bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human-correlated genetic HCC models identify combination therapy for precision medicine
Authors: Müller Miryam , May Stephanie , Hall Holly , Kendall Timothy J. , McGarry Lynn , Blukacz Lauriane , Nuciforo Sandro , Jamieson Thomas , Phinichkusolchit Narisa , Dhayade Sandeep , Leslie Jack , Sprangers Joep , Malviya Gaurav , Mrowinska Agata , Johnson Emma , McCain Misti , Halpin John , Kiourtis Christos , Georgakopoulou Anastasia , Nixon Colin , Clark William , Shaw Robin , Hedley Ann , Drake Thomas M. , Tan Ee Hong , Neilson Matt , Murphy Daniel J. , Lewis David , Reeves Helen L. , Mann Derek A. , Blyth Karen , Heim Markus H. , Carlin Leo M. , Sansom Owen J. , Miller Crispin , Bird Thomas G. 
Published: May 2022

Abstract

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer related mortality worldwide. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulated progressive driver mutations, with hepatocytes the most likely cell of origin. However, the landscape of driver mutations in HCC is independent of the underlying aetiologies.
Despite an increasing range of systemic treatment options for advanced HCC outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations. Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC.
We generated over twenty-five new genetically-driven in vivo and in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance, and metastasis to distant organs. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with histopathology.
In a proof-of-principle analysis, we verified response to standard of care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not been linked to HCC treatment before. Cladribine acts in a highly effective subtype-specific manner in combination with standard of care therapy.
Performances of noninvasive prenatal detection for fetal chromosome aneuploidy based on Semiconductor Sequencing Platform (SSP) of difference sequencing depths
Authors: Yang Jiexia , Wu Jing , Wang Dongmei , Peng Haishan , Wang Yixia , Guo Fangfang , Hou Yaping , Yin Aihua 
Published: May 2022

Abstract
Objective：To evaluate the performance of non-invasive prenatal testing (NIPT) for chromosome aneuploidy in different sequencing depths for all chromosome aneuploidies.Methods: A cohort of 61581 pregnancies were recruited to review the results, which contained 49393 cases of NIPT and 12188 cases of NIPT- plus respectively. Cell-free DNA from plasma samples were sequenced by Ion Proton sequencer, with sequencing depths included 0.15X (3 Mb reads) with NIPT and 0.4X (8 Mb reads) with NIPT- plus. All high-risk cases were recommended to undergo invasive prenatal diagnosis, and all pregnant women were followed up.Results: A total of 910 cases were high risk of chromosome aneuploidies predicted by NIPT and NIPT- plus. in which NIPT predicted 682 high risk of chromosome aneuploidies , and NIPT- plus predicted 210, The positive rates were 1.38% and 1.72%, respectively. A total of 811 cases accepted prenatal diagnosis with 627 cases of NIPT and 184 cases of NIPT- plus. The PPV of autosomal aneuploidies in NIPT were 81.99%, 69.23%, 25.00%, 4.55%, respectively. and The PPV of autosomal aneuploidies in NIPT- plus were 86.96%, 80.00%, 35.00%, 8.77%,respectively. The PPV of sex chromosome aneuploidies in NIPT- plus was 50%，which consistent with NIPT. In addition, through follow-up, found 1 cases of false negative with trisomy 18 , both of which was detected by NIPT, and termination of pregnancy after prenatal diagnosis due to ultrasound abnormalities.Conclusion: The PPV of autosomal aneuploidies in NIPT- plus was slightly better than NIPT. It shows that increasing the sequencing depth can improve the detection performance of aneuploidy, which has certain guiding value for clinical application.
Blockchain based Data Integrity Framework for Internet of Things
Authors: Chanal Poornima M. , Kakkasageri Mahabaleshwar S. 
Published: May 2022

Abstract
The Internet of Things (IoT) is one important digital revolution in both the academic world and commerce. It brings convenience to people`s daily lives; but, the challenges of security and privacy have become a very big task in IoT. Attaining safety and data integrity verification of information in IoT networks is one of the hot topics for future IoT applications. The provision of security to any information in an IoT network is a big challenge, which must be given the top priority for many current and future applications of IoT. Traditional data integrity verification approaches only use encryption algorithms to secure information, depending on Third-Party Auditors (TPAs). The blockchain's basic principle is that information produced by users or nodes is tested for accuracy and cannot be altered once it is updated on the blockchain. Blockchain based data integrity schemes can effectively overcome TPA's issues. In this paper, we propose a blockchain based data integrity technique with a bilinear design for IoT information. We achieve data integrity according to the characteristics of bilinear design in the form of blockchain communications. The proposed blockchain based framework for data integrity verification consists of different entities such as client, Key Generation Centre (KGC), cloud storage server, and blockchain. Proposed data integrity verification operates in three stages: Setup stage, Processing stage and Verification stage. Simulation results show that the performance of the proposed blockchain approach for data integrity in IoT is better as compared with the blockchain based cloud data integrity verification scheme with high efficiency (DICF). The results demonstrate that our scheme is better interms of signature generation time, end to end delay, memory utilization as compared to DICF.
A protocol to evaluate unsupervised text clustering to screen and categorize studies in systematic reviews
Authors: Muller Ashley Elizabeth , Ames Heather Melanie R , Borge Tiril C , Hestevik Christine Hillestad , Meneses-Echavez Jose Francisco , Rose Christopher James 
Published: May 2022

