bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative-omics for discovery of network-level disease biomarkers: a case study in Alzheimer’s disease
Authors: Xie Linhui , He Bing , Varathan Pradeep , Nho Kwangsik , Risacher Shannon L , Saykin Andrew J , Salama Paul , Yan Jingwen 
Published: March 2021

Abstract
A large number of genetic variations have been identified to be associated with Alzheimer’s disease (AD) and related quantitative traits. However, majority of existing studies focused on single types of omics data, lacking the power of generating a community including multi-omic markers and their functional connections. Because of this, the immense value of multi-omics data on AD has attracted much attention. Leveraging genomic, transcriptomic and proteomic data, and their backbone network through functional relations, we proposed a modularity-constrained logistic regression model to mine the association between disease status and a group of functionally connected multi-omic features, i.e. single-nucleotide polymorphisms (SNPs), genes and proteins. This new model was applied to the real data collected from the frontal cortex tissue in the Religious Orders Study and Memory and Aging Project cohort. Compared with other state-of-art methods, it provided overall the best prediction performance during cross-validation. This new method helped identify a group of densely connected SNPs, genes and proteins predictive of AD status. These SNPs are mostly expression quantitative trait loci in the frontal region. Brain-wide gene expression profile of these genes and proteins were highly correlated with the brain activation map of ‘vision’, a brain function partly controlled by frontal cortex. These genes and proteins were also found to be associated with the amyloid deposition, cortical volume and average thickness of frontal regions. Taken together, these results suggested a potential pathway underlying the development of AD from SNPs to gene expression, protein expression and ultimately brain functional and structural changes.
Elucidating transcriptomic profiles from single-cell RNA sequencing data using nature-inspired compressed sensing
Authors: Yu Zhuohan , Bian Chuang , Liu Genggeng , Zhang Shixiong , Wong Ka-Chun , Li Xiangtao 
Published: March 2021

AbstractGene-expression profiling can define the cell state and gene-expression pattern of cells at the genetic level in a high-throughput manner. With the development of transcriptome techniques, processing high-dimensional genetic data has become a major challenge in expression profiling. Thanks to the recent widespread use of matrix decomposition methods in bioinformatics, a computational framework based on compressed sensing was adopted to reduce dimensionality. However, compressed sensing requires an optimization strategy to learn the modular dictionaries and activity levels from the low-dimensional random composite measurements to reconstruct the high-dimensional gene-expression data. Considering this, here we introduce and compare four compressed sensing frameworks coming from nature-inspired optimization algorithms (CSCS, ABCCS, BACS and FACS) to improve the quality of the decompression process. Several experiments establish that the three proposed methods outperform benchmark methods on nine different datasets, especially the FACS method. We illustrate therefore, the robustness and convergence of FACS in various aspects; notably, time complexity and parameter analyses highlight properties of our proposed FACS. Furthermore, differential gene-expression analysis, cell-type clustering, gene ontology enrichment and pathology analysis are conducted, which bring novel insights into cell-type identification and characterization mechanisms from different perspectives. All algorithms are written in Python and available at https://github.com/Philyzh8/Nature-inspired-CS.
Bioinformatics and system biology approaches to identify the diseasome and comorbidities complexities of SARS-CoV-2 infection with the digestive tract disorders
Authors: Nashiry Md Asif , Sumi Shauli Sarmin , Sharif Shohan Mohammad Umer , Alyami Salem A , Azad A K M , Moni Mohammad Ali 
Published: March 2021

