bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer
Authors: Dekhne Aamod S. , Hou Zhanjun , Gangjee Aleem , Matherly Larry H. 
Published: September 2020

Abstract
One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria, and nucleus. 1C metabolism in the cytosol has been an important therapeutic target for cancer since the inception of modern chemotherapy, and “antifolates” targeting cytosolic 1C pathways continue to be a mainstay of the chemotherapy armamentarium for cancer. Recent insights into the complexities of 1C metabolism in cancer cells, including the critical role of the mitochondrial 1C pathway as a source of 1C units, glycine, reducing equivalents, and ATP, have spurred the discovery of novel compounds that target these reactions, with particular focus on 5,10-methylene tetrahydrofolate dehydrogenase 2 and serine hydroxymethyltransferase 2. In this review, we discuss key aspects of 1C metabolism, with emphasis on the importance of mitochondrial 1C metabolism to metabolic homeostasis, its relationship with the oncogenic phenotype, and its therapeutic potential for cancer.
Tumor-Infiltrating Regulatory T-cell Accumulation in the Tumor Microenvironment Is Mediated by IL33/ST2 Signaling
Authors: Son Jimin , Cho Jae-Won , Park Hyo Jin , Moon Jihyun , Park Seyeon , Lee Hoyoung , Lee Jeewon , Kim Gamin , Park Su-Myeong , Lira Sergio A. , Mckenzie Andrew N. , Kim Hye Young , Choi Cheol Yong , Lim Yong Taik , Park Seong Yong , Kim Hye Ryun , Park Su-Hyung , Shin Eui-Cheol , Lee Insuk , Ha Sang-Jun 
Published: September 2020

Abstract
Regulatory T cells (Treg) are enriched in the tumor microenvironment (TME) and suppress antitumor immunity; however, the molecular mechanism underlying the accumulation of Tregs in the TME is poorly understood. In various tumor models, tumor-infiltrating Tregs were highly enriched in the TME and had significantly higher expression of immune checkpoint molecules. To characterize tumor-infiltrating Tregs, we performed bulk RNA sequencing (RNA-seq) and found that proliferation-related genes, immune suppression–related genes, and cytokine/chemokine receptor genes were upregulated in tumor-infiltrating Tregs compared with tumor-infiltrating CD4+Foxp3− conventional T cells or splenic Tregs from the same tumor-bearing mice. Single-cell RNA-seq and T-cell receptor sequencing also revealed active proliferation of tumor infiltrating Tregs by clonal expansion. One of these genes, ST2, an IL33 receptor, was identified as a potential factor driving Treg accumulation in the TME. Indeed, IL33-directed ST2 signaling induced the preferential proliferation of tumor-infiltrating Tregs and enhanced tumor progression, whereas genetic deletion of ST2 in Tregs limited their TME accumulation and delayed tumor growth. These data demonstrated the IL33/ST2 axis in Tregs as one of the critical pathways for the preferential accumulation of Tregs in the TME and suggests that the IL33/ST2 axis may be a potential therapeutic target for cancer immunotherapy.
The Genetics of Circulating Resistin Level, A Biomarker for Cardiovascular Diseases, Is Informed by Mendelian Randomization and the Unique Characteristics of African Genomes
Authors: Meeks Karlijn A.C. , Doumatey Ayo P. , Bentley Amy R. , Gouveia Mateus H. , Chen Guanjie , Zhou Jie , Lei Lin , Adeyemo Adebowale A. , Rotimi Charles N. 
Published: September 2020

