Prognostic importance of splicing-triggered aberrations of protein complex interfaces in cancer.

Aberrant alternative splicing (AS) is a prominent hallmark of cancer. AS can perturb protein-protein interactions (PPIs) by adding or removing interface regions encoded by individual exons. Identifying prognostic exon-exon interactions (EEIs) from PPI interfaces can help discover AS-affected cancer-driving PPIs that can serve as potential drug targets.

Relationship between the inner setting of CFIR and the delivery of the Healthy School Recognized Campus initiative: a mixed-methods analysis.

Introduction: Healthy School Recognized Campus (HSRC) is a Texas A&M AgriLife Extension initiative that promotes the delivery of multiple evidence-based physical activity and nutrition programs in schools. Simultaneous delivery of programs as part of HSRC can result in critical implementation challenges. The study examines how the inner setting constructs from the Consolidated Framework for Implementation Research (CFIR) impact HSRC program delivery.

Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial.

Background: Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)-based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a 3-part, first-in-human, phase 1/2 clinical trial.

Methods: In Parts 1-3 of this stratified, observer-blind study, adults aged ≥18 years old were randomly assigned to receive a single dose (6.

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis.

Background: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen.

Boosting the Accuracy of Commercial Real Estate Appraisals: An Interpretable Machine Learning Approach.

In this article, we examine the accuracy and bias of market valuations in the U.S. commercial real estate sector using properties included in the NCREIF Property Index (NPI) between 1997 and 2021 and assess the potential of machine learning algorithms (i.

Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause.

Objective: Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS.

Methods: The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance.

Effects of the nerve agent VX on hiPSC-derived motor neurons.

Poisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans.

Cystic Fibrosis Mice Are Highly Susceptible to Repeated Acute Pneumonia after Intranasal Inoculation.

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that controls chloride current. A number of different CFTR transgenic mouse lines have been developed and subjected to both acute and chronic infection models. However, prior studies showed no substantial differences in bacterial clearance between CF and non-CF mice after single inoculations.

Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial.

Background: Respiratory syncytial virus (RSV) presents a global health concern. A lipid nanoparticle-encapsulated mRNA-based RSV vaccine (mRNA-1345) that encodes the membrane-anchored RSV prefusion-stabilized F glycoprotein is under clinical investigation.

Methods: This phase 1 dose escalation study was based on a randomized, observer-blind, placebo-controlled design, and it assessed the safety and immunogenicity of mRNA-1345 in healthy adults aged 18 to 49 years.

Small-molecule activators of a bacterial signaling pathway inhibit virulence.

The genus encompasses multiple human pathogens, including potential bioterrorism agents, that are often extensively antibiotic resistant. The FixLJ pathway in is a two-component system that regulates virulence. Previous work showed that mutations arising during chronic infection confer increased virulence while decreasing the activity of the FixLJ pathway.

A Delphi Survey Study to Formulate Statements on the Treatability of Inherited Metabolic Disorders to Decide on Eligibility for Newborn Screening.

The Wilson and Jungner (W&J) and Andermann criteria are meant to help select diseases eligible for population-based screening. With the introduction of next-generation sequencing (NGS) methods for newborn screening (NBS), more inherited metabolic diseases (IMDs) can technically be included, and a revision of the criteria was attempted. This study aimed to formulate statements and investigate whether those statements could elaborate on the criterion of for IMDs to decide on eligibility for NBS.

Population-based study on coverage and healthcare processes for cancer during implementation of national healthcare insurance in Indonesia.

Background: A national healthcare insurance has been implemented in Indonesia since 2014. Although cancer care currently represents a smaller part of the healthcare support, the demographic development will lead to a rapid growth of the population within age groups at cancer risk. This requires strategic and developmental planning of cancer care resources.

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis.

Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains.

Numerical approach to investigate MR imaging artifacts from orthopedic implants at different field strengths according to ASTM F2119.

Objective: This study presents an extended evaluation of a numerical approach to simulate artifacts of metallic implants in an MR environment.

Methods: The numerical approach is validated by comparing the artifact shape of the simulations and measurements of two metallic orthopedic implants at three different field strengths (1.5 T, 3 T, and 7 T).

Increased incidence of immune thrombocytopenia (ITP) in 2021 correlating with the ongoing vaccination campaign against COVID-19 in a tertiary center - A monocentric analysis.

Immune thrombocytopenia (ITP) was reported as a rare complication of COVID-19 vaccines. We conducted a retrospective single-center analysis of all ITP cases detected in 2021 and compared the quantity with the pre-vaccination years, from 2018 to 2020. In 2021, a two-fold increase in ITP cases was identified compared to previous years; 11 of 40 cases (27.

Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection.

Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma.

The Efficiency of Direct Maturation: the Comparison of Two hiPSC Differentiation Approaches into Motor Neurons.

Motor neurons (MNs) derived from human-induced pluripotent stem cells (hiPSC) hold great potential for the treatment of various motor neurodegenerative diseases as transplantations with a low-risk of rejection are made possible. There are many hiPSC differentiation protocols that pursue to imitate the multistep process of motor neurogenesis . However, these often apply viral vectors, feeder cells, or antibiotics to generate hiPSC and MNs, limiting their translational potential.

Decision Conflicts in Clinical Care during COVID-19: A Multi-Perspective Inquiry.

Background: The early COVID-19-pandemic was characterized by changes in decision making, decision-relevant value systems and the related perception of decisional uncertainties and conflicts resulting in decisional burden and stress. The vulnerability of clinical care professionals to these decisional dilemmas has not been characterized yet. Methods: A cross-sectional questionnaire study (540 patients, 322 physicians and 369 nurses in 11 institutions throughout Germany) was carried out.

Multicomponent Pseudomonas aeruginosa Vaccines Eliciting Th17 Cells and Functional Antibody Responses Confer Enhanced Protection against Experimental Acute Pneumonia in Mice.

The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P.

A pyramid model to describe changing decision making under high uncertainty during the COVID-19 pandemic.

The COVID-19 pandemic put healthcare systems, hospitals and medical personal under great pressure. Based on observations in Germany, we theorise a general model of rapid decision-making that makes sense of the growing complexity, risks and impact of missing evidence. While adapting decision-making algorithms, management, physicians, nurses and other healthcare professionals had to move into uncharted territory while addressing practical challenges and resolving normative (legal and ethical) conflicts.

Economic Perspective of Cancer Care and Its Consequences for Vulnerable Groups.

Within healthcare systems in all countries, vulnerable groups of patients can be identified and are characterized by the reduced utilization of available healthcare. Many different reasons can be attributed to this observation, summarized as implementation barriers involving acceptance, accessibility, affordability, acceptability and quality of care. For many patients, cancer care is specifically associated with the occurrence of vulnerability due to the complex disease, very different target groups and delivery situations (from prevention to palliative care) as well as cost-intensive care.