Mutant Cooperates with a Fusion to Induce Early Immature Thymocyte Precursor ALL.

Mutations in the isocitrate dehydrogenase 1 () and genes are frequently observed in a wide variety of hematologic malignancies, including myeloid and T-cell leukemias. In this study, we generated transgenic mice to examine the role of the mutation in leukemia. No leukemia developed in transgenic mice, suggesting a need for additional genetic events for leukemia development.

A Simplified Approach to Quantifying a Child's Bilingual Language Experience.

Purpose Bilingual children's linguistic experience can vary markedly from child to child. For appropriate audiological assessment and intervention, audiologists need accurate and efficient ways to describe and understand a bilingual child's dynamic linguistic experience. This report documents an approach for quantitatively capturing a child's language exposure and usage in a time-efficient manner.

Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS-mutant lung cancer.

Lack of sustained response to therapeutic agents in patients with KRAS-mutant lung cancer poses a major challenge and arises partly due to intratumor heterogeneity that defines phenotypically distinct tumor subpopulations. To attain better therapeutic outcomes, it is important to understand the differential therapeutic sensitivities of tumor cell subsets. Epithelial-mesenchymal transition is a biological phenomenon that can alter the state of cells along a phenotypic spectrum and cause transcriptional rewiring to produce distinct tumor cell subpopulations.

[Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant].

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods.

Effect of intermittent high-frequency stimulation on muscle velocity recovery cycle recordings.

The technique of multifiber muscle velocity recovery cycle recordings was developed as a diagnostic tool to assess muscle membrane potential changes and ion channel function in vivo. This study was undertaken to assess the impact of intermittent high-frequency stimulation on muscle velocity recovery cycle components and to study whether the changes can be modified by endurance training. We recorded muscle velocity recovery cycles with 1 and 2 conditioning stimuli in the left tibialis anterior muscle in 15 healthy subjects during intermittent 37-Hz stimulation and analyzed its effects on the different phases of supernormality.

Inference of ventricular activation properties from non-invasive electrocardiography.

The realisation of precision cardiology requires novel techniques for the non-invasive characterisation of individual patients' cardiac function to inform therapeutic and diagnostic decision-making. Both electrocardiography and imaging are used for the clinical diagnosis of cardiac disease. The integration of multi-modal datasets through advanced computational methods could enable the development of the cardiac 'digital twin', a comprehensive virtual tool that mechanistically reveals a patient's heart condition from clinical data and simulates treatment outcomes.

Translocated microbiome composition determines immunological outcome in treated HIV infection.

The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera.

Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort.

Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort.

Risk assessment and seroprevalence of SARS-CoV-2 infection in healthcare workers of COVID-19 and non-COVID-19 hospitals in Southern Switzerland.

Background: Hospital healthcare workers (HCW), in particular those involved in the clinical care of COVID-19 cases, are presumably exposed to a higher risk of acquiring the disease than the general population.

Methods: Between April 16 and 30, 2020 we conducted a prospective, SARS-CoV-2 seroprevalence study in HCWs in Southern Switzerland. Participants were hospital personnel with varying COVID-19 exposure risk depending on job function and working site.

p53 loss activates prometastatic secretory vesicle biogenesis in the Golgi.

Cancer cells exhibit hyperactive secretory states that maintain cancer cell viability and remodel the tumor microenvironment. However, the oncogenic signals that heighten secretion remain unclear. Here, we show that p53 loss activates prometastatic secretory vesicle biogenesis in the Golgi.

Mechanical writing of electrical polarization in poly (L-lactic) acid.

Stimuli responsive materials are found in a broad range of applications, from energy harvesters to biomolecular sensors. Here, we report the production of poly (L-lactic acid) (PLLA) thin films that exhibit a mechanical stress responsive behaviour. By simply applying a mechanical stress through an AFM tip, a local electrical polarization was generated and measured by Kelvin Probe Force Microscopy.

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation.

Boosting Polarization Switching-Induced Current Injection by Mechanical Force in Ferroelectric Thin Films.

When scaling the lateral size of a ferroelectric random access memory (FeRAM) device down to the nanometer range, the polarization switching-induced displacement current becomes small and challenging to detect, which greatly limits the storage density of FeRAM. Here, we report the observation of significantly enhanced injection currents, much larger than typical switching currents, induced by polarization switching in BiFeO thin films via conductive atomic force microscopy. Interestingly, this injected current can be effectively modulated by applying mechanical force.

CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes.

[Figure: see text].

Mission impossible: Reach the carrion in a lithium pollution and marine warming scenario.

In this study we investigated the independent and synergistic effects of lithium (Li, 0.08 mM) contamination and the rising seawater temperature (21 °C; control- 15 °C) on survival and trophic interactions (foraging behaviour, success, search time, carrion preference, feeding time, and tissue consumption-the dry weight basis) of the opportunistic intertidal scavenger Tritia neritea. Trophic interactions were assessed in a two-choice test using a Y-maze design using the same amount of two carrion species (Solen marginatus and Mytilus galloprovincialis) given to all snails simultaneously.

Replica Exchange Molecular Dynamics of Diphenylalanine Amyloid Peptides in Electric Fields.

The self-assembling propensity of amyloid peptides such as diphenylalanine (FF) allows them to form ordered, nanoscale structures, with biocompatible properties important for biomedical applications. Moreover, piezoelectric properties allow FF molecules and their aggregates (e.g.

Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers.

Understanding resistance mechanisms to targeted therapies and immune checkpoint blockade in mutant KRAS lung cancers is critical to developing novel combination therapies and improving patient survival. Here, we show that MEK inhibition enhanced PD-L1 expression while PD-L1 blockade upregulated MAPK signaling in mutant KRAS lung tumors. Combined MEK inhibition with anti-PD-L1 synergistically reduced lung tumor growth and metastasis, but tumors eventually developed resistance to sustained combinatorial therapy.

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women.

Background And Aims: Many dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women.

Methods And Results: Dairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers' Cohort (MTC) study who were free of CVD or cancer.

Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB harmonization project comparing three NGS panels.

Background: Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.

Gsx1 promotes locomotor functional recovery after spinal cord injury.

Promoting residential cells, particularly endogenous neural stem and progenitor cells (NSPCs), for tissue regeneration represents a potential strategy for the treatment of spinal cord injury (SCI). However, adult NSPCs differentiate mainly into glial cells and contribute to glial scar formation at the site of injury. Gsx1 is known to regulate the generation of excitatory and inhibitory interneurons during embryonic development of the spinal cord.

Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity.

Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum.

Natural variation in Caenorhabditis elegans responses to the anthelmintic emodepside.

Treatment of parasitic nematode infections depends primarily on the use of anthelmintics. However, this drug arsenal is limited, and resistance against most anthelmintics is widespread. Emodepside is a new anthelmintic drug effective against gastrointestinal and filarial nematodes.