bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement factor I deficiency: a not so rare immune defect. Characterization of new mutations and the first large gene deletion
Authors: Alba-Domínguez María , López-Lera Alberto , Garrido Sofía , Nozal Pilar , González-Granado Ignacio , Melero Josefa , Soler-Palacín Pere , Cámara Carmen , López-Trascasa Margarita 
Published: June 2012

AbstractBackgroundComplement Factor I (CFI) is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide.Patients and methodsWe have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included.ResultsMolecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1.ConclusionCFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.
Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult
Authors: Rodgers Shaefali P , Born Heather A , Das Pritam , Jankowsky Joanna L 
Published: June 2012

Abstract

Background
Transgenic mice expressing disease-associated proteins have become standard tools for studying human neurological disorders. Transgenes are often expressed using promoters chosen to drive continuous high-level expression throughout life rather than temporal and spatial fidelity to the endogenous gene. This approach has allowed us to recapitulate diseases of aging within the two-year lifespan of the laboratory mouse, but has the potential for creating aberrant phenotypes by mechanisms unrelated to the human disorder.

Results
We show that overexpression of the Alzheimer’s-related amyloid precursor protein (APP) during early postnatal development leads to severe locomotor hyperactivity that can be significantly attenuated by delaying transgene onset until adulthood. Our data suggest that exposure to transgenic APP during maturation influences the development of neuronal circuits controlling motor activity. Both when matched for total duration of APP overexpression and when matched for cortical amyloid burden, animals exposed to transgenic APP as juveniles are more active in locomotor assays than animals in which APP overexpression was delayed until adulthood. In contrast to motor activity, the age of APP onset had no effect on thigmotaxis in the open field as a rough measure of anxiety, suggesting that the interaction between APP overexpression and brain development is not unilateral.

Conclusions
Our findings indicate that locomotor hyperactivity displayed by the tet-off APP transgenic mice and several other transgenic models of Alzheimer’s disease may result from overexpression of mutant APP during postnatal brain development. Our results serve as a reminder of the potential for unexpected interactions between foreign transgenes and brain development to cause long-lasting effects on neuronal function in the adult. The tet-off APP model provides an easy means of avoiding developmental confounds by allowing transgene expression to be delayed until the mice reach adulthood.
PathCase-SB: integrating data sources and providing tools for systems biology research
Authors: Coskun Sarp A , Qi Xinjian , Cakmak Ali , Cheng En , Cicek A Ercument , Yang Lei , Jadeja Rishiraj , Dash Ranjan K , Lai Nicola , Ozsoyoglu Gultekin , Ozsoyoglu Zehra Meral 
Published: June 2012

Abstract

Background
Integration of metabolic pathways resources and metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation of metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks.

Results
PathCase Systems Biology (PathCase-SB) is built and released. This paper describes PathCase-SB user interfaces developed to date. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate systems biology models data and metabolic network data of selected biological data sources on the web (currently, BioModels Database and KEGG, respectively), and to provide more powerful and/or new capabilities via the new web-based integrative framework.

Conclusions
Each of the c urrent four PathCase-SB interfaces, namely, Browser, Visualization, Querying, and Simulation interfaces, have expanded and new capabilities as compared with the original data sources. PathCase-SB is already available on the web and being used by researchers across the globe.
Screening significantly hypermethylated genes in fetal tissues compared with maternal blood using a methylated-CpG island recovery assay-based microarray
Authors: Yin Aihua , Zhang Xiangzhong , Wu Jing , Du Li , He Tianwen , Zhang Xiaozhuang 
Published: June 2012

Abstract

Background
The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorders. However, such efforts have covered only chromosomal aneuploidy, and fetal methylated DNA biomarkers in maternal whole blood for detecting single-gene diseases remain to be discovered.

Methods
To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues and compared them with maternal peripheral blood potential in an attempt to detect fetal genes in maternal peripheral blood. First, the methylated-CpG island recovery assay combined with a CpG island array was performed for four fetus-toward placental tissues and the corresponding maternal peripheral bloods. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the methylation status of the hypermethylated genes that were identified by the microarray analysis.

Results
Three hundred and ten significantly hypermethylated genes in the placental tissues were detected by microarray. From the top 15 hypermethylated genes detected by microarray, two were selected for sequencing validation in placental tissue and chorionic villus samples and four were selected for COBRA validation in four placental tissues, ten amniotic fluids and five chorionic villus samples. The six selected genes were confirmed to be hypermethylated in placental tissue and chorionic villus samples, but methylation of the genes could not be detected in the amniotic fluids.

