bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Cognitive Rehabilitation Versus Usual Treatment at Home in Patients With Early Stages of Alzheimer Disease
Authors: Kurth Sophie , Wojtasik Vinciane , Lekeu Françoise , Quittre Anne , Olivier Catherine , Godichard Vinciane , Bastin Christine , Salmon Eric 
Published: May 2020

Introduction: Assessing the benefit of cognitive rehabilitation (CR) remains difficult. Method: An observational study was conducted in 33 patients with early-stage Alzheimer disease and their caregiver included in a clinical CR program at home, compared to 17 patients who received usual treatment. Evaluation of patient’s dependence and objective and subjective caregiver’s burden was performed by the caregiver with a research tool focusing on impairment in daily activities related to cognitive deficits. Results: Repeated measures analysis of variance showed a time by group interaction ( P < .05), with decreased patient’s dependence for adapted activities at 1 year in the CR group. Lawton scale for daily activities showed also a time by group interaction ( P < .05), with increased dependence at 1 year in the control group. There was a significant decrease in Mini-Mental State Examination scores in both groups at 1-year follow-up ( P < .05). Concerning caregiver’s subjective burden, there was a trend for the time by group interaction ( P = .07), and post hoc Tukey test showed that subjective burden was decreased in the CR group ( P < .05). This was confirmed by nonparametric Mann-Whitney analysis on differences between follow-up and baseline evaluation ( P < .05). Conclusion: This observational study in a clinical setting is in line with the benefit of CR reported in recent randomized controlled trials. The benefit obtained for adapted daily activities remained after 1 year, even if global cognition declined. Moreover, caregiver’s subjective burden related to all relevant daily activities evaluated within the CR program was decreased after 1 year in our clinical setting.
Mid-term results of a prospective randomised controlled trial comparing large-head metal-on-metal hip replacement to hip resurfacing using patient-reported outcome measures and objective functional task-based outcomes
Authors: Konan Sujith , Waugh Charlotte , Ohly Nick , Duncan Clive P , Masri Bassam A , Garbuz Donald S 
Published: May 2020

Background: The early outcomes of large head-metal-on-metal total hip arthroplasty (MoM THA) are compromised by adverse local tissue reaction to metal debris. This study is the mid-term follow-up of a prospective randomised control trial (pRCT) comparing MoM THA to MoM HR. We sought to answer whether there was a difference between MoM THA and MoM HR at mid-term follow-up in the implant survival; patient-reported outcome measures (PROMs); and when performing objective functional tasks? Methods: A total of 104 patients were studied. Of these 56 had MoM THA (50 male) and 48 had HR (43 male). Mean age at surgery was 52 years in both groups. We reviewed this cohort at mid-term follow-up [minimum 8 years (mean 9 years; range 8–10; SD 0.7)]. PROMs that were completed were OHS, WOMAC, SF-12, and the UCLA. For objective functional task-based outcomes, gait parameters for operated legs were assessed in a subgroup of 17 patients with high UCLA. Results: Revision rate in MoM THA group was 7/56 (12.5%) and in the HR group was 1/48 (2.1%). Overall revision rate at minimum 8-year follow-up was 7.7% (8 of 104 patients). PROMs data comparing MoM THA versus HR showed no difference between the groups. 4 (8.5%) of the non-revised (47) HR patients had WOMAC function or pain score below 70. 3 (6.4%) patients had both pain and function scores <70. In the THA group, 5 (10.2%) of the non-revised (49) patients had WOMAC pain or function scores <70. 3 (6.1%) patients had both pain and function scores <70. The comparison of HA versus THA showed several gait parameters in the HR group to be better but not statistically significant ( p > 0.05 Mann-Whitney U-test). Conclusions: At mid-term follow-up, the revision rate of MoM articulation for THA is high (7.7%), being higher in large head MoM total hips versus resurfacing. Overall probability of 10-year survival is 92.3% (KM analysis, 95% for MoM THA and 98% for HR). The HR group had better functional parameters on gait-based tasks compared to THA group but this difference did not reach statistical significance.
In vivo three-dimensional scapular kinematic alterations after reverse total shoulder arthroplasty
Authors: Kim Eugene , Jang Taedong , Park Hee Jin , Ikemoto Sumika , Murase Tsuyoshi , Sugamoto Kazuomi , Hong Seok Woo 
Published: May 2020

