Posaconazole for Prevention of COVID-19-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients: A European Multicentre Case-Control Study (POSACOVID).

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).

Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.

Comparison of the efficacy and safety of Landiolol and Esmolol in critically ill patients: a propensity score-matched study.

Background: Excessive tachycardia is associated with impaired hemodynamics and worse outcome in critically ill patients. Previous studies suggested beneficial effect of β-blockers administration in ICU patients, including those with septic shock. However, comparisons in ICU settings are lacking.

The effect of degenerative scolioisis on segmental thoracolumbar sagittal alignment compared to age- and pelvic incidence-matched reference values.

Introduction: In asymptomatic subjects, variations of sagittal alignment parameters according to age and pelvic incidence (PI) has been reported. The aim of this observational study was to describe thoraco-lumbar sagittal alignment in patients with degenerative scoliosis and to compare them to asymptomatic individuals, seeking for the specific effect of deformity in similar age and PI groups.

Materials And Methods: Full spine radiographs of 235 asymptomatic subjects and 243 scoliosis patients were analyzed: cervico-thoracic inflexion point (CTIP), thoraco-lumbar inflexion point (TLIP), lumbar lordosis (LL) L1-S1, LL (TLIP-S1), LL superior arch (TLIP-lumbar apex), LL inferior arch (lumbar apex-S1), PI, thoracic kyphosis (TK) T5-T12, TK T1-T12, number of vertebrae CTIP-TLIPandTLIP-S1.

Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer.

Immunotherapy is improving the survival of patients with metastatic non-small cell lung cancer (NSCLC), yet reliable biomarkers are needed to identify responders prospectively and optimize patient care. In this study, we explore the benefits of multimodal approaches to predict immunotherapy outcome using multiple machine learning algorithms and integration strategies. We analyze baseline multimodal data from a cohort of 317 metastatic NSCLC patients treated with first-line immunotherapy, including positron emission tomography images, digitized pathological slides, bulk transcriptomic profiles, and clinical information.

Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature.

Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features.

H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts.

Post-translational modifications of histone H3 on lysine 9, specifically acetylation (H3K9ac) and tri-methylation (H3K9me3), play a critical role in regulating chromatin accessibility. However, the role of these modifications in lineage segregation in the mammalian blastocyst remains poorly understood. We demonstrate that di- and tri-methylation marks, H3K9me2 and H3K9me3, decrease during cavitation and expansion of the rabbit blastocyst.

Transformation and articulation of clinical data to understand students' clinical reasoning: a scoping review.

Background: Despite the importance of effective educational strategies to promote the transformation and articulation of clinical data while teaching and learning clinical reasoning, unanswered questions remain. Understanding how these cognitive operations can be observed and assessed is crucial, particularly considering the rapid growth of artificial intelligence and its integration into health education. A scoping review was conducted to map the literature regarding educational strategies to support transformation and articulation of clinical data, the learning tasks expected of students when exposed to these strategies and methods used to assess individuals' proficiency METHODS: Based on the Joanna Briggs Institute methodology, the authors searched 5 databases (CINAHL, MEDLINE, EMBASE, PsycINFO and Web of Science), ProQuest Dissertations & Theses electronic database and Google Scholar.

Dysfunctional eating attitudes and behaviors among athletes: The role and potential of virtual reality.

This brief article discusses the current state of knowledge on the use of virtual reality in assessing and/or treating body image and body image disturbances among athletes with dysfunctional eating attitudes and behaviors ( i.e., eating disorders and disordered eating).

CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis.

Background: Cystic Fibrosis-related Bone Disease is an emerging challenge faced by 50 % of adult people with cystic fibrosis (CF). The multifactorial causes of this comorbidity remain elusive. However, congenital bone defects have been observed in animal models with CFTR mutations, suggesting its importance.

Patient views on continued immune checkpoint inhibition following progression in advanced melanoma: A qualitative study.

Introduction: Immune checkpoint inhibition has revolutionized the management of metastatic melanoma, including in the final stages of disease progression: because it is well tolerated, some teams do not discontinue it in hopes of slowing disease progression. The risks are that treatment may be continued unnecessarily, causing side effects, and reduce access to specialist palliative care, in addition to increasing the cost of treatment.

Method: We explored the experiences of 10 patients in a university hospital with metastatic melanoma under continued immune checkpoint inhibitors combined with specialist palliative care.

Prevalence of orofacial and head pain: an umbrella review of systematic reviews.

Head pain (HP) and orofacial pain (OFP) are the most prevalent types of pain worldwide, encompassing cranial, oral and facial pain. The aim of this umbrella review was to answer the following questions: "What is the overall prevalence of HP/OFP and the different prevalences of HP/OFP conditions in adults and children?". We searched for studies investigating the prevalence of HP/OFP in four major databases and two databases from the grey literature, based on the following PECOS inclusion criteria: (P)opulation: Adults and children; (E)xposure: Orofacial or head pain conditions such as (1) dental, periodontal and gingival, (2) temporomandibular disorders (TMD), (3) neuropathic conditions, (4) headaches, and (5) idiopathic pain conditions; (C)omparison: None; (O)utcome: Prevalence; (S)tudies: Systematic reviews and/or meta-analyses.

Highly parallel simulation tool for the design of isotachophoresis experiments.

Background: Isotachophoresis (ITP) is a well-established electrokinetic method for separation and preconcentration of analytes. Several simulation tools for ITP have been published, but their use for experimental design is limited by the computational time for a single run and/or by the number of conditions that can be investigated per simulation run. A large fraction of the existing solvers also do not account for ionic strength effects, which can influence whether an analyte focuses in ITP.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Usefulness of Cerebrospinal Fluid Alzheimer's disease biomarkers in older patients: Evidence from a national multicenter prospective study.

Background: The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated.

Objectives: To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Can aortic valve calcium score predict a need for permanent pacemaker implantation after transcatheter aortic valve implantation?

Introduction: Conductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI).

Aims: To assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring PPM after TAVI.

Methods: All patients who underwent TAVI with accessible AVCS from the preprocedural CT scan report were included in this retrospective single-centre study.

Long-term outcome of oesophageal atresia in adolescence (TransEAsome): a national French cohort study protocol.

Introduction: The project, funded by the Agence Nationale de la Recherche, aims to evaluate the long-term outcomes of patients with oesophageal atresia (OA) between 13 and 14 years old and establish multiomics profiles using data from the world's biggest OA registry.

Methods And Analysis: is a national multicentre population-based cohort study recruiting participants from all qualified French centres for OA surgery at birth. The primary objective is to assess the prevalence of gastro-oesophageal reflux disease in adolescence among patients with OA, with several secondary objectives including the identification of risk factors and multiomic profiles from oesophageal biopsies and blood samples collected between 13 and 14 years old, compared with a control group.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke.

Objectives: To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018-2019.

Design: This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.

Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype characterized by aggressive clinical behavior and poor prognosis. The immune landscape associated with TNBC often reveals high immunogenicity. Therefore, immunotherapy, which has demonstrated its efficacy in different cancer types, could be a promising strategy for TNBC, given the limited therapeutic options currently available besides conventional chemotherapy.