Conclusions
Of the many hypermethylated genes and methylation sites that were found in the fetal tissues, some have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical studies are warranted to confirm these findings.
How do alignment programs perform on sequencing data with varying qualities and from repetitive regions?
Authors: Yu Xiaoqing , Guda Kishore , Willis Joseph , Veigl Martina , Wang Zhenghe , Markowitz Sanford , Adams Mark D , Sun Shuying 
Published: June 2012

Abstract

Background
Next-generation sequencing technologies generate a significant number of short reads that are utilized to address a variety of biological questions. However, quite often, sequencing reads tend to have low quality at the 3’ end and are generated from the repetitive regions of a genome. It is unclear how different alignment programs perform under these different cases. In order to investigate this question, we use both real data and simulated data with the above issues to evaluate the performance of four commonly used algorithms: SOAP2, Bowtie, BWA, and Novoalign.

Methods
The performance of different alignment algorithms are measured in terms of concordance between any pair of aligners (for real sequencing data without known truth) and the accuracy of simulated read alignment.

Results
Our results show that, for sequencing data with reads that have relatively good quality or that have had low quality bases trimmed off, all four alignment programs perform similarly. We have also demonstrated that trimming off low quality ends markedly increases the number of aligned reads and improves the consistency among different aligners as well, especially for low quality data. However, Novoalign is more sensitive to the improvement of data quality. Trimming off low quality ends significantly increases the concordance between Novoalign and other aligners. As for aligning reads from repetitive regions, our simulation data show that reads from repetitive regions tend to be aligned incorrectly, and suppressing reads with multiple hits can improve alignment accuracy.

Conclusions
This study provides a systematic comparison of commonly used alignment algorithms in the context of sequencing data with varying qualities and from repetitive regions. Our approach can be applied to different sequencing data sets generated from different platforms. It can also be utilized to study the performance of other alignment programs.
Prevalence and risk factors associated with self-reported carpal tunnel syndrome (CTS) among office workers in Kuwait
Authors: Raman Sudha R , Al-Halabi Becher , Hamdan Elham , Landry Michel D 
Published: June 2012

Abstract

Background
The prevalence of carpal tunnel syndrome (CTS) is not well understood in many Arabian Peninsula countries. The objective of this study was to investigate the prevalence and factors associated with self-reported CTS in Kuwait.

Findings
A cross-sectional, self-administered survey of CTS-related symptoms was used in this study. Multivariate logistic regression was also used to estimate adjusted odds ratios for factors of interest. Participants in this study were adult office workers in Kuwait (n = 470, 55.6% males), who worked in companies employing more than 50 people. Self-reported CTS was reported in 18.7% of the group (88/470). CTS was significantly associated with the following demographic factors: female gender, obesity and number of comorbid conditions. Self-identification of CTS was also associated with key symptoms and impairment in daily activities (e.g., wrist pain, numbness, weakness, night pain, difficulty carrying bags, difficulty grasping [Chi-Square Test for Association: P < 0.05 for all symptoms/activities]). However, symptoms such as wrist pain, weakness, and functional disabilities were also frequently reported among those who do not self report CTS (range: 12.1%–38.2%).

Conclusions
Prevalence of self-reported CTS among office workers in Kuwait is 18.7%, and the risk factors for CTS in this population included female gender, obesity and number of related comorbidities. The frequency of symptoms in the sample who did not self report CTS suggest that CTS may be under-recognized, however further research is required to assess the prevalence of clinically diagnosed CTS.
Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Northern Bavaria, Germany
Authors: Wieching Anna , Benser Jasmin , Kohlhauser-Vollmuth Christina , Weissbrich Benedikt , Streng Andrea , Liese Johannes G 
Published: June 2012

Abstract

Background
The 2009 pandemic influenza A (H1N1) (PIA) virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate. The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1) 2009-associated hospitalizations (PIAH) in children <18 years of age. All hospitalized cases of children <18 years of age with laboratory-confirmed pandemic influenza A (H1N1) 2009 in the region of Wuerzburg (Northern Bavaria, Germany) between July 2009 and March 2010 were identified. For these children a medical chart review was performed to determine their clinical characteristics and complications.

