bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newborn bloodspot results: predictive value of screen positive test for thalassaemia major
Authors: Streetly Allison , Latinovic Radoslav , Henthorn Joan , Daniel Yvonne , Dormandy Elizabeth , Darbyshire Phil , Mantio Debbie , Fraser Laura , Farrar Lisa , Will Andrew , Tetlow Lesley 
Published: November 2013

Aim There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. Methods Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). Results Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. Conclusion A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.
Genetic burden of common variants in progressive and bout-onset multiple sclerosis
Authors: Sorosina Melissa , Brambilla Paola , Clarelli Ferdinando , Barizzone Nadia , Lupoli Sara , Guaschino Clara , Osiceanu Ana Maria , Moiola Lucia , Ghezzi Angelo , Coniglio Gabriella , Patti Francesco , Mancardi Gianluigi , Manunta Paolo , Glorioso Nicola , Guerini Franca R , Bergamaschi Roberto , Perla Franco ,   PROGRESSO,   PROGEMUS, Martinelli Vittorio , Cusi Daniele , Leone Maurizio , Comi Giancarlo , D’Alfonso Sandra , Martinelli-Boneschi Filippo , Esposito F. , Liberatore G. , Rodegher M. , Rossi P. , Radaelli M. , Moiola L. , Colombo B. , Ghezzi A. , Annovazzi P. , Capra R. , Coniglio G. , Amato M. P. , Nacmias B. , D’Ambrosio A. , Tedeschi G. , Cavalla P. , D’Amico E. , Patti F. , Galimberti D. , Scarpini E. , Atzori M. , Gallo P. , Bucello S. , Grimaldi L. , Capello E. , Mancardi G. , Naldi P. , Bergamaschi R. , Galimberti D. , Scarpini E. , Di Sapio A. , Caputo D. , Rosso G. , Cordera S. , Cavalla P. , Cavallo R. , Benedetti D. , Salvetti M. 
Published: November 2013

Background: The contribution of genetic variants underlying the susceptibility to different clinical courses of multiple sclerosis (MS) is still unclear. Objective: The aim of the study is to evaluate and compare the proportion of liability explained by common SNPs and the genetic burden of MS-associated SNPs in progressive onset (PrMS) and bout-onset (BOMS) cases. Methods: We estimated the proportion of variance in disease liability explained by 296,391 autosomal SNPs in cohorts of Italian PrMS and BOMS patients using the genome-wide complex trait analysis (GCTA) tool, and we calculated a weighted genetic risk score (wGRS) based on the known MS-associated loci. Results: Our results identified that common SNPs explain a greater proportion of phenotypic variance in BOMS (36.5%±10.1%) than PrMS (20.8%±6.0%) cases, and a trend of decrease was observed when testing primary progressive (PPMS) without brain MRI inflammatory activity ( p = 7.9 × 10−3). Similarly, the wGRS and the variance explained by MS-associated SNPs were higher in BOMS than PPMS in males (wGRS: 6.63 vs 6.51, p = 0.04; explained variance: 4.8%±1.5% vs 1.7%±0.6%; p = 0.05). Conclusions: Our results suggest that the liability of disease is better captured by common genetic variants in BOMS than PrMS cases. The absence of inflammatory activity and male gender further raise the difference between clinical courses.
Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis
Authors: Teter Barbara , Agashivala Neetu , Kavak Katelyn , Chouhfeh Lynn , Hashmonay Ron , Weinstock-Guttman Bianca 
Published: November 2013

Background: Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. Objective: The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. Methods: This retrospective study analyzed patients with relapsing–remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Results: Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset ( p = 0.012), MS diagnosis ( p = 0.004), DMT initiation ( p < 0.001), and first MS event ( p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1–12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1–7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1–5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2–4.1; p = 0.009). Conclusions: Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation.
Cerebrospinal Fluid Apolipoprotein E Concentration and Severity of Cognitive Impairment in Patients With Newly Diagnosed Alzheimer’s Disease
Authors: Schmidt Christian , Becker Harry , Zerr Inga 
Published: November 2013

