bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection
Authors: Jolissaint Joshua S. , Soares Kevin C. , Seier Kenneth P. , Kundra Ritika , Gönen Mithat , Shin Paul J. , Boerner Thomas , Sigel Carlie , Madupuri Ramyasree , Vakiani Efsevia , Cercek Andrea , Harding James J. , Kemeny Nancy E. , Connell Louise C. , Balachandran Vinod P. , D'Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Wei Alice C. , Jarnagin William R. 
Published: May 2021

Abstract

Purpose:
Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions.

Experimental Design:
Patients with liver-limited IHC with or without LNM treated with resection (N = 237), hepatic arterial infusion chemotherapy (HAIC; N = 196), or systemic chemotherapy alone (SYS; N = 140) at our institution between 2000 and 2018 were included. Genomic sequencing was analyzed to determine whether genetic alterations could stratify outcomes for patients with LNM.

Results:
For node-negative patients, resection was associated with the longest median overall survival [OS, 59.9 months; 95% confidence interval (CI), 47.2–74.31], followed by HAIC (24.9 months; 95% CI, 20.3–29.6), and SYS (13.7 months; 95% CI, 8.9–15.9; P &lt; 0.001). There was no difference in survival for node-positive patients treated with resection (median OS, 19.7 months; 95% CI, 12.1–27.2) or HAIC (18.1 months; 95% CI, 14.1–26.6; P = 0.560); however, survival in both groups was greater than SYS (11.2 months; 95% CI, 14.1–26.6; P = 0.024). Node-positive patients with at least one high-risk genetic alteration (TP53 mutation, KRAS mutation, CDKN2A/B deletion) had worse survival compared to wild-type patients (median OS, 12.1 months; 95% CI, 5.7–21.5; P = 0.002), regardless of treatment. Conversely, there was no difference in survival for node-positive patients with IDH1/2 mutations compared to wild-type patients.

Conclusions:
There was no difference in OS for patients with node-positive IHC treated by resection versus HAIC, and both treatments had better survival than SYS alone. The presence of high-risk genetic alterations provides valuable prognostic information that may help guide treatment.
Comorbidity Burden and Adverse Outcomes After Transcatheter Aortic Valve Replacement
Authors: Feldman Daniel R. , Romashko Mikhail D. , Koethe Benjamin , Patel Sonika , Rastegar Hassan , Zhan Yong , Resor Charles D. , Connors Annie C. , Kimmelstiel Carey , Allen David , Weintraub Andrew R. , Wessler Benjamin S. 
Published: May 2021

Background
Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for symptomatic patients with aortic stenosis and elevated procedural risk. Many deaths following TAVR are because of noncardiac causes and comorbid disease burden may be a major determinant of postprocedure outcomes. The prevalence of comorbid conditions and associations with outcomes after TAVR has not been studied.

Methods and Results

This was a retrospective single‐center study of patients treated with TAVR from January 2015 to October 2018. The association between 21 chronic conditions and short‐ and medium‐term outcomes was assessed. A total of 341 patients underwent TAVR and had 1‐year follow‐up. The mean age was 81.4 (SD 8.0) years with a mean Society of Thoracic Surgeons predicted risk of mortality score of 6.7% (SD 4.8). Two hundred twenty (65%) patients had ≥4 chronic conditions present at the time of TAVR. There was modest correlation between Society of Thoracic Surgeons predicted risk of mortality and comorbid disease burden (
r
=0.32,
P
<0.001). After adjusting for Society of Thoracic Surgeons predicted risk of mortality, age, and vascular access, each additional comorbid condition was associated with increased rates of 30‐day rehospitalizations (odds ratio, 1.21; 95% CI, 1.02–1.44), a composite of 30‐day rehospitalization and 30‐day mortality (odds ratio, 1.20; 95% CI, 1.02–1.42), and 1‐year mortality (odds ratio, 1.29; 95% CI, 1.05–1.59).

Conclusions
Comorbid disease burden is associated with worse clinical outcomes in high‐risk patients treated with TAVR. The risks associated with comorbid disease burden are not adequately captured by standard risk assessment. A systematic assessment of comorbid conditions may improve risk stratification efforts.
Predicting Infarct Core From Computed Tomography Perfusion in Acute Ischemia With Machine Learning: Lessons From the ISLES Challenge
Authors: Hakim Arsany , Christensen Søren , Winzeck Stefan , Lansberg Maarten G. , Parsons Mark W. , Lucas Christian , Robben David , Wiest Roland , Reyes Mauricio , Zaharchuk Greg 
Published: May 2021

Background and Purpose:
The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally diverse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard.

Methods:
The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance.

