Underlying biology, challenges and emergent concepts in the treatment of relapsed and refractory pediatric T-cell acute lymphoblastic leukemia.

Relapsed and refractory disease in children with T-cell acute lymphoblastic leukemia (R/R T-ALL) remains a major clinical challenge. Outcomes for children who relapse or exhibit resistance to initial treatments are dismal, with survival rates frequently below 25% despite aggressive therapy. To minimize toxicities and improve outcomes, individualized precision medicine approaches targeting the underlying biology of R/R T-ALL are especially important, considering that T-ALL is characterized by genetic, epigenetic and posttranscriptional heterogeneity, and organ and niche specificities (e.

Identifying dynamic reproducible brain states using a predictive modelling approach.

Conceptually, brain states reflect some combination of the internal mental processes of a person, and the influence of their external environment. Importantly, for neuroimaging, brain states may impact brain-based modeling of a person's traits, which should be independent of moment-to-moment changes in behavior. Investigation of brain states, and modeling of traits or behaviors are both often done using fMRI-based functional connectivity.

Amplicon sequencing of pasteurized retail dairy enables genomic surveillance of H5N1 avian influenza virus in United States cattle.

Highly pathogenic avian influenza (HPAI) viruses with H5 hemagglutinin (HA) genes (clade 2.3.4.

Detecting SARS-CoV-2 cryptic lineages using publicly available whole genome wastewater sequencing data.

Beginning in early 2021, unique and highly divergent lineages of SARS-CoV-2 were sporadically found in wastewater sewersheds using a sequencing strategy focused on amplifying the most rapidly evolving region of SARS-CoV-2, the receptor binding domain (RBD). Because these RBD sequences did not match known circulating strains and their source was not known, we termed them "cryptic lineages". To date, more than 20 cryptic lineages have been identified using the RBD-focused sequencing strategy.

Community-Scale Molecular Surveillance for Human Viruses.

Environmental surveillance, including wastewater and air sampling, has emerged as a powerful complement to traditional clinical surveillance for monitoring viral circulation. Advances in sampling and detection technologies, many spurred by the COVID-19 pandemic, have enabled more sensitive and comprehensive characterization of viruses in diverse types of commingled samples from multiple individuals. Expanding environmental monitoring globally presents challenges and opportunities, particularly in low- and middle-income countries where centralized sewage infrastructure may be limited.

CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition.

B-cell acute lymphoblastic leukemia (B-ALL) is a leading cause of death in childhood and outcomes in adults remain dismal. There is therefore an urgent clinical need for therapies that target the highest risk cases. Mutations in the histone acetyltransferase CREBBP confer high-risk and increased chemoresistance in ALL.

Transcription factor cooperativity at a GATA3 tandem DNA sequence determines oncogenic enhancer-mediated activation.

The TAL1 oncogene driving T cell lymphoblastic leukemia is frequently activated through mutated cis-regulatory elements, whereby small insertions or deletions (indels) create a binding site for the transcription factor MYB. Unraveling how non-coding mutations create oncogenic enhancers is key to understanding cancer biology and can provide important insights into fundamental mechanisms of gene regulation. Utilizing a CRISPR-Cas9 screening approach, we identify GATA3 as the key transcriptional regulator of enhancer-mediated TAL1 overexpression.

SARS-CoV-2 Genomic Surveillance from Community-Distributed Rapid Antigen Tests, Wisconsin, USA.

In the United States, SARS-CoV-2 genomic surveillance initially relied almost entirely on residual diagnostic specimens from nucleic acid amplification-based tests. However, use of those tests waned after the end of the COVID-19 Public Health Emergency on May 11, 2023. In Dane County, Wisconsin, we partnered with local- and state-level public health agencies and the South Central Library System to continue genomic surveillance by obtaining SARS-CoV-2 genome sequences from freely available community rapid antigen tests (RATs).

Longitudinal Assessment of Solid Organ Transplant Recipients With SARS-CoV-2 Infection.

Background: Compared with immunocompetent individuals, those who are immunocompromised, including solid organ transplant (SOT) recipients, have higher SARS-CoV-2-related morbidity and mortality. We determined the duration of SARS-CoV-2 RNA positivity to evaluate viral persistence in SOT recipients.

Methods: This study prospectively followed SOT recipients who recently tested positive for SARS-CoV-2.

Global soil pollution by toxic metals threatens agriculture and human health.

