bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the graded prognostic assessment for gastrointestinal cancers with brain metastases (GI-GPA)
Authors: Nieder Carsten , Hintz Mandy , Popp Ilinca , Bilger Angelika , Grosu Anca L. 
Published: February 2020

Abstract
Purpose
The purpose of this study was to validate a new prognostic model (GI-GPA) originally derived from a multi-center database (USA, Canada, Japan).

Patients and Methods
This retrospective study included 92 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. The GI-GPA score was calculated as described by Sperduto et al.

Results
Median survival was 4 months. The corresponding figures for the 4 different prognostic strata were 2.3, 4.4, 9.4 and 12.7 months, respectively (p = 0.0001). Patients whose management included surgical resection had longer median survival than those who were treated with other approaches (median 11.9 versus 3.0 months, p = 0.002). Comparable results were seen for additional systemic therapy (median 8.5 versus 3.5 months, p = 0.01).

Conclusion
These results confirm the validity of the GI-GPA in an independent dataset from a different geographical region, despite the fact that overall survival was shorter in all prognostic strata, compared to Sperduto et al. Potential explanations include differences in molecular tumor characteristics and treatment selection, both brain metastases-directed and extracranially. Long-term survival beyond 5 years is possible in a small minority of patients.
Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
Authors: Gupta Ashim , El-Amin Saadiq F. , Levy Howard J. , Sze-Tu Rebecca , Ibim Sobrasua E. , Maffulli Nicola 
Published: February 2020

Abstract
Background
The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton’s Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton’s jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes.

Methods
Human umbilical cords were obtained from consenting caesarian section donors. The Wharton’s jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles.

Results
All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles.

Conclusion
There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton’s jelly formulation analyzed. The amount of these factors in Wharton’s jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.
Estrogen receptor β induces autophagy of osteosarcoma through the mTOR signaling pathway
Authors: Yang Zhengming , Yu Wei , Liu Bing , Yang Minfei , Tao Huimin 
Published: February 2020

AbstractBackgroundEstrogen receptor beta (ERβ) was considered as a tumor-inhibiting factor in estrogen-sensitive malignant tumors. In this study, we intended to investigate whether ERβ was involved in inducing autophagy in osteosarcoma.MethodsThis is an experimental study. The associations between ERβ and autophagy were detected in osteosarcoma U2-OS cells which were treated with E2, E2 + 2,3-Bis (4-hydroxyphenyl) propionitrile (DPN, ERβ agonists), E2 + DPN + water, E2 + DPN + 3-Methyladenine (3-MA, autophagy inhibitor), respectively. Cell viability and death were detected using cell counting kit 8 assay and flow cytometry, respectively. In addition, the expression of autophagy marker LC3II/I, sequestosome 1 (P62), mammalian target of rapamycin (mTOR), and phosphorylated-mTOR (p-mTOR) was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting.ResultsCell viability was significantly decreased with DPN treatment, while was reversed with 3-MA treatment. DPN treatment decreased living cells proportion and increased cell apoptosis proportion, while 3-MA treatment reversed those changes. However, there were significant differences between the E2 group and the E2 + DPN + 3-MA group for the living cell proportion and cell apoptosis proportion, suggesting apoptosis and autophagy all were induced. In addition, DPN treatment upregulated the LC3II/I expression level and downregulated P62 and mTOR (mRNA level) and p-mTOR (protein level) expression levels.ConclusionERβ inhibited the cell viability and mediated cell death by inducing apoptosis and autophagy in osteosarcoma. ERβ-induced autophagy in osteosarcoma was associated with downregulating the P62 expression level and inhibiting mTOR activation.
The chloroplasts genomic analyses of Rosa laevigata, R. rugosa and R. canina
Authors: Yin Xianmei , Liao Baosheng , Guo Shuai , Liang Conglian , Pei Jin , Xu Jiang , Chen Shilin 
Published: February 2020

AbstractBackgroundMany species of the genusRosahave been used as ornamental plants and traditional medicines. However, industrial development of roses is hampered due to highly divergent characteristics.MethodsWe analyzed the chloroplast (cp) genomes ofRosa laevigata, R. rugosaandR. canina, including the repeat sequences, inverted-repeat (IR) contractions and expansions, and mutation sites.ResultsThe size of the cp genome ofR. laevigata, R. rugosaandR. caninawas between 156 333 bp and 156 533 bp, and contained 113 genes (30 tRNA genes, 4 rRNA genes and 79 protein-coding genes). The regions with a higher degree of variation were screened out (trnH-GUU,trnS-GCU,trnG-GCC,psbA-trnH,trnC-GCA,petN,trnT-GGU,psbD,petA,psbJ,ndhF,rpl32,psaCandndhE). Such higher-resolution loci lay the foundation of barcode-based identification of cp genomes inRosagenus. A phylogenetic tree of the genusRosawas reconstructed using the full sequences of the cp genome. These results were largely in accordance with the current taxonomic status ofRosa.ConclusionsOur data: (i) reveal that cp genomes can be used for the identification and classification ofRosaspecies; (ii) can aid studies on molecular identification, genetic transformation, expression of secondary metabolic pathways and resistant proteins; (iii) can lay a theoretical foundation for the discovery of disease-resistance genes and cultivation ofRosaspecies.
Adverse event rates and economic burden associated with purine nucleoside analogs in patients with hairy cell leukemia: a US population-retrospective claims analysis
Authors: Epperla Narendranath , Pavilack Melissa , Olufade Temitope , Bashyal Richa , Li Jieni , Kabadi Shaum M. , Yuce Huseyin , Andritsos Leslie 
Published: February 2020

