A platform for multimodal pooled genetic screens reveals regulators of liver function.

Organ function requires coordinated activities of thousands of genes in distinct, spatially organized cell types. Understanding the basis of emergent tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes . Here, we develop paired imaging and sequencing methods to construct large-scale, multi-modal genotype-phenotypes maps in tissue with pooled genetic perturbations.

Spatiotemporal modeling of molecular holograms.

Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo (https://github.com/aristoteleo/spateo-release), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.

Decision Fusion Model for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Multi-MR Habitat Imaging and Machine-Learning Classifiers.

Rationale And Objectives: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers.

Materials And Methods: We retrospectively included 300 HCC patients.

Sexual Dimorphism of Radiomic Features in the Brain: An Exploratory Study Using 700 μm MP2RAGE MRI at 7 T.

Objectives: The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution.

Materials And Methods: Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.

Characterization of Expression in Renal Cell Carcinoma.

Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of expression in RCC and their impacts on RCC outcomes.

Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. -high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM).

Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study.

Background: The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD).

Methods: Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data.

CT-Based Super-Resolution Deep Learning Models with Attention Mechanisms for Predicting Spread Through Air Spaces of Solid or Part-Solid Lung Adenocarcinoma.

Rationale And Objectives: Spread through air space (STAS) is a novel invasive pattern of lung adenocarcinoma (LUAD), and preoperative knowledge of STAS status is helpful in choosing an appropriate surgical approach.

Materials And Methods: This retrospective study collected and analyzed 602 patients diagnosed with LUAD from two medical centers: center 1 was randomly partitioned into training (n = 358) and validation cohorts (n = 154) at a 7:3 ratio; and center 2 was the external test cohort (n = 90). Super resolution was performed on all images to acquire high-resolution images, which were used to train the SE-ResNet50 model, before creating an equivalent parameter ResNet50 model.

Contrast-Enhanced Mammography Radiomics Analysis for Preoperative Prediction of Breast Cancer Molecular Subtypes.

Background: Predicting breast cancer molecular subtypes can help guide individualised clinical treatment of patients who need the rational preoperative treatment. This study aimed to investigate the efficacy of preoperative prediction of breast cancer molecular subtypes by contrast-enhanced mammography (CEM) radiomic features.

Methods: This retrospective two-centre study included women with breast cancer who underwent CEM preoperatively between August 2016 and May 2022.

Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.

Background: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function.

Methods: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS).

Long-Term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

Introduction: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years.

Methods: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years.

Mediation of Systemic Inflammation on Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke.

Background: Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation.

Methods: Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset.

Smartphone imaging repository: a novel method for creating a CT image bank.

Background: Imaging repositories are commonly attached to ongoing clinical trials, but capturing, transmitting, and storing images can be complicated and labor-intensive. Typical methods include outdated technologies such as compact discs. Electronic file transfer is becoming more common, but even this requires hours of staff time on dedicated computers in the radiology department.

Proteomic profiling of urinary small extracellular vesicles in children with pneumonia: a pilot study.

Background: Small extracellular vesicles (sEV) play a crucial role in immune responses to viral infection. However, the composition of sEV derived from children with viral pneumonia remains ill defined.

Methods: First, we performed mass spectrometry-based label-free proteomic analysis of urinary sEV in 7 children with viral pneumonia, 4 children with Mycoplasma pneumoniae pneumonia and 20 healthy children.

The Discovery, Enzymatic Characterization and Functional Analysis of a Newly Isolated Chitinase from Marine-Derived Fungus df347.

In order to discover a broad-specificity and high stability chitinase, a marine fungus, df347, was identified in the sediments of mangrove wetlands in Qinzhou Bay, China. The chitinase gene (Chi28) from df347 was cloned and heterologously expressed in , and the recombinant enzyme Chi28 was purified and characterized. Chi28 is an acido-halotolerant- and temperature-resistant bifunctional enzyme with both endo- and exo-cleavage functions.

Associations of Life's Simple 7 With Cerebral Small Vessel Disease.

Background: The purpose of this study is to examine the associations of Life's Simple 7 (LS7) with risks of cerebral small vessel disease (CSVD) and its magnetic resonance imaging markers.

Methods: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included in this study from 2017 to 2019. LS7 was analyzed as the total score, medical score (derived from the 3 metrics based on medical history and testing), and behavioral score (based on 4 metrics based on behaviors), and categorized as poor, intermediate, or ideal.

Association of Serum Cystatin C With Cerebral Small Vessel Disease in Community-Based Population.

Background: The aim of this study was to investigate the relationship between serum cystatin C levels and the presence and severity of cerebral small vessel disease (CSVD).

Methods: Community-dwelling residents in the Lishui city in China from the cross-sectional survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study from 2017 to 2019. Total CSVD burden and modified total CSVD burden score, as well as the markers of CSVD on magnetic resonance imaging, including white matter hyperintensity, lacunes, cerebral microbleeds, and perivascular spaces, were assessed at baseline survey.

Macrophage ALDH2 (Aldehyde Dehydrogenase 2) Stabilizing Rac2 Is Required for Efferocytosis Internalization and Reduction of Atherosclerosis Development.

Background: Clinical studies show that the most common single-point mutation in humans, ALDH2 (aldehyde dehydrogenase 2) rs671 mutation, is a risk factor for the development and poor prognosis of atherosclerotic cardiovascular diseases, but the underlying mechanism remains unclear. Apoptotic cells are phagocytosed and eliminated by macrophage efferocytosis during atherosclerosis, and enhancement of arterial macrophage efferocytosis reduces atherosclerosis development.

Methods: Plaque areas, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated in APOE mice with bone marrow transplanted from APOEALDH2 and APOE mice.

Effectiveness of a Workplace-Based, Multicomponent Hypertension Management Program in Real-World Practice: A Propensity-Matched Analysis.

Limited studies had investigated the potential benefits of workplace-based hypertension management programs on long-term blood pressure (BP) control and health outcomes. This study used the propensity score matching to examine the effectiveness of a workplace-based hypertension management program on BP control and risks of major adverse cardiovascular events and all-cause mortality. Within the Kailuan study, a workplace-based hypertension management program was initiated in 2009 among men with hypertension, which included regular BP measuring (twice a month), free antihypertensive medications, and individualized health consultation.

Predicting drug approvals: The Novartis data science and artificial intelligence challenge.

We describe a novel collaboration between academia and industry, an in-house data science and artificial intelligence challenge held by Novartis to develop machine-learning models for predicting drug-development outcomes, building upon research at MIT using data from Informa as the starting point. With over 50 cross-functional teams from 25 Novartis offices around the world participating in the challenge, the domain expertise of these Novartis researchers was leveraged to create predictive models with greater sophistication. Ultimately, two winning teams developed models that outperformed the baseline MIT model-areas under the curve of 0.

Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture.

The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type (WT) and Tet2 fetal livers, by multiplexed error robust fluorescence in situ hybridization. We find that specific pairs of fetal liver cell types are preferentially positioned next to each other.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites.