bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aragonite-associated biomineralization proteins are disordered and contain interactive motifs
Authors: Evans John Spencer 
Published: October 2012

Abstract
Motivation: The formation of aragonite mineral in the mollusk shell or pearl nacre requires the participation of a diverse set of proteins that form the mineralized extracellular matrix. Although self-assembly processes have been identified for several nacre proteins, these proteins do not contain known globular protein–protein binding domains. Thus, we hypothesize that other sequence features are responsible for nacre matrix protein–protein assembly processes and ultimately aragonite biosynthesis.
Results: Of 39 mollusk aragonite-associated protein sequences, 100% contain at least one region of intrinsic disorder or unfolding, with the highest percentages found in framework and pearl-associated proteins relative to the intracrystalline proteins. In some instances, these intrinsically disordered regions were identified as bind/fold sequences, and a limited number correlate with known biomineral-relevant sequences. Interestingly, 95% of the aragonite-associated protein sequences were found to contain at least one occurrence of amyloid-like or cross-β strand aggregation-prone supersecondary motifs, and this correlates with known aggregation and aragonite formation functions in three experimentally tested protein sequences. Collectively, our findings indicate that aragonite-associated proteins have evolved signature sequence traits of intrinsic disorder and aggregation-prone regions that are important for their role(s) in matrix assembly and mineralization.
Contact: jse1@nyu.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Tools for mapping high-throughput sequencing data
Authors: Fonseca Nuno A. , Rung Johan , Brazma Alvis , Marioni John C. 
Published: October 2012

Abstract
Motivation: A ubiquitous and fundamental step in high-throughput sequencing analysis is the alignment (mapping) of the generated reads to a reference sequence. To accomplish this task, numerous software tools have been proposed. Determining the mappers that are most suitable for a specific application is not trivial.
Results: This survey focuses on classifying mappers through a wide number of characteristics. The goal is to allow practitioners to compare the mappers more easily and find those that are most suitable for their specific problem.
Availability: A regularly updated compendium of mappers can be found at http://wwwdev.ebi.ac.uk/fg/hts_mappers/.
Contact: nf@ebi.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Olorin: combining gene flow with exome sequencing in large family studies of complex disease
Authors: Morris James A. , Barrett Jeffrey C. 
Published: October 2012

Abstract
Motivation: The existence of families with many individuals affected by the same complex disease has long suggested the possibility of rare alleles of high penetrance. In contrast to Mendelian diseases, however, linkage studies have identified very few reproducibly linked loci in diseases such as diabetes and autism. Genome-wide association studies have had greater success with such diseases, but these results explain neither the extreme disease load nor the within-family linkage peaks, of some large pedigrees. Combining linkage information with exome or genome sequencing from large complex disease pedigrees might finally identify family-specific, high-penetrance mutations.
Results: Olorin is a tool, which integrates gene flow within families with next generation sequencing data to enable the analysis of complex disease pedigrees. Users can interactively filter and prioritize variants based on haplotype sharing across selected individuals and other measures of importance, including predicted functional consequence and population frequency.
Availability: http://www.sanger.ac.uk/resources/software/olorin
Contact: olorin@sanger.ac.uk
Association between diabetes mellitus and post‐discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial
Authors: Sarma Satyam , Mentz Robert J. , Kwasny Mary J. , Fought Angela J. , Huffman Mark , Subacius Haris , Nodari Savina , Konstam Marvin , Swedberg Karl , Maggioni Aldo P. , Zannad Faiez , Bonow Robert O. , Gheorghiade Mihai ,   on behalf of the EVEREST investigators
Published: October 2012

