bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of synthetic molecular reporters for a mesenchymal glioblastoma transcriptional program by integer programing
Authors: Breitenbach Tim , Schmitt Matthias Jürgen , Dandekar Thomas 
Published: July 2022

AbstractMotivationA recent approach to perform genetic tracing of complex biological problems involves the generation of synthetic deoxyribonucleic acid (DNA) probes that specifically mark cells with a phenotype of interest. These synthetic locus control regions (sLCRs), in turn, drive the expression of a reporter gene, such as fluorescent protein. To build functional and specific sLCRs, it is critical to accurately select multiple bona fide cis-regulatory elements from the target cell phenotype cistrome. This selection occurs by maximizing the number and diversity of transcription factors (TFs) within the sLCR, yet the size of the final sLCR should remain limited.ResultsIn this work, we discuss how optimization, in particular integer programing, can be used to systematically address the construction of a specific sLCR and optimize pre-defined properties of the sLCR. Our presented instance of a linear optimization problem maximizes the activation potential of the sLCR such that its size is limited to a pre-defined length and a minimum number of all TFs deemed sufficiently characteristic for the phenotype of interest is covered. We generated an sLCR to trace the mesenchymal glioblastoma program in patients by solving our corresponding linear program with the software optimizer Gurobi. Considering the binding strength of transcription factor binding sites (TFBSs) with their TFs as a proxy for activation potential, the optimized sLCR scores similarly to an sLCR experimentally validated in vivo, and is smaller in size while having the same coverage of TFBSs.Availability and implementationWe provide a Python implementation of the presented framework in the Supplementary Material with which an optimal selection of cis-regulatory elements can be calculated once the target set of TFs and their binding strength with their TFBSs is known.Supplementary informationSupplementary data are available at Bioinformatics online.
DiffChIPL: a differential peak analysis method for high-throughput sequencing data with biological replicates based on limma
Authors: Chen Yang , Chen Shue , Lei Elissa P 
Published: July 2022

AbstractMotivationChIP-seq detects protein–DNA interactions within chromatin, such as that of chromatin structural components and transcription machinery. ChIP-seq profiles are often noisy and variable across replicates, posing a challenge to the development of effective algorithms to accurately detect differential peaks. Methods have recently been designed for this purpose but sometimes yield conflicting results that are inconsistent with the underlying biology. Most existing algorithms perform well on limited datasets. To improve differential analysis of ChIP-seq, we present a novel Differential analysis method for ChIP-seq based on Limma (DiffChIPL).ResultsDiffChIPL is adaptive to asymmetrical or symmetrical data and can accurately report global differences. We used simulated and real datasets for transcription factors (TFs) and histone modification marks to validate and benchmark our algorithm. DiffChIPL shows superior performance in sensitivity and false positive rate in different simulations and control datasets. DiffChIPL also performs well on real ChIP-seq, CUT&RUN, CUT&Tag and ATAC-seq datasets. DiffChIPL is an accurate and robust method, exhibiting better performance in differential analysis for a variety of applications including TF binding, histone modifications and chromatin accessibility.Availability and implementationhttps://github.com/yancychy/DiffChIPL.Supplementary informationSupplementary data are available at Bioinformatics online.
Evaluating causes of effects by posterior effects of causes
Authors: Lu Zitong , Geng Zhi , Li Wei , Zhu Shengyu , Jia Jinzhu 
Published: July 2022

SummaryFor the case with a single causal variable, Dawid et al. (2014) defined the probability of causation, and Pearl (2000) defined the probability of necessity to assess the causes of effects. For a case with multiple causes that could affect each other, this paper defines the posterior total and direct causal effects based on the evidence observed for post-treatment variables, which could be viewed as measurements of causes of effects. Posterior causal effects involve the probabilities of counterfactual variables. Thus, as with the probability of causation, the probability of necessity and direct causal effects, the identifiability of posterior total and direct causal effects requires more assumptions than the identifiability of traditional causal effects conditional on pre-treatment variables. We present assumptions required for the identifiability of posterior causal effects and provide identification equations. Further, when the causal relationships between multiple causes and an endpoint can be depicted by causal networks, we can simplify both the required assumptions and the identification equations of the posterior total and direct causal effects. Finally, using numerical examples, we compare the posterior total and direct causal effects with other measures for evaluating the causes of effects and the population attributable risks.
Reciprocal Contributions between People and Nature: A Conceptual Intervention
Authors: Ojeda Jaime , Salomon Anne K , Rowe James K , Ban Natalie C 
Published: July 2022