Abstract
Background
Purine nucleoside analogs (PNAs) are the recommended first-line treatment for patients with hairy cell leukemia (HCL), but they are associated with adverse events (AEs). Due to a lack of real-world evidence regarding AEs that are associated with PNAs, we used commercial data to assess AE rates, AE-related health care resource utilization (HCRU), and costs among PNA-treated patients with HCL. Adults aged ≥18 years with ≥2 claims for HCL ≥30 days apart from 1 January 2006 through 31 December 2015 were included. Included patients had ≥1 claim for HCL therapy (cladribine ± rituximab or pentostatin ± rituximab [index date: first claim date]) and continuous enrollment for a ≥ 6-month baseline and ≥ 12-month follow-up period. Patient sub-cohorts were based on the occurrence of myelosuppression and opportunistic infections (OIs). Generalized linear models were used to compare HCRU and costs.

Results
In total, 647 PNA-treated patients were identified (mean age: 57.1 years). Myelosuppression and OI incidence were 461 and 42 per 1000 patient-years, respectively. Adjusted results indicated that those with myelosuppression had higher rates of hospitalization (47.4% vs 12.4%; P < .0001) and incurred higher mean inpatient costs ($23,517 vs $12,729; P = .011) and total costs ($57,325 vs $34,733; P = .001) as compared with those without myelosuppression. Similarly, patients with OIs had higher rates of hospitalization (53.8% vs 30.8%; P = .025) and incurred higher mean inpatient costs ($21,494 vs $11,229; P < .0001) as compared with those without OIs.

Conclusions
PNA therapy is highly effective but associated with significant toxicities that increase costs; these findings indicate a need for therapies with improved toxicity profiles and better risk stratification of patients at risk of developing myelosuppression and OIs.
Cervical cancer prevention among long-term screening non-attendees by vaginal self-collected samples for hr-HPV mRNA detection
Authors: Ernstson Avalon , Urdell Annika , Forslund Ola , Borgfeldt Christer 
Published: February 2020

Abstract
Background
The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.
The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample.

Methods
A vaginal self-sampling kit was sent to 6023 women aged 30–70 years who had not provided a cervical screening sample for ≥7 years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14 months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons.

Results
The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4–14.1%] and 9.9% [(79/796), 95% CI 7.9–12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6–2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1–1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed.

Conclusions
Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.
Challenges and lessons learned in re-filming the WHO mhGAP training videos for Sri Lankan context - a qualitative study
Authors: Doherty Shannon , Dass Giselle , Edward Anne , Manolova Gergana , Solomon Madonna 
Published: February 2020

Abstract
Background
Understanding and addressing the unmet mental health needs burden in the Northern Province of Sri Lanka is the subject of the COMGAP-S two-phase study. Phase Two involves the implementation of the World Health Organization’s mental health Gap Action Programme (mhGAP) in primary healthcare settings. As part of the contextual adaptation of mhGAP, eleven of the videos provided in the mhGAP training package have been re-filmed by a local team. We investigated the challenges, barriers and good practices of this adaptation effort from the point of view of team participants.

Methods
Twelve persons from the adaptation team, including students of medicine and drama, doctors, drama lecturers and professionals, consented to in-depth individual interviews following an open-ended topic guide with a member of the COMGAP-S study team. Interviews were recorded, transcribed, translated as necessary, and subjected to thematic analysis.

Results
The majority of participants perceived the process positively and had pride in their involvement. Expectations, opportunities, and exposure were discussed as stemming from the video production. The main challenges derived from the analysis were lack of discussion around budgeting, logistical difficulties, struggles with team cooperation, and creative differences. Issues around exact translation into the local Tamil dialect and modelling around mental health were emphasised by the majority of participants. Potential uses for the videos were identified beyond the current study and recommendations included setting out clear guidance around available funding and role allocation, and increasing the flexibility in adapting the material.

Conclusions
This study illustrated details of the adaptation of existing video materials to facilitate locally-based training for non-specialists on mhGAP curricula. With this, we have added to the knowledge base on conducting cultural and language adaptations and our findings indicate participants felt adapting the mhGAP films to local context was vital to ensuring training materials were culturally appropriate and valid.

