bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Transcriptomics of Frog Virus 3 in Infected Frog Tissues Reveal Non-Coding Regulatory Elements and microRNAs in the Ranaviral Genome and Their Potential Interaction With Host Immune Response
Authors: Tian Yun (Simon) , Khwatenge Collins , Li Jiuyi , Andino Francisco De Jesus , Robert Jacques , Sang Yongming (Simon) 
Published: April 2021

Abstract
Background: Frog Virus 3 (FV3) is a large dsDNA virus belonging to Ranaviruses of family Iridoviridae . Ranaviruses infect cold-blood vertebrates including amphibians, fish and reptiles, and contribute to catastrophic amphibian declines. FV3 has a genome at ~105 kb that contains nearly 100 coding genes and 50 intergenic regions as annotated in its reference genome. Previous studies have mainly focused on coding genes and rarely addressed potential non-coding regulatory role of intergenic regions. Results: Using a whole transcriptomic analysis of total RNA samples containing both the viral and cellular transcripts from FV3-infected frog tissues, we detected virus-specific reads mapping in non-coding intergenic regions, in addition to reads from coding genes. Further analyses identified multiple cis -regulatory elements ( CREs ) in intergenic regions neighboring highly transcribed coding genes. These CREs include not only a virus TATA-Box present in FV3 core promoters as in eukaryotic genes, but also viral mimics of CREs interacting with several transcription factors including CEBPs, CREBs, IRFs, NF-κB, and STATs, which are critical for regulation of cellular immunity and cytokine responses. Our study suggests that intergenic regions immediately upstream of highly expressed FV3 genes have evolved to bind IRFs, NF-κB, and STATs more efficiently. Moreover, we found an enrichment of putative microRNA (miRNA) sequences in more than five intergenic regions of the FV3 genome. Our sequence analysis indicates that a fraction of these viral miRNAs is targeting the 3’-UTR regions of Xenopus genes involved in interferon (IFN)-dependent responses, including particularly those encoding IFN receptor subunits and IFN-regulatory factors (IRFs). Conclusions: Using the FV3 model, this study provides a first genome-wide analysis of non-coding regulatory mechanisms adopted by ranaviruses to epigenetically regulate both viral and host gene expressions, which have co-evolved to interact especially in the host IFN response.
Melatonin Ameliorates The Toxicity Induced By Deoxynivalenol In Murine Ovary Granulosa Cells By Antioxidative And Anti-Inflammatory
Authors: Fan Hairui , Wang Shiqin , Wang Haifei , Sun Mingan , Wu Shenglong , Bao Wenbin 
Published: April 2021

Abstract
Background: Deoxynivalenol (DON) is a common fusarium mycotoxin contaminant of food and feedstuff, posing a serious threat to human and animal reproductive system by inducing oxidative stress and inflammation. The antioxidant melatonin participates in immunoregulation, playing a crucial role in animal development. So, our present study aimed to explore DON-induced toxicity in murine ovary granulosa cells (GCs), and assess the potential protective effect of melatonin. Results: Melatonin inhibits DON-induced oxidative stress in murine ovary GCs by decreased the generation of intracellular reactive oxygen species, ameliorates DON-induced mitochondrial dysfunction. And inhibits the inflammatory response through inhibits reduce the activation of NF-κB and phosphorylation of ERK, JNK, and p38 MAPKs induced by DON. Moreover, melatonin significantly improved the down-regulation of reproductive hormone gene expression induced by DON contaminant. These results once again demonstrate the properties of melatonin: antioxidant and anti-inflammatory.Conclusions: Melatonin have beneficial effects on mitigating the toxicity induced by deoxynivalenol in ovary Granulosa Cells. Offer a novel therapeutic strategy against mycotoxin contamination-induce diseases
Safety and Risk Factors of Tinavi Robot-assisted Percutaneous Pedicle Screw Placement in Spinal Surgery
Authors: Zhang Ren-Jie , Zhou Lu-Ping , Zhang Lai , Zhang Hua-Qing , Zhang Jian-Xiang , Shen Cailiang 
Published: April 2021

Abstract
Objective To determine the rates and risk factors of pedicle screw placement accuracy and the proximal facet joint violation (FJV) using TINAVI robot-assisted technique.Methods Patients with thoracolumbar fractures or degenerative diseases were retrospectively recruited from June 2018 and June 2020. The pedicle penetration and proximal FJV were compared in different instrumental levels to identify the safe and risk segments during insertion. Moreover, the factors were also assessed using univariate and multivariate analyses.Results A total of 72 patients with 332 pedicle screws were included in the current study. The optimal and clinically acceptable screw positions were 85.8% and 93.4%. Of the 332 screws concerning the intra-pedicular accuracy, 285 screws (85.8%) were evaluated as grade A according to the Gertzbein and Robbins scale, with the remaining 25 (7.6%), 10 (3.0%), 6 (1.8%), and 6 screws (1.8%) as grade B, C, D, and E. Moreover, in terms of the proximal FJV, 255 screws (76.8%) screws were assessed as grade 0 according to the Babu scale, with the remaining 34 (10.3%), 22 (6.6%), and 21 screws (6.3%) as grade 1, 2, and 3. Furthermore, the univariate analysis showed significantly higher rate of penetration for patients with age＜61 years old, sex of female, thoracolumbar insertion, shorter distance from skin to insertion point, and smaller facet angle. Meanwhile, the patients with the sex of female, BMI <25.9, grade I spondylolisthesis, lumbosacral insertion, longer distance from skin to insertion point, and larger facet angle had a significantly higher rate of proximal FJV. The outcomes of multivariate analyses showed that sex of male (adjusted OR 0.320, 95% CI 0.140–0.732; p =0.007), facet angle ≥45° (adjusted OR 0.266, 95% CI 0.090–0.786; p =0.017), distance from skin to insertion point ≥4.5cm (adjusted OR 0.342, 95% CI 0.134–0.868; p =0.024), and lumbosacral instrumentation (adjusted OR 0.227, 95% CI 0.091–0.566; p =0.001) were independently associated with intra-pedicular accuracy; the L5 insertion (adjusted OR 2.020, 95% CI 1.084–3.766; p =0.027) and facet angle ≥45° (adjusted OR 1.839, 95% CI 1.026–3.298; p =0.041) were independently associated with the proximal FJV.Conclusion TINAVI robot-assisted technique was associated with a high rate of pedicle screw placement and a low rate of proximal FJV. This new technique showed a safe and precise performance for pedicle screw placement in spinal surgery. Facet angle ≥45° is independently associated with both the intra-pedicular accuracy and proximal FJV.
Recurrent Heart Failure in a Patient With the Parachute Device Implantation: A Case Report
Authors: Li Jianghua , Xiong Wei , Dong Shaohong , Li Tangzhiming 
Published: April 2021

Abstract
Background: The parachute device is made to isolate of the aneurysm to exclude the dysfunctional myocardium might be a promising concept to improve clinical prognosis. However, the clinical practice revealed the device might result in death and worsen heart failure (HF). Case presentation: Herein, we report a male subject who received parachute device implantation after the ventricular aneurysm development caused by myocardial infarction. Even with standard treatment, the patient was still hospitalized for six times because of heart failure in the next 19 months and passed away before the transplantation was scheduled. This is a very rare case that a HF subject received parachute device implantation with early death.Conclusions: The progressive maladaptive remodeling would delay the reendothelialization of the device. The subsequent device displacement may enhance the mitral regurgitation and result in poor clinical outcome.Clinical Trial Registration: PARACHUTE China Approval Trial, NCT02240940, Registered September 16, 2014, https://clinicaltrials.gov/ct2/show/NCT02240940
Neutral evolution test of the spike protein of SARS-CoV-2 and its implications in the binding to ACE2
Authors: López-Cortés Georgina I. , Palacios-Pérez Miryam , Zamudio Gabriel S. , Veledíaz Hannya F. , Ortega Enrique , José Marco V. 
Published: April 2021

Abstract
As the SARS-CoV-2 has spread and the pandemic has dragged on, the virus continued to evolve rapidly resulting in the emergence of new highly transmissible variants that can be of public health concern. The evolutionary mechanisms that drove this rapid diversity are not well understood but neutral evolution should open the first insight. The neutral theory of evolution states that most mutations in the nucleic acid sequences are random and they can be fixed or disappear by purifying selection. Herein, we performed a neutrality test to better understand the selective pressures exerted over SARS-CoV-2 Spike protein, as well as in four of the identified health concern variants. Lys and Thr have higher occurrence rate on the Receptor Binding Domain (RBD) than in the overall sequence whereas Cys, His, and importantly Arg have low occurrence rate both in the whole protein and the RBD. Amino acids that have lower occurrence than the expected neutral control influence in the stability and or functionality of the protein. Our results show that most unique mutations either for SARS-CoV-2 or the variants of health concern are under selective pressures, which could be related either to the evasion of the immune system, increasing the virus’ fitness or altering protein – protein interactions with host proteins. Altogether all these forces have shaped the Spike protein. Understanding the evolutionary forces that act upon Spike protein may help designing better treatments and vaccines that target variants of health concern.
Cancer Immunotherapy Based on Carbon-Quantum-Dots
Authors: Liang Tao , Lei Josh Haipeng , Tao Jinsong , Guo Sen , Gao Hanlu , Zhu Lipeng , Zhou Yinning , Liu Youcheng , Xi Long , Tong Haibo , Liu Enshan , Zhang Bohan , Sun Heng , Zhang Huiqi , Luo Kathy Qian , Zhao Qi , Liu Tzu-Ming , Ouyang Defang , Ge Wei , Zheng Ying , Deng Chuxia , Tang Zikang , Qu Songnan 
Published: April 2021

