Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Insights from a century of data reveal global trends in ex situ living plant collections.

Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.

Durability of response of UGN-101: Longitudinal follow up of multicenter study.

Purpose: UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.

Cognitive neuroscience: How the brain navigates abstract task spaces.

Humans and other animals learn the abstract structure of a task and then use this structure to rapidly generalize to new situations. A recent study reveals how the brain builds and uses abstract task representations.

The 2025 Motile Active Matter Roadmap.

Activity and autonomous motion are fundamental aspects of many living and engineering systems. Here, the scale of biological agents covers a wide range, from nanomotors, cytoskeleton, and cells, to insects, fish, birds, and people. Inspired by biological active systems, various types of autonomous synthetic nano- and micromachines have been designed, which provide the basis for multifunctional, highly responsive, intelligent active materials.

A randomized controlled trial comparing embryo vitrification with slush nitrogen to liquid nitrogen in women undergoing frozen embryo transfer: embryology and clinical outcomes.

Study Question: Does the use of slush nitrogen (SN) for embryo vitrification improve embryo transfer outcomes compared to liquid nitrogen (LN)?

Summary Answer: SN is a safe method for embryo preservation and significantly improves post-warming survival rates during repeated vitrification-warming cycles; however, after a single freeze-thaw cycle, pregnancy outcomes are not improved when embryos are vitrified with SN compared to LN.

What Is Known Already: SN is a combination of solid and LN, with a temperature lower than regular LN, and it is an alternative to conventional LN in achieving a faster cooling speed. Studies have shown that SN improves survival in non-human embryos and human oocytes.

Arthritis: Septic Arthritis.

Septic arthritis is acute onset of monoarticular inflammation of a joint due to an infectious etiology. It is usually bacterial but can be viral or fungal. Septic arthritis causes significant morbidity and mortality and requires prompt diagnosis and treatment.

Arthritis: Knee and Hip Arthroplasty.

Approximately 800,000 total knee arthroplasties and 450,000 total hip arthroplasties are performed annually in the United States. These procedures provide significant pain relief and restore function in patients with advanced osteoarthritis, rheumatoid arthritis, and other degenerative joint conditions. Patient evaluation before surgery includes a history, physical examination, laboratory tests, and imaging.

Arthritis: Knee and Hip Osteoarthritis.

Knee and hip osteoarthritis (OA) are two of the leading causes of disability globally. Knee OA is characterized by gradual degeneration of articular cartilage, leading to pain, stiffness, and functional limitations. Patients older than 50 years typically present with knee OA, but it can manifest earlier, particularly following traumatic knee injuries.

A Systematic Literature Review on the Burden of Disease for Patients With Moderate to Severe Acute Ischemic Stroke.

Background: A vast amount of literature is available on the burden of acute ischemic stroke (AIS). Yet, most information on AIS burden does not stratify by stroke severity, and the inclusion of mild strokes (National Institute of Health Stroke Scale < 5) might obscure the true impact of moderate-to-severe AIS. Therefore, it is important to understand the literature as it pertains to the epidemiological, clinical, humanistic, and economic burden of moderate-to-severe AIS from a global perspective.

Population Pharmacokinetics of Orvacabtagene Autoleucel, an Autologous BCMA-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed/Refractory Multiple Myeloma.

Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).

Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.

Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark - A national registry study.

Background: Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Method: Among all adults (>18 years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics.

Onabotulinum Toxin A-Led Urinary Tract Infections-Should we Safeguard? A Randomized Controlled Trial.

Introduction And Hypothesis: The objective of our study was to evaluate the need for antibiotic prophylaxis for urinary tract infection (UTI) prevention before Onabotulinum toxin A injection for overactive bladder (OAB). We hypothesize that the lack of antibiotic prophylaxis might not be inferior to administering prophylaxis.

Methods: This was a multi-centered, nonblinded, randomized controlled trial conducted between August 2022 and September 2024.

Tailoring Exercise Prescription for Effective Diabetes Glucose Management.

Context: Physical activity, exercise, or both are a staple of lifestyle management approaches both for type 1 diabetes mellitus (T1DM) and type 2 diabetes (T2DM). While the current literature supports both physical activity and exercise for improving glycemic control, reducing cardiovascular risk, maintaining proper weight, and enhancing overall well-being, the optimal prescription regimen remains debated.

Evidence Acquisition: We searched PubMed and Google Scholar databases for relevant studies on exercise, insulin sensitivity, and glycemic control in people with T1DM and T2DM.

Pinch-off dynamics of emulsion filaments before and after polymerization of the internal phase.

The capillary break-up of complex fluid filaments occurs in many scientific and industrial applications, particularly in bio-printing where both liquid and polymerized droplets exist in the fluid. The simultaneous presence of fluid and solid particles within a carrier fluid and their interactions lead to deviations in the filament break-up from the well-established capillary breakup dynamics of single-phase liquids. To examine the significance of the dispersed phase and the internal interactions between liquid droplets and solid particles, we prepare emulsions through photopolymerization and conduct experimental investigations into the pinch-off dynamics of fluid filaments, focusing on the impact of varying concentrations of liquid droplets (before polymerization) and polymerized droplets.

Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.

To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics Data Mart between 8 August 2017 and 31 December 2021.

Real-world trends and future projections of the prevalence of cirrhosis and hepatic encephalopathy among commercially and Medicare-insured adults in the United States.

Objectives: Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using health care claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated health care resource utilization among commercially and Medicare-insured adults in the United States (US).

Methods: Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020).

Development of a microvessel density gene signature and its application in precision medicine.

Combination therapy with anti-angiogenic drugs and immune checkpoint inhibitors has shown enhanced clinical activity and has been approved for the treatment of multiple tumor types. Despite extensive research, predictive biomarkers for combination therapy remain poorly understood. Microvessel density (MVD), a surrogate marker for aberrant angiogenesis measured by immunohistochemistry (IHC), has been associated with response to monotherapy with anti-angiogenesis inhibitors.

SyncGenie: A programmable event synchronization device for neuroscience research.

In neuroscience, accurately correlating brain activity with stimuli and other events requires precise synchronization between neural data and event timing. To achieve this, purpose-built synchronization devices are often used to detect events. This paper introduces SyncGenie, a programmable synchronization device designed for a range of uses in neuroscience research-primarily as a "trigger box" to align neurophysiological data with physical stimulus events, among other possibilities.

Cosmology of belonging: The role of community in the therapeutic use of psychedelics.

Background: The recent wave of clinical trials of psychedelic substances among patients with life-limiting illness has largely focused on individual healing. This most often translates to a single patient receiving an intervention with researchers guiding them. As social isolation and lack of connection are major drivers of current mental health crises and group work is expected to be an important aspect of psychedelic assisted psychotherapy, it is essential that we understand the role of community in psychedelic healing.