bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-state network meta-analysis of progression and survival data
Authors: Jansen Jeroen P. , Incerti Devin , Trikalinos Thomas A. 
Published: November 2020

AbstractMultiple randomized controlled trials, each comparing a subset of competing interventions, can be synthesized by means of a network meta-analysis to estimate relative treatment effects between all interventions in the evidence base. Here we focus on estimating relative treatment effects for time-to-event outcomes. Cancer treatment effectiveness is frequently quantified by analyzing overall survival (OS) and progression-free survival (PFS). We introduce a method for the joint network meta-analysis of PFS and OS that is based on a time-inhomogeneous tri-state (stable, progression, and death) Markov model where time-varying transition rates and relative treatment effects are modeled with parametric survival functions or fractional polynomials. The data needed to run these analyses can be extracted directly from published survival curves. We demonstrate use by applying the methodology to a network of trials for the treatment of non-small-cell lung cancer. The proposed approach allows the joint synthesis of OS and PFS, relaxes the proportional hazards assumption, extends to a network of more than two treatments, and simplifies the parameterization of decision and cost-effectiveness analyses.
Trecode: a FAIR eco-system for the analysis and archiving of omics data in a combined diagnostic and research setting
Authors: Kerstens Hindrik HD , Hehir-Kwa Jayne Y , van de Geer Ellen , van Run Chris , Verwiel Eugène TP , van der Leest Douwe , Tops Bastiaan BJ , Kemmeren Patrick 
Published: November 2020

AbstractMotivationThe increase in speed, reliability and cost-effectiveness of high-throughput sequencing has led to the widespread clinical application of genome (WGS), exome (WXS) and transcriptome analysis. WXS and RNA sequencing is now being implemented as standard of care for patients and for patients included in clinical studies. To keep track of sample relationships and analyses, a platform is needed that can unify metadata for diverse sequencing strategies with sample metadata whilst supporting automated and reproducible analyses. In essence ensuring that analysis is conducted consistently, and data is Findable, Accessible, Interoperable and Reusable (FAIR).ResultsWe present “Trecode”, a framework that records both clinical and research sample (meta) data and manages computational genome analysis workflows executed for both settings. Thereby achieving tight integration between analyses results and sample metadata. With complete, consistent and FAIR (meta) data management in a single platform, stacked bioinformatic analyses are performed automatically and tracked by the database ensuring data provenance, reproducibility and reusability which is key in worldwide collaborative translational research.Availability and implementationThe Trecode data model, codebooks, NGS workflows and client programs are currently being cleared from local compute infrastructure dependencies and will become publicly available in spring 2021.Contactp.kemmeren@prinsesmaximacentrum.nl
Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19
Authors: Gottschalk Gunnar , Keating James F , Kesler Kris , Knox Konstance , Roy Avik 
Published: November 2020