Abstract
Coronavirus Disease 2019 (COVID-19), although most commonly demonstrates respiratory symptoms, but there is a growing set of evidence reporting its correlation with the digestive tract and faeces. Interestingly, recent studies have shown the association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with gastrointestinal symptoms in infected patients but any sign of respiratory issues. Moreover, some studies have also shown that the presence of live SARS-CoV-2 virus in the faeces of patients with COVID-19. Therefore, the pathophysiology of digestive symptoms associated with COVID-19 has raised a critical need for comprehensive investigative efforts. To address this issue we have developed a bioinformatics pipeline involving a system biological framework to identify the effects of SARS-CoV-2 messenger RNA expression on deciphering its association with digestive symptoms in COVID-19 positive patients. Using two RNA-seq datasets derived from COVID-19 positive patients with celiac (CEL), Crohn’s (CRO) and ulcerative colitis (ULC) as digestive disorders, we have found a significant overlap between the sets of differentially expressed genes from SARS-CoV-2 exposed tissue and digestive tract disordered tissues, reporting 7, 22 and 13 such overlapping genes, respectively. Moreover, gene set enrichment analysis, comprehensive analyses of protein–protein interaction network, gene regulatory network, protein–chemical agent interaction network revealed some critical association between SARS-CoV-2 infection and the presence of digestive disorders. The infectome, diseasome and comorbidity analyses also discover the influences of the identified signature genes in other risk factors of SARS-CoV-2 infection to human health. We hope the findings from this pathogenetic analysis may reveal important insights in deciphering the complex interplay between COVID-19 and digestive disorders and underpins its significance in therapeutic development strategy to combat against COVID-19 pandemic.
Understanding Successes and Failures of Family Group Conferencing: An in-Depth Multiple Case Study
Authors: Bredewold F , Tonkens E 
Published: March 2021

Abstract
Family group conferencing (FGC) is considered to be a promising method for empowerment and community building of people in need of care and their families. However, empirical studies on the effects of FGC show mixed results, and often fail to explain these. In this article, we critically reflect under which conditions FGCs may or may not become successful, on the basis of a small-scale longitudinal research of four cases in which FGC was used, supplemented by analysis of research on FGC, interviews with social workers and observations of trainings of social workers who intend to apply FGC. Our data point to four conditions for successful application of FGC, concerning (i) the presence of a (positive) network, (ii) the need for formal care in addition to informal care by way of the FGC, (iii) active protection against paternalism and humiliation and (iv) taking seriously client’s reluctance to ask social network members for help. The possible risks and conditions, we formulate, hopefully help social workers to decide case by case whether the use of FGC indeed promises to be helpful or, conversely, it may be harmful.
Ethics of ICU triage during COVID-19
Authors: Vinay Rasita , Baumann Holger , Biller-Andorno Nikola 
Published: March 2021

Abstract

Introduction
The coronavirus disease 2019 pandemic has placed intensive care units (ICU) triage at the center of bioethical discussions. National and international triage guidelines emerged from professional and governmental bodies and have led to controversial discussions about which criteria—e.g. medical prognosis, age, life-expectancy or quality of life—are ethically acceptable. The paper presents the main points of agreement and disagreement in triage protocols and reviews the ethical debate surrounding them.

Sources of data
Published articles, news articles, book chapters, ICU triage guidelines set out by professional societies and health authorities.

Areas of agreement
Points of agreement in the guidelines that are widely supported by ethical arguments are (i) to avoid using a first come, first served policy or quality-adjusted life-years and (ii) to rely on medical prognosis, maximizing lives saved, justice as fairness and non-discrimination.

Areas of controversy
Points of disagreement in existing guidelines and the ethics literature more broadly regard the use of exclusion criteria, the role of life expectancy, the prioritization of healthcare workers and the reassessment of triage decisions.

Growing points
Improve outcome predictions, possibly aided by Artificial intelligence (AI); develop participatory approaches to drafting, assessing and revising triaging protocols; learn from experiences with implementation of guidelines with a view to continuously improve decision-making.

