bluuebunny/crossref_metadata_2025_split huggingface dataset:
Text-mining clinically relevant cancer biomarkers for curation into the CIViC database
Authors: Lever Jake , Jones Martin R. , Danos Arpad M. , Krysiak Kilannin , Bonakdar Melika , Grewal Jasleen K. , Culibrk Luka , Griffith Obi L. , Griffith Malachi , Jones Steven J. M. 
Published: December 2019

AbstractBackgroundPrecision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic, prognostic, predisposing, and drug response markers is essential. Several knowledgebases have been created by different groups to collate evidence for these associations. These include the open-access Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase. These databases rely on time-consuming manual curation from skilled experts who read and interpret the relevant biomedical literature.MethodsTo aid in this curation and provide the greatest coverage for these databases, particularly CIViC, we propose the use of text mining approaches to extract these clinically relevant biomarkers from all available published literature. To this end, a group of cancer genomics experts annotated sentences that discussed biomarkers with their clinical associations and achieved good inter-annotator agreement. We then used a supervised learning approach to construct the CIViCmine knowledgebase.ResultsWe extracted 121,589 relevant sentences from PubMed abstracts and PubMed Central Open Access full-text papers. CIViCmine contains over 87,412 biomarkers associated with 8035 genes, 337 drugs, and 572 cancer types, representing 25,818 abstracts and 39,795 full-text publications.ConclusionsThrough integration with CIVIC, we provide a prioritized list of curatable clinically relevant cancer biomarkers as well as a resource that is valuable to other knowledgebases and precision cancer analysts in general. All data is publically available and distributed with a Creative Commons Zero license. The CIViCmine knowledgebase is available athttp://bionlp.bcgsc.ca/civicmine/.
Acetylsalicylic acid rescues the immunomodulation of inflamed gingiva-derived mesenchymal stem cells via upregulating FasL in mice
Authors: Yu Tingting , Yan Boxi , Li Jing , Zhang Ting , Yang Ruili , Wang Xuedong , Liu Yan , Liu Dawei 
Published: December 2019

Abstract
Background
Gingiva-derived mesenchymal stem cells (GMSCs) obtained multipotent differentiation and immunomodulatory properties. However, collecting healthy gingival tissues may be challenging in the clinical situation. Thus, in our present study, we aim to evaluate whether the immunomodulatory capacity of gingiva-derived mesenchymal stem cells from inflamed gingival tissues (iGMSCs) is impaired and find a way to rescue their deficient properties.

Methods
We compared the immunomodulation capacity of GMSCs and iGMSCs using an in vitro co-culture system and a mouse colitis model. T cell apoptosis, T helper 17 (Th17), and regulatory T (Treg) cell differentiation were detected by flow cytometry analysis.

Results
We demonstrated that iGMSCs obtained a decreased immunomodulatory capacity compared with GMSCs. Acetylsalicylic acid (ASA) pretreatment was able to rescue iGMSCs’ impaired immunomodulatory properties. Mechanistically, ASA was capable of upregulating the expression of Fas ligand (FasL) in iGMSCs, leading to an improvement in iGMSC-mediated T cell apoptosis and therapeutic efficacy in the treatment in colitis mice.

Conclusions
This study indicates that the deficient immunomodulatory function of iGMSCs could be rescued by ASA pretreatment via upregulating of FasL in mice. This strategy might serve as a practical approach to rescue deficient MSC function for further therapeutic application.
Anti-HIV, antitumor and immunomodulatory activities of paclitaxel from fermentation broth using molecular imprinting technique
Authors: Ryang Junhyok , Yan Yan , Song Yangyang , Liu Fang , Ng Tzi Bun 
Published: December 2019

AbstractIn this study, a single component paclitaxel was obtained from fermentation broth by molecular imprinting technique, and its antiviral, antitumor and immunomodulatory activities were studied. The results showed that paclitaxel had a good inhibitory activity on human breast cancer MCF-7 cells and showed a concentration- dependent relationship with an IC50 of about 15 μg/mL in the sulforhodamine B assay. At the same time, paclitaxel exerted a weak inhibitory activity on cervical cancer Hela cells. In addition, paclitaxel not only inhibited the invasion of HIV-1 pseudovirus into cells, but also exhibited inhibitory activity to a certain extent after viral invasion of the cells. At a paclitaxel concentration of 20 μg/mL, the inhibition of HIV-1 pseudovirus reached about 66%. The inhibition of HIV-1 protease activity was concentration-dependent. At a concentration of 20 μg/mL, the inhibitory effect of paclitaxel on HIV-1 protease was similar to that of the positive control pepstatin A, being 15.8%. The HIV-1 integrase inhibiting activity of paclitaxel was relatively weak. Paclitaxel significantly up-regulated the expression of interleukin-6.
Evaluation of antiviral activity of Bacillus licheniformis-fermented products against porcine epidemic diarrhea virus
Authors: Peng Ju-Yi , Horng Yi-Bing , Wu Ching-Ho , Chang Chia-Yu , Chang Yen-Chen , Tsai Pei-Shiue , Jeng Chian-Ren , Cheng Yeong-Hsiang , Chang Hui-Wen 
Published: December 2019

