bluuebunny/crossref_metadata_2025_split huggingface dataset:
QuantifyPoly(A): reshaping alternative polyadenylation landscapes of eukaryotes with weighted density peak clustering
Authors: Ye Congting , Zhao Danhui , Ye Wenbin , Wu Xiaohui , Ji Guoli , Li Qingshun Q , Lin Juncheng 
Published: June 2021

Abstract
The dynamic choice of different polyadenylation sites in a gene is referred to as alternative polyadenylation, which functions in many important biological processes. Large-scale messenger RNA 3′ end sequencing has revealed that cleavage sites for polyadenylation are presented with microheterogeneity. To date, the conventional determination of polyadenylation site clusters is subjective and arbitrary, leading to inaccurate annotations. Here, we present a weighted density peak clustering method, QuantifyPoly(A), to accurately quantify genome-wide polyadenylation choices. Applying QuantifyPoly(A) on published 3′ end sequencing datasets from both animals and plants, their polyadenylation profiles are reshaped into myriads of novel polyadenylation site clusters. Most of these novel polyadenylation site clusters show significantly dynamic usage across different biological samples or associate with binding sites of trans-acting factors. Upstream sequences of these clusters are enriched with polyadenylation signals UGUA, UAAA and/or AAUAAA in a species-dependent manner. Polyadenylation site clusters also exhibit species specificity, while plants ones generally show higher microheterogeneity than that of animals. QuantifyPoly(A) is broadly applicable to any types of 3′ end sequencing data and species for accurate quantification and construction of the complex and dynamic polyadenylation landscape and enables us to decode alternative polyadenylation events invisible to conventional methods at a much higher resolution.
Deep learning-based real-time detection of novel pathogens during sequencing
Authors: Bartoszewicz Jakub M , Genske Ulrich , Renard Bernhard Y 
Published: June 2021

AbstractNovel pathogens evolve quickly and may emerge rapidly, causing dangerous outbreaks or even global pandemics. Next-generation sequencing is the state of the art in open-view pathogen detection, and one of the few methods available at the earliest stages of an epidemic, even when the biological threat is unknown. Analyzing the samples as the sequencer is running can greatly reduce the turnaround time, but existing tools rely on close matches to lists of known pathogens and perform poorly on novel species. Machine learning approaches can predict if single reads originate from more distant, unknown pathogens but require relatively long input sequences and processed data from a finished sequencing run. Incomplete sequences contain less information, leading to a trade-off between sequencing time and detection accuracy. Using a workflow for real-time pathogenic potential prediction, we investigate which subsequences already allow accurate inference. We train deep neural networks to classify Illumina and Nanopore reads and integrate the models with HiLive2, a real-time Illumina mapper. This approach outperforms alternatives based on machine learning and sequence alignment on simulated and real data, including SARS-CoV-2 sequencing runs. After just 50 Illumina cycles, we observe an 80-fold sensitivity increase compared to real-time mapping. The first 250 bp of Nanopore reads, corresponding to 0.5 s of sequencing time, are enough to yield predictions more accurate than mapping the finished long reads. The approach could also be used for screening synthetic sequences against biosecurity threats.
Elucidation of dynamic microRNA regulations in cancer progression using integrative machine learning
Authors: Dogan Haluk , Hakguder Zeynep , Madadjim Roland , Scott Stephen , Pierobon Massimiliano , Cui Juan 
Published: June 2021