AbstractPreviously, we have demonstrated that ACIS KEPTIDE™, a chemically modified peptide, selectively binds to ACE-2 receptor and prevents the entry of SARS-CoV2 virionsin vitroin primate kidney Cells. However, it is not known if ACIS KEPTIDE™ attenuates the entry of SARS-CoV2 virusin vivoin lung and kidney tissues, protects health, and prevent death once applied through intranasal route. In our current manuscript, we demonstrated that the intranasal administration of SARS-CoV2 (1*106) strongly induced the expression of ACE-2, promoted the entry of virions into the lung and kidney cells, caused acute histopathological toxicities, and mortality (28%). Interestingly, thirty-minutes of pre-treatment with 50 μg/Kg Body weight ACIS normalized the expression of ACE-2 via receptor internalization, strongly mitigated that viral entry, and prevented mortality suggesting its prospect as a prophylactic therapy in the treatment of COVID-19. On the contrary, the peptide backbone of ACIS was unable to normalize the expression of ACE-2, failed to improve the health vital signs and histopathological abnormalities. In summary, our results suggest that ACIS is a potential vaccine-alternative, prophylactic agent that prevents entry of SARS-CoV2in vivo, significantly improves respiratory health and also dramatically prevents acute mortality in K18-hACE2 humanized mice.HighlightsACIS KEPTIDE stimulates the internalization of ACE-2 receptor (Fig. 2) and buffers the membrane localization of ACE-2 receptors (Fig. 2, 6 & 8). Intranasal inoculation of SARS-CoV2 upregulates the expression of ACE-2 in lung epithelium (Fig.6) and kidney tubular cells (Fig.8). ACIS KEPTIDE normalizes the expression of ACE-2 in the kidney tubular cells of virus-treated K18-hACE2mice (Fig. 8).ACIS KEPTIDE™completely preventsthe entry of SARS-CoV2 in Bronchiolar epithelium (Fig.6), alveolar parenchyma (Fig. 6), and kidney tubular cells (Fig.8).ACIS KEPTIDE™ improves the pulmonary (Fig. 5) and renal pathological changes (Fig. 7) caused by the SARS-CoV2 virus insult.Intranasal administration of 0.05% Beta-propiolactone (βPL)-inactivated SARS-CoV2 (1 *106) causes significant death (28%) in K18-hACE2 humanized mice after 24 hrs of intranasal inoculation (Supplemental videos) suggesting that SARS-CoV2 doesnotrequire its infective properties and genetic mechanism to be functional to cause mortality.The peptide backbone of ACIS KEPTIDE™ provides much less and insignificant protection in the prevention of pathological changes in Lungs (Fig.5 & 6) and Kidney (Fig.7 & 8). Peptide failed to normalize the upscaled expression of ACE-2 in kidney tubular cells (Fig.8) of SARS-CoV2-treated K18-hACE2 mice.
Combining climatic and genomic data improves range-wide tree height growth prediction in a forest tree
Authors: Archambeau Juliette , Garzón Marta Benito , Barraquand Frédéric , de Miguel Vega Marina , Plomion Christophe , González-Martínez Santiago C. 
Published: November 2020

AbstractPopulation response functions based on climatic and phenotypic data from common gardens have long been the gold standard for predicting quantitative trait variation in new environments. However, prediction accuracy might be enhanced by incorporating genomic information that captures the neutral and adaptive processes behind intra-population genetic variation. We used five clonal common gardens containing 34 provenances (523 genotypes) of maritime pine (Pinus pinasterAiton) to determine whether models combining climatic and genomic data capture the underlying drivers of height-growth variation, and thus improve predictions at large geographical scales. The plastic component explained most of the height-growth variation, probably resulting from population responses to multiple environmental factors. The genetic component stemmed mainly from climate adaptation, and the distinct demographic and selective histories of the different maritime pine gene pools. Models combining climate-of-origin and gene pool of the provenances, and positive-effect height-associated alleles (PEAs) captured most of the genetic component of height-growth and better predicted new provenances compared to the climate-based population response functions. Regionally-selected PEAs were better predictors than globally-selected PEAs, showing high predictive ability in some environments, even when included alone in the models. These results are therefore promising for the future use of genome-based prediction of quantitative traits.
Chest CT features of COVID-19 in the region of Abu Dhabi, UAE- A single institute study
Authors: Saeed Ghufran Aref , Al Helali Abeer Ahmed , Almazrouei Safaa , Shah Asad , Ahmed Luai A. 
Published: November 2020