Areas timely for developing research
Examine the universality vs. context-dependence of triaging principles and criteria; empirically test the appropriateness of triaging guidelines, including impact on vulnerable groups and risk of discrimination; study the potential and challenges of AI for outcome and preference prediction and decision-support.
Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Authors: Akin Elizabeth J , Alsaloum Matthew , Higerd Grant P , Liu Shujun , Zhao Peng , Dib-Hajj Fadia B , Waxman Stephen G , Dib-Hajj Sulayman D 
Published: March 2021

AbstractThe microtubule-stabilizing chemotherapy drug paclitaxel (PTX) causes dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), which is often accompanied by pain. Among the multifaceted effects of PTX is an increased expression of sodium channel Nav1.7 in rat and human sensory neurons, enhancing their excitability. However, the mechanisms underlying this increased Nav1.7 expression have not been explored, and the effects of PTX treatment on the dynamics of trafficking and localization of Nav1.7 channels in sensory axons have not been possible to investigate to date. In this study we used a recently developed live imaging approach that allows visualization of Nav1.7 surface channels and long-distance axonal vesicular transport in sensory neurons to fill this basic knowledge gap. We demonstrate concentration and time-dependent effects of PTX on vesicular trafficking and membrane localization of Nav1.7 in real-time in sensory axons. Low concentrations of PTX increase surface channel expression and vesicular flux (number of vesicles per axon). By contrast, treatment with a higher concentration of PTX decreases vesicular flux. Interestingly, vesicular velocity is increased for both concentrations of PTX. Treatment with PTX increased levels of endogenous Nav1.7 mRNA and current density in dorsal root ganglion neurons. However, the current produced by transfection of dorsal root ganglion neurons with Halo-tag Nav1.7 was not increased after exposure to PTX. Taken together, this suggests that the increased trafficking and surface localization of Halo-Nav1.7 that we observed by live imaging in transfected dorsal root ganglion neurons after treatment with PTX might be independent of an increased pool of Nav1.7 channels. After exposure to inflammatory mediators to mimic the inflammatory condition seen during chemotherapy, both Nav1.7 surface levels and vesicular transport are increased for both low and high concentrations of PTX. Overall, our results show that PTX treatment increases levels of functional endogenous Nav1.7 channels in dorsal root ganglion neurons and enhances trafficking and surface distribution of Nav1.7 in sensory axons, with outcomes that depend on the presence of an inflammatory milieu, providing a mechanistic explanation for increased excitability of primary afferents and pain in CIPN.
A decision-neuroscientific intervention to improve cognitive recovery after stroke
Authors: Studer Bettina , Timm Alicja , Sahakian Barbara J , Kalenscher Tobias , Knecht Stefan 
Published: March 2021

Abstract
Functional recovery after stroke is dose-dependent on the amount of rehabilitative training. However, rehabilitative training is subject to motivational hurdles. Decision neuroscience formalizes drivers and dampers of behaviour and provides strategies for tipping motivational trade-offs and behaviour change. Here, we used one such strategy, upfront voluntary choice restriction (‘precommitment’), and tested if it can increase the amount of self-directed rehabilitative training in severely impaired stroke patients. In this randomized controlled study, stroke patients with working memory deficits (n = 83) were prescribed daily self-directed gamified cognitive training as an add-on to standard therapy during post-acute inpatient neurorehabilitation. Patients allocated to the precommitment intervention could choose to restrict competing options to self-directed training, specifically the possibility to meet visitors. This upfront choice restriction was opted for by all patients in the intervention group and highly effective. Patients in the precommitment group performed the prescribed self-directed gamified cognitive training twice as often as control group patients who were not offered precommitment [on 50% versus 21% of days, Pcorr = 0.004, d = 0.87, 95% confidence interval (CI95%) = 0.31 to 1.42], and, as a consequence, reached a 3-fold higher total training dose (90.21 versus 33.60 min, Pcorr = 0.004, d = 0.83, CI95% = 0.27 to 1.38). Moreover, add-on self-directed cognitive training was associated with stronger improvements in visuospatial and verbal working memory performance (Pcorr = 0.002, d = 0.72 and Pcorr = 0.036, d = 0.62). Our neuroscientific decision add-on intervention strongly increased the amount of effective cognitive training performed by severely impaired stroke patients. These results warrant a full clinical trial to link decision-based neuroscientific interventions directly with clinical outcome.
Innate immunity stimulation via CpG oligodeoxynucleotides ameliorates Alzheimer’s disease pathology in aged squirrel monkeys
Authors: Patel Akash G , Nehete Pramod N , Krivoshik Sara R , Pei Xuewei , Cho Elizabeth L , Nehete Bharti P , Ramani Margish D , Shao Yongzhao , Williams Lawrence E , Wisniewski Thomas , Scholtzova Henrieta 
Published: March 2021

