tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3
Authors: Nigel M. Williams, Barbara Franke, Eric Mick, Richard J.L. Anney, Christine M. Freitag, Michael Gill, Anita Thapar, Michael C. O'Donovan, Michael J. Owen, Peter Holmans, Lindsey Kent, Frank Middleton, Yanli Zhang-James, Lu Liu, Jobst Meyer, Thuy Trang Nguyen, Jasmin Romanos, Marcel Romanos, Christiane Seitz, Tobias J. Renner, Susanne Walitza, Andreas Warnke, Haukur Palmason, Jan Buitelaar, Nanda Rommelse, Alejandro Arias Vasquez, Ziarih Hawi, Kate Langley, Joseph Sergeant, Hans-Christoph Steinhausen, Herbert Roeyers, Joseph Biederman, Irina Zaharieva, Hakon Hakonarson, Josephine Elia, Anath C. Lionel, Jennifer Crosbie, Christian R. Marshall, Russell Schachar, Stephen W. Scherer, Alexandre Todorov, Susan L. Smalley, Sandra Loo, Stanley Nelson, Corina Shtir, Philip Asherson, Andreas Reif, Klaus-Peter Lesch, Stephen V. Faraone
Journal: American Journal of Psychiatry (2011)

Objective: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. Method: The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. Results: The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. Conclusions: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.
Role of primary care in the follow-up of patients with obstructive sleep apnoea undergoing CPAP treatment: a randomised controlled trial
Authors: M. Sanchez-de-la-Torre, N. Nadal, A. Cortijo, J. Masa, J. Duran-Cantolla, J. Valls, S. Serra, A. Sanchez-de-la-Torre, M. Gracia, F. Ferrer, I. Lorente, M. C. Urgeles, T. Alonso, A. Fuentes, F. Armengol, M. Lumbierres, F. J. Vazquez-Polo, F. Barbe, E. Paredes, N. Roquet, M. Lavega, J. Sangra, N. Tribo, B. Malla, E. Obis, C. Juni, M. Regany, O. Minguez, L. Pasual, S. Gomez, A. Castro, N. Tarraubella, C. Turino, M. A. Negrin
Journal: Thorax (2015)

To evaluate whether follow-up of patients with obstructive sleep apnoea (OSA) undergoing CPAP treatment could be performed in primary care (PC) settings.Non-inferiority, randomised, prospective controlled study.Sleep unit (SU) at the University Hospital and in 8 PC units in Lleida, Spain.Patients with OSA were randomised to be followed up at the SU or PC units over a 6-month period.The primary outcome was CPAP compliance at 6 months. The secondary outcomes were Epworth Sleep Scale (ESS) score, EuroQoL, patient satisfaction, body mass index (BMI), blood pressure and cost-effectiveness.We included 101 patients in PC ((mean±SD) apnoea-hypopnoea index (AHI) 50.8±22.9/h, age 56.2±11 years, 74% male) and 109 in the SU (AHI 51.4±24.4/h, age 55.8±11 years, 77% male)). The CPAP compliance was (mean (95% CI) 4.94 (4.47 to 5.5) vs 5.23 (4.79 to 5.66) h, p=0.18) in PC and SU groups, respectively. In the SU group, there were greater improvements in ESS scores (mean change 1.79, 95% CI +0.05 to +3.53, p=0.04) and patient satisfaction (-1.49, 95% CI -2.22 to -0.76); there was a significant mean difference in BMI between the groups (0.57, 95% CI +0.01 to +1.13, p=0.04). In the PC setting, there was a cost saving of 60%, with similar effectiveness, as well as a decrease in systolic blood pressure (-5.32; 95% CI -10.91 to +0.28, p=0.06).For patients with OSA, treatment provided in a PC setting did not result in worse CPAP compliance compared with a specialist model and was shown to be a cost-effective alternative.Clinical Trials NCT01918449.
Influence of sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)
Authors: Virginia J Howard, Helmi L Lutsep, Ariane Mackey, Bart M Demaerschalk, Albert D Sam, Nicole R Gonzales, Alice J Sheffet, Jenifer H Voeks, James F Meschia, Thomas G Brott
Journal: The Lancet Neurology (2011)
Identification of two variant short chain acyl-coenzyme A dehydrogenase alleles, each containing a different point mutation in a patient with short chain acyl-coenzyme A dehydrogenase deficiency.
Authors: E Naito, Y Indo, K Tanaka
Journal: Journal of Clinical Investigation (1990)