AbstractBacillus licheniformis (B. licheniformis) is commonly used as probiotic and its secondary metabolites are attractive anti-microbial candidate. In the present study, we aimed to evaluate the antiviral activity of crude extracts from B. licheniformis against porcine epidemic diarrhea virus (PEDV), a highly contagious enveloped porcine virus that has caused great economic loss in pigs. In vivo, PEDV-infected piglets supplemented with air-dried solid state fermentative cultivate containing B. licheniformis-fermented products (BLFP) showed milder clinical symptoms and decreased viral shedding. Importantly, no significant systemic pathological lesions and no reduction in average daily gain were noted in pigs supplemented with the BLFP, which suggests that it is safe for use in pigs. In vitro experiments revealed that while B. licheniformis crude extracts exhibited no toxicity in Vero cells, co-cultivation of B. licheniformis crude extracts with PEDV significantly reduced viral infection and replication. Summarized current results suggest that the B. licheniformis-fermented products could be a novel candidate food additive for reducing the impact of PED on the swine industry.
The occurrence of the multidrug resistance (MDR) and the prevalence of virulence genes and QACs resistance genes in E. coli isolated from environmental and avian sources
Authors: Enany Mohamed E. , Algammal Abdelazeem M. , Nasef Soad A. , Abo-Eillil Sara A. M. , Bin-Jumah May , Taha Ayman E. , Allam Ahmed A. 
Published: December 2019

AbstractColibacillosis is a major disease affecting poultry leads to high morbidity and mortality which causing tremendous economic losses worldwide. These economic disparities are amplified among low and middle-income where sanitation and hygiene are challenged by the increasing demand for quality sources of animal protein. With a view to investigating the prevalence of virulence genes and QACs resistance genes as well as monitoring the antibiogram of E. coli strains, a total of 368 specimens were collected from diseased broiler chickens (n = 226) and environmental sources (n = 142) at large-scale poultry farms in Ismailia Governorate, Egypt. The bacteriological examination proved that E. coli prevalence was 26.76% and 50.44% in the farm environment and diseased broilers, respectively. In tandem, the isolated E. coli strains were serogrouped, determining the most common serotypes were O78, O1:H7, O91:H21 and O126. Isolates were tested for antimicrobial susceptibility against 12 antibiotics, screened for 4 virulence genes (iss, papC, eaeA, and cfaI), and screened for 3 QACs resistance genes (qacEΔ1, qacA/B, and qacC/D). All the tested strains were positive for iss and papC genes, only 20.3% of the tested strains were positive for eaeA gene, moreover, the examined strains were negative to CFAI gene. Furthermore, all the tested strains were positive for qacEΔ1, qacA/B, and qacC/D genes. In conclusion; virulence genes (iss, papC) as well as QACs resistance genes are common in avian Pathogenic E. coli and environmental strains and are mainly associated with multi-drug resistance phenomena.
Existence of traveling wave solutions with critical speed in a delayed diffusive epidemic model
Authors: Cheng Yueling , Lu Dianchen , Zhou Jiangbo , Wei Jingdong 
Published: December 2019

AbstractIn this paper, we prove the existence of a critical traveling wave solution for a delayed diffusive SIR epidemic model with saturated incidence. Moreover, we establish the nonexistence of traveling wave solutions with nonpositive wave speed for this model. Our results solve some open problems left in the recent paper (Z. Xu in Nonlinear Anal. 111:66–81, 2014).
Secernin-1 is a novel phosphorylated tau binding protein that accumulates in Alzheimer’s disease and not in other tauopathies
Authors: Pires Geoffrey , McElligott Sacha , Drusinsky Shiron , Halliday Glenda , Potier Marie-Claude , Wisniewski Thomas , Drummond Eleanor 
Published: December 2019