Toxic metal pollution is ubiquitous in soils, yet its worldwide distribution is unknown. We analyzed a global database of soil pollution by arsenic, cadmium, cobalt, chromium, copper, nickel, and lead at 796,084 sampling points from 1493 regional studies and used machine learning techniques to map areas with exceedance of agricultural and human health thresholds. We reveal a previously unrecognized high-risk, metal-enriched zone in low-latitude Eurasia, which is attributed to influential climatic, topographic, and anthropogenic conditions.

Preclinical development of anti-CD21 chimeric antigen receptor T cells to treat T cell acute lymphoblastic leukemia.

Patients with relapsed/refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) have a dismal prognosis, highlighting the urgent need for effective therapies. Chimeric antigen receptor (CAR)-T cell approaches targeting pan-T cell antigens may be limited by T cell aplasia and fratricide, necessitating "rescue" allogeneic hematopoietic stem cell transplantation. In this study, we identify CD21, a pan-B cell marker, as a promising target for T-ALL immunotherapy.

Clade IIb Mpox virus (MPXV) vertical transmission and fetal demise in a pregnant rhesus macaque model.

Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We sought to establish a pregnant rhesus macaque model of clade IIb MPXV infection with early gestation inoculation to understand if infection results in vertical transmission and adverse pregnancy outcomes. Three pregnant rhesus macaques were inoculated intradermally with 1.

Establishing Methods to Monitor Influenza (A)H5N1 Virus in Dairy Cattle Milk, Massachusetts, USA.

Highly pathogenic avian influenza A(H5N1) virus has caused a multistate outbreak among US dairy cattle, spreading across 16 states and infecting hundreds of herds since its onset. We rapidly developed and optimized PCR-based detection assays and sequencing protocols to support H5N1 molecular surveillance. Using 214 retail milk samples from 20 states for methods development, we found that H5N1 virus concentrations by digital PCR strongly correlated with quantitative PCR cycle threshold values; digital PCR exhibited greater sensitivity.

Retraction notice to "Strengthening social-environmental management at contaminated sites to bolster Green and Sustainable Remediation via a survey" [Chemosphere 225 (2019) 295-303].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).

Role of non-human primate models in accelerating research and developing countermeasures against Zika virus infection.

Zika virus, a mosquito-transmitted orthoflavivirus, has become a pathogen of global health concern ever since the virus caused an epidemic in Brazil in 2015 associated with approximately 700 000 laboratory-confirmed cases of congenital microcephaly. The subsequent spread of the epidemic in 2016 resulted in a wide spectrum of congenital neurological, ophthalmological, and developmental abnormalities across the Americas, Africa, and Asia. In this context, non-human primate models have become essential tools for Zika virus research to understand the pathogenesis of congenital brain injury and perinatal complications and for developing and testing medical countermeasures such as vaccines, diagnostics, and therapeutics.

PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (ventriculomegaly) is a defining feature of congenital hydrocephalus (CH) and an under-recognized concomitant of autism. Here, we show that de novo mutations in the autism risk gene PTEN are among the most frequent monogenic causes of CH and primary ventriculomegaly. Mouse Pten-mutant ventriculomegaly results from aqueductal stenosis due to hyperproliferation of periventricular Nkx2.

Comparing different viral strains in identifying risk factors for the development of venous thromboembolism in hospitalized COVID-19 patients.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been nearly seven million deaths associated with COVID-19 and over thirteen billion total vaccine doses administered worldwide. This study aimed to evaluate the patient demographics and laboratory values that might help predict individuals at risk of having a deep vein thrombosis (DVT) formation while hospitalized with COVID-19. Focusing on the four major strains alongside the associated vaccination availability periods in the United States to devise risk stratification and management algorithms.

What is the best brain state to predict autistic traits?

Autism is a heterogeneous condition, and functional magnetic resonance imaging-based studies have advanced understanding of neurobiological correlates of autistic features. Nevertheless, little work has focused on the optimal brain states to reveal brain-phenotype relationships. In addition, there is a need to better understand the relevance of attentional abilities in mediating autistic features.

Establishing methods to monitor H5N1 influenza virus in dairy cattle milk.

Highly Pathogenic Avian Influenza strain H5N1 has caused a multi-state outbreak among US dairy cattle, spreading across 15 states and infecting hundreds of herds since its onset. We rapidly developed and optimized PCR-based detection assays and sequencing protocols to support H5N1 molecular surveillance. Using 214 retail milk from 20 states for methods development, we found that H5N1 concentrations by digital PCR strongly correlated with qPCR cycle threshold (Ct) values, with dPCR exhibiting greater sensitivity.

Aging-dependent loss of functional connectivity in a mouse model of Alzheimer's disease and reversal by mGluR5 modulator.

Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (App/hMapt), monitoring brain connectivity by means of resting-state fMRI.