bluuebunny/crossref_metadata_2025_split huggingface dataset:
The OncoLifeS data-biobank for oncology: a comprehensive repository of clinical data, biological samples, and the patient’s perspective
Authors: Sidorenkov Grigory , Nagel Janny , Meijer Coby , Duker Jacko J. , Groen Harry J. M. , Halmos Gyorgy B. , Oonk Maaike H. M. , Oostergo Rene J. , van der Vegt Bert , Witjes Max J. H. , Nijland Marcel , Havenga Klaas , Maduro John H. , Gietema Jourik A. , de Bock Gertruida H. 
Published: November 2019

Abstract
Background
Understanding cancer heterogeneity, its temporal evolution over time, and the outcomes of guided treatment depend on accurate data collection in a context of routine clinical care. We have developed a hospital-based data-biobank for oncology, entitled OncoLifeS (Oncological Life Study: Living well as a cancer survivor), that links routine clinical data with preserved biological specimens and quality of life assessments. The aim of this study is to describe the organization and development of a data-biobank for cancer research.

Results
We have enrolled 3704 patients aged ≥ 18 years diagnosed with cancer, of which 45 with hereditary breast-ovarian cancer (70% participation rate) as of October 24th, 2019. The average age is 63.6 ± 14.2 years and 1892 (51.1%) are female. The following data are collected: clinical and treatment details, comorbidities, lifestyle, radiological and pathological findings, and long-term outcomes. We also collect and store various biomaterials of patients as well as information from quality of life assessments.

Conclusion
Embedding a data-biobank in clinical care can ensure the collection of high-quality data. Moreover, the inclusion of longitudinal quality of life data allows us to incorporate patients’ perspectives and inclusion of imaging data provides an opportunity for analyzing raw imaging data using artificial intelligence (AI) methods, thus adding new dimensions to the collected data.
Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis
Authors: Spiering Rachel , Jansen Manon A. A. , Wood Matthew J. , Fath Anshorulloh A. , Eltherington Oliver , Anderson Amy E. , Pratt Arthur G. , van Eden Willem , Isaacs John D. , Broere Femke , Hilkens Catharien M. U. 
Published: November 2019

AbstractBackgroundAutologous tolerogenic dendritic cells (tolDC) are a promising therapeutic strategy for inflammatory arthritis (IA) as they can regulate autoantigen-specific T cell responses. Here, we investigated two outstanding priorities for clinical development: (i) the suitability of using heat-shock proteins (HSP), abundant in inflamed synovia, as surrogate autoantigens to be presented by tolDC and (ii) identification of functional biomarkers that confirm tolDC regulatory activity.MethodsCell proliferation dye-labelled human peripheral blood mononuclear cells of IA (rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) patients or healthy donors were cultured with HSP40-, HSP60- and HSP70-derived peptides or recall antigens (e.g. tuberculin purified protein derivative (PPD)) in the presence or absence of tolDC or control DC for 9 days. Functional characteristics of proliferated antigen-specific T-cells were measured using flow cytometry, gene expression profiling and cytokine secretion immunoassays. Repeated measures analysis of variance (ANOVA) with Bonferroni correction for comparisons between multiple groups and paired Studentttest for comparisons between two groups were used to determine significance.ResultsAll groups showed robust CD4+T-cell responses towards one or more HSP-derived peptide(s) as assessed by a stimulation index > 2 (healthy donors: 78%, RA: 73%, PsA: 90%) and production of the cytokines IFNγ, IL-17A and GM-CSF. Addition of tolDC but not control DC induced a type 1 regulatory (Tr1) phenotype in the antigen-specific CD4+T-cell population, as identified by high expression of LAG3, CD49b and secretion of IL-10. Furthermore, tolDC inhibited bystander natural killer (NK) cell activation in a TGFβ dependent manner.ConclusionsHSP-specific CD4+T-cells are detectable in the majority of RA and PsA patients and can be converted into Tr1 cells by tolDC. HSP-loaded tolDC may therefore be suitable for directing T regulatory responses to antigens in inflamed synovia of IA patients. Tr1 markers LAG3, CD49b and IL-10 are suitable biomarkers for future tolDC clinical trials.
The 164 K, 165 K, and 167 K residues of VP1 are vital for goose parvovirus proliferation in GEFs based on PCR-based reverse genetics system
Authors: Liu Peng , Yang Liqin , Zhang Jingyue , Wang Tao , Wu Yuanyuan , Wang Mingshu , Jia Renyong , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Liu Yunya , Yu Yanling , Zhang Ling , Pan Leichang , Chen Shun , Cheng Anchun 
Published: November 2019

