bluuebunny/crossref_metadata_2025_split huggingface dataset:
iGRLCDA: identifying circRNA–disease association based on graph representation learning
Authors: Zhang Han-Yuan , Wang Lei , You Zhu-Hong , Hu Lun , Zhao Bo-Wei , Li Zheng-Wei , Li Yang-Ming 
Published: February 2022

Abstract
While the technologies of ribonucleic acid-sequence (RNA-seq) and transcript assembly analysis have continued to improve, a novel topology of RNA transcript was uncovered in the last decade and is called circular RNA (circRNA). Recently, researchers have revealed that they compete with messenger RNA (mRNA) and long noncoding for combining with microRNA in gene regulation. Therefore, circRNA was assumed to be associated with complex disease and discovering the relationship between them would contribute to medical research. However, the work of identifying the association between circRNA and disease in vitro takes a long time and usually without direction. During these years, more and more associations were verified by experiments. Hence, we proposed a computational method named identifying circRNA–disease association based on graph representation learning (iGRLCDA) for the prediction of the potential association of circRNA and disease, which utilized a deep learning model of graph convolution network (GCN) and graph factorization (GF). In detail, iGRLCDA first derived the hidden feature of known associations between circRNA and disease using the Gaussian interaction profile (GIP) kernel combined with disease semantic information to form a numeric descriptor. After that, it further used the deep learning model of GCN and GF to extract hidden features from the descriptor. Finally, the random forest classifier is introduced to identify the potential circRNA–disease association. The five-fold cross-validation of iGRLCDA shows strong competitiveness in comparison with other excellent prediction models at the gold standard data and achieved an average area under the receiver operating characteristic curve of 0.9289 and an area under the precision-recall curve of 0.9377. On reviewing the prediction results from the relevant literature, 22 of the top 30 predicted circRNA–disease associations were noted in recent published papers. These exceptional results make us believe that iGRLCDA can provide reliable circRNA–disease associations for medical research and reduce the blindness of wet-lab experiments.
TRScore: a 3D RepVGG-based scoring method for ranking protein docking models
Authors: Guo Linyuan , He Jiahua , Lin Peicong , Huang Sheng-You , Wang Jianxin 
Published: February 2022

AbstractMotivationProtein–protein interactions (PPI) play important roles in cellular activities. Due to the technical difficulty and high cost of experimental methods, there are considerable interests towards the development of computational approaches, such as protein docking, to decipher PPI patterns. One of the important and difficult aspects in protein docking is recognizing near-native conformations from a set of decoys, but unfortunately, traditional scoring functions still suffer from limited accuracy. Therefore, new scoring methods are pressingly needed in methodological and/or practical implications.ResultsWe present a new deep learning-based scoring method for ranking protein–protein docking models based on a 3D RepVGG network, named TRScore. To recognize near-native conformations from a set of decoys, TRScore voxelizes the protein–protein interface into a 3D grid labeled by the number of atoms in different physicochemical classes. Benefiting from the deep convolutional RepVGG architecture, TRScore can effectively capture the subtle differences between energetically favorable near-native models and unfavorable non-native decoys without needing extra information. TRScore was extensively evaluated on diverse test sets including protein–protein docking benchmark 5.0 update set, DockGround decoy set, as well as realistic CAPRI decoy set and overall obtained a significant improvement over existing methods in cross-validation and independent evaluations.Availability and implementationCodes available at: https://github.com/BioinformaticsCSU/TRScore
Agency, teleonomy and signal transduction in plant systems
Authors: Gilroy Simon , Trewavas Tony 
Published: February 2022

AbstractPlants are the basis of nearly all food chains. The evolutionary response to inevitable predatory and other contingent hazards has provided plants with remarkable regenerative and plastic capabilities. Teleonomy has been characterized as purposive, adaptive and goal-directed behaviour. The evidence that plants are agents, that they act purposefully, is indicated by numerous behaviours, most notably plasticity. Through recurrent information exchange, growing roots construct a dynamic niche with bacterial and fungal symbionts. Purposeful shoot plasticity enables adaptive responses to abiotic and biotic hazards, with the goal of survival. Transgenerational inheritance furthers that goal for sibling survival. Teleonomic goals in shoot growth use proprioception to ensure successful tropic responses. Unlike animals that acquire energy biotically, nearly all plants are dependent solely on the physical environment. Convergent evolution is common and may result from the constraints of unchanging physical laws. Phenotypic plasticity initially provides a direction for evolutionary change. Our article indicates that there are features to evolutionary change in plants additional to those indicated by the modern synthesis and thus supports the extended evolutionary hypothesis.
Using InSAR for evaluating the accuracy of locations and focal mechanism solutions of local earthquake catalogues
Authors: Ghayournajarkar Nematollah , Fukushima Yo 
Published: February 2022

