Somatic PTEN and ARID1A loss and endometriosis disease burden: a longitudinal study.

Study Question: Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?

Summary Answer: Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.

What Is Known Already: Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.

Study Design, Size, Duration: This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.

Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam.

Background: Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating infection among contacts of persons with drug-resistant tuberculosis are lacking.

Methods: We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat infection.

Aortic Stenosis and Coronary Artery Disease: Decision-Making Between Surgical and Transcatheter Management.

Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist and share pathophysiological mechanisms. The proportion of patients with AS and CAD requiring revascularization varies widely because of uncertainty about best clinical practices. Although combined surgical aortic valve replacement and coronary artery bypass grafting has been the standard of care, management options in patients with AS and CAD requiring revascularization have expanded with the advent of transcatheter aortic valve replacement (TAVR).

Thoracic and Cardiovascular Imaging Manifestations of Lupus.

Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a widely prevalent chronic autoimmune disease that can affect any organ system in the body. Although the pathogenesis of this disease is rather complex and poorly understood, ultimately there is an overproduction of multiple self-reactive antinuclear antibodies. These autoantibodies are one of the laboratory hallmarks of the diagnosis and disease activity of SLE.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

FastAd: A versatile toolkit for rapid generation of single adenoviruses or diverse adenoviral vector libraries.

Adenoviruses (Ads) are potent gene delivery vectors for and applications. However, current methods for their construction are time-consuming and inefficient, limiting their rapid production and utility in generating complex genetic libraries. Here, we introduce FastAd, a rapid and easy-to-use technology for inserting recombinant "donor" DNA directly into infectious "receiver" Ads in mammalian cells by the concerted action of two efficient recombinases: Cre and Bxb1.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

Outcomes of Community-Acquired Acute Kidney Injury: A Cohort Study of US Veterans.

Background: Community-acquired acute kidney injury (CA-AKI) occurs outside of the hospital and is the most common form of AKI. CA-AKI is not well understood, which hinders efforts to prevent, identify, and manage CA-AKI.

Objective: Examine 30-day outcomes following CA-AKI using national administrative and lab data from the Veterans Health Administration (VA).

Crucial Roles of Brassinosteroids in Cell Wall Composition and Structure Across Species: New Insights and Biotechnological Applications.

Brassinosteroids (BR) are steroidal phytohormones essential for plant growth, development, and stress resistance. They fulfil this role partially by modulating cell wall structure and composition through the control of gene expression involved in primary and secondary cell wall biosynthesis and metabolism. This affects the deposition of cellulose, lignin, and other components, and modifies the inner architecture of the wall, allowing it to adapt to the developmental status and environmental conditions.

Real-World Performance of Pneumothorax-Detecting Artificial Intelligence Algorithm and its Impact on Radiologist Reporting Times.

Rationale And Objectives: Artificial intelligence (AI) algorithms in radiology capable of detecting urgent findings have gained significant traction in recent years, but the impact of these algorithms on real-world clinical practice remains unclear with need for scientific investigation. Our study investigates the diagnostic accuracy and impact on radiologist report turnaround times of an FDA-approved AI tool for pneumothorax (PTx) detection on inpatient chest X-rays (CXR) in our institution's radiology practice at a large academic medical center.

Materials And Methods: This retrospective study included 27,397 frontal, single-view CXRs of adult inpatients collected consecutively between August 2020 and April 2021 following deployment of an AI-based PTx detection and picture archiving and communication system (PACS) alert system.

In Silico Modeling of Fabry Disease Pathophysiology for the Identification of Early Cellular Damage Biomarker Candidates.

Fabry disease (FD) is an X-linked lysosomal disease whose ultimate consequences are the accumulation of sphingolipids and subsequent inflammatory events, mainly at the endothelial level. The outcomes include different nervous system manifestations as well as multiple organ damage. Despite the availability of known biomarkers, early detection of FD remains a medical need.

Manufacturing of breathable, washable, and fabric-integrated squid skin-inspired thermoregulatory materials.

Advanced thermal management technologies represent an important research frontier because such materials and systems show promise for enhancing personal physiological comfort and reducing building energy consumption. These technologies typically offer the advantages of excellent portability, user-friendly tunability, energy efficiency, and straightforward manufacturability, but they frequently suffer from critical challenges associated with poor breathability, inadequate wash stability, and difficult fabric integration. Within this broader context, our laboratory has previously developed heat-managing composite materials by drawing inspiration from the color-changing skin of the common squid.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Background: Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SS (Dahl SS CD247 knockout rat; lacking T cells), and SS (Dahl SS p67 [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states.

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

Background: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.

Methods: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation.

Preclinical Efficacy of VTX-0811: A Humanized First-in-Class PSGL-1 mAb Targeting TAMs to Suppress Tumor Growth.

Omnipresent suppressive myeloid populations in the tumor microenvironment limit the efficacy of T-cell-directed immunotherapies, become more inhibitory after administration of T-cell checkpoint inhibitors, and are overall associated with worse survival of cancer patients. In early clinical trials, positive outcomes have been demonstrated for therapies aimed at repolarizing suppressive myeloid populations in the tumor microenvironment. We have previously described the key role of P-selectin glycoprotein ligand-1 (PSGL-1) in maintaining an inhibitory state of tumor-associated macrophages (TAMs), most of which express high levels of PSGL-1.

Neoadjuvant cabozantinib restores CD8+ T cells in patients with locally advanced non-metastatic clear cell renal cell carcinoma: a phase 2 trial.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We hypothesized that neoadjuvant cabozantinib could downstage localized tumors, facilitating partial nephrectomy, and facilitating surgery in patients with locally advanced tumors that would require significant adjacent organ resection. We, therefore, conducted a phase 2, single-arm trial of cabozantinib treatment for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection.

The role of HnrnpF/H as a driver of oligoteratozoospermia.

Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms.

The Chemistry-Process-Structure Relationships of a Functionally Graded Ti-6Al-4V/Ti-1B Alloy Processed with Laser-Engineered Net Shaping Creates Borlite.

We quantify the chemistry-process-structure-property relationships of a Ti-6Al-4V alloy in which titanium-boron alloy (Ti-B) was added in a functionally graded assembly through a laser-engineered net shaping (LENS) process. The material gradient was made by pre-alloyed powder additions to form an in situ melt of the prescribed alloy concentration. The complex heterogeneous structures arising from the LENS thermal history are completely discussed for the first time, and we introduce a new term called "Borlite", a eutectic structure containing orthorhombic titanium monoboride (TiB) and titanium.

Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents.

Background And Objectives: In Parkinson disease (PD), α-synuclein spreading through connected brain regions leads to neuronal loss and brain network disruptions. With diffusion-weighted imaging (DWI), it is possible to capture conventional measures of brain network organization and more advanced measures of brain network resilience. We aimed to investigate which neuropathologic processes contribute to regional network topologic changes and brain network resilience in PD.