AimsWe evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post‐discharge outcomes of this patient population.Methods and resultsPost‐hoc analysis was performed on the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) study, a randomized trial of patients hospitalized with HF (n = 4133) with median follow‐up of 9.9 months. DM status was determined from intake questionnaires and cross‐verified by medication history. Univariate relationships were examined using χ test, t‐test, and Wilcoxon tests. The two primary outcomes of (i) all‐cause mortality (ACM) and (ii) cardiovascular mortality or HF hospitalization (CVM + HFH) were assessed for those with and without DM and by diabetic treatment strategy using log rank tests and multivariable Cox regression models. DM was present in 40% of participants. Patients with DM were more likely to have hypertension, coronary artery disease, and chronic kidney disease. Diabetes was associated with ACM and CVM + HFH (both P < 0.001). Following multivariate risk adjustment, DM was associated with ACM, but this estimate was imprecise [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.00–1.34] and remained associated with CVM or HFH (HR 1.17; 95% CI 1.04–1.31). Diabetic control strategy did not independently affect outcomes.ConclusionDiabetes is common in patients hospitalized for heart failure with a reduced EF. These patients have a higher post‐discharge CVM and higher HF hospitalizations compared with patients with no diabetes. Different diabetic treatment regimens did not appear to influence post‐discharge outcomes.
Severe adhesive arachnoiditis resulting in progressive paraplegia following obstetric spinal anaesthesia: a case report and review
Authors: Killeen T. , Kamat A. , Walsh D. , Parker A. , Aliashkevich A. 
Published: October 2012

SummaryA 27‐year‐old woman developed severe adhesive arachnoiditis after an obstetric spinal anaesthetic with bupivacaine and fentanyl, complicated by back pain and headache. No other precipitating cause could be identified. She presented one week postpartum with communicating hydrocephalus and syringomyelia and underwent ventriculoperitoneal shunting and foramen magnum decompression. Two months later, she developed rapid, progressive paraplegia and sphincter dysfunction. Attempted treatments included exploratory laminectomy, external drainage of the syrinx and intravenous steroids, but these were unsuccessful and the patient remains significantly disabled 21 months later. We discuss the pathophysiology of adhesive arachnoiditis following central neuraxial anaesthesia and possible causative factors, including contamination of the injectate, intrathecal blood and local anaesthetic neurotoxicity, with reference to other published cases. In the absence of more conclusive data, practitioners of central neuraxial anaesthesia can only continue to ensure meticulous, aseptic, atraumatic technique and avoid all potential sources of contamination. It seems appropriate to discuss with patients the possibility of delayed, permanent neurological deficit while taking informed consent.
Neurodevelopment in children with and without congenital heart block born to anti‐Ro/SSA‐positive mothers
Authors: Skog Amanda , Tingström Joanna , Salomonsson Stina , Sonesson Sven‐Erik , Wahren‐Herlenius Marie 
Published: October 2012

AbstractObjectiveTo define factors influencing neurodevelopment in children with and without complete congenital heart block (CHB) born to mothers with Ro/SSA autoantibodies.Patients and methodsMedical records of a population‐based cohort of siblings with (n = 60) and without (n = 54) CHB born 1974–2009 to anti‐Ro/SSA‐positive mothers were retrieved from children primary healthcare centres and school health services and used to extract data on neurodevelopment.ResultsImpaired neurodevelopment was reported in 16% of the children (18/114) during the follow‐up time of 13.0 (8.2–17.5) years, median (quartiles). Reported problems included speech (9%), motor (8%) and learning (8%) impairment, attention deficit (5%) and behavioural impairment (4%). Impairment in motor skill development was more common in boys (p < 0.001) if the child was born preterm (p < 0.001). Learning impairment was significantly influenced by maternal SLE (p < 0.005), while attention deficits was influenced by both maternal SLE (p < 0.05) and CHB in the child (p < 0.05).ConclusionsOur data indicate that in addition to well‐established factors such as male sex and being born preterm, both maternal SLE and CHB may influence neurodevelopment. Follow‐up of neurodevelopment should therefore be considered for children with CHB, especially if the mother is diagnosed with SLE.
Physician specialty is associated with adherence to treatment guidelines for acute otitis media in children
Authors: Grossman Zachi , Silverman Barbara G , Miron Dan 
Published: October 2012