Trial registration
This project was nested within the larger COMGAP-S clinical trial. Ethics approval was granted from the Ethics Review Committee, Faculty of Medicine, University of Jaffna (J/ERC/17/81/NDR/0170) and the Faculty Research Ethics Panel, Faculty of Medical Science, Anglia Ruskin University (SC/jc/FMSFREP/16/17076). The project is registered with the Sri Lankan Clinical Trial Registry (SLCTR/2018/008) and listed on the ISRCTN registry (trial ID ISRCTN62598070).
Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT)
Authors: Katulka Riley Jeremy , Al Saadon Abdalrhman , Sebastianski Meghan , Featherstone Robin , Vandermeer Ben , Silver Samuel A. , Gibney R. T. Noel , Bagshaw Sean M. , Rewa Oleksa G. 
Published: February 2020

AbstractIntroductionRenal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT.MethodsA systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis.ResultsOur search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6–76.9%) and specificity of 73.6% (95% CI, 67.5–79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined.ConclusionsNumerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.
Predictability of drug-induced liver injury by machine learning
Authors: Chierici Marco , Francescatto Margherita , Bussola Nicole , Jurman Giuseppe , Furlanello Cesare 
Published: February 2020

Abstract
Background
Drug-induced liver injury (DILI) is a major concern in drug development, as hepatotoxicity may not be apparent at early stages but can lead to life threatening consequences. The ability to predict DILI from in vitro data would be a crucial advantage. In 2018, the Critical Assessment Massive Data Analysis group proposed the CMap Drug Safety challenge focusing on DILI prediction.

Methods and results
The challenge data included Affymetrix GeneChip expression profiles for the two cancer cell lines MCF7 and PC3 treated with 276 drug compounds and empty vehicles. Binary DILI labeling and a recommended train/test split for the development of predictive classification approaches were also provided. We devised three deep learning architectures for DILI prediction on the challenge data and compared them to random forest and multi-layer perceptron classifiers. On a subset of the data and for some of the models we additionally tested several strategies for balancing the two DILI classes and to identify alternative informative train/test splits. All the models were trained with the MAQC data analysis protocol (DAP), i.e., 10x5 cross-validation over the training set. In all the experiments, the classification performance in both cross-validation and external validation gave Matthews correlation coefficient (MCC) values below 0.2. We observed minimal differences between the two cell lines. Notably, deep learning approaches did not give an advantage on the classification performance.

Discussion
We extensively tested multiple machine learning approaches for the DILI classification task obtaining poor to mediocre performance. The results suggest that the CMap expression data on the two cell lines MCF7 and PC3 are not sufficient for accurate DILI label prediction.

Reviewers
This article was reviewed by Maciej Kandula and Paweł P. Labaj.
Effect of an educational booklet for prevention and treatment of foot musculoskeletal dysfunctions in people with diabetic neuropathy: the FOotCAre (FOCA) trial II, a study protocol of a randomized controlled trial
Authors: Silva E. Q. , Suda E. Y. , Santos D. P. , Veríssimo J. L. , Ferreira J. S. S. P. , Cruvinel Júnior R. H. , Monteiro R. L. , Sartor C. D. , Sacco I. C. N. 
Published: February 2020

AbstractBackgroundThis study is a part of a series of two clinical trials. We consider diabetic polyneuropathy (DPN), a common chronic and progressive complication of diabetes mellitus that has several impacts on individuals’ foot health and quality of life. Based on the current trends of self-monitoring and self-care, providing a tool with foot-related exercises and educational care may help patients to avoid or reduce the musculoskeletal complications resulting from DPN, improving autonomous performance in daily living tasks. The aim of this trial is to evaluate the effects of an educational booklet for foot care and foot muscle strengthening on DPN symptoms and severity, clinical outcomes, and gait biomechanics in patients with DPN.Methods/designThe FOotCAre (FOCA) trial II study has been designed as a single-blind, two-parallel-arm randomized controlled trial. It will include 48 patients with DPN who will be randomly allocated to a control (recommended foot care by international consensus with no foot exercises) group or an intervention (foot-related exercises using an educational booklet three times/week at home for 8 weeks) group. Participants from both groups will be assessed at baseline, after 8 weeks, and at 16 weeks for follow-up. The primary outcomes are the DPN symptoms and severity, and the secondary outcomes are foot–ankle kinematics, gait kinetics, plantar pressure distribution during gait, tactile and vibratory sensitivities, foot strength, functional balance, and foot health and functionality.DiscussionThe booklet is a management tool that allows users to be autonomous in their treatment by choosing how and where to perform the exercises. This allows the patients to perform the exercises regularly as a continuous habit for foot care and health, which is an important element in the management of the diabetic foot. As the booklet focuses on specific foot–ankle exercises, we expect that it will improve the clinical aspects of DPN and produce beneficial biomechanical changes during gait, becoming a powerful self-management tool that can be easily implemented to improve the performance of daily living tasks.Trial registrationClinicalTrials.gov,NCT04008745. Registered on 2 July 2019.