A Model of Zymogen Factor XII: Insights into Protease Activation.

In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.

Assessment of the underreporting of rhinitis in patients with asthma: A MASK-air® real-world study.

Rhinitis is a common comorbidity in patients with asthma. However, the frequency of underreported rhinitis in asthma is not known. In this study, we aimed to assess the characteristics of patients with self-reported asthma and no self-reported rhinitis, as well as the extent of the underreporting of rhinitis.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

A Phase 3B, Open-Label Study to Evaluate the Immunogenicity and Safety of the Quadrivalent Meningococcal Nimenrix Vaccine When Given to Healthy Infants at 3 and 12 Months of Age.

Introduction: Infants and young children typically have the highest age-related risk of invasive meningococcal disease. The immunogenicity and safety of a single primary dose and a booster of a meningococcal A/C/W/Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) in infants were evaluated.

Methods: In this phase 3b, open-label, single-arm study, healthy 3-month-old infants received a single Nimenrix dose followed by a booster at age 12 months (1 + 1 series).

An early evaluation of robot-assisted and conventional techniques for posterior approach atlantoaxial displacement instrumentation - a systematic review and meta-analysis.

Atlantoaxial dislocation (AAD) is a serious condition in which the first two cervical vertebrae lose their anatomical position and stability. This may lead to neurological complications, including death. The treatment of AAD remains controversial, and posterior instrumentation with pedicle screw placement is one of the commonly used methods.

Shear wave elastography primer for the abdominal radiologist.

Purpose: Shear wave elastography (SWE) provides a means for adding information about the mechanical properties of tissues to a diagnostic ultrasound examination. It is important to understand the physics and methods by which the measurements are made to aid interpretation of the results as they relate to disease processes.

Methods: The components of how ultrasound is used to generate shear waves and make measurements of the induced motion are reviewed.

Distinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).

The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.

Collaborative Development of Feedback Concept Maps for Virtual Patient-Based Clinical Reasoning Education: Mixed Methods Study.

Background: Concept maps are a suitable method for teaching clinical reasoning (CR). For example, in a concept map, findings, tests, differential diagnoses, and treatment options can be documented and connected to each other. When combined with virtual patients, automated feedback can be provided to the students' concept maps.

Exploring the Impact of the Multimodal CAPABLE eHealth Intervention on Health-Related Quality of Life in Patients With Melanoma Undergoing Immune-Checkpoint Inhibition: Prospective Pilot Study.

Background: Patients with melanoma receiving immunotherapy with immune-checkpoint inhibitors often experience immune-related adverse events, cancer-related fatigue, and emotional distress, affecting health-related quality of life (HRQoL) and clinical outcome to immunotherapy. eHealth tools can aid patients with cancer in addressing issues, such as adverse events and psychosocial well-being, from various perspectives.

Objective: This study aimed to explore the effect of the Cancer Patients Better Life Experience (CAPABLE) system, accessed through a mobile app, on HRQoL compared with a matched historical control group receiving standard care.

Neoantigen mRNA vaccines and AA receptor antagonism: A strategy to enhance T cell immunity.

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine AA receptor (AAR) inhibits dendritic cell (DC) function and weakens antitumor T cell responses through hypoxia-driven mechanisms within the TME. This review explores a novel strategy combining neo-antigen mRNA vaccines with AAR antagonists (AARi).

Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy.

Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity.

A novel ,,-coordinated organofluoroboron probe for amyloid detection: insight from experiment and theory.

This work presents the results of photophysical studies for a newly synthesized BF-based organoboron dye of D-A-D topology. The one- and two-photon properties of the dye are compared with the D-A parent compound and commercially available amyloid marker: methoxy-X04. We demonstrate that the new dye exhibits better optical properties upon binding to amyloids than methoxy-X04, including emission above 600 nm, higher values of 2PA cross section, broader excitation range and higher increment of emission intensity upon binding to amyloids.

Nutrition users' guides: systematic reviews part 1 -structured guide for methodological assessment, interpretation and application of systematic reviews and meta-analyses of non-randomised nutritional epidemiology studies.

Due to the challenges of conducting randomised controlled trials (randomised trials) of dietary interventions, evidence in nutrition often comes from non-randomised (observational) studies of nutritional exposures-called nutritional epidemiology studies. When using systematic reviews of such studies to advise patients or populations on optimal dietary habits, users of the evidence (eg, healthcare professionals such as clinicians, health service and policy workers) should first evaluate the rigour (validity) and utility (applicability) of the systematic review. Issues in making this judgement include whether the review addressed a sensible question; included an exhaustive literature search; was scrupulous in the selection of studies and the collection of data; and presented results in a useful manner.