Results
Between July 2009 and March 2010, 94 PIAH (62% males) occurred in children <18 years of age, with a median age of 7 years (IQR: 3–12 years). Underlying diseases and predisposing factors were documented in 40 (43%) children; obesity (n = 12, 30%), asthma (n = 10, 25%) and neurologic disorders (n = 8, 20%) were most frequently reported. Sixteen (17%) children received oxygen supplementation; three (3%) children required mechanical ventilation. Six (6%) children were admitted to an intensive care unit, four of them with underlying chronic diseases.

Conclusions
Most PIAH demonstrated a benign course of disease. However, six children (6%) needed treatment at an intensive care unit for severe complications.
Alterations in the ribosomal machinery in cancer and hematologic disorders
Authors: Shenoy Niraj , Kessel Rachel , Bhagat Tushar D , Bhattacharyya Sanchari , Yu Yiting , Mcmahon Christine , Verma Amit 
Published: June 2012

Abstract
Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases.
Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats
Authors: Taylor Patrick V , Veenema Alexa H , Paul Matthew J , Bredewold Remco , Isaacs Stephanie , de Vries Geert J 
Published: June 2012

Abstract

Background
Infectious diseases and inflammation during pregnancy increase the offspring’s risk for behavioral disorders. However, how immune stress affects neural circuitry during development is not well known. We tested whether a prenatal immune challenge interferes with the development of social play and with neural circuits implicated in social behavior.

Methods
Pregnant rats were given intraperitoneal injections of the bacterial endotoxin lipopolysaccharide (LPS – 100 μg /kg) or saline on the 15th day of pregnancy. Offspring were tested for social play behaviors between postnatal days 26–40. Brains were harvested on postnatal day 45 and processed for arginine vasopressin (AVP) mRNA in situ hybridization.

Results
In males, LPS treatment reduced the frequency of juvenile play behavior and reduced AVP mRNA expression in the medial amygdala and bed nucleus of the stria terminalis. These effects were not found in females. LPS treatment did not change AVP mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, or supraoptic nucleus of either sex, nor did it affect the sex difference in the size of the sexually dimorphic nucleus of the preoptic area.

Conclusions
Given AVP’s central role in regulating social behavior, the sexually dimorphic effects of prenatal LPS treatment on male AVP mRNA expression may contribute to the sexually dimorphic effect of LPS on male social play and may, therefore, increase understanding of factors that contribute to sex differences in social psychopathology.
Comprehensive allergy work‐up is mandatory in cystic fibrosis patients who report a history suggestive of drug allergy to beta‐lactam antibiotics
Authors: Caimmi Silvia , Sanfiorenzo Céline , Caimmi Davide , Bousquet Philippe‐Jean , Chiron Raphael , Demoly Pascal 
Published: June 2012

AbstractBackgroundIn the general population, reports on suspected ß‐lactam hypersensitivity are common. After a drug allergy work‐up at best 20% of the selected patients are positive. However, these considerations have not been explored in cystic fibrosis patients for whom antibiotics are even more crucial.MethodsThe study, part of the Drug Allergy and Hypersensitivity (DAHD) cohort, was performed in the regional cystic fibrosis center of Montpellier, France. After identifying patients with a clinical history suggestive of drug allergy to ß‐lactams, a complete drug allergy work‐up, was carried out according to the EAACI recommendations.ResultsAmong the 171 patients involved, 23 reported clinical manifestations potentially compatible with a drug allergy to ß‐lactams. After performing the complete drug‐allergy work‐up, 7 were considered as drug hypersensitive (3 had positive skin tests, 1 a positive provocation test, 3 declined the tests). Excluding the latter 3 patients with incomplete drug allergy work‐up, the rate of proven drug allergy was 2.3%.ConclusionsDrug allergy to ß‐lactams in cystic fibrosis patients is of importance. A full drug allergy work‐up is mandatory in case of suspicion, because ß‐lactam responsibility is often ruled out.
Vascular diaphragmatic hernia in a patient with cirrhosis first case report
Authors: Lazăr Mihai I , Ion Daniela Adriana IF 
Published: June 2012

Abstract
We report the case of an adult patient recently diagnosed with cirrhosis. The ultrasound evaluation described a multinodular inhomogeneous liver, requiring a magnetic resonance imaging scan for further characterization. The performed magnetic resonance imaging examination confirmed the diagnosis of cirrhosis associated with portal hypertension and detected a vascular left transdiaphragmatic hernia. Although various types of diaphragmatic hernias have been described - congenital or acquired - to the best of our knowledge, this type of pathology has never been reported.
Neuropsychological outcomes of mild traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army soldiers
Authors: Vasterling Jennifer J. , Brailey Kevin , Proctor Susan P. , Kane Robert , Heeren Timothy , Franz Molly 
Published: June 2012

