Intralesional and Infusional Updates for Metastatic Melanoma.

Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of advanced melanoma, followed by the utilization of isolated extremity perfusion (ILP). Following this, intralesional oncolytic viruses, xanthene dyes, and cytokines were introduced for the management of in-transit metastases as well as unresectable, advanced melanoma.

A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology.

Polymeric nanomaterials-based theranostic platforms for triple-negative breast cancer (TNBC) treatment.

Breast cancer, the second leading global cause of death, affects 2.1 million women annually, with an alarming 15 percent mortality rate. Among its diverse forms, Triple-negative breast cancer (TNBC) emerges as the deadliest, characterized by the absence of hormone receptors.

Future of neurocritical care: Integrating neurophysics, multimodal monitoring, and machine learning.

Multimodal monitoring (MMM) in the intensive care unit (ICU) has become increasingly sophisticated with the integration of neurophysical principles. However, the challenge remains to select and interpret the most appropriate combination of neuromonitoring modalities to optimize patient outcomes. This manuscript reviewed current neuromonitoring tools, focusing on intracranial pressure, cerebral electrical activity, metabolism, and invasive and noninvasive autoregulation monitoring.

BioInstruct: instruction tuning of large language models for biomedical natural language processing.

Objectives: To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles.

Materials And Methods: We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-seed samples randomly drawn from an 80 human curated instructions.

Understanding barriers to well-child visit attendance among racial and ethnic minority parents.

Objectives: To assess racial and ethnic minority parents' perceptions about barriers to well-child visit attendance.

Methods: For this cross-sectional qualitative study, we recruited parents of pediatric primary care patients who were overdue for a well-child visit from the largest safety net healthcare organization in central Massachusetts to participate in semi-structured interviews. The interviews focused on understanding potential knowledge, structural, and experiential barriers for well-child visit attendance.

A novel mouse home cage lickometer system reveals sex- and housing-based influences on alcohol drinking.

Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment.

Methods for structural sexism and population health research: Introducing a novel analytic framework to capture life-course and intersectional effects.

Accumulating evidence links structural sexism to gendered health inequities, yet methodological challenges have precluded comprehensive examinations into life-course and/or intersectional effects. To help address this gap, we introduce an analytic framework that uses sequential conditional mean models (SCMMs) to jointly account for longitudinal exposure trajectories and moderation by multiple dimensions of social identity/position, which we then apply to study how early life-course exposure to U.S.

Mobilizing Meaning: Religion and Spirituality Among Future Generations.

Religion and spirituality have long been known to impact both physical and mental health. Considering religion and spirituality as possible additions to social determinants of health, this article examines the current state of religion and spirituality in the United States and also discusses the ways in which they can contribute to the mental health of children and adolescents. Further, this article also discusses new approaches within religion and spirituality to address the changing needs of future generations.

RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.

TAR DNA-binding protein 43 (TDP43) is increasingly recognized for its involvement in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP43 proteinopathy, characterized by dysregulated nuclear export and cytoplasmic aggregation, is present in most ALS/FTD cases and is associated with a loss of nuclear function and genomic instability in neurons. Building on prior evidence linking TDP43 pathology to DNA double-strand breaks (DSBs), this study identifies a novel regulatory role for TDP43 in the DNA mismatch repair (MMR) pathway.

Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM.

Background: Down syndrome, or Trisomy 21, is the leading genetic cause of cognitive disability in children and is associated with a high risk of several comorbidities, particularly congenital heart defects, early onset Alzheimer's disease, leukaemia, and autoimmune disorders.

Objective: This study describes the design, methods, and operational procedures employed to establish a biobank dedicated to Down syndrome that can support research projects investigating the effects of various genetic and environmental factors on this complex disease.

Methods: Blood was collected from all recruited subjects, processed, aliquoted and immediately frozen at -80 °C in the Interinstitutional Multidisciplinary BioBank (BioBIM) facilities.

piRNA-Guided Transposon Silencing and Response to Stress in Germline.

Transposons are integral genome constituents that can be domesticated for host functions, but they also represent a significant threat to genome stability. Transposon silencing is especially critical in the germline, which is dedicated to transmitting inherited genetic material. The small Piwi-interacting RNAs (piRNAs) have a deeply conserved function in transposon silencing in the germline.

TIGIT stimulation suppresses autoimmune uveitis by inhibiting Th17 cell infiltration.

T cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint molecule that suppresses T cell activation and promotes an immunosuppressive environment to suppress autoimmune diseases. However, the impact of a TIGIT agonist as a treatment for ocular autoimmune disease has not been investigated. We examined TIGIT expression on T helper 17 (Th17) and regulatory T cells (Tregs), the role of TIGIT on experimental autoimmune uveitis and Th17 cells, and the impact of Treg generation following TIGIT stimulation.

Interprofessional reconstruction of a policy for academic advancement: The evolution and evaluation of scholarship for today, tomorrow, and beyond.

Within higher education, scholarship is narrowly and inconsistently defined, limiting recognition of evolving faculty expectations, particularly for nursing faculty. At this academic medical center, a campus-wide, multi-school, academic advancement policy was achieved with a broader definition of scholarship that included: peer-reviewed publication of federally funded research, as well as innovation in curriculum development, teaching methodology, community engagement, safety and quality improvement, clinical practice, and health policy that would be applicable to tenure and non-tenure track faculty. The background, process, and outcomes of developing an expanded definition of scholarship that encompasses new and evolving areas of scholarship for a reconstructed academic personnel policy is presented.

Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe.

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making.

A taxonomy for advancing systematic error analysis in multi-site electronic health record-based clinical concept extraction.

Background: Error analysis plays a crucial role in clinical concept extraction, a fundamental subtask within clinical natural language processing (NLP). The process typically involves a manual review of error types, such as contextual and linguistic factors contributing to their occurrence, and the identification of underlying causes to refine the NLP model and improve its performance. Conducting error analysis can be complex, requiring a combination of NLP expertise and domain-specific knowledge.

Closing the Digital Divide in Interventions for Substance Use Disorder.

Digital health interventions are exploding in today's medical practice and have tremendous potential to support the treatment of substance use disorders (SUD). Developers and healthcare providers alike must be cognizant of the potential for digital interventions to exacerbate existing inequities in SUD treatment, particularly as they relate to Social Determinants of Health (SDoH). To explore this evolving area of study, this manuscript will review the existing concepts of the digital divide and digital inequities, and the role SDoH play as drivers of digital inequities.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.