Background/Objective: Apolipoprotein E (apoE) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Altered cerebrospinal fluid (CSF) and plasma levels have been previously reported in patients with AD. We hypothesized that CSF apoE levels of patients with newly diagnosed AD might be associated with their cognitive performance. Methods: Patients with AD (N = 71) enrolled into an observational study underwent neuropsychological testing (Consortium to Establish a Registry for AD [CERAD] plus) at time of diagnosis. The CSF was obtained, and apoE concentrations were determined. Generalized linear models were constructed to assess the associations of apoE and neuropsychological measures while adjusting for important potential confounders. Results: No association of CSF apoE levels and cognitive function could be demonstrated. Still, the use of neuroleptic drugs, female gender, preprogression time, and lower education were linked to worse cognitive function in some domains. Conclusion: The CSF apoE appears not to be suitable as a biochemical surrogate of cognitive function in AD under the given circumstances. By means of longitudinal analyses, potential associations with the velocity of decline will be investigated in the near future.
Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH‐impedance monitoring
Authors: Desjardin Marie , Roman Sabine , des Varannes Stanislas Bruley , Gourcerol Guillaume , Coffin Benoit , Ropert Alain , Mion François , Zerbib Frank 
Published: November 2013

BackgroundPharyngeal pH probes and pH‐impedance catheters have been developed for the diagnosis of laryngo‐pharyngeal reflux.ObjectiveTo determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events.Methods24‐h pH‐impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro‐oesophageal reflux, and swallows, according to impedance patterns.ResultsOnly 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro‐oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro‐oesophageal reflux events, respectively.ConclusionsThis study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus.
Guidelines for the diagnosis, prevention and management of chemical- and radiation-induced cystitis
Authors: Thompson A , Adamson A , Bahl A , Borwell J , Dodds D , Heath C , Huddart R , Mcmenemin R , Patel P , Peters J , Payne H 
Published: November 2013

Objective Haemorrhagic cystitis (HC) is a relatively common complication of chemotherapy and radiotherapy to the pelvic area, but can be a challenging condition to treat, particularly since there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. Materials and methods A comprehensive literature search was undertaken to evaluate the evidence for the diagnosis, prevention and management of cancer treatment-induced HC. Results Recommendations and a proposed management algorithm for the diagnosis, prevention and treatment of HC, as well as the management of intractable haematuria, have been developed based on the expert opinion of the multidisciplinary consensus panel following a comprehensive review of the available clinical data. Conclusion These guidelines are relevant and applicable to current clinical practice and will help clinicians optimally define and manage this potentially serious condition.
Cooperative transcriptional repression by BCL6 and BACH2 in germinal center B-cell differentiation
Authors: Huang Chuanxin , Geng Huimin , Boss Isaac , Wang Ling , Melnick Ari 
Published: November 2013

Key PointsBCL6 and BACH2 cooperatively regulate GC B-cell development. The cooperative action of BCL6 and BACH2 is through both transcriptional and biochemical mechanisms.
Inhibition of thrombotic properties of persistent autoimmune anti-β2GPI antibodies in the mouse model of antiphospholipid syndrome
Authors: Kolyada Alexey , Porter Andrew , Beglova Natalia 
Published: November 2013

Key PointsA1-A1 inhibits thrombotic properties of anti-β2GPI antibodies in mice. A1-A1 does not affect thrombus size in the absence of anti-β2GPI antibodies.
Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates
Authors: Dijkstra Johannes M , Grimholt Unni , Leong Jong , Koop Ben F , Hashimoto Keiichiro 
Published: November 2013

Abstract

Background
Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system.

Results
We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.

Conclusions
Teleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage.
The M3 phosphorylation motif has been functionally conserved for intracellular trafficking of long-looped PIN-FORMEDs in the Arabidopsis root hair cell
Authors: Sasayama Daisuke , Ganguly Anindya , Park Minho , Cho Hyung-Taeg 
Published: November 2013

Abstract

Background
PIN-FORMED (PIN) efflux carriers contribute to polar auxin transport and plant development by exhibiting dynamic and diverse asymmetrical localization patterns in the plasma membrane (PM). Phosphorylation of the central hydrophilic loop (HL) of PINs has been implicated in the regulation of PIN trafficking. Recently, we reported that a phosphorylatable motif (M3) in the PIN3-HL is necessary for the polarity, intracellular trafficking, and biological functions of PIN3. In this study, using the root hair system for PIN activity assay, we investigated whether this motif has been functionally conserved among long-HL PINs.