AbstractOBJECTIVEOur aim is to investigate high resolution CT features of COVID-19 infection in Abu Dhabi, UAE, and to compare the diagnostic performance of CT scan with RT-PCR test.METHODSData of consecutive patients who were suspected to have COVID-19 infection and presented to our hospital, was collected from March 2, 2020, until April 12, 2020. All patients underwent RT-PCR test; out of which 53.8% had chest CT scan done. Using RT-PCR as a standard reference, the sensitivity and specify of CT scan was calculated. We also analyzed the most common imaging findings in patients with positive RT-PCR results.RESULTSThe typical HRCT findings were seen in 50 scans (65.8%) out of total positive ones; 44 (77.2%) with positive RT-PCR results and 6 (31.6%) with negative results. The peripheral disease distribution was seen in 86%, multilobe involvement in 70%, bilateral in 82%, and posterior in 82% of the 50 scans.The ground glass opacities were seen in 50/74 (89.3%) of positive RT-PCR group. The recognized GGO patterns in these scans were: rounded 50%, linear 38%, and crazy-paving 24%.Using RT-PCR as a standard of reference, chest HRCT scan revealed sensitivity of 68.8% and specificity of 70%.CONCLUSIONThe commonest HRCT findings in patients with COVID-19 pneumonia were peripheral, posterior, bilateral, multilobe rounded ground glass opacities.
Melt into the group Electrophysiological Evidence of Gestalt Perception of Human Dyad
Authors: Mersad Karima , Caristan Céline 
Published: November 2020

AbstractIt has been shown recently that the human brain has dedicated networks for perception of human bodies in synchronous motion or in situation of interaction. However, below motion and interaction, how does the brain process a simple plurality of humans in close positioning? We used EEG frequency tagging technique to investigate integration of human dyad elements in a global percept. We presented to participants images of two silhouettes, a man and a woman flickering at different frequencies (5.88 vs.7.14Hz). Clear response at these stimulation frequencies reflected response to dyad parts, both when the dyad was presented upright and inverted. However, an emerging intermodulation component (7.14 + 5.88 = 13.02 Hz), a nonlinear response regarded as an objective signature of holistic representation, was significantly enhanced in upright relatively to inverted position. Inversion effect was significant only for the intermodulation component as opposed to stimulation frequencies revealing that dyad configuration perception overrides structural properties of dyad elements. Inversion effect was not significant for a pair of non-human objects. Our results show that merely facing two humans in close positioning leads to perceptually bind them and suggest that the perception of individuals is of different nature when they form a plurality.
Set-Min sketch: a probabilistic map for power-law distributions with application tok-mer annotation
Authors: Shibuya Yoshihiro , Belazzougui Djamal , Kucherov Gregory 
Published: November 2020

AbstractMotivationIn many bioinformatics pipelines,k-mer counting is often a required step, with existing methods focusing on optimizing time or memory usage. These methods usually produce very large count tables explicitly representingk-mers themselves. Solutions avoiding explicit representation ofk-mers include Minimal Perfect Hash Functions (MPHFs) or Count-Min sketches. The former is only applicable to static maps not subject to updates, while the latter suffers from potentially very large point-query errors, making it unsuitable when counters are required to be highly accurate.ResultsWe introduce Set-Min sketch – a sketching technique for representing associative maps inspired by Count-Min sketch – and apply it to the problem of representingk-mer count tables. Set-Min is provably more accurate than both Count-Min and Max-Min – an improved variant of Count-Min for static datasets that we define here. We show that Set-Min sketch provides a very low error rate, both in terms of the probability and the size of errors, at the expense of a very moderate memory increase. On the other hand, Set-Min sketches are shown to take up to an order of magnitude less space than MPHF-based solutions, especially for large values ofk. Space-efficiency of Set-Min takes advantage of the power-law distribution ofk-mer counts in genomic datasets.Availabilityhttps://github.com/yhhshb/fress
Leveraging Hardy–Weinberg disequilibrium for association testing in case-control studies
Authors: Zhang Lin , Sun Lei 
Published: November 2020