SUMMARYEarthquake source parameters play a fundamental role in evaluating seismic hazard. In many countries, the relatively low accuracy of the earthquake source parameters owing to sparse seismic monitoring networks prevents accurate seismic hazard evaluation. Interferometric Synthetic Aperture Radar (InSAR) is a useful tool for accurate fault parameter determination of shallow inland earthquakes. We compared the fault parameters (location and rupture geometry) derived from InSAR with those derived from local and global seismic data to assess the credibility of the earthquake catalogues. We set our targets to Iran and Japan, where seismic networks are relatively sparse and dense, respectively, and analysed a total of 10 shallow inland earthquakes. To compare the fault parameters for each studied earthquake, we first created interferograms using InSAR data from multiple satellites and conducted fault model inversions assuming uniform slip on a rectangular finite fault. For the studied Iranian earthquakes, the epicentres of the United States Geological Survey (USGS) catalogue were more consistent with the InSAR-derived fault model compared to those of the local catalogue of the Iranian Seismological Center (IRSC). For the studied Japanese earthquakes, the epicentres of the Japan Meteorological Agency (JMA) catalogue were more consistent with the InSAR-derived fault model compared to those of the USGS. Assuming that the accuracy of the USGS locations is comparable for the two countries, the JMA catalogue has a higher accuracy than the IRSC catalogue. The difference in the accuracy for the two local catalogues can be explained by the larger azimuthal gaps of the IRSC seismic network. We also showed that the IRSC- and JMA-derived centroids were more consistent with the InSAR-derived fault model compared to those of the Global Centroid Moment Tensor (GCMT) catalogue. The focal mechanism solutions derived from InSAR and seismic CMT solutions were significantly different, highlighting the difficulties in determining the focal mechanism parameters from seismic data, even when the seismic station coverage is dense. As InSAR data can be easily accessed, this study presents a cost-effective method to assess and improve the accuracy of the local earthquake catalogues anywhere in the world.
Sustaining a Nonviolent Self: Mahatma Gandhi, Madeleine Slade, and Manu Gandhi
Authors: Arora Nikita 
Published: February 2022

Abstract
Mohandas Karamchand Gandhi (1869-1948) articulated and practised a unique ideology of ahimsa, nonviolence, in his life. Most importantly, ahimsa included refusing the needs and pleasures of the body – sex, food, care, and desire. For Gandhi, embodiment was an intrinsically violent condition, but he ultimately did live in his body. In this paper, I argue that while he perfected a nonviolent selfhood for himself, he relied on the physical and emotional labour of others, particularly the women in his ashrams (and life), to do so. I analyse the writings of two of his women followers, Madeleine Slade (Mirabehn) and Manu Gandhi (his grandniece, with whom he did his infamous experiment of celibacy), to investigate the contours of Gandhi’s selfhood through his interpersonal relationships and quotidian interactions with others. I argue that Gandhi developed a higher-than-human and nonviolent self by denying and repressing his human needs and desires, and by outsourcing some parts of his human self to Madeleine Slade and Manu Gandhi rather violently.
Dietary supplementation with fiber, “biotics,” and spray-dried plasma affects apparent total tract macronutrient digestibility and the fecal characteristics, fecal microbiota, and immune function of adult dogs
Authors: Lee Anne H , Lin Ching-Yen , Do Sungho , Oba Patricia M , Belchik Sara E , Steelman Andrew J , Schauwecker Amy , Swanson Kelly S 
Published: February 2022

