bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype
Authors: Zhou Yuan , Claflin Suzi B , Stankovich Jim , van der Mei Ingrid , Simpson Steve , Roxburgh Richard H , Kalincik Tomas , Blizzard Leigh , Lugaresi Alessandra , Alroughani Raed , Sajedi Seyed Aidin , Butzkueven Helmut , Pucci Eugenio , Spitaleri Daniele LA , Granella Franco , Cristiano Edgardo , Yamout Bassem , Hughes Stella , Gouider Riadh , Sánchez Menoyo José Luis , Olascoaga Javier , McGuigan Chris , Shaw Cameron , Kermode Allan G , Kasa Krisztian , Al-Harbi Talal , Altintas Ayse , Laureys Guy , Fragoso Yara , Hardy Todd A , Csepany Tunde , Sirbu Carmen-Adella , Decoo Danny , Sas Attila , Alvarez-Cermeño Jose C , Kotkata Karim , Millán-Pascual Jorge , Taylor Bruce V 
Published: October 2019

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. Objective: We evaluated sex-specific and onset phenotype–specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype–specific MSSS matrices. We compared matrices using permutation analysis. Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.
Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis
Authors: Bsteh Gabriel , Berek Klaus , Hegen Harald , Teuchner Barbara , Buchmann Arabella , Voortman Margarete M , Auer Michael , Wurth Sebastian , Zinganell Anne , Di Pauli Franziska , Deisenhammer Florian , Khalil Michael , Berger Thomas 
Published: October 2019

Background: Serum neurofilament light chain (sNfL) levels and peripapillary retinal nerve fiber layer (pRNFL) are both emerging biomarkers of neuro-axonal damage in multiple sclerosis (MS). However, data on the relation between sNfL and pRNFL are scarce. Objective: We aimed to determine the relation of sNfL levels with pRNFL thinning in a large cohort of relapsing–remitting (RR) MS patients. Methods: We identified 80 patients from a prospective, 3-year observational study on retinal changes in RRMS with annual blood samples available. sNfL levels were measured using single-molecule array (SimoaTM) assay. Annualized loss of pRNFL (aLpRNFL) was determined by individual linear regression models. Correlations between single and repeated sNfL levels and aLpRNFL were analyzed using multivariate linear regression and mixed-effect models. Results: After correction for sex, age, and baseline sNfL, an sNfL increase of 10 pg/mL was associated with an aLpRNFL of −0.7 µm (95% confidence interval (CI): (−1.3, −0.2), p < 0.001). Patients with ⩾2 sNfL measurements >75th percentile displayed higher aLpRNFL (2.2 µm, standard deviation (SD) 0.6) compared to patients with no sNfL measure >75th percentile (0.4 µm, SD 0.2, p < 0.001). Between 15% and 20% of the aLpRNFL variance could be predicted from sNfL levels. Conclusion: sNfL levels contribute to the prediction of retinal thinning in patients with RRMS, strengthening its value as a biomarker of neuro-axonal damage.
Objective Comparison Between Spreader Grafts and Flaps for Mid-Nasal Vault Reconstruction: A Randomized Controlled Trial
Authors: Zeid Nabil Galal , Mohamed Ahmed Shawky , ElSayed ElFouly Mahmoud , Azooz Khaled Omar , Aleryan Mohamed Muddather , Abd Elmottaleb Sabaa Mohamed 
Published: October 2019

Objective: The goal of rhinoplasty is not exclusively aesthetic and the nasal function should always be considered. Several rhinoplasty techniques can participate in nasal valve dysfunction (eg, dorsal hump reductions). Therefore, mid-nasal vault reconstruction by spreader grafts or flaps is mandatory in these cases. To date, there is a literature gap in comparing both techniques objectively. This study shows an objective comparison between spreader grafts and flaps for mid-nasal vault reconstruction. Material and Methods: This study was a double-blind randomized controlled trial including 40 patients who were randomly divided into 2 groups. Group 1 (20 patients) underwent spreader grafts insertion, whereas group 2 (20 patients) underwent spreader flap placement technique. Pre-operative active anterior rhinomanometry measurements were compared to 6-month post-operative measurements. Data were summarized as mean (standard deviation) for the quantitative variables. Comparisons between the 2 groups were done using unpaired t test. Results: In both groups, a significant decrease in nasal resistance was noted in both the right and left sides 6 months post-operatively ( P < .001). However, the comparison between the 2 both groups showed no statistical significance. Conclusion: Both spreader grafts and flaps, which are used for the mid-nasal vault reconstruction, have comparable and effective results in reducing the nasal resistance as evidenced by active anterior rhinomanometry measurements.
High-Risk Plastic Surgery: An Analysis of 108,303 Cases From the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)
Authors: Wan Melissa , Zhang Jacques X. , Ding Yichuan , Jin Yiwen , Bedford Julie , Nagarajan Mahesh , Bucevska Marija , Courtemanche Douglas J. , Arneja Jugpal S. 
Published: October 2019

