Investigating the association between choroid plexus volume and the pathogenesis of Parkinson's disease.

Background And Objective: Parkinson's disease (PD) involves motor and cognitive impairments, with recent evidence suggesting that changes in choroid plexus volume (CPV) may contribute to disease progression by affecting protein accumulation in the brain. This study aims to assess the relationship between CPV and PD symptoms, and explore its potential as a biomarker for tracking disease progression.

Methods: Data from 236 newly diagnosed, untreated PD patients and 47 healthy controls were retrospectively obtained from a large (n = 412) longitudinal study of patients.

PhyloTune: An efficient method to accelerate phylogenetic updates using a pretrained DNA language model.

Understanding the phylogenetic relationships among species is crucial for comprehending major evolutionary transitions. Despite the ever-growing volume of sequence data, constructing reliable phylogenetic trees effectively becomes more challenging for current analytical methods. In this study, we introduce a new solution to accelerate the integration of novel taxa into an existing phylogenetic tree using a pretrained DNA language model.

The connection between peripheral inflammation links and functional prognosis in patients with acute ischemic stroke.

Objective: Investigate the peripheral inflammation links (PIL) as predictors of acute ischemic stroke (AIS) severity and long-term outcomes.

Methods: Analyzing AIS patient data, linear mixed and logistic regression was employed for PIL with National Institute of Health stroke scale (NIHSS) and 3, 6 and 12 months prognosis outcomes. Restricted cubic splines (RCS) were utilized to visualize the relationships between inflammation and outcomes.

DivPro: diverse protein sequence design with direct structure recovery guidance.

Motivation: Structure-based protein design is crucial for designing proteins with novel structures and functions, which aims to generate sequences that fold into desired structures. Current deep learning-based methods primarily focus on training and evaluating models using sequence recovery-based metrics. However, this approach overlooks the inherent ambiguity in the relationship between protein sequences and structures.

Analysis of clinicopathological and immunohistochemical features of pheochromocytoma/paraganglioma.

This study aimed to analyze the expression of three immune markers, succinate dehydrogenase (SDHB), S-100, and alpha thalassemia retardation syndrome X-linked (ATRX), in pheochromocytoma and paraganglioma (PPGL) tumor tissues and to evaluate their correlation with histopathological parameters to predict the recurrence risk in PPGLs. A retrospective analysis was conducted using a cohort of 173 patients with PPGLs with definite pathological diagnoses and complete follow-up data. The expression of SDHB, S-100, and ATRX in the tumor tissues was detected using the EnVision immunohistochemical method.

PAL: Boosting Skin Lesion Segmentation via Probabilistic Attribute Learning.

Skin lesion segmentation is vital for the early detection, diagnosis, and treatment of melanoma, yet it remains challenging due to significant variations in lesion attributes (e.g., color, size, shape), ambiguous boundaries, and noise interference.

LMT++: Adaptively Collaborating LLMs with Multi-specialized Teachers for Continual VQA in Robotic Surgical Videos.

Visual question answering (VQA) plays a vital role in advancing surgical education. However, due to the privacy concern of patient data, training VQA model with previously used data becomes restricted, making it necessary to use the exemplar-free continual learning (CL) approach. Previous CL studies in the surgical field neglected two critical issues: i) significant domain shifts caused by the wide range of surgical procedures collected from various sources, and ii) the data imbalance problem caused by the unequal occurrence of medical instruments or surgical procedures.

Diagnostic accuracy and pitfalls of MRI for restaging locally advanced rectal cancer in patients following anti-PD1 therapy plus neoadjuvant chemoradiotherapy: a multicenter study.

Purpose: Effectiveness of programmed cell death 1 blockade (anti-PD1) treatment plus neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer and proficient mismatch repair (pMMR-LARC) has been recently proven. However, the role of MRI in tumor restaging following anti-PD1 plus NCRT is less established. This study aims to evaluate the diagnostic performance and challenges of MRI for restaging pMMR-LARC patients after anti-PD1 plus NCRT treatment.