Background- Resistin, a protein linked with inflammation and cardiometabolic diseases, is one of few proteins for which GWAS consistently report variants within and near the coding gene (RETN). Here, we took advantage of the reduced linkage disequilibrium in African populations to infer genetic causality for circulating resistin levels by performing GWAS, whole-exome analysis, fine-mapping, Mendelian randomization and transcriptomic data analyses.Methods- GWAS and fine-mapping analyses for resistin were performed in 5621 African ancestry individuals, including 3754 continental Africans (AF) and 1867 African Americans (AA). Causal variants identified were subsequently used as an instrumental variable in Mendelian randomization analyses for homeostatic modelling (HOMA) derived insulin resistance index, BMI and type 2 diabetes.Results- The lead variant (rs3219175, in the promoter region ofRETN) for the single locus detected was the same for AF (P-value 5.0×10-111) and for AA (9.5×10-38), respectively explaining 12.1% and 8.5% of variance in circulating resistin. Fine-mapping analyses and functional annotation revealed this variant as likely causal affecting circulating resistin levels as acis-eQTL increasingRETNexpression. Additional variants regulating resistin levels were upstream ofRETNwith genesPCP2,STXBP2andXAB2showing the strongest association using integrative analysis of GWAS with transcriptomic data. Mendelian randomization analyses did not provide evidence for resistin increasing insulin resistance, BMI or type 2 diabetes risk in African-ancestry populations.Conclusions- Taking advantage of the fine-mapping resolution power of African genomes, we identified a single variant (rs3219175) as the likely causal variant responsible for most of the variability in circulating resistin levels. In contrast to findings in some other ancestry populations, we showed that resistin does not seem to increase insulin resistance and related cardiometabolic traits in African-ancestry populations.
Clinical Characteristics and Outcomes From Percutaneous Coronary Intervention of Last Remaining Coronary Artery
Authors: Shoaib Ahmad , Rashid Muhammad , Kontopantelis Evangelos , Sharp Andrew , Fahy Eoin F. , Nolan James , Townend John , Ludman Peter , Ratib Karim , Azam Ziyad A. , Ahmad Ayesha , McEntegart Margaret , Mohamed Mohamed , Kinnaird Tim , Mamas Mamas A. ,   on behalf of the British Cardiovascular Intervention Society (BCIS) and the National Institute for Cardiovascular Outcomes Research (NICOR)
Published: September 2020

Background:
Patients with complex high-risk coronary anatomy, such as those with a last remaining patent vessel (LRPV), are increasingly revascularized with percutaneous coronary intervention (PCI) in contemporary practice. There are limited data on the outcomes of these high-risk procedures.

Methods:
We analyzed a large longitudinal PCI cohort (2007–2014, n=501 841) from the British Cardiovascular Intervention Society database. Clinical, demographic, procedural, and outcome data were analyzed by dividing patients into 2 groups; LRPV group (n=2432) and all other PCI groups (n=506 691).

Results:

Patients in the LRPV PCI group were older, had more comorbidities, and higher prevalence of moderate-severe left ventricular systolic dysfunction. Mortality was higher in the LRPV PCI group during hospital admission (12 % versus 1.5 %,
P
<0.001), at 30 days (15% versus 2%,
P
<0.001), and at one-year (24% versus 5%,
P
<0.001). In a propensity score matching analysis the adjusted risk of mortality during index admission (odds ratio, 2.05 [95% CI, 1.65–2.44],
P
<0.001), at 30 days (odds ratio, 2.13 [95% CI, 1.78–2.5],
P
<0.001), at 1 year (odds ratio, 1.81 [95% CI, 1.59–2.03],
P
<0.001), and in-hospital major adverse cardiovascular events (odds ratio, 1.8 [95% CI, 1.42–2.19],
P
<0.001) were higher in LRPV PCI group as compared to control group. In sensitivity analyses, similar clinical outcomes were observed irrespective of which major epicardial coronary artery was treated.

Conclusions:
In this contemporary cohort, patients who had PCI to their LRPV had a higher-risk profile and more adverse clinical outcomes, irrespective of the vessel treated.
Fully Automated Cardiac Assessment for Diagnostic and Prognostic Stratification Following Myocardial Infarction
Authors: Schuster Andreas , Lange Torben , Backhaus Sören J. , Strohmeyer Carolin , Boom Patricia C. , Matz Jonas , Kowallick Johannes T. , Lotz Joachim , Steinmetz Michael , Kutty Shelby , Bigalke Boris , Gutberlet Matthias , de Waha‐Thiele Suzanne , Desch Steffen , Hasenfuß Gerd , Thiele Holger , Stiermaier Thomas , Eitel Ingo 
Published: September 2020

Background
Cardiovascular magnetic resonance imaging is considered the reference methodology for cardiac morphology and function but requires manual postprocessing. Whether novel artificial intelligence–based automated analyses deliver similar information for risk stratification is unknown. Therefore, this study aimed to investigate feasibility and prognostic implications of artificial intelligence–based, commercially available software analyses.

