bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid publications risk the integrity of science in the era of COVID-19
Authors: Bagdasarian N. , Cross G. B. , Fisher D. 
Published: June 2020

Abstract
Background
Preprint manuscripts, rapid publications and opinion pieces have been essential in permitting the lay press and public health authorities to preview data relating to coronavirus disease 2019 (COVID-19), including the range of clinical manifestations and the basic epidemiology early on in the pandemic. However, the rapid dissemination of information has highlighted some issues with communication of scientific results and opinions in this time of heightened sensitivity and global concern.

Main text
Rapid publication of COVID-19 literature through expedited review, preprint publications and opinion pieces are important resources for the medical scientific community. Yet the risks of unverified information loom large in times when the healthcare community is desperate for information. Information that has not been properly vetted, or opinion pieces without solid evidence, may be used to influence public health policy decisions. We discuss three examples of unverified information and the consequences in this time of high anxiety surrounding COVID-19.

Conclusions
In an era when information can be widely and swiftly disseminated, it is important to ensure that the scientific community is not an inadvertent source of misinformation. This will require a multimodal approach, with buy-in from editors, publishers, preprint servers, authors and journalists. The landscape of medical publications has changed, and a collaborative approach is required to maintain a high standard of scientific communications.
Association between ceramides and coronary artery stenosis in patients with coronary artery disease
Authors: Tu Chenchen , Xie Lan , Wang Zhenjie , Zhang Lili , Wu Hongmei , Ni Wei , Li Caixia , Li Lin , Zeng Yong 
Published: June 2020

Abstract
Background
Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome.

Methods
Five hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk.

Results
After the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642–0.822.

Conclusion
The severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.
Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19)
Authors: Kim Jason , Zhang Jenny , Cha Yoonjeong , Kolitz Sarah , Funt Jason , Escalante Chong Renan , Barrett Scott , Kusko Rebecca , Zeskind Ben , Kaufman Howard 
Published: June 2020

Abstract
Background
The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease-2019 (COVID-19).

Methods
We applied two computational approaches to identify potential therapeutics. First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform. Second, we sought to identify FDA approved drugs that could attenuate the gene expression patterns induced by coronaviruses, using our Disease Cancelling Technology (DCT) platform.

Results
Top results for ACE2 binding iincluded several ACE inhibitors, a beta-lactam antibiotic, two antiviral agents (Fosamprenavir and Emricasan) and glutathione. The platform also assessed specificity for ACE2 over ACE1, important for avoiding counterregulatory effects. Further studies are needed to weigh the benefit of blocking virus entry against potential counterregulatory effects and possible protective effects of ACE2. However, the data herein suggest readily available drugs that warrant experimental evaluation to assess potential benefit. DCT was run on an animal model of SARS-CoV, and ranked compounds by their ability to induce gene expression signals that counteract disease-associated signals. Top hits included Vitamin E, ruxolitinib, and glutamine. Glutathione and its precursor glutamine were highly ranked by two independent methods, suggesting both warrant further investigation for potential benefit against SARS-CoV-2.

Conclusions
While these findings are not yet ready for clinical translation, this report highlights the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warrant further investigation for established and emerging disease processes.
Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder by inducing neutrophil apoptosis
Authors: Gong Ye , Zhang Ya-ling , Wang Zhen , Song Huan-huan , Liu Yuan-chu , Lv Ao-wei , Tian Li-li , Zhu Wen-li , Fu Ying , Ding Xiao-li , Cui Lang-jun , Yan Ya-ping 
Published: June 2020

Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils.

Objective
The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro.

Results
There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo.

Conclusion
Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.
Investigation of Atyp.C using UF-5000 flow cytometer in patients with a suspected diagnosis of urothelial carcinoma: a single-center study
Authors: Ren Chunyun , Wang Xing , Yang Chunwei , Li Shengchao , Liu Shuangchun , Cao Hongcui 
Published: June 2020

Abstract
Background
This study evaluated the predictive power of Atyp.C (a parameter of UF-5000 flow cytometer) for patients with a suspected diagnosis of urothelial carcinoma.

