Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Medical Students' Perspectives on Family Planning and Impact on Specialty Choice.

Importance: Physicians are known to delay childbearing compared with nonphysicians and to experience higher rates of age-related pregnancy complications. Delay of childbearing is more pronounced in surgical specialties, and family planning and building goals may influence specialty choice.

Objective: To assess medical students' perspectives on the development of family planning goals and the timing of family building within a medical career to elucidate how these perceptions impact their choice of specialty.

The NYU Data Catalog: a modular, flexible infrastructure for data discovery.

Objective: Researchers at New York University (NYU) Grossman School of Medicine contacted the Health Sciences Library for help with locating large datasets for reuse. In response, the library developed and maintained the NYU Data Catalog, a public-facing data catalog that has supported not only faculty acquisition of data but also the dissemination of the products of their research in various ways.

Materials And Methods: The current NYU Data Catalog is built upon the Symfony framework with a tailored metadata schema reflecting the scope of faculty research areas.

A Review of the Application of Natural and Synthetic Scaffolds in Bone Regeneration.

The management of bone defects is complicated by the presence of clinical conditions, such as critical-sized defects created by high-energy trauma, tumour resection, infection, and skeletal abnormalities, whereby the bone regeneration capacity is compromised. A bone scaffold is a three-dimensional structure matrix serving as a template to be implanted into the defects to promote vascularisation, growth factor recruitment, osteogenesis, osteoconduction, and mechanical support. This review aims to summarise the types and applications of natural and synthetic scaffolds currently adopted in bone tissue engineering.

Co-designing a web-based education platform for patients with early pregnancy loss.

Canadian emergency departments (EDs) frequently provide care to patients undergoing early pregnancy loss. Unfortunately, in this setting, patients commonly have negative experiences, in part due to lack of appropriate follow-up and education on symptoms that may arise after discharge. In response to this gap, our team created a free, web-based, patient-informed educational platform for women to access accurate information on early pregnancy loss.

Divergent Plasmodium actin residues are essential for filament localization, mosquito salivary gland invasion and malaria transmission.

Actin is one of the most conserved and ubiquitous proteins in eukaryotes. Its sequence has been highly conserved for its monomers to self-assemble into filaments that mediate essential cell functions such as trafficking, cell shape and motility. The malaria-causing parasite, Plasmodium, expresses a highly sequence divergent actin that is critical for its rapid motility at different stages within its mammalian and mosquito hosts.

Pyrazinamide triggers degradation of its target aspartate decarboxylase.

Pyrazinamide is a sterilizing first-line tuberculosis drug. Genetic, metabolomic and biophysical analyses previously demonstrated that pyrazinoic acid, the bioactive form of the prodrug pyrazinamide (PZA), interrupts biosynthesis of coenzyme A in Mycobacterium tuberculosis by binding to aspartate decarboxylase PanD. While most drugs act by inhibiting protein function upon target binding, we find here that pyrazinoic acid is only a weak enzyme inhibitor.

Phase variation in produces transiently heritable drug tolerance.

The length and complexity of tuberculosis (TB) therapy, as well as the propensity of to develop drug resistance, are major barriers to global TB control efforts. is known to have the ability to enter into a drug-tolerant state, which may explain many of these impediments to TB treatment. We have identified a mechanism of genetically encoded but rapidly reversible drug tolerance in caused by transient frameshift mutations in a homopolymeric tract (HT) of 7 cytosines (7C) in the gene.

Pyrazinoic Acid Inhibits Mycobacterial Coenzyme A Biosynthesis by Binding to Aspartate Decarboxylase PanD.

Previously, we showed that a major in vitro and in vivo mechanism of resistance to pyrazinoic acid (POA), the bioactive component of the critical tuberculosis (TB) prodrug pyrazinamide (PZA), involves missense mutations in the aspartate decarboxylase PanD, an enzyme required for coenzyme A biosynthesis. What is the mechanism of action of POA? Upon demonstrating that treatment of M. bovis BCG with POA resulted in a depletion of intracellular coenzyme A and confirming that this POA-mediated depletion is prevented by either missense mutations in PanD or exogenous supplementation of pantothenate, we hypothesized that POA binds to PanD and that this binding blocks the biosynthetic pathway.