AbstractMotivationEmpowered by advanced genomics discovery tools, recent biomedical research has produced a massive amount of genomic data on (post-)transcriptional regulations related to transcription factors, microRNAs, long non-coding RNAs, epigenetic modifications and genetic variations. Computational modeling, as an essential research method, has generated promising testable quantitative models that represent complex interplay among different gene regulatory mechanisms based on these data in many biological systems. However, given the dynamic changes of interactome in chaotic systems such as cancers, and the dramatic growth of heterogeneous data on this topic, such promise has encountered unprecedented challenges in terms of model complexity and scalability. In this study, we introduce a new integrative machine learning approach that can infer multifaceted gene regulations in cancers with a particular focus on microRNA regulation. In addition to new strategies for data integration and graphical model fusion, a supervised deep learning model was integrated to identify conditional microRNA-mRNA interactions across different cancer stages.ResultsIn a case study of human breast cancer, we have identified distinct gene regulatory networks associated with four progressive stages. The subsequent functional analysis focusing on microRNA-mediated dysregulation across stages has revealed significant changes in major cancer hallmarks, as well as novel pathological signaling and metabolic processes, which shed light on microRNAs’ regulatory roles in breast cancer progression. We believe this integrative model can be a robust and effective discovery tool to understand key regulatory characteristics in complex biological systems.Availabilityhttp://sbbi-panda.unl.edu/pin/
Extracellular vesicles derived from cancer-associated fibroblast carries miR-224-5p targeting SLC4A4 to promote the proliferation, invasion and migration of colorectal cancer cells
Authors: Zheng Yu , Zeng Jintao , Lin Dajia , Xia Haoyun , Wang Xiangyu , Chen Liqi , Chen Hongyuan , Huang Liangxiang , Zeng Changqing 
Published: June 2021

Abstract
More and more studies indicated that extracellular vesicles (EVs) carrying miRNAs have been potential biomarkers of various cancers including colorectal cancer (CRC). This study aims to explore the function of miR-224-5p carried by EVs derived from cancer-associated fibroblasts (CAFs) in CRC. Here, we found that miR-224-5p was highly expressed while SLC4A4 was lowly expressed in CRC cells. Moreover, dual-luciferase reporter gene assay testified that miR-224-5p targeted SLC4A4. The expression of miR-224-5p in CAFs-derived EVs was found to be elevated. It was also testified that CAFs-derived EVs could transfer miR-224-5p into CRC cells. miR-224-5p in CAFs-derived EVs facilitated the proliferation, migration, invasion and anti-apoptosis of CRC cells. Overexpressing miR-224-5p increased the proliferative, migratory and invasive abilities of CRC cells and inhibit CRC cell apoptosis, while overexpressing SLC4A4 caused the opposite result. Research in vitro and in vivo further indicated that miR-224-5p promoted CRC cell progression via binding to its downstream target gene SLC4A4. Rescue assay also demonstrated that overexpressing miR-224-5p reversed the inhibitory effect of overexpressed SLC4A4 on cancer cell growth. In addition, in vivo assay identified that high level of miR-224-5p promoted the growth of cancer cells in mice in vivo. In conclusion, we explored the effect of miR-224-5p in CRC, which helps for further exploration of new methods for CRC targeted therapy.
“K-pop is Rupturing Chilean Society”: Fighting With Globalized Objects in Localized Conflicts
Authors: Diaz Pino Camilo 
Published: June 2021

Abstract
Amid a rapidly growing wave of anti-neoliberal protest emerging in late 2019, Chile’s government scrambled to respond to the massive scale of this dissidence by attempting to find some external agent to pin the blame on. Initially seeking evidence of Venezuelan or Russian involvement, the state eventually pinned the blame on K-pop as an agent of “social rupture.” This article examines this framing of K-pop by Chilean authorities and what this says about the position of Korean media’s integration into a Latin American pop-culture landscape that is growing ever more globalized and non-Western. It likewise examines the contestatory embracing of K-pop by Chilean anti-neoliberal activists, their broader integration of globalized cultural objects, and how this reflects on wider current anti-neoliberal activist cultures operating in the Global South.
Cortical Morphology in Autism: Findings from a Cortical Shape-Adaptive Approach to Local Gyrification Indexing
Authors: Zoltowski Alisa R , Lyu Ilwoo , Failla Michelle , Mash Lisa E , Dunham Kacie , Feldman Jacob I , Woynaroski Tiffany G , Wallace Mark T , Barquero Laura A , Nguyen Tin Q , Cutting Laurie E , Kang Hakmook , Landman Bennett A , Cascio Carissa J 
Published: June 2021