Abstract
Background
Goose parvovirus (GPV) is the etiological agent of Derzsy’s disease and is fatal for gosling. Research on the molecular basis of GPV pathogenicity has been hampered by the lack of a reliable reverse genetics system. At present, the GPV infectious clone has been rescued by transfection in the goose embryo, but the growth character of it is unclear in vitro.

Methods
In this study, we identified the full-length genome of GPV RC16 from the clinical sample, which was cloned into the pACYC177, generating the pIRC16. The recombinant virus (rGPV RC16) was rescued by the transfection of pIRC16 into goose embryo fibroblasts (GEFs). The rescued virus was characterized by whole genome sequencing, indirect immunofluorescence assays (IFA) and western blot (WB) using rabbit anti-GPV Rep polyclonal antibody as the primary antibody. Previously, we found the 164 K, 165 K, and 167 K residues in the 160YPVVKKPKLTEE171 are required for the nuclear import of VP1 (Chen S, Liu P, He Y, et al. Virology 519:17–22). According to that, the GPV infectious clones with mutated K164A, K165A, or K167A in VP1 were constructed, rescued and passaged.

Results
The rGPV RC16 has been successfully rescued by transfection of pIRC16 into the GEFs and can proliferate in vitro. Furthermore, the progeny virus produced by pIRC16 transfected cells was infectious in GEFs. Moreover, mutagenesis experiments showed that the rGPV RC16 with mutated 164 K, 165 K and 167 K in VP1 could not proliferate in GEFs based on the data of IFA and WB in parental virus and progeny virus.

Conclusions
The rGPV RC16 containing genetic maker and the progeny virus are infectious in GEFs. The 164 K, 165 K, and 167 K of VP1 are vital for the proliferation of rGPV RC16 in vitro.
The prevalence of alcohol use disorders among people living with HIV/AIDS: a systematic review and meta-analysis
Authors: Duko Bereket , Ayalew Mohammed , Ayano Getinet 
Published: November 2019

Abstract
Background
Alcohol use disorder (AUD) is common among people living with HIV/AIDS (PLWHA) and associated with a greater risk of poor medication adherence, unsafe sexual behaviors as well as poor quality of life. To our knowledge, there is no previous systematic review and meta-analysis that reported the pooled prevalence estimate of AUD among PLWHA. Therefore, this review aimed to systematically review the available studies on the prevalence of AUD among PLWHA and forward possible recommendations for future clinical practice and research.

Methods
PubMed, EMBASE, Psych INFO and SCOPUS databases were searched to identify the relevant studies. We have also scanned the reference lists of the eligible studies to supplement our electronic search. We used the Comprehensive Meta-Analysis software versions 3.0 to conduct a meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I2- test were employed to see the heterogeneity. The presence of publication bias was explored by utilizing Egger’s test and visual inspection of the symmetry in funnel plots.

Results
A total of 25 studies with 25,154 participants across developed and developing countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence estimate of AUD among PLWHA was found to be 29.80% (95% CI; 24.10–35.76). The prevalence of AUD was higher in males (26.90%) than female (13.37%) HIV patients. In this study, the pooled prevalence of AUD was considerably higher (31.52%) when measured by Alcohol Use Disorders Identification Test (AUDIT) as compared to Composite International Diagnostic Interview (CIDI) (13.51%). In addition, the pooled prevalence of AUD was higher in the developed countries (42.09%) while lower for developing countries (24.52%).

