Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models - Of mice and men.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties.

Frontal plane mechanical leg alignment estimation from knee x-rays using deep learning.

Objective: Lower limb malalignment can complicate symptoms and accelerate knee osteoarthritis (OA), necessitating consideration in study population selection. In this study, we develop and validate a deep learning model that classifies leg alignment as "normal" or "malaligned" from knee antero-posterior (AP)/postero-anterior (PA) radiographs alone, using an adjustable hip-knee-ankle (HKA) angle threshold.

Material And Methods: We utilized 8878 digital radiographs, including 6181 AP/PA full-leg x-rays (LLRs) and 2697 AP/PA knee x-rays (2292 with positioning frame, 405 without).

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

New Directions for Ophthalmic OCT - Handhelds, Surgery, and Robotics.

The introduction of optical coherence tomography (OCT) in the 1990s revolutionized diagnostic ophthalmic imaging. Initially, OCT's role was primarily in the adult ambulatory ophthalmic clinics. Subsequent advances in handheld form factors, integration into surgical microscopes, and robotic assistance have expanded OCT's utility and impact outside of its initial environment in the adult outpatient ophthalmic clinic.

Validation Status of Electronic Sphygmomanometers in China: A National Survey.

Background: Although the information on the validation status of electronic sphygmomanometer (ES) devices in use in health care institutions and households is much more clinically relevant than that of ES models available on the market, it remains insufficient.

Methods: A national survey was conducted across all administrative regions of mainland China to assess the validation status of ESs. Fifty-eight cities were selected with stratification by municipality, provincial capital, and other cities, and health care institutions and households in each city were chosen by convenience to identify ES devices in use according to the study protocol.

CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

Patient and Healthcare Professional Perspectives on Crohn's Perianal Fistula Treatment: Results From a Discrete Choice Experiment.

Background: Crohn's perianal fistulas (CPF) are difficult to manage and often require multiple interventions. This study aimed to assess the preferences of patients and healthcare professionals (HCPs) for attributes of CPF-related procedures/surgeries to better inform CPF management.

Methods: This US cross-sectional, observational study was conducted via a web-enabled questionnaire (October 2021-January 2022) among patients aged 21-89 years with a self-reported physician diagnosis of CPF (with or without CPF-related surgery experience) and HCPs (gastroenterologists and colorectal surgeons who managed ≥3 patients with CPF in the past 12 months).

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Reaction kinetics and molecular characterization of the compounds formed by photosensitized degradation of the plastic additive bisphenol A in the atmospheric aqueous phase.

Bisphenol A (BPA, 4,4'-(propane-2,2-diyl)diphenol) is a common plasticizer that is very widespread in the environment and is also found at significant concentrations in the global oceans, due to contamination by plastics. Here we show that triplet sensitization is an important degradation pathway for BPA in natural surface waters, which could prevail if the water dissolved organic carbon is above 2-3 mg L. Bromide levels as per seawater conditions have the potential to slow down BPA photodegradation, a phenomenon that could not be offset by reaction of BPA with Br (second-order reaction rate constant of (2.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Global Fatty Degeneration Index on Preoperative Magnetic Resonance Imaging Predicts Early Postoperative Shoulder Stiffness at 3 Months After Primary Rotator Cuff Repair.

Purpose: To determine whether the fatty infiltration of rotator cuff muscles, as measured by magnetic resonance imaging (MRI) preoperatively and assessed using the Goutallier fatty degeneration index (GFDI), can predict early postoperative shoulder stiffness (POSS) after rotator cuff repair (RCR).

Methods: This retrospective longitudinal cohort study included patients who underwent primary RCR, had available medical records, and underwent MRI before RCR between November 2012 and July 2022. Patients were excluded on the basis of the following criteria: (1) preoperative shoulder stiffness, (2) additional procedures (e.

Identification of plasma protein biomarkers for endometriosis and the development of statistical models for disease diagnosis.

Study Question: Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis?

Summary Answer: A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis.

What Is Known Already: Endometriosis poses intricate medical challenges for affected individuals and their physicians, yet diagnosis currently takes an average of 7 years and normally requires invasive laparoscopy. Consequently, the need for a simple, accurate non-invasive diagnostic tool is paramount.

Favorable Outcomes of Patients With High-Risk Uveal Melanoma Treated With a Novel Linear Accelerator-Based Frameless Fractionated Stereotactic Radiosurgery.

Purpose: Uveal melanoma (UM) represents the most prevalent and aggressive intraocular malignancy in adults. This study examined the outcomes of patients diagnosed with high-risk UM who underwent fractionated stereotactic radiosurgery (fSRS) treatment utilizing a novel Linear Accelerator (LINAC)-based frameless technique.

Design: Retrospective, interventional case series.

Comparative Efficacy of Non-contrast vs. Contrast-enhanced CT Radiomics in Predicting Coronary Artery Plaques Among Patients with Low Agatston Scores.

Rationale And Objectives: Patients with a low Agatston score often present with clinical signs and symptoms suggestive of coronary artery disease, despite having minimal calcium deposits. This study aimed to compare the efficacy of low-dose non-contrast cardiac CT with coronary computed tomography angiography (CCTA) in pericoronary adipose tissue (PCAT) radiomics for predicting coronary artery plaques, using CCTA as the reference standard.

Materials And Methods: This retrospective study analyzed 459 patients with suspected coronary artery disease and a coronary artery calcium score < 100 Agatston units, who were treated between June 2021 and December 2023 at a tertiary hospital.

Characterization and Safety Evaluation of Autoclaved Gut Commensal RV-01.

Gut commensals play important roles in maintaining the homeostasis of human health. Previous studies indicated that the abundance of in animal hosts was increased by the administration of prebiotics such as polysaccharides purified from iconic oriental medicinal fungi. Subsequently, was found to exert beneficial effects on the amelioration of multiple chronic inflammation-associated diseases.

Prognostic Value of Coronary CT Angiography-Derived Quantitative Flow Ratio in Suspected Coronary Artery Disease.

Background The prognostic value of coronary CT angiography (CTA)-derived quantitative flow ratio (CT-QFR) remains unknown. Purpose To determine the prognostic value of CT-QFR in predicting the long-term outcomes of patients with suspected coronary artery disease (CAD) in comparison with invasive coronary angiography (ICA)/SPECT and to determine the influence of prior percutaneous coronary intervention (PCI) on the prognostic value of CT-QFR. Materials and Methods In this secondary analysis of the prospective international CORE320 study, 379 participants who underwent coronary CTA and SPECT within 60 days before ICA between November 2009 and July 2011 were included for follow-up.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Clinical Classification and Management Outcomes of Anterior Segment-Dominated Persistent Fetal Vasculature: The CCPMOH Report.

Purpose: To describe clinical features, management, and outcomes of anterior segment-dominated persistent fetal vasculature (aPFV).

Design: A secondary analysis of aPFV data from a longitudinal cohort study.

Methods: The age and gender of each participant upon initial presentation, along with biological parameters, best-corrected visual acuity, and biomicroscopic assessments were collected.