Low-Intensity Online Intervention for Mental Distress Among Help-Seeking Young People in Hong Kong: A Randomized Clinical Trial.

Importance: Mental health issues among young people are increasingly concerning. Conventional psychological interventions face challenges, including limited staffing, time commitment, and low completion rates.

Objective: To evaluate the effect of a low-intensity online intervention on young people in Hong Kong experiencing moderate or greater mental distress.

Unsupervised representation learning on high-dimensional clinical data improves genomic discovery and prediction.

Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS).

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer.

Radiation therapy (RT) is one of the primary options for clinical cancer therapy, in particular advanced head and neck squamous cell carcinoma (HNSCC). Herein, the crucial role of bromodomain-containing protein 4 (BRD4)-RAD51 associated protein 1 (RAD51AP1) axis in sensitizing RT of HNSCC is revealed. A versatile nanosensitizer (RPB7H) is thus innovatively engineered by integrating a PROteolysis TArgeting Chimeras (PROTAC) prodrug (BPA771) and hafnium dioxide (HfO) nanoparticles to downregulate BRD4-RAD51AP1 pathway and sensitize HNSCC tumor to RT.

Suppression of MUC1-Overexpressing Tumors by a Novel MUC1/CD3 Bispecific Antibody.

Mucin1 (MUC1) is abnormally glycosylated and overexpressed in a variety of epithelial cancers and plays a critical role in tumor progression. MUC1 has received remark attention as an oncogenic molecule and is considered a valuable tumor target for immunotherapy, while many monoclonal antibodies (mAbs) targeting MUC1-positive cancers in clinical studies lack satisfactory results. It would be highly desirable to develop an effective therapy against MUC1-expressing cancers.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

Background: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain.

Objective: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak.

Design: Target trial emulation study.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

Introduction: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR.

Methods: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367).

Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq).

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required.

Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

Background: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear.

Predictors of 30-day mortality after endovascular thrombectomy for large vessel occlusion in the elderly.

Objectives: Elderly acute ischemic stroke (AIS) patients (≥80 years) would have dismal clinical outcomes even after successful endovascular revascularization for large vessel occlusion (LVO) in the anterior circulation. We aimed to identify predictors of 30-day mortality after endovascular thrombectomy (EVT) in the elderly.

Materials And Methods: We included older patients who underwent EVT for AIS due to LVO within 6 h after stroke onset in the anterior circulation between 2017 and 2019.

Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.

Background: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants.

Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model.

Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage.

Somatosensory Gating Responses Are Associated with Prognosis in Patients with Migraine.

Sensory gating, a habituation-related but more basic protective mechanism against brain sensory overload, is altered in patients with migraine and linked to headache severity. This study investigated whether somatosensory (SI) gating responses determined 3-months treatment outcomes in patients with episodic migraine (EM) and chronic migraine (CM). A 306-channel magnetoencephalography (MEG) with paired-pulse stimulation paradigm was used to record their neuromagnetic responses.

Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysis.

Background: Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection.

Methods: We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections.

Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

Objective: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis.

Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China.

The novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors.

Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China.

The pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors.

Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome: SADS-TW BrS Registry.

Background: Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events.

Total White Blood Cell Count Mediated the Association Between Increased Arterial Stiffness and Risk of Type 2 Diabetes Mellitus in Chinese Adults.

Objective: Type 2 diabetes mellitus (T2DM) is known to be related to increased arterial stiffness. However, little is known about the risk of T2DM due to accelerated arterial stiffness and the underlying mechanism involved. We aimed to examine arterial stiffness, as determined by brachial-ankle pulse wave velocity (baPWV), in relation to T2DM among a community-based population and whether the association was mediated by white blood cell (WBC) counts.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

Background: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation.

Objective: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics.

Methods: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018.

Patterns of human social contact and contact with animals in Shanghai, China.

East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City.

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption.

Clinical features of 2041 human brucellosis cases in China.

Background: Human brucellosis has become a major public health problem in China. However, the available clinical data on brucellosis cases are limited.

Methods: We retrospectively reviewed medical charts of 2041 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview.