Genome-wide in vivo and ex vivo mapping of R-loops using engineered N-terminal hybrid-binding domain of RNase H3 (enDR3).

R-loops are nucleic acid structures composed of an RNA/DNA hybrid and a displaced single-stranded DNA that form during transcription. Their defective processing has been implicated in genome instability, which is associated with severe human diseases. Despite their biological significance, the mechanisms regulating R-loops remain incompletely understood, underscoring the need for improved tools to accurately map R-loops across the genome.

Transosseous Quadriceps Tendon Repair With Knotless All-Suture Anchors Is Biomechanically Superior to Traditional Transosseous Fixation.

Background: Reruptures and functional deficits can occur with conventional transosseous quadriceps tendon repair. Previous work has demonstrated the biomechanical superiority of adjustable transosseous metal cortical button fixation over conventional repair. Knotless all-suture anchor (ASA) buttons may provide a similar improvement but have not yet been investigated.

Transcatheter Aortic Valve Replacement With Balloon- Versus Self-Expandable Bioprostheses for the Treatment of Bicuspid Aortic Valve Stenosis.

Background: Differences between balloon- and self-expandable transcatheter heart valves (BE-THVs and SE-THVs, respectively) may influence the outcomes of transcatheter aortic valve replacement for bicuspid aortic valve (BAV) stenosis.

Methods: Consecutive patients undergoing transcatheter aortic valve replacement with BE-THV or SE-THV for computed tomography-diagnosed bicuspid aortic valve stenosis at 29 centers were included. The primary outcome was death or stroke.

Functionalized Mildly Oxidized MXene-Based Injectable Hydrogel with Enhanced Photothermal Performance for Precision Therapy of Uterine Sarcoma.

Uterine sarcoma is an extremely malignant gynecological tumor, characterized by rapid growth, early metastasis, and a high recurrence rate. Current treatments like surgery, radiotherapy, and chemotherapy, have limited effectiveness, highlighting the urgent need for innovative noninvasive alternatives. Here, we report a novel photosensitive nanocomposite hydrogel (O1-M&F) designed for NIR-induced photothermal therapy (PTT), comprising mildly oxidized MXene (O1-M) and a thermosensitive Pluronic F127 hydrogel.

Establishing Centers of Excellence for Psoriatic Disease in Latin America: Consensus Recommendations from the REAL-PANLAR Group.

Objective: Psoriatic Disease (PsD) is a chronic, multisystem inflammatory condition characterized by heterogeneous manifestations, including peripheral arthritis, axial involvement, enthesitis, and cutaneous and nail psoriasis. The condition has significant physical, emotional, and psychosocial impacts on patients. In Latin America, healthcare disparities exacerbate delays in diagnosis and treatment, increasing the burden of PsD and associated comorbidities.

The role of Fezolinetant in fear memory consolidation.

Modulation of fear memories has important implications for the treatment of different psychiatric disorders including fear-based disorders such as posttraumatic stress disorder (PTSD). The Tachykinin2 (Tac2)/Neurokinin B (NkB)/neurokinin 3 receptor (Nk3R) pathway is a potential candidate for treating fear-based disorders built on animal and human studies. Here we demonstrate that the Nk3R antagonist Fezolinetant presents sex-divergent effects in the processing of fear memories in mice exposed to cued-fear conditioning.

Long-term Outcomes of ACL Reconstruction and Posterior Tibial Slope Correction: A 20-Year Retrospective Analysis.

Background: Despite advancements in surgical techniques, the recurrence rate of anterior cruciate ligament (ACL) rupture after reconstruction remains between 2% and 20%. An increased posterior tibial slope (PTS) is associated with higher ACL rupture and reconstruction failure rates.

Hypothesis: Anterior closing wedge high tibial osteotomy (ACW-HTO) combined with ACL reconstruction will result in a lower rate of failure and better functional outcomes for patients with excessive PTS.

Skin Autofluorescence May Contribute to Prediction of Low Bone Quality in Type 1 Diabetes-A Clinical Cross-Sectional Study.

Introduction: People with type 1 diabetes are at risk of complications, including impaired bone health. Hyperglycaemia and accumulation of advanced glycation end products (AGEs) are involved in the development of those. Bone measurements such as trabecular bone score (TBS), high-resolution periphery quantitative computed tomography (HR-pQCT), and impact microindentation may detect impaired bone health better than bone mineral density (BMD).

Derivation, expansion and cryopreservation of primary fetal organoids from second and third trimester human amniotic fluid cells.

Human primary fetal stem cell-derived organoids are used to model developing tissues in vitro. However, ethical and legislative constraints restrict fresh fetal tissue collection in several countries. Amniotic fluid (AF) is easily accessible with minimal ethical and regulatory constraints for collection.

Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma.

Background & Aims: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies; alternative treatments are needed. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP).

Methods: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection that progressed on, were intolerant to, or refused prior systemic therapy.

Plasma proteomic analysis identifies proteins and pathways related to Alzheimer's risk.

Introduction: We investigated associations of plasma proteins with blood-based amyloid/tau/neurodegeneration/inflammation (A/T/N/I) biomarkers for Alzheimer's disease (AD).

Methods: Plasma proteomics and clinical data from the Indiana AD Research Center (N = 498) were used. Association analysis of plasma proteins with blood A/T/N/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort (N = 323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk.

The Current State of American Flag Football Injuries Among Female Athletes: A 10-Year Epidemiological Review of National Injury Data.

Background: Flag football, a noncontact variant of American football, has gained significant interest in the United States and globally, which has been attributed to its accessibility, low cost, and perceived safety compared with traditional tackle football.

Purpose: To identify the trends, primary mechanisms, and distributions of American flag football injuries among female athletes to better inform prevention and safety measures.

