Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations.

Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (MD) simulations, we identified a novel, positively charged α-helical domain in H3 that is essential for HS binding.

Target-agnostic identification of human antibodies to sexual forms reveals cross-stage recognition of glutamate-rich repeats.

Circulating sexual stages of ) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of in the form of gametes and gametocyte extracts.

Knowledge of Mandatory Reporting Laws and Recording of Clients' Abuse Data: Effects of a Sexual Health Curriculum Training for Health Students in Tanzania.

Tanzania mandated reporting laws aim to identify and address child abuse, yet healthcare students' awareness and reporting are limited. This study assessed training's impact on their knowledge of reporting laws and handling confidential child abuse data. The study involved 412 medical and nursing students in a randomized controlled trial (RCT), with 206 participants receiving sexual health training and a waitlist control group of equal size receiving no intervention.

Development and Evaluation of an Automated Multimodal Mobile Detection of Oral Cancer (mDOC) Imaging System to Aid in Risk-based Management of Oral Mucosal Lesions.

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders associated with an increased risk for oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation.

Ankle-foot orthoses for improving walking in adults with calf muscle weakness due to neuromuscular disorders.

Background: Calf muscle weakness is a common symptom in slowly progressive neuromuscular disorders that lead to walking problems like instability and increased walking effort. The mainstay of treatment to improve walking in this population is the provision of ankle-foot-orthoses (AFOs). Since we are not aware of an up-to-date and complete overview of the effects of AFOs used for calf muscle weakness in slowly progressive neuromuscular disorders, we reviewed the evidence for the effectiveness of AFOs to improve walking in this patient group, in order to support clinical decision-making.

A Meta-Analysis on the Efficacy of Noninvasive Positive Pressure Ventilation Combined With Pressure Support Ventilation in Treating Chronic Heart Failure.

Objective: To evaluate the clinical efficacy and safety of noninvasive positive pressure ventilation combined with pressure support ventilation (NPPV-PSV) in the treatment of chronic heart failure (CHF) through a meta-analysis.

Methods: A systematic search was conducted using PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases to find randomized controlled trials and cohort studies on NPPV-PSV treatment for CHF. The period of search was set from inception until 2024.

A systematic review and network meta-analysis of RCTs: The effect of systemic immunotherapies on treatment outcomes and quality of life in patients with metastatic colorectal cancer.

Background: The impact of different systemic treatments on the health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) is still unclear.

Objectives: To compare and evaluate the effects of various systemic interventions on the HRQoL in patients with mCRC.

Material And Methods: A thorough search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to locate relevant literature published in peer-reviewed journals.

A case for broadening our view of mechanism in developmental biology.

Developmental biologists can perform studies that describe a phenomenon (descriptive work) and/or explain how the phenomenon works (mechanistic work). There is a prevalent perception that molecular/genetic explanations achieved via perturbations of gene function are the primary means of advancing mechanistic knowledge. We believe this to be a limited perspective, one that does not effectively represent the breadth of work in our field.

Percutaneous treatment of de Quervain's disease using Sono-Instruments®: A feasibility study.

We investigated the safety and effectiveness of percutaneous release for de Quervain's disease using Sono-Instruments® in cadaveric specimens. The mean procedure duration was 4 minutes, and complete release was achieved in all specimens.

Diagnosing Epilepsy with Normal Interictal EEG Using Dynamic Network Models.

Objective: Whereas a scalp electroencephalogram (EEG) is important for diagnosing epilepsy, a single routine EEG is limited in its diagnostic value. Only a small percentage of routine EEGs show interictal epileptiform discharges (IEDs) and overall misdiagnosis rates of epilepsy are 20% to 30%. We aim to demonstrate how network properties in EEG recordings can be used to improve the speed and accuracy differentiating epilepsy from mimics, such as functional seizures - even in the absence of IEDs.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Ordered Interfacial Water Generated at Poly(ionic liquid) Membrane Surface Imparts Ultrafast Water Transport and Superoleophobicity.

Achieving ultrahigh permeance and superoleophobicity is crucial for membrane application. Here, we demonstrated that a poly(ionic liquid)/PES hydrogel membrane can achieve dual goals. The high polarity of the ionic liquids induces the water molecules on the membrane surface to be arranged more ordered, as verified by molecular dynamics (MD) simulation and advanced femtosecond sum frequency generation (SFG) vibrational spectroscopy.