Abstract
Background: The evidence base is steadily increasing regarding the time savings of using machine learning (ML) within evidence synthesis, particularly supervised methods such as classification. Unsupervised methods such as clustering have been less explored. Yet clustering – a method to uncover groups of similar data, from a large and heterogenous dataset – may be a particularly relevant tool within the study identification and data extraction processes of reviews, during which researchers must often read thousands of studies to identify the handful relevant to their review. This protocol is for a mixed methods evaluation of clustering implemented within systematic reviews.Research questions: We will answer the following questions: 1) Can clustering while screening at title/abstract level provide useful automatic categorizations of studies that help reviewers extra data to categorize studies? 2) What are reviewers’ perceptions of and experiences with clustering in relation to acceptability and feasibility in future reviews? Methods: We will identify one or two systematic reviews as models to answer these research questions. Reviewers will use the clustering algorithm Lingo3G built into EPPI Reviewer during the screening process. The main outcome to answer research question 1 is content validity, as an indicator of usefulness, defined by similarities between automatic clusters and reviewer-generated categories. We will display multi-class confusion matrices and use these to estimate precision, recall, and F1-score for each useful cluster. Research question 2 will be answered qualitatively, through semi-structured interviews with participating reviewers before and after having been trained on clustering and implementing it in the model review(s), followed by a focus group presenting results and exploring reviewer trust. Conclusion: The planned evaluation will provide important information as to the feasibility of an unsupervised ML method, clustering, in bridging and aligning two currently linear steps in evidence synthesis. We invite interested evidence synthesis organizations to follow this protocol and subsequently share data with us, or to tailor it to produce a more relevant evaluation.
Does women’s literacy affect maternal health services utilization in Ethiopia? A stratified analysis of 2019 mini Ethiopian Demographic and Health Survey
Authors: Handebo Simegnew , Demie Takele Gezahegn , Gessese Getachew Tilahun , Woldeamanuel Berhanu Teshome , Biratu Tolosa Diriba 
Published: May 2022

Abstract
Background: Maternal mortality remains unacceptably high in sub-Saharan Africa with 533 maternal deaths per 100,000 live births, or 200,000 maternal deaths a year. This is over two-thirds (68%) of all maternal deaths per year worldwide. The lifetime risk of maternal death in low-income countries is 1 in 45. Most maternal deaths can be prevented if births are attended by skilled health personnel. Therefore, the current study examined the utilization of maternal health services among women in different sociodemographic statuses within different literacy strata in Ethiopia.Methods: A total weighted sample of 3,839 women who gave birth within five years preceding the survey and whose literacy status was measured in the survey were included in this study. The dataset from the most recent Ethiopia Mini Demographic and Health Surveys (EMDHS) 2019 was used for this study. The EMDHS was a community-based cross-sectional study conducted in Ethiopia from March 21 to June 28, 2019. The survey used a two-stage stratified cluster sampling technique. Bivariate and multivariable logistic regression analyses were employed. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was reported and statistical significance was set at a p-value < 0.05.Results: In this study, nearly two-thirds (63.8%) of reproductive-age women were illiterate. The overall prevalence of ANC 1, ANC 4, skilled birth attendance, and postnatal care utilization was 74.9%, 43.5%, 51.9%, and 32.0%, respectively. Our analysis also revealed that literate women are more likely to receive ANC 1 (literate vs illiterate, 87.9% vs 67.5%), ANC 4 (59.4% vs 34.5%), skilled birth attendance (73.3% vs 39.7%), and PNC (51.2% vs 21.1) as compared to their illiterate counterparts. Regional variation, wealth status, age at first birth, birth order, and birth intervals were found significant factors associated with maternal health care service utilization among both literate and illiterate reproductive-age women in Ethiopia. Similar to this, ANC booking timing and utilization, age of household head, and religious affiliation were associated with institutional delivery and PNC utilization.Conclusion: Women’s literacy is an important associate for utilizing appropriate maternal healthcare, with other sociodemographic and obstetric related factors as modifying factors. Hence, wholehearted efforts should be directed toward educating and empowering women. On the other hand, literacy levels and other modifying factors should be considered when designing interventions that enhance maternal health care service utilization. For instance, such programs need to stratify the interventions according to the literacy level of the women.
The effectiveness and acceptability of evidence synthesis summary formats for clinical guideline development groups: A mixed-methods systematic review
Authors: Sharp Melissa Kathleen , Baki Dayang Anis Binti Awang , Quigley Joan , Tyner Barrie , Devane Declan , Mahtani Kamal R. , Smith Susan M. , O'Neill Michelle , Ryan Mairin , Clyne Barbara 
Published: May 2022

