A study protocol for an interrupted time series analysis and pre-post surveys to assess the effects a community-wide sanitation system on environmental contamination, infection risk, and well-being in Alabama's Black Belt.

Introduction: Rural sanitation deficits in the United States represent an important source of non-point source pollution and may present risks to public health. We propose an interrupted time series analysis to measure the effect of a town-wide sanitation expansion program on the release of pathogens to the environment. This work is expected to yield valuable insight into the potential for rural sanitation improvements to reduce pathogen releases and support public health and well-being.

Decoding Cellular Stress States for Toxicology Using Single-Cell Transcriptomics.

We applied the TempO-LINC platform to generate single-cell transcriptomic (SCTr) profiles of ~40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes (, ) along with HSR and UPR activation, with co-expression of , , and in subsets of cells.

A map of enhancer regions in primary human neural progenitor cells using capture STARR-seq.

Genome-wide association studies (GWASs) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. Here, we perform capture STARR-sequencing of over 70,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We select candidate regions by integrating data from NPCs, prefrontal cortex, developmental timepoints, and GWASs.

Mapping global floods with 10 years of satellite radar data.

Floods cause extensive global damage annually, making effective monitoring essential. While satellite observations have proven invaluable for flood detection and tracking, comprehensive global flood datasets spanning extended time periods remain scarce. In this study, we introduce a deep learning flood detection model that leverages the cloud-penetrating capabilities of Sentinel-1 Synthetic Aperture Radar (SAR) satellite imagery, enabling consistent flood extent mapping through cloud cover and in both day and night conditions.

Artifacts affecting dual-energy X-ray absorptiometry and bone mineral density measurements: a case report and review of the literature.

Introduction: It is important to recognize artifacts of dual-energy X-ray absorptiometry because they may alter bone mineral density measurements. To prevent erroneous decisions and misdiagnosis regarding treatment and follow-up, bone mineral density measurement adjustments are needed.

Case Presentation: We present three cases in which artifacts altered the measurements of bone mineral density in the lumbar field of a dual-energy X-ray absorptiometry scan.

Kidney cystogenesis in embryonic- and adult-onset ADPKD is suppressed from lack of adenylyl cyclase targeting to cilia.

Multiple cellular pathways are dysregulated in autosomal dominant polycystic kidney disease (ADPKD), but mechanisms initiating cyst formation are unknown. ADPKD is caused by mutations in genes that encode for polycystins that localize to primary cilia. The primary cilium is a miniscule subcellular compartment for generating signaling outputs that profoundly affect cellular function.

A Concordance Study among 26 NGS Laboratories Participating in the NCI Molecular Analysis for Therapy Choice Clinical Trial.

Purpose: NCI selected a network of Clinical Laboratory Improvement Amendments-certified laboratories performing routine next-generation sequencing (NGS) tumor testing to identify patients for the NCI Molecular Analysis for Therapy Choice (NCI-MATCH) trial. This large network provided a unique opportunity to compare variant detection and reporting between a wide range of testing platforms.

Experimental Design: Twenty-eight NGS assays from 26 laboratories within the NCI-MATCH Network, including the NCI-MATCH central laboratory (CL) and 11 commercial and 14 academic designated laboratories (DL), were used for this study.

Hypopigmented Junctional BAP1-Inactivated Melanocytoma: A Paradigm Shift.

Since their original description by Wiesner et al., the spectrum of clinical, histopathologic, and molecular findings of BAP1 (BRCA1-associated protein 1)-inactivated melanocytomas has been more fully characterized. Herein, we report an exceptional presentation of multiple junctional melanocytic BAP1-inactivated melanocytomas with a clinically hypopigmented appearance in a patient.

Oregon primary care providers as a frontline defense in the War on Melanoma™: improving access to melanoma education.

