with VHR NMIBC between 2000 and 2020 were identified from our institutional NMIBC registry.