Conclusion
In the current study, the pooled prevalence estimates of AUD among PLWHA was considerably high (29.80%). Screening and appropriate management of AUD among PLWHA are recommended.
Steinmann pin retractor-assisted reduction with circle plate fixation via sinus tarsi approach for intra-articular calcaneal fractures: a retrospective cohort study
Authors: Zhao Bin , Zhao Wenqian , Assan Isaac 
Published: November 2019

Abstract
Background
Sinus tarsi approach and mini-calc plate have been used for intra-articular calcaneal fractures. However, the sinus tarsi approach has limited exposure to the lateral wall, which makes it challenging to obtain an excellent anatomic reduction of the calcaneal body. What is more! To restore the width of the calcaneal body entirely and prevent the heel varus simultaneously with mini-calc plate was tough as well. Aimed to solve the aforementioned problems, our study focused on using the Steinmann pin retractor for reduction and the circle plate for fixation via the sinus tarsi approach.

Methods
From March 2017 to January 2019, 15 patients with closed calcaneal fractures were treated with the method of Steinmann pin retractor-assisted reduction and circle plate fixation via the sinus tarsi approach. All these patients received a positive postoperative clinical and radiological evaluation.

Results
A postoperative follow-up was done for each of the 15 patients, and the following scores and parameters were observed: value of visual analogue scale (VAS) was 1.44 ± 0.63, and The American Orthopaedic Foot and Ankle Score (AOFAS) Ankle-Hindfoot score was 84.31 ± 5.03 at the last follow-up. The Böhler angle (30.81 ± 3.56°), width (37.83 ± 4.87 mm), length (87.4 ± 3.33 mm), and height (86.23 ± 5.36 mm) of the calcaneus were improved significantly in comparison with preoperative values (− 0.94 ± 10.06°, 45.67 ± 5.68 mm, 82.72 ± 5.54 mm, 76.32 ± 7.98 mm), and these parameters were maintained excellently after 6–19 months’ follow-up.

Conclusion
Our present study suggested that Steinmann pin retractor-assisted reduction with circle plate fixation via the sinus tarsi approach may serve as a safe and effective method for Sanders type II and type III calcaneus fractures. The Böhler angle, height, length, and body of the calcaneus were excellently restored postoperatively and maintained at last follow-up and rare postoperative complications.

Trial registration
This study has been registered. The unique identifying number is research registry 5092.
The diagnostic value of soluble urokinase-type plasminogen activator receptor (suPAR) for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine
Authors: Scharrenberg Jan Simon , Yagdiran Ayla , Brinkmann Julia , Brune Maik , Siewe Jan , Jung Norma , Mahabir Esther 
Published: November 2019

Abstract
Background
There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP.

Methods
Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3–5, 6–11, 40–56, and 63–142.

Results
The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3–5 days post-OP, and 6–11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6–11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37–0.79), p < 0.0001. The values for the area under the receiver operating characteristics curve (AUC) for pre-OP and the overall model post-OP were 0.88 (95% CI: 0.76–1.00) and 0.84 (95% CI: 0.71–0.97) for suPAR, 0.93 (95% CI: 0.85–1.00) and 0.77 (95% CI: 0.62–0.93) for CRP, and 0.98 (95% CI: 0.96–1.00) and 0.91 (95% CI: 0.82–1.00) for the combination of suPAR and CRP. The AUC for suPAR pre-OP revealed an optimum cut-off value, sensitivity, specificity, NPV, and PPV of 2.96 ng/mL, 0.69, 1.00, 0.80, and 1.00, respectively. For CRP, these values were 11.58 mg/L, 0.88, 0.90, 0.90, and 0.88, respectively.

Conclusion
The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP.

Trial registration
ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019
Pathway to diagnosis and burden of illness in mucopolysaccharidosis type VII – a European caregiver survey
Authors: Morrison Alexandra , Oussoren Esmee , Friedel Tabea , Cruz Jordi , Yilmaz Nalan 
Published: November 2019

Abstract
Background
Mucopolysaccharidosis type VII (Sly disease, MPS VII), is an ultra-rare, multi-symptom disease with variable clinical presentations which can present challenges with diagnosis, management and care. We believe this survey is the first to explore the patient experience through direct questioning of the caregivers of 13 individuals with MPS VII.