Melanoma is one of the deadliest forms of skin cancer but is typically cured with surgical excision when detected early. As an access point to medical care, primary care providers (PCP) play an integral role in early skin cancer detection. However, limited time for examinations and dermatologic training may present barriers to effective skin examination in the primary care setting.

Discovery of GJG057, a Potent and Highly Selective Inhibitor of Leukotriene C4 Synthase.

Leukotriene C4 synthase (LTC4S) is a glutathione -transferase that mediates the biosynthesis of cysteinyl leukotriene C4 (LTC4). Cysteinyl leukotrienes (CysLTs) are lipid mediators that drive type 2 inflammation, bronchoconstriction, and itch. Thus, LTC4S represents an attractive drug target for the treatment of allergic inflammatory diseases, but to date, no LTC4S inhibitor has been tested in patients.

Muco-Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery.

Intranasal delivery of mRNA vaccines offers promising opportunities to combat airborne viruses like SARS-CoV-2 by provoking mucosal immunity, which not only defends against respiratory infection but also prevents contagious transmission. However, the development of nasal mRNA vaccines has been hampered by the lack of effective means to overcome the mucus barrier. Herein, ionizable lipid-incorporated liquid lipid nanoparticles (iLLNs) capable of delivering mRNA cargo across airway mucosa are designed.

Plasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression.

Background: Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death.

Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes.

Introduction: Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods: We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.

High-throughput gene expression analysis with TempO-LINC sensitively resolves complex brain, lung and kidney heterogeneity at single-cell resolution.

We report the development and performance of a novel genomics platform, TempO-LINC, for conducting high-throughput transcriptomic analysis on single cells and nuclei. TempO-LINC works by adding cell-identifying molecular barcodes onto highly selective and high-sensitivity gene expression probes within fixed cells, without having to first generate cDNA. Using an instrument-free combinatorial indexing approach, all probes within the same fixed cell receive an identical barcode, enabling the reconstruction of single-cell gene expression profiles across as few as several hundred cells and up to 100,000 + cells per sample.

Permanent cilia loss during cerebellar granule cell neurogenesis involves withdrawal of cilia maintenance and centriole capping.

Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles.

Conventional Radiotherapy Timing and Wound Complication Avoidance After Surgery for Metastatic Spine Disease. A LatAm Modified Delphi Study.

Background: Combining surgery and radiotherapy is the gold standard in treating spinal metastasis when spinal stabilization or surgical decompression is required. Determining the optimal timing for radiotherapy postsurgery is crucial to balance treatment efficacy minimizing wound complications. The study aimed to identify consensus and nonconsensus areas among Latin American spinal surgeons regarding the use, timing, risks, and surgical approach to conventional external beam radiotherapy (cEBRT) following spinal surgery for metastases, specifically focusing on the risk of radiotherapy-related wound complications.

Of goats and heat, the differential impact of summer temperature on habitat selection and activity patterns in mountain goats of different ecotypes.

Climate change disproportionately affects northern and alpine environments, with faster rates of warming than the global average. Because alpine and northern species are particularly well adapted to cool temperatures, most species must modify their behavior when temperatures exceed a critical threshold. Evaluating how temperature increases affect species inhabiting northern and alpine environments is therefore essential to understand the effects of projected climate change on these ecosystems.

A trainee-informed model for undergraduate neuroscience research programs serving marginalized students.

Undergraduate research programs improve career outcomes for historically marginalized students in the US, but low retention rates in postgraduate research persist. As graduate students and postdocs, we present a combination of trainee-informed approaches for tailoring summer research programs to these students’ needs and share key materials to facilitate adoption of these approaches at other institutions.

Binding profiles for 961 and transcription factors reveal tissue-specific regulatory relationships.

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here, we present the culmination of the efforts of the modENCODE (model organism Encyclopedia of DNA Elements) and modERN (model organism Encyclopedia of Regulatory Networks) consortia to systematically assay TF binding events in vivo in two major model organisms, (fly) and (worm). These data sets comprise 605 TFs identifying 3.