Background: There is a lack of large-scale data that examine complications in plastic surgery. A description of baseline rates and patient outcomes allows better understanding of ways to improve patient care and cost-savings for health systems. Herein, we determine the most frequent complications in plastic surgery, identify procedures with high complication rates, and examine predictive risk factors. Methods: A retrospective analysis of the 2012 to 2016 American College of Surgeons National Surgical Quality Improvement Program plastic surgery data set was conducted. Complication rates were calculated for the entire cohort and each procedure therein. Microsurgical procedures were analyzed as a subgroup, where multivariate logistic regression models determined the risk factors for surgical site infection (SSI) and related reoperation. Results: We identified 108 303 patients undergoing a plastic surgery procedure of which 6 264 (5.78%) experienced ≥1 complication. The outcome with the highest incidence was related reoperation (3.31%), followed by SSI (3.11%). Microsurgical cases comprised 6 148 (5.68%) of all cases, and 1211 (19.33%) experienced ≥1 complication. Similar to the entire cohort, the related reoperation (12.83%) and SSI (5.66%) were common complications. Increased operative time was a common independent risk factor predictive of a related reoperation or development of an SSI ( P < 001). Of all microsurgeries, 23.3% had an operative time larger than 10 hours which lead to faster increase in reoperation likelihood. Conclusions: The complication rate in plastic surgery remains relatively low but is significantly increased for microsurgery. Increased operative time is a common risk factor. Two-team approaches and staged operations could be explored, as a large portion of microsurgeries are vulnerable to increased complications.
Changes in Aqueous and Vitreous Inflammatory Cytokine Levels in Retinal Vein Occlusion: A Systematic Review and Meta-analysis
Authors: Minaker Samuel A. , Mason Ryan H. , Bamakrid Motaz , Lee Yung , Muni Rajeev H. 
Published: October 2019

Purpose: Evidence suggests that inflammatory cytokines not only play a role in the pathogenesis of retinal vein occlusion (RVO) but also may be useful as biomarkers to predict disease severity and response to treatment. We aimed to quantitatively summarize data on inflammatory cytokines associated with RVO. Methods: A systematic search of peer-reviewed English-language articles was performed without year limitation up to August 19, 2019. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with RVO. Data were extracted from 116 studies that encompassed 3242 study eyes with RVO and 1402 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with RVO vs controls. Results: Among the 4644 eyes in 116 studies, aqueous and vitreous concentrations (SMD, 95% CI, and P value) of interleukin (IL)-6 (aqueous: 1.23, 0.65 to 1.81, P < .001 vitreous: 0.70, 0.49 to 0.90, P < .001), IL-8 (aqueous: 1.11, 0.73 to 1.49, P < .001; vitreous: 1.19, 0.73 to 1.65, P < .001), monocyte chemoattractant protein 1(aqueous: 1.22, 0.72 to 1.72, P < .001; vitreous 1.42, 0.92 to 1.91, P < .001), vascular endothelial growth factor (VEGF) (aqueous: 1.52, 1.09 to 1.94, P < .001; vitreous: 0.99, 0.78 to 1.21, P < .001) were significantly higher in patients with RVO than in healthy controls. Only aqueous concentrations of IL-10 (0.81, 0.45 to 1.18, P < .001), angiopoietin 4 (1.96, 0.92 to 3.00, P < .001), and platelet-derived growth factor (PDGF)-AA (0.82, 0.35 to 1.30, P < .001) were significantly higher in patients with RVO than in healthy controls. Only the vitreous concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (1.23, 0.83 to 1.63, P < .001) was significantly higher in patients with RVO. No differences, failed sensitivity analyses, or insufficient data were found between patients with RVO and healthy controls for the concentrations of the remaining cytokines. Conclusions: Several cytokines in addition to VEGF have the potential to be useful biomarkers and therapeutic targets in RVO.
Specific stimulation of T lymphocytes with erythropoietin for adoptive immunotherapy
Authors: Vinanica Natasha , Yong Arthur , Wong Desmond , Png Yi Tian , Seow See Voon , Imamura Masaru , Campana Dario 
Published: October 2019