Abstract
Cancer immunotherapy based on carbon-quantum-dots (CQDs) has proven effective. The CQDs composited cancer cell (CM-cancer) exhibit robust customized immunogenicity, which can recruit macrophages and dendritic cells to effectively deliver the cancer antigens into lymph nodes to activate CD8+ T cells, and eventually leads to an anti-cancer immune response all over the body. The CM-cancer is not only able to inhibit primary tumors, but also clearly eliminate metastatic tumors. Our research demonstrates a promising personalized cancer immunotheraputic technology for potential clinical applications.
Assessment of Discharge and Sediment Flows in a River Through a Combined Hydraulic and Hydrologic Routing Technique
Authors: Bulti Abebe Tadesse 
Published: April 2021

Abstract
An advancement on flood routing techniques is important for a good perdiction and forecast of the flow discharge in a river basins. Hydraulic and hydrologic routing techniques are widely applied in most simulation models separately. A combined hydrologic and hydraulic routing method is a recent approach that used to improve the modeling effort in hydrological studies. The main drawback of hydrologic routing methods was inaccuracy on downstream areas of the river basin, where the effect of hydraulic structures and the river dynamics processes are dominant. The hydraulic routing approaches are relatively good on a downstream reaches of a river. This research was done on the Awash River basin, at the upstream areas of a Koka dam. A combined hydrologic and hydraulic approach was used to assess the discharge and sediment flow in the river basin. The hydrologic routing method was applied at an upstream part of a river basin through a SWAT model. HEC-RAS model was applied at the middle and downstream areas of the study basin based on hydraulic routing principle. A combined routing method can improve the result from a simulation process and increases an accuracy on a prediction of the peak flow. It can simulate a flow discharges for both short and long-term duration, with good model performance indicators. Besides, sediment modeling was done by comparing a regression model, SWAT model, and combination of HEC-RAS and SWAT model. The result from the sediment modeling indicates that the regression model and combined model show good agreement in predicting the suspended sediment in the river basin. The integrated application of such different type of models can be one of the option for sediment modeling.
Prevalence and predicting factors of perceived stress among Bangladeshi university students using machine learning algorithms
Authors: Rois Rumana , Ray Manik , Rahman Atikur , Roy Swapan. K. 
Published: April 2021

Abstract
Background: Stress-related mental health problems are one of the most common causes of the burden in university students worldwide. Many studies have been conducted to predict the prevalence of stress among university students, however most of these analyses were predominantly performed using the basic logistic regression model. As an alternative, we used the advanced machine learning approaches for detecting significant risk factors and to predict the prevalence of stress among Bangladeshi university students.Methods: This prevalence study surveyed 355 students from twenty-eight different Bangladeshi universities using questions concerning anthropometric measurements, academic, lifestyles, and health-related information, which referred to the perceived stress status of the respondents (yes or no). Boruta algorithm was used in determining the significant prognostic factors of the prevalence of stress. Prediction models were built using decision tree (DT), random forest (RF), support vector machine (SVM), and logistic regression (LR), and their performances were evaluated using parameters of confusion matrix, ROC curves, and k-fold cross-validation techniques. Results: One-third of university students reported stress within the last 12 months. Students’ pulse rate, systolic and diastolic blood pressures, sleep status, smoking status, and academic background were selected as the important features for predicting the prevalence of stress. Evaluated performance revealed that the highest performance observed from RF (accuracy=0.8972, precision=0.9241, sensitivity=0.9250, specificity=0.8148, AUC=0.8715, k-fold accuracy=0.8983) and the lowest from LR (accuracy=0.7476, precision=0.8354, sensitivity=0.8250, specificity=0.5185, AUC=0.7822, k-fold accuracy=07713) and SVM with polynomial kernel of degree 2 (accuracy=0.7570, precision=0.7975, sensitivity=0.8630, specificity=0.5294, AUC=0.7717, k-fold accuracy=0.7855). The RF model perfectly predicted stress including individual and interaction effects of predictors.Conclusion: The machine learning framework can be detected the significant prognostic factors and predicted this psychological problem more accurately, thereby helping the policy-makers, stakeholders, and families to understand and prevent this serious crisis by improving policy-making strategies, mental health promotion, and establishing effective university counseling services.
Skull Modulated Strategy to Intensify Tumor Treating Fields on Brain Tumor: a Finite Element Study
Authors: Xin Yang , Liu Penghao , Xing Hao , Wen Xiaoyan , Wang Yu , Hu Chunhua , Li Luming , Ma Wenbin 
Published: April 2021