Two distinct mutant alleles of the precursor (p) short chain acyl-CoA dehydrogenase (SCAD) gene were identified in a SCAD-deficient patient (YH2065) using the polymerase chain reaction to amplify cDNA synthesized from total RNA from her fibroblasts. Cells from this patient had previously been shown to synthesize a labile variant SCAD in contrast to the normal stability of variant SCADs in two other SCAD-deficient cell lines (Naito, E., Y. Indo, and K. Tanaka. 1989. J. Clin. Invest. 84:1671-1674). In the present study, both mutant alleles of YH2065 were found to contain a C----T transition, one at position 136 and the other at position 319 of the coding region of pSCAD cDNA. Clones of cDNA amplified from this region showed only one of the C----T transitions, indicating that each mutation was derived from different pSCAD alleles. Each of these mutations altered a known restriction endonuclease site, and restriction analysis of additional cDNA clones from amplified mutant cDNA and Southern blotting of mutant genomic DNA confirmed the presence of two unique mutant alleles in YH2065, indicating YH2065 is a compound heterozygote. These C----T transitions result in the substitution of Arg-22 and Arg-83 of the mature SCAD with Trp and Cys, respectively.
The Incidence of Anorexia Nervosa on Curaçao
Authors: Hans W Hoek, Peter N van Harten, Karin M E Hermans, Melanie A Katzman, Glenn E Matroos, Ezra S Susser
Journal: American Journal of Psychiatry (2005)

Although anorexia nervosa was once thought to occur only in affluent societies, cases have now been documented across the globe. To examine whether anorexia nervosa emerges in societies undergoing socioeconomic transition, the authors studied the incidence of anorexia nervosa on the Caribbean island of Curaçao.
Injury initiates unfavourable weight gain and obesity markers in youth
Authors: Gregory D Myer, Avery D Faigenbaum, Kim Barber Foss, Yingying Xu, Jane Khoury, Lawrence M Dolan, Teri M McCambridge, Timothy E Hewett
Journal: British Journal of Sports Medicine (2013)

Objective The purpose of this study was to examine the association of knee injuries with subsequent changes in body mass index and body composition during maturation in young females. Methods A prospective longitudinal study design was employed to evaluate young females active in soccer or basketball (N=862). Participants who completed at least 1-year follow-up to provide consecutive annual measures of BMIZ and %fat were included in the study analysis to determine the effect of knee injuries on the trajectory of these obesity markers in youth. Results Of the 71 reported knee injuries, 12 (17%) occurred in athletes at the prepubertal stage, 24 (34%) in athletes at the pubertal stage, and 35 (49%) in postpubertal athletes. Controlling for the effects of maturation, female athletes who reported knee injury demonstrated a greater yearly increase in BMIZ (LS means and 95% CI for the injured group=0.039 (−0.012 to 0.089), for the non-injured group=−0.019 (−0.066 to 0.029), and group difference=0.057 (0.005 to 0.11), p=0.03) and in %body fat (LS means and 95% CI for the injured group=1.05 (0.45 to 1.65), for the non-injured group=0.22 (−0.21 to 0.064), and group difference=0.83 (0.21 to 1.45), p=0.009), compared to those without knee injuries. This indicates that the athletes with knee injuries will increase their body mass index percentile by up to 5 units more than someone of the same age without an injury, and in body fat by up to 1.5%, compared to their non-injured peers. Conclusions The present findings indicate that knee injury during the growing years may be associated with unfavourable changes in body composition.
Control of Plasma Uric Acid in Adults at Risk for Tumor Lysis Syndrome: Efficacy and Safety of Rasburicase Alone and Rasburicase Followed by Allopurinol Compared With Allopurinol Alone—Results of a Multicenter Phase III Study
Authors: Jorge Cortes, Joseph O. Moore, Richard T. Maziarz, Meir Wetzler, Michael Craig, Jeffrey Matous, Selina Luger, Bimalangshu R. Dey, Gary J. Schiller, Dat Pham, Camille N. Abboud, Muthuswamy Krishnamurthy, Archie Brown, Abderrahmane Laadem, Karen Seiter
Journal: Journal of Clinical Oncology (2010)

Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid.Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7.Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol.In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol.
Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis
Authors: M.J. Vercammen, A. Verloes, H. Van de Velde, P. Haentjens
Journal: Human Reproduction Update (2008)

