bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of COVID-19-related Clinical Studies and Factors Affecting the Recruitment and Completeness: a Large Cross-sectional Study
Authors: Lei Mingxing , Li Jinglan , Lv Houchen , Lin Feng , Zhang Licheng 
Published: August 2021

Abstract
Background: Coronavirus disease 2019 (COVID-19) has generated an unprecedented clinical research response, but the data about the characteristics of COVID-19-related clinical studies were scarce. The study aimed to describe the characteristics of COVID-19-related clinical studies registered at ClinicalTrials.gov and further identify factors affecting the recruitment and completeness of these studies.Methods: The study extracted 5,672 studies and included 5,430 studies relating to COVID-19 registered at ClinicalTrials.gov. We presented the characteristics of all included clinical studies. Identification of risk factors for recruitment status was achieved using the multiple logistic regression models, and identification of risk factors for completion time was obtained using the multiple Cox proportional hazards regression models. Subgroup analyses were also performed in the interventional studies. Results: Of the included studies, only 19.59% (1064/5430) had completed recruitment, and 55.93% (3037/5430) were interventional studies. The peak of the number of clinical studies relating to COVID-19 was seven months earlier than the first peak of the number of COVID-19 cases globally. In all included studies, participants only including male (P=0.02), Participants including child (P=0.01), smaller enrollment (P<0.01), and studies not being funded by industry (P=0.01) and the National Institutes of Health (NIH) (P<0.01), and observational studies (P<0.01) tended to be associated to higher completed recruitment rates. Regarding the interventional studies, Participants including child (P=0.04), smaller enrollment (P<0.01), a crossover intervention model (P<0.01), and primary purpose involving in device feasibility (P<0.01) and treatment (P=0.03) were associated with shorter completion time, while being funded by industry (P=0.01) and NIH (P<0.01), primary purpose involving in basic science (P<0.01), and biological interventions (P<0.01) were associated with longer completion time.Conclusion: A multitude of clinical studies relating to COVID-19 are registered in responding to the pandemic and the response is rapid and timely, but these clinical studies are frequently not completed. Increased focus on establishing global initiatives and networks to coordinate recruitment efforts may be needed. Several independent risk factors are identified to guide the design of COVID-19-related clinical studies. This may be significant to avoid waste and ensure that the participation of all participants in clinical researches contributes to the treatment or prevention of COVID-19.
Novel Therapeutic Mechanism of Action of Metformin and Its Nanoformulation in Alzheimer's Disease and Role of AKT/ERK/GSK Pathway.
Authors: Kumar Harish , Chakrabarti Amitava , Sarma Phulen , Modi Manish , Banerjee Dibyajyoti , Radotra B.D. , Bhatia Alka , Medhi Bikash 
Published: August 2021

Abstract

Background: Insulin resistance in brain plays a critical role in the pathogenesis of Alzheimer's disease (AD). Metformin is a blood brain barrier crossing anti-diabetic insulin-sensitizer drug. Current study has evaluated the therapeutic and mechanistic role of conventional as well as solid lipid nanoformulation (SLN) of metformin in intracerebro ventricular (ICV) Aβ (1-42) rat-model of AD. Methods: SLN-metformin was prepared by the micro-emulsification method and further evaluated by zetasizer and scanning electron-microscopy. In the animal experimental phase, AD was induced by bilateral ICV injection of Aβ using stereotaxic technique, whereas control group (sham) received ICV-NS. 14 days post-model induction, ICV- Aβ treated rats were further divided into 5 groups: disease control (no treatment), Metformin dose of (50mg/kg, 100mg/kg and 150 mg/kg), SLN of metformin 50mg/kg and memantine 1.8mg/kg (positive-control). Animals were tested for cognitive performance (in EPM, MWM) after 21 days of therapy, and then sacrificed. Brain homogenate was evaluated using ELISA for (Aβ (1-42), hyperphosphorylated tau, pAKTser473, GSK-3β, p-ERK,) and HPLC (metformin level). Brain histopathology was used to evaluate neuronal injury score (H&E) and Bcl2 and BAX (IHC). Results: The average size of SLN-metformin was <200 nm and was of spherical in shape with 94.08% entrapment efficiency. Compared to sham, the disease-control group showed significantly higher (p≤0.05) memory impairment (in MWM and EPM), higher hyperphosphorylated tau, Aβ (1-42), and Bax and lower Bcl-2 expression. Metformin was detectable in brain. Treatment with metformin and its SLN form significantly decreased the memory impairment as well as decreased the expression of hyperphosphorylated tau, Aβ(1-42), Bax expression and increased expression of Bcl-2 in brain. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway can be implicated in the protective efficacy of metformin. Conclusion: Both metformin and SLN metformin is found to be effective as therapeutic agent in ICV-AB rat model of AD. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway is found to be involved in the protective efficacy of metformin.
Landscape configuration affects probability of apex predator presence and community structure in experimental metacommunities
Authors: Wolfe Ellie , Hammill Edd , Memmott Jane , Clements Christopher F. 
Published: August 2021