Results:
Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180–238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25–79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7–45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team’s algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3; volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance.

Conclusions:
Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.
Multiscale dynamic mean field (MDMF) model relates resting-state brain dynamics with local cortical excitatory–inhibitory neurotransmitter homeostasis
Authors: Naskar Amit , Vattikonda Anirudh , Deco Gustavo , Roy Dipanjan , Banerjee Arpan 
Published: May 2021

Abstract
Previous computational models have related spontaneous resting-state brain activity with local excitatory–inhibitory balance in neuronal populations. However, how underlying neurotransmitter kinetics associated with E–I balance govern resting-state spontaneous brain dynamics remains unknown. Understanding the mechanisms by virtue of which fluctuations in neurotransmitter concentrations, a hallmark of a variety of clinical conditions, relate to functional brain activity is of critical importance. We propose a multiscale dynamic mean field (MDMF) model—a system of coupled differential equations for capturing the synaptic gating dynamics in excitatory and inhibitory neural populations as a function of neurotransmitter kinetics. Individual brain regions are modeled as population of MDMF and are connected by realistic connection topologies estimated from diffusion tensor imaging data. First, MDMF successfully predicts resting-state functional connectivity. Second, our results show that optimal range of glutamate and GABA neurotransmitter concentrations subserve as the dynamic working point of the brain, that is, the state of heightened metastability observed in empirical blood-oxygen-level-dependent signals. Third, for predictive validity the network measures of segregation (modularity and clustering coefficient) and integration (global efficiency and characteristic path length) from existing healthy and pathological brain network studies could be captured by simulated functional connectivity from an MDMF model.
<strong><em>Impatiens ramasubbuana</em>, a new name for <em>Impatiens palniensis</em> Ramasubbu (Balsaminaceae)</strong>
Authors: KOTTAIMUTHU RAMALINGAM , MURUGAN PERUMAL , KUMAR JOHN KENNEDY JOHN PRAVEEN , BASU MUTHURAMALINGAM JOTHI 
Published: May 2021

The genus Impatiens Linnaeus (1753: 937) contains a wealth of untapped treasures for gardeners and it is one of the mega diverse genera of angiosperms comprise about 1059 species (POWO 2020). According to the recent estimate, India is known to have 250 species and majority of them occur in Eastern Himalayas (Gogoi et al. 2018) and the Western Ghats (Bhaskar 2012). Tamil Nadu is one of the plant-rich states in the country and with 5674 angiosperm taxa, it ranks first among all the states in the country (Lakshminarasimhan et al. 2014).
On the Literature and Thought of the German Classical Era
Authors: Nisbet Hugh Barr 
Published: May 2021

This elegant collection of essays ranges across eighteenth and nineteenth-century thought, covering philosophy, science, literature and religion in the ‘Age of Goethe.’ A recognised authority in the field, Nisbet grapples with the major voices of the Enlightenment and gives pride of place to the figures of Lessing, Herder, Goethe and Schiller.
These eleven essays range widely in their compass of thought and intellectual discourse, dealing incisively with themes including the philosophical implications of literature and the relationship between religion, science and politics. The result is an accomplished reflection on German thought, but also on its rebirth, as Nisbet argues for the relevance of these Enlightenment thinkers for the readers of today.
The first half of this collection focuses predominantly on eighteenth-century thought, where names like Lessing, Goethe and Herder, but also Locke and Voltaire, feature. The second has a wider chronological scope, discussing authors such as Winckelmann and Schiller, while branching out from discussions of religion, philosophy and literature to explore the sciences. Issues of biology, early environmentalism, and natural history also form part of this volume. The collection concludes with an examination of changing attitudes towards art in the aftermath of the ‘Age of Goethe.’
The essays in this volume have been previously published separately, but are brought together in this collection to present Nisbet’s widely-acclaimed perspectives on this fascinating period of German thought. It will be of interest to scholars and students of the intellectual life of Europe during the Enlightenment, while its engaging and lucid style will also appeal to the general reader.
Writing and Publishing Scientific Papers
Authors: Lövei Gábor L. 
Published: May 2021