Background: In vivo three-dimensional (3D) kinematics of the scapula after reverse total shoulder arthroplasty (rTSA) have been sparsely investigated. The aim of this study was to analyze static and dynamic kinematic alterations of the scapula after rTSA in vivo with the use of computer-aided 3D reconstruction program. Methods: A total of 15 patients with cuff tear arthropathy treated by rTSA participated. Scapulae with rTSA and the contralateral scapulae were evaluated with computed tomography scan data in 0° and 120° forward flexion positions of the glenohumeral joint. To examine static scapular kinematic alterations, the angular position and distance from the thorax were evaluated in the shoulder neutral position. 3D rotational and translational movements of the scapula in relation to the thorax were also measured during arm elevation to evaluate dynamic scapular kinematic alterations. Results: Scapulae with rTSA were more anteriorly tilted in the sagittal plane and more internally rotated in the axial plane than were the contralateral scapulae. However, no significant differences were observed in the upward rotated position in the coronal plane or in the distance from the thorax in any plane between the scapulae with rTSA and the contralateral scapulae. In dynamic analyses, upward rotational movement in the coronal plane, external rotation in the axial plane, and posterior tilting in the sagittal plane showed significant differences between the scapulae with rTSA and the contralateral scapulae during elevation. In contrast, translational movements in coordination revealed no statistical differences between the two scapular groups except for lateral translation. Conclusion: Data from the 3D reconstruction program showed that rTSA might result in static positional changes and dynamic movement alterations. Level of Evidence: Therapeutic, IV
Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
Authors: Tulstrup Morten , Moriyama Takaya , Jiang Chuang , Grosjean Marie , Nersting Jacob , Abrahamsson Jonas , Grell Kathrine , Hjalgrim Lisa Lyngsie , Jónsson Ólafur Gísli , Kanerva Jukka , Lund Bendik , Nielsen Stine Nygaard , Nielsen Rikke Linnemann , Overgaard Ulrik , Quist-Paulsen Petter , Pruunsild Kaie , Vaitkeviciene Goda , Wolthers Benjamin Ole , Zhang Hui , Gupta Ramneek , Yang Jun J. , Schmiegelow Kjeld 
Published: May 2020

Abstract
Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 × 10−8) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 × 10−9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL
Authors: Assouline Sarit , Li Shen , Gisselbrecht Christian , Fogarty Patrick , Hay Annette , van den Neste Eric , Shepherd Lois E. , Schmitz Norbert , Baetz Tara , Keating Armand , Robinson Sue , Seftel Matthew , Stelitano Caterina , Djurfeldt Marina S. , Meyer Ralph , Chen Bingshu E. , Crump Michael 
Published: May 2020

Abstract
The conditional survival of patients after frontline therapy for diffuse large B-cell lymphoma (DLBCL) approaches that of the general population once patients have survived disease free for 2 years. We sought to determine the conditional survival of patients among patients with relapsed de novo DLBCL successfully undergoing an autologous stem-cell transplant (ASCT) after first relapse. A total of 478 patients with de novo DLBCL, relapsed after 1 treatment from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) and LY.12, were included. Patients were followed prospectively after ASCT for a median of 5.3 and 8.2 years, respectively. Individual patient data were analyzed for event-free survival (EFS) and overall survival. Standardized mortality ratios (SMRs) were estimated using French and Canadian life tables. The EFS estimates declined with each year of follow-up after ASCT and were 50.1% (95% confidence interval [CI]: 43.7% to 56.3%) and 43.4% (95% CI: 36.7% to 49.9%) at 5 years in CORAL and LY.12, respectively. The rate of death stabilized once patients achieved at least 4 years of EFS. Compared with the age- and sex-matched population, the SMR was significantly higher until 5 years after ASCT, when values were no longer statistically significant. Patients undergoing ASCT for relapsed DLBCL continue to have a higher rate of death at least until they have survived event free for 5 years. These observations can help to determine endpoints for future clinical trials in this population and for patient counseling. This trial was registered at www.clinicaltrials.gov as #NCT00078949.
Development of an anti-human complement C6 monoclonal antibody that inhibits the assembly of membrane attack complexes
Authors: Lin Kimberly , Zhang Lingjun , Kong Michael , Yang Maojing , Chen Yinghua , Poptic Earl , Hoffner Melanie , Xu Jijun , Tam Connie , Lin Feng 
Published: May 2020

