APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus.

Aminoglycoside-phosphotransferases (APHs) are a class of bacterial enzymes that mediate acquired resistance to aminoglycoside antibiotics. Here we report the identification of small molecules counteracting aminoglycoside resistance in Enterococcus casseliflavus. Molecular dynamics simulations were performed to identify an allosteric pocket in three APH enzymes belonging to 3' and 2'' subfamilies in which we then screened, in silico, 12,000 small molecules.

The nuclear lamin network passively responds to both active or passive cell movement through confinements.

Physical models of cell motility rely mostly on cytoskeletal dynamical assembly. However, when cells move through the complex 3D environment of living tissues, they have to squeeze their nucleus that is stiffer than the rest of the cell. The lamin network, organised as a shell right underneath the nuclear membrane, contributes to the nuclear integrity and stiffness.

Synchrotron X-ray micro-computed tomography enhances our knowledge of the skull anatomy of a Late Triassic ecteniniid cynodont with hypercanines.

Hypercanines, or hypertrophied canines, are observed in a wide range of both extinct and extant synapsids. In non-mammaliaform cynodonts, the Permo-Triassic forerunners of mammals, long canines are not uncommon, appearing in several unrelated taxa within the clade. Among them is Trucidocynodon riograndensis, a carnivorous ecteniniid cynodont from the Late Triassic of Brazil, which exhibits a specialized dentition, including spear-shaped incisors, very long and narrow canines, and sectorial postcanines with distally oriented cusps, all of which have finely serrated margins.

Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics.

Schizophrenia is a frequent and disabling disease. The persistence of the disorder despite its harmful consequences represents an evolutionary paradox. Based on recent discoveries in genetics, scientists have formulated the "price-to-pay" hypothesis: schizophrenia would be intimately related to human evolution, particularly to brain development and human-specific higher cognitive functions.

Scaling up morphological differentiation of pangolin scales: Serial, ontogenetic and evolutionary variation.

Pangolins are the most heavily trafficked mammals in the world, largely because of the high demand for their keratinous scales from the traditional Chinese medicine market. While seizures of pangolin material are largely composed of isolated scales, efficient approaches to reach species-level identification are missing. This mostly originates from the lack of comparative studies on the shape of pangolin scales, resulting in knowledge gaps on the imbricated effects of serial, ontogenetic, and evolutionary variations.

Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.

Exploring the Impact of Minor Water Content on Polymer Electrolytes with Molecular Dynamics.

Solid-state polymer electrolytes (SPEs) are increasingly favored over liquid electrolytes for emerging energy storage devices due to their safety features, enhanced stability, and multifunctionality. Minor solvents (such as water) are often introduced unintentionally or intentionally into SPEs. Although it can significantly affect SPEs' electrochemical and mechanical properties, the fundamental role of such solvent content has rarely been studied.

Medical Treatment of Cushing's Syndrome.

Endogenous Cushing's syndrome (CS) refers to the manifestations of chronic cortisol excess. This rare disease is associated with multiple comorbidities, impaired quality of life, and increased mortality. The management of CS remains challenging.

Minimal invasive biopsies are highly sensitive for amyloid detection in hereditary transthyretin amyloidosis with polyneuropathy.

Objective: To assess the effectiveness of labial minor salivary gland biopsy (LSGB) alone or in combination with punch skin biopsy (SB) for the detection of amyloid deposits in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Methods: In this single-center retrospective study, Congo red staining of minimal invasive LSGB (4 mm) and SB (3 mm) was assessed in ATTRv-PN patients consecutively evaluated between 2012 and 2023.

Results: Histopathological data of 171 ATTRv-PN, including 49 early-onset p.

First-Principles Assessment of ZnTe and CdSe as Prospective Tunnel Barriers at the InAs/Al Interface.

Majorana zero modes are predicted to emerge in semiconductor/superconductor interfaces, such as InAs/Al. Majorana modes could be utilized for fault tolerant topological qubits. However, their realization is hindered by materials challenges.

Linear Modelling of the V̇O2/PO-Relationship during Constant Work Rate Exercise.

Introduction: The linear and continuous increase in power output (PO) during ramp incremental (RI) exercise causes a distinct V̇O2/PO relationship compared to constant work rate (CWR) exercise. Current methods enabling a translation of ramp-derived PO to CWR PO assume a linear development of the CWR V̇O2/PO relationship in the heavy-intensity domain. This study aimed to model the RI versus CWR V̇O2/PO relationship to investigate whether the loss of mechanical efficiency above GET develops linearly.

Understanding Cardiovascular Events With JAK Inhibitors: Tofacitinib Reduces Synovial and Vascular Inflammation but not the Prothrombotic Effects of Inflammatory Cytokines on Endothelium.

Objective: Inflammation drives cardiovascular disease in rheumatoid arthritis (RA). Treatment with tofacitinib, a JAK1/JAK3 inhibitor, is associated with increased cardiovascular events in patients with RA. Here, we determined its effects on cytokine production during interactions between immune cells at the synovial and vascular levels and its impact on endothelial activation and coagulation during inflammation.

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).