In-depth computational analysis reveals the significant dysregulation of key gap junction proteins (GJPs) driving thoracic aortic aneurysm development.

Objective: Thoracic aortic aneurysm (TAA) represents an aortic pathology that is caused by the deranged integrity of the three layers of the aortic wall and is related to severe morbidity and mortality. Consequently, it is crucial to identify the biomarkers implicated in the pathogenesis and biology of TAA. The aim of the current computational study was to assess the differential gene expression profile of the gap junction proteins (GJPs) in patients with TAA to identify novel potential biomarkers for the diagnosis and treatment of this disease.

Relationships between Chronic Cough and Asthma Control and Quality-of-Life in Patients with Severe Asthma: A 6-Month Longitudinal Analysis.

Background: The prevalence and clinical implications of chronic cough (CC) in patients with severe asthma receiving asthma treatment remain relatively unknown.

Objective: This study aimed to evaluate the relationships between CC and asthma control and quality-of-life (QoL) in patients with severe asthma through longitudinal analysis.

Methods: Baseline and 6-month follow-up data from the Korean Severe Asthma Registry were analyzed.

Whole examination AI estimation of fetal biometrics from 20-week ultrasound scans.

The current approach to fetal anomaly screening is based on biometric measurements derived from individually selected ultrasound images. In this paper, we introduce a paradigm shift that attains human-level performance in biometric measurement by aggregating automatically extracted biometrics from every frame across an entire scan, with no need for operator intervention. We use a neural network to classify each frame of an ultrasound video recording.

Efgartigimod efficacy and safety in refractory myasthenia gravis: UK's first real-world experience.

Background: We report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.

Methods: Data from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need).

Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in [F]PI-2620 PET Scans.

Aim: Standardized evaluation of [F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility.

Methods: A total of 83 individuals with [F]PI-2620 PET scans were included.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Rising cardiovascular mortality among obstructive sleep apnea patients: United States epidemiological trends (1999-2019).

Background: Obstructive sleep apnea (OSA) prevalence has risen significantly, affecting millions globally and posing a major healthcare burden. OSA is strongly associated with cardiovascular diseases (CVD) such as heart failure, stroke, and ischemic heart disease. However, trends in CVD-related mortality among individuals with OSA remain underexplored.

Neural invasion severity is a strong predictor of local recurrence in pancreatic ductal adenocarcinoma.

Background: In pancreatic ductal adenocarcinoma, neural invasion is being increasingly recognized as an unfavorable predictor of patient outcomes. Neural invasion severity seems to have a stronger clinical impact on patient prognosis than neural invasion status alone. Therefore, this study aims to assess the impact of severity of neural invasion on overall survival and disease-free survival in pancreatic ductal adenocarcinoma.

Ovarian cancer staging and follow-up: updated guidelines from the European Society of Urogenital Radiology female pelvic imaging working group.

Objective: To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC).

Methods: Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group's annual meeting.

Indications for the addition of a patellofemoral joint arthroplasty following a previous unicondylar knee arthroplasty- a literature review and Delphi consensus.

Introduction: The aim of this study was to establish an international consensus statement on the indications for the addition of a patellofemoral joint arthroplasty (PFJA) in patients with a unicondylar knee arthroplasty (UKA) and symptomatic progression of patellofemoral compartment osteoarthritis.

Materials And Methods: A systematic review of the literature was conducted, and the results used to inform the development of a statement by an expert working group. This was then evaluated and modified, using a Delphi process, by members of the European Knee Society (EKS).

EBSA at 40 - an updated history.

The European Biophysical Societies' Association (EBSA) is an association of 32 biophysical societies in Europe dedicated to the promotion of excellence in biophysics. Through cooperation and collaborative activities, EBSA makes a major and positive impact on the European and International biophysics community. Biennial congresses at various European locations, organized by host societies, are a major activity that engages biophysicists with the wider international scientific community.

Coherent Excitation of the CH Stretching Vibrations in CH : The Role of the Derivative Coupling Studied by the Quantum Ehrenfest Method.

We report nonadiabatic dynamics computations on CH initiated on a coherent superposition of the five lowest cationic states, employing the Quantum Ehrenfest method. In addition to the totally symmetric carbon-carbon double bond stretch and carbon-hydrogen stretches, we see that the three non-totally symmetric modes become stimulated; torsion and three different CH stretching patterns. Thus, a coherent superposition of states, of the type involved in an attochemistry experiment, leads to the stimulation of specific non-totally symmetric motions.

S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.

S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer.

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

PSTK exerts protective role in cisplatin-tubular cell injury via BAX/BCL2/Caspase3 pathway.

Cisplatin is a widely used anticancer drug, but its accumulation in renal tubular epithelial cells (TECs) can cause acute kidney injury. Phosphoseryl-tRNA kinase (PSTK) is an intermediate product produced under oxidative stress conditions. This study aimed to elucidate whether PSTK could protect TECs and its possible mechanisms.

Not seeing the trees for the forest. The impact of neighbours on graph-based configurations in histopathology.

Background: Deep learning (DL) has set new standards in cancer diagnosis, significantly enhancing the accuracy of automated classification of whole slide images (WSIs) derived from biopsied tissue samples. To enable DL models to process these large images, WSIs are typically divided into thousands of smaller tiles, each containing 10-50 cells. Multiple Instance Learning (MIL) is a commonly used approach, where WSIs are treated as bags comprising numerous tiles (instances) and only bag-level labels are provided during training.

BenchAMRking: a Galaxy-based platform for illustrating the major issues associated with current antimicrobial resistance (AMR) gene prediction workflows.

Background: The Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) networks 'Seq4AMR' and 'B2B2B AMR Dx' were established to promote collaboration between microbial whole genome sequencing (WGS) and antimicrobial resistance (AMR) stakeholders. A key topic discussed was the frequent variability in results obtained between different microbial WGS-related AMR gene prediction workflows. Further, comparative benchmarking studies are difficult to perform due to differences in AMR gene prediction accuracy and a lack of agreement in the naming of AMR genes (semantic conformity) for the results obtained.

Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Longitudinal study of care needs and behavioural changes in people living with dementia using in-home assessment data.

Background: People living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability.

Methods: We use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data.

Building the capacity of young professionals in family planning to publish: Insights from the ICFP2022 WHO scientific writing, mentoring and coaching course.

Objectives: We describe the development, delivery, and evaluation of a program to support junior professionals to publish their work in a scientific journal.

Study Design: Conference delegates with an accepted abstract at the International Conference on Family Planning (ICFP), self-identifying as junior professionals and from a low- or middle-income country (LMIC) or working predominantly in LMIC settings, were eligible for the program. The program involved: (1) Four face-to-face workshops at ICFP from the 14th to 17th of November 2022; (2) mentoring meetings at ICFP; (3) a six-month post-conference online coaching program; and (4) post-conference learning webinars from December 2022 to May 2023.