Abstract
Membrane attack complexes (MACs; C5b-9) assembled after complement activation can directly injure self-tissues, leading to various diseases. Eculizumab, a monoclonal antibody (mAb) against complement component C5, is being used in the clinic to treat diseases in which MAC-mediated tissue damage is a primary cause. However, C5 is not a selective target for MAC assembly inhibition, and some patients respond incompletely or not at all to the eculizumab treatment. Therefore, C6, the next essential component in the terminal pathway of complement activation, may be an alternative target for the selective inhibition of MAC formation. Surprisingly, few reports describe a functional blockade of C6 using a specific mAb. Here, we report the development of an anti-human C6 mAb (clone 1C9) that recognizes C6 both in free circulation and within C5b6 complexes. This mAb blocked C7 binding to C5b6 complexes and consequently inhibited MAC formation and protected affected paroxysmal nocturnal hemoglobinuria patient red blood cells from MAC-mediated damage in vitro. In addition, this mAb cross-reacts with rhesus monkey but not mouse complement C6. Finally, 1C9 significantly reduced human complement–mediated intravascular hemolysis in vivo in a mouse model. These results suggest that the anti-C6 mAb holds promise as a new therapeutic agent that selectively targets MAC for many complement-mediated pathological conditions.
Assessment methods in respiratory medicine training in Europe: current status and future needs
Authors: Primhak Robert 
Published: May 2020

There is a perceived need for harmonisation of training standards in medicine across Europe. Assessment methodology is a fundamental part of this harmonisation. Assessment may be: summative, measuring competency at the end of training, usually in a pass/fail mode; or formative, assessing strengths and weaknesses during training with a view to optimising performance. A survey of experienced respiratory medicine trainers in Europe was undertaken to discover the formative and summative assessment methods being used, and to explore the use of workplace-based assessments (WBAs). Structured interviews were sought with experienced trainers in adult and paediatric respiratory medicine. 35 trainers from 22 (71%) out of 31 countries were interviewed.The number of types of summative assessments required at the end of training varied from 0 to 4 including clinical (25%), written (44%) and oral (47%) examinations. Four respondents required a research thesis as a proof of clinical competence.WBA was not commonly used. Only 14% of respondents reported using a formal case-based discussion, 20% used a form of multisource feedback and 25% described some form of formal assessment of procedural skills. However, 77% of all respondents expressed a wish to have access to case-based discussion and 72% wanted to have a facility for multisource feedback. The majority also wanted training in the use of these tools. Almost half of the respondents had received no formal training in educational supervision and 80% of all respondents expressed a wish to receive such training.The findings suggest that there is no adequate process of ensuring uniform standards for specialist accreditation in Europe, and demonstrate a need and desire among trainers for more WBA tools and training in their use to be made available.
Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Authors: Liu Hequn , Barnes Jesse , Pedrosa Erika , Herman Nathaniel S. , Salas Franklin , Wang Ping , Zheng Deyou , Lachman Herbert M. 
Published: May 2020

Abstract
Background
Lowe syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL, which codes for an inositol polyphosphate 5-phosphatase that plays a key role in endosome recycling, clathrin-coated pit formation, and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. We recently developed induced pluripotent stem cell (iPSC) lines from three patients with LS who have hypomorphic variants affecting the 3′ end of the gene, and their neurotypical brothers to serve as controls.