Abstract
Biodiversity is declining at an unprecedented rate, highlighting the urgent requirement for well-designed protected areas. Design tactics previously proposed to promote biodiversity include enhancing the number, connectivity, and heterogeneity of reserve patches. However, how the importance of these features changes depending on what the conservation objective is remains poorly understood. Here we use experimental landscapes containing ciliate protozoa to investigate how the number and heterogeneity in size of habitat patches, rates of dispersal between neighbouring patches, and mortality risk of dispersal across the nonhabitat ‘matrix’ interact to affect a number of diversity measures. We show that increasing the number of patches significantly increases γ diversity and reduces the overall number of extinctions, whilst landscapes with heterogeneous patch sizes have significantly higher γ diversity than those with homogeneous patch sizes. Furthermore, the responses of predators depended on their feeding specialism, with generalist predator presence being highest in a single large patch, whilst specialist predator presence was highest in several-small patches with matrix dispersal. Our evidence emphasises the importance of considering how top-down effects can drive community responses to patch configuration.
Oral Health Status Assessment of an African Population: Rationale, Methods and Population Characteristics
Authors: Hewlett Sandra Ama. , Blankson Paa-Kwesi , Aheto Justice M.K. , Anto Francis , Appiah Tony Danso , Sackeyfio Josephine , Koram Kwadwo , Amoah Albert 
Published: August 2021

Abstract
Objectives: Oral health surveys aid in estimating the oral health of a population and provide a projection for future oral health care needs. We report the procedures and rationale of a survey carried out to assess the oral health status and risk factors for oral disease among adults in the Greater Accra Region (GAR) of Ghana. It’s objective was to provide prevalence estimates on dental diseases, oral health behaviour and risk factors, and to establish baseline epidemiological data on the population’s oral health for further research.Methods: This was a population-based cross-sectional study of adults aged 25 years and above. A random, stratified two-stage sampling method was used to select participants from rural and urban communities in three types of districts (Metropolitan, Municipal, Ordinary). A semi- structured questionnaire was used to collect data on socio-demographic characteristics, oral health behaviours and risk factors for oral disease. Anthropometric data and a full-mouth clinical examination was carried out including: soft tissue assessment, tooth count, prosthodontic status, dental caries assessment and periodontal assessment.Results: A total of 729 participants were included in the study with a mean age of 43.9 (±14.6). Majority 425 (61%) were females. Though the metropolitan districts had more dental clinics and personnel, along with better health insurance coverage, they had a higher prevalence of missing teeth, retained roots, severe periodontitis and poorer oral health coverage. The findings also show some significant differences in disease prevalence, within the different localities and districts.Conclusions: Availability and access to oral health services is not the most important determinant of good oral health outcomes in this region. We recommend exploring socio-behavioral and cultural factors as well. This study provides district level data to inform policy and guide further research.
Establish a Prediction Model for the Recurrence Time of Hormone Receptor Positive /human Epidermal Growth Factor Receptor 2-negative Breast Cancer
Authors: Hu Mengyu , Xing Huajie , Li Huiping , Liu Yaxin , Zhang Jiayang 
Published: August 2021

