bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic meta-analysis: a method of using global evidence for local decision making
Authors: Shackelford Gorm E. , Martin Philip A. , Hood Amelia S. C. , Christie Alec P. , Kulinskaya Elena , Sutherland William J. 
Published: February 2021

Abstract
Background
Meta-analysis is often used to make generalisations across all available evidence at the global scale. But how can these global generalisations be used for evidence-based decision making at the local scale, if the global evidence is not perceived to be relevant to local decisions? We show how an interactive method of meta-analysis—dynamic meta-analysis—can be used to assess the local relevance of global evidence.

Results
We developed Metadataset (www.metadataset.com) as a proof-of-concept for dynamic meta-analysis. Using Metadataset, we show how evidence can be filtered and weighted, and results can be recalculated, using dynamic methods of subgroup analysis, meta-regression, and recalibration. With an example from agroecology, we show how dynamic meta-analysis could lead to different conclusions for different subsets of the global evidence. Dynamic meta-analysis could also lead to a rebalancing of power and responsibility in evidence synthesis, since evidence users would be able to make decisions that are typically made by systematic reviewers—decisions about which studies to include (e.g. critical appraisal) and how to handle missing or poorly reported data (e.g. sensitivity analysis).

Conclusions
In this study, we show how dynamic meta-analysis can meet an important challenge in evidence-based decision making—the challenge of using global evidence for local decisions. We suggest that dynamic meta-analysis can be used for subject-wide evidence synthesis in several scientific disciplines, including agroecology and conservation biology. Future studies should develop standardised classification systems for the metadata that are used to filter and weight the evidence. Future studies should also develop standardised software packages, so that researchers can efficiently publish dynamic versions of their meta-analyses and keep them up-to-date as living systematic reviews. Metadataset is a proof-of-concept for this type of software, and it is open source. Future studies should improve the user experience, scale the software architecture, agree on standards for data and metadata storage and processing, and develop protocols for responsible evidence use.
The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment
Authors:   CMMID COVID-19 working group, Jarvis Christopher I. , Gimma Amy , van Zandvoort Kevin , Wong Kerry L. M. , Edmunds W. John 
Published: February 2021

Abstract
Background
England’s COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods
We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results
Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03–1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01–0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions
The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.
Prevalence of bovine abortion, calf mortality, and bovine viral diarrhea virus (BVDV) persistently infected calves among pastoral, peri-urban, and mixed-crop livestock farms in central and Northwest Ethiopia
Authors: Yitagesu Erdachew , Jackson Wendi , Kebede Nigatu , Smith Woutrina , Fentie Tsegaw 
Published: February 2021

Abstract
Background
Bovine Viral Diarrhea virus (BVDV) is one of important diseases of cattle worldwide causing economic losses to the cattle industry primarily due to increased premature culling and decreased reproductive performance. The virus can cross the placenta during early pregnancy and result in the birth of persistently infected (PI) calves that are efficient transmitters of BVDV and serving as the primary reservoirs for BVDV. Relatively few studies have focused on understanding BVDV seroprevalence, virus detection, genotyping and its distribution in Africa. Most BVDV research in Ethiopia has involved serologic surveys in adult cattle, rather than the identification of PI calves, despite their role in viral shedding and recurring infections. A cross-sectional study was undertaken in three different livestock production systems of Ethiopia with the objective to estimate the prevalence of bovine abortion, calf mortality, and BVDV persistently infected calves.

Results
Ear notch samples (882) collected from calves in 349 households were tested for BVDV antigen using antigen capture enzyme-linked immunosorbent assay (ACE). All samples tested were negative for BVDV antigen. The overall animal level crude abortion and calf mortality prevalence were 4.0% (95% CI: 2.9–5.2) and 9.2% (95% CI: 7.7–11.0) respectively. The lower BVDV PI prevalence may be due to a lower effective contact rate between cattle reared in small-scale extensive production systems in Ethiopia.

Conclusions
This is the first report of BVDV Ag test in Ethiopia and no PI was detected in calves in the study areas. Since BVDV is a disease of great economic importance, this study finding must be interpreted with care since absence of evidence is not evidence of absence and even a single BVDV infected animal can serve as source of infection and contribute to the persistent spread of the virus. Greater attention needs to be given to screening for PI animals through testing large number of animals and culling positive animals. Hence, future research should focus on regions and production systems with high BVDV seroprevalence followed by antigen ELISA or BVDV real-time PCR to detect persistently infected and acutely viremic animals.
Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
Authors: Hao Yi , Ye Ming , Chen Xiaona , Zhao Hongli , Hasim Ayshamgul , Guo Xia 
Published: February 2021

Abstract
Background
To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections.

Methods
Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers.

Results
While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection.

