Mitoxantrone inhibits and downregulates ER through binding at the DBD-LBD interface.

Targeting the estrogen receptor (ER or ERα) through competitive antagonists, receptor downregulators, or estrogen synthesis inhibition remains the primary therapeutic strategy for luminal breast cancer. We have identified a novel mechanism of ER inhibition by targeting the critical interface between its DNA-binding domain (DBD) and ligand-binding domain (LBD). We demonstrate that mitoxantrone (MTO), a topoisomerase II inhibitor, binds at this previously unexplored DBD-LBD interface.

Reoperations as an Outcome Indicator for Developmental Dysplasia of the Hip Treated at Walking Age.

Background: Reoperation is a major adverse event following surgical treatment but has yet to be used as a primary outcome measure in population studies to assess current treatments for developmental dysplasia of the hip (DDH). The purpose of the present study was to explore the risk factors associated with reoperations following procedures under anesthesia ("operations") for DDH in patients between the ages of 1 and 3.00 years, with the goal of deriving treatment recommendations.

The Potential for High-Priority Care Based on Pain Through Facial Expression Detection with Patients Experiencing Chest Pain.

Background And Objective: Cardiovascular disease (CVD), one of the chronic non-communicable diseases (NCDs), is defined as a cardiac and vascular disorder that includes coronary heart disease, heart failure, peripheral arterial disease, cerebrovascular disease (stroke), congenital heart disease, rheumatic heart disease, and elevated blood pressure (hypertension). Having CVD increases the mortality rate. Emotional stress, an indirect indicator associated with CVD, can often manifest through facial expressions.

The sequence-structure-function relationship of intrinsic ERα disorder.

The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.

The Development of a System for Elbow Joint Range of Motion Measurement Based on Image Recognition and Myoelectric Signals.

After a fracture, patients have reduced willingness to bend and extend their elbow joint due to pain, resulting in muscle atrophy, contracture, and stiffness around the elbow. Moreover, this may lead to progressive atrophy of the muscles around the elbow, resulting in permanent functional loss. Currently, a goniometer is used to measure the range of motion, ROM, to evaluate the recovery of the affected limb.

Downregulation of PAX1 in OSCC Enhances Stemness and Immunosuppression via IFIT1 and PD-L1 Pathways.

Objective: Our study investigated how arecoline-induced extracellular vesicle (EV) secretion suppresses PAX1 protein production through DNA hypermethylation and examined whether PAX1 downregulation enhances cancer stemness and immunosuppression in the tumor microenvironment.

Materials And Methods: EVs were isolated from SAS/TW2.6 cancer cell lines using ultracentrifugation and identified using transmission electron microscopy.

Assessment of targets of antibody drug conjugates in SCLC.

Antibody-drug conjugate (ADC) therapy has transformed treatment for several solid tumors, including small cell lung cancer (SCLC). However, significant challenges remain, including systemic toxicity, acquired resistance, and the lack of reliable biomarkers for patient selection. To enhance the effectiveness of ADC therapies in SCLC, we focused on target selection in this study by investigating the expression of ADC targets - SEZ6, DLL3, CD276, and TACSTD2 - in cell lines and patient samples.

Gut microbes with the genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition.

Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including , the operon, and the recently identified gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored.

Biomechanical assessment of Kirschner wires integrated with a novel external fixation device for treatment of pediatric supracondylar humeral fracture: a finite element analysis.

Background: Pediatric supracondylar humeral fractures present considerable surgical challenges due to the difficulty of achieving proper fracture alignment and stable fixation while avoiding injury to the ulnar nerve. This study assesses the biomechanical performance of a novel Kirschner wire (K-wire) fixation device (KFD), designed to enhance stability and reduce complications linked to traditional K-wire configurations.

Methods: Using finite element analysis (FEA), we evaluated four fixation strategies for treatment of pediatric supracondylar humeral simple transverse fractures: crossed pin fixation, crossed pin fixation with KFD, two lateral pin fixation, and two lateral pin fixation with KFD, under various mechanical loads.

