In his medical school application essay in 2011, my cousin Joey, a ping-pong champion, described the way the sport connected him to the world, from which he’d long felt separated: it gave him a sense of control. "The angles, velocities, and trajectories of the ball," he wrote, "give way to…
Thu Sep 19, 2019 03:00
Cardiovascular disease remains the leading cause of death and disability in the United States. Persons with low socioeconomic status and nonwhite persons are particularly vulnerable and have high cardiovascular mortality. There is wide geographic variation, with disproportionate disease burden in…
Thu Sep 19, 2019 03:00
Five days after undergoing major surgery, Mr. Jackson is found to have a subsegmental pulmonary embolus, with symptoms for which no alternative diagnosis is found. Regardless of whether we consider this to be a symptomatic or incidental embolus, the patient would require a limited 3-month course of…
Thu Sep 19, 2019 03:00
I recently had the following exchange with my 4-year-old daughter while reading her favorite book at bedtime: Me: " . . . with Emma Rose inside." Daughter: "Why was Emma Rose in the house?" Me: "Because she was sleeping." Daughter: "Why was she sleeping?" Me: "Because it was nighttime." Daughter:…
Thu Sep 19, 2019 03:00
The Food and Drug Administration approved the first direct oral anticoagulant nearly a decade ago. Since then, antithrombotic therapy has evolved swiftly, with research systematically addressing the use of these agents for the treatment of common medical conditions, such as atrial fibrillation. Of…
Thu Sep 19, 2019 03:00
Last year at NYU Langone Health, we showed millions of best-practice alerts in the electronic health record system to prompt physicians to avoid adverse events and to promote guideline-based care. We called hundreds of patients to remind them that they were overdue for their annual physical…
Thu Sep 19, 2019 03:00
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Polymyxins, namely colistimethate sodium (colistin or polymyxin E) and polymyxin B, are used for multi-drug resistant gram-negative bacterial infections, including Pseudomonas aeruginosa and Acinetobacter baumannii 1. As treatments and therapy have advanced, patients with cystic fibrosis are living longer. However, these patients have high exposure to intravenous antibiotics, most commonly penicillins, cephalosporins, and aminoglycosides. With colonization or infections with resistant gram-negative...
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Data from cone beam computed tomography (CBCT) and optical scans (intraoral or model scanner) are required for computer-assisted implant surgery (CAIS). This study compared the accuracy of implant position when placed with CAIS guides produced by intraoral and extraoral (model) scanning. Forty-seven patients received 60 single implants by means of CAIS. Each implant was randomly assigned to either the intraoral group (n=30) (Trios Scanner, 3Shape) or extraoral group (n=30), in which stereolithographic...
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Horm Metab ResDOI: 10.1055/a-0966-8784Early weaning (EW) is a risk factor for metabolic syndrome. Male rats that were precociously weaned present neonatal malnutrition and, in adulthood, developed overweight, accumulation of body fat, dyslipidemia, changes in glycemic homeostasis, hyperleptinemia, and increase of vitamin D. As metabolic profile of early-weaned females is not known, we investigated the endocrine-metabolic parameters in adolescence and adult female rats of 2 different EW models. Wistar...
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Purpose: Preclinical studies have demonstrated that post-irradiation tumor revascularization is dependent on a stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-driven process in which myeloid cells are recruited from bone marrow. Blocking this axis results in survival improvement in preclinical models of solid tumors, including glioblastoma (GBM). We conducted a phase I/II study to determine the safety and efficacy of Macrophage Exclusion after Radiation Therapy (MERT)...
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The aim of this prospective case series study is to assess the three-dimensional (3D) skeletal and soft tissue effects of the alternate rapid maxillary expansion and constriction (Alt-RAMEC) protocol in conjun...