Conclusions
FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.
Ring finger protein 152-dependent degradation of TSPAN12 suppresses hepatocellular carcinoma progression
Authors: Wan Jian , Liu Shunfang , Sun Wanju , Yu Haiyi , Tang Wenlian , Liu Wei , Ji Jing , Liu Bin 
Published: February 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is the third cause of cancer death in the world, and few molecularly targeted anticancer therapies have been developed to treat it. The E3 ubiquitin ligase RNF152 has been reported to regulate the activity of the mechanistic target of rapamycin complex 1 (mTORC1), induce autophagy and apoptosis. However, the relationship between RNF152 and HCC is unclear.

Methods
Transcriptome RNA-sequencing data of HCC samples and normal tissues were used to detect the mRNA expression of RNF152. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to determine the transcriptional regulation of RNF152 in HCC by FoxO1. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of RNF152. Mouse xenograft models were used to study the in vivo effects of RNF152. The immunoprecipitation assay was used to determine the interaction between RNF152 and TSPAN12. The in vivo ubiquitination assay was performed to determine the regulation of TSPAN12 by RNF152.

Results
We found that RNF152 is significantly down-regulated in clinic HCC samples, and its down-regulation is associated with pool overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) in HCC patients. The transcription factor FoxO1 was significantly positively correlated RNF152 expression in HCC tissues. FoxO1 recognizes a classic insulin response element (IRE) on the RNF152 promoter to regulate its expression in HCC. RNF152 suppressed HCC cell proliferation, clonogenic survival, invasion in vitro, and tumorigenesis in vivo. Mechanistically, RNF152 interacted with TSPAN12 and targeted it for ubiquitination and proteasomal degradation, thereby inhibiting TSPAN12-dependent CXCL6 expression and HCC progression.

Conclusion
Collectively, our data revealed a tumor suppressor role of RNF152 and a connection between RNF152 and FoxO1 in HCC. Our results support an important role of the FoxO1-RNF152-TSPAN12 axis in the development of HCC. Therapeutic targeting this axis may be an effective means of treating HCC.
Identification of four genes and biological characteristics of esophageal squamous cell carcinoma by integrated bioinformatics analysis
Authors: Song Yexun , Wang Xianyao , Wang Fengjun , Peng Xiaowei , Li Peiyu , Liu Shaojun , Zhang Decai 
Published: February 2021

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated.

Methods

The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein–protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR).

Results
In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival.

Conclusions
SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
The immune‐related biomarker TEK inhibits the development of clear cell renal cell carcinoma (ccRCC) by regulating AKT phosphorylation
Authors: Chen Siming , Yu Mengxue , Ju Lingao , Wang Gang , Qian Kaiyu , Xiao Yu , Wang Xinghuan 
Published: February 2021

AbstractBackgroundHigh immunogenicity is an important feature of ccRCC, but its underlying immune-related molecular mechanisms remain unclear. This study aimed to investigate the effect of immune-related gene TEK on ccRCC and its prognostic value.MethodsThe immune-related differentially expressed genes (DEGs) and transcription factors (TFs) in ccRCC were screened based on The Cancer Genome Atlas (TCGA) database, and a regulatory network of TF was constructed. Prognostic-related immune genes were screened by univariate Cox regression analysis and functional annotation was performed. Univariate and multivariate Cox regression analyses were performed to construct the immune gene risk model and identify the hub gene TEK that independently affected the prognosis of ccRCC. The effectiveness of the TEK was verified by external microarray datasets. The relationship between TEK and immune cells in ccRCC was evaluated based on Tumor Immune Estimation Resource (TIMER). The expression of TEK in clinical specimens was verified by qRT-PCR and immunohistochemical (IHC) staining. MTT and cloning formation assay were used to evaluate cell proliferation. Transwell assays were used to assess cell migration. Apoptosis was assessed by flow cytometry, and the expression of related proteins was detected by Western blot and immunofluorescence.ResultsWe constructed a prognostic model consisting of 12 hub genes and performed risk scores to determine the relationship between these scores and prognosis. Through Cox regression analysis and survival analysis, TEK, an immune marker highly related to survival prognosis, was obtained and validated.In vitroexperiments showed that knockdown ofTEKpromoted the proliferation and migration of ccRCC cells, and we found that TEK promoted apoptosis by regulating the phosphorylation of AKT, thereby inhibiting cell proliferation.ConclusionsTEK plays an important role in risk assessment and survival prediction for ccRCC patients as a new immune gene and maybe an emerging target for immunotherapy for ccRCC patients.
Evaluation of the durability and use of long‐lasting insecticidal nets in Nicaragua
Authors: Villalta Emperatriz Lugo , Soto Bravo Aida Mercedes , Vizcaino Lucrecia , Dzuris Nicole , Delgado Marco , Green Michael , Smith Stephen C. , Lenhart Audrey , Macedo de Oliveira Alexandre 
Published: February 2021

Abstract
Background
Vector control for malaria prevention relies most often on the use of insecticide-treated bed net (ITNs) and indoor residual spraying. Little is known about the longevity of long-lasting insecticidal nets (LLINs) in the Americas. The physical integrity and insecticide retention of LLINs over time were monitored after a bed net distribution campaign to assess community practices around LLIN care and use in Waspam, northeastern Nicaragua.