AbstractAimTo identify physician and visit characteristics affecting adherence to guidelines recommending delayed antibiotic therapy for acute otitis media (AOM).MethodsWe used physician visit data from an Israeli health maintenance organization to identify children ages 0–15 diagnosed with AOM. We defined early antibiotic treatment as purchase, within 3 days of diagnosis, of antibiotics prescribed by the diagnosing physician. We considered the effect of physician specialty (paediatrician, otolaryngologist, and family physician), day of the week, setting (urgent care/clinic) and clinic location (peripheral/central) on the rate of early treatment.ResultsProportion of cases receiving early treatment dropped from 2002 to 2009 in cases treated by otolaryngologists (47–36%) and paediatricians (46–42%) and increased in cases treated by family physicians (43–50%). Treatment rate was higher in cases treated on weekends than on weekdays (48% vs. 44%), in urgent care as compared to clinic settings (51% vs. 44%), and in children living in peripheral as compared to central areas (52% vs. 38%).ConclusionsSuccessful implementation of delayed treatment of otitis media guidelines requires addressing factors associated with increased early treatment rates.
Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non‐alcoholic fatty liver disease
Authors: Zarrinpar A. , Loomba R. 
Published: October 2012

SummaryBackgroundRecent research has led to an interest in the role of the gut and liver in type 2 diabetes mellitus (T2DM).AimTo review the role of the gastrointestinal system in glucose homoeostasis, with particular focus on the effects of incretin hormones, hepatic steatosis and bile acids.MethodsPubMed and Google Scholar were searched using terms such as incretin, glucose‐dependent insulinotropic polypeptide (GIP), glucagon‐like peptide‐1 (GLP‐1), dipeptidyl peptidase‐4 (DPP‐4), hepatic steatosis, bile acid and gastric bypass. Additional relevant references were identified by reviewing the reference lists of articles.ResultsPerturbations of incretin hormones and bile acid secretion contribute to the pathogenesis ofT2DM, leading to their potential as therapeutic targets. The incretin hormones (GIPandGLP‐1) are deactivated byDPP‐4.GLP‐1 agonists andDPP‐4 inhibitors improve glycaemic control in patients withT2DM. Hepatic steatosis, along with insulin resistance, may precede the development ofT2DM, and may benefit from anti‐diabetes medications. Bile acids play an important role in glucose homoeostasis, with effects mediated via the farnesoidXreceptor (FXR) and the cell surface receptorTGR5. The bile acid sequestrant colesevelam has been shown to be effective in improving glycaemic control in patients withT2DM. Altered gastrointestinal anatomy after gastric bypass surgery may also affect enterohepatic recirculation of bile acids and contribute to improved glycaemic control.ConclusionsResearch in recent years has led to new pathways and processes with a role in glucose homoeostasis, and new therapeutic targets and options for type 2 diabetes mellitus.
The relationship between sub‐clinical obsessive‐compulsive symptoms and social cognition in chronic schizophrenia
Authors: Whitton Alexis E. , Henry Julie D. 
Published: October 2012

ObjectivesComorbid obsessive‐compulsive (OC) symptoms in individuals with a primary diagnosis of schizophrenia are related to poorer cognitive performance and functional outcomes, but no study to date has assessed whether this comorbidity might also have implications for social cognition. The aim of the present study was to provide the first test of this possibility.Design and methodsIndividuals with schizophrenia (n = 34) and demographically matched non‐clinical controls (n = 44) were assessed on two of the most important aspects of social cognitive function (1) facial affect recognition and (2) theory of mind, alongside more standard measures of cognitive function.ResultsThe presence of OC symptoms was related to poorer performance on some of the cognitive measures, as well as one of the social cognitive measures (facial affect recognition). However, these relationships disappeared after controlling for scores on more general indices of schizophrenia psychopathology.ConclusionsThe presence of OC symptoms in schizophrenia is not only associated with increased cognitive impairment but also increased difficulties with at least some aspects of social cognitive function. However, these relationships appear to reflect the elevated levels of psychopathology seen in this cohort more generally, rather than being uniquely attributable to OC symptomatology.Practitioner Points