Abstract
In adoptive T-cell immunotherapy of cancer, expansion and persistence of effector cells is a key determinant of response. We tested whether T lymphocytes could be rendered sensitive to erythropoietin (Epo) through ectopic expression of its wild-type receptor or a truncated form (EpoRm), which augments Epo signaling in erythrocyte progenitors. Both receptors could be expressed in human T lymphocytes; Epo ligation induced STAT5 phosphorylation, which was abrogated by nontoxic concentrations of the JAK1/2 inhibitor ruxolitinib. EpoRm had higher expression and triggered more potent stimulation than its wild-type counterpart, including superior T-cell survival and proliferation. Using a bicistronic vector, we expressed EpoRm together with an anti–CD19-41BB-CD3ζ chimeric antigen receptor (CAR), while maintaining the functions of each receptor. In the presence of Epo, EpoRm-CAR T cells had greater ex vivo expansion than CAR T cells and killed CD19+ leukemic cells more effectively in long-term cultures. In immunodeficient mice, physiologic levels of murine Epo were sufficient to preferentially expand EpoRm-CAR T cells, yielding a significantly higher antileukemic activity. Thus, outfitting adoptive T cells with EpoRm should yield greater effector-to-target ratios with a smaller number of infused cells; Epo or ruxolitinib administration could be used to adjust their levels postinfusion, maximizing antitumor activity and minimizing toxicity.
Excess mucus viscosity and airway dehydration impact COPD airway clearance
Authors: Lin Vivian Y. , Kaza Niroop , Birket Susan E. , Kim Harrison , Edwards Lloyd J. , LaFontaine Jennifer , Liu Linbo , Mazur Marina , Byzek Stephen A. , Hanes Justin , Tearney Guillermo J. , Raju S. Vamsee , Rowe Steven M. 
Published: October 2019

The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT).Adult ferrets were exposed to cigarette smoke for 6 months, within vivomucociliary clearance measured by technetium-labelled DTPA retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells andex vivoferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified key determinants of MCT.Compared to air controls, cigarette smoke-exposed ferrets exhibited mucus hypersecretion, delayed mucociliary clearance (−89.0%, p<0.01) and impaired tracheal MCT (−29.4%, p<0.05). Cholinergic stimulus augmented airway surface liquid (ASL) depth (5.8±0.3 to 7.3±0.6 µm, p<0.0001) and restored MCT (6.8±0.8 to 12.9±1.2 mm·min−1, p<0.0001). Mixed model analysis controlling for covariates indicated smoking exposure, mucus hydration (ASL) and ciliary beat frequency were important predictors of MCT. Ferret mucus was hyperviscous following smoke exposurein vivoorin vitro, and contributed to diminished MCT. Primary cells from smokers with and without COPD recapitulated these findings, which persisted despite the absence of continued smoke exposure.Cigarette smoke impairs MCT by inducing airway dehydration and increased mucus viscosity, and can be partially abrogated by cholinergic secretion of fluid secretion. These data elucidate the detrimental effects of cigarette smoke exposure on mucus clearance and suggest additional avenues for therapeutic intervention.
Circulating plasma exosomes in obstructive sleep apnoea and reverse dipping blood pressure
Authors: Khalyfa Abdelnaby , Gozal David , Chan Wen-Ching , Andrade Jorge , Prasad Bharati 
Published: October 2019

BackgroundObstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA.Methods46 patients (15 RDBPversus31 NDBP) matched for OSA severity (respiratory event index 32.6±22.5versus32.2±18.1 events·h−1; p=0.9), age (54.8±12.9versus49±9.9 years; p=0.09) and body mass index (36.2±6.6versus34.4±6.8 kg·m−2; p=0.4) were included. Plasma exosomes were characterised by flow cytometry and functionalin vitroreporter assays were conducted on cultured endothelial cells. Exosome miRNA cargo was profiled with microarrays followed by bioinformatics analyses.ResultsExosomes from RDBP patients increased the permeability of endothelial cell tight junctions and adhesion molecule expression. Principal component analyses of miRNA array data showed strict separation and identification of the two groups. A restricted and validated signature of exosomal miRNAs was identified in the RDBPversusNDBP group. Their predicted target genes involved phosphatidylinositol 3-kinase-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003) and hypoxia inducible factor-1 signalling (p=0.04), inflammatory mediator regulation of transient receptor potential channels (p=0.01), and several cancer-related pathways.ConclusionsPatients with RDBP have altered miRNA cargoes in circulating exosomes that invokein vitroendothelial dysfunction. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of CVD risk in OSA.
Association mapping of a locus that confers southern stem canker resistance in soybean and SNP marker development
Authors: Maldonado dos Santos João Vitor , Ferreira Everton Geraldo Capote , Passianotto André Luiz de Lima , Brumer Bruna Bley , Santos Adriana Brombini Dos , Soares Rafael Moreira , Torkamaneh Davoud , Arias Carlos Alberto Arrabal , Belzile François , Abdelnoor Ricardo Vilela , Marcelino-Guimarães Francismar Corrêa 
Published: October 2019

Abstract

Background
Southern stem canker (SSC), caused by Diaporthe aspalathi (E. Jansen, Castl. & Crous), is an important soybean disease that has been responsible for severe losses in the past. The main strategy for controlling this fungus involves the introgression of resistance genes. Thus far, five main loci have been associated with resistance to SSC. However, there is a lack of information about useful allelic variation at these loci. In this work, a genome-wide association study (GWAS) was performed to identify allelic variation associated with resistance against Diaporthe aspalathi and to provide molecular markers that will be useful in breeding programs.

Results
We characterized the response to SSC infection in a panel of 295 accessions from different regions of the world, including important Brazilian elite cultivars. Using a GBS approach, the panel was genotyped, and we identified marker loci associated with Diaporthe aspalathi resistance through GWAS. We identified 19 SNPs associated with southern stem canker resistance, all on chromosome 14. The peak SNP showed an extremely high degree of association (p-value = 6.35E-27) and explained a large amount of the observed phenotypic variance (R2 = 70%). This strongly suggests that a single major gene is responsible for resistance to D. aspalathi in most of the lines constituting this panel. In resequenced soybean materials, we identified other SNPs in the region identified through GWAS in the same LD block that clearly differentiate resistant and susceptible accessions. The peak SNP was selected and used to develop a cost-effective molecular marker assay, which was validated in a subset of the initial panel. In an accuracy test, this SNP assay demonstrated 98% selection efficiency.

Conclusions
Our results suggest relevance of this locus to SSC resistance in soybean cultivars and accessions from different countries, and the SNP marker assay developed in this study can be directly applied in MAS studies in breeding programs to select materials that are resistant against this pathogen and support its introgression.
A novel approach with holmium laser ablation for endoscopic management of intrahepatic biliary stricture
Authors: Lou Jianying , Hu Qida , Ma Tao , Chen Wei , Wang Ji , Pankaj Prasoon 
Published: November 2019

Abstract

Background
Hepatolithiasis, featuring high incidence, severe symptoms, and common recurrence, poses a heavy disease burden. Endoscopic management provides an opportunity to cure hepatolithiasis, but fails to properly resolve biliary stricture without additional interventional techniques. An innovative approach towards endoscopic management of biliary stricture is required.

Methods
Holmium laser ablation was applied to biliary strictures via endoscopic access. Patients’ demographic, operative, and follow-up data after receiving holmium laser ablation were retrospectively collected for analysis.

Results
A total of 15 patients (4 males and 11 females) underwent stricture ablation by holmium laser via cholangioscopy. All the patients successfully received holmium laser ablation, indicating a technical success rate of 100%. No postoperative mortality or no major perioperative complication was observed. During the follow-up period, the recurrence-free rate was 73% at 2 years and 67% at 5 years.

Conclusions
We successfully developed a novel technique of biliary stricture removal by cholangioscopic holmium laser ablation with satisfying clinical outcomes.
CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
Authors: Papizh Svetlana , Serzhanova Victoria , Filatova Alexandra , Skoblov Mikhail , Tabakov Vyacheslav , van den Heuvel Lambert , Levtchenko Elena , Prikhodina Larisa 
Published: October 2019

AbstractBackgroundCystinosis is an autosomal recessive lysosomal storage disorder characterized by accumulation of cystine in lysosomes throughout the body. Cystinosis is caused by mutations in theCTNSgene that encodes the lysosomal cystine carrier protein cystinosin.CTNSmutations result in either complete absence or reduced cystine transporting function of the protein. The diagnosis of nephropathic cystinosis is generally based on measuring leukocyte cystine level, demonstration of corneal cystine crystals by the slit lamp examination and confirmed by genetic analysis of theCTNSgene.Case presentationA boy born to consanguineous Caucasian parents had the characteristic clinical features of the infantile nephropathic cystinosis including renal Fanconi syndrome (polydipsia/polyuria, metabolic acidosis, hypokalemia, hypophosphatemia, low molecular weight proteinuria, glycosuria, cystine crystals in the cornea) and elevated WBC cystine levels. Initially we performed RFLP analysis of the common in the Northern European population 57-kb deletion of proband’s DNA, then a direct Sanger sequencing which revealed no mutations in the coding part of theCTNSgene. To confirm the diagnosis we performed RT-PCR analysis of total RNA obtained from patient-derived fibroblasts in combination with cDNA sequencing. This revealed the skipping of exon 4 and exon 5 in theCTNSin our patient. Therefore, we detected a novel 9-kb homozygous deletion in theCTNSgene at genomic DNA level, spanning region from intron 3 to intron 5. In order to identify the inheritance pattern of the deletion we analyzed DNA of proband’s mother and father. Both parents were found to be heterozygous carriers of theCTNSmutation.ConclusionsAnalysis ofCTNSgene transcript allowed to identify a large homozygous deletion in the patient with infantile nephropathic cystinosis. Mutational detection at RNA level may be an efficient tool to establish the genetic defect in some cystinosis patients.