Methods
At least 30 nets were collected at 6, 12, 24, and 36 months post distribution. Physical integrity was measured by counting holes and classifying nets into categories (good, damaged, and too torn) depending on a proportionate hole index (pHI). Insecticide bioefficacy was assessed using cone bioassays, and insecticide content measured using a cyanopyrethroid field test (CFT).

Results
At 6 months, 87.3 % of LLINs were in good physical condition, while by 36 months this decreased to 20.6 %, with 38.2 % considered ‘too torn.’ The median pHI increased from 7 at the 6-month time point to 480.5 by 36 months. After 36 months of use, median mortality in cone bioassays was 2 % (range: 0–6 %) compared to 16 % (range: 2–70 %) at 6 months. There was a decrease in the level of deltamethrin detected on the surface of the LLINs with 100 % of tested LLINs tested at 12 months and 24 months crossing the threshold for being considered a failed net by CFT.

Conclusions
This first comprehensive analysis of LLIN durability in Central America revealed rapid loss of chemical bioefficacy and progressive physical damage over a 36-month period. Use of these findings to guide future LLIN interventions in malaria elimination settings in Nicaragua, and potentially elsewhere in the Americas, could help optimize the successful implementation of vector control strategies.
Genomic investigation of atypical malaria cases in Kanel, northern Senegal
Authors: Sy Mouhamad , Badiane Aida Sadikh , Deme Awa Bineta , Gaye Amy , Ndiaye Tolla , Fall Fatou Ba , Siddle Katherine J. , Dieye Baba , Ndiaye Yaye Die , Diallo Mamadou Alpha , Diongue Khadim , Seck Mame Cheikh , Ndiaye Ibrahima Mbaye , Cissé Moustapha , Gueye Alioune Badara , Sène Doudou , Dieye Yakou , Souané Tamba , MacInnis Bronwyn , Volkman Sarah K. , Wirth Dyann F. , Ndiaye Daouda 
Published: February 2021

Abstract
Background
The diagnosis of malaria cases in regions where the malaria burden has decreased significantly and prevalence is very low is more challenging, in part because of reduced clinical presumption of malaria. The appearance of a cluster of malaria cases with atypical symptoms in Mbounguiel, a village in northern Senegal where malaria transmission is low, in September 2018 exemplifies this scenario. The collaboration between the National Malaria Control Programme (NMCP) at the Senegal Ministry of Health and the Laboratory of Parasitology and Mycology at Cheikh Anta Diop University worked together to evaluate this cluster of malaria cases using molecular and serological tools.

Methods
Malaria cases were diagnosed primarily by rapid diagnostic test (RDT), and confirmed by photo-induced electron transfer-polymerase chain reaction (PET-PCR). 24 single nucleotide polymorphisms (SNPs) barcoding was used for Plasmodium falciparum genotyping. Unbiased metagenomic sequencing and Luminex-based multi-pathogen antibody and antigen profiling were used to assess exposure to other pathogens.

Results
Nine patients, of 15 suspected cases, were evaluated, and all nine samples were found to be positive for P. falciparum only. The 24 SNPs molecular barcode showed the predominance of polygenomic infections, with identifiable strains being different from one another. All patients tested positive for the P. falciparum antigens. No other pathogenic infection was detected by either the serological panel or metagenomic sequencing.

Conclusions
This work, undertaken locally within Senegal as a collaboration between the NMCP and a research laboratory at University of Cheikh Anta Diop (UCAD) revealed that a cluster of malaria cases were caused by different strains of P. falciparum. The public health response in real time demonstrates the value of local molecular and genomics capacity in affected countries for disease control and elimination.
Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms
Authors: O’Donnell Aidan J. , Reece Sarah E. 
Published: February 2021

AbstractBackgroundDaily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species ofPlasmodiumappear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for examplePlasmodium chabaudi,is governed by host rhythms, yet seems completely independent of host rhythms inPlasmodium berghei,another rodent malaria species, is mysterious.MethodsThis study reports a series of five experiments probing the relationships between the asynchronous IDC schedule ofP. bergheiand the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.ResultsThe results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs onP. berghei; (ii) the IDC schedule ofP. bergheiis impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.ConclusionsOverall, host rhythms do not affect the performance ofP. bergheiand its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.