bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial Intelligence Improves the Accuracy of Residents in the Diagnosis of Hip Fractures –A Multicenter Study
Authors: SATO YOICHI , TAKEGAMI YASUHIKO , ASAMOTO TAKAMUNE , ONO YUTARO , TSUGENO HIDETOSHI , GOTO RYOSUKE , KITAMURA AKIRA , HONDA SEIWA 
Published: September 2020

Abstract
BackgroundLess experienced clinicians sometimes make misdiagnosis of hip fractures. We developed computer-aided diagnosis (CAD) system for hip fractures on plain X-rays using a deep learning model trained on a large dataset. In this study, we examined whether the accuracy of the diagnosis of hip fracture of the residents could be improved by using this system.MethodsA deep convolutional neural network approach was used for machine learning. Pytorch 1.3 and Fast.ai 1.0 were applied as frameworks, and an EfficientNet-B4 model (a pre-trained ImageNet model) was used. We handled the 5295 X-rays from the patients with femoral neck fracture or femoral trochanteric fracture from 2009 to 2019. We excluded cases in which the bilateral hips were not included within an image range, and cases of femoral shaft fracture and periprosthetic fracture. Finally, we included 5242 AP pelvic X-rays from 4,851 cases. These images were divided into 5242 images that included the fracture site and 5242 images that did not. Thus, a total of 10484 images were used for machine learning. The accuracy, sensitivity, specificity, F-value, and area under the curve (AUC) were assessed. Gradient-weighted class activation mapping (Grad-CAM) was used to conceptualize the basis for the diagnosis of the fracture by the deep learning algorithm. Secondly, we conducted a controlled experiment with clinicians. Thirty-one residents and four orthopedic surgery fellows were tested using 300 hip fracture images that were randomly extracted from the dataset. We evaluated the diagnostic accuracy with and without the use of the CAD system for each of the 300 images.ResultsThe accuracy, sensitivity, specificity, F-value, and AUC were 96.1%, 95.2%, 96.9%, 0.961, and 0.99, respectively, with the correct diagnostic basis generated by Grad-CAM. In the controlled experiment, the diagnostic accuracy of the residents significantly improved when they used the CAD system.ConclusionsWe developed a newly CAD system with a deep learning algorithm from a relatively large dataset from multiple institutions. Our system achieved high diagnostic performance. Our system improved the diagnostic accuracy of residents for hip fractures.Level of EvidenceLevel Ⅲ, Foundational evidence, before-after study. Clinical relevance: high
Neuropilin 1 and Neuropilin 2 Gene Invalidation or Pharmacological Inhibition Reveals Their Relevance for the Treatment of Metastatic Renal Cell Carcinoma
Authors: Dumond Aurore , Brachet Etienne , Durivault Jérôme , Vial Valérie , Puszko Anna K. , Lepelletier Yves , Montemagno Christopher , Pagnuzzi-Boncompagni Marina , Hermine Olivier , Garbay Christiane , Lagarde Nathalie , Montes Matthieu , Demange Luc , Grépin Renaud , Pagès Gilles 
Published: September 2020

Abstract
Background: Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent ®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analysed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.Methods: We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. Their proliferation and migration were evaluated by XTT or impedance tests and by wound closure. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were performed in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking on both NRPs was performed.Results: Invalidation of the NRP1 and NRP2 genes inhibited cell proliferation and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell proliferation and migration more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice in a reverse dose dependent manner. Such inhibition was associated with a decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that NRP2, more than NRP1 correlates with tumor aggressiveness only in metastatic patients.Conclusion: Our study strongly suggests that inhibiting NRP is a good therapeutic strategy for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.
Modulation of human mesenchymal stem cells by electrical stimulation using an enzymatic biofuel cell
Authors: Jeon Won-Yong , Mun Seyoung , Ng WeiBeng , Kang Keunsoo , Han Kyudong , Hwang Sohyun , Kim Hyug-Han , Lee Jae Ho 
Published: September 2020