Abstract
Throughout human history, Indigenous and local communities have stewarded nature. In the present article, we revisit the ancestral principle of reciprocity between people and nature and consider it as a conceptual intervention to the current notion of ecosystem services commonly used to inform sustainability transformation. We propose the concept of reciprocal contributions to encompass actions, interactions, and experiences between people and other components of nature that result in positive contributions and feedback loops that accrue to both, directly or indirectly, across different dimensions and levels. We identify reciprocal contributions and showcase examples that denote the importance of reciprocity for our ecological legacy and its relevance for biocultural continuity. We suggest that the concept of reciprocal contribution can support transformation pathways by resituating people as active components of nature and restructuring institutions so that ethical principles and practices from Indigenous and local communities can redirect policy approaches and interventions worldwide.
Secondary Sclerosing Cholangitis Following Coronavirus Disease 2019 (COVID-19): A Multicenter Retrospective Study
Authors: Hunyady Peter , Streller Lea , Rüther Darius F , Groba Sara Reinartz , Bettinger Dominik , Fitting Daniel , Hamesch Karim , Marquardt Jens U , Mücke Victoria T , Finkelmeier Fabian , Sekandarzad Asieb , Wengenmayer Tobias , Bounidane Ayoub , Weiss Felicitas , Peiffer Kai-Henrik , Schlevogt Bernhard , Zeuzem Stefan , Waidmann Oliver , Hollenbach Marcus , Kirstein Martha M , Kluwe Johannes , Kütting Fabian , Mücke Marcus M 
Published: July 2022

Abstract

Background
Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival.

Methods
In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival.

Results
Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P = .443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio [OR], 0.36 [95% confidence interval {CI}, .16–.80], P = .013; log-rank P &lt; .001) and high serum albumin levels (OR, 0.40 [95% CI, .17–.96], P = .040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 [95% CI, 1.01–6.25], P = .047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients’ survival.

Conclusions
COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings.
Universal behaviour of the growth method and importance of local hubs in cascading failure
Authors: Jeong Wonhee , Yu Unjong 
Published: July 2022

Abstract
We introduce hub centrality and study the relation between hub centrality and the degree of each node in the networks. We discover and verify a universal relation between them in various networks generated by the growth method, but the relation is not applied to real-world networks due to the rich-club phenomenon and the presence of local hubs. Through the study of a targeted attack and overload cascading failure, we prove that hub centrality is a meaningful parameter that gives extra insight beyond degree in real-world networks. Especially, we show that the local hubs occupy key positions in real-world networks with higher probabilities to incur global cascading failure. Therefore, we conclude that networks generated by the growth method, which do not include local hubs, have inevitable limitations to describe real-world networks.
Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging
Authors: Mavrogeni S , Pepe A , Nijveldt R , Ntusi N , Sierra-Galan L M , Bratis K , Wei J , Mukherjee M , Markousis-Mavrogenis G , Gargani L , Sade L E , Ajmone-Marsan N , Seferovic P , Donal E , Nurmohamed M , Cerinic M Matucci , Sfikakis P , Kitas G , Schwitter J , Lima J A C , Dawson Dana , Dweck Marc , Haugaa Kristina H , Keenan Niall , Moon James , Stankovic Ivan , Donal Erwan , Cosyns Bernard 
Published: July 2022

Abstract
Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy.
Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients.
Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.
Impact of sex, race and socioeconomic status on survival after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension
Authors: Su Austin Y , Vinogradsky Alice , Wang Amy S , Ning Yuming , Abrahams Elizabeth , Bacchetta Matthew , Kurlansky Paul , Rosenzweig Erika B , Takeda Koji 
Published: July 2022

Abstract

OBJECTIVES
Pulmonary thromboendarterectomy (PTE) is a definitive treatment for chronic thromboembolic pulmonary hypertension. Demographic-based disparities in PTE outcomes have not been well-studied.

METHODS
We reviewed all patients who underwent PTE for chronic thromboembolic pulmonary hypertension between 2009 and 2019 at our institution, tracking demographic information including self-identified race, preoperative characteristics and 2-year survival. Socioeconomic status was assessed using the zip code-linked Distressed Communities Index, a validated holistic measure of community well-being. Survival was estimated using Kaplan–Meier method and factors associated with mortality were estimated using Cox regression.