AbstractIn a case-control association study, deviation from Hardy-Weinberg equilibrium (HWE) or Hardy-Weinberg dis-equilibrium (HWD) in the control group is usually considered as evidence for potential genotyping error, and the corresponding SNP is then removed from the study. On the other hand, assuming HWE holds in the study population, a truly associated SNP is expected to be out of HWE in the case group. Efforts have been made in combining association tests with tests of HWE in the cases to increase the power of detecting disease susceptibility loci (Song and Elston (2006), Wang and Shete (2010)). However, these existing methods are ad-hoc and sensitive to model assumptions. Utilizing the recent robust allele-based (RA) regression model for conducting allelic association tests (Zhang and Sun (2020)), here we propose a joint RA test that naturally integrates association evidence from the traditional association test and a test that evaluates the difference in HWD between the case and control groups. The proposed test is robust to genotyping error, as well as to potential HWD in the population attributed to factors that are unrelated to phenotype-genotype association. We provide the asymptotic distribution of the proposed test statistic so that it is easy to implement, and we demonstrate the accuracy and efficiency of the test through extensive simulation studies and an application.
Transcriptome Profiling of different types of human respiratory tract cells infected by SARS-CoV-2 Highlight an unique Role for Inflammatory and Interferon Response
Authors: Yang Minghui , Lei Luping , Cao Qiumei , Yang Yang , Wang Jun , Jiang Xiao , Huang Kun , Lai Jinzhi , Qing Ling , Wang Yu , Liu Yingxia 
Published: November 2020

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) at the end of 2019 has caused a large global outbreak and now become a major public health issue. Lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cells infected with SARS-CoV-2. We selected four studies through a systematic search of the Gene Expression Omnibus (GEO) database or published article about SARS-CoV-2 infection in different types of respiratory tract cells. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these DEGs are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappaB/NF-kappaB complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF, NF-kappa B, Cytokine-cytokine receptor interaction and IL17 signaling pathways during SARS-CoV-2 infection with CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, IL32, CX3CL1, CCL20, IRF1, NFKB2 and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19.
The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects
Authors: Fridman Hila , Yntema Helger G. , Mägi Reedik , Andreson Reidar , Metspalu Andres , Mezzavila Massimo , Tyler-Smith Chris , Xue Yali , Carmi Shai , Levy-Lahad Ephrat , Gilissen Christian , Brunner Han G. 
Published: November 2020

AbstractThe number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6447 exome-sequences of healthy, genetically-unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal recessive (AR) genes, and that 0.8-1% of European couples are at-risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins, but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture.
C. eleganshermaphrodites undergo semelparous reproductive death
Authors: Kern Carina C. , Srivastava Shivangi , Ezcurra Marina , Hui Nancy , Townsend StJohn , Maczik Dominik , Tse Victoria , Bähler Jürg , Gems David 
Published: November 2020

AbstractAgeing in the nematodeCaenorhabditis elegansis unusual in terms of the severity and early onset of senescent pathology, particularly affecting organs involved in reproduction (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002). In post-reproductiveC. eleganshermaphrodites, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (Ezcurra et al., 2018; Sornda et al., 2019). We recently showed that post-reproductive mothers vent yolk which functions as a milk (yolk milk), supporting larval growth that is consumed by larvae (Kern et al., 2020). This form of massive reproductive effort involving biomass repurposing leading to organ degeneration is characteristic of semelparous organisms (i.e. that exhibit only a single reproductive episode) ranging from monocarpic plants to Pacific salmon where it leads to rapid death (reproductive death) (Finch, 1990; Gems et al., 2020). Removal of the germline greatly increases lifespan in bothC. elegansand Pacific salmon, in the latter case by suppressing semelparous reproductive death (Hsin and Kenyon, 1999; Robertson, 1961). Here we present evidence that reproductive death occurs inC. elegans, and that it is suppressed by germline removal, leading to extension of lifespan. Comparing threeCaenorhabditissibling species pairs with hermaphrodites and females, we show that lactation and massive early pathology only occurs in the former. In each case, hermaphrodites are shorter lived and only in hermaphrodites does germline removal markedly increase lifespan. Semelparous reproductive death has previously been viewed as distinct from ageing; however, drawing on recent theories of ageing (Blagosklonny, 2006; de Magalhães and Church, 2005; Maklakov and Chapman, 2019), we argue that it involves exaggerated versions of programmatic mechanisms that to a smaller extent contribute to ageing in non-semelparous species. Thus, despite the presence of reproductive death, mechanisms of ageing inC. elegansare informative about ageing in general.
Effect of corporate governance attributes on IFRS compliance: evidence from a developing country
Authors: Kabwe Martin , Mwanaumo Erastus , Chalu Henry 
Published: November 2020

Purpose
This study aims to analyze the relationship between corporate governance attributes and the International Financial Reporting Standard (IFRS) compliance among Zambian listed companies.