Gated-GPS: enhancing protein-protein interaction site prediction with scalable learning and imbalance-aware optimization.

In protein-protein interaction site (PPIS) prediction, existing machine learning models struggle with small datasets, limiting their predictive accuracy for unseen proteins. Additionally, class imbalance in protein complexes, where binding residues constitute a small fraction of all residues, hinders model performance. To address these challenges, we constructed a training dataset 9$\times $ larger than previous benchmarks by filtering the latest protein-protein complex data, improving diversity and generalization.

Electrolyte Levels in Poor Prognosis and Early Neurological Deterioration in Patients With Acute Ischemic Stroke.

Discrepancies in serum electrolyte levels have been observed between stroke patients and healthy individuals. Previous studies have indicated an association between electrolytes and all-cause mortality as well as cardiovascular events in stroke patients. However, there still lacks comprehensive analysis on the connection between electrolytes and negative outcomes in hypertensive individuals with early neurological deterioration (END).

Impact of PD1 blockade added to neoadjuvant chemoradiotherapy on rectal cancer surgery: post-hoc analysis of the randomized POLARSTAR trial.

Background: The addition of PD1 blockade to neoadjuvant chemoradiotherapy (CRT) has been shown to significantly increase pCR rates in locally advanced rectal cancer (LARC). Yet, its impact on total mesorectal excision (TME) remains unknown.

Methods: A post-hoc analysis of the randomized POLARSTAR trial, which enrolled patients with LARC at eight major colorectal cancer centres in Beijing to compare neoadjuvant CRT plus PD1 blockade with CRT alone, was undertaken.

scHeteroNet: A Heterophily-Aware Graph Neural Network for Accurate Cell Type Annotation and Novel Cell Detection.

Single-cell RNA sequencing (scRNA-seq) has unveiled extensive cellular heterogeneity, yet precise cell type annotation and the identification of novel cell populations remain significant challenges. scHeteroNet, a novel graph neural network framework specifically designed to leverage heterophily in scRNA-seq data, is presented. Unlike traditional methods that assume homophily, scHeteroNet captures complex cell-cell interactions by integrating information from both immediate and extended cellular neighborhoods, resulting in highly accurate cell representations.

Multi-Scale Spatio-Temporal Transformer-Based Imbalanced Longitudinal Learning for Glaucoma Forecasting From Irregular Time Series Images.

Glaucoma is one of the major eye diseases that leads to progressive optic nerve fiber damage and irreversible blindness, afflicting millions of individuals. Glaucoma forecast is a good solution to early screening and intervention of potential patients, which is helpful to prevent further deterioration of the disease. It leverages a series of historical fundus images of an eye and forecasts the likelihood of glaucoma occurrence in the future.

Hepatic Fibrosis Predicts the Prognosis of Patients with Acute Ischemic Stroke Through the Mediation of Cardioembolism.

Background: Hepatic fibrosis, a chronic pathological condition, is associated with adverse outcomes in stroke patients. Cardioembolism (CE) is a common etiology of stroke, yet the association between hepatic fibrosis and CE remains understudied.

Aim: This study aims to investigate the association between hepatic fibrosis and CE-induced stroke, as well as its impact on stroke patient prognosis.

SMARCB1-deficient Medullary-Like Renal Cell Carcinoma Without Gene Deletion.

High-grade renal cell carcinoma with morphology and immunophenotypic features identical to renal medullary carcinoma, occurring in a patient without evidence of sickle cell trait or disease, is proposed to be diagnosed as renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) and classified as a subtype of SMARCB1-deficient renal medullary carcinoma in the World Health Organization (WHO) 2022 edition. So far, about twelve tumors of RCCU-MP have been reported in the literature. Herein, we extend this observation to a tumor of RCCU-MP in a 39-year-old patient, morphologically similar to renal medullary carcinoma.

Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma.

Sex disparity is a hepatocellular carcinoma (HCC) hallmark, demonstrating aggressiveness and mortality more frequently in men than in women. However, the components of its basis remain largely unknown. It was identified in HCC frequent loss of heterozygosity of general transcript factor IIH subunit 2 (GTF2H2), a potential estrogen pathway gene.

Glymphatic system dysfunction as a biomarker of disease progression in Parkinson's disease: neuroimaging evidence from longitudinal cohort studies.

Background And Objective: The brain glymphatic system is involved in the clearance of misfolded α-synuclein, and the impaired glymphatic system may contribute to the progression of Parkinson's disease (PD). This study aimed to investigate the association between glymphatic function, as assessed by the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, and disease progression in PD.

Methods: One hundred thirty nine PD patients and 62 healthy controls (HCs) were enrolled in this prospective cohort study and followed up for 4 years.

Small-molecule BTK inhibitors: From discovery to clinical application.

Bruton's tyrosine kinase (BTK) inhibitors constitute a promising category of small molecules for the therapy of diverse B-cell malignancies and autoimmune disorders. This review examines the journey of BTK inhibitors from their discovery to clinical development, highlighting key milestones in their design, mechanism of action, and progression through preclinical and clinical stages. Initially identified through high-throughput screening of compound libraries, early BTK inhibitors were optimized for selectivity and potency.

Small CAG Repeat RNA Forms a Duplex Structure with Sticky Ends That Promote RNA Condensation.

Biomolecular condensation lays the foundation of forming biologically important membraneless organelles, but abnormal condensation processes are often associated with human diseases. Ribonucleic acid (RNA) plays a critical role in the formation of biomolecular condensates by mediating the phase transition through its interactions with proteins and other RNAs. However, the physicochemical principles governing RNA phase transitions, especially for short RNAs, remain inadequately understood.

Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial.

Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation-immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled.

Discovery of novel XPO1 PROTAC degraders for the treatment of acute myeloid leukemia.

Targeting XPO1 inhibition has emerged as a promising therapeutic strategy in cancer treatment. Despite the numerous XPO1 inhibitors reported to date, no XPO1 degraders have been disclosed. In this study, we reported the design, synthesis and biological characterization of small-molecule XPO1 degraders based upon the proteolysis targeting chimera (PROTAC), marking the first public disclosure of XPO1 degraders.

Longitudinal associations between cerebrospinal fluid glial activation markers, depression, and dopamine transporter availability in patients with Parkinson's disease.

Background: Depression and decreased dopamine transporter (DAT) availability are prevalent in Parkinson's disease (PD), yet early predictive biomarkers are lacking. This study investigates the longitudinal associations between cerebrospinal fluid (CSF) neuroglial activation markers, sTREM2 and YKL-40, and depression, as well as DAT availability, in PD patients.

Methods: We analyzed data from 172 PD subjects and 80 matched healthy controls from a large longitudinal study.

Clinical applications of small-molecule GABAR modulators for neurological disorders.

Gamma-aminobutyric acid type A receptor (GABAR) modulators are crucial in treating neurological and psychiatric disorders, including epilepsy, anxiety, insomnia, and depression. This review examines the synthetic approaches and clinical applications of representative small-molecule GABAR modulators. Benzodiazepines, such as Diazepam, are well-known positive allosteric modulators (PAMs) that enhance GABAR function, providing therapeutic effects but also associated with side effects like sedation and dependence.

The role of the immune system in Parkinson's disease pathogenesis: A focus on Th17 cells - A systematic review and meta-analysis.

Background: Parkinson's disease (PD) has been linked to T helper 17 (Th17) cells in prior investigations, but the evidence remains inconclusive. To gain a deeper understanding of this potential connection, we conducted a systematic review and meta-analysis.

Methods: A comprehensive search for relevant studies published up to July 8, 2023, was performed across PubMed, EMBASE, and Cochrane Library databases.