bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-Driven Knowledge Graph Filtering Improves Prioritizing Drugs for Repurposing
Authors: Ratajczak Florin , Joblin Mitchell , Ringsquandl Martin , Hildebrandt Marcel 
Published: August 2021

Abstract
Background Drug repurposing aims at finding new targets for already developed drugs. It becomes more relevant as the cost of discovering new drugs steadily increases. To find new potential targets for a drug, an abundance of methods and existing biomedical knowledge from different domains can be leveraged. Recently, knowledge graphs have emerged in the biomedical domain that integrate information about genes, drugs, diseases and other biological domains. Knowledge graphs can be used to predict new connections between compounds and diseases, leveraging the interconnected biomedical data around them. While real world use cases such as drug repurposing are only interested in one specific relation type, widely used knowledge graph embedding models simultaneously optimize over all relation types in the graph. This can lead the models to underfit the data that is most relevant for the desired relation type. We propose a method that leverages domain knowledge in the form of metapaths and use them to filter two biomedical knowledge graphs (Hetionet and DRKG) for the purpose of improving performance on the prediction task of drug repurposing while simultaneously increasing computational efficiency. Results We find that our method reduces the number of entities by 60% on Hetionet and 26% on DRKG, while leading to an improvement in prediction performance of up to 40.8% on Hetionet and 12.4% on DRKG, with an average improvement of 17.5% on Hetionet and 5.1% on DRKG. Additionally, prioritization of antiviral compounds for SARS CoV-2 improves after task-driven filtering is applied. Conclusion Knowledge graphs contain facts that are counter productive for specific tasks, in our case drug repurposing. We also demonstrate that these facts can be removed, resulting in an improved performance in that task and a more efficient learning process.
Integrative RNA-seq and ATAC-seq Analysis of Retinitis Pigmentosa Caused by PDE6 Mutation
Authors: Xu Wenrong , Li Yan , Feng Xiaoxiao , Xiao Libo , Li Lan , Jiao Kangwei 
Published: August 2021

Abstract
Purpose: Inhibition of PARP1 could relieve PDE6 mutation-induced Retinitis pigmentosa (RP). However, the mechanism related with PARP1 overexpression in the RP has not been clarified. We attempted to explore the potential regulatory mechanism related with PARP1 underlying RP. Methods: ATAC-seq and RNA-seq were preformed for retina tissues of C3H and rd1 mice. The differential expressed genes (DEGs) were identified, followed by PARP1-DEG coexpression network, and PPI network construction. GO-BP and pathway enrichment of DEGs of interest were performed by clusterprofiler software. The overlapped genes that might play regulatory role in PARP1 expression were mined by integrated analysis of RNA-seq and ATAC-seq data. Results: Total 1061 DEGs were identified between C3H and rd1 group. Co-expression network was constructed with 313 PARP1-gene coexpression pairs. The down-regulated DEGs were closely related with visual perception, light stimulus related biological process, while the up-regulated DEGs were significantly enriched in phototransduction and PPAR signaling pathway. PPI network was constructed with 202 nodes and 375 edges, which was clustered into 3 modules. Module 1 genes were closely related with detection of light stimulus, visual perception related biological process and phototransduction pathway (involved with Gnat1/Guca1b/Gnat2/Sag/Pde6g). By integrated analysis of the RNA-seq and ATAC-seq, the overlapped up-regulated genes were Asxl3 and Nyap2, while the down-regulated genes were Tmem136 and Susd3. Conclusion: Gnat1 may play a key role in RP development by interacting with PARP1. Susd3 may play a regulatory role in PARP1 expression and affect RP formation.
Comparative Study of the Efficacy of Biofeedback-Assisted Jacobsons Progressive Muscle Relaxation (Jpmr) for Managingmild/Moderate Depression
Authors: baral Swayamprava prava , Raghuvanshi Gyanendra , paliwal Abhay 
Published: August 2021