AbstractIt has been challenging to elucidate the differences in brain structure that underlie behavioral features of autism. Prior studies have begun to identify patterns of changes in autism across multiple structural indices, including cortical thickness, local gyrification, and sulcal depth. However, common approaches to local gyrification indexing used in prior studies have been limited by low spatial resolution relative to functional brain topography. In this study, we analyze the aforementioned structural indices, utilizing a new method of local gyrification indexing that quantifies this index adaptively in relation to specific sulci/gyri, improving interpretation with respect to functional organization. Our sample included n = 115 autistic and n = 254 neurotypical participants aged 5–54, and we investigated structural patterns by group, age, and autism-related behaviors. Differing structural patterns by group emerged in many regions, with age moderating group differences particularly in frontal and limbic regions. There were also several regions, particularly in sensory areas, in which one or more of the structural indices of interest either positively or negatively covaried with autism-related behaviors. Given the advantages of this approach, future studies may benefit from its application in hypothesis-driven examinations of specific brain regions and/or longitudinal studies to assess brain development in autism.
Using Patient Completed Screening Tools to Predict Risk of Malnutrition in Patients With Inflammatory Bowel Disease
Authors: Taylor Lorian M , Eslamparast Tannaz , Farhat Kamal , Kroeker Karen , Halloran Brendan , Shommu Nusrat , Kumar Ankush , Fitzgerald Quinn , Gramlich Leah , Abraldes Juan G , Tandon Puneeta , Raman Maitreyi 
Published: June 2021

Abstract

Background
Malnutrition is associated with adverse clinical outcomes in patients with inflammatory bowel disease (IBD), however, malnutrition screening is not routinely performed. This study aimed to identify the prevalence of malnutrition in patients with IBD and compare the accuracy of patient completed screens to a gold-standard malnutrition assessment tool: the dietitian-completed subjective global assessment (SGA).

Methods
This cross-sectional study was conducted at 2 hospitals and 2 ambulatory care clinics in Alberta, Canada. Patients with IBD completed 4 malnutrition screening tools: abridged patient-generated SGA (abPG-SGA), Malnutrition Universal Screening Tool (MUST), Canadian Nutrition Screening Tool (CNST), and Saskatchewan IBD–nutrition risk (SaskIBD-NR). Risk of malnutrition was calculated for each tool and differences were compared between IBD subtype and body mass index (BMI) categories. Sensitivity and specificity, negative and positive predictive values (NPV and PPV), and area under the receiver operating characteristic curve (AUC) were calculated compared to SGA.

Results
Patients with Crohn’s disease (n = 149) and ulcerative colitis (n = 96) participated in this study. Overall prevalence of malnutrition using SGA was 23% and malnutrition risk for CNST, abPG-SGA, SaskIBD-NR, and MUST was 37%, 36%, 36%, and 27%, respectively. Overall, the abPG-SGA had the highest sensitivity (83%), PPV (53%), and NPV (94%), and largest AUC (0.837) compared to SGA. For patients with a BMI ≥25 kg/m2, sensitivity and PPV of the abPG-SGA decreased to 73% and 41%, respectively, with a AUC of 0.841.

Conclusions
Malnutrition is prevalent in patients with IBD and using malnutrition risk screening tools such as the abPG-SGA may be useful to identify patients who would benefit from further assessment.
Treatment and posttreatment effects of Herbst appliance therapy on trabecular structure of the mandible using fractal dimension analysis
Authors: Amuk Mehmet , Gul Amuk Nisa , Yılmaz Serkan 
Published: June 2021

Summary

Objectives
This controlled study aimed to evaluate the effects of Herbst therapy on the trabecular structure of the condyle and angulus mandible using fractal dimension analysis (FD-A) accompanied by skeletal cephalometric changes.