Methods
We analyzed 163 urine specimens from 128 patients with suspected urothelial carcinoma using a fully automated fluorescence flow cytometry analyzer (UF-5000) and evaluated its performance on identifying atypical/malignant urothelial cells. From January 1, 2019 to April 4, 2019, all consecutive specimens for urinary cytopathology were enrolled.

Results
Of the specimens with urinary cytopathology, 67 specimens (41.1%) revealed abnormal findings in cytology analysis. Among them, 20 specimens (12.3%) were diagnosed as atypical urothelial cells, 26 specimens (16.0%) as suspicious for malignancy (S-malignancy), and 21 specimens (12.9%) as confirmed malignancy. The UF-5000 findings were positive in 59 specimens (36.2%); therefore, the agreement with cytopathology was 73.0%. Using follow-up histologic diagnosis of urothelial carcinoma with or without urinary tract cytology (UTCy) as a reference standard (suspicious and confirmed malignancy were the positive criteria for UTCy), the sensitivity was 59.0%, specificity was 82.1%, positive predictive value was 75.0%, negative predictive value was 68.8%, and the agreement was 71.1%.

Conclusions
It is worth knowing and reporting that the Atyp.C assay may be used as an accessory test for patients with suspected urothelial carcinoma, based on its ability to identify high-risk patients who might need closer follow-up or additional medical treatment.
The predictive value of variables measurable in the ambulance and the development of the Predict Sepsis screening tools: a prospective cohort study
Authors: Wallgren Ulrika Margareta , Sjölin Jan , Järnbert-Pettersson Hans , Kurland Lisa 
Published: June 2020

Abstract
Background
Despite sepsis being a time critical condition with a high mortality, it is often not identified in a timely fashion. The aim of the current study was to create a screening tool based on bedside measurable variables predictive of sepsis among ambulance patients with infection according to clinical judgment by ambulance personnel.

Methods
Prospective cohort study of 551 adult patients presenting with suspected infection, performed in the ambulance setting of Stockholm during 2017–2018. 18 variables were measured in the ambulance (8 keywords related to medical history, 6 vital signs, 4 point-of-care blood tests, in addition to age, gender, and comorbidity. Logistic regression, area under the curve (AUC) and classification trees were used to study the association with sepsis. The AUC, sensitivity, specificity, predictive values and likelihood ratios were used to evaluate the predictive ability of sepsis screening models.

Results
The six variables with the strongest association with sepsis were: systolic blood pressure ≤ 100 mmHg, temperature > 38.5 °C, GCS < 15, lactate > 4 mmol/L, gastrointestinal symptoms, and a history of acute altered mental status. These were combined into the Predict Sepsis screening tool 1, with a sensitivity of 0.90, specificity 0.41, AUC 0.77; 95% confidence interval [CI] 0.73–0.81, PPV 0.52, and NPV 0.86. Combining a history of acute altered mental status with GCS < 15 and excluding lactate in the Predict Sepsis screening tool 2 did not noticeably affect the AUC. In addition, the AUCs of these models did not differ noticeably when compared to a model including vital signs alone, with novel calculated cut-offs; the Predict Sepsis screening tool 3.

Conclusions
Systolic blood pressure ≤ 100 mmHg, temperature > 38.5 °C, GCS < 15, lactate > 4 mmol/L, gastrointestinal symptoms, and a history of acute altered mental status demonstrated the strongest association with sepsis. We present three screening tools to predict sepsis with similar sensitivity. The results indicated no noticeable increase of predictive ability by including symptom-variables and blood tests to a sepsis screening tool in the current study population.

Trial registration
NCT03249597.
Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing
Authors: Guo Yusi , Chi Xiaopei , Wang Yifan , Heng Boon Chin , Wei Yan , Zhang Xuehui , Zhao Han , Yin Ying , Deng Xuliang 
Published: June 2020

Abstract
Background
Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging, and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ.

