Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension.

Background: Idiopathic pulmonary hypertension (IPAH) is a rare and devastating disease often accompanied by persistent inflammation and immune responses. We aim to provide a reference atlas of neutrophils to facilitate a better understanding of cellular phenotypes and discovery of candidate genes.

Methods: Peripheral neutrophils from naive patients with IPAH and matched controls were profiled.

Local resection versus radical resection after neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer: a propensity-score matched cohort analysis.

Background: We aimed to address the shortage of evidence regarding the safety of the local resection approach by comparing long-term oncological outcomes between patients managed by local resection and those who underwent radical resection.

Methods: This was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible.

An MRI Deep Learning Model Predicts Outcome in Rectal Cancer.

Background Deep learning (DL) models can potentially improve prognostication of rectal cancer but have not been systematically assessed. Purpose To develop and validate an MRI DL model for predicting survival in patients with rectal cancer based on segmented tumor volumes from pretreatment T2-weighted MRI scans. Materials and Methods DL models were trained and validated on retrospectively collected MRI scans of patients with rectal cancer diagnosed between August 2003 and April 2021 at two centers.

Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones.

Ferroptosis, a cell death process driven by iron-dependent phospholipid peroxidation, has been implicated in various diseases. There are two major surveillance mechanisms to suppress ferroptosis: one mediated by glutathione peroxidase 4 (GPX4) that catalyzes the reduction of phospholipid peroxides and the other mediated by enzymes, such as FSP1, that produce metabolites with free radical-trapping antioxidant activity. In this study, through a whole-genome CRISPR activation screen, followed by mechanistic investigation, we identified phospholipid-modifying enzymes MBOAT1 and MBOAT2 as ferroptosis suppressors.

Association of Polymorphisms in ZFHX1B and PAX6 With Anisometropia in Chinese Children: The Hong Kong Children Eye Genetics Study.

Purpose: To identify gene variants associated with anisometropia development in children.

Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children.

HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients.

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts.

A cell transmembrane peptide chimeric M(27-39)-HTPP targeted therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, with a growing incidence and death rate worldwide. The aims and challenges of treating HCC include targeting the tumor, entering the tumor tissue, inhibiting the spread and growth of tumor cells. M27-39 is a small peptide isolated from the antimicrobial peptide cecropin (MDC), whereas HTPP is a liver-targeting, cell-penetrating peptide obtained from the circumsporozoite protein (CSP) of parasites.

Late-Onset Anti-GABA Receptor Encephalitis: Clinical Characteristics and Outcomes Differing From Early-Onset Patients.

Background And Objectives: Existing evidence indicates anti-GABA receptor encephalitis (GABAR-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABAR-E and identify predictors of favorable long-term outcomes.

Methods: This is an observational retrospective study conducted in 19 centers from China.

Utility of Six Ultrasound-Based Risk Stratification Systems in the Diagnosis of AUS/FLUS Thyroid Nodules.

Rationale And Objectives: To estimate the diagnostic performance of the currently used ultrasound (US)-based risk stratification systems (RSSs) (American Thyroid Association, American Association of Clinical Endocrinologists, American College of Endocrinology, and Association Medici Endocrinology Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules, European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults [EU-TIRADS], American College of Radiology Thyroid Imaging Reporting and Data System [ACR-TIRADS], Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules [C-TIRADS], and Thyroid Imaging Reporting and Data System Developed by Kwak et al [Kwak-TIRADS]) for atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules.

Materials And Methods: This retrospective study included 514 consecutive AUS/FLUS nodules in 481 patients with final diagnosis. The US characteristics were reviewed and classified using the categories defined by each RSS.

Machine Learning Classifier for Preoperative Prediction of Early Recurrence After Bronchial Arterial Chemoembolization Treatment in Lung Cancer Patients.

Rationale And Objectives: Bronchial arterial chemoembolization (BACE) was deemed as an effective and safe approach for advanced standard treatment-ineligible/rejected lung cancer patients. However, the therapeutic outcome of BACE varies greatly and there is no reliable prognostic tool in clinical practice. This study aimed to investigate the effectiveness of radiomics features in predicting tumor recurrence after BACE treatment in lung cancer patients.

Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool.

Objective: To assess whether an electronic health record (EHR)-based diabetes intensification tool can improve the rate of A1C goal attainment among patients with type 2 diabetes and an A1C ≥8%.

