Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.

Inhibition of CD36 ameliorates mouse spinal cord injury by accelerating microglial lipophagy.

Spinal cord injury (SCI) is a serious trauma of the central nervous system (CNS). SCI induces a unique lipid-dense environment that results in the deposition of large amounts of lipid droplets (LDs). The presence of LDs has been shown to contribute to the progression of other diseases.

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.

Leveraging survival analysis and machine learning for accurate prediction of breast cancer recurrence and metastasis.

Breast cancer, with its high incidence and mortality globally, necessitates early prediction of local and distant recurrence to improve treatment outcomes. This study develops and validates predictive models for breast cancer recurrence and metastasis using Recurrence-Free Survival Analysis and machine learning techniques. We merged datasets from the Molecular Taxonomy of Breast Cancer International Consortium, Memorial Sloan Kettering Cancer Center, Duke University, and the SEER program, creating a comprehensive dataset of 272, 252 rows and 23 columns.

VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis.

Ferroptosis is a form of iron-dependent programmed cell death, which is distinct from apoptosis, necrosis, and autophagy. Mitochondria play a critical role in initiating and amplifying ferroptosis in cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded in the mitochondrial outer membrane, exerts roles in regulation of ferroptosis.

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.

Prospective, crossover, comparative study of two methods of chlorhexidine bathing.

Background: Bathing intensive care unit (ICU) patients with chlorhexidine gluconate (CHG) decreases healthcare-associated infections (HAIs). The optimal method of CHG bathing remains undefined.

Methods: Prospective crossover study comparing CHG daily bathing with 2% CHG-impregnated cloths versus 4% CHG solution.

Posterior urethral valves: Examining the relationship of socioeconomic factors in disease presentation and progression.

Introduction: A significant portion of posterior urethral valve patients continue to progress to end stage renal disease despite improvements in medical care. Socioeconomic status has been connected to various healthcare outcomes but has not been evaluated in relation to longitudinal outcomes of posterior urethral valves.

Objective: To evaluate the effect of socioeconomic status on the progression to renal failure among patients with posterior urethral valves.

Temporary mechanical circulatory support utilization and outcomes in cardiogenic shock phenotypes: A comparative analysis of heart failure and acute myocardial infarction.

Introduction: Cardiogenic shock (CS) is marked by substantial morbidity and mortality. The two major CS etiologies include heart failure (HF) and acute myocardial infarction (AMI). The utilization trends of mechanical circulatory support (MCS) and their clinical outcomes are not well described.

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.