"The Environment Fostered True Growth": Harnessing Coaching on an Innovative Medicine Sub-internship.

Background: Medicine sub-internships aim to prepare students for residency. However, the traditional sub-internship structure, with multiple learners at varied levels, poses obstacles to providing the clinical exposure, learning environment, and direct observation and feedback necessary to develop essential skills.

Aim: Investigate the educational experience of learners on a coaching-centered sub-internship (CCSI) on a resident uncovered ward service.

A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients.

Objectives: To assess the efficacy and safety of an intra-articular (IA) CLK/DYRK inhibitor, lorecivivint (LOR), for the treatment of moderate to severe symptomatic knee osteoarthritis (OA).

Methods: This was a Phase 3, 28-week, multicentre, double-blind, placebo-controlled study evaluating the efficacy and safety of a single IA injection of LOR. Patients with ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and pain Numeric Rating Scale (NRS) ≥4 and ≤8 in the target knee were randomised (1:1) to receive LOR 0.

Phase 3, 56-week, randomised, double-blind, placebo-controlled study utilising patient-reported and radiographic outcomes evaluating the efficacy and safety of a lorecivivint injection in patients with moderate to severe knee osteoarthritis: OA-11 Study.

Objectives: To determine the efficacy, safety, and tolerability of intraarticular (IA) lorecivivint (LOR) in the treatment of knee osteoarthritis (OA).

Methods: Patients with American College of Rheumatology criteria-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and medial Joint Space Width (JSW) by radiograph between 1.5 and 4 mm in the target knee were enrolled in this phase 3, 56-week, multicentre, double-blind, placebo-controlled study.

A Neighborhood-Level Hispanic Paradox: the Interaction between Hispanic Density, Neighborhood Disadvantage, and Survival in Breast Cancer Patients.

Background: To evaluate the impact of Hispanic ethnic enclaves (EE) on the relationship between neighborhood disadvantage and overall survival (OS) in breast cancer (BCa) patients.

Methods: Data from BCa patients with stage I-IV disease diagnosed between 2005-2017 was used to analyze the effects of Area Deprivation Index (ADI) scores, a measure of neighborhood disadvantage, and census-tract level Hispanic density, a measure of EE, on OS using mixed-effects Cox regression models. The final model included the following individual-level factors (age, income, race, Hispanic/Latino origin, nativity, insurance status, and comorbidities (hypertension, diabetes, and body mass index) and clinical factors (National Comprehensive Cancer Network guideline-concordant treatment, stage, and receptor subtype).

Cu-Ni Oxidation Mechanism Unveiled: A Machine Learning-Accelerated First-Principles and TEM Study.

The development of accurate methods for determining how alloy surfaces spontaneously restructure under reactive and corrosive environments is a key, long-standing, grand challenge in materials science. Using machine learning-accelerated density functional theory and rare-event methods, in conjunction with environmental transmission electron microscopy (ETEM), we examine the interplay between surface reconstructions and preferential segregation tendencies of CuNi(100) surfaces under oxidation conditions. Our modeling approach predicts that oxygen-induced Ni segregation in CuNi alloys favors Cu(100)-O c(2 × 2) reconstruction and destabilizes the Cu(100)-O (2√2 × √2)45° missing row reconstruction (MRR).

Insulin and insulin-like growth factor and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Background: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Further, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer.

Methods: This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study.

Cancer Incidence in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) - The Onco-SOL Ancillary Study.

Background: Few studies have examined how cancer incidence varies by country of origin among United States Hispanic/Latino adults. Herein, we describe the incidence rates of cancer overall and for screen-detectable, tobacco-related, and obesity-related cancers among 16,415 participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an ongoing population-based cohort study of Hispanic/Latino adults from diverse backgrounds.

Methods: Cohort participant records were linked to the state cancer registries in New York, Florida, California, and Illinois to ascertain cancer incidence from baseline (2008-2011) through 2021.

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait.

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial.

Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy.

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

PrEP Use in a US National Sample of Trans Men and Other Transmasculine People Who Have Sex With Men: A Longitudinal Analysis.

Introduction: Efforts to improve pre-exposure prophylaxis (PrEP) uptake among gay men, transgender women, and Black cisgender women are evident across the United States, responding to epidemiologic data showing a disproportionate HIV burden in these communities. However, transgender men and other transmasculine people who have sex with men (TMSM)-those assigned female at birth who identify otherwise and have sex with cisgender men-are often excluded from these statistics. This community has unique vulnerabilities and prevention needs.

CT Predictors of Angiolymphatic Invasion in Non-Small Cell Lung Cancer 30 mm or Smaller.

Background Angiolymphatic invasion (ALI) is an important prognostic indicator in non-small cell lung cancer (NSCLC). However, few studies focus on radiologic features for predicting ALI in patients with early-stage NSCLCs 30 mm or smaller. Purpose To identify radiologic features for predicting ALI in NSCLCs 30 mm or smaller in maximum diameter.

Multi-Cancer Early Detection Tests: State of the Art and Implications for Radiologists.

Multi-cancer early detection (MCED) tests are already being marketed as noninvasive, convenient opportunities to test for multiple cancer types with a single blood sample. The technology varies-involving detection of circulating tumor DNA, fragments of DNA, RNA, or proteins unique to each targeted cancer. The priorities and tradeoffs of reaching diagnostic resolution in the setting of possible false positives and negatives remain under active study.

Variable surface antigen expression, virulence, and persistent infection by malaria parasites.

SUMMARYThe human malaria parasite is known for its ability to maintain lengthy infections that can extend for over a year. This property is derived from the parasite's capacity to continuously alter the antigens expressed on the surface of the infected red blood cell, thereby avoiding antibody recognition and immune destruction. The primary target of the immune system is an antigen called PfEMP1 that serves as a cell surface receptor and enables infected cells to adhere to the vascular endothelium and thus avoid filtration by the spleen.

Addressing the Shortage of Academic Nurse Educators: An Opportunity for Collaboration Between Academic and Healthcare Organization Leaders.

Background: The numbers of nursing school admissions and, thus, future nursing graduates are directly affected by the lack of qualified ANEs.

Methods: A consortium of diverse ANEs was formed to research these questions using the nominal group technique.

Results: Two central themes emerged from the consortium: support and collaboration.

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design.

Background: Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the RANO meningioma group.

Methods: PubMed, ClinicalTrials.

Serendipitous Discovery of Dearomatized Dimers in Anthracene Derivative Oxidation.

We present the serendipitous discovery of an unusual dimer formed from anthracene-derived polyarenes. Unlike the typical oxidative coupling of substituted aromatic scaffolds, the reaction yielded a dearomatized enone dimer as the sole product. This dearomatized motif, notably, does not undergo the commonly observed rearomatization, and no biaryl products were detected.

Stanniocalcin 1 in patients with refractory colorectal cancer treated with regorafenib: A post-hoc biomarker analysis of the TEXCAN and CORRECT trials.

Biomarkers for anti-angiogenic drugs in chemo-refractory metastatic colorectal cancer (mCRC) are lacking. We investigated the relationship between stanniocalcin 1 (STC1) and outcomes in patients treated with regorafenib in the TEXCAN and CORRECT trials. Baseline plasma STC1 protein levels were measured by ELISA from patients with chemo-refractory mCRC enrolled in TEXCAN (regorafenib n=48) and CORRECT (placebo n=211; regorafenib n=435).

Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.