Abstract
Purpose Tumor treating fields (TTFields) are a breakthrough in treating glioblastoma (GBM). Whereas, the intensity cannot be further enhanced, due to the limitation of scalp lesions. Skull remodeling (SR) surgery can elevate the treatment dose of TTFields in the intracranial foci. This study was aimed at exploring the characteristics of SR surgery towards TTFields augmentation.
Methods The simplified multiple-tissue-layer model (MTL) model and realistic head (RH) model were reconstructed through finite element methods (FEM), to simulate the remodeling of the skull, which included skull drilling, thinning, and cranioplasty with PEEK, titanium, cerebrospinal fluid (CSF), connective tissue and autologous bone.
Results Skull thinning could enhance the intensity of TTFields in the brain tumor, with a 10% of increase of average peritumoral intensity (API) by every 1 cm decrease in skull thickness. Cranioplasty with titanium accompanied the most enhancement of TTFields in the MTL model, but CSF was superior in TTFields enhancement when simulated in the RH model. Besides, API increased nonlinearly with the expansion of drilled burr holes. In comparison with the single drill replaced by titanium, 9 burr holes could reach 96.98% of enhancement in API, but it could only reach 63.08% of enhancement under craniectomy of 9-times skull defect area.
Conclusion Skull thinning and drilling could enhance API, which was correlated with the number and area of skull drilling. Cranioplasty with highly conductive material could also augment API, but might not provide clinical benefits as expected.
Keywords Tumor treating fields, skull remodeling, cranioplasty, skull replacement, brain tumor, finite element analysis
Synthesis, In Silico Pharmacokinetics, and Biological Evaluation of Some New Thiazolidinedione as PPAR-γ Agonists and Antibacterial Agents
Authors: Alzhrani Zohor Mohammad Mahdi , Alam Mohammad Mahboob , Nazreen Syed 
Published: April 2021

Background:
The frequent use of antimicrobial agents to treat infections in diabetic patients
make them more drug resistant than non-diabetic patients, which accounts for a higher mortality
rate of diabetic patients. Therefore, it is a necessity today to synthesize new drugs with dual
modes of action as antidiabetic and antibacterial agents. In the present work, new derivatives containing
thiazolidinedione and 1,3,4-oxadiaozle have been synthesized and screened for PPAR-γ and
antibacterial activities.

Methods:
Compounds 5-12 have been synthesized from 2-methoxy benzaldehyde and thiazolidinedione
and characterized using different spectroscopic techniques such as IR, NMR, and mass spectrometry.
These compounds were tested for in vitro PPAR-γ transactivation, PPAR-γ gene expression,
and antibacterial activities. Finally, molecular docking was carried out to see the binding interactions
of molecules with the target protein.

Results:
All the compounds follow the Lipinski rule suggesting the synthesized derivatives have
good drug-likeness properties. Compounds 11 and 12 exhibited promising PPAR-γ transactivation
with 73.69% and 76.50%, respectively, as well as showed significant antibacterial activity with comparable
MIC of 3.12 μg/disc to standard drug amoxicillin. The docking result was found to be consistent
with the in vitro PPAR-γ transactivation results.

Conclusion:
Compounds 11 and 12 can be further investigated as lead molecules for the development
of new and effective antidiabetic and antibacterial agents.
Body Mass Index and Association of Psychological Stress with Exercise
Performance in Military Members: The Cardiorespiratory Fitness and
Hospitalization Events in Armed Forces (CHIEF) Study
Authors: Lin Ko-Huan , Su Fang-Ying , Yang Szu-Nian , Liu Ming-Wei , Kao Chung-Cheng , Nagamine Masanori , Lin Gen-Min 
Published: April 2021

Aims:
To investigate the influence of body mass index (BMI) on the association between psychological stress and physical fitness.
Background: Both obesity and psychological stress reduce exercise performance.
Objective: It is unknown whether obesity may modify the relationship.

