The Role of Cytonemes and Diffusive Transport in the Establishment of Morphogen Gradients.

Spatial distributions of morphogens provide positional information in developing systems, but how the distributions are established and maintained remains an open problem. Transport by diffusion has been the traditional mechanism, but recent experimental work has shown that cells can also communicate by filopodia-like structures called cytonemes that make direct cell-to-cell contacts. Here we investigate the roles each may play individually in a complex tissue and how they can jointly establish a reliable spatial distribution of a morphogen.

Defining Textbook Outcomes for Minimally Invasive Surgical Resection of Small Gastrointestinal Stromal Tumors (GIST) of the Stomach.

Background: Textbook outcome (TO) has been utilized to assess the quality of surgical care. This study aimed to define TO rates for minimally invasive gastric gastrointestinal stromal tumor (GIST) resections in a bi-institutional cohort.

Methods: Patients with gastric GIST (≤ 5 cm) who underwent laparoscopic or robotic resection (January 2014 to January 2024) were retrospectively identified from two GIST centers.

Identification of immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma.

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model.

Diagnosis and treatment of autonomic failure, pain and sleep disturbances in Parkinson's disease: guideline "Parkinson's disease" of the German Society of Neurology.

Background And Objective: Non-motor symptoms frequently develop throughout the disease course of Parkinson's disease (PD), and pose affected individuals at risk of complications, more rapid disease progression and poorer quality of life. Addressing such symptom burden, the 2023 revised "Parkinson's disease" guideline of the German Society of Neurology aimed at providing evidence-based recommendations for managing PD non-motor symptoms, including autonomic failure, pain and sleep disturbances.

Methods: Key PICO (Patient, Intervention, Comparison, Outcome) questions were formulated by the steering committee and refined by the assigned authors.

Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings.

Ipsilateral restriction of chromosome movement along a centrosome, and apical-basal axis during the cell cycle.

Little is known about how distance between homologous chromosomes are controlled during the cell cycle. Here, we show that the distribution of centromere components display two discrete clusters placed to either side of the centrosome and apical/basal axis from prophase to G interphase. 4-Dimensional live cell imaging analysis of centromere and centrosome tracking reveals that centromeres oscillate largely within one cluster, but do not cross over to the other cluster.

Prognostic immune markers in esophageal cancer patients managed with trimodal therapy.

Background: Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication.

Is the cortisol awakening response truly a response to awakening? Replication and extension using overnight sampling.

The cortisol awakening response (CAR) is a discrete component of the circadian cortisol profile. Evidence suggests that the CAR is a deviation from the pre-awakening increase in cortisol concentration, although this has yet to be replicated. Therefore, the purpose of this study was to replicate this finding and to investigate further the extent to which the CAR is distinct from the circadian profile.

Patient Characteristics, Diagnoses, and Management in a Combined Uveitis-Rheumatology Clinic.

Introduction: Combined uveitis-rheumatology clinics (combined clinics) are a relatively recent clinical care model. Here we report the demographics, ocular and systemic disease characteristics, and medications utilized in patients seen in a combined clinic at a tertiary care hospital in the USA.

Methods: Medical records were reviewed of patients seen at the Combined Clinic at the University of Colorado Hospital between January 1, 2016 and November 1, 2023.

Hormonal Therapies for Acne: A Comprehensive Update for Dermatologists.

Introduction: Acne impairs quality of life, often leads to permanent scars, and causes psychological distress. This review aims to update dermatologists on the Federal Drug Administration (FDA)-approved and off-label use of combined oral contraceptives (COC), clascoterone, spironolactone, and emerging hormonal therapies for acne treatment.

Methods: We reviewed current literature on hormonal acne treatments and discussed common patient concerns, barriers to care, and individualized care needs.

Exposure to Lead, Cadmium, Mercury and Arsenic Among Asian and Non-Asian Children and Adolescents in the United States: NHANES 2015-2018.

Higher concentrations of heavy metals were reported mainly among adult Asian persons compared to other racial/ethnic groups in earlier NHANES cycles' studies. We aimed to examine concentrations of metals among Asian children/adolescents compared to children/adolescents identifying with other racial/ethnic groups, considering socio-demographic factors and potential mediation by fish/shellfish consumption. Using NHANES data (2015-2018), 5293 participants (1-19 years) with blood/urinary measurements of lead, cadmium, mercury and arsenic were included.

Complex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.

Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively.

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.

Cytokine profile of bronchoalveolar lavage in patients with and without checkpoint inhibitor pneumonitis.