Abstract
Introduction
: Clinical guideline development often involves a rigorous synthesis of evidence involving multidisciplinary stakeholders with different priorities and knowledge of evidence synthesis; this makes communicating findings complex. Summary formats are typically used to communicate the results of evidence syntheses, however, there is little consensus on which formats are most effective and acceptable for different stakeholders.
Methods
This mixed-methods systematic review (MMSR) aimed to evaluate the effectiveness and acceptability (e.g., usability preferences, and attitudes and preferences towards) of evidence synthesis summary formats for GDG members. We followed the PRISMA 2020 guideline and Joanna Briggs Institute Manual for Evidence Synthesis for MMSRs. We searched six databases (inception to April 20, 2021) for randomised controlled trials (RCTs), RCTs with a qualitative component, and qualitative studies. Screening, data extraction, and quality appraisal was performed in duplicate. Qualitative findings were synthesised using meta-aggregation and quantitative findings are described narratively.
Results
We identified 17,240 citations and screened 54 full-text articles, resulting in 22 eligible articles (20 unique studies): 4 articles reported the results of 5 RCTs, one of which also had a qualitative component. The other 18 articles discussed the results of 16 qualitative studies. Therefore we had 5 trials and 17 qualitative studies to extract data from. Studies were geographically heterogeneous and included a variety of stakeholders and summary formats. All 5 RCTs assessed knowledge or understanding with 3 reporting improvement with newer formats. The qualitative analysis identified 6 themes: ‘presenting information’, ‘tailoring content for end users’, ‘trust in synthesis producers’, ‘knowledge requirements’, ‘quality of included studies’, and ‘properly contextualising findings’. Across these themes, the synthesis resulted in 130 recommendations for practice. Nine recommendations were supported by both quantitative and qualitative evidence and 121 by only qualitative. A majority focused on how to present information (n = 68) and tailor content for different end users (n = 24).
Conclusions
This MMSR provides guidance on how to improve evidence summary structure and layout. This can be used by synthesis producers to better communicate to GDGs. Study findings will inform the co-creation of evidence summary format prototypes based on GDG member’s needs.
Word Count:
345
Registration:
The protocol for this project was previously published and the project was pre-registered on Open Science Framework. [1, 2]
Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs
Authors: Wu Ning , Gou Xiaoqin , Hu Pan , Chen Yao , Ji Jinzhong , Wang Yuanying , Zuo Li 
Published: May 2022

Abstract
Background: Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM. Results: Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P < 0.001). The TEM results indicated that HUVEC autolysosomes increased and autophagy was inhibited after TRIM22 knockdown. The qRT-PCR results revealed that after TRIM22 knockdown, the expression levels of antithymocyte globulin 7 (ATG7), antithymocyte globulin 5 (ATG5), Beclin1, ERK, and mTOR genes decreased (P < 0.01); however, the expression of AMPK genes (P < 0.05) and P62 genes (P < 0.001) increased. FCM revealed that following TRIM22 knockdown, the percentage of HUVECs in the G2 phase increased (P < 0.001) along with cell apoptosis. The effect of TRIM22 overexpression on HUVEC autophagy induced by DENV-2 infection and AMPK pathways decreased after adding an autophagy inhibitor. Conclusions: In HUVECs, TRIM22 protein positively regulates autophagy and may affect autophagy through the AMPK/ERK/mTOR signaling pathway. Autophagy is induced by activation of the AMPK/ERK/mTOR signaling pathway following TRIM22-mediated DENV-2 infection of HUVECs.
Reporting and interpretation of effects in nutritional and environmental epidemiology: a methods study
Authors: Pitre Tyler , Jassal Tanvir , Park Louis , Coello Pablo Alonso , de Souza Russel , Zeraatkar Dena 
Published: May 2022

