bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell Chromatin Accessibility Analysis Reveals the Epigenetic Basis and Signature Transcription Factors for the Molecular Subtypes of Colorectal Cancers
Authors: Liu Zhenyu , Hu Yuqiong , Xie Haoling , Chen Kexuan , Wen Lu , Fu Wei , Zhou Xin , Tang Fuchou 
Published: March 2024

Abstract

Colorectal cancer is a highly heterogeneous disease, with well-characterized subtypes based on genome, DNA methylome, and transcriptome signatures. To chart the epigenetic landscape of colorectal cancers, we generated a high-quality single-cell chromatin accessibility atlas of epithelial cells for 29 patients. Abnormal chromatin states acquired in adenomas were largely retained in colorectal cancers, which were tightly accompanied by opposite changes of DNA methylation. Unsupervised analysis on malignant cells revealed two epigenetic subtypes, exactly matching the iCMS classification, and key iCMS-specific transcription factors (TFs) were identified, including HNF4A and PPARA for iCMS2 tumors and FOXA3 and MAFK for iCMS3 tumors. Notably, subtype-specific TFs bind to distinct target gene sets and contribute to both interpatient similarities and diversities for both chromatin accessibilities and RNA expressions. Moreover, we identified CpG-island methylator phenotypes and pinpointed chromatin state signatures and TF regulators for the CIMP-high subtype. Our work systematically revealed the epigenetic basis of the well-known iCMS and CIMP classifications of colorectal cancers.

Significance:
Our work revealed the epigenetic basis of the well-known iCMS and CIMP classifications of colorectal cancers. Moreover, interpatient minor similarities and major diversities of chromatin accessibility signatures of TF target genes can faithfully explain the corresponding interpatient minor similarities and major diversities of RNA expression signatures of colorectal cancers, respectively.
This article is featured in Selected Articles from This Issue, p. 897
Impact of Rapid Up-Titration of Guideline-Directed Medical Therapies on Quality of Life: Insights From the STRONG-HF Trial
Authors: Čelutkienė Jelena , Čerlinskaitė-Bajorė Kamilė , Cotter Gad , Edwards Christopher , Adamo Marianna , Arrigo Mattia , Barros Marianela , Biegus Jan , Chioncel Ovidiu , Cohen-Solal Alain , Damasceno Albertino , Diaz Rafael , Filippatos Gerasimos , Gayat Etienne , Kimmoun Antoine , Léopold Valentine , Metra Marco , Novosadova Maria , Pagnesi Matteo , Pang Peter S. , Ponikowski Piotr , Saidu Hadiza , Sliwa Karen , Takagi Koji , Ter Maaten Jozine M. , Tomasoni Daniela , Lam Carolyn S.P. , Voors Adriaan A. , Mebazaa Alexandre , Davison Beth 
Published: March 2024

BACKGROUND:
This analysis provides details on baseline and changes in quality of life (QoL) and its components as measured by EQ-5D-5L questionnaire, as well as association with objective outcomes, applying high-intensity heart failure (HF) care in patients with acute HF.

METHODS:
In STRONG-HF trial (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) patients with acute HF were randomized just before discharge to either usual care or a high-intensity care strategy of guideline-directed medical therapy up-titration. Patients ranked their state of health on the EQ-5D visual analog scale score ranging from 0 (the worst imaginable health) to 100 (the best imaginable health) at baseline and at 90 days follow-up.

RESULTS:

In 1072 patients with acute HF with available assessment of QoL (539/533 patients assigned high-intensity care/usual care) the mean baseline EQ-visual analog scale score was 59.2 (SD, 15.1) with no difference between the treatment groups. Patients with lower baseline EQ-visual analog scale (meaning worse QoL) were more likely to be women, self-reported Black and non-European (
P
<0.001). The strongest independent predictors of a greater improvement in QoL were younger age (
P
<0.001), no HF hospitalization in the previous year (
P
<0.001), lower NYHA class before hospital admission (
P
<0.001) and high-intensity care treatment (mean difference, 4.2 [95% CI, 2.5–5.8];
P
<0.001). No statistically significant heterogeneity in the benefits of high-intensity care was seen across patient subgroups of different ages, with left ventricular ejection fraction above or below 40%, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic blood pressure above or below the median value. The treatment effect on the primary end point did not vary significantly across baseline EQ-visual analog scale (
P
interaction
=0.87).