Methods
Mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same batch and passage. Subsequently, changes in proliferative capacity and cell senescence were evaluated by live cell imaging, Cell Counting Kit-8 assay, cell cycle analysis, Ki67 staining, qPCR and Western blot analysis of c-Myc expression, and β-galactosidase staining. Migration ability was evaluated by the transwell migration assay, wound scratch healing, and cell motility tests. Alkaline phosphatase (ALP) staining, Alizarin Red staining, and combined with qPCR and Western blot analyses of Runx2 and BMP2 were performed to elucidate the effects of mitochondria transfer on the osteogenic potential of BMSCs in vitro. After that, in vivo experiments were performed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted at 4 and 8 weeks after transplantation to evaluate osteogenesis in situ. Finally, in order to establish the correlation between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was performed.

Results
Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenesis upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ. Increased OXPHOS activity and ATP production were observed, which upon inhibition by oligomycin attenuated the enhancement of proliferation, migration, and osteogenic differentiation induced by mitochondria transfer.

Conclusions
Mitochondria transfer is a feasible technique to enhance BMSC function in vitro and promote bone defect repair in situ through the upregulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell therapeutic function.
Endothelial colony-forming cells reduced the lung injury induced by cardiopulmonary bypass in rats
Authors: Sun Haibin , Zhao Xiaoqing , Tai Qihang , Xu Guangxiao , Ju Yingnan , Gao Wei 
Published: June 2020

Abstract
Background
Cardiopulmonary bypass (CPB) results in severe lung injury via inflammation and endothelial injury. The aim of this study was to evaluate the effect of endothelial colony-forming cells (ECFCs) on lung injury in rats subjected to CPB.

Methods
Thirty-two rats were randomized into the sham, CPB, CPB/ECFC and CPB/ECFC/L-NIO groups. The rats in the sham group received anaesthesia, and the rats in the other groups received CPB. The rats also received PBS, ECFCs and L-NIO-pre-treated ECFCs. After 24 h of CPB, pulmonary capillary permeability, including the PaO2/FiO2 ratio, protein levels in bronchoalveolar lavage fluid (BALF) and lung tissue wet/dry weight were evaluated. The cell numbers and cytokines in BALF and peripheral blood were tested. Endothelial injury, lung histological injury and apoptosis were assessed. The oxidative stress response and apoptosis-related proteins were analysed.

Results
After CPB, all the data deteriorated compared with those obtained in the S group (sham vs CPB vs CPB/ECFC vs CPB/ECFC/L-NIO: histological score 1.62 ± 0.51 vs 5.37 ± 0.91 vs 3.37 ± 0.89 vs 4.37 ± 0.74; PaO2/FiO2 389 ± 12 vs 233 ± 36 vs 338 ± 28 vs 287 ± 30; wet/dry weight 3.11 ± 0.32 vs 6.71 ± 0.73 vs 4.66 ± 0.55 vs 5.52 ± 0.57; protein levels in BALF: 134 ± 22 vs 442 ± 99 vs 225 ± 41 vs 337 ± 53, all P < 0.05). Compared to the CPB treatment, ECFCs significantly improved pulmonary capillary permeability and PaO2/FiO2. Similarly, ECFCs also decreased the inflammatory cell number and pro-inflammatory factors in BALF and peripheral blood, as well as the oxidative stress response in the lung tissue. ECFCs reduced the lung histological injury score and apoptosis and regulated apoptosis-related proteins in the lung tissue. Compared with the CPB/ECFC group, all the indicators were partly reversed by the L-NIO.

Conclusions
ECFCs significantly reduced lung injury induced by inflammation after CPB.
Shrimp miR-965 induced the human melanoma stem-like cell apoptosis and inhibited their stemness by disrupting the MCL-1-ER stress-XBP1 feedback loop in a cross-species manner
Authors: Wu Wenlin , Xu Chenxi , Zhang Xiaobo , Yu An , Shu Le 
Published: June 2020