The presence of obsessive‐compulsive (OC) symptoms in chronic schizophrenia is not only associated with greater cognitive impairment but also with increased difficulties in at least some aspects of social cognitive function.
These increased difficulties appear to reflect a more severe presentation of schizophrenia overall rather than the presence of OC symptoms specifically.
A limitation of this research design was the inclusion of only chronic, medicated participants with schizophrenia. Individuals at early or more acute phases of schizophrenia may present with a different profile of impairment.
Further research is needed to assess whether or not different results emerge where there is a comorbid diagnosis of obsessive‐compulsive disorder (as opposed to sub‐clinical OC symptoms).
The Limits on Pay as a Strategic Tool: Obstacles to Alignment in Non‐Union Environments
Authors: Trevor Jonathan , Brown William 
Published: October 2012

AbstractStrategic human resource management literature emphasizes the potential of pay to secure strategically desirable employee outcomes for the employer. Strategic pay, in contrast with pluralist models of pay determination, assumes an absence of collective bargaining constraints. This article analyses the process of determination of non‐unionized managerial, professional and technical pay in seven leading consumer goods firms that claim to use pay as a strategic tool. It demonstrates that implemented pay practice is often remote from what is aspired to strategically. Despite the absence of collective bargaining constraints, there remain unavoidable obstacles to the ability of management to implement pay systems aligned to strategic goals. These constraints impose fundamental limitations on the use of pay as a strategic tool.
A study of subunit selectivity, mechanism and site of action of the delta selective compound 2 (DS2) at human recombinant and rodent native GABAA receptors
Authors: Jensen ML , Wafford KA , Brown AR , Belelli D , Lambert JJ , Mirza NR 
Published: October 2012

Background and PurposeMost GABAA receptor subtypes comprise 2α, 2β and 1γ subunit, although for some isoforms, a δ replaces a γ‐subunit. Extrasynaptic δ‐GABAA receptors are important therapeutic targets, but there are few suitable pharmacological tools. We profiled DS2, the purported positive allosteric modulator (PAM) of δ‐GABAA receptors to better understand subtype selectivity, mechanism/site of action and activity at native δ‐GABAA receptors.Experimental ApproachSubunit specificity of DS2 was determined using electrophysiological recordings of Xenopus laevis oocytes expressing human recombinant GABAA receptor isoforms. Effects of DS2 on GABA concentration–response curves were assessed to define mechanisms of action. Radioligand binding and electrophysiology utilising mutant receptors and pharmacology were used to define site of action. Using brain‐slice electrophysiology, we assessed the influence of DS2 on thalamic inhibition in wild‐type and δ0/0 mice.Key ResultsActions of DS2 were primarily determined by the δ‐subunit but were additionally influenced by the α, but not the β, subunit (α4/6βxδ > α1βxδ >> γ2‐GABAA receptors > α4β3). For δ‐GABAA receptors, DS2 enhanced maximum responses to GABA, with minimal influence on GABA potency. (iii) DS2 did not act via the orthosteric, or known modulatory sites on GABAA receptors. (iv) DS2 enhanced tonic currents of thalamocortical neurones from wild‐type but not δ0/0 mice.Conclusions and ImplicationsDS2 is the first PAM selective for α4/6βxδ receptors, providing a novel tool to investigate extrasynaptic δ‐GABAA receptors. The effects of DS2 are mediated by an unknown site leading to GABAA receptor isoform selectivity.
Negative automatic thoughts and emotional and behavioural problems in adolescence
Authors: Flouri Eirini , Panourgia Constantina 
Published: October 2012