RESULTS
Of 235 PTE patients, 101 (42.9%) were white and 87 (37.0%) were black. White patients had a higher median age at surgery (57 vs 51 years, P = 0.035) and a lower degree of economic distress (33.6 vs 61.2 percentile, P &lt; 0.001). Regarding sex, 106 (45.1%) patients were male and 129 (53.6%) were female. Male patients had a higher median age (59 vs 50 years, P = 0.004), greater rates of dyslipidaemia (34% vs 20.2%, P = 0.025), a lower ejection fraction (55% vs 57%, P = 0.046) and longer cross-clamp (77 vs 67.50 min, P = 0.004) and circulatory arrest times (42 vs 37.50 min, P = 0.007). No difference was observed in unadjusted 2-year survival after PTE between patients stratified by race and sex (P = 0.35). After adjustment for clinically relevant variables, neither socioeconomic status, sex nor race were associated with mortality in Cox proportional hazard analysis.

CONCLUSIONS
Sex, socioeconomic status and race were not associated with adverse outcomes after PTE in our single-centre experience.
The arch remodelling stent for DeBakey I acute aortic dissection: experience with 100 implantations
Authors: Montagner Matteo , Kofler Markus , Seeber Fabian , Pitts Leonard , Starck Christoph , Sündermann Simon H , Kurz Stephan , Grubitzsch Herko , Falk Volkmar , Kempfert Jörg 
Published: July 2022

Abstract

OBJECTIVES
A novel hybrid non-covered stent was developed to treat malperfusion and prevent aneurysm formation following hemiarch procedure for DeBakey I acute aortic dissection (AAD). The present analysis investigates the performance of the device in 100 consecutive implantations.

METHODS
Between 2018 and 2021, 100 patients underwent surgical repair of DeBakey I AAD with implantation of a non-covered stent in the arch and descending aorta. The primary entry tear was located in the root or the ascending aorta. Clinical and imaging data were collected and analysed retrospectively. The endpoints of the study were 30-day mortality, neurological outcome and need of additional procedures due to postoperative malperfusion. Technical success was assessed in the first postoperative computed tomography in regard to the induction of false lumen thrombosis in the descending aorta.

RESULTS
The median age was 61 (54–73) years. Preoperative malperfusion was present in 46 (46%) patients. The primary arterial cannulation strategy was the right axillary artery and an open distal anastomosis was performed in a median caudal circulatory arrest of 40 (34–52) min. In 48% of cases, a 55–40 tapered stent was implanted. The 30-day mortality was 18%, and the operation-related new postoperative neurological deficit was present in 8%. Technical success was achieved in 76% of patients.

CONCLUSIONS
The novel non-covered stent can be safely applied to complement aortic repair with the hemiarch procedure for DeBakey I AAD. The expansion of the true lumen through the device may prevent postoperative malperfusion and induces positive vascular remodelling with the thrombosis of the false lumen.
Discrimination unveiled: a field experiment on the barriers faced by Muslim women in Germany, the Netherlands, and Spain
Authors: Fernández-Reino Mariña , Di Stasio Valentina , Veit Susanne 
Published: July 2022

Abstract
We examine the penalties faced by veiled and unveiled Muslim women when applying for jobs in three European labour markets: Germany, the Netherlands, and Spain. We rely on recent literature comparing public opposition towards Muslims in general and opposition to Muslims’ religious practices, such as the wearing of the hijab. Based on a cross-nationally harmonized field experiment on hiring discrimination, we use two different signals of Muslimness (volunteering activities in a Muslim community centre or wearing the Muslim headscarf) to identify whether employers discriminate against Muslims as a group or against Muslims adhering to specific Muslim practices—in this case, wearing the headscarf. We present robust evidence that veiled Muslim women are discriminated against in Germany and the Netherlands, but only when applying for jobs that require a high level of customer contact. In Spain, however, the level of discrimination against veiled Muslim women is much smaller than in the other two countries. The high level of discrimination we found in the Netherlands, where the institutional context has traditionally been open to the accommodation of religious minority rights, is particularly surprising and points to the possibly stigmatizing effect of recent policies geared towards the cultural assimilation of immigrants.
Health outcomes in primary care: a 20-year evidence map of randomized controlled trials
Authors: Missiou Aristea , Lionis Christos , Evangelou Evangelos , Tatsioni Athina 
Published: July 2022

Abstract

Objective
To quantify the different types of health outcomes assessed as primary outcomes in randomized controlled trials (RCTs) in the primary care (PC) setting during the last 20 years and identify whether potential gaps exist in specific types of health care and types of intervention.