Methods and Results

Cardiovascular magnetic resonance data (n=1017 patients) from 2 myocardial infarction multicenter trials were included. Analyses of biventricular parameters including ejection fraction (EF) were manually and automatically assessed using conventional and artificial intelligence–based software. Obtained parameters entered regression analyses for prediction of major adverse cardiac events, defined as death, reinfarction, or congestive heart failure, within 1 year after the acute event. Both manual and uncorrected automated volumetric assessments showed similar impact on outcome in univariate analyses (left ventricular EF, manual: hazard ratio [HR], 0.93 [95% CI 0.91–0.95];
P
<0.001; automated: HR, 0.94 [95% CI, 0.92–0.96];
P
<0.001) and multivariable analyses (left ventricular EF, manual: HR, 0.95 [95% CI, 0.92–0.98];
P
=0.001; automated: HR, 0.95 [95% CI, 0.92–0.98];
P
=0.001). Manual correction of the automated contours did not lead to improved risk prediction (left ventricular EF, area under the curve: 0.67 automated versus 0.68 automated corrected;
P
=0.49). There was acceptable agreement (left ventricular EF: bias, 2.6%; 95% limits of agreement, −9.1% to 14.2%; intraclass correlation coefficient, 0.88 [95% CI, 0.77–0.93]) of manual and automated volumetric assessments.

Conclusions
User‐independent volumetric analyses performed by fully automated software are feasible, and results are equally predictive of major adverse cardiac events compared with conventional analyses in patients following myocardial infarction.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT00712101 and NCT01612312.
Vascular Calcification as an Underrecognized Risk Factor for Frailty in 1783 Community‐Dwelling Elderly Individuals
Authors: Lee Szu‐Ying , Chao Chia‐Ter , Huang Jenq‐Wen , Huang Kuo‐Chin 
Published: September 2020

Background
Vascular calcification (VC) is associated with high morbidity and mortality among older adults, a population that exhibits a higher tendency for developing frailty at the same time. Whether VC serves as a risk factor for the development of frailty in this population remains unclear.

Methods and Results
We analyzed a prospectively assembled cohort of community‐dwelling older adults between 2014 and 2017 (n=1783). Frailty and prefrailty were determined on the basis of the Study of Osteoporotic Fractures criteria, and VC was measured using semiquantitative aortic arch calcification (AAC) and abdominal aortic calcification scoring. We conducted multiple logistic regression with prefrailty or frailty as the dependent variable, incorporating sociodemographic profiles, comorbidities, medications, laboratory data, AAC status/severity, and other geriatric phenotypes. Among all participants, 327 (18.3%) exhibited either prefrailty (15.3%) or frailty (3.1%), and 648 (36.3%) exhibited AAC. After adjusting for multiple confounders, we found that AAC incidence was associated with a substantially higher probability of prefrailty or frailty (odds ratio [OR], 11.9; 95% CI, 7.9–15.4), with a dose‐responsive relationship (OR for older adults with AAC categories 1, 2, and 3 was 9.3, 13.6, and 52.5, respectively). Similar association was observed for older adults with abdominal aortic calcification (OR, 5.0; 95% CI, 1.3–19.5), and might be replicable in another cohort of patients with end‐stage renal disease.

Conclusions
Severity of VC exhibited a linear positive relationship with frailty in older adults. Our findings suggest that a prompt diagnosis and potential management of VC may assist in risk mitigation for patients with frailty.
Responses to a poached conspecific in wild forest elephants (Loxodonta africana cyclotis)
Authors: Stephan Claudia , Bahamboula Jess J.D. , Brncic Terry M. 
Published: September 2020

