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Found 34428 matches. Displaying 81-90
Arterburn D, Wellman R, Emiliano A, Smith SR, Odegaard AO, Murali S, Williams N, Coleman KJ, Courcoulas A, Coley RY, Anau J, Pardee R, Toh S, Janning C, Cook A, Sturtevant J, Horgan C, McTigue KM
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Comparative Effectiveness and Safety of Bariatric Procedures for Weight Loss A PCORnet Cohort Study

ANNALS OF INTERNAL MEDICINE 2018 DEC 4; 169(11):741-+
Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674) Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m(2) or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One- year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m(2), those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics. Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data. Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed.
Braiman C, Fridman EA, Conte MM, Voss HU, Reichenbach CS, Reichenbach T, Schiff ND
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Cortical Response to the Natural Speech Envelope Correlates with Neuroimaging Evidence of Cognition in Severe Brain Injury

CURRENT BIOLOGY 2018 DEC 3; 28(23):3833-3839.e3
Recent studies identify severely brain-injured patients with limited or no behavioral responses who successfully perform functional magnetic resonance imaging (fMRI) or electroencephalogram (EEG) mental imagery tasks [1-5]. Such tasks are cognitively demanding [1]; accordingly, recent studies support that fMRI command following in brain-injured patients associates with preserved cerebral metabolism and preserved sleep-wake EEG [5, 6]. We investigated the use of an EEG response that tracks the natural speech envelope (NSE) of spoken language [7-22] in healthy controls and brain-injured patients (vegetative state to emergence from minimally conscious state). As audition is typically preserved after brain injury, auditory paradigms may be preferred in searching for covert cognitive function [23-25]. NSE measures are obtained by cross-correlating EEG with the NSE. We compared NSE latencies and amplitudes with and without consideration of fMRI assessments. NSE latencies showed significant and progressive delay across diagnostic categories. Patients who could carry out fMRI-based mental imagery tasks showed no statistically significant difference in NSE latencies relative to healthy controls; this subgroup included patients without behavioral command following. The NSE may stratify patients with severe brain injuries and identify those patients demonstrating "cognitive motor dissociation" (CMD) [26] who show only covert evidence of command following utilizing neuroimaging or electrophysiological methods that demand high levels of cognitive function. Thus, the NSE is a passive measure that may provide a useful screening tool to improve detection of covert cognition with fMRI or other methods and improve stratification of patients with disorders of consciousness in research studies.
Cheleuitte-Nieves C, Gulvik CA, McQuiston JR, Humrighouse BW, Bell ME, Villarma A, Fischetti VA, Westblade LF, Lipman NS
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Genotypic differences between strains of the opportunistic pathogen Corynebacterium bovis isolated from humans, cows, and rodents

PLOS ONE 2018 DEC 26; 13(12):? Article e0209231
Corynebacterium bovis is an opportunistic bacterial pathogen shown to cause eye and prosthetic joint infections as well as abscesses in humans, mastitis in dairy cattle, and skin disease in laboratory mice and rats. Little is known about the genetic characteristics and genomic diversity of C. bovis because only a single draft genome is available for the species. The overall aim of this study was to sequence and compare the genome of C. bovis isolates obtained from different species, locations, and time points. Whole-genome sequencing was conducted on 20 C. bovis isolates (six human, four bovine, nine mouse and one rat) using the Illumina MiSeq platform and submitted to various comparative analysis tools. Sequencing generated high-quality contigs (over 2.53 Mbp) that were comparable to the only reported assembly using C. bovis DSM 20582(T) (97.8 +/- 0.36% completeness). The number of protein-coding DNA sequences (2,174 +/- 12.4) was similar among all isolates. A Corynebacterium genus neighbor-joining tree was created, which revealed Corynebacterium falsenii as the nearest neighbor to C. bovis (95.87% similarity), although the reciprocal comparison shows Corynebacterium jeikeium as closest neighbor to C. falsenii. Interestingly, the average nucleotide identity demonstrated that the C. bovis isolates clustered by host, with human and bovine isolates clustering together, and the mouse and rat isolates forming a separate group. The average number of genomic islands and putative virulence factors were significantly higher (p<0.001) in the mouse and rat isolates as compared to human/bovine isolates. Corynebacterium bovis' pan-genome contained a total of 3,067 genes of which 1,354 represented core genes. The known core genes of all isolates were primarily related to "metabolism" and "information storage/processing." However, most genes were classified as "function unknown" or "unclassified". Surprisingly, no intact prophages were found in any isolate; however, almost all isolates had at least one complete CRISPR-Cas system.
Melinda E
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Molecular genetic studies in primary immunodeficiencies