Abstract
Background
The presentation of absolute effects, in addition to relative effects, is critical to the optimal interpretation of effect estimates. Failure to present and interpret absolute effects may obscure the magnitude of the effect of an intervention or exposure and mislead evidence users.
Objective
In this study, we estimate the proportion of systematic reviews and meta-analyses (SRMAs) addressing the health effects of nutritional and environmental exposures that report absolute effects.
Methods
We searched MEDLINE and EMBASE from 2019 through 2021 for SRMAs addressing the health effects of nutritional and environmental exposures and patient-important health outcomes. We included a sample of 200 SRMAs. Pairs of reviewers, working independently and in duplicate, reviewed search records for eligibility and collected data from SRMAs.
Results
More than two-thirds (153/200; 76.5%) of eligible systematic reviews reported on one or more dichotomous outcomes that could be translated to absolute effects. Only a handful of these reviews (8/153; 5.2%), however, reported absolute effects. A similar proportion of reviews published in high-impact journals and in other journals reported absolute effects (4/131; 3.1% vs. 4/69; 5.9%). Among reviews that reported absolute effects, six reviews (6/8; 75%) reported absolute risk differences as fractions (e.g., 2 fewer cases per 1,000 people) and two reviews (2/8; 25%) presented the number of cases prevented by modifying the exposure (e.g., 2,000 cases prevented in United States annually).
Conclusion
Reviews addressing the effects of nutritional and environmental exposures on health outcomes rarely report absolute effects, which precludes effective interpretation of magnitudes of effects and their importance. We present guidance for review authors, editors, peer reviewers, and evidence users to calculate and interpret absolute effects.
Analysis of active earth pressure behind rigid retaining walls considering curved slip surface
Authors: Yu Pengqiang , Liu Yang 
Published: May 2022

Abstract
The active earth pressure acting on the rigid vertical retaining walls under translation mode has been investigated in this paper with a two-dimensional analytical method without prior hypotheses of the shape of soil arch, i.e. the trajectory of minor principle stress, which is totally different from with the existing method of combination of soil arch shape and horizontal flat-element analysis. Different emerging failure surface was compared and a parabolic surface was especially discussed in details. The proposed formula can be employed to predict the distribution of earth pressure and stresses in the failure zone. Furthermore, the analytical expression of the minor principle stress trajectory in the failure zone was derived from the stress equations. The results of the proposed analysis were compared with test data as well as the results of existing theories to validate its accuracy and applicability. The proposed distribution of earth pressure is in good agreement with the test data. Finally, a simple yet practical formulation was established to conveniently estimate active earth pressure in field.
Histones of Neutrophil Extracellular Traps (NETs) Activate Brain Pericyte via Dectin-1 in Traumatic Brain Injury
Authors: Liu Yang-Wuyue , Zhang Jingyu , Bi Wanda , Zhou Mi , Li Jiabo , Xiong Tiantian , Yang Nan , Zhao Li , Chen Xing , Zhou Yuanguo , He Wenhui , Yang Teng , Wang Hao , Xu Lunshan , Dai Shuang-Shuang 
Published: May 2022

Abstract
Brain pericyte is unique and indispensable part of blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms about how pericyte is regulated in damaged brain are largely unknown. Here, we show that neutrophil extracellular traps (NETs) formation induces the appearance of CD11b+ pericytes post TBI. These CD11b+ pericytes subsets are characterized with increased permeability and pro-inflammatory profiles compared to CD11b- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction on brain pericytes in PKC-c-Jun dependent manner, conferring neuroinflammation and BBB dysfunction post TBI. These data indicate that "neutrophil-NETs-pericyte" and "histones-Dectin-1-CD11b" are possible mechanisms for pericyte’s activation and dysfunction. Targeting at NETs formation and Dectin-1 are promising ways for TBI treatments.
Empirical evidence on the efficiency of backward contact tracing in COVID-19
Authors: Raymenants Joren , Geenen Caspar , Thibaut Jonathan , Nelissen  , Gorissen Sarah , André Emmanuel 
Published: May 2022

Abstract
Standard contact tracing practice for COVID-19 is to identify persons exposed to an infected person during the contagious period, assumed to start two days before symptom onset or diagnosis. In the first large cohort study on backward contact tracing for COVID-19, we extended the contact tracing window by 5 days, aiming to identify the source of the infection and persons infected by the same source. The risk of infection amongst these additional contacts was similar to contacts exposed during the standard tracing window and significantly higher than symptomatic individuals in a control group, leading to 42% more cases identified through contact tracing. Compared to standard practice, backward traced contacts required fewer tests and shorter quarantine, but if infected they were identified later in their infectious cycle. Our results support implementing backward contact tracing when rigorous suppression of viral transmission is warranted.