Impact of diabetes on epicardial reperfusion and mortality in a contemporary STEMI population undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

Background And Aim: Diabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic.

Methods And Results: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020.

Colchicine to prevent cardiovascular death after an acute myocardial infarction.

Background: Clinical and experimental evidence have demonstrated the protective benefits of colchicine in acute myocardial infarction (AMI) through its potential anti-inflammatory effect. However, investigations on the Asian population are limited.

Methods: This retrospective longitudinal cohort study used electronic medical records from a tertiary medical center in Taiwan.

Bimetallic NiCo Nanoparticles Embedded in Organic Group Functionalized Mesoporous Silica for Efficient Hydrogen Production from Ammonia Borane Hydrolysis.

In this study, bimetallic NiCo nanoparticles (NPs) were encapsulated within the mesopores of carboxylic acid functionalized mesoporous silica (CMS) through the chemical reduction approach. Both NaBH and NHBH were used as reducing agents to reduce the metal ions simultaneously. The resulting composite was used as a catalyst for hydrolysis of ammonia borane (NHBH, AB) to produce H.

Hardware Complication Risks in Head and Neck Cancer Patients Undergoing Reconstructive Surgery With Segmental Mandibulectomy.

Background: The primary objective of this study was to ascertain the risk factors associated with hardware complications following segmental mandibular reconstruction in head and neck cancer patients. Additionally, we sought to develop a nomogram model that enables accurate risk prediction.

Methods: Patients who underwent segmental mandibulectomy with immediate free or local regional tissue transfer between January 2016 and December 2020 were reviewed.

A randomized controlled trial evaluated the efficacy and safety of apixaban for prevention of recurrent thrombosis after thrombectomy of hemodialysis vascular access.

Dialysis vascular access thrombosis poses a substantial challenge for individuals undergoing hemodialysis. The efficacy and safety of apixaban, a direct oral coagulation factor Xa inhibitor, in preventing recurrent access thrombosis have yet to be explored. Here, a multicenter randomized control study (NCT04489849) enrolled hemodialysis patients to evaluate this who underwent successful endovascular thrombectomy within 48 hours.

Upfront Surgery Versus Upfront Concurrent Chemoradiotherapy as Primary Modality in Hypopharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Importance: The management of hypopharyngeal squamous cell carcinoma (HPSCC) continues to be one of the most formidable challenges in the realm of head and neck oncology.

Objectives: The aim of this meta-analysis was to evaluate the disparity in survival outcomes between upfront surgery and upfront concurrent chemoradiotherapy as the primary treatment modality in patients with HPSCC.

Design: Systemic review with meta-analysis.

Features and allele frequency of JAK2 Exon 12-mutated polycythemia vera in comparison with JAK2V617F-mutated disease.

Background And Aim: JAK2 exon 12 mutation status and the clinical characteristics of patients with polycythemia vera (PV) in Asia remain to be defined.

Method: We analyzed the clinical, molecular, and genetic features and outcomes of patients with PV harboring exon 12 mutation and compared them with the JAK2V617F-mutated patients in Taiwan. JAK2V617F with allele burden was measured by pyrosequencing and/or RT/qPCR.

Impact of hypertension on mortality in patients with ST-elevation myocardial infarction undergoing primary angioplasty: insights from the international multicenter ISACS-STEMI registry.

Background: Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic.

Functional connectivity compensation in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled.

Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia.

Methods: Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities.

Results: Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, and RBM43, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts.

The branched N-glycan of PD-L1 predicts immunotherapy responses in patients with recurrent/metastatic HNSCC.

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products.

Composite Polycaprolactone/Gelatin Nanofiber Membrane Scaffolds for Mesothelial Cell Culture and Delivery in Mesothelium Repair.

To repair damaged mesothelium tissue, which lines internal organs and cavities, a tissue engineering approach with mesothelial cells seeded to a functional nanostructured scaffold is a promising approach. Therefore, this study explored the uses of electrospun nanofiber membrane scaffolds (NMSs) as scaffolds for mesothelial cell culture and transplantation. We fabricated a composite NMS through electrospinning by blending polycaprolactone (PCL) with gelatin.