Novel MRI-based Hyper-Fused Radiomics for Predicting Pathologic Complete Response to Neoadjuvant Therapy in Breast Cancer.

Rationale And Objectives: To propose a novel MRI-based hyper-fused radiomic approach to predict pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer (BC).

Materials And Methods: Pretreatment dynamic contrast-enhanced (DCE) MRI and ultra-multi-b-value (UMB) diffusion-weighted imaging (DWI) data were acquired in BC patients who received NAT followed by surgery at two centers. Hyper-fused radiomic features (RFs) and conventional RFs were extracted from DCE-MRI or UMB-DWI.

α-Cyclodextrin supplementation improves endurance exercise performance and reduces post-exercise fatigue in human males: a randomized, double-blind, placebo-controlled, parallel-group study.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood.

Cellular cartography reveals mouse prostate organization and determinants of castration resistance.

Inadequate response to androgen deprivation therapy (ADT) frequently arises in prostate cancer, driven by cellular mechanisms that remain poorly understood. Here, we integrated single-cell RNA sequencing, single-cell multiomics, and spatial transcriptomics to define the transcriptional, epigenetic, and spatial basis of cell identity and castration response in the mouse prostate. Leveraging these data along with a meta-analysis of human prostates and prostate cancer, we identified cellular orthologs and key determinants of ADT response and resistance.

A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

Age at Menarche and Coronary Artery Disease Risk: Divergent Associations with Different Sources of Variation.

Background: In women, both earlier and later age at menarche (AAM) are associated with increased risk of coronary artery disease (CAD). This study sought to determine if the relationship of AAM with CAD and CAD risk factors differs for different underlying sources of variation in AAM - specifically, variation attributable to common genetic variants as represented by a polygenic score (PGS) vs. variation in AAM adjusted for the PGS.

MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

In HF with mildly reduced or preserved ejection fraction, finerenone reduced worsening HF or CV death at 32 mo.

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Longitudinal changes of macular neurodegenerative and vascular abnormalities on OCTA in sickle cell disease.

Purpose: To evaluate the presence and progression of maculopathy in patients with sickle cell disease (SCD) using Optical Coherence Tomography (OCT) and OCT-Angiography (OCTA), and to identify clinical/laboratory risk factors for progression during follow-up.

Methods: Complete ophthalmic examination, including fundoscopy and macular SD-OCT/OCTA scans, was performed in consecutive SCD-patients (HbSS/HbSβ0/HbSβ+/HbSC genotype) during baseline and follow-up visits. SCR stage was based on fundoscopy instead of the Goldberg classification, since fluorescein angiography was not routinely used.

High-Resolution Free-Breathing Chemical-Shift-Encoded MRI for Characterizing Lymph Nodes in the Upper Abdomen.

Objectives: Accurate lymph node (LN) staging is crucial for managing upper abdominal cancers. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging effectively distinguishes healthy and metastatic LNs through fat/water and -weighted imaging. However, respiratory motion artifacts complicate detection of abdominal LNs.

National analysis of health-related social needs among adult injury survivors.

Background: Despite advances in trauma care, the effects of social determinants of health continue to be a barrier to optimal health outcomes. Health-related social needs (HRSNs), now the basis of a Centers for Medicare and Medicaid Services national screening program, may contribute to poor health outcomes, inequities, and low-value care, but the impact of HRSNs among injured patients remains poorly understood at the national level.

Methods: Using data from the nationally representative 2021 Medical Expenditure Panel Survey, injured patients were matched with uninjured controls via coarsened exact matching on age and sex.

Comparison of Ceramic Bonding to Cobalt-Chromium, Zirconia and Nickel-Chromium Alloys Fabricated Using of Various Techniques.

