Orthopedic Resident Intern Foundations: A Cross-Institutional, Month-Long Skills Training Boot Camp for PGY-1 Residents.

Objective: Orthopedic residents are tasked with rapidly acquiring clinical and surgical skills, especially during their PGY-1 year. However, resource constraints and other factors frequently cause skills training to fall short of established guidelines. We aimed to design and evaluate a cross-institutional, month-long curriculum aimed at pooling resources to optimize training.

Is Specific Consent for Educational Sensitive Exams on Anesthetized Patients Necessary? Arguments for and Against From Canadian Medical Students.

Objective: Discussions related to the importance of seeking specific consent for sensitive (e.g., pelvic, rectal) exams performed on anesthetized patients by medical students have been growing.

Who is coming in? Evaluation of physician performance within multi-physician emergency departments.

Background: This study aimed to examine how physician performance metrics are affected by the speed of other attendings (co-attendings) concurrently staffing the ED.

Methods: A retrospective study was conducted using patient data from two EDs between January-2018 and February-2020. Machine learning was used to predict patient length of stay (LOS) conditional on being assigned a physician of average speed, using patient- and departmental-level variables.

National early warning score 2 plus non-invasive capnography and perfusion index to estimate poor outcomes in emergency departments.

Background: The study of the inclusion of new variables in already existing early warning scores is a growing field. The aim of this work was to determine how capnometry measurements, in the form of end-tidal CO2 (ETCO2) and the perfusion index (PI), could improve the National Early Warning Score (NEWS2).

Methods: A secondary, prospective, multicenter, cohort study was undertaken in adult patients with unselected acute diseases who needed continuous monitoring in the emergency department (ED), involving two tertiary hospitals in Spain from October 1, 2022, to June 30, 2023.

Multimodal multiview bilinear graph convolutional network for mild cognitive impairment diagnosis.

Mild cognitive impairment (MCI) is a significant predictor of the early progression of Alzheimer's disease, and it can be used as an important indicator of disease progression. However, many existing methods focus mainly on the image itself when processing brain imaging data, ignoring other non-imaging data (e.g.

A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.

Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.

Practical Steps Supporting Professional Publications for Leadership and Teams.

Disseminating research or evidence-based practice is not straightforward. As more clinical nurses, executive nurse leaders, nurse scientists, and faculty contribute to new knowledge, there is an increasing need to support the processes to publish and disseminate manuscripts to advance healthcare. Nurse administrators and leaders are key influencers and supporters to bolster expertise and resources to publish.

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

Tetrameric PilZ protein stabilizes stator ring in complex flagellar motor and is required for motility in .

Rotation of the bacterial flagellum, the first identified biological rotary machine, is driven by its stator units. Knowledge gained about the function of stator units has increasingly led to studies of rotary complexes in different cellular pathways. Here, we report that a tetrameric PilZ family protein, FlgX, is a structural component underneath the stator units in the flagellar motor of .

Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells.

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.

Gonadal sex and temperature independently influence germ cell differentiation and meiotic progression in .

In species with genetic sex determination (GSD), the sex identity of the soma determines germ cell fate. For example, in mice, XY germ cells that enter an ovary differentiate as oogonia, whereas XX germ cells that enter a testis initiate differentiation as spermatogonia. However, numerous species lack a GSD system and instead display temperature-dependent sex determination (TSD).

Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

Modular DNA origami-based electrochemical detection of DNA and proteins.

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte.

Integrin-activating protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets.

Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato , , 262-265 (2009); T. Sato , , 1762-1772 (2011)].

Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.

infection accelerates postnatal maturation of the intestinal epithelium.

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.

Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.

Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.

Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.

Comparing integrative ventilatory and renal acid-base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m.

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.

Palmitoylation-dependent association with Annexin II directs hepatitis E virus ORF3 sorting into vesicles and quasi-enveloped virions.

Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.

Comparing Virtual Reality-Based and Traditional Physical Objective Structured Clinical Examination (OSCE) Stations for Clinical Competency Assessments: Randomized Controlled Trial.

Background: Objective structured clinical examinations (OSCEs) are a widely recognized and accepted method to assess clinical competencies but are often resource-intensive.

Objective: This study aimed to evaluate the feasibility and effectiveness of a virtual reality (VR)-based station (VRS) compared with a traditional physical station (PHS) in an already established curricular OSCE.

Methods: Fifth-year medical students participated in an OSCE consisting of 10 stations.

Clinical outcomes and cost-utility analysis of GKRS plus TKIs versus TKIs in patients with EGFR-mutant lung adenocarcinoma and brain metastases: a Markov decision model.

Objective: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.

Methods: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW).