Publications by authors named "Nhat Le"

Genetic prion diseases are caused by mutations in PRNP, which encodes the prion protein (PrP). Why these mutations are pathogenic, and how they alter the properties of PrP are poorly understood. We have consented and accessed 22 individuals of a multi-generational Israeli family harboring the highly penetrant E200K PRNP mutation and generated a library of induced pluripotent stem cells (iPSCs) representing nine carriers and four non-carriers.

View Article and Find Full Text PDF

Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. However, what role these inclusions play in pathogenesis remains unclear.

View Article and Find Full Text PDF

Antibiotic tolerance in reduces bacterial killing, worsens treatment outcomes, and contributes to resistance. We studied rifampicin tolerance in isolates with or without isoniazid resistance (IR). Using a minimum duration of killing assay, we measured rifampicin survival in isoniazid-susceptible (IS, n=119) and resistant (IR, n=84) isolates, correlating tolerance with bacterial growth, rifampicin minimum inhibitory concentrations (MICs), and isoniazid-resistant mutations.

View Article and Find Full Text PDF

Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no effective treatment options. Previous work from our laboratory identified phenethylpiperidines as a novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel antiprion compounds based on their known ability to bind to the sigma receptors, σR and σR, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders.

View Article and Find Full Text PDF

The synergy of long-range dependencies from transformers and local representations of image content from convolutional neural networks (CNNs) has led to advanced architectures and increased performance for various medical image analysis tasks due to their complementary benefits. However, compared with CNNs, transformers require considerably more training data, due to a larger number of parameters and an absence of inductive bias. The need for increasingly large datasets continues to be problematic, particularly in the context of medical imaging, where both annotation efforts and data protection result in limited data availability.

View Article and Find Full Text PDF

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies.

View Article and Find Full Text PDF
Article Synopsis
  • Mycobacterium tuberculosis, which causes tuberculosis (TB), can affect various organs, including the brain, leading to a serious condition called TB meningitis (TBM), yet the immune mechanisms behind these differences in disease presentation are not fully understood.
  • Research has shifted focus from T cell responses to the role of antibodies in controlling M. tuberculosis, particularly looking at how these antibodies respond differently in the lungs versus the brain.
  • Using an advanced serology technique, the study analyzed antibody responses in TBM patients compared to those with pulmonary TB, revealing distinct profiles in the cerebrospinal fluid that highlight a unique immune response in TBM, potentially serving as markers for disease severity and prognosis.
View Article and Find Full Text PDF

Background: Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections.

Methods: The expression of 3 genes (dual specificity phosphatase 3 [DUSP3], guanylate-binding protein [GBP5], krupple-like factor 2 [KLF2]) was analyzed by RNA sequencing of archived whole blood from 4 cohorts of Vietnamese adults: 281 with TBM, 279 with pulmonary tuberculosis, 50 with other brain infections, and 30 healthy controls.

View Article and Find Full Text PDF

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages.

View Article and Find Full Text PDF

Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from our laboratory identified phenethyl piperidines as novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel anti-prion compounds based on their known ability to bind to the sigma receptors, σ R and R, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders.

View Article and Find Full Text PDF

Antibiotic tolerance in leads to less effective bacterial killing, poor treatment responses and resistant emergence. Therefore, we investigated the rifampicin tolerance of isolates, with or without pre-existing isoniazid-resistance. We determined the rifampicin survival fraction by minimum duration of killing assay in isoniazid susceptible (IS, n=119) and resistant (IR, n=84) isolates.

View Article and Find Full Text PDF

In reversal learning tasks, the behavior of humans and animals is often assumed to be uniform within single experimental sessions to facilitate data analysis and model fitting. However, behavior of agents can display substantial variability in single experimental sessions, as they execute different blocks of trials with different transition dynamics. Here, we observed that in a deterministic reversal learning task, mice display noisy and sub-optimal choice transitions even at the expert stages of learning.

View Article and Find Full Text PDF

Elimination of chemically synthesized pesticides, such as fungicides and nematicides, in agricultural products is a key to successful practice of the Vietnamese agriculture. We describe here the route for developing successful biostimulants based on members of the species complex. A number of endospore-forming Gram-positive bacterial strains with antagonistic action against plant pathogens were isolated from Vietnamese crop plants.

View Article and Find Full Text PDF

New or enlarged lesions in malignant gliomas after surgery and chemoradiation can be associated with tumor recurrence or treatment effect. Due to similar radiographic characteristics, conventional-and even some advanced MRI techniques-are limited in distinguishing these two pathologies. Amide proton transfer-weighted (APTw) MRI, a protein-based molecular imaging technique that does not require the administration of any exogenous contrast agent, was recently introduced into the clinical setting.

View Article and Find Full Text PDF

Objective: To assess the Covid-19 pandemic's effects on college students' stress, life satisfaction, and college experiences and investigate sources of resilience.

Participants: 1,042 students from 11 U.S.

View Article and Find Full Text PDF

Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is common in CRCs.

View Article and Find Full Text PDF

Background: Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.

Methods: We studied 1069 Indonesian and Vietnamese adults with TBM (26.

View Article and Find Full Text PDF

Eight lineages of are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries.

View Article and Find Full Text PDF

Sepsis is a major cause of neonatal mortality and children born in low- and middle-income countries (LMICs) are at greater risk of severe neonatal infections than those in higher-income countries. Despite this disparity, there are limited contemporaneous data linking the clinical features of neonatal sepsis with outcome in LMICs. Here, we aimed to identify factors associated with mortality from neonatal sepsis in Vietnam.

View Article and Find Full Text PDF

Background: Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.

Methods: We studied 1069 Indonesian and Vietnamese adults with TBM (26.

View Article and Find Full Text PDF

Introduction: The use of surgical resection for large anterior skull base (ASB) tumors and sinonasal malignancies with intracranial extension will result in a large skull base defect. Reconstruction of large ASB defects using traditional techniques is high risk and may lead to postoperative cerebral spinal fluid (CSF) leakage, meningitis, and an increase in mortality rate. The use of a pedicled double flap technique to reconstruct the ASB defect may decrease complications.

View Article and Find Full Text PDF

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks.

View Article and Find Full Text PDF

<b>Background and Objectives:</b> Biofloc culture system has been used in aquaculture as an effective technology for water treatment due to many advantages of being biodegradable and environmentally friendly. This study aims to isolate bioflocculant-producing bacteria antagonistic to pathogenic <i>Vibrio</i> species from Pacific white shrimp ponds in Thua Thien Hue, Vietnam. <b>Materials and Methods:</b> <i>Vibrio</i> isolates were isolated by screening on medium with and without antibiotics.

View Article and Find Full Text PDF