AbstractA variety of functional ingredients, including fibers, prebiotics, probiotics, and postbiotics may be added to pet foods to support gastrointestinal and immune health. While many of these ingredients have been tested individually, commercial foods often include blends that also require testing. This study was conducted to evaluate the effects of diets containing blends of fibers, “biotics,” and/or spray-dried plasma on apparent total tract digestibility (ATTD), stool quality, fecal microbiota and metabolites, and immune health outcomes of adult dogs. A total of 12 healthy adult intact English pointer dogs (6 M, 6 F; age = 6.4 ± 2.0 yr; BW = 25.8 ± 2.6 kg) were used in a replicated 3 × 3 Latin square design to test diets formulated to: 1) contain a low concentration of fermentative substances (control diet, CT); 2) be enriched with a fiber–prebiotic–probiotic blend (FPPB); and 3) be enriched with a fiber–prebiotic–probiotic blend + immune-modulating ingredients (iFFPB). In each 28-d period, 22 d of diet adaptation was followed by a 5-d fecal collection phase and 1 d for blood sample collection. All data were analyzed using SAS 9.4, with significance being P &lt; 0.05 and trends being P &lt; 0.10. FPPB and iFPPB diets led to shifts in numerous outcome measures. Dry matter (DM), organic matter, fat, fiber, and energy ATTD were lower (P &lt; 0.01), fecal scores were lower (P &lt; 0.01; firmer stools), and fecal DM% was higher (P &lt; 0.0001) in dogs fed FPPB or iFPPB than those fed CT. Serum triglycerides and cholesterol were lower (P &lt; 0.01) in dogs fed FPPB or iFPPB than those fed CT. Fecal protein catabolites (isobutyrate, isovalerate, indole, and ammonia) and butyrate were lower (P &lt; 0.05), while fecal immunoglobulin A (IgA) was higher (P &lt; 0.01) in dogs fed FPPB and iFPPB than those fed CT. Fecal microbiota populations were affected by diet, with alpha-diversity being lower (P &lt; 0.05) in dogs fed iFPPB and the relative abundance of 20 bacterial genera being altered in dogs fed FPPB or iFPPB compared with CT. The circulating helper T cell:cytotoxic T cell ratio was higher (P &lt; 0.05) in dogs fed iFPPB than those fed CT. Circulating B cells were lower (P &lt; 0.05) in dogs fed FPPB than those fed iFPPB, and lower (P &lt; 0.05) in dogs fed iFPPB than those fed CT. Our results demonstrate that feeding a fiber–prebiotic–probiotic blend may provide many benefits to canine health, including improved stool quality, beneficial shifts to fecal microbiota and metabolite profiles, reduced blood lipids, and increased fecal IgA.
A26 DECONSTRUCTING DISTRESS: STAKEHOLDER ENGAGEMENT FOR EVIDENCE-BASED, PATIENT-CENTERED INTERVENTIONS FOR THE MANAGEMENT OF IBD-ASSOCIATED PSYCHOLOGICAL DISTRESS
Authors: Heisler C , Rohatinsky N , Stewart M , Vallis M , Shepherd T , Wozney L , Cassidy C , Currie B , Phalen-Kelly K , Robar J , Targownik L E , Huard T , Neil E , Jones J 
Published: February 2022

Abstract

Background
The growing prevalence of Inflammatory Bowel Disease (IBD) along with increasing complexity of providing high-quality, patient-centered care within a resource-constrained healthcare environment presents a major challenge. IBD-related psychological distress (IBD-PD) is the emotional impact of IBD and is associated with mental health disorders, increased disease severity, and premature mortality. With estimates of nearly 90% of IBD patients experiencing PD, the inability to provide high-quality, person-centered care for IBD-PD that is proportionate to clinical need is a significant care gap in the Canadian healthcare system.

Aims
To generate stakeholder-derived data to inform the design and development of stepped-intensity, cognitive behavioral therapy-based interventions for IBD-PD using evidence-based, patient–centered interventions and implementation strategies.

Methods
Virtual semi-structured interviews were conducted from September to October 2021. The interview guide was developed iteratively by researchers, IBD care providers, and patient research partners and guided by the COM-B Model of Behaviour and the Theoretical Domains Framework. Questions assessed perceptions, experiences, barriers, and facilitators to accessing IBD-PD care. Adults diagnosed with IBD were recruited from academic centers across Canada. Interviews were co-facilitated by a researcher and patient research partner, audio recorded, and transcribed. Using thematic analysis, codes were generated to identify themes using an inductive approach.

Results
As of October 2021, six interviews have been completed, with data collection ongoing. The mean participant age was 34.3 years (range 21–55 years) with 100% of respondents being female. The majority of participants worked full time (4/6, 67%) and all had completed at least high school. Diagnoses of Crohn’s Disease (3/6, 50%) and ulcerative colitis (3/6, 50%) were evenly distributed. Thematic analyses identified five major themes: 1) Lack of holistic care and acknowledgement of IBD-PD; 2) System-level and financial barriers to psychological support; 3) Lack of psychological support from providers with an understanding of IBD; 4) Preference for individualized virtual-based support; 5) Heavy reliance on informal support structures (caregivers) due to lack of access to formal psychological support.