Abstract
Alzheimer’s disease is the most common cause of dementia and the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The failure rate of clinical trials is very high, in part due to the premature translation of successful results in transgenic mouse models to patients. Extensive evidence suggests that dysregulation of innate immunity and microglia/macrophages plays a key role in Alzheimer’s disease pathogenesis. Activated resident microglia and peripheral macrophages can display protective or detrimental phenotypes depending on the stimulus and environment. Toll-like receptors (TLRs) are a family of innate immune regulators known to play an important role in governing the phenotypic status of microglia. We have shown in multiple transgenic Alzheimer’s disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-β, tau pathology, and cerebral amyloid angiopathy (CAA) while promoting cognitive benefits. In the current study we have used a non-human primate model of sporadic Alzheimer’s disease pathology that develops extensive CAA—elderly squirrel monkeys. The major complications in current immunotherapeutic trials for Alzheimer’s disease are amyloid-related imaging abnormalities, which are linked to the presence and extent of CAA; hence, the prominence of CAA in elderly squirrel monkeys makes them a valuable model for studying the safety of the CpG ODN-based concept of immunomodulation. We demonstrate that long-term use of Class B CpG ODN 2006 induces a favourable degree of innate immunity stimulation without producing excessive or sustained inflammation, resulting in efficient amelioration of both CAA and tau Alzheimer’s disease-related pathologies in association with behavioural improvements and in the absence of microhaemorrhages in aged elderly squirrel monkeys. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. The present evidence together with our earlier, extensive preclinical research, validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach, increasing the likelihood of CpG ODN therapeutic efficacy in future clinical trials.
Left-Handers Are Less Lateralized Than Right-Handers for Both Left and Right Hemispheric Functions
Authors: Johnstone Leah T , Karlsson Emma M , Carey David P 
Published: March 2021

Abstract
Many neuroscientific techniques have revealed that more left- than right-handers will have unusual cerebral asymmetries for language. After the original emphasis on frequency in the aphasia and epilepsy literatures, most neuropsychology, and neuroimaging efforts rely on estimates of central tendency to compare these two handedness groups on any given measure of asymmetry. The inevitable reduction in mean lateralization in the left-handed group is often postulated as being due to reversed asymmetry in a small subset of them, but it could also be due to a reduced asymmetry in many of the left-handers. These two possibilities have hugely different theoretical interpretations. Using functional magnetic resonance imaging localizer paradigms, we matched left- and right-handers for hemispheric dominance across four functions (verbal fluency, face perception, body perception, and scene perception). We then compared the degree of dominance between the two handedness groups for each of these four measures, conducting t-tests on the mean laterality indices. The results demonstrate that left-handers with typical cerebral asymmetries are less lateralized for language, faces, and bodies than their right-handed counterparts. These results are difficult to reconcile with current theories of language asymmetry or of handedness.
Maintaining Low Prevalence of Schistosoma mansoni: Modeling the Effect of Less Frequent Treatment
Authors: Ayabina Diepreye , Kura Klodeta , Toor Jaspreet , Graham Matt , Anderson Roy M , Hollingsworth T Deirdre 
Published: March 2021

Abstract

Background
The World Health Organization previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals.

Methods
We used 2 independently developed, individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multiyear program to maintain the morbidity control and the EPHP goals.

Results
We found that, in moderate-prevalence settings, once the morbidity control and EPHP goals are reached it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high-transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence.