Results
Root hair-specific overexpression of wild-type PIN1, 2, or 7 greatly inhibited root hair growth by depleting auxin levels in the root hair cell, whereas overexpression of M3 phosphorylation-defective PIN mutants failed to inhibit root hair growth. Consistent with this root hair phenotype, the PM localization of M3 phosphorylation-defective PIN1 and PIN7 was partially disrupted, resulting in less auxin efflux and restoration of root hair growth. Partial formation of brefeldin A-compartments in these phosphorylation-mutant PIN lines also suggested that their PM targeting was partially disrupted. On the other hand, compared with the PIN1 and PIN7 mutant proteins, M3-phosphorylation-defective PIN2 proteins were almost undetectable. However, the mutant PIN2 protein levels were restored by wortmannin treatment almost to the wild-type PIN2 level, indicating that the M3 motif of PIN2, unlike that of other PINs, is implicated in PIN2 trafficking to the vacuolar lytic pathway.

Conclusions
These results suggest that the M3 phosphorylation motif has been functionally conserved to modulate the intracellular trafficking of long-HL PINs, but its specific function in trafficking has diverged among PIN members.
Design of the PRINCESS trial: pre-hospital resuscitation intra-nasal cooling effectiveness survival study (PRINCESS)
Authors: Nordberg Per , Taccone Fabio Silvio , Castren Maaret , Truhlár Anatolij , Desruelles Didier , Forsberg Sune , Hollenberg Jacob , Vincent Jean-Louis , Svensoon Leif 
Published: November 2013

Abstract

Background
Therapeutic hypothermia (TH, 32-34°C) has been shown to improve neurological outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA) with ventricular tachycardia or fibrillation. Earlier initiation of TH may increase the beneficial effects. Experimental studies have suggested that starting TH during cardiopulmonary resuscitation (CPR) may further enhance its neuroprotective effects. The aim of this study was to evaluate whether intra-arrest TH (IATH), initiated in the field with trans nasal evaporative cooling (TNEC), would provide outcome benefits when compared to standard of care in patients being resuscitated from OHCA.

Methods/design
We describe the methodology of a multi-centre, randomized, controlled trial comparing IATH delivered through TNEC device (Rhinochill, Benechill Inc., San Diego, CA, USA) during CPR to standard treatment, including TH initiated after hospital admission. The primary outcome is neurological intact survival defined as cerebral performance category 1–2 at 90 days among those patients who are admitted to the hospital. Secondary outcomes include survival at 90 days, proportion of patients achieving a return to spontaneous circulation (ROSC), the proportion of patients admitted alive to the hospital and the proportion of patients achieving target temperature (<34°C) within the first 4 hours since CA.

Discussion
This ongoing trial will assess the impact of IATH with TNEC, which may be able to rapidly induce brain cooling and have fewer side effects than other methods, such as cold fluid infusion. If this intervention is found to improve neurological outcome, its early use in the pre-hospital setting will be considered as an early neuro-protective strategy in OHCA.

Trial registration

NCT01400373.
Effects of a six-month intradialytic physical ACTIvity program and adequate NUTritional support on protein-energy wasting, physical functioning and quality of life in chronic hemodialysis patients: ACTINUT study protocol for a randomised controlled trial
Authors: Magnard Justine , Deschamps Thibault , Cornu Christophe , Paris Anne , Hristea Dan 
Published: November 2013

Abstract

Background
Protein-energy wasting (PEW) is common in hemodialysis patients and is a powerful predictor of morbidity and mortality. Although much progress has been made in recent years in identifying the causes and pathogenesis of PEW in hemodialysis patients, actual management by nutritional interventions is not always able to correct PEW. Some investigators suggest that physical exercise may increase the anabolic effects of nutritional interventions, and therefore may have a potential to reverse PEW. The aim of this study is to investigate the effect of intra-dialytic progressive exercise training and adequate nutritional supplementation on markers of PEW, functional capacities and quality of life of adult hemodialysis patients.