CONCLUSIONS:
Early up-titration of guideline-directed medical therapy significantly improves all dimensions of QoL in patients with HF and improves prognosis regardless of baseline self-assessed health status. The likelihood of achieving optimal doses of HF medications does not depend on baseline QoL.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03412201.
Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study
Authors: Slavova Nedelina , Muenger Robin , Sanchez-Albisua Iciar , Regényi Maria , Oesch Gabriela , Fluss Joël , Hackenberg Annette , Lebon Sébastien , Maier Oliver , Datta Alexandre N. , Bigi Sandra , Grunt Sebastian , Steinlin Maja 
Published: March 2024

BACKGROUND:
Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases.

METHODS:
In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion–weighted imaging score in the PC.

RESULTS:
Thirty-five children with a median age of 6.3 (interquartile range, 2.7–8.2 [95% CI, 0.9–15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11–0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75–21.0) compared with 4.5 (interquartile range, 2.0–8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54).

CONCLUSIONS:
FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.
Inhibition of Anaplastic Lymphoma Kinase Protects From Ischemic Stroke
Authors: Hu Yue , Chang Luping , Zhu Yuanbo , Geng Xue , Liu Zhongwang , Wang Ranran , Wang Yiheng , Zhao Bing-Qiao , Fan Wenying 
Published: March 2024

BACKGROUND:
Ischemic stroke is often accompanied by oxidative stress and inflammatory response, both of which work synergistically to exacerbate the disruption of the blood-brain barrier and ischemic brain injury. ALK (anaplastic lymphoma kinase), a cancer-associated receptor tyrosine kinase, was found to play a role in oxidative stress and inflammation. In this study, we investigated the role of ALK inhibition in a murine model of ischemic stroke.

METHODS:
Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery in mice with a filament. The ALK inhibitor alectinib was administered following the stroke. ALOX15 (arachidonic acid 15-lipoxygenase) was overexpressed by adenovirus injection. The immunohistochemistry, Western blot, oxidative stress, inflammation, blood-brain barrier leakage, infarct volume, and functional outcomes were determined.

RESULTS:
We found that the expression of ALK was markedly increased in the neurovascular unit after cerebral ischemia. Treatment with the ALK inhibitor alectinib reduced the accumulation of reactive oxygen species, lipid peroxidation, and oxidative DNA, increased the vascular levels of antioxidant enzymes, inactivated the vascular NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome pathway, and reduced vascular inflammation (ICAM-1 [intercellular adhesion molecule-1] and MCP-1 [monocyte chemoattractant protein-1]) after ischemia. Moreover, alectinib reduced the loss of cerebrovascular integrity and blood-brain barrier damage, consequently decreasing brain infarction and neurological deficits. Furthermore, alectinib reduced stroke-evoked ALOX15 expression, whereas virus-mediated overexpression of ALOX15 abolished alectinib-dependent inhibition of oxidative stress and vascular inflammation, blood-brain barrier protection, and neuroprotection, suggesting the protective effects of alectinib for stroke may involve ALOX15.

