Metabolic reprogramming and macrophage expansion define ACPA-negative rheumatoid arthritis: insights from single-cell RNA sequencing.

Background: Anti-citrullinated peptide antibodies (ACPA)-negative (ACPA-) rheumatoid arthritis (RA) presents significant diagnostic and therapeutic challenges due to the absence of specific biomarkers, underscoring the need to elucidate its distinctive cellular and metabolic profiles for more targeted interventions.

Methods: Single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) and synovial tissues of patients with ACPA- and ACPA+ RA, as well as healthy controls, were analyzed. Immune cell populations were classified based on clustering and marker gene expression, with pseudotime trajectory analysis, weighted gene co-expression network analysis (WGCNA), and transcription factor network inference providing further insights.

Risk of Severe Hypoglycemia After Initiation of Noninsulin Glucose-Lowering Therapies in Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.

In this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously.

Preservation of sexual function with Optilume-a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Background: The Optilume benign prostatic hyperplasia (BPH) catheter system is a novel minimally invasive paclitaxel-coated dilation system that has demonstrated substantial and durable results in urinary flow and symptoms.

Aim: We now assess the impact of Optilume BPH procedure on sexual function.

Methods: Prior published results have described the methods of data collection during the PINNACLE study, which demonstrated durable improvement in urinary symptoms.

The efficacy of second-line chemotherapy for advanced biliary tract cancer: A systematic review and network meta-analysis.

Background: This network meta-analysis (NMA) aims to provide evidence-based guidance for selecting the second-line chemotherapy for biliary tract cancer (BTC).

Methods: A comprehensive literature search was conducted on PubMed, Cochrane, and EMBASE through July 2024. Inclusion criteria involved: (1) patients underwent second-line chemotherapy following platinum-based first-line therapy, (2) intervention/comparator groups consisted of various chemotherapeutic agents, and (3) outcomes measured as hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) in randomized controlled trials (RCTs) and cohort studies.

Trojan Horse-Like Biohybrid Nanozyme for Ameliorating Liver Ischemia-Reperfusion Injury.

Liver ischemia and reperfusion (I/R) injury is a reactive oxygen species (ROS)-related disease that occurs during liver transplantation and resection and hinders postoperative liver function recovery. Current approaches to alleviate liver I/R injury have limited effectiveness due to the short circulation time, poor solubility, and severe side effects of conventional antioxidants and anti-inflammatory drugs. Herein, a universal strategy is proposed to fabricate a Trojan horse-like biohybrid nanozyme (THBN) with hepatic-targeting capabilities.

The complexities of aeronautical transfer of acutely unwell neurosurgical patients.

Objective: Neurosurgical care is difficult to access in many scenarios. Aeromedical evacuation of acutely unwell neurosurgical patients from remote, isolated or poorly equipped locations can be considered. This article aims to provide a framework of logistical factors which deserve special consideration in the preparation of these patients for transfer.

Nanoparticles (NPs)-mediated silencing of GSTP1 expression to reverse chemoresistance for effective breast cancer therapy.

Chemotherapy remains the primary treatment modality for breast cancer (BCa) patients. However, chemoresistance commonly arises in clinical settings, contributing to poor prognosis. The development of chemoresistance is a dynamic and complex process involving the activation of oncogenes and inactivation of tumor suppressor genes.

The natural product-derived JM-9 alleviates high-fat diet-induced fatty liver in mice by targeting MD2.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), is gradually emerging as one of the most prevalent liver diseases worldwide. Previous research demonstrated the involvement of myeloid differentiation factor 2 (MD2), a co-receptor of TLR4, as a key mediator in MASLD pathogenesis. The current study identifies JM-9 as a novel MD2 inhibitor, and focuses on evaluating its potential therapeutic effects in mitigating MASLD progression.

Advancements in Frank's sign Identification using deep learning on 3D brain MRI.

Frank's sign (FS) is a diagnostic marker associated with aging and various health conditions. Despite its clinical significance, there lacks a standardized method for its identification. This study aimed to develop a deep learning model for automated FS detection in 3D facial images derived from MRI scans.

Vitamin D deficiency may accelerate cognitive decline in female apolipoprotein E ε4 non-carriers.

Background & Aims: The impact of vitamin D deficiency (VDD) on cognition remains controversial. Evidences suggest that variability based on apolipoprotein E (APOE) ε4 status and gender, given APOE ε4's influence on vitamin D metabolism and women's heightened vitamin D sensitivity. We investigated the interplay between APOE ε4, gender, and VDD in cognitive decline among older adults.

Associations between anthropogenic heat emissions and serum lipids among adults in northeastern China.

Few epidemiological studies have investigated associations between anthropogenic heat emissions (AE) and serum lipids. We recruited 15,477 adults from 33 communities in northeastern China in 2009. We estimated AE flux by using data on energy consumption and socio-economic statistics covering building, transportation, industry, and human metabolism.

Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis.

Purpose: Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis.

The Role of SIRT1-BDNF Signaling Pathway in Fluoride-Induced Toxicity for Glial BV-2 Cells.

