Long-term oncologic outcomes and complications of robot-assisted radical cystectomy for the treatment of urothelial carcinoma of the bladder.

Introduction: To report the long-term outcomes of robot-assisted radical cystectomy (RARC) for the treatment of muscle invasive and high-risk non-muscle invasive bladder cancer.

Methods: We reviewed a single tertiary center database of RARC from 2004 to 2020. Concomitant extended pelvic lymph node dissection and extracorporeal urinary diversion were performed.

AlphaFold with conformational sampling reveals the structural landscape of homorepeats.

Homorepeats are motifs with reiterations of the same amino acid. They are prevalent in proteins associated with diverse physiological functions but also linked to several pathologies. Structural characterization of homorepeats has remained largely elusive, primarily because they generally occur in the disordered regions or proteins.

Childhood obesity from the genes to the epigenome.

The prevalence of obesity and its associated comorbidities has surged dramatically in recent decades. Especially concerning is the increased rate of childhood obesity, resulting in diseases traditionally associated only with adulthood. While obesity fundamentally arises from energy imbalance, emerging evidence over the past decade has revealed the involvement of additional factors.

Minimally invasive cytoreductive radical prostatectomy, exploring the safety and feasibility of a single-port or multi-port robotic platform.

Background: Consolidative resection or cytoreductive radical prostatectomy (CRP) may benefit men with non-organ confined prostate cancer. We report the safety, feasibility, and outcomes of robot-assisted laparoscopic CRP using a single-port (SP) or multi-port (MP) platform.

Methods: We reviewed consecutive men with clinical node positive or metastatic castrate-sensitive prostate cancer who underwent IRB-approved CRP and extended pelvic lymph node dissection using the da Vinci SP or MP Surgical Systems (Intuitive Surgical, Sunnyvale, CA) from 2015-2022.

A druggable conformational switch in the c-MYC transactivation domain.

The c-MYC oncogene is activated in over 70% of all human cancers. The intrinsic disorder of the c-MYC transcription factor facilitates molecular interactions that regulate numerous biological pathways, but severely limits efforts to target its function for cancer therapy. Here, we use a reductionist strategy to characterize the dynamic and structural heterogeneity of the c-MYC protein.

Long-term Outcomes and Patient Satisfaction Following Salvage Robot-assisted Radical Prostatectomy: A Modern Perspective.

Background And Objective: Approximately two-thirds of men who undergo primary treatment for prostate cancer (PC) will experience biochemical recurrence (BCR). Salvage robot-assisted radical prostatectomy (sRARP) offers curative treatment in this disease setting and men who choose this option may avoid palliative androgen deprivation therapy (ADT). The purpose of this study was to describe long-term outcomes and patient feedback following sRARP.

Sepsis among Patients Admitted to the Intensive Care Unit of a Tertiary Care Centre.

Introduction: Sepsis is a life-threatening dysfunction and is one of the common causes of admission in intensive care units. Early diagnosis and management improves the outcome of patients. The aim of this study was to find out the prevalence of sepsis among patients admitted to the intensive care unit of a tertiary care centre.

Magnetic resonance imaging-ultrasound fusion guided focal cryoablation for men with intermediate-risk prostate cancer.

Introduction: Focal therapy (FT) is a form of ablative treatment offered to men with localized, organ-confined prostate cancer (CaP). Pelvic multiparametric magnetic resonance imaging (mpMRI) and mpMRI/transrectal ultrasound fusion (MRI-US) guidance enable the precise delivery of FT with limited ablation of adjacent benign tissue or vital genitourinary structures. This article presents our findings on using MRI-US to perform FT as a primary treatment for men with intermediate-risk CaP.

Groin Pain Syndrome Italian Consensus Conference update 2023.

Groin pain syndrome (GPS) is a controversial topic in Sports Medicine. The GPS Italian Consensus Conference on terminology, clinical evaluation and imaging assessment of groin pain in athletes was organized by the Italian Society of Arthroscopy in Milan, on 5 February 2016. In this Consensus Conference (CC) GPS etiology was divided into 11 different categories for a total of 63 pathologies.

Adrenergic Reprogramming of Preexisting Adipogenic Trajectories Steer Naïve Mural Cells Toward Beige Differentiation.

In adult white adipose tissue, cold or β3-adrenoceptor activation promotes the appearance of thermogenic beige adipocytes. Our comprehensive single-cell analysis revealed that these cells arise through the reprogramming of existing adipogenic trajectories, rather than from a single precursor. These trajectories predominantly arise from SM22-expressing vascular mural progenitor cells.

Mass Spectrometry of RNA-Binding Proteins during Liquid-Liquid Phase Separation Reveals Distinct Assembly Mechanisms and Droplet Architectures.

Liquid-liquid phase separation (LLPS) of heterogeneous ribonucleoproteins (hnRNPs) drives the formation of membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination of protein engineering, native ion mobility mass spectrometry, and molecular dynamics simulations. We used an LLPS-compatible spider silk domain and pH changes to control the self-assembly of the hnRNPs FUS, TDP-43, and hCPEB3, which are implicated in neurodegeneration, cancer, and memory storage.

Liquid-Liquid Phase Separation Primes Spider Silk Proteins for Fiber Formation via a Conditional Sticker Domain.

Many protein condensates can convert to fibrillar aggregates, but the underlying mechanisms are unclear. Liquid-liquid phase separation (LLPS) of spider silk proteins, spidroins, suggests a regulatory switch between both states. Here, we combine microscopy and native mass spectrometry to investigate the influence of protein sequence, ions, and regulatory domains on spidroin LLPS.

The MDM2 Inhibitor Navtemadlin Arrests Mouse Melanoma Growth and Potentiates Radiotherapy.

Unlabelled: The tumor suppressor protein p53 is mutated in close to 50% of human tumors and is dysregulated in many others, for instance by silencing or loss of p14. Under steady-state conditions, the two E3 ligases MDM2/MDM4 interact with and inhibit the transcriptional activity of p53. Inhibition of p53-MDM2/4 interaction to reactivate p53 in tumors with wild-type (WT) p53 has therefore been considered a therapeutic strategy.

A "grappling hook" interaction connects self-assembly and chaperone activity of Nucleophosmin 1.

How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant nucleolar protein that forms large oligomers and undergoes liquid-liquid phase separation by binding RNA or ribosomal proteins. It provides the scaffold for ribosome assembly but also prevents protein aggregation as part of the cellular stress response.

Risk Factors for Acute Gastroenteritis Among Patients Hospitalized in 5 Veterans Affairs Medical Centers, 2016-2019.

Background: In the United States, ∼179 million acute gastroenteritis (AGE) episodes occur annually. We aimed to identify risk factors for all-cause AGE, norovirus-associated vs non-norovirus AGE, and severe vs mild/moderate AGE among hospitalized adults.

Methods: We enrolled 1029 AGE cases and 624 non-AGE controls from December 1, 2016, to November 30, 2019, at 5 Veterans Affairs Medical Centers.

Development of a novel peptide aptamer that interacts with the eIF4E capped-mRNA binding site using peptide epitope linker evolution (PELE).

Identifying new binding sites and poses that modify biological function are an important step towards drug discovery. We have identified a novel disulphide constrained peptide that interacts with the cap-binding site of eIF4E, an attractive therapeutic target that is commonly overexpressed in many cancers and plays a significant role in initiating a cancer specific protein synthesis program though binding the 5'cap (7'methyl-guanoisine) moiety found on mammalian mRNAs. The use of disulphide constrained peptides to explore intracellular biological targets is limited by their lack of cell permeability and the instability of the disulphide bond in the reducing environment of the cell, loss of which results in abrogation of binding.

TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.

Unlabelled: Patients with bladder cancer often have a poor prognosis due to the highly invasive and metastatic characteristics of bladder cancer cells. Epithelial-to-mesenchymal transition (EMT) has been causally linked to bladder cancer invasion. The E3 ubiquitin ligase, tumor necrosis factor receptor-associated factor 4 (TRAF4) has been implicated as a tumor promoter in a wide range of cancers.

Hundred years of transperineal prostate biopsy.

The earliest recorded efforts to biopsy prostate, in the early 20th century, were made through transperineal (TP) approach, with open perineal prostate biopsy (PBx) being considered the gold standard for prostate cancer (PCa) diagnosis in that era. Later, to minimize morbidity and increase diagnostic accuracy, several technical modifications and transrectal ultrasound (TRUS) assistance were incorporated. However, in the 1980s, the transrectal (TR) approach became the predominant PBx method following the introduction of TRUS-TR PBx with sextant sampling, providing a convenient and efficacious method for prostate sampling.

Electrospray ionization of native membrane proteins proceeds a charge equilibration step.

Electrospray ionization mass spectrometry is increasingly applied to study the structures and interactions of membrane protein complexes. However, the charging mechanism is complicated by the presence of detergent micelles during ionization. Here, we show that the final charge of membrane proteins can be predicted by their molecular weight when released from the non-charge reducing saccharide detergents.

A "spindle and thread" mechanism unblocks p53 translation by modulating N-terminal disorder.

Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of "life on the edge of solubility.

Prospective, Randomized Comparison of Dual-Lumen Single-Lumen Flexible Ureteroscopes in Proximal Ureteral and Renal Stone Management.

We sought to compare the safety, efficacy, efficiency, and surgeon experience during upper urinary tract stone management with single-lumen (SLFU) dual-lumen flexible ureteroscopes (DLFU). Seventy-nine patients with proximal ureteral or renal stone burden <2 cm were randomized to a SLFU or DLFU. We recorded times for ureteroscopy (URS), laser lithotripsy, stone basketing, as well as intraoperative and postoperative complications.

Does the type of biopsy used for diagnosis impact subsequent treatment selection in prostate cancer patients?

Purpose: Multiparametric magnetic resonance imaging (mpMRI) targeted biopsy has emerged as an augmentation to systematic prostate biopsy (SBx) with improved diagnostic accuracy. The purpose of this study was to determine whether biopsy modality impacted management of prostate cancer (PCa).

Methods: We performed a retrospective review of patients with newly diagnosed non-metastatic PCa at our institution (2014-2020).

Current Opinion Regarding Multidisciplinary Cancer Clinic Utilization for the Management of Prostate Cancer.

Objectives: Multidisciplinary cancer clinic (MDC) is an evaluation option for the management of prostate cancer (PCa). The purpose of MDC is to provide the patient with a comprehensive assessment and risk/benefit discussion of all pertinent treatment options. Our objective was to obtain a contemporary measure and analysis of urologists' opinion regarding PCa MDC.

Pleckstrin-2 is essential for erythropoiesis in β-thalassemic mice, reducing apoptosis and enhancing enucleation.

Erythropoiesis involves complex interrelated molecular signals influencing cell survival, differentiation, and enucleation. Diseases associated with ineffective erythropoiesis, such as β-thalassemias, exhibit erythroid expansion and defective enucleation. Clear mechanistic determinants of what make erythropoiesis effective are lacking.