ORVOSI HETILAP 2018 DEC; 159(49):2095-2112
Next generation sequencing methods represent the latest era of molecular genetic diagnostics. After a general introduction on primary immunodeficiencies, the author summarizes the importance of molecular genetic studies, especially next generation sequencing in the diagnosis of primary immunodeficiencies. Another purpose of the manuscript is to give a brief summary on the methodological basis of next generation sequencing. The author analyzes the advantages and disadvantages of primary immunodeficiency gene-panel sequencing and whole-exome and wholegenome sequencing. Primary immunodeficiency genes and diseases recognized by next generation sequencing is also summarized. Finally, the author emphasizes the indispensability of gene level diagnostics in primary immunodeficiencies and presents the results achieved in this field in Hungary.
Rinaudo P, Albertini D
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Promising noninvasive microscopy imaging technique evaluates metabolic markers in mouse oocytes

FERTILITY AND STERILITY 2018 DEC; 110(7):1271-1271
Gupta I, Collier PG, Haase B, Mahfouz A, Joglekar A, Floyd T, Koopmans F, Barres B, Smit AB, Sloan SA, Luo WJ, Fedrigo O, Ross ME, Tilgner HU
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Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells

NATURE BIOTECHNOLOGY 2018 DEC; 36(12):1197-1202
Full-length RNA sequencing (RNA-Seq) has been applied to bulk tissue, cell lines and sorted cells to characterize transcriptomes(1)(-11), but applying this technology to single cells has proven to be difficult, with less than ten single-cell transcriptomes having been analyzed thus far(12)(,)(13). Although single splicing events have been described for <= 200 single cells with statistical confidence(14,)(15), full-length mRNA analyses for hundreds of cells have not been reported. Single-cell short-read 3' sequencing enables the identification of cellular subtypes(16)(-21), but full-length mRNA isoforms for these cell types cannot be profiled. We developed a method that starts with bulk tissue and identifies single-cell types and their full-length RNA isoforms without fluorescence-activated cell sorting. Using single-cell isoform RNA-Seq (ScISOr-Seq), we identified RNA isoforms in neurons, astrocytes, microglia, and cell subtypes such as Purkinje and Granule cells, and cell-type-specific combination patterns of distant splice sites(6)(-9.)(22)(,)(23) We used ScISOr-Seq to improve genome annotation in mouse Gencode version 10 by determining the cell-type-specific expression of 18,173 known and 16,872 novel isoforms.
Wang Q, Barad DH, Darmon SK, Kushnir VA, Wu YG, Lazzaroni-Tealdi E, Zhang L, Albertini DF, Gleicher N
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Reduced RNA expression of the FMR1 gene in women with low (CGG(n<26)) repeats