CONCLUSIONS:
Our findings demonstrated that alectinib protects from stroke by regulating ischemic signaling cascades and suggest that ALK may be a novel therapeutic target for ischemic stroke.
Decreasing alpha flow releases task-specific processing paths
Authors: Hanna Jevri , Kim Cora , Rampp Stefan , Buchfelder Michael , Müller-Voggel Nadia 
Published: March 2024

Abstract
Directing and maintaining attention toward relevant information and away from non-relevant information is a critical competence of higher-order nervous systems. Here, we used directed connectivity to investigate how the human brain prioritizes appropriate processing paths when participants are performing a behavioral task requiring attention in the visual or the auditory modality. We show that the efficient transfer of information relevant for the task is mediated by a region- and task-specific decrease of alpha band connectivity from the parietal and, in case a motor response is required, motor cortex to the relevant sensory cortices. Further, alpha-band connectivity modulations reliably predict alpha power modulations in the task-related sensory cortices, particularly where the task-irrelevant cortex is inhibited via local alpha power increases. We suggest that the task- and region-specific modulation of alpha-band connectivity in the present study is a basic neuronal mechanism orchestrating the allocation of task-relevant neuronal resources related to and possibly underlying the previously reported sensory alpha power modulations in association with the allocation of competing attentional resources.
The Moment the Mahāvīra Attained Omniscience
Authors: Tieken Herman 
Published: March 2024

Abstract
In the accounts of the Mahāvīra’s life in the first suyakkhaṃdha of the Āyāra(ṃga) and the Jinacaritra several turning points are mentioned. As will be shown, the periods between these turning points are delimited in a highly exact way, which accounts for the intercalary months. However, the modern translators have failed to recognize the terms involved. And so have the authors of the texts themselves and the subsequent copyists, which in the case of Āyāra I becomes clear from an interpolation and in that of the Jinacaritra from the introduction of an alternative system of dating the main events in the Mahāvīra’s life. The latter system is also found in the second suyakkhaṃdha of the Āyāra, which contains an account of the Mahāvīra’s life which, as will be shown, might well have been based on the one in the Jinacaritra. The exact calculations lend the biography in Āyāra I the character of a handbook providing strict rules for prospective monks. The author of the Jinacaritra, who was unaware of the function of the calculations, produced instead a veritable hagiography. It will be argued that while the phenomenon of intercalarity must have been widely known, knowledge of the calculations seems to have been passed on mainly in royal administrative circles involved in taxation and revenue collection. This is a world from which the ascetic monks, however learned, must have been far removed. This might explain the misunderstandings visible in the Jinacaritra and, with it, Āyāra II. The authors of what is by general agreement the earliest version, in Āyāra I, seem instead to have been familiar with the work carried out in these administrative centres.
The Alleged Jesuit-Led Rebellion in 1606: Missionary Conditions in Early Seventeenth- Century China
Authors: Xie Jingzhen 
Published: March 2024

Abstract
In early 1606, the Chinese in Guangdong Province mobilized militarily upon learning that the Jesuits in Macau were rising up in an attempt to occupy China. However, the incident did not develop into persecution of the missionaries and was quickly put to an end with the restoration of the Jesuits’ innocence. The peaceful resolution of the alleged Jesuit-led rebellion shed new light on the rich yet complex missionary conditions in early seventeenth-century China. During this period, the Ming Dynasty was in decline, but its loyal statesmen were eager to rejuvenate Confucian values. This article argues that there were various factors contributing to the favorable atmosphere around the missionary work, including the Valignano-Ricci policy, the support provided by reliable Chinese Jesuits, the friendship and brotherhood that the Jesuits formed with Chinese scholar-officials, Ming statesmen’s various aspirations, and Ming China’s conciliatory policy toward the Portuguese in Macau.
‘Your Father the Devil’: Relations between Catholic and Protestant Missionaries in Nineteenth Century Taiwan
Authors: Charouz Ladislav 
Published: March 2024

Abstract
This article argues that interaction between Dominican and Presbyterian missionaries in nineteenth-century Taiwan had a profound significance for both missions. The Catholics and Protestants contended over the same areas and groups of people, which led to conflicts but also to religiously motivated innovations. Understanding this competitive relationship helps to explain the actions and strategies of both churches, as well as to identify unexpected sources of their power. Finally, the article shows that the missionaries’ slights and criticisms of each other, often performed in front of a Taiwanese audience, help to illustrate the impact that religious competition had on the missionaries’ acculturation to local belief systems.
Rush to Charge, Dead to Drive: Application of Deadline Rush Model to Electric Vehicle User’s Charging Behavior
Authors: Khaleghikarahrodi Mehrsa , Macht Gretchen A. 
Published: March 2024