Abstract
Biofeedback is the way of gaining greater awareness of physiological functions with a goal of self-regulation. JPMR (Jacobsons progressive muscle relaxation) causes release of tension in the skeletal muscles, neuro-muscular system is thus seen as a mediator in the relief of depressive symptoms. This study aimed to see the Comparative efficacy of Biofeedback assisted JPMR, Escitalopram and Bimodal use of both in management in mild/moderate depression. The study was conducted at Mental hospital, Indore, with a Sample Size of 30 [Group A 10 ; biofeedback ,Group B 10 ; Escitalopram ,Group C 10;both]. 8 sessions of biofeedback assisted JPMR was given to group A and C .Escitalopram was given group B and C. HAM-D and BDI was applied at baseline , 4 weeks and 8 weeks. As per BDI scale scores, Biofeedback assisted JPMR combined with escitalopram has significantly better response than only biofeedback or only Escitalopram in patients of mild to moderate depression. As per HAM-D scale scores, Biofeedback assisted JPMR combined with escitalopram has significantly better response than only biofeedback or only Escitalopram in patients of mild to moderate depression. Thus Biofeedback appears to be a useful adjunctive treatment for mild to moderate depressive episode.
A Large-Scale Bibliometric Analysis of Global Climate Change Research Between 2001 and 2018
Authors: Fu Hui-Zhen , Waltman Ludo 
Published: August 2021

Abstract
Global climate change is attracting widespread scientific, political, and public attention owing to the involvement of international initiatives such as the Paris Agreement and the Intergovernmental Panel on Climate Change. We present a large-scale bibliometric analysis based on approximately 120,000 climate change publications between 2001 and 2018 to examine how climate change is studied in scientific research. Our analysis provides an overview of scientific knowledge, shifts of research hotspots, global geographical distribution of research, and focus of individual countries. In our analysis, we identify five key fields in climate change research: physical sciences, paleoclimatology, climate-change ecology, climate technology, and climate policy. We draw the following key conclusions: (1) Over the investigated time period, the focus of climate change research has shifted from understanding the climate system toward climate technologies and policies, such as efficient energy use and legislation. (2) There is an imbalance in scientific production between developed and developing countries. (3) Geography, national demands, and national strategies have been important drivers that influence the research interests and concerns of researchers in different countries. Our study can be used by researchers and policy makers to reflect on the directions in which climate change research is developing and discuss priorities for future research.
Relativity and View Effects
Authors: Fischli Bernard 
Published: August 2021

Abstract
Relativity has been based on the implicit assumption that it would exclusively describe interactions. Relativistic view effects are included as well, and they act with no force and no energy exchanges. The Ehrenfest paradox is solved. View effects specific to each point of view are the solution. The calculation of the deflection of light by the sun explains in detail why the deflection angle must be almost double the value obtained with Newton’s laws. The compatibility of General Relativity with the new interpretation is discussed. An object has no speed limit due to gravitation but it is limited in speed with electromagnetism. Inertial behavior is examined. The equivalence principle does not introduce gravitation to General Relativity. Relativity impacts the energy formula of electromagnetism using the Lorentz factor which also introduces view effects that are optical illusions with no impact on energy.
Ventricular Function in Congenital Diaphragmatic Hernia: A Systematic Review and Meta-Analysis
Authors: Prasad Rameshwar , Saha Bijan , Kumar Amit 
Published: August 2021