Methods and design
Fifty end-stage renal disease patients undergoing hemodialysis, who meet the diagnostic criteria for PEW, will be randomly allocated into an exercise or control group for 6 months. The exercise consists of a progressive submaximal individualized cycling exertion using an adapted cycle ergometer, during the three weekly dialysis sessions. Biological markers of nutrition (albumin, prealbumin) will be followed monthly and all patients will be assessed for body composition, walk function, muscle strength, postural stability and quality of life at baseline and during the eighth week (t+2), the sixteenth week (t+4) and the twenty-fourth week (t+6) of the 6-month adapted rehabilitation program.

Discussion
The successful completion of this current trial may give precious clues in understanding PEW and encourage nephrologists to extend prescription of exercise programs as well as therapeutic and as preventive interventions in this high-risk population.

Trial registration
The protocol for this study was registered with the France Clinical Trials Registry NCT01813851.
RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients
Authors: Huang Xin , Hao Cuifang , Shen Xiaofang , Zhang Yuhua , Liu Xiaoyan 
Published: November 2013

Abstract

Background
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. The developmental competence of oocytes and embryos in PCOS patients is reduced to a certain extent (comparing to non-PCOS patients, the high quality embryo rate was decreased by 16% from the data of our centre) during the in vitro fertilization (IVF) process. Cross-talk between the oocyte and cumulus cells is critical for oocyte maturation and embryo competence. In this study, we have evaluated the transcription of specific genes in cumulus cells harvested from pre-ovulatory follicles of PCOS patients before IVF, according to individual oocyte nuclear maturity and developmental competence. Seven genes (RUNX2, PSAT1, ADAMTS9, CXCL1, CXCL2, CXCL3, and ITGB5) were targeted from our previous cDNA microarray data which isolated genes related to oocyte nuclear maturation in PCOS patients. Two additional genes which had been found to be associated with oocyte maturation or embryo quality in non-PCOS patients (GPX3 and PTX3) were also studied.

Methods
The mRNA expression levels of cumulus cells were detected by qRT- PCR.

Results
Consistent with our previous cDNA microarray data, with the exception of GPX3 and PTX3, the selected 7 genes were related to oocyte nuclear maturation in PCOS patients. Noticeably, the expression level of RUNX2 was lower in cumulus cells derived from oocytes that could develop into blastocysts than the level of expression from oocytes that could not. The PTX3 expression level was significantly lower in cumulus cells from oocytes with two normal pronuclei than that from oocytes that formed >2 pronuclei (MPN) after fertilization. GPX3 mRNA levels were decreased in cumulus cells isolated from oocytes that developed into blastocysts with high potential development competence.

Conclusions
Several cumulus cell genes were associated with oocyte maturation, fertilization and embryo quality in PCOS patients. RUNX2 and GPX3 are candidate genetic markers in the monitoring of embryo quality for PCOS patients, whereas PTX3 mainly played a role in fertilization process. Together with morphological evaluation, cumulus cells genes may serve as biomarkers of oocyte and embryo selection during the IVF process for PCOS patients and may advance our understanding of PCOS.
Large current difference in Au-coated vertical silicon nanowire electrode array with functionalization of peptides
Authors: Kim Ilsoo , Kim So-Eun , Han Sanghun , Kim Hyungsuk , Lee Jaehyung , Jeong Du-Won , Kim Ju-Jin , Lim Yong-beom , Choi Heon-Jin 
Published: November 2013

Abstract
Au-coated vertical silicon nanowire electrode array (VSNEA) was fabricated using a combination of bottom-up and top-down approaches by chemical vapor deposition and complementary metal-oxide-semiconductor process for biomolecule sensing. To verify the feasibility for the detection of biomolecules, Au-coated VSNEA was functionalized using peptides having a fluorescent probe. Cyclic voltammograms of the peptide-functionalized Au-coated VSNEA show a steady-state electrochemical current behavior. Because of the critically small dimension and vertically aligned nature of VSNEA, the current density of Au-coated VSNEA was dramatically higher than that of Au film electrodes. Au-coated VSNEA further showed a large current difference with and without peptides that was nine times more than that of Au film electrodes. These results indicate that Au-coated VSENA is highly effective device to detect peptides compared to conventional thin-film electrodes. Au-coated VSNEA can also be used as a divergent biosensor platform in many applications.