AbstractBackgroundMelanoma is a type of aggressive skin cancer with a poor survival rate. The resistance to conventional therapy of this disease is, at least in part, attributed to its cancer stem cell population. However, the mechanism of survival and stemness maintenance of cancer stem cells remains to be investigated.MethodsTumorsphere formation assay was used to study the stem-like property of melanoma stem-like cells (MSLC). Chromatin immunoprecipitation (ChIP), promoter luciferase reporter assay were included for exploring the role of MCL-1 in MSLC and electrophoretic mobility shift assay were used to evaluate the interaction between shrimp miR-965 and human Ago2 protein. Melanoma xenograft nude mice were used to study the inhibition of tumor development.ResultsIn the present study, our results showed that myeloid cell leukemia sequence 1 (MCL-1) knocking down induced ER stress and apoptosis, and the expression reduction of stemness associated genes in MSLC, which implied a significant role of MCL-1 in MSLC. Further study indicated that ER stress agonist (tunicamycin) treatment in MSLC results in the translocation of XBP1, an ER stress sensor, into the nucleus to induce MCL-1 expression through direct binding to the − 313- to − 308-bp region of MCL-1 promoter. In addition, we found that a shrimp-derived miRNA (shrimp miR-965) could interact with the human Ago2 protein and suppressed the human MCL-1 expression by binding to the 3′ UTR of MCL-1 mRNA, thereby inhibiting the MSLC proliferation and stemness in vitro and in vivo in a cross-species manner.ConclusionIn conclusion, we identified an important role of MCL-1-ER stress-XBP1 feedback loop in the stemness and survival maintenance of MSLC, and shrimp miR-965, a natural food derived miRNA, could regulate MSLC stemness and survival by targeting MCL-1 and disrupting the balance of MCL-1-ER stress-XBP1 feedback loop. In conclusion, this study indicated an important mechanism of the regulation of MSLC stemness and survival, otherwise it also demonstrated the significance of cross-species-derived miRNA as promising natural drugs in melanoma therapy.
Existence and Ulam stability results of a coupled system for terminal value problems involving ψ-Hilfer fractional operator
Authors: Abdo Mohammed S. , Shah Kamal , Panchal Satish K. , Wahash Hanan A. 
Published: June 2020

AbstractThe work reported in this paper deals with the study of a coupled system for fractional terminal value problems involving ψ-Hilfer fractional derivative. The existence and uniqueness theorems to the problem at hand are investigated. Besides, the stability analysis in the Ulam–Hyers sense of a given system is studied. Our discussion is based upon known fixed point theorems of Banach and Krasnoselskii. Examples are also provided to demonstrate the applicability of our results.
Generalization of movements in quadruped robot locomotion by learning specialized motion data
Authors: Yamamoto Hiroki , Kim Sungi , Ishii Yuichiro , Ikemoto Yusuke 
Published: June 2020

AbstractMachines that are sensitive to environmental fluctuations, such as autonomous and pet robots, are currently in demand, rendering the ability to control huge and complex systems crucial. However, controlling such a system in its entirety using only one control device is difficult; for this purpose, a system must be both diverse and flexible. Herein, we derive and analyze the feature values of robot sensor and actuator data, thereby investigating the role that each feature value plays in robot locomotion. We conduct experiments using a developed quadruped robot from which we acquire multi-point motion information as the movement data; we extract the features of these movement data using an autoencoder. Next, we decompose the movement data into three features and extract various gait patterns. Despite learning only the “walking” movement, the movement patterns of trotting and bounding are also extracted herein, which suggests that movement data obtained via hardware contain various gait patterns. Although the present robot cannot locomote with these movements, this research suggests the possibility of generating unlearned movements.
Consumer resistance to innovation: smart clothing
Authors: Ju Naan , Lee Kyu-Hye 
Published: June 2020

AbstractSmart clothing is believed to have an enormous growth potential, but at present, it is not so attractive in terms of sales. This study identified various obstacles affecting consumers’ interest in smart clothing. Interviews were conducted with consumers who are resistant to innovation, those who would continue to use their phones and wearable devices of which safety and functionality have already been proven but reject smart clothing. Availability, which refers to the extent to which consumers can use a product or service, is also a significant factor influencing the innovation resistance of smart clothing. It was also observed that consumers reject smart clothing as an act of resisting innovation; many stated that they would not buy smart clothing unless a trustable brand produces it with appropriate functions and lower prices. Some people said that they refuse to purchase smart clothing due to aesthetic dissatisfaction despite the improved quality and performance. These results indicate that manufacturers should consider what functionality or technology would be appropriate to incorporate in clothing while ensuring fashionable styles and availability in many sizes.