Adding checkpoint inhibitors to first-line chemotherapy for NUT carcinoma patients.

Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.

Comparative analysis of efficacy and quality of life between totally extraperitoneal sublay and intraperitoneal onlay mesh repair for ventral hernia.

Ventral hernias pose a prevalent challenge in abdominal wall surgery, with ongoing advancements in repair techniques designed to enhance patient outcomes. This study evaluates the efficacy, safety, and socio-economic impact of Totally Extraperitoneal Sublay Repair (TES) versus Laparoscopic Intraperitoneal Onlay Mesh Repair (IPOM) for small to medium-sized ventral hernias, with a particular focus on postoperative quality of life and patient satisfaction. A retrospective cohort study was conducted, encompassing 125 patients who underwent ventral hernia repair between May 2018 and November 2023.

Machine Learning-Based predictive model for adolescent metabolic syndrome: Utilizing data from NHANES 2007-2016.

Metabolic syndrome (Mets) in adolescents is a growing public health issue linked to obesity, hypertension, and insulin resistance, increasing risks of cardiovascular disease and mental health problems. Early detection and intervention are crucial but often hindered by complex diagnostic requirements. This study aims to develop a predictive model using NHANES data, excluding biochemical indicators, to provide a simple, cost-effective tool for large-scale, non-medical screening and early prevention of adolescent MetS.

Adjusting on-scene CPR duration based on transport time interval in out-of-hospital cardiac arrest: a nationwide multicenter study.

The optimal duration of on-scene cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) patients remains uncertain. Determining this critical time period requires outweighing the potential risks associated with intra-arrest transport while minimizing delays in accessing definitive hospital-based treatments. This study evaluated the association between on-scene CPR duration and 30-day neurologically favorable survival based on the transport time interval (TTI) in patients with OHCA.

Deep learning classification of MGMT status of glioblastomas using multiparametric MRI with a novel domain knowledge augmented mask fusion approach.

We aimed to build a robust classifier for the MGMT methylation status of glioblastoma in multiparametric MRI. We focused on multi-habitat deep image descriptors as our basic focus. A subset of the BRATS 2021 MGMT methylation dataset containing both MGMT class labels and segmentation masks was used.

Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice.

In most patients with type 1 xanthinuria caused by mutations in the xanthine dehydrogenase gene (XDH), no clinical complications, except for urinary stones, are observed. In contrast, all Xdh(- / -) mice die due to renal failure before reaching adulthood at 8 weeks of age. Hypoxanthine or xanthine levels become excessive and thus toxic in Xdh(- / -) mice because enhancing the activity of hypoxanthine phosphoribosyl transferase (HPRT), which is an enzyme that uses hypoxanthine as a substrate, slightly increases the life span of these mice.

Oocytes with impaired meiotic maturation contain increased mtDNA deletions.

Purpose: Induction of meiotic competence is a major goal of the controlled ovarian stimulation used in ART. Do factors intrinsic to the oocyte contribute to oocyte maturation? Deletions in mtDNA accumulate in long-lived post mitotic tissues and are found in human oocytes. If oogenesis cleanses the germline of deleterious deletions in mtDNA, meiotically competent oocytes should contain lower levels of mtDNA deletions vs.

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.

Left atrial shunting devices: why, what, how, and… when?

Left atrial (LA) hypertension is central in the pathophysiology of heart failure (HF) in general and of HF with preserved ejection fraction (HFpEF) in particular. Despite approved treatments, a number of HF patients continue experiencing disabling symptoms due to LA hypertension, causing pulmonary congestion, pulmonary hypertension, and right heart dysfunction, at rest and/or during exercise. LA decompression therapies, i.

Targeting aldehyde dehydrogenase ALDH3A1 increases ferroptosis vulnerability in squamous cancer.

Ferroptosis is a unique modality of regulated cell death induced by excessive lipid peroxidation, playing a crucial role in tumor suppression and providing potential therapeutic strategy for cancer treatment. Here, we find that aldehyde dehydrogenase-ALDH3A1 tightly links to ferroptosis in squamous cell carcinomas (SCCs). Functional assays demonstrate the enzymatic activity-dependent regulation of ALDH3A1 in protecting SCC cells against ferroptosis through catalyzing aldehydes and mitigating lipid peroxidation.

Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.

Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle in a haystack at the genetic level. In cancer research, gene mutations are closely related to tumor development, metastasis, and recurrence, and the use of state-of-the-art powerful screening technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), to search for the most critical genes or coding products provides us with a new possibility to further refine the cancer mapping and provide new possibilities for the treatment of cancer patients. The use of CRISPR screening for the most critical genes or coding products has further refined the cancer atlas and provided new possibilities for the treatment of cancer patients.