Conclusions
As part of human-centered design, stakeholder engagement is key to understanding behavioral, social, attitudinal, and environmental barriers and facilitators for accessing IBD-PD care. Interviews are ongoing and specific intervention functions will be defined and incorporated into patient-centered implementation strategies.

Funding Agencies
None
A35 DNA HYPOMETHYLATION INHIBITS TUFT CELL-DERIVED COLITIS-ASSOCIATED CANCER
Authors: Larsen F , Good H J , Shin A E , Zhang L , Asfaha S 
Published: February 2022

Abstract

Background
Colorectal cancer is the second leading cause of cancer death in Canada. A major risk factor for the development of colorectal cancer is chronic inflammation leading to colitis-associated cancer (CAC). We previously described a CAC mouse mode in which tumors arise from DCLK1+ tuft cells following loss of the tumor suppressor adenomatous polyposis coli (APC) and induction of colitis. Interestingly, both colitis and CAC display epigenetic changes that modulate gene expression. Specifically, DNA methylation is altered in colitis, but its role in colonic tumorigenesis is not known. We hypothesize that inhibition of DNA methylation in DCLK1+ tuft cells reduces colonic tumorigenesis.

Aims
In this study, we aim to investigate the role of DNA methylation in CAC by inhibiting DNA methylation by genetic and pharmacologic means.

Methods
We crossed our Dclk1-CreERT2/Apcf/f mice to DNMT1f/f mice to delete the DNA methyltransferase DNMT1 in DCLK1+ tuft cells. We induced CAC in Dclk1/Apcf/f and Dclk1/Apcf/f/DNMT1f/f mice by administering three doses of tamoxifen followed by 2.5% dextran sodium sulfate (DSS) for five days. Fourteen weeks later we assessed colonic tumor number and size. Lineage tracing of Dclk1+ cells was also examined in colonic tissues from all mice. In a separate cohort of Dclk1/Apcf/f mice, we induced colitis and treated the mice with six doses of the DNA de-methylating drug 5-AZA-2’-deoxycytidine (5-AZA) or vehicle. Ki67 immunostaining was additionally performed to assess cellular proliferation in the colon.

Results
Deletion of DNMT1 in DCLK1+ cells significantly inhibited the number and size of colonic tumors. Treatment of mice with 5-AZA similarly reduced the overall number of mice with tumors, as well as, the number and size of tumors per mouse. Interestingly, 5-AZA treatment was associated with reduced colonic proliferation as assessed by fewer Ki67+ cells, and quiescent DCLK1+ cells that did not lineage trace. Furthermore, deletion of DNMT1 or treatment with 5-AZA reduced the number of lineage tracing events detected upon exposure to low DSS.

Conclusions
Our findings demonstrate that loss of Dnmt1 or 5-AZA treatment reduces CAC formation. Furthermore, 5-AZA appears to exert its anti-tumor effects by reducing proliferation and preventing tuft cell stemness. Our data demonstrates that altering DNA methylation plays an important role in CAC.

Funding Agencies
CIHR
A46 BIOGEOGRAPHIC VARIATION AND FUNCTIONAL PATHWAYS OF THE GUT MICROBIOTA IN CELIAC DISEASE
Authors: Libertucci J , Constante M , Galipeau H J , Szamosi J C , Rueda G H , Pinto-Sanchez M I , Southward C M , Rossi L M , Fontes M E , Chirdo F G , Surette M , Bercik P , CAMINERO FERNANDEZ A , Verdu E 
Published: February 2022

Abstract

Background
Genes and gluten are necessary, but insufficient to cause celiac disease (CeD), as risk alleles (DQ2 or DQ8) are prevalent in ~30–40% of the healthy population consuming gluten. Gut microbiota shifts and infections have been proposed as risk modulators. Biogeographic characterization of the microbiota in CeD patients and its functional significance are limited, particularly at the duodenum, the main site of inflammation.

Aims
We studied microbiota composition and predicted function along the gastrointestinal tract and investigated the impact of host genetics and CeD activity.

Methods
We used 16S rRNA gene sequencing (Illumina) and predicted gene function analysis (PICRUSt2), to study the microbiota in duodenal biopsies (D1, D2 and D3), duodenal aspirates, and fecal samples from patients with active CeD (n= 24) (biopsy and serology confirmed) and controls (non-celiac, n= 41). CeD alleles were determined in consented participants using DQ-CD typing. Small intestinal samples from controls (DQ2-/- = 14; DQ2+/- = 7) and CeD (DQ2+/- = 12) were used for further analysis and to colonize C57BL/6 germ-free mice for gluten metabolism studies.