Methods
This European survey, using a specifically designed questionnaire, was conducted in order to describe the pathway to diagnosis and the burden of illness of MPS VII. Information on early symptoms, clinicians seen, and current symptoms was collected. Questions on the caregivers’ ability to work and the use and availability of health, social and educational support were included.

Results
Caregivers of 13 patients from Germany, Spain, The Netherlands and Turkey responded to the survey. Five patients with non-immune hydrops fetalis (NIHF) were diagnosed with MPS VII at a mean age of 1.9 years (median 0.3 years, range 0.2 to 6 years). Those without NIHF (n = 7) were diagnosed at a mean age of 6.1 years (median 6.0 years, range 1.9 to 14 years). The symptoms most likely to raise a suspicion of MPS VII, excluding NIHF, did not appear until a median age of at least three years.
Over one half of patients required assistance with daily living and mobility. Reduction of the working hours of caregivers was often necessary (46.2% reduced hours, 30.8% stopped working).
Patients attended frequent medical appointments (12.7/year), over 80% had surgery and 30% had been hospitalised for respiratory issues.
While support for learning and behavioural needs was generally available, support for mobility was not available to 50% of patients. Half of the respondents (6/12) said they were not offered genetic counselling.

Conclusions
For children that do not present with NIHF, diagnosis can take several years as early symptoms can be non-specific and mistaken for other conditions. Increased awareness of the early signs of disease and more information for parents/caregivers at diagnosis are needed. MPS VII poses significant burden to patients, caregivers, healthcare, social and educational services. Access to information and support varies across Europe and the availability of genetic counselling is limited in some countries.
Systemic bevacizumab for high-output cardiac failure in hereditary hemorrhagic telangiectasia: an international survey of HHT centers
Authors: Al-Samkari Hanny , Albitar Hasan A. , Olitsky Scott E. , Clancy Marianne S. , Iyer Vivek N. 
Published: November 2019

Abstract
Background
Systemic bevacizumab is a novel targeted anti-angiogenic therapy for high-output cardiac failure (HOCF) in hereditary hemorrhagic telangiectasia (HHT) but published data is limited. This survey-based study measured physician-reported safety, effectiveness and current treatment practices for systemic bevacizumab in HHT-HOCF.

Methods
A 27-item survey was sent to center directors of 31 international HHT Centers of Excellence.

Results
Response rate was 74% with centers reporting 150 total patients receiving systemic bevacizumab for HHT-HOCF. Approximately two-thirds of centers had treated ≥5 patients. All centers utilize a 5 mg/kg dose for induction treatment and most administer 6 doses (range, 4–6) every 2 weeks, although maintenance regimens varied considerably. Center directors reported bevacizumab to be effective, with 55% reporting significant improvement in cardiac index and HOCF symptoms in most patients treated with bevacizumab, although normalization of cardiac parameters was uncommon. Adverse events were uncommon with three-quarters of centers reporting adverse event rates < 10%. Discontinuation for adverse events or ineffectiveness was rare. Bevacizumab was typically administered by hematologists and pulmonologists (50 and 39% of centers, respectively), with highly variable thresholds for initiation. Although half the centers reported difficulty with the insurance approval process, 70% of centers were ultimately able to obtain coverage for most or all of their patients.