Abstract
The increased attention towards deceased conspecifics in various social animal species is one of the most intriguing conundrums in animal behaviour. The factors that might explain the observed behavioural variation amongst individuals remain nebulous. Here we analyse forest elephants’ (Loxodonta africana cyclotis) responses to a poached adult male conspecific, using remote camera trapping during a period of eight months. After completely avoiding the carcass site for over a week, females and males substantially differed in behavioural responses. Males consistently stayed longer around the remains, showed signs of increased arousal, interacted with the dead body, and twisted trunks with each other. Females, in contrast, were more passively explorative and preferred to visit the site without their dependent offspring. Findings show a previously unknown sexual-dimorphism in forest elephant behaviour towards a poached conspecific and raise the possibility that individuals might be able to infer further context-specific information about the event.
Morphological and molecular characterisation of Coslenchus persicus n. sp. (Nematoda: Tylenchidae) from Iran
Authors: Hosseinvand Manouchehr , Eskandari Ali , Ghaderi Reza 
Published: September 2020

Summary
A new species of Coslenchus from north-western Iran is illustrated and described using morphological, morphometric and molecular data. Coslenchus persicus n. sp. is characterised by a medium-sized body of 694-810 μm, often 18 (seldom 20-22) longitudinal ridges excluding lateral field, head with four distinct annuli, stylet 9.6-10.8 μm long, pharyngeal basal bulb large and cylindrical, spermatheca offset and ovate, without sperm, vulval flaps extending for two annuli, 5-7 μm in length, tail striated with finely to bluntly rounded tip, 110-153 μm long and without males. The new species comes close to C. assamensis, C. diversus, C. japonicus, C. leiocephalus, C. maritus, C. multigyrus, C. paramaritus, C. pastor, and C. polonicus, but can be distinguished from all by differences in body length, stylet length and shape of basal bulb, post-vulval uterine sac, tail and certain morphometric data. Molecular data are provided for the characterisation of the new species using ribosomal genes (18S and 28S rRNA). In the 18S rRNA tree, the new species was placed in a clade including one isolate of Coslenchus sp. from Iran. In the reconstructed 28S rRNA phylogenetic tree, C. persicus n. sp. clustered with other known Coslenchus species.
Spatial genetic structure in the Eurasian otter (Lutra lutra) meta-population from its core range in Italy
Authors: Buglione Maria , Petrelli Simona , Troiano Claudia , Notomista Tommaso , Petrella Antonio , De Riso Laura , Poerio Luigi , Cascini Vito , Bartolomei Remo , Fulgione Domenico 
Published: September 2020

Abstract
We characterized the genetic structure of the Eurasian otter (Lutra lutra) meta-population living in the core of its Italian distribution range providing results from 191 fresh spraints, collected from 24 watercourses included in Southern Italy. Furthermore, according to ecological corridors and barriers, we discuss the likely ways of movement and possible evolutionary fate of these populations. We genotyped 136 samples using 11 Lut microsatellite nuclear markers amplified from faecal dna. Microsatellites were moderately variable (Ho = 0.45; He = 0.46), with a total number of alleles and average number of alleles per locus in the meta-population of 50 and 4.54, respectively. No significant heterozygosity excess was observed in meta-population suggesting no recent population bottlenecks. Bayesian clustering discriminated a sub-structuring of the meta-population in five putative clusters, indicating that local populations are genetically differentiated: three of these seem to be identifiable with geographically defined sub-populations (from the Cilento, Agri and Basento river basins). The fourth is represented by multiple sub-populations with admixed genotype, that include genotypes from the Lao, Sinni and Abatemaco river basins, living in a landscape with the higher environmental permeability. Landscape genetic analysis could provide evidence of an unexpected ecological corridor: the seacoast, highlighted, for the first time as a new way for the dispersion of the South-Italian otters. Deepening the knowledge of these perspectives is crucial to identify solid strategies aimed at the future health of the populations of the Italian otters, by restoring dispersal corridors and managing the watercourses.
How Neoliberalism Comes to Town: Policy Convergence, (Under)Development, and Jordanian Economics under King Abdullah
Authors: Powers Colin 
Published: September 2020

Abstract
This article explores the development strategies articulated and implemented in the Hashemite Kingdom of Jordan during the tenure of King Abdullah ii. It begins by establishing the consistency with which national planners have adopted ideas, recommendations, and ideological scripts initially authored by the international financial institutions (ifis). Having documented the endurance of Jordan’s “policy convergence”, it explains this outcome as a dialectical function of foreign interference and local agency. Demonstrating how the lines between the national, international, and transnational blur in constituting the contemporary Jordanian political economy, this case study in actually existing neoliberalism will provide a unique look at the actors, interests, ideas and processes at the heart of the country’s enduring underdevelopment.
“In the Name of the People?” Understanding the Role of Egypt’s Supreme Constitutional Court in Times of Political Crisis
Authors: Taha Noura Hamdan , Khalil Asem 
Published: September 2020

