Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

Discovery of a MET-driven monogenic cause of steatotic liver disease.

Background Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about a third of adults worldwide and is projected soon to be the leading cause of cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and hepatocellular carcinoma. MASLD pathogenesis is believed to involve a combination of genetic and environmental risk factors.

Epstein-Barr virus-driven cardiolipin synthesis sustains metabolic remodeling during B cell transformation.

The Epstein-Barr virus (EBV) infects nearly 90% of adults globally and is linked to over 200,000 annual cancer cases. Immunocompromised individuals from conditions such as primary immune disorders, HIV, or posttransplant immunosuppressive therapies are particularly vulnerable because of EBV's transformative capability. EBV remodels B cell metabolism to support energy, biosynthetic precursors, and redox equivalents necessary for transformation.

Ketogenesis supports hepatic polyunsaturated fatty acid homeostasis via fatty acid elongation.

Ketogenesis is a dynamic metabolic conduit supporting hepatic fat oxidation particularly when carbohydrates are in short supply. Ketone bodies may be recycled into anabolic substrates, but a physiological role for this process has not been identified. Here, we use mass spectrometry-based C-isotope tracing and shotgun lipidomics to establish a link between hepatic ketogenesis and lipid anabolism.

chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover.

bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase-like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion.

Exploring the relationship between established HIV risk factors and depressive symptoms amongst young women without HIV in two sites in South Africa.

Purpose: Adolescent girls are at high risk for depression and human immunodeficiency virus (HIV) acquisition. Poor mental health can increase vulnerability to risky sexual behaviours. Therefore, this study aims to determine the prevalence of depressive symptomology and explore the convergence of HIV risk factors with depressive symptoms amongst cis-gender adolescent girls and young women (AGYW) in rural KwaZulu-Natal (KZN) and peri-urban Western Cape (WC) communities in South Africa.

Performance of spondyloarthritis-specific health utilities based on ASAS Health Index: an ancillary analysis from ASAS-HI validation study.

Objectives: To compare the utility values of Spondyloarthritis (SpA)-specific ASAS Health Index (U-ASAS-HI) to generic utilities and to understand the contribution of health outcomes, personal- and country-level factors to the U-ASAS-HI.

Methods: Ancillary analysis of the ASAS-HI international validation study. SpA patients who completed the ASAS-HI, 5-level EuroQol-5D (EQ-5D-5L) and Short Form-36 (SF-36) questionnaires were selected, and utilities calculated.

Establishment of a human ovarian endometrioid carcinoma cell line by constitutive expression of cyclin-dependent kinase 4, cyclin D1 and telomerase reverse transcriptase.

Only a few human ovarian endometrioid carcinoma cell lines are currently available, partly due to the difficulty of establishing cell lines from low-grade cancers. Here, using a cell immortalization strategy consisting of i) inactivation of the p16-pRb pathway by constitutive expression of mutant cyclin-dependent kinase 4 (R24C) (CDK4) and cyclin D1, and ii) acquisition of telomerase reverse transcriptase (TERT) activity, we established a human ovarian endometrioid carcinoma cell line from a 46-year-old Japanese woman. That line, designated JFE-21, has proliferated continuously for over 6 months with a doubling time of ~ 55 h.

Fibroblast transcriptomics uncovers pathogenic genomic variants in individuals with exome-negative childhood onset epilepsy.

Objective: This study aims to improve genetic diagnosis in childhood onset epilepsy with neurodevelopmental problems by utilizing RNA sequencing of fibroblasts to identify pathogenic variants that may be missed by exome sequencing and copy number variation analysis.

Methods: We enrolled 41 individuals with childhood onset epilepsy and neurodevelopmental problems who previously had inconclusive genetic testing. Fibroblast samples were cultured and analyzed using RNA sequencing to detect aberrant expression, aberrant splicing, and monoallelic expression using the Detection of RNA Outlier Pipeline (DROP) pipeline.

EZH2 inhibition enhances the activity of Carboplatin in aggressive-variant prostate cancer cell lines.

Background: Aggressive Variant Prostate Cancers (AVPCs) are incurable malignancies. Platinum-based chemotherapies are used for the palliative treatment of AVPC. The Polycomb Repressive Complex 2 (PRC2) promotes prostate cancer progression histone H3 Lysine 27 tri-methylation (H3K27me3).

Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.

Streptococcal pyogenic exotoxins (Spe proteins) secreted by (group A , GAS) are responsible for scarlet fever and streptococcal toxic shock syndrome. Most Spes are superantigens that cause excessive inflammation by activating large numbers of T cells. However, Streptococcal pyogenic exotoxin B (SpeB) is an exception, which is pro-inflammatory through its protease activity.

