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A detailed manual segmentation procedure for the hypothalamus for 3T T1-weighted MRI

1 day 11 hours ago
The hypothalamus is a small grey matter structure which plays a crucial role in many physiological functions. Some studies have found an association between hypothalamic volume and psychopathology, which stresses the need for a standardized method to maximize segmentation accuracy. Here, we provide a detailed step-by-step method outlining the procedures to manually segment the hypothalamus using anatomical T1w images from 3T scanners, which many neuroimaging studies collect as a standard...
Mohammad Ali

BIONIC: biological network integration using convolutions

2 days 11 hours ago
Biological networks constructed from varied data can be used to map cellular function, but each data type has limitations. Network integration promises to address these limitations by combining and automatically weighting input information to obtain a more accurate and comprehensive representation of the underlying biology. We developed a deep learning-based network integration algorithm that incorporates a graph convolutional network framework. Our method, BIONIC (Biological Network Integration...
Duncan T Forster

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium

2 days 11 hours ago
INTRODUCTION: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of...
Gabriel A de Erausquin

The DNA repair function of BCL11A suppresses senescence and promotes continued proliferation of triple-negative breast cancer cells

2 days 11 hours ago
We identified the BCL11A protein in a proximity-dependent biotinylation screen performed with the DNA glycosylase NTHL1. In vitro, DNA repair assays demonstrate that both BCL11A and a small recombinant BCL11A^(160-520) protein that is devoid of DNA binding and transcription regulatory domains can stimulate the enzymatic activities of two base excision repair enzymes: NTHL1 and DNA Pol β. Increased DNA repair efficiency, in particular of the base excision repair pathway, is essential for many...
Elise Vickridge

The proteomic landscape of glioblastoma recurrence reveals novel and targetable immunoregulatory drivers

5 days 11 hours ago
Glioblastoma (GBM) is characterized by extensive cellular and genetic heterogeneity. Its initial presentation as primary disease (pGBM) has been subject to exhaustive molecular and cellular profiling. By contrast, our understanding of how GBM evolves to evade the selective pressure of therapy is starkly limited. The proteomic landscape of recurrent GBM (rGBM), which is refractory to most treatments used for pGBM, are poorly known. We, therefore, quantified the transcriptome and proteome of 134...
Nazanin Tatari

Characterization of the minimal residual disease state reveals distinct evolutionary trajectories of human glioblastoma

1 week ago
Recurrence of solid tumors renders patients vulnerable to advanced, treatment-refractory disease state with mutational and oncogenic landscape distinctive from initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profile barcoded tumor stem cell populations through therapy at tumor initiation, MRD, and recurrence in our therapy-adapted, patient-derived xenograft...
Maleeha A Qazi

Developmental dynamics of RNA translation in the human brain

1 week ago
The precise regulation of gene expression is fundamental to neurodevelopment, plasticity and cognitive function. Although several studies have profiled transcription in the developing human brain, there is a gap in understanding of accompanying translational regulation. In this study, we performed ribosome profiling on 73 human prenatal and adult cortex samples. We characterized the translational regulation of annotated open reading frames (ORFs) and identified thousands of previously unknown...
Erin E Duffy

AML-131 ERG: From a Fortuitous Discovery to Potential Treatment for AML

1 week 1 day ago
CONCLUSIONS: Our findings indicate that the aberrant overexpression of ERG maintains HSPCs in an undifferentiated state and promotes AML development. We suggest that the interaction between ERG and the NCoR-HDAC3 complex has an important role in the leukemogenic process, and that HDAC3 inhibition could be beneficial in AML characterized by high ERG expression.
Eitan Kugler

CML-395 Efficacy and Safety Results From ASCEMBL, a Phase III Study of Asciminib vs. Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): Week 96 Update

1 week 1 day ago
CONCLUSIONS: After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.
Delphine Réa

Kinetics of phagosome maturation is coupled to their intracellular motility

1 week 1 day ago
Immune cells degrade internalized pathogens in phagosomes through sequential biochemical changes. The degradation must be fast enough for effective infection control. The presumption is that each phagosome degrades cargos autonomously with a distinct but stochastic kinetic rate. However, here we show that the degradation kinetics of individual phagosomes is not stochastic but coupled to their intracellular motility. By engineering RotSensors that are optically anisotropic, magnetic responsive,...
Yanqi Yu

Dealloying-Derived Nanoporous Bismuth for Selective CO<sub>2</sub> Electroreduction to Formate

1 week 2 days ago
Electrochemical CO(2) reduction (CO(2)ER) to formate is an attractive approach for CO(2) utilization. Here, we report a nanoporous bismuth (np-Bi) catalyst fabricated by chemically dealloying a rapidly solidified Mg(92)Bi(8) alloy for CO(2)ER. The np-Bi catalyst exhibits a three-dimensional interconnected ligament-channel network structure, which can efficiently convert CO(2) to formate with a selectivity of ≤94% and an activity of 62 mA cm^(-2) in a wide potential range. Remarkably, the np-Bi...
Qingru Wei

Occurrence, variations, and risk assessment of neonicotinoid insecticides in Harbin section of the Songhua River, northeast China

1 week 2 days ago
Neonicotinoid insecticides (NNIs) have been intensively used and exploited, resulting in their presence and accumulation in multiple environmental media. We herein investigated the current levels of eight major NNIs in the Harbin section of the Songhua River in northeast China, providing the first systematic report on NNIs in this region. At least four NNIs in water and three in sediment were detected, with total concentrations ranging from 30.8 to 135 ng L^(-1) and from 0.61 to 14.7 ng g^(-1)...
Zhikun Liu

Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

1 week 2 days ago
Cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) identifies genomic regions with DNA methylation, using a protocol adapted to work with low-input DNA samples and with cell-free DNA (cfDNA). We developed a set of synthetic spike-in DNA controls for cfMeDIP-seq to provide a simple and inexpensive reference for quantitative normalization. We designed 54 DNA fragments with combinations of methylation status (methylated and unmethylated), fragment length (80 bp, 160 bp, 320 bp),...
Samantha L Wilson

Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia

1 week 5 days ago
Secondary-type mutations (STMs), namely SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, are more frequently detected in secondary acute myeloid leukemia (AML) than in de novo AML. Whether de novo AML with STMs should be differently managed is, however, unclear. In 394 patients diagnosed with de novo AML who had a normal karyotype, the genetic profiling via targeted deep sequencing of 45 genes revealed 59 patients carrying STMs (STM^(+)). The STM^(+) group showed shorter overall...
Ga-Young Song

The End of "One Size Fits All" Sepsis Therapies: Toward an Individualized Approach

1 week 5 days ago
Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection, remains a major challenge for clinicians and trialists. Despite decades of research and multiple randomized clinical trials, a specific therapeutic for sepsis is not available. The evaluation of therapeutics targeting components of host response anomalies in patients with sepsis has been complicated by the inability to identify those in this very heterogeneous population who are more...
Jean-Louis Vincent

Biallelic Loss of Function Mutation in Sodium Channel Gene <em>SCN10A</em> in an Autism Spectrum Disorder Trio from Pakistan

1 week 5 days ago
The genetic dissection of autism spectrum disorders (ASD) has uncovered the contribution of de novo mutations in many single genes as well as de novo copy number variants. More recent work also suggests a strong contribution from recessively inherited variants, particularly in populations in which consanguineous marriages are common. What is also becoming more apparent is the degree of pleiotropy, whereby mutations in the same gene may have quite different phenotypic and clinical consequences....
Ansa Rabia
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