Abstract
ObjectivesThis study aimed to develop a model to predict recurrence time of hormone receptor-positive (HR+) /human epidermal growth factor receptor 2 negative (HER2-) breast cancer patients. MethodsWe included HR+ HER2- metastatic breast cancer (MBC) female patients who arrived at the Department of Breast Oncology in Peking University Cancer Hospital. Data were collected through consulting medical records. Patients were divided into early recurrence group and late recurrence group according to disease-free survival (DFS). Predictors of recurrence time were identified and a nomogram was developed and validated using concordance index (C-index), AUC (area under the curve), and calibration plots. ResultsA total of 639 patients coming to the hospital between April 2007 and October 2019 were included. Median DFS was 50.0 months. 382 patients (59.8%) were presented with early recurrence (DFS ≤5 years), and 257 patients (40.2%) were presented with late recurrence (DFS >5 years). A nomogram based on potentially associated clinicopathological factors was developed and validation results showed the nomogram was well-calibrated to predict recurrence time (AUC=0.703, C-index=0.697). ConclusionsWe have established a well-calibrated nomogram through 639 patients. HR+/HER2- BC patients with premenopausal status at initial diagnosis, less positive lymph nodes, lower level of Ki-67 were more common in late recurrence. The nomogram can predict the risk of late recurrence. Prospectively designed studies are needed to further validate our model.
First Report on the Diversity and Distribution of Parasitic Monogenoids (Platyhelminthes) From Catfishes (Siluriformes) in Arunachal Pradesh, India
Authors: Tripathi Amit , Wangchuk Leki , Narba Dobium , Matey Chawan 
Published: August 2021

Abstract
Monogenoidea (Platyhelminthes), one of the largest groups of ectoparasitic metazoans worldwide, comprises over 10,000 nominal species distributed globally, many of which may represent a serious threat to their fish hosts in aquaculture conditions. The fish fauna of Arunachal Pradesh, India– a global hotspot of biodiversity– is reasonably well-documented, with at least 213 known species (including 69 Siluriformes). These faunas are an essential resource for this tribal state’s economy. In sharp contrast, information on parasitic monogenoids of fish from the region is extremely limited, with only nine species described to date. In this study, 21 species of catfishes were collected and examined with the aim of expanding the current knowledge of the diversity and distribution of monogenoid species from Arunachal Pradesh. 15 (62.5%) of the 21 catfish species studied were infected with a total of 25 monogenoid species (11 previously described and 14 newly discovered in this study). Ten species of catfish were the first host records for new parasite species, while two species of catfish were new host records for previously known monogenoids. Arunachal Pradesh represents new geographic locality records for all 11 previously described parasite species, thus significantly expanding their distribution area from North and South India to extreme Northeast India. The patterns of parasite species richness in relation to three ecological traits (fish habitat, body size, and elevation) as well as host specificity across the 21 examined species of catfishes, the unique problem of too many parasite species in Wallago attu, and the future of parasitology in Arunachal Pradesh, India are discussed.
Expression of M2 Macrophages and Regulatory T Cells in Colorectal Cancer and Their Correlation with Lymph Node Metastasis
Authors: Chen Yanlei , Yang Chunyu , Wang Yue , Ma Xueqian , Wang Yanping , Liu Jinhao , Sun Yan , Song Xiaoyu , Feng Yang , Qiao Shifeng 
Published: August 2021

Abstract
BackgroundColorectal cancer (CRC) is among the most common malignancies worldwide. M2 macrophages and regulatory T cells (Tregs) are immunosuppressive cells that can promote tumor progression via inhibiting anti-tumor immunities. However, the significance and correlation of the two types of cells in colorectal cancer are still inconclusive. The purpose of this study is to detect the number of M2 macrophages and Tregs in colorectal cancer and lymph nodes and to explore the clinical and pathological significance of their existence.MethodsThe pathologic specimens and clinical data of 197 patients with Colorectal cancer after radical resection were collected. Immunohistochemical methods were used to detect the expression of M2 macrophages and Tregs in colorectal cancer tissues, adjacent tissues, and lymph node tissues in each group.ResultsCompared with adjacent tissues and non-metastatic lymph node tissues, M2 macrophages and Tregs not only increased significantly in cancer tissues and metastatic lymph node tissues (P < 0.001), but also M2 macrophages in non-metastatic lymph node tissues adjacent to cancer tissues the number of phages expressed also increased significantly (P < 0.05). In addition, there was a positive correlation between the number of cancer tissues and lymph nodes (P < 0.001).ConclusionM2 macrophages are involved in the formation of lymph node immunosuppressive environment and promote the development of CRC and lymph node metastasis together with Tregs. Upregulation of M2 macrophages and Tregs expression is a prognostic marker for monitoring the condition of colorectal cancer and judging the prognosis.
Comparative Analysis of the Mutational Profile in HBV-Related and Non-HBV-Related Hepatocellular Carcinoma
Authors: Du Bingqing , Wang Haifeng , Yang Jie , Wei Yisheng , Shao Zili 
Published: August 2021