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Large clinical trials involving patients with type 2 diabetes have shown that inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of hospitalization for heart failure. Most patients in these trials did not have heart failure at baseline, so the benefit of treatment with an SGLT2…
Nasopharyngeal carcinoma is a head and neck cancer with a specific geographic distribution. It affected an estimated 130,000 patients worldwide in 2018, with the highest rates occurring in regions in South China, Southeastern Asia, and North Africa. More than 70% of patients receive a diagnosis of…
Cytomegalovirus (CMV) infection commonly complicates hematopoietic-cell and solid-organ transplantation and is associated with increased morbidity and mortality. The available anti-CMV agents are effective but are limited by their toxic effects, including myelosuppression (ganciclovir and…
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Abstract Through four decades’ development, DNA sequencing has inched into the era of single-molecule sequencing (SMS), or the third-generation sequencing (TGS), as represented by two distinct technical approaches developed independently by Pacific Bioscience (PacBio) and Oxford Nanopore Technologies (ONT). Historically, each generation of sequencing technologies was marked by innovative technological achievements and novel applications. Long reads (LRs) are considered as the most...
Abstract The reversible oxidation of l-malate to oxaloacetate is catalyzed by NAD(H)-dependent malate dehydrogenase (MDH). MDH plays essential roles in the malate–aspartate shuttle and the tricarboxylic acid cycle. These metabolic processes are important in mitochondrial NADH supply for oxidative phosphorylation. Recently, bi-allelic mutations in mitochondrial MDH2 were identified in patients with global developmental delay, epilepsy and lactic acidosis. We now report two patients...
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Abstract Tumor necrosis factor‐α (TNF‐α) induced keratinocyte inflammation plays a key role in the pathogenesis of multiple inflammatory skin diseases. Here we investigated the anti‐inflammatory effect of S‐allyl cysteine (SAC) on TNF‐α induced HaCaT keratinocyte cells and the mechanism behind its anti‐inflammatory potential. SAC was found to inhibit TNF‐α stimulated cytokine expression. Further SAC was found to inhibit TNF‐α induced activation of p38, JNK and NF‐kB pathways. Interestingly, SAC...
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Cnidaria is the sister taxon to bilaterian animals, and therefore, represents a key reference lineage to understand early origins and evolution of the neural systems. The hydromedusa Aglantha digitale is arguably the best electrophysiologically studied jellyfish because of its system of giant axons and unique fast swimming/escape behaviors. Here, using a combination of scanning electron microscopy and immunohistochemistry together with phalloidin labeling, we systematically characterize both neural...
Background and objectivesMycobacterium bovis and Mycobacterium caprae are the two most important agents of tuberculosis (TB) in livestock and the most important causes of zoonotic TB in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens. MethodologyWe compiled a global collection of 3364 whole-genome sequences from M. bovis and M. caprae originating from 35 countries and inferred their phylogenetic relationships, geographic...
The evolutionary transition between winglessness and a full-winged morphology requires selective advantage for intermediate forms. Conversely, repeated secondary wing reductions among the pterygotes indicates relaxation of such selection. However, evolutionary trajectories of such transitions are not well characterized. The stick insects (Phasmatodea) exhibit diverse wing sizes at both interspecific and intersexual levels, and thus provide a system for examining how selection on flight capability,...
Long-term evolution of quantitative traits is classically and usefully described as the directional change in phenotype due to the recurrent fixation of new mutations. A formal justification for such continual evolution ultimately relies on the "invasion implies substitution" principle. This states that whenever a mutant allele causing a small phenotypic change can successfully invade a population, the ancestral (or wild-type) allele will be replaced, whereby fostering gradual phenotypic change if...
The deep ocean is the largest biome on Earth and yet it is among the least studied environments of our planet. Life at great depths requires several specific adaptations, however their molecular mechanisms remain understudied. We examined patterns of positive selection in 416 genes from four brittle star (Ophiuroidea) families displaying independent events of deep-sea colonization (288 individuals from 216 species). We found consistent signatures of molecular convergence in five genes, including...