The purpose of this study was to evaluate the characteristics of the ceramic bonding to cobalt-chromium (Co-Cr) alloys fabricated by casting, milling, and additive manufacturing, compared with zirconia and nickel-chromium. One hundred specimens (N = 100), prepared with the dimensions of 25 × 3 × 0.5 mm, were assigned to five groups (n = 20): presintered milled Co-Cr (Group M), additively manufactured Co-Cr (Group SLM), cast Co-Cr (Group C), presintered zirconia (Group Zi), and cast Ni-Cr (Group Ni).

Personalized Heart Digital Twins Detect Substrate Abnormalities in Scar-Dependent Ventricular Tachycardia.

Background: Current outcomes from catheter ablation for scar-dependent ventricular tachycardia (VT) are limited by high recurrence rates and long procedure durations. Personalized heart digital twin technology presents a noninvasive method of predicting critical substrate in VT, and its integration into clinical VT ablation offers a promising solution. The accuracy of the predictions of digital twins to detect invasive substrate abnormalities is unknown.

Beyond conventional characterization: Defect engineering role for sensitivity and selectivity of room-temperature UV-assisted graphene-based NO₂ sensors.

The term graphene-based gas sensors may be too broad, as there are many physicochemical differences within the graphene-based materials (GBM) used for chemiresistive gas sensors. These differences condition the sensitivity, selectivity, recovery, and ultimately the sensing performance of these devices towards air pollutants. Continuous ultraviolet irradiation aids in the desorption of gas molecules and enhances sensor performance.

Complementary and Alternative Medicine Use in the Last Year of Life: The COMPASS Cancer Cohort Study.

Context: There has been growing interest in the role of complementary and alternative medicine (CAM) as part of end-of-life care.

Objectives: This study prospectively examined the prevalence, predictors and outcomes of ingestible CAM use among cancer patients in their last year of life in Singapore.

Methods: This study (N = 427) utilized data across 12 months (four time points) prior to patient death.

Luteinizing hormone receptor deficiency in immature cumulus-oocyte complexes retrieved for assisted reproduction.

This study investigated whether luteinizing hormone receptor (LHR) expression varies in the granulosa cells of individual follicles according to the maturation stage of the oocytes harvested for assisted reproductive technology treatment. We observed minimal to no LHR messenger ribonucleic acid and protein expression in cumulus cells surrounding oocytes arrested in the germinal vesicle stage. Interestingly, their ability to mature was confirmed by rescue in vitro maturation, suggesting somatic cell LHR deficiency as a key factor for the retrieval of germinal vesicle oocytes in assisted reproductive technology procedures.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Implementing a closed loop clinical decision support system for sustainable preoperative care.

Unnecessary preoperative testing poses a risk to patient safety, causes surgical delays, and increases healthcare costs. We describe the effects of implementing a fully EHR-integrated closed-loop clinical decision support system (CDSS) for placing automatic preprocedural test orders at two teaching hospitals in Madrid, Spain. Interrupted time series analysis was performed to evaluate changes in rates of preoperative testing after CDSS implementation, which took place from September 2019 to December 2019.

Pivotal role of exogenous pyruvate in human natural killer cell metabolism.

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

Circadian clock communication during homeostasis and ageing.

Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs.

Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update.

Since the first derivation of human pluripotent stem cells (hPSCs) 27 years ago, technologies to control their differentiation and manufacturing have advanced immensely, enabling increasing numbers of clinical trials with hPSC-derived products. Here, we revew the landscape of interventional hPSC trials worldwide, highlighting available data on clinical safety and efficacy. As of December 2024, we identify 116 clinical trials with regulatory approval, testing 83 hPSC products.

Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

A safety and feasibility randomized placebo controlled trial exploring electroencephalographic effective connectivity neurofeedback treatment for fibromyalgia.

Fibromyalgia is a chronic pain condition contributing to significant disability worldwide. Neuroimaging studies identify abnormal effective connectivity between cortical areas responsible for descending pain modulation (pregenual anterior cingulate cortex, pgACC) and sensory components of pain experience (primary somatosensory cortex, S1). Neurofeedback, a brain-computer interface technique, can normalise dysfunctional brain activity, thereby improving pain and function.