Objective This work aims to estimate the portion of electric vehicle (EV) users who exhibit procrastination-like behavior, almost equivalent to an “empty” battery, before they decide to charge their vehicles. Background There is a human tendency to procrastinate when a deadline approaches. Human behavior in the presence of deadlines has been studied in different fields to evaluate individuals’ performance or organizational efficiency and effectiveness. However, this phenomenon has not been investigated among EV users. Method This study explores users’ procrastination-like behavior among 69 Rhode Island public charging stations’ data representing 70,611 charging events. The Deadline Rush Model is incorporated to model frequent users’ charging profiles. To conduct a robust estimation, the Bayesian Mixture Model is implemented. Results With the selection of an informative prior, the Bayesian Mixture Model estimated that almost one-third of frequent users procrastinate charging. Conclusion The majority of procrastination-like users have small battery sizes. Although procrastination-like users need to charge when they arrive at a location, that might not necessarily be true for a plug-in hybrid; thus, systematically, they can clog the system for other users whose needs are more pressing. Understanding unique and unexplored charging behaviors among EV users is beneficial to EV infrastructure stakeholders in reducing the adoption threshold by providing a reliable and ubiquitous charging network. Application The findings identify a different kind of demand on the EV infrastructure than previously modeled and can directly influence future decision-making criteria in terms of planning to optimize to accommodate EV drivers with different charging behaviors.
Social determinants of health and dialysis modality selection in patients with advanced chronic kidney disease: A retrospective cohort study
Authors: Thanabalasingam Susan J , Akbari Ayub , Sood Manish M , Brown Pierre A , White Christine A , Moorman Danielle , Salman Maria , Sriperumbuduri Sriram , Hundemer Gregory L 
Published: March 2024

Background: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood. Methods: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation. Results: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m2, respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34–0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27–0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39–0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39–0.78)). Conclusions: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these ‘upstream’ social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure.
Effects of Gamification on Motivations of Elementary School Students: An Action Research Field Experiment
Authors: Mohammed Mohammed , Fatemah Amal , Hassan Lobna 
Published: March 2024

Background Gamification research and practice have gained popularity, but there is a lack of experimental and field evidence regarding the effectiveness of specific design elements and their use contexts especially in developing countries. Aim This research aimed to measure the effect of gamifying digital learning environments and compare the effects of badges and leaderboards on the development of cognitive and achievement motivation of elementary school students. Method A gamified environment focused on the circulatory system and employing interactive storytelling was developed. It was tested through an in-field experiment at an elementary school in Egypt. The research sample was of 30 students in the 5th grade, divided into two equal experimental groups (badges - leaderboard). Results The results indicated an increase in cognitive and achievement motivation among students in both experimental groups. However, there were no significant differences in the effects of badges and leaderboards on the cognitive and achievement motivations of the participants in the two experimental groups. Conclusions These findings suggest that the effects of gamification are more likely due to the holistic design and novelty, rather than the specific use of a specific game element.
The role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study)
Authors: Zakaria Izyan Atiqah , Mohammed Zain Nur Aini , Teik Chew Kah , Abu Muhammad Azrai , Zainuddin Ani Amelia , Abdul Aziz Nor Haslinda , Safian Nazarudin , Mohd Mokhtar Norfilza , Raja Ali Raja Affendi , Beng Kwang Ng , Mohamed Ismail Nor Azlin , Hamizan Muhammad Rafiuddin , Ab Razak Wira Sorfan , Nur Azurah Abdul Ghani 
Published: March 2024

Background: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. Objective: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. Design: Randomized placebo-controlled trial. Methods: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. Results: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26–1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. Conclusion: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. Registration: This study is registered under ClinicalTrials.gov (NCT04119011).