Background:
Both obesity and psychological stress reduce exercise performance.

Objective:
It is unknown whether obesity may modify the relationship.

Methods:
A population of 4,080 military subjects in Taiwan was divided to three groups according to the BMI ≥27.0 kg/m2 (obesity), 24.0-26.9 kg/m2 (overweight) and 18.5-23.9 kg/m2 (normal weight). Normal, slight, and great psychological stress was evaluated by the Brief Symptoms Rating Scale (BSRS-5) score ≤5, 6-9, and ≥10, respectively. Aerobic and anaerobic fitness were respectively evaluated by time for a 3000-meter run and numbers of 2-minute sit-ups and 2-minute push-ups. Analysis of covariance (ANCOVA) with adjustments for age and sex was used to determine the relationship.

Results:
The mean time (sec) for a 3000-meter run (standard error) under slight and great stress differed from that under normal stress in the normal weight (881.0 (11.0) and 877.9 (5.8) vs. 862.2 (1.7), p=0.089 and 0.0088, respectively) and in the obesity (928.1 (16.8) and 921.8 (10.7) vs. 895.2 (1.6), p=0.054 and 0.016, respectively), while the differences were not significant in the overweight (877.1 (12.7) and 877.5 (7.1) vs. 867.1 (2.1), both p >0.5). The impacts of the BMI on 2-minute sit-ups had a similar pattern with that on a 3000-meter run whereas the impact of the BMI on 2-minute push-ups was insignificant.

Conclusions:
Mental stress may not affect physical fitness in overweight military personnel. The mechanism is not clear and should be further investigated.
Impact of an Educational Comic to Enhance Patient-Physician–Electronic Health Record Engagement: Prospective Observational Study
Authors: Alkureishi Maria A , Johnson Tyrone , Nichols Jacqueline , Dhodapkar Meera , Czerwiec M K , Wroblewski Kristen , Arora Vineet M , Lee Wei Wei 
Published: April 2021

Background
Electronic health record (EHR) use can impede or augment patient-physician communication. However, little research explores the use of an educational comic to improve patient-physician-EHR interactions.

Objective
To evaluate the impact of an educational comic on patient EHR self-advocacy behaviors to promote patient engagement with the EHR during clinic visits.

Methods
We conducted a prospective observational study with adult patients and parents of pediatric patients at the University of Chicago General Internal Medicine (GIM) and Pediatric Primary Care (PPC) clinics. We developed an educational comic highlighting EHR self-advocacy behaviors and distributed it to study participants during check-in for their primary care visits between May 2017 and May 2018. Participants completed a survey immediately after their visit, which included a question on whether they would be interested in a follow-up telephone interview. Of those who expressed interest, 50 participants each from the adult and pediatric parent cohorts were selected at random for follow-up telephone interviews 8 months (range 3-12 months) post visit.

Results
Overall, 71.0% (115/162) of adult patients and 71.6% (224/313) of pediatric parents agreed the comic encouraged EHR involvement. African American and Hispanic participants were more likely to ask to see the screen and become involved in EHR use due to the comic (adult P=.01, P=.01; parent P=.02, P=.006, respectively). Lower educational attainment was associated with an increase in parents asking to see the screen and to be involved (ρ=−0.18, P=.003; ρ=−0.19, P<.001, respectively) and in adults calling for physician attention (ρ=−0.17, P=.04), which was confirmed in multivariate analyses. Female GIM patients were more likely than males to ask to be involved (median 4 vs 3, P=.003). During follow-up phone interviews, 90% (45/50) of adult patients and all pediatric parents (50/50) remembered the comic. Almost half of all participants (GIM 23/50, 46%; PPC 21/50, 42%) recalled at least one best-practice behavior. At subsequent visits, adult patients reported increases in asking to see the screen (median 3 vs 4, P=.006), and pediatric parents reported increases in asking to see the screen and calling for physician attention (median 3 vs 4, Ps<.001 for both). Pediatric parents also felt that the comic had encouraged them to speak up and get more involved with physician computer use since the index visit (median 4 vs 4, P=.02) and that it made them feel more empowered to get involved with computer use at future visits (median 3 vs 4, P<.001).

Conclusions
Our study found that an educational comic may improve patient advocacy for enhanced patient-physician-EHR engagement, with higher impacts on African American and Hispanic patients and patients with low educational attainment.