AbstractWe recently identified Secernin-1 (SCRN1) as a novel amyloid plaque associated protein using localized proteomics. Immunohistochemistry studies confirmed that SCRN1 was present in plaque-associated dystrophic neurites and also revealed distinct and abundant co-localization with neurofibrillary tangles (NFTs). Little is known about the physiological function of SCRN1 and its role in Alzheimer’s disease (AD) and other neurodegenerative diseases has not been studied. Therefore, we performed a comprehensive study of SCRN1 distribution in neurodegenerative diseases. Immunohistochemistry was used to map SCRN1 accumulation throughout the progression of AD in a cohort of 58 patients with a range of NFT pathology (Abundant NFT,n = 21; Moderate NFT,n = 22; Low/No NFT,n = 15), who were clinically diagnosed as having AD, mild cognitive impairment or normal cognition. SCRN1 accumulation was also examined in two cases with both Frontotemporal Lobar Degeneration (FTLD)-Tau and AD-related neuropathology, cases of Down Syndrome (DS) with AD (n = 5), one case of hereditary cerebral hemorrhage with amyloidosis – Dutch type (HCHWA-D) and other non-AD tauopathies including: primary age-related tauopathy (PART, [n = 5]), Corticobasal Degeneration (CBD, [n = 5]), Progressive Supranuclear Palsy (PSP, [n = 5]) and Pick’s disease (PiD, [n = 4]). Immunohistochemistry showed that SCRN1 was a neuronal protein that abundantly accumulated in NFTs and plaque-associated dystrophic neurites throughout the progression of AD. Quantification of SCRN1 immunohistochemistry confirmed that SCRN1 preferentially accumulated in NFTs in comparison to surrounding non-tangle containing neurons at both early and late stages of AD. Similar results were observed in DS with AD and PART. However, SCRN1 did not co-localize with phosphorylated tau inclusions in CBD, PSP or PiD. Co-immunoprecipitation revealed that SCRN1 interacted with phosphorylated tau in human AD brain tissue. Together, these results suggest that SCRN1 is uniquely associated with tau pathology in AD, DS and PART. As such, SCRN1 has potential as a novel therapeutic target and could serve as a useful biomarker to distinguish AD from other tauopathies.
A metastable subproteome underlies inclusion formation in muscle proteinopathies
Authors: Ciryam Prajwal , Antalek Matthew , Cid Fernando , Tartaglia Gian Gaetano , Dobson Christopher M. , Guettsches Anne-Katrin , Eggers Britta , Vorgerd Matthias , Marcus Katrin , Kley Rudolf A. , Morimoto Richard I. , Vendruscolo Michele , Weihl Conrad C. 
Published: December 2019

AbstractProtein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and aggregation-prone, and form a metastable subproteome. It is not yet clear, however, whether this phenomenon is also associated with non-neuronal protein conformational disorders. To respond to this question, we analyzed proteomic datasets from biopsies of patients with genetic and acquired protein aggregate myopathy (PAM) by quantifying the changes in composition, concentration and aggregation propensity of proteins in the fibers containing inclusions and those surrounding them. We found that a metastable subproteome is present in skeletal muscle from healthy patients. The expression of this subproteome escalate as proteomic samples are taken more proximal to the pathologic inclusion, eventually exceeding its solubility limits and aggregating. While most supersaturated proteins decrease or maintain steady abundance across healthy fibers and inclusion-containing fibers, proteins within the metastable subproteome rise in abundance, suggesting that they escape regulation. Taken together, our results show in the context of a human conformational disorder that the supersaturation of a metastable subproteome underlies widespread aggregation and correlates with the histopathological state of the tissue.
Lifelong Machine Learning and root cause analysis for large-scale cancer patient data
Authors: Pal Gautam , Hong Xianbin , Wang Zhuo , Wu Hongyi , Li Gangmin , Atkinson Katie 
Published: December 2019

Abstract
Introduction
This paper presents a lifelong learning framework which constantly adapts with changing data patterns over time through incremental learning approach. In many big data systems, iterative re-training high dimensional data from scratch is computationally infeasible since constant data stream ingestion on top of a historical data pool increases the training time exponentially. Therefore, the need arises on how to retain past learning and fast update the model incrementally based on the new data. Also, the current machine learning approaches do the model prediction without providing a comprehensive root cause analysis. To resolve these limitations, our framework lays foundations on an ensemble process between stream data with historical batch data for an incremental lifelong learning (LML) model.

Case description
A cancer patient’s pathological tests like blood, DNA, urine or tissue analysis provide a unique signature based on the DNA combinations. Our analysis allows personalized and targeted medications and achieves a therapeutic response. Model is evaluated through data from The National Cancer Institute’s Genomic Data Commons unified data repository. The aim is to prescribe personalized medicine based on the thousands of genotype and phenotype parameters for each patient.

Discussion and evaluation
The model uses a dimension reduction method to reduce training time at an online sliding window setting. We identify the Gleason score as a determining factor for cancer possibility and substantiate our claim through Lilliefors and Kolmogorov–Smirnov test. We present clustering and Random Decision Forest results. The model’s prediction accuracy is compared with standard machine learning algorithms for numeric and categorical fields.