Methods
In this study, we used RNA sequencing (RNA-seq) to obtain transcriptome profiles in LS and control neural progenitor cells (NPCs).

Results
In a comparison of the patient and control NPCs (n = 3), we found 16 differentially expressed genes (DEGs) at the multiple test adjusted p value (padj) < 0.1, with nine at padj < 0.05. Using nominal p value < 0.05, 319 DEGs were detected. The relatively small number of DEGs could be due to the fact that OCRL is not a transcription factor per se, although it could have secondary effects on gene expression through several different mechanisms. Although the number of DEGs passing multiple test correction was small, those that were found are quite consistent with some of the known molecular effects of OCRL protein, and the clinical manifestations of LS. Furthermore, using gene set enrichment analysis (GSEA), we found that genes increased expression in the patient NPCs showed enrichments of several gene ontology (GO) terms (false discovery rate < 0.25): telencephalon development, pallium development, NPC proliferation, and cortex development, which are consistent with a condition characterized by intellectual disabilities and psychiatric manifestations. In addition, a significant enrichment among the nominal DEGs for genes implicated in autism spectrum disorder (ASD) was found (e.g., AFF2, DNER, DPP6, DPP10, RELN, CACNA1C), as well as several that are strong candidate genes for the development of eye problems found in LS, including glaucoma. The most notable example is EFEMP1, a well-known candidate gene for glaucoma and other eye pathologies.

Conclusion
Overall, the RNA-seq findings present several candidate genes that could help explain the underlying basis for the neurodevelopmental and eye problems seen in boys with LS.
Male infant patient with a mesenteric cyst in the greater and lesser omenta: a case report
Authors: del Pilar Pereira-Ospina Rocio , Montoya-Sanchez Laura Catherine , Abella-Morales Diana María , Pinzón-Salamanca Javier Yesid , Suescún-Vargas José Miguel , Rueda-Martínez Sergio 
Published: May 2020

Abstract
Background
Mesenteric cysts are intra-abdominal masses of congenital origin, which most frequently occur in children, with an incidence of approximately 1 case per 20,000 pediatric admissions. Its progression can be asymptomatic, and its diagnosis can be incidental. However, it usually occurs with symptoms such as nausea, vomiting, constipation, sensation of a mass, and/or diarrhea. The diagnostic imaging method of choice is abdominal ultrasound.

Case presentation
Below, we present the case of a previously healthy 1-year-old male patient with nonspecific symptoms, who was referred to a tertiary hospital. The presence of a mesenteric cyst was detected at the end of the diagnostic approach.

Conclusion
It is important to know these pathologies even though they are infrequent, because although they are benign masses by definition, they can lead to complications such as intestinal torsion, intestinal obstruction, and even peritonitis.
Cluster correlation based method for lncRNA-disease association prediction
Authors: Yuan Qianqian , Guo Xingli , Ren Yang , Wen Xiao , Gao Lin 
Published: May 2020

AbstractBackgroundIn recent years, increasing evidences have indicated that long non-coding RNAs (lncRNAs) are deeply involved in a wide range of human biological pathways. The mutations and disorders of lncRNAs are closely associated with many human diseases. Therefore, it is of great importance to predict potential associations between lncRNAs and complex diseases for the diagnosis and cure of complex diseases. However, the functional mechanisms of the majority of lncRNAs are still remain unclear. As a result, it remains a great challenge to predict potential associations between lncRNAs and diseases.ResultsHere, we proposed a new method to predict potential lncRNA-disease associations. First, we constructed a bipartite network based on known associations between diseases and lncRNAs/protein coding genes. Then the cluster association scores were calculated to evaluate the strength of the inner relationships between disease clusters and gene clusters. Finally, the gene-disease association scores are defined based on disease-gene cluster association scores and used to measure the strength for potential gene-disease associations.ConclusionsLeave-One Out Cross Validation (LOOCV) and 5-fold cross validation tests were implemented to evaluate the performance of our method. As a result, our method achieved reliable performance in the LOOCV (AUCs of 0.8169 and 0.8410 based on Yang’s dataset and Lnc2cancer 2.0 database, respectively), and 5-fold cross validation (AUCs of 0.7573 and 0.8198 based on Yang’s dataset and Lnc2cancer 2.0 database, respectively), which were significantly higher than the other three comparative methods. Furthermore, our method is simple and efficient. Only the known gene-disease associations are exploited in a graph manner and further new gene-disease associations can be easily incorporated in our model. The results for melanoma and ovarian cancer have been verified by other researches. The case studies indicated that our method can provide informative clues for further investigation.
methCancer-gen: a DNA methylome dataset generator for user-specified cancer type based on conditional variational autoencoder
Authors: Choi Joungmin , Chae Heejoon 
Published: May 2020