Gábor Lövei’s scientific communication course for students and scientists explores the intricacies involved in publishing primary scientific papers, and has been taught in more than twenty countries. Writing and Publishing Scientific Papers is the distillation of Lövei’s lecture notes and experience gathered over two decades; it is the coursebook many have been waiting for.
The book’s three main sections correspond with the three main stages of a paper’s journey from idea to print: planning, writing, and publishing. Within the book’s chapters, complex questions such as ‘How to write the introduction?’ or ‘How to submit a manuscript?’ are broken down into smaller, more manageable problems that are then discussed in a straightforward, conversational manner, providing an easy and enjoyable reading experience.
Writing and Publishing Scientific Papers stands out from its field by targeting scientists whose first language is not English. While also touching on matters of style and grammar, the book’s main goal is to advise on first principles of communication.
This book is an excellent resource for any student or scientist wishing to learn more about the scientific publishing process and scientific communication. It will be especially useful to those coming from outside the English-speaking world and looking for a comprehensive guide for publishing their work in English.
Phosphorylation of islet-1 serine 269 by CDK1 increases its transcriptional activity and promotes cell proliferation in gastric cancer
Authors: Shi Qiong , Ni Xiaomei , Lei Ming , Xia Quansong , Dong Yan , Zhang Qiao , Wang Weiping 
Published: May 2021

Abstract
Background
Despite recent advances in diagnostic and therapeutic approaches for gastric cancer (GC), the survival of patients with advanced GC remains very low. Islet-1 (ISL1) is a LIM-homeodomain transcription factor, which is upregulated and promotes cell proliferation in GC. The exact mechanism by which ISL1 influences GC development is unclear.

Methods
Co-immunoprecipitation (co-IP) and glutathione S-transferase (GST)-pulldown assays were employed to evaluate the interaction of ISL1 with CDK1. Western blot and immunohistochemistry analyses were performed to evaluate the ability of CDK1 to phosphorylate ISL1 at Ser 269 in GC cell and tissue specimens. Chromatin immunoprecipitation (ChIP), ChIP re-IP, luciferase reporter, and CCK-8 assays were combined with flow cytometry cell cycle analysis to detect the transactivation potency of ISL1-S269-p and its ability to promote cell proliferation. The self-stability and interaction with CDK1 of ISL1-S269-p were also determined.

Results
ISL1 is phosphorylated by CDK1 at serine 269 (S269) in vivo. Phosphorylation of ISL1 by CDK1 on serine 269 strengthened its binding on the cyclin B1 and cyclin B2 promoters and increased its transcriptional activity in GC. Furthermore, CDK1-dependent phosphorylation of ISL1 correlated positively with ISL1 protein self-stability in NIH3T3 cells.

Conclusions
ISL1-S269-p increased ISL1 transcriptional activity and self-stability while binding to the cyclinB1 and cyclinB2 promoters promotes cell proliferation. ISL1-S269-p is therefore crucial for tumorigenesis and potentially a direct therapeutic target for GC.
Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy
Authors: Zhao Jianan , Hu Yiyang , Peng Jinghua 
Published: May 2021

AbstractMost currently recommended therapies for metabolic dysfunction-associated fatty liver disease (MAFLD) involve diet control and exercise therapy. We searched PubMed and compiled the most recent research into possible forms of programmed cell death in MAFLD, including apoptosis, necroptosis, autophagy, pyroptosis and ferroptosis. Here, we summarize the state of knowledge on the signaling mechanisms for each type and, based on their characteristics, discuss how they might be relevant in MAFLD-related pathological mechanisms. Although significant challenges exist in the translation of fundamental science into clinical therapy, this review should provide a theoretical basis for innovative MAFLD clinical treatment plans that target programmed cell death.
MOCCA: a flexible suite for modelling DNA sequence motif occurrence combinatorics
Authors: Bredesen Bjørn André , Rehmsmeier Marc 
Published: May 2021

Abstract
Background
Cis-regulatory elements (CREs) are DNA sequence segments that regulate gene expression. Among CREs are promoters, enhancers, Boundary Elements (BEs) and Polycomb Response Elements (PREs), all of which are enriched in specific sequence motifs that form particular occurrence landscapes. We have recently introduced a hierarchical machine learning approach (SVM-MOCCA) in which Support Vector Machines (SVMs) are applied on the level of individual motif occurrences, modelling local sequence composition, and then combined for the prediction of whole regulatory elements. We used SVM-MOCCA to predict PREs in Drosophila and found that it was superior to other methods. However, we did not publish a polished implementation of SVM-MOCCA, which can be useful for other researchers, and we only tested SVM-MOCCA with IUPAC motifs and PREs.

Results
We here present an expanded suite for modelling CRE sequences in terms of motif occurrence combinatorics—Motif Occurrence Combinatorics Classification Algorithms (MOCCA). MOCCA contains efficient implementations of several modelling methods, including SVM-MOCCA, and a new method, RF-MOCCA, a Random Forest–derivative of SVM-MOCCA. We used SVM-MOCCA and RF-MOCCA to model Drosophila PREs and BEs in cross-validation experiments, making this the first study to model PREs with Random Forests and the first study that applies the hierarchical MOCCA approach to the prediction of BEs. Both models significantly improve generalization to PREs and boundary elements beyond that of previous methods—including 4-spectrum and motif occurrence frequency Support Vector Machines and Random Forests—, with RF-MOCCA yielding the best results.