Regional species diversity is ultimately explained by speciation, extinction, and dispersal. Here we estimate dispersal and speciation rates in Neotropical rainforest biomes to propose an explanation for the distribution and diversity of extant butterfly species. We focus on the butterfly tribe Brassolini (Owl butterflies and allies): a Neotropical group that comprises 17 genera and 108 species, most of them endemic to rainforest biomes. We infer a total-evidence species tree of Brassolini using...
A critical goal in drug discovery is the rational design of therapeutics that last longer in the face of biological evolution. However, this goal is thwarted by the astonishing diversity and stochasticity of mutational paths in the clinic. Beyond biophysical predictions of thermodynamics, we present stochastic, first principles models of evolution built on a large in vitro dataset that accurately predict the epidemiologic abundance of mutations to three different drugs across multiple leukemia clinical...
The sequencing of whole or partial (e.g. reduced representation) genomes are commonly employed in molecular ecology and conservation genetics studies. However, due to sequencing costs, a trade-off between the number of samples and genome coverage can hinder research for non-model organisms. Furthermore, the processing of raw sequences requires familiarity with coding and bioinformatic tools that are not always available. Here, we present a guide for isolating a set of short, SNP-containing genomic...
Propulsion of sperm cells via movement of the flagellum is of vital importance for successful fertilization. Presumably, the energy for this movement comes from the mitochondria in the sperm midpiece. Larger midpieces may contain more mitochondria, which should enhance the energetic capacity and hence promote mobility. Due to an inversion polymorphism on their sex chromosome TguZ, zebra finches (Taeniopygia guttata castanotis) exhibit large within-species variation in sperm midpiece length, and those...
The vertebrate jaw is a versatile feeding apparatus that facilitated explosive diversification. Its functions require a joint between the upper and lower jaws, so jaw joint defects - such as osteoarthritis or even ankylosis - are often highly disruptive and difficult to study. To describe consequences of jaw joint dysfunction, we engineered two independent null alleles of a single jaw-joint marker gene, nkx3.2, in zebrafish. The mutations caused the fish to become functionally jawless via a fusion...
The Dobzhansky-Muller model provides a widely accepted mechanism for the evolution of reproductive isolation: incompatible substitutions disrupt interactions between genes. To date, few candidate incompatibility genes have been identified, leaving the genes driving speciation mostly uncharacterized. The importance of interactions in the Dobzhansky-Muller model suggests that gene coexpression networks provide a powerful framework to understand disrupted pathways associated with postzygotic isolation....
Fitness landscapes are widely used to visualize the dynamics and long-term outcomes of evolution. The fitness landscapes of genetic sequences are characterized by high dimensionality and "ruggedness" due to sign epistasis. Ascending from low to high fitness on such landscapes can be difficult because adaptive trajectories get stuck at low-fitness local peaks. Compounding matters, recent computational complexity arguments have proposed that extremely long, winding adaptive paths may be required to...
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Analytical ChemistryDOI: 10.1021/acs.analchem.9b02280
Analytical ChemistryDOI: 10.1021/acs.analchem.9b02664
Analytical ChemistryDOI: 10.1021/acs.analchem.9b02075
Analytical ChemistryDOI: 10.1021/acs.analchem.9b02983
Analytical ChemistryDOI: 10.1021/acs.analchem.9b02496
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03560
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Fibroblast growth factor receptor 3 (FGFR3) plays an important regulatory role in tumor cell proliferation and drug resistance. FGFR3 is often constitutively active in many tumors. To deliver drugs into tumor ...
Engineering of fungal laccases with optimum catalytic activity at alkaline pH has been a long-lasting challenge. In this study, a mutant library containing 3000 clones was obtained by error-prone PCR to adapt ...
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Abstract Objectives to evaluate the impact on peri‐implant bone support (as assessed on periapical radiographs) of the remodeling dynamics of varying graft biomaterials used for transcrestal sinus floor elevation (tSFE). Methods The study is a multicenter, retrospective series of cases undergone tSFE (performed according to the Smart Lift technique) and concomitant implant placement. At operator's discretion, tSFE was performed with bone core (BC) alone or supplemented by deproteinized...
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