Conclusions
Systemic bevacizumab is a widely-used therapy for HHT-HOCF with reasonable safety and effectiveness. HHT centers appear to vary considerably in maintenance treatment practices and disease severity thresholds for initiation of bevacizumab in HHT-related HOCF.
Application of CRISPR genetic screens to investigate neurological diseases
Authors: So Raphaella W. L. , Chung Sai Wai , Lau Heather H. C. , Watts Jeremy J. , Gaudette Erin , Al-Azzawi Zaid A. M. , Bishay Jossana , Lin Lilian Tsai-Wei , Joung Julia , Wang Xinzhu , Schmitt-Ulms Gerold 
Published: November 2019

AbstractThe adoption of CRISPR-Cas9 technology for functional genetic screens has been a transformative advance. Due to its modular nature, this technology can be customized to address a myriad of questions. To date, pooled, genome-scale studies have uncovered genes responsible for survival, proliferation, drug resistance, viral susceptibility, and many other functions. The technology has even been applied to the functional interrogation of the non-coding genome. However, applications of this technology to neurological diseases remain scarce. This shortfall motivated the assembly of a review that will hopefully help researchers moving in this direction find their footing. The emphasis here will be on design considerations and concepts underlying this methodology. We will highlight groundbreaking studies in the CRISPR-Cas9 functional genetics field and discuss strengths and limitations of this technology for neurological disease applications. Finally, we will provide practical guidance on navigating the many choices that need to be made when implementing a CRISPR-Cas9 functional genetic screen for the study of neurological diseases.
Redesigning N-glycosylation sites in a GH3 β-xylosidase improves the enzymatic efficiency
Authors: Rubio Marcelo Ventura , Terrasan César Rafael Fanchini , Contesini Fabiano Jares , Zubieta Mariane Paludetti , Gerhardt Jaqueline Aline , Oliveira Leandro Cristante , de Souza Schmidt Gonçalves Any Elisa , Almeida Fausto , Smith Bradley Joseph , de Souza Gustavo Henrique Martins Ferreira , Dias Artur Hermano Sampaio , Skaf Munir , Damasio André 
Published: November 2019

Abstract
Background
β-Xylosidases are glycoside hydrolases (GHs) that cleave xylooligosaccharides and/or xylobiose into shorter oligosaccharides and xylose. Aspergillus nidulans is an established genetic model and good source of carbohydrate-active enzymes (CAZymes). Most fungal enzymes are N-glycosylated, which influences their secretion, stability, activity, signalization, and protease protection. A greater understanding of the N-glycosylation process would contribute to better address the current bottlenecks in obtaining high secretion yields of fungal proteins for industrial applications.

Results
In this study, BxlB—a highly secreted GH3 β-xylosidase from A. nidulans, presenting high activity and several N-glycosylation sites—was selected for N-glycosylation engineering. Several glycomutants were designed to investigate the influence of N-glycans on BxlB secretion and function. The non-glycosylated mutant (BxlBnon-glyc) showed similar levels of enzyme secretion and activity compared to the wild-type (BxlBwt), while a partially glycosylated mutant (BxlBN1;5;7) exhibited increased activity. Additionally, there was no enzyme secretion in the mutant in which the N-glycosylation context was changed by the introduction of four new N-glycosylation sites (BxlBCC), despite the high transcript levels. BxlBwt, BxlBnon-glyc, and BxlBN1;5;7 formed similar secondary structures, though the mutants had lower melting temperatures compared to the wild type. Six additional glycomutants were designed based on BxlBN1;5;7, to better understand its increased activity. Among them, the two glycomutants which maintained only two N-glycosylation sites each (BxlBN1;5 and BxlBN5;7) showed improved catalytic efficiency, whereas the other four mutants’ catalytic efficiencies were reduced. The N-glycosylation site N5 is important for improved BxlB catalytic efficiency, but needs to be complemented by N1 and/or N7. Molecular dynamics simulations of BxlBnon-glyc and BxlBN1;5 reveals that the mobility pattern of structural elements in the vicinity of the catalytic pocket changes upon N1 and N5 N-glycosylation sites, enhancing substrate binding properties which may underlie the observed differences in catalytic efficiency between BxlBnon-glyc and BxlBN1;5.

Conclusions
This study demonstrates the influence of N-glycosylation on A. nidulans BxlB production and function, reinforcing that protein glycoengineering is a promising tool for enhancing thermal stability, secretion, and enzymatic activity. Our report may also support biotechnological applications for N-glycosylation modification of other CAZymes.