Conclusion
MOCCA is a flexible and powerful suite of tools for the motif-based modelling of CRE sequences in terms of motif composition. MOCCA can be applied to any new CRE modelling problems where motifs have been identified. MOCCA supports IUPAC and Position Weight Matrix (PWM) motifs. For ease of use, MOCCA implements generation of negative training data, and additionally a mode that requires only that the user specifies positives, motifs and a genome. MOCCA is licensed under the MIT license and is available on Github at https://github.com/bjornbredesen/MOCCA.
Metabolome and transcriptome profiling reveals anthocyanin contents and anthocyanin-related genes of chimeric leaves in Ananas comosus var. bracteatus
Authors: Zhou Xuzixin , Xue Yanbin , Mao Meiqin , He Yehua , Adjei Mark Owusu , Yang Wei , Hu Hao , Liu Jiawen , Feng Lijun , Zhang Huiling , Luo Jiaheng , Li Xi , Sun Lingxia , Huang Zhuo , Ma Jun 
Published: May 2021

Abstract
Background
Ananas comosus var. bracteatus is a colorful plant used as a cut flower or landscape ornamental. The unique foliage color of this plant includes both green and red leaves and, as a trait of interest, deserves investigation. In order to explore the pigments behind the red section of the chimeric leaves, the green and red parts of chimeric leaves of Ananas comosus var. bracteatus were sampled and analyzed at phenotypic, cellular and molecular levels in this study.

Results
The CIELAB results indicated that the a* values and L* values samples had significant differences between two parts. Freehand sections showed that anthocyanin presented limited accumulation in the green leaf tissues but obviously accumulation in the epidermal cells of red tissues. Transcriptomic and metabolomic analyses were performed by RNA-seq and LC-ESI-MS/MS. Among the 508 identified metabolites, 10 kinds of anthocyanins were detected, with 6 significantly different between the two samples. The cyanidin-3,5-O-diglucoside content that accounts for nearly 95.6% in red samples was significantly higher than green samples. RNA-Seq analyses showed that 11 out of 40 anthocyanin-related genes were differentially expressed between the green and red samples. Transcriptome and metabolome correlations were determined by nine quadrant analyses, and 9 anthocyanin-related genes, including MYB5 and MYB82, were correlated with 7 anthocyanin-related metabolites in the third quadrant in which genes and metabolites showing consistent change. Particularly, the PCCs between these two MYB genes and cyanidin-3,5-O-diglucoside were above 0.95.

Conclusion
Phenotypic colors are closely related to the tissue structures of different leaf parts of Ananas comosus var. bracteatus, and two MYB transcription factors might contribute to differences of anthocyanin accumulation in two parts of Ananas comosus var. bracteatus chimeric leaves. This study lay a foundation for further researches on functions of MYBs in Ananas comosus var. bracteatus and provides new insights to anthocyanin accumulation in different parts of chimeric leaves.
A qualitative study of home care client and caregiver experiences with a complex cardio-respiratory management model
Authors: Schumacher Connie , Dash Darly , Mowbray Fabrice , Klea Lindsay , Costa Andrew 
Published: May 2021

AbstractBackgroundHome care clients are typically older and have some degree of medical, physical, cognitive or social conditions that require formal or informal support to promote healthy aging in the community. Home care clients contribute a significant proportion of health service use, including emergency department visits. The DIVERT-CARE trial introduced a cardio-respiratory management model to improve client motivation, symptoms and rates of unwarranted health service use. Our objective was to explore the perceptions and experiences of individuals who participated in the DIVERT-CARE self-management support and education intervention.MethodsA qualitative study was nested within a pragmatic randomized control trial and conducted following a 15-week multi-component cardio-respiratory intervention. A phenomenological descriptive design was employed using thematic analysis. Post-intervention, clients and their caregivers were invited to participate in a semi-structured telephone interview. Interview questions were designed to elicit the experience with the intervention components.ResultsA total of 29 interviews were completed from June 2018 to March 2020 from participants in Ontario, Newfoundland, and British Columbia. Three themes were identified; self-care trajectory and burden of responsibility, learning and behaviour change, and feeling connected pre-emptively to care providers, the information and medical advice, and connection through the therapeutic relationship.ConclusionsHome care clients experience unique challenges in managing cardio-respiratory related chronic disease. Home-based interventions fostered a therapeutic relationship of connectedness while equipping clients with necessary knowledge and skills. These results inform recommendations for community nursing, and home-based self-management supports for older community-residing individuals.