Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.

Effect of hearing experience on preschool-aged children's eye gaze to a talker during spoken language processing.

Speechreading-gathering speech information from talkers' faces-supports speech perception when speech acoustics are degraded. Benefitting from speechreading, however, requires listeners to visually fixate talkers during face-to-face interactions. The purpose of this study is to test the hypothesis that preschool-aged children allocate their eye gaze to a talker when speech acoustics are degraded.

ROAR-CAT: Rapid Online Assessment of Reading ability with Computerized Adaptive Testing.

The Rapid Online Assessment of Reading (ROAR) is a web-based lexical decision task that measures single-word reading abilities in children and adults without a proctor. Here we study whether item response theory (IRT) and computerized adaptive testing (CAT) can be used to create a more efficient online measure of word recognition. To construct an item bank, we first analyzed data taken from four groups of students (N = 1960) who differed in age, socioeconomic status, and language-based learning disabilities.

Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival.

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.

Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.

Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput.

Factors Associated With Prolonged Venous Transit in Large Vessel Occlusion Acute Ischemic Strokes.

Background And Purpose: Prolonged venous transit (PVT), derived from computed tomography perfusion (CTP) time-to-maximum (T) maps, reflects compromised venous outflow (VO) in acute ischemic stroke due to large vessel occlusion (AIS-LVO). Poor VO is associated with worse clinical outcomes, but pre-treatment markers predictive of PVT are not well described.

Methods: We conducted a retrospective analysis of 189 patients with anterior circulation AIS-LVO who underwent baseline CT evaluation, including non-contrast CT, CT angiography, and CTP.

Microproteins: emerging roles as antibiotics.

Recent advances in computational prediction and experimental techniques have detected previously unknown microproteins, particularly in the human microbiome. These small proteins, produced by diverse microbial species, are emerging as promising candidates for new antibiotics.

Conditional Generative Models for Synthetic Tabular Data: Applications for Precision Medicine and Diverse Representations.

Tabular medical datasets, like electronic health records (EHRs), biobanks, and structured clinical trial data, are rich sources of information with the potential to advance precision medicine and optimize patient care. However, real-world medical datasets have limited patient diversity and cannot simulate hypothetical outcomes, both of which are necessary for equitable and effective medical research. Fueled by recent advancements in machine learning, generative models offer a promising solution to these data limitations by generating enhanced synthetic data.

Distinct retinal ganglion cell types in strictly subterranean, naturally microphthalmic mammals.

African mole-rats (Bathyergidae, Rodentia) are subterranean rodents that live in extensive dark underground tunnel systems and rarely emerge aboveground. They can discriminate between light and dark but show no overt visually driven behaviours except for light-avoidance responses. Their eyes and central visual system are strongly reduced but not degenerated.

Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing.

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.

Comparison of clinical outcomes between Castor single-branched stent graft and in situ fenestration in treating Stanford type B aortic dissection involving the left subclavian artery: A retrospective case-control study.

Stanford type B aortic dissection involving the left subclavian artery (LSA) poses significant clinical challenges. The Castor single-branch stent graft and in situ fenestration are commonly used techniques, but the better endovascular treatment remains debated. This study evaluates the clinical effects of the Castor single-branched stent graft versus in situ fenestration in treating Stanford type B aortic dissection involving the LSA.

A graph neural network-based model with out-of-distribution robustness for enhancing antiretroviral therapy outcome prediction for HIV-1.

Predicting the outcome of antiretroviral therapies (ART) for HIV-1 is a pressing clinical challenge, especially when the ART includes drugs with limited effectiveness data. This scarcity of data can arise either due to the introduction of a new drug to the market or due to limited use in clinical settings, resulting in clinical dataset with highly unbalanced therapy representation. To tackle this issue, we introduce a novel joint fusion model, which combines features from a Fully Connected (FC) Neural Network and a Graph Neural Network (GNN) in a multi-modality fashion.

Attention incorporated network for sharing low-rank, image and k-space information during MR image reconstruction to achieve single breath-hold cardiac Cine imaging.

Cardiac Cine Magnetic Resonance Imaging (MRI) provides an accurate assessment of heart morphology and function in clinical practice. However, MRI requires long acquisition times, with recent deep learning-based methods showing great promise to accelerate imaging and enhance reconstruction quality. Existing networks exhibit some common limitations that constrain further acceleration possibilities, including single-domain learning, reliance on a single regularization term, and equal feature contribution.

Person-Specific Analyses of Smartphone Use and Mental Health: An Intensive Longitudinal Study Over One Year.

Background: Contrary to popular concerns about the harmful effects of media use on mental health, research on this relationship is ambiguous, stalling advances in theory, interventions, and policy. Scientific explorations of the relationship between media and mental health have mostly found null or small associations, with the results often blamed on the use of cross-sectional study designs or imprecise measures of media use and mental health.

Objective: This exploratory empirical demonstration aimed to answer whether mental health effects are associated with media use experiences by (1) redirecting research investments to granular and intensive longitudinal recordings of digital experiences to build models of media use and mental health for single individuals over the course of one entire year, (2) using new metrics of fragmented media use to propose explanations of mental health effects that will advance person-specific theorizing in media psychology, and (3) identifying combinations of media behaviors and mental health symptoms that may be more useful for studying media effects than single measures of dosage and affect or assessments of clinical symptoms related to specific disorders.

Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study.

Background Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed.

Pleural Space Management in Thoracic Trauma.

Thoracic injuries are common, occurring in up to 60% of polytrauma patients and represent 25% of trauma deaths. Thoracic trauma frequently involves injury to the pleural space resulting in hemothorax and pneumothorax-effective management of the pleural space is essential. Reviewed in this article is management of the pleural space in chest wall trauma (including pneumothorax and hemothorax), and chest tube placement, indications for video-assisted thoracoscopic surgery, management, and complications.

Assessing Functional Outcomes in the Pediatric Neurocritical Care Population after Discharge: A Pilot Study.

Objectives: Pediatric neurocritical care (PNCC) patients experience high rates of morbidity, but comprehensive follow-up is not universal. We sought to identify predictors of functional decline in these children to guide future resource allocation.

Patients And Methods: We conducted a prospective observational study in a quaternary children's hospital pediatric intensive care unit (PICU) from July 2023 to December 2023.

"When I talk about it, my eyes light up!" Impacts of a national laboratory internship on community college student success.

Participation in technical/research internships may improve undergraduate graduation rates and persistence in science, technology, engineering, and mathematics (STEM), yet little is known about the benefits of these activities a) for community college students, b) when hosted by national laboratories, and c) beyond the first few years after the internship. We applied Social Cognitive Career Theory (SCCT) to investigate alumni perspectives about how CCI at Lawrence Berkeley National Laboratory (LBNL) impacted their academic/career activities. We learned that alumni had low confidence and expectations of success in STEM as community college students.

Code Milk: Finding the Pulse of Lactation Culture, Practices, and Preferences of Pediatric Emergency Medicine Fellows.

Objectives: The aim of the study is to characterize the lactation goals and practice of pediatric emergency medicine (PEM) fellows and to identify areas of improvement related to 1) policy awareness, 2) departmental culture and accommodations, and 3) lactation space and time.

Methods: This study is a national, cross-sectional survey study of PEM fellows and program directors (PDs). Two surveys were developed via iterative review and distributed by the PEM-PD Survey Committee.

Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response.

Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.