Material and method
The panoramic and cephalometric radiographs of 30 patients with skeletal Class II malocclusion treated with the Herbst appliance (C II-H group, mean age: 15.23 ± 1.08), 30 patients with skeletal Class II malocclusion that received fixed orthodontic treatment (C II-C group, mean age: 15.73 ± 1.38), and 30 patients with skeletal Class I malocclusion (C I-C group, mean age: 15.90 ± 1.30) were selected. FD-A was performed on the superoposterior region (C-SP) and centre of the condyles (C-C) and the mandibular angulus (Ang) on the panoramic radiographs taken at the pretreatment (T0), intermediate stage of treatment (T1), and posttreatment (T2) timepoints just like cephalometric analysis.

Results
Herbst therapy provided a statistically significant increase in SNB, ANS-Me, Na-Me, S-Go, Co-Gn and a decrease in ANB and overjet (P &lt; 0.05). All skeletal changes remained stable during the fixed appliance treatment after Herbst. The FD values in C-C increased (P &lt; 0.05), and C-SP values decreased (P &lt; 0.05) during Herbst therapy, while after removal of the Herbst appliance, no significant change was observed despite an increase in C-SP. The Ang value did not change during Herbst treatment, but then increased significantly (P &lt; 0.05). There was no significant change in the FD values of the C I-C and C II-C groups at any stage of treatment. The C-C and C-SP changes at T1–T0 period, C-SP and Ang changes at T2–T1 period, and C-C, C-SP, and Ang values at T2–T0 period were found higher in C II-H group compared with the C II-C group significantly (P &lt; 0.05).

Conclusion
Herbst therapy changed the trabecular structure of the condyles in different directions at the superoposterior and central regions of the condyles, while the structural complexity of the angulus mandible, which did not change during the Herbst treatment, increased during the fixed orthodontic treatment after Herbst.
Lack of specialist care is associated with increased morbidity and mortality in adult congenital heart disease: a population-based study
Authors: Diller Gerhard-Paul , Orwat Stefan , Lammers Astrid Elisabeth , Radke Robert M , De-Torres-Alba Fernando , Schmidt Renate , Marschall Ursula , Bauer Ulrike M , Enders Dominic , Bronstein Leo , Kaleschke Gerrit , Baumgartner Helmut 
Published: June 2021

Abstract

Aims
The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population.

Methods and results
Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (&lt;70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67–0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78–0.92; P &lt; 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up.

Conclusion
Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.
Jan Huygen van Linschoten and the Reys-gheschrift: updating Iberian Science for the Dutch expansion
Authors: Vila-Santa Nuno 
Published: June 2021

Abstract
In 1596 Jan Huygen van Linschoten published his Itinerario. It contained a section called the Reys-gheschrift, which was the first nautical compendium to include sailing routes on the earth’s three main oceans. This publication enabled the Dutch and the English to launch successful maritime strategies. In this article I discuss how Iberian Science, mainly its sources, was employed in the Reys-gheschrift, as well as the major changes made prior to publication and the reasons why Linschoten introduced them. These topics are connected with a major debate concerning the drive for geographical knowledge, in which I attempt to demonstrate the importance of Iberian Science for the onset of the Dutch maritime expansion and for European seamanship more broadly in the sixteenth and seventeenth centuries.
GWAS in Africans identifies novel lipids loci and demonstrates heterogenous association within Africa
Authors: Bentley Amy R , Chen Guanjie , Doumatey Ayo P , Shriner Daniel , Meeks Karlijn A C , Gouveia Mateus H , Ekoru Kenneth , Zhou Jie , Adeyemo Adebowale , Rotimi Charles N 
Published: June 2021