Diabetes mellitus and glymphatic dysfunction: Roles for oxidative stress, mitochondria, circadian rhythm, artificial intelligence, and imaging.

Diabetes mellitus (DM) is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe. DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death. Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles, programmed cell death, and circadian rhythm impairments.

From laboratory to clinical practice: an update of the immunological and molecular tools for neurocysticercosis diagnosis.

Neurocysticercosis (NCC) is caused by the invasion of larvae in the central nervous system (CNS) and stands as the predominant cause of epilepsy and other neurological disorders in many developing nations. NCC diagnosis is challenging because it relies on brain imaging exams (CT or MRI), which are poorly available in endemic rural or resource-limited areas. Moreover, some NCC cases cannot be easily detected by imaging, leading to inconclusive results.

Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study.

Aims: Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements.

Safety and Efficacy of Toripalimab in Patients with Cholangiocarcinoma: An Open-Label, Phase 1 Study.

Introduction: This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.

Methods: Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B.

Selinexor (KPT-330) in Combination with Immune Checkpoint Inhibition in Uveal Melanoma: A Phase 1B Trial.

Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.

Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma.

Reticulocyte Binding Protein Homologue 5 is a target of balancing selection in the population of Papua New Guinea.

Reticulocyte Binding Protein Homologue (RH5), a leading malaria vaccine candidate, is essential for erythrocyte invasion by the parasite, interacting with the human host receptor, basigin. RH5 has a small number of polymorphisms relative to other blood-stage antigens, and studies have shown that vaccine-induced antibodies raised against RH5 are strain-transcending, however most studies investigating RH5 diversity have been done in Africa. Understanding the genetic diversity and evolution of malaria antigens in other regions is important for their validation as vaccine candidates.

Non-instrumented management of traumatic atlanto-axial rotatory subluxation: surgical technique.

Atlantoaxial rotatory subluxation (AARS) in the adult population is primarily trauma-induced. Conservative and surgical treatments have both been used successfully in treating AARS. In cases where AARS cannot be reduced by conservative measures, open reduction and fusion is the conventional treatment approach.

Is musical ability related to second-language acquisition? A meta-analysis.

In our multicultural and interconnected world, the ability to learn new languages is important. However, there are significant differences in how successfully adults can learn aspects of non-native languages. Given robust relationships between musical ability and native-language processing, musical ability might also contribute to successful second-language acquisition.

Hemophagocytic Lymphohistiocytosis (HLH) Following Immune Checkpoint Therapy (ICT).

In the past decade, the use of immune checkpoint therapy (ICT) has increased across many malignancies, including metastatic renal cell carcinoma as an option for frontline and subsequent lines of therapy. Despite the many therapeutic benefits of ICT, its use is complicated by the potential risk of immune-related adverse events (irAEs). One rare but potentially life-threatening irAE is hemophagocytic lymphohistiocytosis (HLH).

Long-term outcomes of patients who received extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest: Analysis of EXCEL registry data.

Objective: To describe the six-month functional outcomes of patients who received extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest (IHCA) in Australia.

Design: Secondary analysis of EXCEL registry data.

Setting: EXCEL is a high-quality, prospective, binational registry including adult patients who receive extracorporeal membrane oxygenation (ECMO) in Australia and New Zealand.

Focusing on antimicrobial resistant infections -are we missing the forest for the trees and the patients for pathogens?

Antimicrobial resistance (AMR) is a challenge because it is associated with worse patient outcomes. To solve the problem will take development of interventions and policies which improve patient outcomes by prolonging survival, improving patient symptoms, function and quality of life. Logically, we should look to focusing resources in areas that would have the greatest impact on public health.

Role of gamma irradiation and disaccharide trehalose to induce immune responses in Syrian hamster model against Iranian SARS-CoV-2 virus isolate.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the causative agent of the emerging zoonotic respiratory disease. One of the most important prerequisites for combating emerging diseases is the development of vaccines within a short period of time. In this study, antigen-irradiated, inactivated SARS-CoV-2 viruses and the disaccharide trehalose were used to enhance immune responses in the Syrian hamster.