Conclusion
We propose an ensemble framework of stream and batch data for incremental lifelong learning. The framework successively applies first streaming clustering technique and then Random Decision Forest Regressor/Classifier to isolate anomalous patient data and provides reasoning through root cause analysis by feature correlations with an aim to improve the overall survival rate. While the stream clustering technique creates groups of patient profiles, RDF further drills down into each group for comparison and reasoning for useful actionable insights. The proposed MALA architecture retains the past learned knowledge and transfer to future learning and iteratively becomes more knowledgeable over time.
Describing a “mass shooting”: the role of databases in understanding burden
Authors: Booty Marisa , O’Dwyer Jayne , Webster Daniel , McCourt Alex , Crifasi Cassandra 
Published: December 2019

Abstract
Background
The mass shooting phenomenon has gained much attention lately as this form of gun violence appears to increase in frequency. Although many organizations collect information on mass shootings (fatal and nonfatal injuries), no federal definition of this phrase exists. The purpose of this study was to highlight the different statistics that result among databases that define and track “mass shootings.” Establishing definitive guidelines for a mass shooting definition could improve research credibility when presenting evidence to policy makers.

Methods
We obtained data for mass shootings that occurred in 2017 from four sources: Gun Violence Archive, Mother Jones Investigation, Everytown for Gun Safety, and FBI’s Supplemental Homicide Report. We also examined FBI’s Active Shooter Report to compare the mass shootings datasets with active shooter situations, which have been federally defined. First, we examined the overlap among databases. Then, we applied the strictest fatal mass shooting definition to the mass shooting datasets to determine whether the differences in databases could be contributing to differences in fatalities and injuries recorded.

Results
Gun Violence Archive recorded the most mass shooting incidents at 346 incidents in 2017, while Mother Jones only recorded 11 cases. Only 2 events were found in all four mass shooting datasets. When the strictest definition – four or more individuals fatally shot – was applied to all datasets, the number of mass shootings in 2017 ranged from 24 (Gun Violence Archive) to 5 (Mother Jones), but incidents collected still varied.

Conclusions
There is much variety in statistics obtained from the different sources that have collected mass shooting information, with little overlap among databases. Researchers should advocate for a standard definition that considers both fatalities and nonfatalities to most appropriately convey the burden of mass shootings on gun violence.
CT-assessed sarcopenia is a predictive factor for both long-term and short-term outcomes in gastrointestinal oncology patients: a systematic review and meta-analysis
Authors: Su Huaiying , Ruan Junxian , Chen Tianfeng , Lin Enyi , Shi Lijing 
Published: December 2019

Abstract
Background
The impact of sarcopenia on the outcome of gastrointestinal (GI) oncological patients is still controversial. We aim to discuss the prevalence of sarcopenia and its relation to the oncological outcome.

Methods
Embase, Medline, PubMed, and the Cochrane library were systematically searched for related keywords. Studies using CT to assess sarcopenia and evaluate its relationship with the outcome of GI oncological patients were included. Long-term outcomes, including overall survival and disease-free survival, were compared by hazard ratios (HRs) with 95% confidence intervals (CIs). Short-term outcomes, including total complications and major complications (Clavien-Dindo ≥IIIa) after curable surgery, were compared by the risk ratio (RR) and 95% CI.

Results
A total of 70 studies including 21,875 patients were included in our study. The median incidence of sarcopenia was 34.7% (range from 2.1 to 83.3%). A total of 88.4% of studies used skeletal muscle index (SMI) in the third lumbar level on CT to define sarcopenia, and a total of 19 cut-offs were used to define sarcopenia. An increasing trend was found in the prevalence of sarcopenia when the cut-off of SMI increased (β = 0.22, 95% CI = 0.12–0.33, p < 0.001). The preoperative incidence of sarcopenia was associated both with an increased risk of overall mortality (HR = 1.602, 95% CI = 1.369–1.873, P < 0.001) and with disease-free mortality (HR = 1.461, 95% CI = 1.297–1.646, P < 0.001). Moreover, preoperative sarcopenia was a risk factor for both total complications (RR = 1.188, 95% CI = 1.083–1.303, P < 0.001) and major complications (RR = 1.228, 95% CI = 1.042–1.448, P = 0.014).

Conclusion
The prevalence of sarcopenia depends mostly on the diagnostic cut-off points of different criteria. Preoperative sarcopenia is a risk factor for both long-term and short-term outcomes.
Advanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d’Oncologie Pédiatrique
Authors: Bouda Gabrielle C. , Traoré Fousseyni , Couitchere Line , Raquin Marie-Anne , Guedenon Koffi M. , Pondy Angele , Moreira Claude , Rakotomahefa Mbola , Harif Mhamed , Patte Catherine 
Published: December 2019

PURPOSE To evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers. PATIENTS AND METHODS Children with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP–Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m2. RESULTS Four hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% ( P = .0062) beyond 34 days. CONCLUSION The GFA-LMB2009 protocol improved patients’ survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.