Recent advancements in the understanding of the alterations in mitochondrial biogenesis in Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive memory loss and cognitive decline. The processes underlying the pathophysiology of AD are still not fully understood despite a great deal of research. Since mitochondrial dysfunction affects cellular energy metabolism, oxidative stress, and neuronal survival, it is becoming increasingly clear that it plays a major role in the development of AD.

Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway.

The inflammatory response of lung tissue and abnormal proliferation of pulmonary artery smooth muscle cells are involved in the pathogenesis of high-altitude pulmonary hypertension (HAPH). Halofuginone (HF), an active ingredient derivative of Chang Shan (Dichroa febrifuga Lour. [Hydrangeaceae]), has antiproliferative, antihypertrophic, antifibrotic, and other effects, but its protective effects on HAPH remains unclear.

Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Sacrum1-pubic angle: a novel and alternative morphologic radiological parameter for assessing spinopelvic sagittal alignment in human adults.

Objective: Spinopelvic sagittal balance ensures efficient posture and minimizes energy expenditure by aligning the spine, pelvis, and lower extremities. Deviations can cause clinical issues like back pain and functional limitations. Key radiographic parameters, including pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and lumbar lordosis (LL), are essential for evaluating spinal pathologies and planning surgeries.

Legalization of surrogacy? Opinions from more than 7700 residents in Taiwan.

This study explores Taiwanese' perspectives on the potential legalization of surrogacy, an issue with diverse legal stances globally. Conducted between 17 December 2023 and 1 January 2024, this mixed-methods cross-sectional study employed Knowledge and Attitudes of Legalizing Surrogacy (KALS) questionnaire. This instrument assessed opinions and ethical considerations on various aspects including ethics and children's rights, surrogate health, offspring welfare, and social justice.

Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.

Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run.

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.

Prognostic scores for predicting overall survival in patients with metastatic renal and urothelial cancer undergoing immunotherapy - which one to use?

Purpose: Evaluation of the prognostic significance of four different scoring systems in a real-world cohort of patients with metastatic urothelial carcinoma (mUC) or renal cell carcinoma (mRCC) undergoing immunotherapy (IO).

Methods: For 120 patients with mUC (n = 67) and mRCC (n = 53) who received IO between July 2016 and December 2020 at the tertiary Urological University Medical Centre Mannheim, the following scores were recorded at pre-treatment baseline: modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER). Overall survival (time between the beginning of IO until the patients' death or last contact) was determined for every patient.

The enlarged perivascular spaces in the hippocampus is associated with memory function in patients with type 2 diabetes mellitus.

Early detection of cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) is important for preventive measures due to the lack of effective treatments. The purpose of this study is to investigate the relationship between enlarged perivascular space in the hippocampus (H-EPVS) and cognitive performance in patients with T2DM, and to determine whether it can serve as an imaging marker for cognitive dysfunction. 66 T2DM patients with cognitive impairment (T2DM-CI) and 71 T2DM patients with normal cognitive function (T2DM-NC) underwent cranial MRI scans and comprehensive neuropsychological assessments.

TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and ranks among the most lethal malignancies globally, primarily due to its high rates of recurrence and metastasis. Despite the urgency, no reliable biomarkers currently exist for predicting tumor recurrence in HCC. Telomerase reverse transcriptase (TERT) promoter mutations (TERTpm) and cellular tumor antigen p53 mutations (TP53m) have been frequently documented in HCC, but their combined clinical significance remains undefined.

Risk factors associated with higher WHO grade in meningiomas: a multicentric study of 552 skull base meningiomas.

The histological grade is crucial for therapeutic management, and its reliable preoperative detection can significantly influence treatment approach. Lacking established risk factors, this study identifies preoperative predictors of high-grade skull base meningiomas and discusses the implications of non-invasive detection. A multicentric study was conducted on 552 patients with skull base meningiomas who underwent primary surgical resection between 2014 and 2019.

Mitochondrial dysfunction-driven AMPK-p53 axis activation underpins the anti-hepatocellular carcinoma effects of sulfane sulfur.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, notoriously refractory to conventional chemotherapy. Historically, sulfane sulfur-based compounds have been explored for the treatment of HCC, but their efficacy has been underwhelming. We recently reported a novel sulfane sulfur donor, PSCP, which exhibited improved chemical stability and structural malleability.

Artificial intelligence for image recognition in diagnosing oral and oropharyngeal cancer and leukoplakia.

Visual diagnosis is one of the key features of squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC), both subsets of head and neck squamous cell carcinoma (HNSCC) with a heterogeneous clinical appearance. Advancements in artificial intelligence led to Image recognition being introduced recently into large language models (LLMs) such as ChatGPT 4.0.

Progress in personalized immunotherapy for patients with brain metastasis.

Brain metastasis leads to poor outcomes and CNS injury, significantly reducing quality of life and survival rates. Advances in understanding the tumor immune microenvironment have revealed the promise of immunotherapies, which, alongside surgery, chemotherapy, and radiation, offer improved survival for some patients. However, resistance to immunotherapy remains a critical challenge.

Diagnostic cholangioscopy for surgical planning of extrahepatic cholangiocarcinoma.

The recent clinical outcomes of multi-regimen chemotherapy included prolonged survival and a high rate of conversion to surgery in Asian patients with advanced biliary tract cancer. The ability of single-operator cholangioscopy (SOC) to detect and stage extrahepatic cholangiocarcinoma (CCC) in intraductal lesions is becoming more important in determining the extent of surgery. The aim of this study was to evaluate the role of SOC in surgical planning for extrahepatic CCC.

Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.

Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.

Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma.

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.

A Systematic Review and Meta-analysis of the Clinical Impact of Prophylactic Quinolones with Adjuvant Bacillus Calmette-Guérin Instillation for Non-muscle-invasive Bladder Cancer.

Background And Objective: Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events.

Efficacy of Voice Therapy for Vocal Fold Masses: Avoidance of Surgery.

Introduction: Voice abuse and misuse are the most common causes of benign vocal fold lesions (BVFL). Treatment may include a combination of voice therapy, singing sessions, or surgical resection. Otolaryngologists and speech language pathologists advocate for preoperative, as well as postoperative, voice therapy.

Effect of Dexmedetomidine on Blood Loss and Patient Outcomes in Orthognathic Surgery: A Randomised Clinical Trial.

Introduction And Aims: Blood loss is a common side-effect in orthognathic surgery. Deliberated hypotensive anaesthesia can reduce blood loss. The purpose was to evaluate the effect of add-on dexmedetomidine compared with the usual hypotensive drug bolus on blood loss and patient outcomes in orthognathic surgery.

Identification of the molecular characterization and tumor microenvironment of thoracic inflammatory myofibroblastic tumors.

Background: Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs.

Primary Renal Lymphoma: A Single-Center Study of 14 Cases.

Objective: To investigate the clinical characteristics, pathology, imaging features, and prognosis of primary renal lymphoma (PRL), a rare malignancy.

Patients And Method: We conducted a retrospective review of 14 PRL cases diagnosed between January 2009 and January 2022, with follow-up data collected from medical records.

Results: The study included 14 patients (7 males, 7 females), with a mean age of 60.

PMP2+ Schwann cells maintain the survival of large-caliber motor axons.

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons.