Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma.

Background: Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear.

Methods: In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for surgical evacuation to undergo middle meningeal artery embolization plus surgery (treatment group) or surgery alone (control group).

Enhancing economic multifunctionality without compromising multidiversity and ecosystem multifunctionality via forest enrichment.

Enriching tree species-poor and less productive forests by introducing economically valuable species is a strategy proposed for achieving multipurpose forest management. However, empirical evidence from managed and mature forests on the impact of this enrichment on ecological (multidiversity and ecosystem multifunctionality) and economic dimensions remains scarce, particularly when nonnative species are used. Here, we propose and test a framework that integrates economic multifunctionality, encompassing timber production-oriented goals and resistance against disturbances, with multidiversity and ecosystem multifunctionality in European beech forest stands enriched with conifers.

Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease.

Introduction: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments.

Methods: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.

PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.

Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC.

Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects.

Background: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein not previously described in the human central nervous system (CNS).

Objectives: We determined MFAP4 CNS expression and measured cerebrospinal fluid (CSF) and serum levels.

Methods: Tissue was sampled at autopsy from patients with acute multiple sclerosis (MS) ( = 3), progressive MS ( = 3), neuromyelitis optica spectrum disorder (NMOSD) ( = 2), and controls ( = 9), including 6 healthy controls (HC).

Artificial intelligence-based opportunistic detection of coronary artery stenosis on aortic computed tomography angiography in emergency department patients with acute chest pain.

Aims: To evaluate a deep-learning model (DLM) for detecting coronary stenoses in emergency room patients with acute chest pain (ACP) explored with electrocardiogram-gated aortic computed tomography angiography (CTA) to rule out aortic dissection.

Methods And Results: This retrospective study included 217 emergency room patients (41% female, mean age 67.2 years) presenting with ACP and evaluated by aortic CTA at our institution.

Efficacy and Safety of Masitinib in Progressive Forms of Multiple Sclerosis: A Randomized, Phase 3, Clinical Trial.

Background And Objectives: Masitinib is a selective tyrosine kinase inhibitor, targeting innate immune cells (mast cells and microglia) that are involved in the pathophysiology of progressive multiple sclerosis (MS). Study AB07002 assessed oral masitinib in patients with progressive MS who were progressing but not clinically active.

Methods: This randomized, double-blind, 2 parallel-group, placebo-controlled trial assessing 2 dose levels of masitinib vs equivalent placebo was conducted at 116 hospital clinics and specialized MS centers in 20 countries.

Cefiderocol for the Treatment of Infections Due to Metallo-B-lactamase-Producing Pathogens in the CREDIBLE-CR and APEKS-NP Phase 3 Randomized Studies.

In the CREDIBLE-CR and APEKS-NP studies, cefiderocol treatment was effective against gram-negative bacteria producing metallo-B-lactamases; rates of clinical cure (70.8% [17/24]), microbiological eradication (58.3% [14/24]), and day 28 all-cause mortality (12.

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.

Background: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far.

Objective: To analyze systematically the CSF profile in COVID-19.

Methods: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.

Leveraging Visual Outcome Measures to Advance Therapy Development in Neuroimmunologic Disorders.

The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible.

Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis: A Randomized, Placebo-Controlled Trial.

Objective: To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial.

Role of diversity-generating retroelements for regulatory pathway tuning in cyanobacteria.

Background: Cyanobacteria maintain extensive repertoires of regulatory genes that are vital for adaptation to environmental stress. Some cyanobacterial genomes have been noted to encode diversity-generating retroelements (DGRs), which promote protein hypervariation through localized retrohoming and codon rewriting in target genes. Past research has shown DGRs to mainly diversify proteins involved in cell-cell attachment or viral-host attachment within viral, bacterial, and archaeal lineages.

Invasive Aspergillosis by : Epidemiology, Diagnosis, Antifungal Resistance, and Management.

is the second most common etiological agent of invasive aspergillosis (IA) after . However, most literature describes IA in relation to or together with other species. Certain differences exist in IA caused by and and studies on infections are increasing.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

Background: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.

Methods: We enrolled adults who were being treated for bone or joint infection at 26 U.

Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions.

Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).

Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013.

Nucleic acid-based polymers effective against hepatitis B Virus infection in patients don't harbor immunostimulatory properties in primary isolated liver cells.

Nucleic acid polymers (NAPs) block the release of subviral particles from hepatocytes, a mechanism consistent with their antiviral activity against hepatitis B virus (HBV) in patients. Analysis of immunostimulatory properties of NAPs were conducted with several NAP species: REP 2006, the prototypic degenerate NAP [dN], containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC] devoid of CpG content; REP 2139 (also clinically active) and REP 2165 (REP 2055 analogues further rendered immunologically inactive by replacing cytidine with 5-methylcytidine and incorporating 2'-O methylation of riboses). These analyses revealed pro-inflammatory responses in human peripheral blood mononuclear cells with REP 2006 and with REP 2139 and REP 2165 only at high dose but displayed no significant antiviral activity.

7T MRI in natalizumab-associated PML and ongoing MS disease activity: A case study.

Objective: To assess the ability of ultra-high-field MRI to distinguish early progressive multifocal leukoencephalopathy (PML) from multiple sclerosis (MS) lesions in a rare case of simultaneous presentation of natalizumab-associated PML and ongoing MS activity.

Methods: Advanced neuroimaging including 1.5T, 3T, and 7T MRI with a spatial resolution of up to 0.

Targeted diversity generation by intraterrestrial archaea and archaeal viruses.

In the evolutionary arms race between microbes, their parasites, and their neighbours, the capacity for rapid protein diversification is a potent weapon. Diversity-generating retroelements (DGRs) use mutagenic reverse transcription and retrohoming to generate myriad variants of a target gene. Originally discovered in pathogens, these retroelements have been identified in bacteria and their viruses, but never in archaea.

Diagnosis of functionally significant coronary stenosis with exercise CT myocardial perfusion imaging.

Purpose: To assess the feasibility of exercise perfusion computed tomography (CT) in patients suspected of having hemodynamically significant coronary stenosis.

Materials And Methods: This study had institutional review board approval, and all patients gave informed consent. Thirty-two consecutive patients (26 men [mean age, 63 years] and six women [mean age, 71 years]) with 55 coronary stenoses of at least 50% underwent coronary CT angiography (one stenosis in 13 patients, two stenoses in 15 patients, and three stenoses in four patients).