There have been concerns about validity and accuracy of the measurement of sHLA-G in embryo culture supernatants. In this systematic review, we quantified the diagnostic accuracy of sHLA-G for predicting the ability to achieve clinical pregnancy in women who are undergoing infertility treatment. Medline and Embase were searched up to 7 September 2007, for full English and non-English articles concerning cohort studies evaluating sHLA-G in embryo culture for predicting clinical pregnancy in women undergoing IVF and ICSI. Eleven studies including 1813 patients met our inclusion criteria. In the individual studies, sensitivity ranged from 0.01 to 0.97, specificity from 0.18 to 0.98, the positive likelihood ratio from 0.34 to 3.21 and the negative likelihood ratio from 0.08 to 1.01. These values were highly heterogeneous with, in each case, I2 values of >75%, and P-values for the Q statistic of <0.001, arguing against generating a pooled estimate for these diagnostic test properties. The diagnostic odds ratios (DORs) ranged from 0.92 to 24.82 in the individual studies with an I2 value of 49% indicating moderate heterogeneity. Therefore, the meta-analysis combined the logs of the DORs, which are derived from sensitivity and specificity. A random-effects model yielded a summary DOR of 4.38 (95% CI, 2.93–6.55), consistent with modest diagnostic accuracy. Interestingly, an a priori defined subgroup analysis restricted to six studies with good quality embryos showed a better diagnostic performance with a DOR of 12.67 (95% CI, 3.66–43.80) to predict the ability to achieve clinical pregnancy in women undergoing infertility treatment. CONCLUSIONS: Further research is needed with single-embryo culture, single-embryo transfer and highly sensitive detection techniques to determine the potential application of measuring sHLA-G in culture supernatant.
Alveolar Hydatid Disease in Minnesota
Authors: William G. Gamble
Journal: JAMA (1979)

A 56-year-old woman from southwestern Minnesota underwent an extended left hepatic lobectomy to remove a large multinodular mass with a necrotic central cavity. The clinical, serological, and pathological findings led to the diagnosis of alveolar hydatid disease, and specific identification of<i>Echinococcus multilocularis</i>was achieved by growing mature larvas in voles inoculated intraperitoneally with tissue from the hepatic lesions. The patient probably acquired her infection some years previously from pet cats or dogs that had become infected by ingesting infected rodents. In North America<i>E multilocularis</i>is enzootic in the northern tundra zone of Alaska and Canada. Since 1964 the cestode has been recognized with increasing frequency in several north-central states, including Minnesota. The parasite may extend its range farther south, since suitable animal hosts occur throughout the United States. (<i>JAMA</i>241:904-907, 1979)
A Prospective Randomized EORTC Intergroup Phase 3 Study Comparing the Complications of Elective Nephron-Sparing Surgery and Radical Nephrectomy for Low-Stage Renal Cell Carcinoma
Authors: Hendrik Van Poppel, Luigi Da Pozzo, Walter Albrecht, Vsevolod Matveev, Aldo Bono, Andrzej Borkowski, Jean-Marie Marechal, Laurence Klotz, Eila Skinner, Thomas Keane, Ilse Claessens, Richard Sylvester
Journal: European Urology (2006)
Effects of progestogens on thrombosis and atherosclerosis
Authors: L Badimon
Journal: Human Reproduction Update (1999)

In contrast with past practice, current hormone replacement usually includes a combination of oestrogens and progestogens. In this article, we review the effect of progestins on haemostasis and in the development of atherosclerosis. Second-generation progestogens produce minor haemostatic changes, and in lipid metabolism they decrease the synthesis of triglycerides and very low density lipoproteins (VLDL) and stimulate hepatic lipoprotein lipase. In combination, progestogens modify the effect of oestrogens on hepatic metabolism, endothelium and platelets. Several new progestins (known as third-generation) have less effect on lipid profiles. In vessel walls, animal studies have shown that progestogens are able dose-dependently to inhibit the beneficial effect of oestrogen without significant changes in lipid concentrations. The endothelium-dependent vasoconstrictor effect of progestogens on the arterial wall has been also evaluated. Large epidemiological studies show a two-fold increase in risk of venous thromboembolism with the use of third-generation progestins. Regarding the risk of myocardial infarction, no definite evidence is yet available with the use of third-generation progestins. The clinical consequence is therefore that second-generation progestins are the first choice in prescription for first-time users.
Cross-shift change and subsequent longitidinal changes in FEV1 in a 6 year follow-up study of wood dust exposed workers
Authors: Gitte Jacobsen, Vivi Schlünsssen, Inger Schaumburg, Torben Sigsgaard
Journal: European Respiratory Journal (2012)

Objective: Cross-shift lung function (LF) changes might predict an accelerated decline in LF. This study investigates the association between cross-shift and annual changes in FEV1 among woodworkers in a 6-yr follow-up study.

Methods: 817 woodworkers and 136 controls participated with cross-shift changes of FEV1 at baseline and FEV1 and FVC at follow-up. Height and weight were measured and questionnaire information on respiratory symptoms, employment and smoking habits were collected. Wood dust exposure was assessed from 3,572 personal dust measurements at baseline and follow-up. Cumulative wood dust exposure was assessed by a study-specific job exposure matrix and exposure time.

Results: The median (range) of inhalable dust at baseline and cumulative wood dust exposure was 1.0 (0.2-9.8) mg/m3 and 3.8 (0-7.1) mg*year/m3 respectively. Mean (SD) for %ΔFEV1/workday and ΔFEV1/year was 0.2 (6.0)%, and -29.1 (41.8)ml. Linear regression models adjusting for smoking, sex, age, height and weight change revealed no association between cross-shift and annual change in FEV1 (table 1). Including different exposure estimates, atopy or cross-shift change dichotomized or as quartiles did not change the results.