Study Design: Descriptive epidemiology study.

Curative intent therapy of stage I-III non-small cell lung cancer: a patient-centered precision approach to assess, measure, and interpret benefits and harms.

Background: The number of people diagnosed with stage I-III non-small cell lung cancer (NSCLC) is increasing, in part due to greater implementation of lung cancer screening and earlier detection. Definitive surgery, radiation, or chemoradiation are increasingly utilized along with adjunctive therapies that include chemotherapy, radiation, immune checkpoint inhibitors (ICIs), and receptor tyrosine kinase inhibitors (rTKIs). However, remedial and adverse effects exist for each modality that must be accounted for in individual treatment plans with curative intent.

GM1 Oligosaccharide Modulates Microglial Activation and α-Synuclein Clearance in a Human In Vitro Model.

Neuroinflammation driven by microglial activation and α-synuclein (αSyn) aggregation is one of the central features driving Parkinson's disease (PD) pathogenesis. GM1 ganglioside's oligosaccharide moiety (OligoGM1) has shown neuroprotective potential in PD neuronal models, but its direct effects on inflammation remain poorly defined. This study investigated the ability of OligoGM1 to modulate microglial activation and αSyn handling in a human in vitro model.

Omics-Mediated Treatment for Advanced Prostate Cancer: Moving Towards Precision Oncology.

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10-20% of patients eventually progress to metastatic castration-resistant disease (mCRPC).

Influence of a Th17-Inducing Cytokine Milieu on Phenotypical and Functional Properties of Regulatory T Cells in Chronic Inflammatory Arthritis.

Considering the high plasticity of FoxP3 regulatory T (Treg) cells and Interleukin (IL)-17-producing Th17 cells, we hypothesized that a Th17 inflammatory milieu may impair the functional properties of Treg cells in chronic inflammatory arthritides. Therefore, a cross-sectional explorative analysis was set up in patients with psoriatic arthritis (PsoA), rheumatoid arthritis, or spondyloarthritis to investigate the features of Th17 and Treg cells. T cell subpopulation counts, mRNA expression, CpG methylation of the gene, and the suppressive capacity of isolated Treg cells were determined.

Scaffold-Free Functional Deconvolution Identifies Clinically Relevant Metastatic Melanoma EV Biomarkers.

Melanoma metastasis, driven by tumor microenvironment (TME)-mediated crosstalk facilitated by extracellular vesicles (EVs), remains a major therapeutic challenge. A critical barrier to clinical translation is the overlap in protein cargo between tumor-derived and healthy cell EVs. To address this, we developed Scaffold-free Functional Deconvolution (SFD), a novel computational approach that leverages a comprehensive healthy cell EV protein database to deconvolute non-oncogenic background signals.

Identifying Infectious Agents in Snakes (Boidae and Pythonidae) with and Without Respiratory Disease.

Mycoplasmas are known respiratory pathogens in tortoises, but few studies exist in snakes. To better understand the correlation with clinical signs and co-infections, samples from mycoplasma-positive snakes with and without clinical respiratory disease were analyzed. Oral swabs from 15 snakes (pythons = 12, boas = 3) were examined using polymerase chain reaction (PCR) and third-generation sequencing (TGS).

Clone copy number diversity is linked to survival in lung cancer.

Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging. Here we present allele-specific phylogenetic analysis of copy number alterations (ALPACA), a method to infer SNV and SCNA coevolution by leveraging phylogenetic trees reconstructed from multi-sample bulk tumour sequencing data using SNV frequencies.

Consensus on acromegaly therapeutic outcomes: an update.

The 15th Acromegaly Consensus Conference in September 2023 updated recommendations on therapeutic outcomes for acromegaly. Since the publication of medical management guidelines in 2018, new pharmacological agents and new treatment approaches have been developed. Fifty-two experts in the management of acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and management.

Nationwide study of spondyloarthritis spectrum and disease characteristics in Egypt.

The aim of this study was to describe the array and disease characteristics of spondyloarthritis (SpA) across Egypt. This work included 1401 SpA patients recruited from 15 specialized Egyptian rheumatology centers representing 20 major cities. The demographic and clinical features, as well as the therapeutic data, were recorded.

From subthalamic local field potentials to the selection of chronic deep brain stimulation contacts in Parkinson's disease - A systematic review.

Background: Programming deep brain stimulation (DBS) of the subthalamic nucleus for optimal symptom control in Parkinson's Disease (PD) requires time and trained personnel. Novel implantable neurostimulators allow local field potentials (LFP) recording, which could be used to identify the optimal (chronic) stimulation contact. However, literature is inconclusive on which LFP features and prediction techniques are most effective.

Mesenteric Lymphangiography as a New Diagnostic and Therapeutic Tool for Refractory Chylous Lymphatic Leakages and Protein Losing Enteropathy.

Purpose: This study aims to evaluate whether mesenteric lymphangiography (mLAG) is technically feasible and clinically useful for patients with refractory chylous ascites, chylothorax and protein-losing enteropathy.

Materials And Methods: A retrospective study of 35 patients (M/F 16:19, mean age 56 years, range 20-78) who underwent mLAG at two institutions between March 2016 and July 2022 was performed. mLAG was performed via intraoperative and/or percutaneous approaches.

Targeting the MYC oncogene with a selective bi-steric mTORC1 inhibitor elicits tumor regression in MYC-driven cancers.

The MYC oncogene is causally involved in the pathogenesis of most human cancers. The mTORC1 complex regulates MYC translation through 4EBP1 and S6K. However, agents that selectively target mTORC1 (without affecting mTORC2) have so far failed to reactivate 4EBP1 and, thus, cannot effectively suppress MYC in vivo.