Canonical androgen response element motifs are tumor suppressive regulatory elements in the prostate.

The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Three-chamber electrochemical reactor for selective lithium extraction from brine.

Efficient lithium recovery from geothermal brines is crucial for the battery industry. Current electrochemical separation methods struggle with the simultaneous presence of Na, K, Mg, and Ca because these cations are similar to Li, making it challenging to separate effectively. We address these challenges with a three-chamber reactor featuring a polymer porous solid electrolyte in the middle layer.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.

Methods: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC).

Unlocking nature's brilliance: using Antarctic extremophile Shewanella baltica to biosynthesize lanthanide-containing nanoparticles with optical up-conversion.

Both lanthanide-containing and fluorine-containing nanomaterials present challenging targets for microbial biosynthesis because these elements are toxic to most bacteria. Here, we overcome these challenges by using an Antarctic Shewanella baltica strain that tolerates these elements and report the first biosynthesis of lanthanide-doped fluoride nanoparticles (NPs) from them. NaYF NPs doped with Er/Yb are prototypical lanthanide-based upconverting nanoparticles (UCNPs) with upconverted luminescence at visible wavelengths under infrared excitation.

Impact of COVID-19 Pandemic on the Prevalence of Metabolic Syndrome in Health Care Workers: A Cohort Study at a Designated COVID-19 Hospital in Taiwan.

Objectives: This cohort study aimed to determine the effect of the COVID-19 pandemic on the prevalence of metabolic syndrome (MetS) among health care workers at a dedicated COVID-19 hospital in Taiwan.

Methods: This study recruited 397 health care workers who completed health checkups before and during the COVID-19 pandemic. The differences of MetS and its components prevalence before and during the COVID-19 pandemic were compared using the paired samples t tests for normally distributed variables, and Wilcoxon signed-rank tests for nonnormally distributed variables.

Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6).

Dietary Polyphenols as Anti-Aging Agents: Targeting the Hallmarks of Aging.

Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis.

Software using artificial intelligence for nodule and cancer detection in CT lung cancer screening: systematic review of test accuracy studies.

Objectives: To examine the accuracy and impact of artificial intelligence (AI) software assistance in lung cancer screening using CT.

Methods: A systematic review of CE-marked, AI-based software for automated detection and analysis of nodules in CT lung cancer screening was conducted. Multiple databases including Medline, Embase and Cochrane CENTRAL were searched from 2012 to March 2023.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF.

Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

Purpose: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded.

Design: Prospective clinical cohort study.

Methods: Setting: Institutional.

Cost-effectiveness of incorporating self-imaging optical coherence tomography into fundus photography-based diabetic retinopathy screening.

Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening.

Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study.

Introduction: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping.

FCSU-Net: A novel full-scale Cross-dimension Self-attention U-Net with collaborative fusion of multi-scale feature for medical image segmentation.

Recently, ViT and CNNs based on encoder-decoder architecture have become the dominant model in the field of medical image segmentation. However, there are some deficiencies for each of them: (1) It is difficult for CNNs to capture the interaction between two locations with consideration of the longer distance. (2) ViT cannot acquire the interaction of local context information and carries high computational complexity.

Impact of Diabetes on Persistent Radiological Abnormalities and Pulmonary Diffusion Dysfunction in COVID-19 Survivors: A 3-Year Prospective Cohort Study.

Rationale And Objectives: Little is known about the long-term impact of diabetes on lung impairment in COVID-19 survivors over a three-year period. This study evaluated the long-term impact of diabetes on persistent radiological pulmonary abnormalities and lung function impairment in COVID-19 survivors over three years.

Materials And Methods: In this prospective, multicenter, cohort study, pulmonary sequelae were compared between COVID-19 survivors with and without diabetes.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699).

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

Background: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.

C646 degrades Exportin-1 to modulate p300 chromatin occupancy and function.

Molecular glues can induce proximity between a target protein and ubiquitin ligases to induce target degradation, but strategies for their discovery remain limited. We screened 3,200 bioactive small molecules and identified that C646 requires neddylation-dependent protein degradation to induce cytotoxicity. Although the histone acetyltransferase p300 is the canonical target of C646, we provide extensive evidence that C646 directly targets and degrades Exportin-1 (XPO1).

Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial.

Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is a major cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab is a gut-selective anti-αβ integrin monoclonal antibody that reduces gut inflammation by inhibiting migration of GI-homing T lymphocytes. The efficacy and safety of vedolizumab added to standard GVHD prophylaxis (calcineurin inhibitor plus methotrexate/mycophenolate mofetil) was evaluated for prevention of lower-GI aGVHD after unrelated donor allo-HSCT in a randomized, double-blind, placebo-controlled phase 3 trial.

Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.