View this table:

Table 1. Linear regression on the association between longitudinal and cross-shift change in FEV1





Conclusion: This study among low exposed woodworkers does not support an association between cross-shift changes and accelerated LF decline.
Ventricular relaxation in the stage 24 chick embryo following changes in volume and blockade of Na+ and Ca2+ channels
Authors: Z.J. Naheed, A. Lahoti, S.F. Hughes, D.W. Benson
Journal: Cardiovascular Research (1996)

Early in cardiac development, regulation of cytosolic Ca2+ has been thought to depend primarily on sarcolemmal Ca2+ transport. We hypothesized that perturbation of cytosolic Ca2+ in the embryonic ventricle would result in a change in ventricular relaxation which could be quantified by a monoexponential model. We reasoned that since it has been difficult to selectively block the Na(+)-Ca2+ exchanger in vivo, that blockade of Na+ (lidocaine) or Ca2+ (verapamil) channels in the embryonic heart may perturb cytosolic Ca2+ and thereby alter ventricular relaxation.All studies were performed in ovo in Hamilton-Hamburger stage 24 chick embryos. Isovolumic relaxation time (mean +/- standard deviation, 58 +/- 19 ms) was derived from dorsal aortic flow and atrioventricular inflow during 61 cardiac cycles in 4 embryos. Ventricular pressure was digitally recorded from 13 embryos during 188 cycles following intravenous injection of chick Ringer's solution (5 embryos), verapamil (4 embryos) or lidocaine (4 embryos). Ventricular relaxation was characterized by a monoexponential model: P(t) = P infinity + Poe-1/tau where P(t) = pressure at time (t), P infinity = pressure asymptote, Po = pressure at the onset of relaxation and tau = the isovolumic relaxation constant. Non-linear least-squares regression was used to estimate tau and P infinity during isovolumic relaxation at baseline and at 30 s and 60 s post-injection.Ventricular end-diastolic pressure was increased by all three interventions. Both lidocaine and verapamil prolonged cycle length. Lidocaine prolonged tau while chick Ringer's solution and verapamil did not. No significant change in P chi was observed.This study demonstrates that blockade of Na+ channels with lidocaine slows ventricular relaxation presumably by perturbing cytosolic Ca2+ via the Na(+)-Ca2+ exchange system. Changes following Ca2+ channel blockade with verapamil are less evident in the stage 24 chick embryo. Evaluation of ventricular relaxation may provide a useful way to study developmental aspects of Ca2+ transport.
Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer
Authors: Jennifer K. Litton, Ana M. Gonzalez-Angulo, Carla L. Warneke, Aman U. Buzdar, Shu-Wan Kau, Melissa Bondy, Somdat Mahabir, Gabriel N. Hortobagyi, Abenaa M. Brewster
Journal: Journal of Clinical Oncology (2008)

To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer.From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI >or= 30 kg/m(2)), overweight (BMI of 25 to < 30 kg/m(2)), or normal/underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer-specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided.Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years.Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.
Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion
Authors: K. Vinnakota, F. Hu, M.-C. Ku, P. B. Georgieva, F. Szulzewsky, A. Pohlmann, S. Waiczies, H. Waiczies, T. Niendorf, S. Lehnardt, U.-K. Hanisch, M. Synowitz, D. Markovic, S. A. Wolf, R. Glass, H. Kettenmann
Journal: Neuro-Oncology (2013)

Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation in and around the tumor correlates with malignancy and poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation of membrane type 1 matrix metalloprotease (MT1-MMP). This upregulation depends on signaling via the Toll-like receptor (TLR) adaptor molecule myeloid differentiation primary response gene 88 (MyD88).Using in vitro, ex vivo, and in vivo techniques, we identified TLR2 as the main TLR controlling microglial MT1-MMP expression and promoting microglia-assisted glioma expansion.The implantation of mouse GL261 glioma cells into TLR2 knockout mice resulted in significantly smaller tumors, reduced MT1-MMP expression, and enhanced survival rates compared with wild-type control mice. Tumor expansion studied in organotypic brain slices depended on both parenchymal TLR2 expression and the presence of microglia. Glioma-derived soluble factors and synthetic TLR2 specific ligands induced MT1-MMP expression in microglia from wild-type mice, but no such change in MT1-MMP gene expression was observed in microglia from TLR2 knockout mice. We also found evidence that TLR1 and TLR6 cofunction with TLR2 as heterodimers in regulating MT1-MMP expression in vitro.Our results thus show that activation of TLR2 along with TLRs 1 and/or 6 converts microglia into a glioma supportive phenotype.