Abstract
Background
Enzymatic biofuel cells (EBFCs) have excellent potential as components in wearable sensors and bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing.
Materials
We tested three different electrical currents,127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). Also we observed changes in cytoskeleton arrangement and analyzed gene expression depends on the electrical stimulation.
Results
The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC.
Conclusion
Taken together, the findings in this study demonstrate that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells and such capabilities can be useful for regenerative medicine applications related to wearable sensors and devices.
An Intrinsic Hydroquinone-Functionalized AIE Core with Dual Sensitivity via Integrated Molecular Design
Authors: Wang Mengshi , Wang Yuanheng , Hu Renjian , Yuan Jinying , Tian Mei , Zhang Xiaoyong , Shuai Zhigang , Wei Yen 
Published: September 2020

Abstract
A new aggregation-induced emission (AIE) luminescence core, 1-hydroquinol-1,2,2-triphenylethene (HQTPE), has been designed and synthesized for the first time. This AIE core is amazingly simple but is fundamentally important to chemistry because of its intrinsic redox and pH activities. The incorporation of hydroquinone (HQ) moiety into a common AIE core tetraphenylethene (TPE) yields HQTPE with unique fluorescent properties over most other AIEgens so far reported. There are tremendous differences of photochemcical properties between HQTPE, 1-benzoquinol-1,2,2-triphenylethene (QTPE, the oxidized counterpart) and its anions. Interestingly, as the solution concentration is increased, AIEgen HQTPE shows stronger fluorescence but QTPE exhibits rapid quenching of fluorescence in a nonlinear fashion, which are in agreement with theoretical studies. The fluorescence of HQTPE is also highly dependent of pH value of media. We have further explored HQTPE as an ultrasensitive redox probe and efficient deoxidizer, which could lead to many potential applications in health care, food security, environmental monitoring, optic and electronic devices.
Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT
Authors: Zhao Yao , Cai Chenchen , Shi Lubing , Wang Jiwei , Zhang Miaomiao , Zhang Haoliang , Ma Ping , Li Shibao 
Published: September 2020

Abstract
Background
Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is still unclear.
Methods
We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting.
Results
We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers.
Conclusions
These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.
Re-Examining Public Debt and Current Account Dynamics in Ethiopia: SVAR Evidence
Authors: Melesse Wondemhunegn Ezezew 
Published: September 2020

Abstract
Public debt management is now an integral part of overall macroeconomic management in many developing and emerging market economies. Preventing unsustainable debt accumulation and maintaining healthy fiscal profile begins with understanding its key drivers both in the short- and in the long run. This study applies structural vector auto-regressive (SVAR) model on annual time series data to study general government debt and current account dynamics in Ethiopia for the period 1980–2018. Both the impulse response and forecast error variance decomposition results confirm that fiscal balance exerts the strongest influence on both government debt and current account balance in the short run. In addition, own shock as well as shocks stemming from gross fixed capital formation and growth have significant effects on general government debt. The findings were robust to alternative data transformation, differing Choleski ordering of the model variables, and inclusion of exogenous deterministic terms that capture changes in the political landscape.JEL classification: E60, E63, C32, H63
Predicting Response to Tocilizumab Monotherapy in Rheumatoid Arthritis: A Real-World Data Analysis Using Machine Learning
Authors: Johansson Fredrik D , Collins Jamie E , Yau Vincent , Guan Hongshu , Kim Seoyoung C , Losina Elena , Sontag David , Stratton Jacklyn , Trinh Huong , Greenberg Jeffrey , Solomon Daniel H 
Published: September 2020

Abstract
Background Tocilizumab (TCZ) had similar efficacy when used as monotherapy or in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCT). Recently, we derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data. Herein, we describe external validation and several extensions of the prediction score using “real world data” (RWD).MethodsWe identified patients in Corrona-RA who used TCZm (n=453), matching the design and patients from four RCTs used in previous work (n=853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic DMARD monotherapies (bDMARDm) to improve prediction.ResultsThe fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n=53) in RWD vs 15% (n=127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTS with AUROC of 0.70 (95% CI 0.64, 0.77). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on TCZm patients to 0.73 (95% CI 0.64, 0.82). Extending the variable set and adding regularization further increased it to 0.77 (95% CI 0.68, 0.85).ConclusionThe remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD, including a larger variable set and learning from patients on similar therapies.
Low levels of PCSK9 are Associated with Remission in Patients with Rheumatoid Arthritis Treated with Anti- TNF-α: Potential Underlying Mechanisms
Authors: Frostegård Johan , Ahmed Sabbir , Hafström Ingiäld , Ajeganova Sofia , Rahman Mizanur 
Published: September 2020