Methods: An EHR-based tool was developed and sequentially implemented in a large, integrated health system using a four-phase, stepped-wedge design (single pilot site [phase 1] and then three practice site clusters [phases 2-4]; 3 months/phase), with full implementation during phase 4. A1C outcomes, tool usage, and treatment intensification metrics were compared retrospectively at implementation (IMP) sites versus nonimplementation (non-IMP) sites with sites matched on patient population characteristics using overlap propensity score weighting.

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain.

Clinical and animal studies have shown that acupuncture may benefit controlling neuropathic pain. However, the underlying molecular mechanisms are poorly understood. In a well-established mouse unilateral tibial nerve injury (TNI) model, we confirmed the efficacy of electroacupuncture (EA) in reducing mechanical allodynia and measured methylation and hydroxy-methylation levels in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC), two cortical regions critically involved in pain processing.

Diffusion-Derived Vessel Density Computed From a Simplified Intravoxel Incoherent Motion Imaging Protocol in Pregnancies Complicated by Early Preeclampsia: A Novel Biomarker of Placental Dysfunction.

Background: Early preeclampsia is associated with significant placental hypoperfusion. We explore the diagnostic value of placental diffusion-derived vessel density (DDVD), a biomarker derived from diffusion-weighted magnetic resonance imaging, which measures in vivo vessel microperfusion, in the differential diagnosis of normal and early preeclampsia pregnancies.

Methods: This was a prospective study involving 29 controls and 17 singleton pregnancies affected by early preeclampsia.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits.

Purpose: Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA).

Design: Prospective cross-sectional study.

Methods: Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart.

CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl Model.

Background: Exposure to chronic psychological stress is a risk factor for metabolic cardiovascular disease. Given the important role of lysosomal CTSS (cathepsin S) in human pathobiology, we examined the role of CTSS in stress-related thrombosis, focusing on inflammation, oxidative stress, and apoptosis.

Methods: Six-week-old wild-type mice (CTSS) and CTSS-deficient mice (CTSS) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl)-induced carotid thrombosis surgery for morphological and biochemical studies.

Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension.

Background: Activins are novel therapeutic targets in pulmonary arterial hypertension (PAH). We therefore studied whether key members of the activin pathway could be used as PAH biomarkers.

Methods: Serum levels of activin A, activin B, α-subunit of inhibin A and B proteins, and the antagonists follistatin and follistatin-like 3 (FSTL3) were measured in controls and in patients with newly diagnosed idiopathic, heritable, or anorexigen-associated PAH (n=80) at baseline and 3 to 4 months after treatment initiation.

Effect of Training on Physicians' Palliative Care-Related Knowledge and Attitudes in Vietnam.

Context: Palliative care remains largely inaccessible in low- and middle-income countries (LMICs), and efforts to increase access are impeded by lack of training of proven effectiveness for physicians.

Objectives: To measure the effectiveness of palliative care training for Vietnamese physicians.

Methods: The palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians were studied prior to a basic course in palliative care (baseline), just after the physicians completed the course (post), and 6-18 months later (follow-up).

Brain Activation Evoked by Motor Imagery in Pediatric Patients with Complete Spinal Cord Injury.

Background And Purpose: Currently, there is no effective treatment for pediatric patients with complete spinal cord injury. Motor imagery has been proposed as an alternative to physical training for patients who are unable to move voluntarily. Our aim was to reveal the potential mechanism of motor imagery in the rehabilitation of pediatric complete spinal cord injury.

Results and lessons learned from the sbv IMPROVER metagenomics diagnostics for inflammatory bowel disease challenge.

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2).

Prevalence and Characteristics of Peripapillary Gamma Zone in Children With Different Refractive Status: The Hong Kong Children Eye Study.

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children.

Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans.

Pharmacophoric-constrained heterogeneous graph transformer model for molecular property prediction.

Informative representation of molecules is a crucial prerequisite in AI-driven drug design and discovery. Pharmacophore information including functional groups and chemical reactions can indicate molecular properties, which have not been fully exploited by prior atom-based molecular graph representation. To obtain a more informative representation of molecules for better molecule property prediction, we propose the Pharmacophoric-constrained Heterogeneous Graph Transformer (PharmHGT).