Abstract
There is emerging evidence supporting ventricular function as a prognostic factor in congenital diaphragmatic hernia (CDH). The present systematic review and meta-analysis aimed to determine the predictive value of early ventricular function for survival and extracorporeal membrane oxygenation (ECMO) requirement in newborns with CDH. PubMed, Google Scholar, Cochrane Central Register, Clinical Trial Registry, and Opengrey were accessed. Studies evaluating associations between echocardiographic ventricular function measured ≤ 48 h after birth and survival or ECMO requirement were included. Two independent authors extracted the following data: study and participant characteristics, prognostic factors, and outcome-related data. Eleven studies met the inclusion criteria. Five studies reported on survival, two on ECMO, and four on both outcomes. A moderate risk of bias was found in most of the studies, mainly because of selection, prognostic factors, and confounding biases. For survival (899 participants), pooled sensitivity and specificity were 86% (95% confidence interval [CI], 77–92%) and 44% (95% CI, 25–65%), respectively, in normal left ventricular function. For ECMO need (815 participants), pooled sensitivity and specificity were 39.8% (95% CI, 27–52%) and 88% (95% CI, 80–96%), respectively, in left ventricular dysfunction. Overall certainty of the evidence was graded very low for survival and low for ECMO. Inconsistent reporting of echocardiographic measurements and lack of adjustment for confounding factors were major limitations. Conclusions: Early ventricular dysfunction is a potential prognostic factor in CDH. Standardized echocardiographic measurement reporting and high-quality studies are needed to further elucidate its prognostic significance.
A novel Long-noncoding RNA LncZFAS1 prevents MPP+-induced neuroinflammation through MIB1 activation
Authors: Zhu Ziman , Huang Peiling , Sun Ruifeng , Li Xiaoling , Li Wenshan , Gong Weijun 
Published: August 2021

Abstract
Parkinson’s disease remains one of the leading neurodegenerative diseases in developed countries. Despite well-defined symptomology and pathology, the complexity of Parkinson’s disease prevents a full understanding of its’ etiological mechanism. Mechanistically, α-synuclein misfolding and aggregation appears central for disease progression, but mitochondrial dysfunction, dysfunctional protein clearance and ubiquitin/proteasome systems, and neuroinflammation have also been associated with Parkinson’s disease. Particularly neuroinflammation, which was initially thought to be a side effect of Parkinson’s disease pathogenesis, has now been recognized as driver of Parkinson’s disease exacerbation. Next-generation sequencing identified a plethora of long noncoding RNAs (lncRNA) with important transcriptional regulatory functions. Moreover, a myriad of lncRNA are known regulators of inflammatory signaling and neurodegenerative diseases including IL-1β secretion and Parkinson’s disease. Here lncZFAS1 was identified as a regulator of inflammasome activation and pyroptosis in human neuroblast SH-SY5Y cells following MPP+ treatment, a common in vitro Parkinson’s disease cell model. Mechanistically, TXNIP ubiquitination through MIB1 E3 ubiquitin ligase regulates NLRP3 inflammasome activation in neuroblast cells. In contrast MPP+ activates the NLPR3 inflammasome through miR590-3p up-regulation, and direct interference with MIB1-dependent TXNIP ubiquitination. LncZFAS overexpression inhibits this entire pathway through direct interference with miR590-3p exposing a novel therapeutic target to prevent excessive inflammasome activation and pyroptosis in neuroblast cells during Parkinson's disease.
Adherence to Antiretroviral and Cancer Chemotherapy, and Associated Factors Among Patients with HIV–Cancer Co-Morbidity at the Uganda Cancer Institute: A Cross Sectional Study
Authors: Achieng Caroline , Bunani Nelson , Kagaayi Joseph , Nuwaha Fred 
Published: August 2021