BackgroundTraumatic brain injury (TBI) is a concern of contemporary military deployments. Whether milder TBI leads to enduring impairment remains controversial.AimsTo determine the influence of deployment TBI, and posttraumatic stress disorder (PTSD) and depression symptoms on neuropsychological and functional outcomes.MethodA sample of 760 US Army soldiers were assessed pre- and post-deployment. Outcomes included neuropsychological performances and subjective functional impairment.ResultsIn total, 9% of the participants reported (predominantly mild) TBI with loss of consciousness between pre- and post-deployment. At post-deployment, 17.6% of individuals with TBI screened positive for PTSD and 31.3% screened positive for depression. Before and after adjustment for psychiatric symptoms, TBI was significantly associated only with functional impairment. Both PTSD and depression symptoms adjusted for TBI were significantly associated with several neuropsychological performance deficits and functional impairment.ConclusionsMilder TBI reported by deployed service members typically has limited lasting neuropsychological consequences; PTSD and depression are associated with more enduring cognitive compromise.
Screening for pre-eclampsia using serum placental growth factor and endoglin with Down's syndrome Quadruple test markers
Authors: Wald Nicholas J , Bestwick Jonathan P , George Lynne M , Wu Tiesheng , Morris Joan K 
Published: June 2012

Objective To estimate the pre-eclampsia screening performance of placental growth factor (PlGF) and endoglin with second-trimester Quadruple test markers used for antenatal Down's syndrome screening. Methods A nested case-control study of 88 pregnant women with known early second-trimester Down's syndrome Quadruple test marker levels who subsequently developed pre-eclampsia and 275 unaffected controls. Frozen maternal serum samples were thawed and assayed for PlGF and endoglin. Monte Carlo simulation was used to estimate the pre-eclampsia screening performance of a pre-eclampsia detection algorithm using the Quadruple test markers with or without the addition of PlGF and/or endoglin. Results Median PlGF was 33% lower (95% confidence interval 24–41%) and endoglin 31% (20–43%) higher in pre-eclampsia than in unaffected pregnancies. Adding PlGF to the Quadruple test markers increased the pre-eclampsia detection rate from 34% to 45% at a 5% false-positive rate – it increased it to 43% with endoglin and to 50% with both. The corresponding estimates for early pre-eclampsia (before 36 weeks’ gestation) were a few percentage points higher (48%, 48% and 55% respectively). Including information on parity, pre-eclampsia in a previous pregnancy, family history (woman's mother) and assuming a pre-eclampsia prevalence of 2%, the detection rates for a 5% false-positive rate were 39% with the Quadruple test markers, 48% with addition of endoglin, 49% with addition of PlGF, and 54% with addition of both. Conclusions Adding PlGF to the Quadruple test Down's syndrome screening markers improves pre-eclampsia screening performance. There is a modest extra benefit in also adding the measurement of endoglin.
The calculation of targets for the cancer and adenoma detection rates for the NHS bowel screening programme
Authors: Blanks Roger G , Moss Susan M 
Published: June 2012

Objectives The NHS bowel screening programme offers people aged 60–69 screening by faecal occult blood (FOB) testing, with colonoscopy as the diagnostic test. This paper describes the calculation of targets for the purpose of monitoring screening performance in the programme. Methods Targets were calculated for the prevalent round of screening in people aged 60–69, and for the ‘steady state’ of the programme when people will be offered their first screen at age 60 and subsequent screens at ages 62–69. Targets for the cancer and adenoma detection rates per 1000 people screened and per 100 colonoscopies were calculated using information from the English bowel cancer screening pilot. Results For the prevalent round, prevalent screen and incident screens the calculated targets for the cancer detection rate are 2.3, 1.3 and 1.7 per 1000 people respectively. For the adenoma detection rate the targets are 6.7, 5.2 and 5.5 per 1000 respectively. Targets for the cancer detection rate per 100 colonoscopies are 11.3, 7.5 and 8.4 and those for the adenoma detection rate are 32.0, 30.4 and 32.5 respectively. Conclusions The purpose of these targets is to ensure that the national bowel cancer screening programme is effective with a high quality of screening. The cancer detection and adenoma detection rates per 1000 people are those estimated to be necessary to achieve the expected mortality reduction. Rates per 100 colonoscopies (equivalent to the positive predictive value of referral to colonoscopy) are designed to maintain a high quality of screening by minimizing the number of false-positive referrals.