PLOS ONE 2018 DEC 21; 13(12):? Article e0209309
Low FMR1 variants (CGG(n<26)) have been associated with premature ovarian aging, female infertility and poor IVF treatment success. Until now, there is little published information concerning possible molecular mechanisms for this effect. We wished to examine whether relative expression of RNA and the FMR1 gene's fragile X mental retardation protein (FMRP) RNA isoforms differ in women with various FMR1 sub-genotypes (normal, low CGG(n<26) and/or high CGG(n >= 34)). This prospective cohort study was conducted between 2014 and 2017 in a clinical research unit of the Center for Human Reproduction in New York City. The study involved a total of 98 study subjects, including 18 young oocyte donors and 80 older infertility patients undergoing routine in vitro fertilization (IVF) cycles. The main outcome measure was RNA expression in human luteinized granulosa cells of 5 groups of FMRP isoforms. The relative expression of FMR1 RNA in human luteinized granulosa cells was measured by real-time PCR and a possible association with CGG(n) was explored. All 5 groups of FMRP RNA isoforms examined were found to be differentially expressed in human luteinized granulosa cells. The relative expression of four FMR1 RNA isoforms showed significant differences among 6 FMR1 sub-genotypes. Women with at least one low allele expressed significantly lower levels of all 5 sets of FRMP isoforms in comparison to the non-low group. While it would be of interest to see whether FMRP is also decreased in the low-group we recognize that in recent years it has been increasingly documented that information flow of genetics may be regulated by non-coding RNA, that is, without translation to a protein product. We, thus, conclude that various CGG expansions of FMR1 allele may lead to changes of RNA levels and ratios of distinct FMRP RNA isoforms, which could regulate the translation and/or cellular localization of FMRP, affect the expression of steroidogenic enzymes and hormonal receptors, or act in some other epigenetic process and therefore result in the ovarian dysfunction in infertility.
Li SC, Li XH, Pope E, Stewart K, Higgins GC, Rabinovich CE, O'Neil KM, Haines KA, Laxer RM, Punaro M, Jacobe H, Andrews T, Wittkowski K, Nyirenda T, Foeldvari I, Torok KS
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New Features for Measuring Disease Activity in Pediatric Localized Scleroderma

JOURNAL OF RHEUMATOLOGY 2018 DEC 1; 45(12):1680-1688
Objective. To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance. Methods. We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician's global assessments of activity (PGA-A). Results. Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA-A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status. Conclusion. We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.
Zhang P, Bigio B, Rapaport F, Zhang SY, Casanova JL, Abel L, Boisson B, Itan Y
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PopViz: a webserver for visualizing minor allele frequencies and damage prediction scores of human genetic variations

BIOINFORMATICS 2018 DEC 15; 34(24):4307-4309
Next-generation sequencing (NGS) generates large amounts of genomic data and reveals about 20 000 genetic coding variants per individual studied. Several mutation damage prediction scores are available to prioritize variants, but there is currently no application to help investigators to determine the relevance of the candidate genes and variants quickly and visually from population genetics data and deleteriousness scores. Here, we present PopViz, a user-friendly, rapid, interactive, mobile-compatible webserver providing a gene-centric visualization of the variants of any human gene, with (i) population-specific minor allele frequencies from the gnomAD population genetic database; (ii) mutation damage prediction scores from CADD, EIGEN and LINSIGHT and (iii) amino-acid positions and protein domains. This application will be particularly useful in investigations of NGS data for new disease-causing genes and variants, by reinforcing or rejecting the plausibility of the candidate genes, and by selecting and prioritizing, the candidate variants for experimental testing.
Maffucci P, Chavez J, Jurkiw TJ, O'Brien PJ, Abbott JK, Reynolds PR, Worth A, Notarangelo LD, Felgentreff K, Cortes P, Boisson B, Radigan L, Cobat A, Dinakar C, Ehlayel M, Ben-Omran T, Gelfand EW, Casanova JL, Cunningham-Rundles C
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Biallelic mutations in DNA ligase 1 underlie a spectrum of immune deficiencies

JOURNAL OF CLINICAL INVESTIGATION 2018 DEC 3; 128(12):5489-5504
We report the molecular, cellular, and clinical features of 5 patients from 3 kindreds with biallelic mutations in the autosomal LIG1 gene encoding DNA ligase 1. The patients exhibited hypogammaglobulinemia, lymphopenia, increased proportions of circulating gamma dT cells, and erythrocyte macrocytosis. Clinical severity ranged from a mild antibody deficiency to a combined immunodeficiency requiring hematopoietic stem cell transplantation. Using engineered LIG1-deficient cell lines, we demonstrated chemical and radiation defects associated with the mutant alleles, which variably impaired the DNA repair pathway. We further showed that these LIG1 mutant alleles are amorphic or hypomorphic, and exhibited variably decreased enzymatic activities, which lead to premature release of unligated adenylated DNA. The variability of the LIG1 genotypes in the patients was consistent with that of their immunological and clinical phenotypes. These data suggest that different forms of autosomal recessive, partial DNA ligase 1 deficiency underlie an immunodeficiency of variable severity.