Conclusions
To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.
The Matching Preclusion of Enhanced Hypercubes
Authors: Wang Shiying , Ma Xiaolei 
Published: March 2021

Abstract
The (conditional) matching preclusion number of a graph is the minimum number of edges whose deletion leaves the resulting graph (with no isolated vertices) that has neither perfect matchings nor almost perfect matchings. The (conditional) strong matching preclusion number of a graph is the minimum number of vertices and edges whose deletion makes the resulting graph (with no isolated vertices) without perfect matching or almost perfect matching. The enhanced hypercube $Q_{n,k}$ $(1\leq k\leq n-1)$ is an extension of hypercube. In this paper, we prove that the matching preclusion number of $Q_{n,k}$ is $n+1$ $(1\leq k\leq n-1)$, the strong matching preclusion number of $Q_{n,k}$ is $n+1$ $(2\leq k\leq n-1)$, the conditional matching preclusion number of $Q_{n,n-1}$ is $2n-1$, the conditional matching preclusion number of $Q_{n,k}$ is $2n$ $(1\leq k\leq n-2)$ and the conditional strong matching preclusion number of $Q_{n,n-2}$ is $2n-3$ $(n\geq 4)$.
Ad Singularitatem: Multiplicity, Commonplaced Selves, and Miscellanies in Siri Hustvedt’s The Blazing World
Authors: Ha Inhye 
Published: March 2021

Abstract
This essay focuses on the intertextual engagement of Siri Hustvedt’s The Blazing World with Margaret Cavendish’s seventeenth-century fiction. Going beyond a single-text reading, the essay argues that Hustvedt’s critical interventions in the making of a woman’s subjectivity—paratextual and intermedial—are informed by early modern manuscript culture and ekphrasis. As commonplacing affords opportunities for a compiler to assume plural voices, the commonplace books created by Burden, the protagonist, present a nuanced unfolding of a woman’s subjectivity on textual and visual levels. Notably, Burden’s self-fashioning and ensuing self-dissolution are prompted by deep-seated anger. Hustvedt, even in the face of her protagonist’s tragic end, celebrates the multiplicity that attends a woman’s heroic journey in attaining singularity.
Population trends in achalasia diagnosis and management: a changing paradigm
Authors: Trieu Judy A , Dua Arshish , Enofe Ikponmwosa , Shastri Nikhil , Venu Mukund 
Published: March 2021

Summary
The Chicago Classification of esophageal motility disorders improved the differentiation of achalasia subtypes and tailored treatment. Heller myotomy (HM) and pneumatic dilation are two established treatments for achalasia. Peroral endoscopic myotomy (POEM) has become a third definitive option and is on the rise. Using the National Inpatient Sample (NIS) database, we evaluated patients hospitalized with achalasia and associated surgical and endoscopic interventions from 2013 to 2017 and compared patients undergoing HM versus POEM. The NIS database was queried to include patients with achalasia. Patients who underwent HM, POEM (only 2017 due to lack of distinct procedure code in 2013), pneumatic dilation, or esophagectomy were identified. Adverse events during the hospitalization were also queried using diagnosis codes. From 2013 to 2017, patients hospitalized with achalasia increased from 16 850 to 19 485. There were reductions in the number of esophageal dilations (10.6–5.4%, P &lt; 0.001) and HM (18.7–13.1%, P &lt; 0.001). In 2017, 580 POEMs were performed. Compared with patients undergoing HM in 2017, patients who had POEM had higher mean age &gt; 64 (P = 0.004), Charlson comorbidity index (P &lt; 0.001), disease severity (P &lt; 0.001), and likelihood of mortality (P &lt; 0.001). There were no differences in length of stay, mortality, or total costs between the HM and POEM groups. Patients hospitalized with achlasia increased from 2013 to 2017, possibly due to the growth and accessibility of high-resolution esophageal manometry. As expertise in POEM increases, the number of POEM performed is anticipated to rise with possible further reductions in other treatment modalities for achalasia.