Draft Genome Sequence of 11.

accounts for most lung disease caused by nontuberculous mycobacteria (NTM). The lack of effective chemotherapy calls for the discovery of new drugs. Here, we report the draft genome sequence of 11, a clinical isolate used as a screening strain for NTM-focused drug discovery.

Draft Genome Sequence of Bamboo.

, an intrinsically multidrug-resistant pathogen, causes chronic incurable lung disease. New drugs for this emerging pathogen represent an urgent unmet medical need. Here, we report a draft genome sequence of Bamboo, a clinical isolate used as a screening strain for drug discovery.

In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1.

Through mutant selection on agar containing pyrazinoic acid (POA), the bioactive form of the prodrug pyrazinamide (PZA), we recently showed that missense mutations in the aspartate decarboxylase PanD and the unfoldase ClpC1, and loss-of-function mutation of polyketide synthases Mas and PpsA-E involved in phthiocerol dimycocerosate synthesis, cause resistance to POA and PZA in Mycobacterium tuberculosis. Here we first asked whether these in vitro-selected POA/PZA-resistant mutants are attenuated in vivo, to potentially explain the lack of evidence of these mutations among PZA-resistant clinical isolates. Infection of mice with panD, clpC1, and mas/ppsA-E mutants showed that whereas growth of clpC1 and mas/ppsA-E mutants was attenuated, the panD mutant grew as well as the wild-type.

Missense Mutations in the Unfoldase ClpC1 of the Caseinolytic Protease Complex Are Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis.

Previously, we showed that mutations in Mycobacterium tuberculosis panD, involved in coenzyme A biosynthesis, cause resistance against pyrazinoic acid, the bioactive component of the prodrug pyrazinamide. To identify additional resistance mechanisms, we isolated mutants resistant against pyrazinoic acid and subjected panD wild-type strains to whole-genome sequencing. Eight of the nine resistant strains harbored missense mutations in the unfoldase ClpC1 associated with the caseinolytic protease complex.

Pyrazinamide Resistance Is Caused by Two Distinct Mechanisms: Prevention of Coenzyme A Depletion and Loss of Virulence Factor Synthesis.

Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM).

The Challenges of Dysphagia Management and Rehabilitation in Two Complex Cases Post Chemical Ingestion Injury.

Purpose: Dysphagia is common sequelae of chemical ingestion injury, resulting from damage to critical swallowing structures. From a speech-language pathology perspective, this study outlines the physiological deficits in 2 individuals with severe injury (1 woman, acid; 1 man, alkali) and the pattern of dysphagia rehabilitation and recovery.

Method: A retrospective chart review of clinical and instrumental assessments was conducted to examine swallow characteristics and speech-language pathology management (compensatory and rehabilitation strategies) at multiple time points.

Dystonia with MPH/Risperidone Combined Therapy for ADHD.

Investigators from Child Neurology and Pediatrics, University of Texas Health Science Center, Houston, report extrapyramidal symptoms in a 13-year-old boy with a psychiatric history of schizophrenia, bipolar disorder, ADHD, and autism, responsive to combination risperidone, oxcarbazepine, and MPH.

Relationship between Age at Diagnosis of ADHD and ASD.

Investigators from the Division of Developmental Medicine and Clinical Research Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, studied the relationship between the timing of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis in children with Autism Spectrum Disorder (ASD) and the age at ASD diagnosis.

Ambient fine particulate matter, nitrogen dioxide, and term birth weight in New York, New York.

Building on a unique exposure assessment project in New York, New York, we examined the relationship of particulate matter with aerodynamic diameter less than 2.5 μm and nitrogen dioxide with birth weight, restricting the population to term births to nonsmokers, along with other restrictions, to isolate the potential impact of air pollution on growth. We included 252,967 births in 2008-2010 identified in vital records, and we assigned exposure at the residential location by using validated models that accounted for spatial and temporal factors.

Spatial and temporal estimation of air pollutants in New York City: exposure assignment for use in a birth outcomes study.

Background: Recent epidemiological studies have examined the associations between air pollution and birth outcomes. Regulatory air quality monitors often used in these studies, however, were spatially sparse and unable to capture relevant within-city variation in exposure during pregnancy.

Methods: This study developed two-week average exposure estimates for fine particles (PM2.