Synthesis and Evaluation of Benzylic F-Labeled -Biphenylalkynyl Nipecotic Acid Derivatives for PET Imaging of GABA Transporter 1.

As the main inhibitory neurotransmission system, the GABAergic system poses an interesting yet underutilized target for molecular brain imaging. While PET imaging of postsynaptic GABAergic neurons has been accomplished using radiolabeled benzodiazepines targeting the GABA receptor, the development of presynaptic radioligands targeting GABA transporter 1 (GAT1) has been unsuccessful thus far. Therefore, we developed a novel GAT1-addressing radioligand and investigated its applicability as a PET tracer in rodents.

Imaging Single Particle Profiler to Study Nanoscale Bioparticles Using Conventional Confocal Microscopy.

Single particle profiling (SPP) is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles, and lipoproteins in a single particle and high throughput manner. The initial version requires the single photon counting modules for data acquisition, which limits its adoptability. Here, we present imaging-based SPP (iSPP) that can be performed by imaging a spot over time in the common imaging mode with confocal detectors.

Persistent cross-species transmission systems dominate Shiga toxin-producing O157:H7 epidemiology in a high incidence region: A genomic epidemiology study.

Several areas of the world suffer a notably high incidence of Shiga toxin-producing . To assess the impact of persistent cross-species transmission systems on the epidemiology of O157:H7 in Alberta, Canada, we sequenced and assembled O157:H7 isolates originating from collocated cattle and human populations, 2007-2015. We constructed a timed phylogeny using BEAST2 using a structured coalescent model.

The prognostic impact of molecular classification in endometrial cancer that undergoes fertility-sparing treatment.

Objective: No biomarkers are available to predict treatment response in patients with endometrial cancers who undergo fertility-sparing treatment. Therefore, we aimed to evaluate the prognostic role of molecular classification.

Methods: Patients with endometrial cancer who underwent fertility-sparing treatment with progestins between 2005 and 2021 were retrospectively identified.

Trends in the incidence and mutational landscape of advanced uterine cancer.

Objective: The aim of this study was to examine disparities in 20-year incidence trends and mutations in advanced-stage uterine cancer in the United States, given poor survival rates.

Methods: Data were obtained from the United States Cancer Statistics for patients from 2001 to 2019 with International Federation of Gynecology and Obstetrics 2009 stage IVA and IVB uterine cancer. SEER∗Stat 8.

Comprehensive Hematological and molecular Characterization of hemoglobin Hekinan [α27(B8)Glu→Asp(α1), :c.84G > T] in a Large Thai cohort.

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.

Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC.

Impact of atrial fibrillation on productivity in working-age patients: an analysis of Swiss-AF prospective cohort study data.

Aims: We aimed to explore atrial fibrillation (AF)-induced productivity losses in working-age atrial fibrillation patients and to estimate atrial fibrillation-related indirect costs.

Methods: Between 2014 and 2017, the Swiss Atrial Fibrillation prospective cohort study (Swiss-AF) enrolled 217 working-age patients with documented atrial fibrillation. Self-reported changes in professional activity and the reasons thereof were descriptively analysed over 8 years of follow-up or until patients reached the retirement age.

Correction: Strategic design of GalNAc-helical peptide ligands for efficient liver targeting.

[This corrects the article DOI: 10.1039/D4SC05606J.].

Emotion recognition deficits in children and adolescents with autism spectrum disorder: a comprehensive meta-analysis of accuracy and response time.

Background: Autism spectrum disorder is a neurodevelopmental condition characterized by persistent challenges in social communication and restricted, repetitive behaviors. Emotion recognition deficits are a core feature of ASD, impairing social functioning and quality of life. This meta-analysis evaluates emotion recognition accuracy and response time in individuals with autism spectrum disorder compared to neurotypical individuals and those with other neurodevelopmental disorders.

Urinary Endotrophin and Long-term Outcomes in Kidney Transplant Recipients.

Background: Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR).

Methods: In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method.

Clinical validation of a biopsy-based six-gene signature prognostic for aggressive prostate cancer.

Objectives: This study aimed to clinically validate the six-gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue.

Methods: MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cancer (UPCA,  = 100). The primary outcome of adverse pathology and secondary outcomes of high primary Gleason (≥G4) and high pathological T-stage (≥T3) were assessed by likelihood ratio statistics and area under the receiver operating characteristic curves from logistic regression models; time to biochemical recurrence was assessed by likelihood ratio statistics and C-indexes from Cox proportional hazard regression models.