Chronic fluorosis is often accompanied by neurological symptoms, leading to attention, memory and learning ability decline and causing tension, anxiety, depression, and other mental symptoms. In the present study, we analyzed the molecular mechanisms of SIRT1-BDNF regulation of PI3K-AKT, MAPK, and FOXO1A in F-treated BV2 cells. The cytotoxic effect of sodium fluoride (NaF) on BV2 cells was assessed using Cell Counting Kit-8 (CCK-8), crystal violet, and 5-ethynyl-2'-deoxyuridine (EdU) staining.

Designing and clinical application of a 3D-printed personalized model of a radiofrequency needle guide with a maxillary fixator for puncture of the gasserian ganglion for trigeminal neuralgia treatment.

Objective: The purpose of this study was to present a newly designed 3D-printed personalized model (3D PPM) of a radiofrequency needle guide with a maxillary fixation for gasserian ganglion (GG) puncture.

Methods: Implementation of 3D CT-guided radiofrequency therapy of the GG with and without use of 3D PPM was analyzed. The following parameters were assessed: radiation time, dose area product, air kerma reference point, pain severity during the puncture needle insertion, prosopalgia regression degree (according to visual analog scale) and the severity of facial numbness (according to the Barrow Neurological Institute scale) in the early postoperative period, and postpuncture complications.

Hypoxia Combined With Interleukin-17 Regulates Hypoxia-Inducible Factor-1α/Endothelial Nitric Oxide Synthase Expression in Pulmonary Artery Endothelial Cells.

The pathogenesis of chronic thromboembolic pulmonary hypertension may be multifactorial and requires further studies. We explored alterations in pulmonary artery endothelial cells under the hypoxic and elevated interleukin-17 conditions that are commonly present in patients with chronic thromboembolic pulmonary hypertension. We measured the serum interleukin-17 levels in 10 chronic thromboembolic pulmonary hypertension patients and 10 healthy control persons.

Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning.

Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.

A Saudi Heart Association Position Statement on Cardiovascular Diseases and Diabetes Mellitus.

Background: Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia.

Methods: A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus.

A 37-Year Retrospective Analysis Reveals a High Rate of Cutaneous Angiosarcoma of the Scalp in Okinawa, Japan.

Angiosarcoma (AS) is a rare, aggressive malignancy originating from vascular or lymphatic endothelial cells. Despite its severity, little is known about its epidemiology, and no geographical regions have previously been identified as having an exceptionally high incidence. We retrospectively analyzed medical records spanning 37 years (1987-2023) in Okinawa, Japan, identifying 135 cases of AS that were used to calculate its incidence.

The High-Affinity IL-2 Receptor Affects White Matter Damage after Cerebral Ischemia by Regulating CD8 + T Lymphocyte Differentiation.

IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencing data of ischemic brain tissue revealed that most of the high-affinity IL-2R would be expressed by CD8 + T cells, especially by a highly-proliferative subset. Interestingly, only the CD8 + T cells with high-affinity IL-2R infiltrated ischemic brain tissues, highly expressing 32 genes (including Cdc20, Cdca3/5, and Asns) and activating 7 signaling pathways (including the interferon-alpha response pathway, a key mediator in the proliferation, migration, and cytotoxicity of CD8 + T cells).

Real-world safety of maribavir: a retrospective study based on signal detection in the FDA adverse event reporting system.

Background: Maribavir is a novel antiviral agent targeting cytomegalovirus through inhibition of the UL97 protein kinase, exhibiting a distinct mechanism of action. However, limited data are available on its safety profile post-marketing.

Aim: This study aimed to evaluate the adverse events (AEs) associated with maribavir using the Food and Drug Administration's Adverse Event Reporting System (FAERS), providing insights to inform clinical practice.

Zinc, copper, copper-to-zinc ratio, and other biometals in blood serum and tumor tissue of patients with colorectal cancer.

The objective of the present study was to assess serum and cancerous tissue biometal levels in colorectal cancer (CRC) patients, and its relation to disease severity. A total of 90 CRC patients and 97 controls were involved in the present study. The level of biometals in blood serum and colon tissues (only in CRC cases) was evaluated by inductively-coupled plasma mass-spectrometry.

Inflammasome activation in melanoma progression: the latest update concerning pathological role and therapeutic value.

The progression of melanoma is a complex process influenced by both internal and external cues which encourage the transition of tumour cells, uncontrolled growth, migration, and metastasis. Additionally, inflammation allows tumours to evade the immune system, contributing to cancer development. The inflammasome, a complex of many proteins, is crucial in enhancing immune responses to external and internal triggers.

Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma.

Approximately 80% of nasopharyngeal carcinoma (NPC) patients exhibit EGFR overexpression. The overexpression of EGFR has been linked to its potential role in modulating major histocompatibility complex class I (MHC-I) molecules. We discovered that EGFR, operating in a kinase-independent manner, played a role in stabilizing the expression of SLC7A11, which subsequently inhibited MHC-I antigen presentation.