Background: Checkpoint inhibitor pneumonitis (CIP) that develops following immune checkpoint inhibitor (ICI) treatment can be difficult to distinguish from other common etiologies of lung inflammation in cancer patients. Here, we evaluate the bronchoalveolar lavage fluid (BAL) for potential biomarkers specific to CIP.

Methods: We conducted a retrospective study of patients who underwent standard of care bronchoscopy to compare the cytokines of interest between patients with and without CIP and with and without immune-mediated pulmonary diseases.

Tissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies.

Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer.

Basic Science and Pathogenesis.

Background: Microglia are key players in Alzheimer's disease (AD): Genetic risk for AD is enriched in microglial enhancers, and microglial gene regulatory networks have been shown to be disrupted in AD. Here, we studied polygenic and variant-specific (APOE) risk burden for AD in a xenotransplantation model of AD and human post-mortem brain tissue.

Method: We profiled gene regulation by RNA-seq and ATAC-seq in human iPS-derived microglia, xenotransplanted into the APPNL-G-F mouse model of AD.

Basic Science and Pathogenesis.

Background: Agora (https://agora.adknowledgeportal.org) is an openly available web resource developed to enable a broad spectrum of Alzheimer's disease (AD) researchers access to target-based evidence generated within the translational research portfolio of the National Institute on Aging (NIA).

Basic Science and Pathogenesis.

Background: Examining the neuropathology of the oldest-old has significantly advanced our understanding of the multiple etiologies in very late life. Most studies have included exclusively White decedents with limited ethnoracial diversity. Our goal was to characterize neuropathology in a cohort of ethnically and racially diverse oldest-old decedents.

Basic Science and Pathogenesis.

Background: Peripheral metabolic health status can reflect and/or contribute to the risk of Alzheimer's disease (AD). Peripheral metabolic health status can be indicated by metabolic health markers, such as inflammatory biomarker glycoprotein acetyls (GlycA) and specific components of lipoproteins (e.g.

Basic Science and Pathogenesis.

Background: Alcohol Use Disorder (AUD) affects over 15 million individuals in the United States, contributing to oxidative stress, neuroinflammation, and elevating the risk of neurodegeneration. Despite this, the connection between AUD and aging conditions, particularly Alzheimer's disease (AD), remains unclear. AD, with a heritability of 60-80%, is genetically linked, necessitating an exploration of the molecular implications of AUD and genetic susceptibility to AD.

Basic Science and Pathogenesis.

Background: NCRAD is a National Institute on Aging (NIA) cooperative grant, awarded to Indiana University since 1990, whose purpose is to serve as a biorepository for AD/ADRD researchers. With 74 participating across 150 unique institutions, NCRAD links specimens to clinical research data. NCRAD maintains over 2 million aliquots from more than 126,000 research participants spanning a wide range of AD/ADRD related phenotypes as well as healthy controls.

Diversity in Notch ligand-receptor signaling interactions.

The Notch signaling pathway uses families of ligands and receptors to transmit signals to nearby cells. These components are expressed in diverse combinations in different cell types, interact in a many-to-many fashion, both within the same cell (in cis) and between cells (in trans), and their interactions are modulated by Fringe glycosyltransferases. A fundamental question is how the strength of Notch signaling depends on which pathway components are expressed, at what levels, and in which cells.

Basic Science and Pathogenesis.

Background: According to data from the Alzheimer's Association, more than two-thirds of patients living with Alzheimer's disease (AD) in the United States are women. The interplay between aging and hormone depletion during menopause has been proposed as a leading cause, but the molecular underpinnings of this vulnerability are not fully understood. On the one hand, approaches that seek to supplement estrogens to rescue pre-menopausal hormonal levels have had contradictory outcomes in clinical trials.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is one of the leading causes of death among seniors in the United States and costs the nation over $300 billion each year. Neuropathologically, AD is characterized by neuronal loss, Aβ deposits in the form of plaques, and intracellular aggregates of tau protein in the form of neurofibrillary tangles (NFT). The amyloid cascade hypothesis, one of the leading hypotheses of AD pathogenesis, suggests that Aβ aggregates are directly neurotoxic, triggering downstream neurodegeneration.

Basic Science and Pathogenesis.

Background: Frontotemporal dementia is the most common form of dementia impacting those under the age of 60. It is estimated that 30% of affected persons have a genetic predisposition to this disease, with mutations in the genes encoding progranulin (GRN), chromosome 9 open reading frame 72(C9orf72), and microtubule associated protein tau (MAPT). Mutations in MAPT were discovered in 1998, yet to date, there have been no therapies or multisite clinical trials available to families.