Abstract
BackgroundHepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.The distinct molecular mechanism that regulates cancer progression associated with HBV-related HCC are still unclear.MethodsThe study population included all HCC patients from TCGA lihc_firehose.Mutational signatures of HBV-related HCC samples were calculated with MuSiCa Online website tools. Overall Survival (OS) and disease-free survival（DFS) were estimated according to the log rank in Cox proportional model.Analysis of differential expressed genes was finished with R (version 3.6.3) package DESeq2.Results AXIN1 and CACNA2D1 were significantly higher tested in patients with HBV-related HCC.Mutational signature 26,6 and 16 were detected in HBV-related HCC.TMB of non-HBV-related HCC was significantly higher than HBV-related . Mutations of TTN, MUC16, RYR2, DNAH7 and ARID2 had significant effects on OS in HBV-related but were not associated with prognosis of non-HBV-related HCC.ConclusionWnt/β-catenin and cell cycle signaling pathway may be potentially targets for treatment of HBV-related HCC.Mutation genes of TTN, MUC16, RYR2, DNAH7 and ARID2 may be used as biomarkers of the clinical prognosis and a useful strategy for management of HBV-related HCC.
LINC00261 Inhibits Esophageal Cancer Radioresistance By Downregulating microRNA-552-3p And Promoting DIRAS1
Authors: Yang Baolong , Ma Hongbing , Bian Yan 
Published: August 2021

Abstract
Background: Esophageal cancer (EC) is a life-threatening tumor with a high increasing incidence rate. Long intergenic non-protein coding RNAs (LINCs) are widely researched in EC. This study set out to investigate the role of LINC00261 in EC radioresistance.Methods: Radioresistant EC cell lines TE-1-R and TE-5-R were established using TE-1 and TE-5 cells. LINC00261, microRNA (miR)-552-3p, and DIRAS1 expression in EC tissues and adjacent normal tissues and EC cells was evaluated. Then, survival fraction (SF), colony formation, apoptosis, and γ-H2AX expression were analyzed. The binding relation between LINC00261 and miR-552-3p and between miR-552-3p and DIRAS1 were detected. Eventually, xenograft transplantation was applied to confirm the effect of LINC00261 on EC radioresistance in vivo.Results: LINC00261 and DIRAS1 were weakly expressed in EC tissues and cells, but miR-552-3p was overexpressed. For EC cells with X-ray radiation, overexpression of LINC00261 reduced SF and cell viability, strengthened γ-H2AX expression, and promoted apoptosis, which were all counteracted by miR-522-3p overexpression or DIRAS1 silencing. Mechanically, the binding relation between LINC00261 and miR-552-3p and between miR-552-3p and DIRAS1 were verified. In addition, LINC00261 overexpression suppressed tumor growth and reduced EC radioresistance in vivo.Conclusion: LINC00261 could suppress EC radioresistance via the competing endogenous RNA network to sponge miR-552-3p and upregulate DIRAS1 transcription.
Sustainable Synthesis of Microwave Assisted IONPs by Using Spinacia Oleracea: Enhances Resistance Against Fungal Wilt Infection by Inducing ROS and Modulating Defense System in Tomato Plants
Authors: Ashraf Hina , Anjum Tehmina , Riaz Saira , Batool Tanzeela , Naseem Shahzad , Ahmad Irfan S. 
Published: August 2021