Results
Microbiota community composition and predicted function was mainly determined by intestinal location (P= 0.001). Within the duodenum, but not in stool, CeD patients had increased abundance of opportunistic pathogens. Escherichia coli was increased in D1, Streptococcus pneumoniae in D2, and Neisseria in D3 versus controls. Predicted bacterial protease and peptidase genes were altered in CeD DQ2+/- patients versus DQ2-/- controls. In DQ2+/- controls, fewer predicted bacterial genes were altered compared to CeD DQ2+/- patients. Impaired capacity to metabolize gluten was confirmed in germ-free mice colonized with microbiota from CeD (DQ2+/-), but not DQ2+/- or DQ2-/- controls.

Conclusions
In the duodenum, CeD is associated with increased opportunistic pathogens and altered bacterial proteolytic profile. These are not determined by genetic predisposition, as CeD and controls with similar genetic background differed in its predicted bacterial proteolytic function, which was confirmed in mice colonized with duodenal microbiota using these cohorts. Our study highlights the need for defining sampling location in studies investigating the role of microbiota in CeD.

Funding Agencies
CAG, CCC, CIHR
A56 TUFT CELL RESPONSES DURING ACUTE- AND LATE-STAGE GIARDIA INFECTION
Authors: Sosnowski O , Allain T , Fekete E , Mckay D M , Buret A 
Published: February 2022

Abstract

Background
Epithelial tuft cells can detect and respond to enteric infections and appear to help clear some intestinal parasites. Through tuft cell luminal surface receptors, tuft cells can sense ligands directly supplied by a parasite, or indirectly via excretory/secretory products. We hypothesize that microbiome alterations may also modulate tuft cell-derived gut responses. Tuft cells release the alarmin cytokine IL-25 which, upon acting on type 2 innate lymphoid cells (ILC2), ultimately lead to tuft and goblet cell hyperplasia. Upon helminth infections, tuft and goblet cell hyperplasia occurred concurrently, and coincided with the peak of infection. The role of tuft cells in infections with the enteric protozoan parasite Giardia sp. is unknown. The aim of our study is to characterize how tuft cells may be implicated in the pathophysiology of giardiasis, in an attempt to uncover novel regulatory pathways of intestinal physiology.

Aims
In this study, we aim to characterise the tuft cell response to Giardia infection during acute and late stages of infection and to assess goblet cell hyperplasia.

Methods
5–7-week-old C57BL/6 mice and tuft cell-deficient mice ( Pou2f3-/-) were orally gavaged with 5x104Giardia muris trophozoites and scarified at days 4, 11 and 21 post-infection. Parasite burden was assessed in the duodenum. Immunofluorescence (IF) staining of doublecortin-like kinase 1 (DCLK1) – a marker of tuft cells – was performed on C57BL/6 mice jejunum tissue sections and the number of tuft cells was quantified. Goblet cells were quantified in PAS/AB-stained jejunum sections. Quantitative PCR (qPCR) was performed on Dclk1, the epithelial secretory cell transcription factor Atoh1, and the mucus gene Muc2.

Results
G. muris infected C57BL/6 mice displayed high parasite load at days 4 ( p&lt;0.05) and 11 ( p&lt;0.05), with no or low parasite burden at day 21 ( p&lt;0.05). Pou2f3-/- mice showed less robust parasite burden at days 4 and 11, and similar low parasite burden at day 21, compared to WT mice. At day 21, tuft cell (DCLK1+) counts ( p&lt;0.05) and Dclk1 mRNA expression levels were increased in Giardia infected mice in the jejunum. Goblet cell number and Atoh1 and Muc2 expression were increased at day 4 post-infection.

Conclusions
The data demonstrate that tuft cells expand late in Giardia infection, suggesting that upon parasite infection, tuft cells may possess roles in tissue repair or clearance of infection. Tuft cell-deficient mice ( Pou2f3-/-) had lower parasite burden early in Giardia infection, counter-intuitively suggesting that tuft cells may facilitate trophozoite colonization, further highlighting the novelty of these findings. The crosstalk between tuft cells, Giardia, and other host responses during acute and late stages of infection remain to be fully characterised.

Funding Agencies
NSERC