Abstract
Background Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) which raises LDL-levels. In addition, PCSK9 has proinflammatory immunological effects. Here we investigate the role of PCSK9 as to the inflammatory activity in patients with rheumatoid arthritis (RA). Methods PCSK9-levels were determined at baseline by ELISA in 160 patients with RA not previously treated with biologics. The patients started anti- TNF-α (adalimumab, infliximab, or etanercept) treatment and were followed up for one year. Disease activity was determined by DAS28. Effects of PCSK9 on cytokine production from macrophages of healthy individuals and synoviocytes from RA patients and inhibition by anti-PCSK9 antibodies were studied in supernatants by ELISA. Results A significantly lower level of PCSK9 at baseline, p=0.035, was observed in patients who reached remission within one year, defined as DAS28<2.6, compared to those not in remission. At 12 months of TNF-α antagonist treatment, the mean DAS28 was reduced but was significantly greater in patients with highest quartile PCSK9 (Q4) compared to those at lowest PCSK9 (Q1) in both crude (p=0.01) and adjusted analysis (p=0.004). In vitro, PCSK9 induced TNF-alpha and IL-1beta in macrophages and monocyte chemoattractant protein-1 (MCP1) in synoviocytes. These effects were inhibited by anti-PCSK9 antibodies. Conclusions Low levels of PCSK9 at baseline is associated with being DAS28-responder to anti-TNF-α treatment in RA. An underlying cause could be that PCSK9 stimulates production of proinflammatory cytokines from macrophages and synoviocytes, effects inhibited by anti-PCSK9 antibodies. PCSK9 could thus play an immunological role in RA.
LncRNA PCED1B-AS1 is Overexpressed in Hepatocellular Carcinoma and Regulates miR-10a/BCL6 axis to Promote Cell Proliferation
Authors: Ding Haitao , He Juan , Xiao Weili , Ren Zhihong , Gao Wanting 
Published: September 2020

Abstract
Background: PCED1B-AS1 has been characterized as an oncogene in glioma, while its role in hepatocellular carcinoma (HCC) is unknown. This study was performed to analyze the involvement of PCED1B-AS1.Methods: Expression of PCED1B-AS1 in paired HCC and non-tumor tissues from 62 HCC patients was determined by RT-qPCR. The correlation between PCED1B-AS1 and miR-10a or BCL6 was analyzed by linear regression. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of PCED1B-AS1 for HCC. The interactions among PCED1B-AS1, miR-10a and BCL6 were analyzed by overexpression experiments. Cell proliferation was analyzed by CCK-8 assay.Results: PCED1B-AS1 was upregulated in HCC and predicted poor survival. Across HCC tissues, PCED1B-AS1 was inversely correlated with miR-10a, and positively correlated with BCL6 mRNA. In HCC cells, PCED1B-AS1 overexpression mediated the downregulation of miR-10a and upregulation of BCL6. Moreover, PCED1B-AS1 overexpression reduced the inhibitory effects of miR-10a overexpression on BCL6 expression and cell proliferation. Conclusions: PCED1B-AS1 is overexpressed in HCC and regulates miR-10a/BCL6 axis to promote cell proliferation.
Body mass index associated with severity and mortality of patients with coronavirus disease 2019: A systematic review and meta-analysis
Authors: Fang Chao , Zhou Zheng , Zhou Mingming , Li Jianping 
Published: September 2020

Abstract
Background

As an important indicator to measure obesity or underweight, body mass index (BMI) can be used to assess the potential risk for various diseases. The present study systematically examined the relationship between BMI and severity and mortality of patients with coronavirus disease 2019 (COVID-19).
Methods

We systematically searched PubMed, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) for studies published as of September 3, 2020 and extracted the relevant data of research endpoints in each study.
Results

