Genomic Evolution and Phylodynamics of the Species (Marburg and Ravn Viruses) to Understand Viral Adaptation and Marburg Virus Disease's Transmission Dynamics.

In this review, we investigated the genetic diversity and evolutionary dynamics of the species that includes both Marburg virus (MARV) and Ravn virus (RAVV). Using sequence data from natural reservoir hosts and human cases reported during outbreaks, we conducted comprehensive analyses to explore the genetic variability, constructing haplotype networks at both the genome and gene levels to elucidate the viral dynamics and evolutionary pathways. Our results revealed distinct evolutionary trajectories for MARV and RAVV, with MARV exhibiting higher adaptability across different ecological regions.

A Core Outcome Set for Adult General ICU Patients.

Objectives: Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers.

Development of point-of-care tests for urinary bladder cancer - an historic review and view to future prospectives.

Urine is an attractive biospecimen for noninvasive tests to facilitate bladder tumor diagnostics. Three different point-of-care (POC) tests based on lateral flow immunoassays (LFAs) are currently commercially available: UBC® Rapid Test, BTA stat®, and NMP22 BladderChek. The present review discusses these different tests based on their performance, clinical utility and the nature of the respective analytes.

Dbi1 is an oxidoreductase and an assembly chaperone for mitochondrial inner membrane proteins.

Import and assembly of mitochondrial proteins into multimeric complexes are essential for cellular function. Yet, many steps of these processes and the proteins involved remain unknown. Here, we identify a novel pathway for disulfide bond formation and assembly of mitochondrial inner membrane (IM) proteins.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.

Background: Sorafenib is a first-line treatment for hepatocellular carcinoma (HCC); however, acquired resistance often results in a poor prognosis, indicating a need for more effective therapies. Sorafenib induces cell death through an iron-dependent mechanism known as ferroptosis, which is closely associated with the onset and progression of HCC.

Methods: This study investigated the role of ACSL3 in sorafenib resistance and ferroptosis in HCC.

Factors associated with retention and adherence on Pre-Exposure Prophylaxis among men who have sex with men in Kigali, Rwanda.

Pre-Exposure Prophylaxis (PrEP) is recommended as an HIV prevention measure for men who have sex with men (MSM). We assessed factors associated with PrEP retention and adherence among MSM in Kigali, Rwanda. We undertook a retrospective cross-sectional study and used a questionnaire to obtain PrEP retention and adherence history from MSM enrolled in the key population (KP) program that attended scheduled follow-up clinics from four (4) health facilities between April 2021 to June 2021.

Differentiation status determines the effects of IFNγ on the expression of PD-L1 and immunomodulatory genes in melanoma.

Background: Melanoma cells frequently dedifferentiate in response to inflammation which can increase responses to certain cytokines. Interferon-γ (IFNγ) is an integral part of the anti-tumor immune response and can directly induce both differentiational changes and expression of immunosuppressive proteins in melanoma cells. How the differentiation status of melanoma cells affects IFNγ responses remains unclear.

Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.

Introduction: Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E.

The factors associated with teenage pregnancy among young women aged between 15 and 19 years in Rwanda: a retrospective cross-sectional study on the Rwanda Demographic Health Survey 2019-2020.

Background: Teenage pregnancy is a significant public health issue and is strongly associated with risky sexual behaviors such as early sexual initiation, unprotected sex, and multiple sexual partners. According to the 2014 World Health Organization report, 11% of all births worldwide were to teenagers aged 15-19 years, with more than 95% of these pregnancies occurring in low- and middle-income countries, particularly in sub-Saharan Africa, which bears much of this burden. In Rwanda, the prevalence of teenage pregnancy has risen from 4.

Serum lipid profiling reveals characteristic lipid signatures associated with stroke in patients with leukoaraiosis.

Many lipid biomarkers of stroke have been identified, but the lipid metabolism in elderly patients with leukoaraiosis remains poorly understood. This study aims to explore lipid metabolic processes in stroke among leukoaraiosis patients, which could provide valuable insights for guiding future antithrombotic therapy. In a cohort of 215 individuals undergoing MRI, 13 stroke patients were matched with controls, and 48 stroke patients with leukoaraiosis were matched with 40 leukoaraiosis patients.

Chemoenzymatic Formation of Oxa-Terpenoids by Sesqui- and Diterpene Synthase-Mediated Biotransformations with 9-Oxy-FPP Ether Derivatives.