Design/methodology/approach
Data was collected through content analysis of annual reports and audited financial statements of 20 Zambian listed companies for the period 2012 to 2018. This is a longitudinal study which involved panel data analysis. A Hausman test was conducted to select the model to use to run the panel regression analysis.

Findings
The results indicate a positive statistically insignificant relationship between board size, board independence and IFRS compliance. A statistically significant negative relationship between audit committee independence and IFRS compliance. However, there is a positive relationship between board members with accounting and auditing experience, the inclusion of women on the board and IFRS compliance.

Research limitations/implications
Limitation includes the narrow focus on listed companies only which cannot be generalized to other public interest and private companies in Zambia.

Practical implications
The study findings imply that corporate governance attributes such as the inclusion of qualified and experienced Chartered Accountants and women on the board will increase IFRS compliance. The appointment criteria of non-executive directors should be strengthened.

Originality/value
This is the first empirical study to analyze the relationship between IFRS compliance and corporate governance in Zambia. The study also responds to the call by the World Bank (2017) to empirically study IFRS compliance in Zambia and contributes to the scant literature in developing countries on determinants of IFRS compliance.
Urgency of financial technology (Fintech) laws in Indonesia
Authors: Kharisma Dona Budi 
Published: November 2020

Purpose
This paper aims to elaborate the reasons why Indonesia needs Law on Fintech. This paper also identifies the flaws in the existing regulations and policies on Fintech, and it also proposes an ideal framework for a fintech law as a strategy to strengthen consumer protection and to accelerate the growth of the digital economy in Indonesia.

Design/methodology/approach
This is normative research with a legal approach. Data were collected through a literature study and analyzed using legal norm method.

Findings
The promising potential and growth of the fintech industry in Indonesia need to be supported by a sound legal framework in the form of Indonesian Law. In regards to fintech, Indonesia does not yet have a specific law on fintech. Existing regulations in the Bank of Indonesia Regulations (PBI) and Indonesia Financial Services Authority Regulations (POJK) only regulate the technical aspects of the industry, thus providing a less sound legal power. Bank of Indonesia (BI) and Indonesia Financial Services Authority (OJK) have limited authority in the making of regulations and the regulations produced by these institutions cannot stipulate criminal provisions. This results in inadequate consumer protection measures. The Investment Alert Task Force reported 2,018 illegal P2P lending, 472 illegal investment companies and 69 illegal pawnbrokers. The accumulation of online lending transactions in December 2019 reached a total of IDR81.50tn, seeing a 259.56% increase from the previous year. Meanwhile, the amount of bad debt reached IDR13.6tn, seeing a 169.48% increase. These reasons illustrate how urgently Indonesia needs Fintech Law.

Research limitations/implications
This research only examines the existing Fintech regulations in Indonesia. The approach method used is normative legal research.

Practical implications
This research is expected to be useful for The House of Representatives of the Republic of Indonesia (DPR), the Ministry of Law and Human Rights, the Indonesia Financial Services Authority (OJK) and Bank of Indonesia (BI) in drafting the Fintech Law.

Social implications
This research is expected to increase protection for consumers, investors and providers of fintech services and accelerate the growth of the digital economy in Indonesia.

Originality/value
Regulating fintech in the Indonesian Law is meant to give legal certainty and better legal protection for consumers, investors and providers of fintech services. Seeing that the value of the Indonesian digital economy in 2019 has reached USD40bn (approximately IDR586tn), Indonesia is philosophically, juridically and sociologically in urgent need of Fintech Law.