Abstract
Serum lipids are biomarkers of cardiometabolic disease risk, and understanding genomic factors contributing to their distribution is of interest. Studies of lipids in Africans are rare, though it is expected that such studies could identify novel loci. We conducted a GWAS of 4317 Africans enrolled from Nigeria, Ghana and Kenya. We evaluated linear mixed models of high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), total cholesterol (CHOL), triglycerides (TG) and TG/HDLC. Replication was attempted in 9542 African Americans (AA).
In our main analysis, we identified 28 novel associations in Africans. Of the 18 of these that could be tested in AA, three associations replicated (GPNMB-TG, ENPP1-TG and SMARCA4-LDLC). Five additional novel loci were discovered upon meta-analysis with AA (rs138282551-TG, PGBD5-HDLC, CD80-TG/HDLC, SLC44A1-CHOL and TLL2-CHOL). Analyses considering only those with predominantly West African ancestry (Nigeria, Ghana and AA) yielded new insights: ORC5-LDLC and chr20:60973327-CHOL.
Among our novel findings are some loci with known connections to lipids pathways. For instance, rs147706369 (TLL2) alters a regulatory motif for sterol regulatory element-binding proteins, a family of transcription factors that control the expression of a range of enzymes involved in cholesterol, fatty acid and TG synthesis, and rs115749422 (SMARCA4), an independent association near the known LDLR locus that is rare or absent in populations without African ancestry. These findings demonstrate the utility of conducting genomic analyses in Africans for discovering novel loci and provide some preliminary evidence for caution against treating ‘African ancestry’ as a monolithic category.
Neural guidance factors as hubs of immunometabolic cross-talk
Authors: Nakanishi Yoshimitsu , Kang Sujin , Kumanogoh Atsushi 
Published: June 2021

Abstract
Semaphorins were originally identified as axon-guidance molecules essential for neural development. In addition to their functions in the neural system, members of the semaphorin family have critical functions in many pathophysiological processes, including immune responses, bone homeostasis, cancer and metabolic disorders. In particular, several lines of evidence indicate that mammalian/mechanistic target of rapamycin (mTOR), a central regulator of cell metabolism, regulates the functions of semaphorins in various types of cells, revealing a novel link between semaphorins and cell metabolism. In this review, we discuss recent advances in the immunometabolic functions of semaphorins, with a particular focus on mTOR signaling.
Differences in Mate Pairings of Hatchery- and Natural-Origin Coho Salmon Inferred from Offspring Genotypes
Authors: Auld H L , Jacobson D P , Rhodes A C , Banks M A 
Published: June 2021

SynopsisCaptive breeding can affect how sexual selection acts on subsequent generations. One context where this is important is in fish hatcheries. In many salmon hatcheries, spawning is controlled artificially and offspring are reared in captivity before release into the wild. While previous studies have suggested that hatchery- and natural-origin fish may make different mate choice decisions, it remains to be determined how hatchery fish may be making different mate choice decisions compared with natural-origin fish at a genetic level. Using genotyping-by-sequencing, we identify single-nucleotide polymorphisms (SNPs) associated with variation in mate pairings from a natural context involving hatchery- and natural-origin coho salmon (Oncorhynchus kisutch). In both natural-origin and hatchery mate pairs, we observed more SNPs with negative assortment than positive assortment. However, only 3% of the negative assortment SNPs were shared between the two mating groups, and 1% of the positive assortment SNPs were shared between the two mating groups, indicating divergence in mating cues between wild and hatchery-raised salmon. These findings shed light on mate choice in general and may have important implications in the conservation management of species as well as for improving other captive breeding scenarios. There remains much to discover about mate choice in salmon and research described here reflects our intent to test the potential of ongoing advances in population genomics to develop new hatchery practices that may improve the performance of hatchery offspring, lessening the differences and thus potential impacts upon wild stocks.
Can UN Peacekeeping Promote Environmental Quality?
Authors: Bakaki Zorzeta , Böhmelt Tobias 
Published: June 2021

AbstractThis research focuses on a positive, and previously largely unknown, implication of United Nations (UN) peacekeeping: better environmental quality. While maintaining international peace and security remains the main goal of peacekeeping operations, we contend that they can also be linked to environmentally friendly outcomes. Mission mandates and UN policies increasingly comprise actions that potentially promote environmental quality. At the same time, positive side effects on the environment materialize due to the cooperation with and activities of other UN bodies. The empirical analyses, also correcting for the likely non-random assignment of peace missions and employing several alternative outcome measures, suggest that UN peace missions are indeed substantively associated with better environmental quality. This research has important implications for our understanding of peacekeeping operations, and it contributes to the literatures on the (unintended) consequences of peacekeeping as well as environmental politics.