Farnesyl pyrophosphate derivatives bearing an additional oxygen atom at position 5 proved to be very suitable for expanding the substrate promiscuity of sesquiterpene synthases (STSs) and the formation of new oxygenated terpenoids. Insertion of an oxygen atom in position 9, however, caused larger restraints that led to restricted acceptance by STSs. In order to reduce some of the proposed restrictions, two FPP-ether derivatives with altered substitution pattern around the terminal olefinic double bond were designed.

Evidence-Based Guidance for One Health Preparedness, Prevention, and Response Strategies to Marburg Virus Disease Outbreaks.

Objectives: Marburg virus disease (MVD) is on the WHO list for pandemic-prone pathogens. The current outbreak in Rwanda provides an opportunity to map outbreaks and generate information to inform policymaking, resource mobilization, and guide the implementation of cost-effective response strategies.

Methods: We synthesized available information about MVD to build holistic, up-to-date evidence to inform policymakers, public health leaders, and healthcare and public health services providers in their development and implementation of cost-effective preparedness, prevention, and control measures.

One-Step Nucleic Acid Amplification Analysis of Sentinel Nodes in Endometrial Cancer Versus Ultrastaging: First Long-Term Follow-Up Data of Discordant Cases.

Aims: Endometrial cancer (EC) is the most common gynecological cancer worldwide and its incidence is rising. The cornerstone of its management is surgical treatment with nodal staging. A monocentric study investigating the potential of the molecular biology method of one-step nucleic acid amplification (OSNA) in sentinel lymph node (SLN) analysis was conducted at our institution between April 2016 and January 2018.

Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes.

The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing.

Physiological shedding and C-terminal proteolytic processing of TMEM106B.

Genetic variants in TMEM106B, coding for a transmembrane protein of unknown function, have been identified as critical genetic modulators in various neurodegenerative diseases with a strong effect in patients with frontotemporal degeneration. The luminal domain of TMEM106B can form amyloid-like fibrils upon proteolysis. Whether this luminal domain is generated under physiological conditions and which protease(s) are involved in shedding remain unclear.

The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages.

The human cathelicidin peptide LL-37 induces autophagy in human macrophages. Different post-translational modifications (PTMs) such as citrullination, acetylation, and formylation impact LL-37, yet their effect on autophagy remains unknown. Thus, we set out to study how the cellular source could impact PTM of LL-37 and subsequent effects on autophagy initiation.

Melatonin-Supplemented Obese Female Mice Show Less Inflammation in Ovarian Adipocytes and Browning in Subcutaneous Adipocytes.

We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (n = 20/group).

Assessing the Effect of Chromatin-Binding Enzymes on Condensed Chromatin with Optical Tweezers.

The formation of biomolecular condensates in vitro and in vivo has become an increasingly important subject of studies. One particular area of interest is the phase separation of chromatin in the nucleus. However, the interplay of condensed chromatin and chromatin-binding enzymes has barely been studied as of now.

Remodeling of Individual Nucleosomes in Nucleosome Arrays.

Adenosin triphosphate (ATP)-dependent nucleosome remodeling factors sculpt the nucleosomal landscape of eukaryotic chromatin. They deposit, evict, or reposition nucleosomes along DNA in a process termed nucleosome sliding. Remodeling has traditionally been analyzed using mononucleosomes as a model substrate.

Cytosolic S100A8/A9 promotes Ca supply at LFA-1 adhesion clusters during neutrophil recruitment.

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions.

Antisense oligonucleotides as a targeted therapeutic approach in model of acute myeloid leukemia.

Background: The genetic and epigenetic alterations observed in acute myeloid leukemia (AML) contribute to its heterogeneity, influencing disease progression response to therapy, and patient outcomes. The use of antisense oligonucleotides (ASOs) technology allows for the design of oligonucleotide inhibitors based on gene sequence information alone, enabling precise targeting of key molecular pathways or specific genes implicated in AML.

Methods And Results: Midostaurin, a FLT3 specific inhibitor and ASOs targeting particular genes, exons, or mutations was conducted using AML models.

Host-directed therapies modulating innate immunity against infection in hematologic malignancies.

Patients with hematologic malignancies (HM) are highly susceptible to bloodstream infection (BSI), particularly those undergoing treatments such as chemotherapy. A common and debilitating side effect of chemotherapy is oral and intestinal mucositis. These Patients are also at high risk of developing sepsis, which can arise from mucosal barrier injuries and significantly increases mortality in these patients.