Methods
We systematically searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from January 2000 to September 2020 for published RCTs in PC. We recorded characteristics of eligible studies and mapped evidence by health outcome category (patient health outcomes, health services outcomes); and for each outcome category, by types of health care (preventive, acute, chronic, palliative), and by types of intervention (drug, behavioural, on structure, and on process). For RCTs assessing patient health outcomes as primary outcomes, we further mapped using the quality-of-care dimensions, that is, effectiveness, safety, and patient-centredness.

Results
Of the 518 eligible RCTs in PC, 357 (68.9%) evaluated a patient health outcome as the primary outcome, and 161 (31.1%) evaluated only health services outcomes as primary outcomes. Many focused on population with chronic illness (224 trials; 43.2%) and evaluated interventions on processes of health care (239 trials; 46.1%). Research gaps identified include preventive and palliative care, behavioural interventions, and safety and patient-centredness outcomes as primary outcomes.

Conclusion
Our evidence map showed research gaps in certain types of health care and interventions. It also showed research gaps in assessing safety and measures to place patient at the centre of health care delivery as primary outcomes.
The Chromosomal Distribution of Sex-Biased MicroRNAs in Drosophila is Nonadaptive
Authors: Marco Antonio 
Published: July 2022

Abstract
Genes are often differentially expressed between males and females. In Drosophila melanogaster, the analysis of sex-biased microRNAs (short noncoding regulatory molecules) has revealed striking differences with protein-coding genes. Mainly, the X chromosome is enriched in male-biased microRNA genes, although it is depleted of male-biased protein-coding genes. The paucity of male-biased genes in the X chromosome is generally explained by an evolutionary process called demasculinization. I suggest that the excess of male-biased microRNAs in the X chromosome is due to high rates of de novo emergence of microRNAs (mostly in other neighboring microRNAs), a tendency of novel microRNAs in the X chromosome to be expressed in testis, and to a lack of a demasculinization process. To test this hypothesis, I analyzed the expression profile of microRNAs in males, females, and gonads in D. pseudoobscura, in which an autosome translocated into the X chromosome effectively becoming part of a sex chromosome (neo-X). I found that the pattern of sex-biased expression is generally conserved between D. melanogaster and D. pseudoobscura. Also, orthologous microRNAs in both species conserve their chromosomal location, indicating that there is no evidence of demasculinization or other interchromosomal movement of microRNAs. Drosophila pseudoobscura-specific microRNAs in the neo-X chromosome tend to be male-biased and particularly expressed in testis. In summary, the apparent paradox resulting from male-biased protein-coding genes depleted in the X chromosome and an enrichment in male-biased microRNAs is consistent with different evolutionary dynamics between coding genes and short RNAs.
Loop detection using Hi-C data with HiCExplorer
Authors: Wolff Joachim , Backofen Rolf , Grüning Björn 
Published: July 2022

Abstract

Background
Chromatin loops are an essential factor in the structural organization of the genome; however, their detection in Hi-C interaction matrices is a challenging and compute-intensive task. The approach presented here, integrated into the HiCExplorer software, shows a chromatin loop detection algorithm that applies a strict candidate selection based on continuous negative binomial distributions and performs a Wilcoxon rank-sum test to detect enriched Hi-C interactions.

Results
HiCExplorer’s loop detection has a high detection rate and accuracy. It is the fastest available CPU implementation and utilizes all threads offered by modern multicore platforms.

Conclusions
HiCExplorer’s method to detect loops by using a continuous negative binomial function combined with the donut approach from HiCCUPS leads to reliable and fast computation of loops. All the loop-calling algorithms investigated provide differing results, which intersect by $\sim 50\%$ at most. The tested in situ Hi-C data contain a large amount of noise; achieving better agreement between loop calling algorithms will require cleaner Hi-C data and therefore future improvements to the experimental methods that generate the data.