Abstract
Background: Human Immunodeficiency Virus is a major global public health issue affecting millions of people, and sub-Saharan Africa where Uganda lies is is disproportionately affected. There has been an increase in cancer among HIV patients which has resulted into use of co-medications that sometimes affect ART and cancer chemotherapy adherence. We aimed to determine adherence to antiretroviral and cancer chemotherapy and the associated factors among patients with HIV-cancer co-morbidity at the Uganda Cancer Institute.Methods: We conducted a cross-sectional study among 200 randomly selected adult cancer patients infected with HIV, attending Uganda cancer institute. Antiretroviral and anti-cancer chemotherapy adherences with associated factors were assessed quantitatively. We collected the data using interviewer administered semi-structured questionnaires. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios at 95% confidence intervals for factors associated with adherence to ART and cancer chemotherapy.Results: Overall, 54% (107/200) of the study participants adhered to both ART and chemotherapy, and 55% (110/200) adhered to ART while 65% (129/200) adhered to cancer chemotherapy. A majority, 61% (122/200) of the respondents were males. The mean age of the respondents was 42(SD±11years), and at least 43% (86/200) belonged to protestant religion. More than half, 56.5% (113/200) were married and at least 45% (90/200) had attained a primary level of education. Patients with good adherence to antiretroviral therapy and chemotherapy were 107(54%, 95% CI=46.5-60.4). No knowledge of cancer stage (PR=0.4, 95% CI=0.25-0.56, P<0.0001), having an AIDS defining cancer (PR=0.7, 95% CI=0.50-0.88, P=0.005), ART clinic in district not near Uganda Cancer Institute (PR=0.7,95% CI=0.84-0.96, P=0.027) and affordability of cancer chemotherapy (PR=1.4, 95% CI=1.02-1.87, P=0.037) were associated with adherence to both ART and cancer chemotherapy.Conclusion: Adherence to both ART and cancer chemotherapy was low. Factors significantly associated with adherence were: knowledge of the cancer stage by the patient, the type of cancer diagnosis, source of ART and affordability/ availability of medications. There is need to provide information on stage of cancer and adherence counseling to patients. Furthermore, Integration of HIV- cancer care will be necessary for efficient and effective care for the patients.
Trends in Opioid Prescribing by County Following Pennsylvania PDMP Implementation.
Authors: MILLER CHAIM , SHERMAN MATTHEW B. , ILYAS ASIF M. 
Published: August 2021

Abstract
Background: The opioid epidemic has hit all corners of the United States but has disproportionately affected geographical areas to varying extents over the last thirty years. Rural areas have had higher rates of opioid prescribing than urban areas. However, urban counties have higher rates of opioid overdose deaths than rural counties. This study aims to outline the trends in opioid prescribing between rural and urban counties in the state of Pennsylvania since the implementation of a statewide prescription drug monitoring program (PDMP).Methods: Data pertaining to opioid prescribing habits as listed below were obtained from the Pennsylvania Department of Health who administers the PDMP in Pennsylvania. Study data that were of interest and provided by the PDMP were: Drug name, quantity of prescriptions, average daily morphine milligram equivalents (MME), and days supplied. Urban and Rural categorizations were provided by The Center for Rural Pennsylvania, a legislative agency of the Pennsylvania General Assembly. The timeline for this study analyses began from Q1 2017 through Q1 2020. T-tests were used to compare the county informationResults: Opioid prescriptions from 2017 to 2020 decreased on average by 35% (SD= 0.13) in rural counties and 33% (SD= 0.10) in urban counties (P= 0.114). Change in average daily MME was 0.13 (SD=0.06) in the rural group and 0.14 (SD=0.03, p=0.229). Days supplied per prescription showed no significant changes between rural and urban counties with regards to; less than 3 days, 4-7 days, 8-21 days, and 31+ days. A significant decrease was seen in the 22–30-day subgroup between the rural (0.36 SD=0.08) and urban counties (0.31 SD=0.04 p=0.003).Conclusion: No significant changes were seen in the decline of opioid prescribing habits between rural and urban counties in Pennsylvania from 2017 to 2020. This compounds on similar state-specific studies showing no significant difference in the rate of decline between rural and urban counties.
Cotton Stalk Compost as a Substitution to Farmyard Manure Along with Mineral Fertilizers and Microbials Enhanced Bt Cotton Productivity and Fibre Quality in Rainfed Vertisols
Authors: Velmourougane Kulandaivelu , Manikandan Angamuthu , Blaise D. , Vellaichamy Mageshwaran 
Published: August 2021

