Benzestrol Isomer Stereochemistry Determines the Distinct Estrogenic Activities and Conformations of the Eight Isomers When Bound to Estrogen Receptor α.

The nonsteroidal estrogen, benzestrol, has potent estrogenic activity, and through a recent stereocontrolled synthesis, we have obtained all eight of its constituent stereoisomers. We find that only one of them, RSS benzestrol, has very high binding affinity for estrogen receptor alpha (ERα); the other seven isomers have 60 to 600-fold lower affinity. We now show that the potencies of the isomers in two cell activity assays, proliferation of ER-positive breast cancer cells and stimulation of estrogenic gene activity, reflect their varying binding affinities for ERα.

Minimally Invasive Total Versus Partial Thymectomy for Early-Stage Thymoma.

: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs.

Implementing capacity-building initiatives addressing health equity through community-academic partnerships: A qualitative study.

Background: Capacity-building is a common goal of community-academic partnerships, but there are literature gaps in the components of capacity-building efforts that support success and how implementation science can contribute to these efforts. We studied the core components and implementation determinants of capacity-building initiatives carried out through Chicagoland CEAL community-academic partnerships.

Methods: We conducted seven focus group discussions with 26 community organization representatives and researchers exploring six capacity-building initiatives.

Discovery of Palazestrant (OP-1250), a Potent and Orally Bioavailable Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD).

Metastatic breast cancer (mBC) is a leading cause of cancer death in women. Most breast cancer patients are administered estrogen-receptor-targeted endocrine therapies to treat or prevent progressive metastatic disease. Development of endocrine resistance through acquisition of mutations in the estrogen receptor gene, , that constitutively activate the estrogen receptor leads to relapse.

Novel control for erectile dysfunction research.

Background: Erectile dysfunction (ED) is a serious medical condition that impacts quality of life. An underlying cause is loss of cavernous nerve (CN) innervation, which initiates remodeling of the corpora cavernosa of the penis, including smooth muscle apoptosis and increased collagen. There are few studies of penile remodeling in patients because of difficulty acquiring patient corpora cavernosa tissue, and appropriate controls; however, it is critical to ensure that our animal models adequately parallel patient conditions.

Challenges in coverage of future hepatitis C vaccines: Review and potential solutions.

Background: Motivated by the high mortality burden of hepatitis C virus (HCV) and the unprecedented rapid development of the COVID-19 and respiratory syncytial virus (RSV) vaccines, we note that a prompt HCV vaccine rollout may streamline the World Health Organization's goal to eliminate HCV before 2030. While progress in the development of HCV vaccine candidates has rapidly flourished, vaccine hesitancy and HCV incidence are both particularly prevalent in people who inject drugs (PWID). The aim of this paper is to document several potential challenges in HCV vaccine uptake and provide a set of preliminary recommendations for public and community health professionals to improve acceptance.

Artificial Intelligence in Vascular Neurology: Applications, Challenges, and a Review of AI Tools for Stroke Imaging, Clinical Decision Making, and Outcome Prediction Models.

Purpose Of Review: Artificial intelligence (AI) promises to compress stroke treatment timelines, yet its clinical return on investment remains uncertain. We interrogate state‑of‑the‑art AI platforms across imaging, workflow orchestration, and outcome prediction to clarify value drivers and execution risks.

Recent Findings: Convolutional, recurrent, and transformer architectures now trigger large‑vessel‑occlusion alerts, delineate ischemic core in seconds, and forecast 90‑day function.

Novel Presentation of Sturge-Weber Syndrome in a Boy With a Port-Wine Birthmark.

Sturge-Weber Syndrome (SWS), also called encephalotrigeminal angiomatosis, is a rare congenital neurological condition classified by the hallmark findings of a port-wine birthmark, leptomeningeal angiomas, and glaucoma. Here, we present a case of a two-year-old patient with a history of a left-sided port-wine birthmark involving the V1-V2 dermatomes who re-presented to the emergency department with focal right-sided seizure-like activity in the setting of a recent head trauma. The patient was admitted for further workup, where video electroencephalography demonstrated the presence of electrographic seizures developing from the left posterior quadrant, with continuous focal slowing over the left hemisphere, and with magnetic resonance venography revealing findings concerning for a pial angiomatosis.

Sport-Related Concussions in High School Athletes: A Comprehensive Update.

Purpose Of Review: Sport-related concussions (SRC) in high school athletes are a growing public health concern, with recent advancements in epidemiology, pathophysiology, diagnosis, management, and prevention. We concisely summarize SRC in high school athletes, emphasizing current research and clinical implications.

Recent Findings: Athletes are at significant risk of SRCs, with incidence varying by sport, sex, and competitive setting.

Gastroesophageal Neuroendocrine Tumors: Outcomes and Management.

: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes.

Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and nonenzymatic functions. Drugs targeting IDO1 enzyme activity have failed to improve the overall survival of patients with cancer. Developing new therapeutics that neutralize both enzyme- and nonenzyme-derived immunosuppressive IDO1 effects is therefore of high interest.

The Potential Roles of IL-1β, IL-6, and RIPK3 in the Pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare but severe skin conditions, often triggered by medications, that can be life-threatening. These conditions frequently affect the eyes, causing ocular surface disease, which can result in visual impairment or blindness. Although the exact mechanisms behind SJS/TEN remain unclear, key inflammatory mediators such as IL-1β, IL-6, and RIPK3 are believed to play critical roles in inflammation, necroptosis, and regulatory processes.

Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing.

Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging.

Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.

Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields.

Pleiotropic anti-cancer activities of novel non-covalent thioredoxin reductase inhibitors against triple negative breast cancer.

Mounting evidence shows that tumor growth and progression rely on thioredoxin reductase 1 (TXNRD1)-mediated detoxification of oxidative stress that results from deregulated metabolism and mitogenic signaling in tumors. TXNRD1 levels are significant higher in triple negative breast cancer (TNBC) compared to normal tissue, making TXNRD1 a compelling TNBC therapeutic target. Despite the many attempts to generate TXNRD1 inhibitors, all known and reported compounds inhibiting TXNRD1 are problematic; they interact with TXNRD1 irreversibly and non-specifically resulting in numerous adverse side effects.

Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection.

Enteroviruses cause significant morbidity and mortality worldwide, and Coxsackievirus B3 (CVB3) is one of the most commonly reported. Coxsackieviruses establish persistent infection, characterized as infection that is not cleared from host cells generating a continuous infection. No antivirals targeting persistent or acute infection are available, and CVB3 may respond differently depending on the type of infection.

SEASONAL MOSQUITO PRODUCTION IN STORM SEWER CATCH BASINS OF THE NORTH SHORE SUBURBS OF CHICAGO, 2021 TO 2024.

From 2021 to 2024, the number of pupae found in storm sewer catch basins in the North Shore suburbs of Chicago were assessed as part of routine quality control and improvement efforts. Over the course of these 4 yr, pupae were collected at least once during all calendar months, allowing for some insight into monthly mosquito production in catch basins. Thus, the intent of this study was to use those data to describe the number of pupae found in these structures across calendar months.

Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium.

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.

Sonic hedgehog suppresses penile remodeling after cavernous nerve injury and sustains long-term normal penis morphology.

Background: Cavernous nerve (CN) injury, which occurs in prostatectomy and diabetic cases, initiates penile remodeling, including smooth muscle apoptosis and increased collagen in the corpora cavernosa, which are underlying causes of erectile dysfunction. Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and SHH treatment suppresses corpora cavernosa remodeling that occurs with CN injury.

Aim: We examine if SHH treatment by peptide amphiphile (PA) in the first week after CN injury is sufficient to prevent long-term penis remodeling and if apoptosis inhibitors also suppress penile remodeling.

An Overview of Laryngologic Manifestations of Neurologic Diseases.

Purpose Of Review: Patients with various neurological disorders often present with or manifest during their disease process laryngologic pathology that can lead to significant morbidity. Recognizing and treating this aspect of their disease may be crucial in optimizing patient outcome.

Recent Findings: We discuss updated information and management regarding various neurological disorders that affect the larynx and how these sequelae are diagnosed and treated.

Deep Learning-Based Kinetic Analysis in Paper-Based Analytical Cartridges Integrated with Field-Effect Transistors.

This study explores the fusion of a field-effect transistor (FET), a paper-based analytical cartridge, and the computational power of deep learning (DL) for quantitative biosensing via kinetic analyses. The FET sensors address the low sensitivity challenge observed in paper analytical devices, enabling electrical measurements with kinetic data. The paper-based cartridge eliminates the need for surface chemistry required in FET sensors, ensuring economical operation (cost < $0.

The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.

Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis.

Biomimetic Proteoglycans Strengthen the Pericellular Matrix of Normal and Osteoarthritic Human Cartilage.

In osteoarthritis (OA), degradation of cartilage pericellular matrix (PCM), the proteoglycan-rich immediate cell microniche, is a leading event of disease initiation. This study demonstrated that biomimetic proteoglycans (BPGs) can diffuse into human cartilage from both normal and osteoarthritic donors and are preferentially localized within the PCM. Applying immunofluorescence (IF)-guided AFM nanomechanical mapping, we show that this localization of BPGs increases the PCM micromodulus of both normal and OA specimens.

A novel artificial intelligence model for diagnosing Acanthamoeba keratitis through confocal microscopy.

Purpose: To develop an artificial intelligence (AI) model to diagnose Acanthamoeba keratitis (AK) based on in vivo confocal microscopy (IVCM) images extracted from the Heidelberg Retinal Tomograph 3 (HRT 3).

Methods: This retrospective cohort study utilized HRT 3 IVCM images from patients who had received a culture-confirmed diagnosis of AK between 2013 and 2021 at Massachusetts Eye and Ear. Two cornea specialists independently labeled the images as AK or nonspecific finding (NSF) in a blind manner.