This study included 16 studies with 6087 patients. This study observed a significant increase in BMI on admission in patients with severe COVID-19 compared with those with non-severe COVID-19 (Mean difference [MD] = 1.95, 95% confidence interval [CI], 1.52 − 2.37, I2 = 33%, P < 0.00001). A significant increase in BMI on admission was observed in patients who died from COVID-19 compared with (MD = 3.01, 95% CI: 1.83 to 4.19, I2 = 0%, P < 0.00001). In the intensive care unit (ICU) or geriatric ward, the study observed a significant decrease in BMI in the non-survivor group compared with the survivor group (MD = -1.61, 95% CI: -3.07 to -0.16, I2 = 72%, P = 0.03).
Conclusions

Higher BMI on admission is associated with severity and mortality of patients with COVID-19, but lower BMI is associated with mortality of patients with COVID-19 in the ICU or geriatric ward. Thus, we strongly recommend that clinicians should closely monitor the BMI of patients with COVID-19, especially those from the ICU or geriatric ward.
Bacterial and Fungal Growth in Sputum Cultures from 165 COVID-19 Pneumonia Patients Requiring Intubation: Evidence for Antimicrobial Resistance Development and Analysis of Risk Factors
Authors: Liu Hans H , Yaron David , Piraino Amanda Stahl , Kapelusznik Luciano 
Published: September 2020

Abstract
Background: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. Methods: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1,058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05.Results: Average patient age was 68.7 years. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall were evaluated and did not suggest acute bacterial or fungal infection in 89 (54%) of 165 individuals sampled within 24 hours of intubation. Cultures > one week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus.Conclusions: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum suggest antibacterials are not needed. Discontinuation of empiric antibacterials should be considered after 48 hours in absence of sputum to culture or results reported "without growth" or "normal flora." Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance.Trial registration: Not applicable as this was a retrospective chart review study without interventional arm.
First detection of a plasmid-encoded New-Delhi metallo-beta-lactamase-1 (NDM-1) producing Acinetobacter baumannii using whole genome sequencing, isolated in a clinical setting in Benin
Authors: YEHOUENOU Carine Laurence , BOGAERTS Bert , VANNESTE Kevin , ROOSENS Nancy , DE KEERSMAECKER Sigrid , MARCHAL Kathleen , AFFOLABI Dissou , SOLEIMANI Reza , RODRIGUEZ_VILLALOBOS Hector , VAN-BAMBEKE Françoise , DALLEUR Olivia , SIMON Anne 
Published: September 2020

Abstract
Background
Carbapenem-resistant Acinetobacter baumannii is considered a top priority pathogen by the World Health Organization for combatting increasing antibiotic resistance and development of new drugs. Since it was originally reported in Klebsiella pneumoniae in 2009, the quick spread of the blaNDM−1 gene encoding a New-Delhi metallo-beta-lactamase-1 (NDM-1) is increasingly recognized as a serious threat. This gene is usually carried by large plasmids and has already been documented in diverse bacterial species, including A. baumannii. Here, we report the first detection of a NDM-1-producing A. baumannii strain isolated in Benin.
Case presentation:
A 31-year-old woman was admitted to a surgical unit with a diagnosis of post-cesarean hematoma. An extensively-drug resistant A. baumannii strain solely susceptible to amikacin, colistin and ciprofloxacin, and resistant to several other antibiotics including ceftazidime, imipenem, meropenem, gentamicin, tobramycin, ceftazidime/avibactam, and sulfamethoxazole-trimethoprim, was isolated from the wound. Production of NDM-1 was demonstrated by immunochromatographic testing. Whole genome sequencing of the isolate confirmed the presence of blaNDM−1, but also antibiotic resistance genes against multiple beta-lactamases and other classes of antibiotics, in addition to several virulence genes. Moreover, the blaNDM−1 gene was found to be present in a Tn125 transposon integrated on a plasmid.
Conclusions
The discovery of this extensively-drug resistant A. baumannii strain carrying blaNDM−1 in Benin is worrying, especially because of its high potential risk of horizontal gene transfer due to being integrated in a transposon located on a plasmid. Strict control and prevention measures should be taken, once NDM-1 positive A. baumannii has been identified to prevent transfer of this resistance gene to other Enterobacterales. Capacity building is required by governmental agencies to provision suitable antibiotic treatment options and strategies, in combination with strengthening laboratory services for detection and surveillance of this pathogen.