Factors associated with care-resistant behavior in the National Alzheimer's Coordinating Center's Uniform Data Set.

Introduction: Little is known about the factors associated with care-resistant behavior in community-dwelling persons living with dementia.

Methods: Regression modeling was performed on 41,143 responses to a standardized questionnaire from the National Alzheimer's Coordinating Center's Uniform Data Set.

Results: In the fully adjusted mixed-effects regression model, collinearity was low, with no variance inflation factor above 1.

GLI3 Is Required for M2 Macrophage Polarization and M2-Mediated Waldenström Macroglobulinemia Growth and Survival.

Waldenstrom macroglobulinemia (WM) is a non-Hodgkin B-cell lymphoma, characterized by bone marrow infiltration with plasma cells and lymphocytes. The tumor microenvironment (TME) plays an important role in mediating WM cell biology, but the effects of macrophages on WM biology remains unclear. Here, we investigated the effects of macrophages on WM growth and survival and identified a novel role for transcription factor GLI3 in macrophage polarization.

Museum-Based Education in Health Professions Learning: A 5-Year Retrospective.

A growing evidence base suggests that the integration of museum-based activities into health professions education can contribute to learner resilience and wellbeing, promote capacity for patient-centered care, and encourage equity in learning environments. However, the styles and methods for implementing museum-based programs vary widely across different institutions. This retrospective leverages the lessons learned from 5 years of experience implementing museum-based programs at one large academic institution to examine the various operational and logistical considerations in implementing a museum-based program for health professions learners.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Comparison of 2 Sets of Immunoassays Used in Modified 2-Tiered Testing Algorithms for the Diagnosis of Lyme Disease.

Background: Since 2019, modified 2-tiered testing (MTTT) algorithms have been available for the diagnosis of Lyme disease. MTTTs replaced the standard algorithms that utilized enzyme immunoassays and immunoblots with sequential enzyme immunoassays that detect different antigens.

Methods: We compared the performance of serological assays from ZEUS Scientific Inc.

Lead Extraction History, Training, Volume, and Location.

Transvenous lead extraction (TLE) has evolved significantly since the introduction of cardiac pacing systems in the 1950s. The need for TLE has grown due to the increasing complexity of cardiac devices and patients, alongside rising infection rates and regulatory recalls. Despite its challenges, improved institutional support and advanced training programs have made TLE more accessible.

Evidence of Human-designated Antiretroviral (ARV) Drug Residues in Broiler Chicken, Domestic Pigs, and Animal Feeds in Tanzania.

Background: Recent reports have indicated the use of antiretroviral (ARV) drugs to boost animal production in neighboring Uganda, with further reports of use in several African countries.

Methods: This cross-sectional study was conducted in nine districts in Tanzania, and involved screening for the presence of three first-line ARVs (lamivudine, nevirapine, and efavirenz) residues in the muscle and blood of domestic pigs and broiler chickens, and in sampled animal feed and water. Residues were determined using liquid chromatography and mass spectrometry (LC-MS/MS).

Multidisciplinary management of adult patients with chylothorax: a consensus statement.

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax.

Persistent and chronic opioid use after ambulatory surgery in US veterans (2011-2018).

Background: Opioid use beyond the perioperative period is a recognized adverse outcome, primarily studied in inpatients after complex major surgeries. Our goals are to determine the risk after ambulatory surgery and identify risk factors associated with long-term opioid prescriptions.

Methods: Our ambulatory surgery cohort included 1,393,332 veterans from October 1, 2011, to September 30, 2018 (fiscal year [FY] 12-18).

Immune checkpoint blockade: timing is everything.

Neoadjuvant immunotherapy effectively uses the in situ tumor as a reservoir of tumor antigens to promote systemic antitumor immunity. Studies indicate that intratumoral responses to immune checkpoint inhibitors (ICIs) are mediated by resident memory T cells cells that are sequestered in tumors and have specificity for a wide range of tumor antigens ICI treatment produces de novo priming of CD8 T cells in tumor and in tumor-draining lymph nodes, and can boost the antitumor immune response by blocking inhibitory checkpoint proteins that can turn off T cells within the tumor. Neoadjuvant ICI treatment can enhance both intratumoral and systemic antitumor immunity, including expansion of intratumoral T-cell clones which is strongly associated with pathological treatment response.

Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy.

This study reveals that Fc-enhanced anti-CTLA-4 harnesses novel mechanisms to overcome the limitations of conventional anti-CTLA-4, effectively treating poorly immunogenic and treatment-refractory cancers. Our findings support the development of a new class of immuno-oncology agents, capable of extending clinical benefit to patients with cancers resistant to current immunotherapies.

The clinical pharmacology and therapeutics course for graduating medical students at Dartmouth: Preparation for internship and residency.

Aims: This manuscript is a description of the clinical pharmacology and therapeutics (CPT) course that is required to be taken, and passed, by all medical students at the Geisel School of Medicine at Dartmouth during their final year of training, prior to entering their internship/residency.

Methods: We present a detailed CPT course curriculum, which includes the novel use of simulated expected professional activities (EPAs) and an analysis of the level of confidence the students who took the course had at the beginning and at the end of the course in performing the three simulated EPAs.

Results: The course currently consists of 31 h of presentations on what are considered major clinical pharmacology topics and is led by two clinical pharmacologists at Dartmouth (D.

A Practical Approach for Developing Shared Decision-Making Knowledge, Skills, and Capability for Busy Health Care Practitioners.

Background: There has been substantial development of shared decision-making (SDM) methods and approaches in the past few decades, but despite this, building capability and scaling application of SDM in clinical practice remains a challenge. Here the authors describe the development and initial experience with a new virtual Practical Approach continuing education program for busy practicing clinicians who care for people with complex, chronic, and costly conditions who are frequently faced with preference-sensitive decisions. This program was designed to provide plain language training in SDM for real-world clinical practice using an easy 4-step approach that does not require prior training or formal education in SDM theory or methods.

PP2A-B56 regulates Mid1 protein levels for proper cytokinesis in fission yeast.

Protein phosphorylation regulates many steps in the cell division process including cytokinesis. In the fission yeast , the anillin-like protein Mid1 sets the cell division plane and is regulated by phosphorylation. Multiple protein kinases act on Mid1, but no protein phosphatases have been shown to regulate Mid1.

Virtual Interviews in the Post-COVID-19 Emergency Era: Insights from the Gastroenterology Fellowship Applicants and Programs.

Background: Virtual interviews are still recommended for fellowship applications, 3 years after the beginning of the COVID-19 pandemic. Improving equity by reducing the cost for the applicants has been the most important reason for continuing virtual interviews. However, some argue that important information may be missed in a virtual setting.