Abstract
Background
Recently, DNA methylation has drawn great attention due to its strong correlation with abnormal gene activities and informative representation of the cancer status. As a number of studies focus on DNA methylation signatures in cancer, demand for utilizing publicly available methylome dataset has been increased. To satisfy this, large-scale projects were launched to discover biological insights into cancer, providing a collection of the dataset. However, public cancer data, especially for certain cancer types, is still limited to be used in research. Several simulation tools for producing epigenetic dataset have been introduced in order to alleviate the issue, still, to date, generation for user-specified cancer type dataset has not been proposed.

Results
In this paper, we present methCancer-gen, a tool for generating DNA methylome dataset considering type for cancer. Employing conditional variational autoencoder, a neural network-based generative model, it estimates the conditional distribution with latent variables and data, and generates samples for specified cancer type.

Conclusions
To evaluate the simulation performance of methCancer-gen for the user-specified cancer type, our proposed model was compared to a benchmark method and it could successfully reproduce cancer type-wise data with high accuracy helping to alleviate the lack of condition-specific data issue. methCancer-gen is publicly available at https://github.com/cbi-bioinfo/methCancer-gen.
Multi-task learning sparse group lasso: a method for quantifying antigenicity of influenza A(H1N1) virus using mutations and variations in glycosylation of Hemagglutinin
Authors: Li Lei , Chang Deborah , Han Lei , Zhang Xiaojian , Zaia Joseph , Wan Xiu-Feng 
Published: May 2020

AbstractBackgroundIn addition to causing the pandemic influenza outbreaks of 1918 and 2009, subtype H1N1 influenza A viruses (IAVs) have caused seasonal epidemics since 1977. Antigenic property of influenza viruses are determined by both protein sequence andN-linked glycosylation of influenza glycoproteins, especially hemagglutinin (HA). The currently available computational methods are only considered features in protein sequence but notN-linked glycosylation.ResultsA multi-task learning sparse group least absolute shrinkage and selection operator (LASSO) (MTL-SGL) regression method was developed and applied to derive two types of predominant features including protein sequence andN-linked glycosylation in hemagglutinin (HA) affecting variations in serologic data for human and swine H1N1 IAVs. Results suggested that mutations and changes inN-linked glycosylation sites are associated with the rise of antigenic variants of H1N1 IAVs. Furthermore, the implicated mutations are predominantly located at five reported antibody-binding sites, and within or close to the HA receptor binding site. All of the threeN-linked glycosylation sites (i.e. sequons NCSV at HA 54, NHTV at HA 125, and NLSK at HA 160) identified by MTL-SGL to determine antigenic changes were experimentally validated in the H1N1 antigenic variants using mass spectrometry analyses. Compared with conventional sparse learning methods, MTL-SGL achieved a lower prediction error and higher accuracy, indicating that grouped features and MTL in the MTL-SGL method are not only able to handle serologic data generated from multiple reagents, supplies, and protocols, but also perform better in genetic sequence-based antigenic quantification.ConclusionsIn summary, the results of this study suggest that mutations and variations inN-glycosylation in HA caused antigenic variations in H1N1 IAVs and that the sequence-based antigenicity predictive model will be useful in understanding antigenic evolution of IAVs.