Basic Considerations for Data Pooling Strategy in Multi-Regional Clinical Trials (MRCTs).

The National Medical Products Administration of China has been implementing ICH E17, which describes the general principles for planning and designing of multi-regional clinical trials (MRCTs), yet there are several ambiguities in the execution and conduct remains in China or East Asia. In specific, pooling strategy, effect modifiers (EMs), statistical analysis, sample size allocation and their impact in alignment with global trial remains a challenge. In this paper, we explore on the criteria mentioned above under the context of China.

The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer.

An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs).

Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

The Receptor for Advanced Glycation End-products in the Mouse Anterior Cingulate Cortex is Involved in Neuron‒Astrocyte Coupling in Chronic Inflammatory Pain and Anxiety Comorbidity.

Previous studies have shown that astrocyte activation in the anterior cingulate cortex (ACC), accompanied by upregulation of the astrocyte marker S100 calcium binding protein B (S100B), contributes to comorbid anxiety in chronic inflammatory pain (CIP), but the exact downstream mechanism is still being explored. The receptor for advanced glycation end-products (RAGE) plays an important role in chronic pain and psychosis by recognizing ligands, including S100B. Therefore, we speculate that RAGE may be involved in astrocyte regulation of the comorbidity between CIP and anxiety by recognizing S100B.

A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a prevalent urinary system disorder. Despite evidence of a significant genetic component from previous studies, the specific pathogenic genes and biological mechanisms are still largely unknown. The study utilized the FinnGen R10 dataset, encompassing 177,901 individuals (36,601 cases and 141,300 controls), and the GTEx v8 EQTLs files to conduct single-tissue and cross-tissue transcriptome-wide association studies (TWAS).

The posterior cruciate ligament angle in the setting of anterior cruciate ligament deficient knees: the effect of gender, age, time from injury and tibial slope.

Purpose: This study aimed to assess the posterior cruciate ligament (PCL) angle in anterior cruciate ligament (ACL) deficient knees and correlate it with anatomical and demographic factors such as tibial slope, anterior tibial translation, age, gender, and time of injury.

Material And Methods: Patients were eligible for inclusion if they were clinically diagnosed with an ACL tear confirmed by MRI. For each patient, the following parameters were evaluated: PCL angle (PCLA), medial tibial slope (MTS), lateral tibial slope (LTS), medial anterior tibial translation (MATT), and lateral anterior tibial translation (LATT).

Abnormal neural circuits and altered brain network topological properties in patients with persistent postural-perceptual dizziness.

Persistent Postural-Perceptual Dizziness (PPPD) is a common cause of chronic vestibular syndrome. Although previous studies have identified central abnormalities in PPPD, the specific neural circuits and the alterations in brain network topological properties, and their association with dizziness and postural instability in PPPD remain unclear. This study includes 30 PPPD patients and 30 healthy controls.

Cardiovascular disease risk in Korean patients with systemic lupus erythematosus compared to diabetes mellitus and the general population.

To evaluate the incidence and risk of cardiovascular disease (CVD) among Korean patients with systemic lupus erythematosus (SLE) comparing them to diabetes patients and the general population. This nationwide cohort study focused on incident SLE patients aged over 40 years, matched with diabetes patients and the general population (1:4:4 ratio). CVD was defined as ischaemic heart disease, ischaemic stroke, and cardiac arrest.

Genetic association of lipid-lowering drug target genes with pancreatic cancer: a Mendelian randomization study.

Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and that lipid-lowering drugs may reduce the risk of PC. However, it is not clear whether dyslipidemia causes PC. The Mendelian randomization (MR) study aimed to investigate the causal role of lipid traits in pancreatic cancer and to assess the potential impact of lipid-lowering drug targets on pancreatic cancer.

Comparison of the diagnostic performance of non-contrast MR angiography and planar V/Q scintigraphy for pulmonary embolism: a systematic review and meta-analysis.

Objectives: To conduct a meta-analysis of the diagnostic performance of non-contrast magnetic resonance pulmonary angiography (NC-MRPA) and ventilation-perfusion (V/Q) scintigraphy for the detection of acute pulmonary embolism (PE).

Materials And Methods: Systematic searches of electronic databases were conducted from 2000 to 2024. Primary outcomes were per-patient sensitivity and specificity of NC-MRPA and V/Q scintigraphy.

Consumer-grade wearable devices in arrhythmia diagnostics for clinicians: where we are and where we are going.

Atrial arrhythmias, including atrial fibrillation (AF), are a major contributor to cardiovascular morbidity and mortality. Early detection and effective management are critical to mitigating adverse outcomes such as stroke, heart failure, and overall mortality. Wearable devices have emerged as promising tools for monitoring, detecting, and managing atrial arrhythmias near-continuously.

Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer.

Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro.