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.

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.

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.

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.

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.

Circadian rhythm of heart rate and activity: A cross-sectional study.

Circadian rhythms are governed by a biological clock, and are known to occur in a variety of physiological processes. We report results on the circadian rhythm of heart rate observed using a wrist-worn wearable device (Fitbit), consisting of over 17,000 individuals over the course of 30 days. We obtain an underlying heart rate circadian rhythm from the time series heart rate by modeling the circadian rhythm as a sum over the first two Fourier harmonics.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

AAPM Truth-based CT (TrueCT) reconstruction grand challenge.

Background: This Special Report summarizes the 2022, AAPM grand challenge on Truth-based CT image reconstruction.

Purpose: To provide an objective framework for evaluating CT reconstruction methods using virtual imaging resources consisting of a library of simulated CT projection images of a population of human models with various diseases.

Methods: Two hundred unique anthropomorphic, computational models were created with varied diseases consisting of 67 emphysema, 67 lung lesions, and 66 liver lesions.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Incidence of cancer-related lymphoedema: a protocol for a living systematic review with meta-analysis.

Introduction: Given the projected rise in the incidence of cancer treatment-related conditions, such as lymphoedema, and the limited research on lymphoedema in cancers with poor prognoses, there is a need for a better understanding of cancer-related lymphoedema incidence and associated risk factors across all types of cancers. The objectives of this review are (1) to produce a resource on an open-access platform that facilitates continuous update of incidence estimates and risk factors as evidence emerges, (2) to provide the most up-to-date estimate of the incidence of cancer-related lymphoedema and (3) to evaluate the strength and consistency of the association between lymphoedema and cancer treatment and non-treatment-related risk factors.

Methods And Analysis: A living systematic and grey literature search will be conducted to identify studies reporting the incidence, prevalence of lymphoedema or associated risk factors in individuals who have undergone treatment for any type of cancer.

Identifying pre-diabetes 'hotspots' in Northern California using geospatial analysis: opportunities to target diabetes prevention strategies and improve health equity.

Objectives: The US Preventive Services Task Force recommends screening of adults aged 35-70 with a body mass index ≥25 kg/m for type 2 diabetes and referral of individuals who screen positive for pre-diabetes to evidence-based prevention strategies. The diabetes burden in the USA is predicted to triple by 2060 necessitating strategic diabetes prevention efforts, particularly in areas of highest need. This study aimed to identify pre-diabetes hotspots using geospatial mapping to inform targeted diabetes prevention strategies.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Specialized pericyte subtypes in the pulmonary capillaries.

Pericytes are essential for capillary stability and homeostasis, with impaired pericyte function linked to diseases like pulmonary arterial hypertension. Investigating pericyte biology has been challenging due to the lack of specific markers, making it difficult to distinguish pericytes from other stromal cells. Using bioinformatic analysis and RNAscope, we identified Higd1b as a unique gene marker for pericytes and subsequently generated a knock-in mouse line, Higd1b-CreERT2, that accurately labels pericytes in the lung and heart.