Abstract
Cotton stalks, remaining after the cotton is harvested, are considered waste material and disposed of by burning. Presently, the supply of good quality manure, such as farmyard manure (FYM) is low. Thus, recycling of cotton stalks as compost can reduce the dependency on FYM apart from reducing inorganic fertilizer use and soil health enhancement. Some studies have reported on the conversion of cotton ginnery wastes into organic manure. However, no studies have reported about the composting of cotton stalks. We conducted field studies over three years on Vertisols to evaluate the impact of integrated use of microbially enriched cotton stalk compost (ECC) as an alternative to FYM along with mineral fertilizers in cotton production. Additionally, we evaluated an option of using native microbial consortia as seed treatment and their synergistic effect along with ECC application on cotton yield, fibre quality, and soil properties. Results indicated that the substitution of FYM with ECC in integrated nutrient management (INM) produced effects similar to that of FYM use in enhancing cotton yield and soil properties. Application of ECC + inorganic fertilizers (modified nutrient management practice) in soil increased boll numbers (8.4%), boll weight (9.9%), seed cotton yield (13%), fibre properties, soil nutrient, and biological activities, which were on par with FYM + inorganic fertilizer application. The use of ECC is estimated to reduce 50% costs on nitrogenous, phosphatic, and potassic fertilizers, and can save approximately US$ 34 ha− 1 on inorganic and manures in the recommended dose of fertilizers (RDF) and INM practice.
The ROCK-Ezrin Signaling Pathway Mediates LPS-Induced Cytokine Production in A549 Cells
Authors: Ding Ning , Li Huiqing , Gao Baofeng , Lei Yunlong , Zhang Zengzhen 
Published: August 2021

Abstract
Background: Ezrin/radixin/moesin proteins (ERMs) are members of the protein 4.1 superfamily and function as linkers that connect the actin cytoskeleton to the plasma membrane of cells. ERMs also play critical role in the Lipopolysaccharide (LPS)-induced inflammatory response. However, the signaling mechanisms involved remain unclear. This study aims to investigate the potential role of the rho-associated coiled-coil containing protein kinase (ROCK) pathway in LPS-induced ezrin phosphorylation and cytokine production in A549 cells. Methods: Cultured A549 cells were treated with LPS. The expression and localization of ezrin in A549 cells were analyzed by Western bloting and immunoflurescence. The activation of RhoA/ROCK was assessed by Western bloting and RhoA activity assays. The interaction of ezrin with Syk and myeloid differentiation factor 88 (MyD88)/IL-1R-associated kinase 1 (IRAK-1) was investigated using co-immunoprecipitation. The activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) was measured with electrophoretic mobility shift assay and Western blotting. ELISA and Western bloting were performed to detect tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and high mobility group box 1 protein (HMGB1) release into the culture supernatant and cellular HMGB1 levels.Results: Here, we show that LPS induced ezrin phosphorylation in a concentration- and time-dependent manner. The blockade of RhoA/ROCK inhibited LPS-induced ezrin phosphorylation and its translocation from the cytoplasm to the cell membrane. Co-immunoprecipitation assays further revealed that ezrin associated with Syk constitutively, but only associated with MyD88/IRAK-1 upon LPS challenge. Moreover, LPS-induced p38 and nuclear NF-κB activation was found to be ezrin dependent. The suppression of ezrin by siRNA or the blockade of ROCK activation with Y-27632 reduced the production of TNF-α, IL-1β, and HMGB1 in response to LPS. Conclusions: Our findings reveal a novel regulatory mechanism involving ezrin in LPS induced the production of pro-inflammatory cytokines, and highlight the importance of the RhoA/ROCK-MyD88/IRAK1-ezrin/Syk axis. Data presented in this manuscript provide novel insights into the signaling pathways activated in A549 cells by LPS.
Genetic Variation And Association Mapping of Phenolic, Flavonoid Content And Antioxidant Capacity In USDA Rice Mini-Core Collection
Authors: Li Qingzhu , Ge Yongyi , Wang Lily Yan , Li Kehu 
Published: August 2021

Abstract
Genotypic diversity of total phenolics, flavonoid content and antioxidant capacity in the USDA rice mini-core collection was analyzed. Wide genotypic variation was found in total phenolics, flavonoid content and ABTS antioxidant capacity. Genome-wide association mapping between the three antioxidant traits and 155 SSR markers was conducted using Q + K model which takes both population structure (Q) and relative kinship (K) into consideration. A total of 23 marker trait association were identified with markers from Rc gene showed the strongest association with the three antioxidant traits. Rid12, RM484, RM162, RM5371 were commonly detected for phenolic content, flavonoids content and antioxidant capacity.