Abstract
Constitutional transformations frequently introduce and open up political spaces for new actors, as was shown during the so-called ‘Arab Spring’ when national movements emerged to demand the removal of long-established authoritarian regimes and instigated a series of institutional power struggles. Subsequent analysis of these events by academics has tended to overlook struggle conducted through and by legal institutions. This article directly addresses this oversight by considering the role of Egypt’s Supreme Constitutional Court (scc) in the 2011 uprisings, with specific attention to its influence on the country’s political transformation/s. It seeks to apply new analytical tools that will assist understanding of the position of judicial institutions in the Arab world, their institutional limits and expected functions. It demonstrates how this can be achieved through a closer analysis of the scc’s structure and the factors that shape its current role.
On null objects in Egyptian Arabic
Authors: Soltan Usama 
Published: September 2020

Abstract
This paper provides a descriptive account and a syntactic analysis of the grammatical distribution and properties of null objects (NOs) in Egyptian Arabic. In particular, it is shown that NOs cannot be analyzed as instances of null pro or as variables bound by a null topic operator. A Verb-Stranding VP-Ellipsis account is also shown to be empirically non-viable. Instead, I argue that NOs result from Argument Ellipsis (AE), an operation that targets arguments for deletion at PF. This AE analysis has several empirical advantages, including an account for (a) the different-entity interpretation of NOs, (b) the fact that PP and CP internal arguments can be null, (c) the availability of both strict identity and sloppy identity readings with null PPs and CPs, (d) the indefiniteness and inanimacy restrictions on the antecedents of NOs, and (e) the fact that subjects, as opposed to objects, cannot undergo AE. Following existing proposals in the generative literature on null arguments, I provide a minimalist implementation of the AE operation, whereby principles of φ-agreement, case licensing, the NP/DP distinction, and a notion of relativized phasehood, all conspire to determine when NOs occur and when they are disallowed in the language.
Mental health implications of COVID-19 pandemic and its response in India
Authors: Roy Adrija , Singh Arvind Kumar , Mishra Shree , Chinnadurai Aravinda , Mitra Arun , Bakshi Ojaswini 
Published: September 2020

Introduction: Mental health concerns and treatment usually take a backseat when the limited resources are geared for pandemic containment. In this global humanitarian crisis of the COVID-19 pandemic, mental health issues have been reported from all over the world. Objectives: In this study, we attempt to review the prevailing mental health issues during the COVID-19 pandemic through global experiences, and reactive strategies established in mental health care with special reference to the Indian context. By performing a rapid synthesis of available evidence, we aim to propose a conceptual and recommendation framework for mental health issues during the COVID-19 pandemic. Methods: A search of the PubMed electronic database and google scholar were undertaken using the search terms ‘novel coronavirus’, ‘COVID-19’, ‘nCoV’, SARS-CoV-2, ‘mental health’, ‘psychiatry’, ‘psychology’, ‘anxiety’, ‘depression’ and ‘stress’ in various permutations and combinations. Published journals, magazines and newspaper articles, official webpages and independent websites of various institutions and non-government organizations, verified social media portals were compiled. Results: The major mental health issues reported were stress, anxiety, depression, insomnia, denial, anger and fear. Children and older people, frontline workers, people with existing mental health illnesses were among the vulnerable in this context. COVID-19 related suicides have also been increasingly common. Globally, measures have been taken to address mental health issues through the use of guidelines and intervention strategies. The role of social media has also been immense in this context. State-specific intervention strategies, telepsychiatry consultations, toll free number specific for psychological and behavioral issues have been issued by the Government of India. Conclusion: Keeping a positive approach, developing vulnerable-group-specific need-based interventions with proper risk communication strategies and keeping at par with the evolving epidemiology of COVID-19 would be instrumental in guiding the planning and prioritization of mental health care resources to serve the most vulnerable.