Abstract
Background: Changing climate enhances the survival of pests and pathogens which eventually affects the crop yield and reduces its economic value. To attain the sustainable food security, novel approaches should be employed. Nanobased agri-chemicals provide a distinctive mechanism to increase productivity and manage phytopathogens with minimum environmental distress. In-vitro and greenhouse studies were conducted to evaluate the potential of green synthesized iron oxide nanoparticles (IONPs) in suppressing the wilt infection caused by Fusarium oxysporum f.sp. lycospersici and to improve tomato growth (Solanum lycopersicum) and fruit quality. Results: Various microwave powers (100 W- 1000 W) were used to modulate the properties of green synthesize IONPs by using spinach as a starting material. The IONPs stabilized with black coffee extract were substantively characterized by X-ray diffraction analysis, fourier transform infrared spectroscopy, dielectric and impedance spectroscopy, X-ray photoelectron spectroscopy, Scanning and transmission electron microscopy and magnetization-analysis. XRD revealed cubic magnetite (Fe3O4) phase with superparamagnetic nature, detected at all microwave powers. Binding energies of Fe 2p3/2 (712.05 eV) and Fe 2p1/2 (723.9 eV) of Fe3O4 NPs was confirmed by XPS analysis observed at microwave power of 1000 W. Uniform, spherical shaped particles with an average diameter of 4 nm were confirmed by SEM and TEM analysis. Significant reduction in mycelial growth and spore germination was perceived after exposure to different treatments of IONPs. Malformed mycelium, DNA fragmentation, alternation in cell membrane and ROS production in F. oxysporum indicates antimicrobial affinity of iron oxide NPs. The particles were applied both through root (before transplantation) and foliar application (after two weeks) to infected seedlings. The IONPs significantly reduced the disease severity by an average of 47.8% resulting in increased plant growth variables at exposure to 10 µg/mL of IONPs. Analysis of photosynthetic pigment, phenolic compounds and antioxidant enzymes in root and shoots signifies an increasing trend after exposure to various concentrations of IONPs. Correspondingly, lycopene, vitamin C, total flavonoids and protein content was substantially improved in tomato fruits after treatment of IONPs. Conclusion: These findings of current investigation suggests that IONPs owned antifungal properties to subdue Fusarium wilt disease by boosting plant growth and fruit quality.
Implementation and Performance of Haemovigilance Systems in 10 Sub-Saharan African Countries
Authors: Samukange Washington T. , Kluempers Verena , Porwal Manvi , Mudyiwenyama Linda , Mutoti Khamusi , Aineplan Noel , Gardarsdottir Helga , Mantel-Teeuwisse Aukje K. , Nuebling C. Micha 
Published: August 2021

Abstract
Background:Haemovigilance is an important element of blood regulation. It includes collecting and evaluating information on adverse events resulting from the use of blood and blood components with the aim to improve donor and patient safety. We assessed how haemovigilance is currently being implemented and performed in 10 sub-Saharan African countries. Methods:We piloted the use of the integrated WHO Global Benchmarking Tool plus Blood (GBT+ Blood) to assess the haemovigilance function of national regulatory authorities (NRAs) in Ethiopia, Kenya, Malawi, Nigeria, Liberia, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. Data obtained from documents and face to face interviews were used to determine the status of implementation and performance of the following six indicators; legal provisions regulations and guidelines, organisation and governance, human resources, regulatory processes, transparency and accountability and finally, monitoring progress and assessing impact, by estimating median scores across 20 sub-indicators. In addition, a cluster analysis was performed.Results:The countries showed inter-organisation variability in implementation and performance of the haemovigilance function. The overall median score (all sub-indicators) was 44% (range: 7.5% - 70%). The lowest average performance scores were for the arrangement for effective organisation and coordination (35%) and human resources (35%) indicators. The highest average scores were observed for the mechanism to promote transparency and mechanism to monitor regulatory performance indicators (50% and 60%, respectively). We identified clusters of best implemented sub-indicators from the procedures for haemovigilance and poorly implemented sub-indicators from the legal provisions, regulations and guidelines for haemovigilance and human resources. Conclusions:Implementation of sub-indicators and performance of haemovigilance systems varied greatly for all countries with a few countries performing reasonably well in implementation of some sub-indicators under procedures for haemovigilance. Most countries were poorly implementing sub-indicators in the legal provisions, arrangement for effective organisation and human resources indicators. The legislative provisions in most countries were at a nascent stage. There is a need to set up targeted and customised technical support coupled with prioritised interventions to strengthen the capacities of NRAs.