Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Microglia-Impaired Phagocytosis Contributes to the Epileptogenesis in a Mouse Model of Dravet Syndrome.

Dravet syndrome (DS) is a genetic disorder caused by a deficit in the Nav1.1 channel, leading to drug-resistant epilepsy. The Nav1.

Zeolite membrane with sub-nanofluidic channels for superior blue energy harvesting.

Blue energy, a clean energy source derived from salinity gradients, has recently drawn increased research attention. It can be harvested using charged membranes, typically composed of amorphous materials that suffer from low power density due to their disordered structure and low charge density. Crystalline materials, with inherently ordered porous structures, offer a promising alternative for overcoming these limitations.

Further Evidence of Anthropogenic Impact: High Levels of Multiple-Antimicrobial-Resistant Bacteria Found in Neritic-Stage Sea Turtles.

Background/objectives: Marine turtles are globally threatened and face daily anthropogenic threats, including pollution. Water pollution from emerging contaminants such as antimicrobials is a major and current environmental concern.

Methods: This study investigated the phenotypic antimicrobial resistance and heavy metal resistance genes of 47 isolates from different stages of sea turtles (oceanic stage vs neritic stage) from the Taiwanese coast.

Oncolytic avian reovirus-sensitized tumor infiltrating CD8 T cells triggering immunogenic apoptosis in gastric cancer.

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway.

Abnormal increased mTOR signaling regulates seizure threshold in Dravet syndrome.

Excessive activation of mTOR has been observed in the brains of mouse models for Dravet syndrome. We aim to confirm whether that the overactivation of mTOR contributes to the neuropathological changes leading to epileptogenesis and neurobehavior deficits to support a novel pharmacological therapeutic approach for Dravet syndrome. The mTOR inhibitor everolimus, as a clinical antiseizure medication, was utilized to investigate whether mTOR is involved in hyperthermia-induced seizures, anxiety-like, and autism-like behaviors, as well as to explore potential pathogenic mechanisms in Scn1a mice, a model of Dravet syndrome.

Characteristics and transcriptional regulators of spontaneous epithelial-mesenchymal transition in genetically unperturbed patient-derived non-spindled breast carcinoma.

Background: Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored.

Methods: We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma.

Effect of Parental Severe Mental Disorders on the Timing of Autism Diagnosis: A Family Linkage Study.

The mean diagnosis age of autism was about 5 years in Taiwan. Whether the delayed diagnosis of autism (≥ 6 years) was associated with parental severe mental disorders remained unknown. The parents of 22,859 autistic individuals and 228,590 age- and sex-matched nonautistic individuals were assessed for the presence of severe mental disorders (schizophrenia, bipolar disorder, major depressive disorder, alcohol use disorder, and substance use disorder).

Electrophysiological functional connectivity and complexity reflecting cognitive processing speed heterogeneity in young children with ADHD.

Early intervention is imperative for young children with attention-deficit/hyperactivity disorder (ADHD) who manifest heterogeneous neurocognitive deficits. The study investigated the functional connectivity and complexity of brain activity among young children with ADHD exhibiting a fast cognitive processing speed (ADHD-F, n = 26), with ADHD exhibiting a slow cognitive processing speed (ADHD-S, n = 17), and typically developing children (n = 35) using wireless electroencephalography (EEG) during rest and task conditions. During rest, compared with the typically developing group, the ADHD-F group displayed lower long-range intra-hemispheric connectivity, while the ADHD-S group had lower frontal beta inter-hemispheric connectivity.

Impact of the Ottawa model on opiate screening and smoking cessation in methadone-treated patients with opioid use disorder: A retrospective cohort analysis.

Introduction: Approximately 60 million individuals worldwide used opioids in 2021, constituting 1.2% of the global adult population. This study aimed to evaluate the effectiveness of integrated treatment strategies for opioid use disorder and nicotine use disorder by assessing the impact of smoking cessation within a methadone treatment framework.

Covalent Organic Framework Membranes with Patterned High-Density Through-Pores for Ultrafast Molecular Sieving.

The creation of uniformly molecular-sized through-pores within polymeric membranes and the direct evidence of these pores are essential for fundamentally understanding the transport mechanism and improving separation efficiency. Herein, we report an electric-field-assisted interface synthesis approach to fabricating large-area covalent organic framework (COF) membranes that consist of preferentially oriented single-crystalline COF domains. These single-crystalline frameworks were translated into high-density, vertically aligned through-pores across the entire membrane, enabling the direct visualization of membrane pores with an ultrahigh resolution of 2 Å using the low-dose high-resolution transmission electron microscopy technique (HRTEM).

Concurrent epirubicin and trastuzumab use increases complete pathological response rate without additional cardiotoxicity in patients with human epidermal growth factor receptor 2-positive early breast cancer: A meta-regression analysis.

Background: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC).

Methods: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

Objective: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning.

Association between alcohol consumption and chronic kidney disease: a population-based survey.

Background: Alcohol consumption is associated with both beneficial and harmful effects, and the role of alcohol consumption in chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the relationship between alcohol consumption and CKD or estimated glomerular filtration rate (eGFR).

Methods: This study enrolled adults from the second Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and Hyperlipidemia, conducted in 2007.

Quantifying payloads of antibody‒drug conjugates using a postcolumn infused-internal standard strategy with LC‒MS.

Background: Antibody‒drug conjugates (ADCs) are innovative biopharmaceutics consisting of a monoclonal antibody, linkers, and cytotoxic payloads. Monitoring circulating payload concentrations has the potential to identify ADC toxicity; however, accurate quantification faces challenges, including low plasma concentrations, severe matrix effects, and the absence of stable isotope-labeled internal standards (SIL-IS) for payloads and their derivatives. Previous studies used structural analogs as internal standards, but different retention times between structural analogs and target analytes may hinder effective matrix correction.

Tau and delirium superimposed on dementia: A case report.

We present a case involving a 60-year-old man with subacute delirium characterized by challenging attention shifts and obstinate behavior, contrasting with his usual mild-mannered personality. The patient developed pneumonia and a urinary tract infection following the onset of subacute delirium. Despite exhaustive investigations, the cause remained elusive until cerebrospinal fluid analysis revealed Tau positivity.

Incidence and predictors of acute kidney injury after elective surgery for lumbar degenerative disease: A 13-year analysis of the US Nationwide Inpatient Sample.

Background: Acute kidney injury (AKI) is a severe postoperative complication associated with poor clinical outcomes, including the development of chronic kidney disease (CKD) and death. This study aimed to investigate the incidence and determinants of AKI following elective surgeries for degenerative lumbar spine disease.

Methods: All patient data were extracted from the US Nationwide Inpatient Sample database.

Optimizing methadone dose adjustment in patients with opioid use disorder.

Introduction: Opioid use disorder is a cause for concern globally. This study aimed to optimize methadone dose adjustments using mixed modeling and machine learning.

Methods: This retrospective study was conducted at Taichung Veterans General Hospital between January 1, 2019, and December 31, 2020.

Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats.

Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear.

Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake.

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown.

Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome.

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1a mice).