Nutrition Users' Guides: RCTs Part 2 - structured guide for interpreting and applying study results from randomised controlled trials on therapy or prevention questions.

This article continues from a prior commentary on evaluating the risk of bias in randomised controlled trials addressing nutritional interventions. Having provided a synopsis of the risk of bias issues, we now address how to understand trial results, including the interpretation of best estimates of effect and the corresponding precision (eg, 95% CIs), as well as the applicability of the evidence to patients based on their unique circumstances (eg, patients' values and preferences when trading off potential desirable and undesirable health outcomes and indicators (eg, cholesterol), and the potential burden and cost of an intervention). Authors can express the estimates of effect for health outcomes and indicators in relative terms (relative risks, relative risk reductions, OR or HRs)-measures that are generally consistent across populations-and absolute terms (risk differences)-measures that are more intuitive to clinicians and patients.

Nutrition users' guides: RCTs part 1 - structured guide for assessing risk of bias in randomised controlled trials that address therapy or prevention questions.

The purpose of this article, part 1 of 2 on randomised controlled trials (RCTs), is to provide readers (eg, clinicians, patients, health service and policy decision-makers) of the nutrition literature structured guidance on interpreting RCTs. Evaluation of a given RCT involves several considerations, including the potential for risk of bias, the assessment of estimates of effect and their corresponding precision, and the applicability of the evidence to one's patient. Risk of bias refers to flaws in the design or conduct of a study that may lead to a deviation from measuring the underlying true effect of an intervention.

Effect of prophylactic doses of enoxaparin on antifactor Xa activity confirmed by rotational thromboelastometry in critically ill patients: a preliminary prospective cohort study.

Introduction: Critically ill patients present multiple risk factors for venous thromboembolism (VTE). Underdosing of antithrombotic medications can result in VTE even as bleeding remains a significant concern for critically ill patients. On the other hand bleeding, remaining a significant concern for the critically ill, can be worsend by overdosing of antithrombotic medications.

First-trimester metabolic profiling of gestational diabetes mellitus: insights into early-onset and late-onset cases compared with healthy controls.

Introduction: Gestational diabetes mellitus (GDM) is a global health concern with significant short and long-term complications for both mother and baby. Early prediction of GDM, particularly late-onset, is crucial for implementing timely interventions to mitigate adverse outcomes. In this study, we conducted a comprehensive metabolomic analysis to explore potential biomarkers for early GDM prediction.

The Potential Proallergenic Activity of and in vitro Studies.

Purpose: Allergic diseases have escalated to epidemic levels worldwide, impacting nearly 30% of the global population. Fungi are a significant source of allergens responsible for up to 6% of respiratory diseases in the general population. However, the specific cause of respiratory allergies often remains unidentified.

The role of vitamin K2 in cognitive impairment: linking vascular health to brain health.

Cognitive impairment, marked by a decline in essential mental aspects such as attention, memory, and problem-solving, is significantly correlated with advancing age. This condition presents a major challenge for the elderly, adversely affecting quality of life, diminishing independence, and imposing substantial burdens on healthcare systems. Recent research indicates that vitamin K2 may be vital for preserving brain health and cognitive function.

Safety and tolerability of intramuscular sotrovimab administered at different injection sites: results from the Phase 1 COSMIC study.

ClinicalTrials.gov identifier, NCT05280717.

Electrochemical Cyclization-Desulfurization Approach for the Synthesis of 1,3-Benzoxazines Using Cascade C-O and C-N Bond Formation.

A cost-effective, eco-friendly, and highly efficient one-pot electrochemical process has been described for the synthesis of 4-1,3-benzoxazine and 4,5-dihydro-1,3-benzoxazepine derivatives by employing 2-aminobenzyl alcohols, 2-(2-aminophenyl)ethan-1-ol, isothiocyanate derivatives, and TBAPF as an electrolyte. The developed method is accomplished at 25 °C with a constant current of 20 mA. Utilizing a graphite anode and a platinum cathode in a dimethyl sulfoxide solvent, the devised metal-free electrochemical approach minimizes the production of waste and eliminates the need for external oxidizing agents.