Adjunctive therapy with an oral HS donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

Background And Purpose: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (HS), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and HS donor in two preclinical models of cardiometabolic HFpEF was investigated.

A Generative Pretrained Transformer (GPT)-Powered Chatbot as a Simulated Patient to Practice History Taking: Prospective, Mixed Methods Study.

Background: Communication is a core competency of medical professionals and of utmost importance for patient safety. Although medical curricula emphasize communication training, traditional formats, such as real or simulated patient interactions, can present psychological stress and are limited in repetition. The recent emergence of large language models (LLMs), such as generative pretrained transformer (GPT), offers an opportunity to overcome these restrictions.

Factors associated with HIV Testing within the National Health Interview Survey (2006-2018).

The Centers for Disease Control and Prevention recommends that individuals aged 13-64 test for HIV at least once during their lifetime. However, screening has been disproportionate among racial/ethnic populations. Using the National Health Interview Survey data (2006-2018), we examined HIV screening prevalence within racial/ethnic groups in the United States (US), and factors associated with testing among 301,191 individuals.

Performance of ChatGPT on free-response, clinical reasoning exams.

Importance: Studies show that ChatGPT, a general purpose large language model chatbot, could pass the multiple-choice US Medical Licensing Exams, but the model's performance on open-ended clinical reasoning is unknown.

Objective: To determine if ChatGPT is capable of consistently meeting the passing threshold on free-response, case-based clinical reasoning assessments.

Design: Fourteen multi-part cases were selected from clinical reasoning exams administered to pre-clerkship medical students between 2019 and 2022.

Perspectives, benefits and challenges of a live OSCE during the COVID-19 pandemic in a cross-sectional study.

Objectives: Restrictions due to the COVID-19 pandemic mandated fundamental changes to student evaluations, including the administration of the observed structured clinical examination (OSCE). This study aims to conduct an in-person OSCE to verify students' practical skills under necessary infection control practices and the impact of face masks on student-patient interactions.

Design: Cross-sectional design.

Reactivated disseminated tuberculosis in pregnancy: Case report and review of the literature.

This case report describes the evaluation and management of a 32-year-old woman who presented shortly after a fetal demise at 23 weeks of gestation with multiple symptoms, including bloody vaginal discharge. Although the initial diagnostic concern was for metastatic malignancy, the patient was ultimately determined to have disseminated tuberculosis. Genital tuberculosis is common worldwide, yet guidelines for evaluation are limited.

Intoxication and pitch control in tonal and non-tonal language speakers.

Alcohol intoxication is known to affect pitch variability in non-tonal languages. In this study, intoxication's effects on pitch were examined in tonal and non-tonal language speakers, in both their native language (L1; German, Korean, Mandarin) and nonnative language (L2; English). Intoxication significantly increased pitch variability in the German group (in L1 and L2), but not in the Korean or Mandarin groups (in L1 or L2), although there were individual differences.

A Call to Action From the California Consortium for the Assessment of Clinical Competence: Making the Case for Regional Collaboration.

The discontinuation of the United States Medical Licensing Examination Step 2 Clinical Skills Examination emphasizes the need for other reliable standardized assessments of medical student clinical skills. For 30 years, the California Consortium for the Assessment of Clinical Competence (CCACC) has collaborated in the development of clinical skills assessments and has become a valuable resource for clinicians, standardized patient educators, psychometricians, and medical educators. There are many merits to strong multi-institutional partnerships, including the integration of data across multiple schools to provide feedback to both students and curricula, pooled test performance statistics for analysis and quality assurance, shared best practices and resources, individual professional development, and opportunities for research and scholarship.

Efficacy and Cardiovascular Safety of SGLT2 Inhibitors.

Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus.

A Multi-Institution Collaboration to Define Core Content and Design Flexible Curricular Components for a Foundational Medical School Course: Implications for National Curriculum Reform.

Medical educators have not reached widespread agreement on core content for a U.S. medical school curriculum.

Clinical, Radiographic, and Histologic Outcome of Regenerative Endodontic Treatment in Human Teeth Using a Novel Collagen-hydroxyapatite Scaffold.

Introduction: Histologic examination of teeth after regenerative endodontic treatment (RET) shows that the type, quality, and quantity of tissues formed in the root canal space are not predictable. The aim of this study was to examine clinically, radiographically, and histologically the outcome of RET in immature noninfected human teeth using SynOss Putty (Collagen Matrix Inc, Oakland, NJ) as a scaffold.

Methods: Three pairs of maxillary/mandibular first premolars in 3 patients scheduled for extraction were included.

Promoting student case creation to enhance instruction of clinical reasoning skills: a pilot feasibility study.

Background: It is a common educational practice for medical students to engage in case-based learning (CBL) exercises by working through clinical cases that have been developed by faculty. While such faculty-developed exercises have educational strengths, there are at least two major drawbacks to learning by this method: the number and diversity of cases is often limited; and students decrease their engagement with CBL cases as they grow accustomed to the teaching method. We sought to explore whether student case creation can address both of these limitations.

Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle.

Recent observations suggest that atypical chemokine receptor (ACKR)3 and chemokine (C-X-C motif) receptor (CXCR)4 regulate human vascular smooth muscle function through hetero-oligomerization with α-adrenoceptors. Here, we show that ACKR3 also regulates arginine vasopressin receptor (AVPR)1A. We observed that ACKR3 agonists inhibit arginine vasopressin (aVP)-induced inositol trisphosphate (IP) production in human vascular smooth muscle cells (hVSMCs) and antagonize aVP-mediated constriction of isolated arteries.

Effects of subject-case marking on agreement processing: ERP evidence from Basque.

Previous cross-linguistic research has found that comprehenders are immediately sensitive to various kinds of agreement violations across languages. We focused on Basque, a verb-final ergative language with both subject-verb (SV) and object-verb (OV) agreement. We compared the effects of SV agreement violations on comprehenders' event-related brain potentials (ERPs) in transitive sentences (where OV agreement is present, and the subject is ergative) and intransitive sentences (where OV agreement is absent, and the subject is absolutive).

When linearity prevails over hierarchy in syntax.

Hierarchical structure has been cherished as a grammatical universal. We use experimental methods to show where linear order is also a relevant syntactic relation. An identical methodology and design were used across six research sites on South Slavic languages.

Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3.

Background And Purpose: Chemokines and their receptors form an intricate interaction and signalling network that plays critical roles in various physiological and pathological cellular processes. The high promiscuity and apparent redundancy of this network makes probing individual chemokine/receptor interactions and functional effects, as well as targeting individual receptor axes for therapeutic applications, challenging. Despite poor sequence identity, the N-terminal regions of chemokines, which play a key role in their activity and selectivity, contain several conserved features.

Detecting Cell Surface Expression of the G Protein-Coupled Receptor CXCR4.

G protein-coupled receptors (GPCRs) are cell surface receptors that relay extracellular signals to the inside of the cells. C-X-C chemokine receptor 4 (CXCR4) is a GPCR that undergoes receptor internalization and recycling upon stimulation with its cognate ligand, C-X-C chemokine 12 (CXCL12). Using this receptor/ligand pair we describe the use of two techniques, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, widely used to quantify GPCR internalization from the plasma membrane and its return to the cell surface by recycling.

Validity Evidence and Scoring Guidelines for Standardized Patient Encounters and Patient Notes From a Multisite Study of Clinical Performance Examinations in Seven Medical Schools.

Purpose: To examine validity evidence of local graduation competency examination scores from seven medical schools using shared cases and to provide rater training protocols and guidelines for scoring patient notes (PNs).

Method: Between May and August 2016, clinical cases were developed, shared, and administered across seven medical schools (990 students participated). Raters were calibrated using training protocols, and guidelines were developed collaboratively across sites to standardize scoring.

A Requirement for Metamorphic Interconversion in the Antimicrobial Activity of Chemokine XCL1.

Chemokines make up a superfamily of ∼50 small secreted proteins (8-12 kDa) involved in a host of physiological processes and disease states, with several previously shown to have direct antimicrobial activity comparable to that of defensins in efficacy. XCL1 is a unique metamorphic protein that interconverts between the canonical chemokine fold and a novel all-β-sheet dimer. Phylogenetic analysis suggests that, within the chemokine family, XCL1 is most closely related to CCL20, which exhibits antibacterial activity.

New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.

Chemokine receptor (CKR) signaling forms the basis of essential immune cellular functions, and dysregulated CKR signaling underpins numerous disease processes of the immune system and beyond. CKRs, which belong to the seven transmembrane domain receptor (7TMR) superfamily, initiate signaling upon binding of endogenous, secreted chemokine ligands. Chemokine-CKR interactions are traditionally described by a two-step/two-site mechanism, in which the CKR N-terminus recognizes the chemokine globular core (i.

Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface.

CXCL12 is a human chemokine that recognizes the CXCR4 receptor and is involved in immune responses and metastatic cancer. Interactions between CXCL12 and CXCR4 are an important drug target but, like other elongated protein-protein interfaces, present challenges for small molecule ligand discovery due to the relatively shallow and featureless binding surfaces. Calculations using an NMR complex structure revealed a binding hot spot on CXCL12 that normally interacts with the I4/I6 residues from CXCR4.

Revitalization of open apex teeth with apical periodontitis using a collagen-hydroxyapatite scaffold.

An enhanced revision of the revitalization endodontic technique for immature teeth with apical periodontitis has been described. It includes the addition of collagen-hydroxyapatite scaffold to the currently practiced revascularization technique. Four cases treated in series are presented in this report, 1 case involving 2 teeth.

Structure-function analysis of CCL28 in the development of post-viral asthma.

CCL28 is a human chemokine constitutively expressed by epithelial cells in diverse mucosal tissues and is known to attract a variety of immune cell types including T-cell subsets and eosinophils. Elevated levels of CCL28 have been found in the airways of individuals with asthma, and previous studies have indicated that CCL28 plays a vital role in the acute development of post-viral asthma. Our study builds on this, demonstrating that CCL28 is also important in the chronic post-viral asthma phenotype.

Assessing 3rd year medical students' interprofessional collaborative practice behaviors during a standardized patient encounter: A multi-institutional, cross-sectional study.

Background: To understand how third-year medical student interprofessional collaborative practice (IPCP) is affected by self-efficacy and interprofessional experiences (extracurricular experiences and formal curricula).

Methods: The authors measured learner IPCP using an objective structured clinical examination (OSCE) with a standardized nurse (SN) and standardized patient (SP) during a statewide clinical performance examination. At four California medical schools from April to August 2012, SPs and SNs rated learner IPCP (10 items, range 0-100) and patient-centered communication (10 items, range 0-100).