BackgroundThe aim of this study was to test whether maladaptive cognitions or difficulties in emotion regulation mediate the association between change in number of adverse life events (i.e. change in life stress) and emotional and behavioural problems in adolescence.MethodOur sample consisted of 557 young people, aged 10–19 years from a state secondary school in London. We fitted a multiple mediator model to contrast five mediators: three maladaptive cognitions (negative cognitive errors, negative automatic thoughts, and dysfunctional attitudes) and the two emotion regulatory processes of cognitive reappraisal and expressive suppression. We adjusted for gender, age, ethnicity, special educational needs and family poverty.ResultsTaken as a set, our mediators explained the effect of change in life stress on adolescent emotional and behavioural problems. However, cognitive reappraisal, expressive suppression, dysfunctional attitudes and negative cognitive errors did not contribute to the indirect effect above and beyond negative automatic thoughts.ConclusionsOnly negative automatic thoughts mediated the association between change in life stress and emotional and behavioural problems. This suggests the possibility that negative automatic thoughts is the pathway through which an increase in life stress may lead to emotional and behavioural problems in adolescents.
Prevalence and long‐term follow‐up outcomes of testicular adrenal rest tumours in children and adolescent males with congenital adrenal hyperplasia
Authors: Aycan Zehra , Bas Veysel N. , Cetinkaya Semra , Yilmaz Agladioglu Sebahat , Tiryaki Tuğrul 
Published: October 2012

AbstractObjectiveThere are a few studies regarding the prevalence of testicular adrenal rest tumours (TARTs) in boys and adolescent males with congenital adrenal hyperplasia (CAH), and there is little information regarding the treatment outcomes in patients with TARTs. The aim of this study was to determine the long‐term treatment outcomes in boys and adolescent males with CAH.Patients and methodsSixty boys and adolescent males with CAH, who were between 2 and 18 years of age, were included in the study. Fifty‐five patients had 21‐hydroxylase deficiency (21‐OHD), and five patients had 11‐β hydroxylase deficiency (11β‐OHD). All patients were screened for TARTs by scrotal ultrasonography (US) performed by an experienced radiologist.ResultsTART prevalence was 18·3% in 2–18 years’ of age; eight patients had 21‐OHD, and three had 11β‐OHD. The youngest patient with TART was 4 years old, whereas eight patients with RTs were at puberty. Only two patients had tight metabolic control: eight patients had stage 2, one had stage 4, and two had stage five rest tumours. In four patients with stage 2 TARTs, tumours disappeared after high‐dose steroid treatment and did not recur. Shrinkage of tumour was observed in two patients. Testis‐sparing surgery was performed in one patient with stage five tumour. Gonadal functions were normal in patients with partially regressed tumours. Two patients became fathers of healthy male off‐springs.ConclusionsDetection and treatment for TARTs in children with CAH at younger ages, earlier stages, may prevent infertility in adulthood. Therefore, we recommend that scrotal US screening should be performed in every 1–2 years starting from early childhood.
Emergency transanal haemorrhoidal Doppler guided dearterialization for acute and persistent haemorrhoidal bleeding
Authors: Cavazzoni E. , Bugiantella W. , Graziosi L. , Silvia Franceschini M. , Cantarella F. , Rosati E. , Donini A. 
Published: October 2012

AbstractAimThe effectiveness of Doppler guided transanal haemorrhoidal dearterialization (THD) for arresting persistent haemorrhoidal bleeding in patients admitted as an emergency was studied.MethodEleven patients with severe anal bleeding underwent emergency THD as definitive treatment for haemorrhoids. In the majority of patients antiplatelet or anticoagulant therapy was ongoing and severe anaemia was present in six patients.ResultsThe mean operative time was 39.7 min. Six to nine feeding arteries were ligated. Intra‐operative blood loss was nil. Bleeding was well controlled in all patients. No blood transfusion was required. Mean pain score per verbal numeric scale was 3.6 and 1.4 on day 1 and day 3 respectively. The mean time to resumption of normal activities was 8 days. No major complications were experienced. Six months follow‐up demonstrated good control of haemorrhoidal disease.ConclusionTHD is effective in controlling acute haemorrhoidal bleeding with a low incidence of postoperative complications.