bluuebunny/crossref_metadata_2025_split huggingface dataset:
DROEG: a method for cancer drug response prediction based on omics and essential genes integration
Authors: Wu Peike , Sun Renliang , Fahira Aamir , Chen Yongzhou , Jiangzhou Huiting , Wang Ke , Yang Qiangzhen , Dai Yang , Pan Dun , Shi Yongyong , Wang Zhuo 
Published: January 2023

AbstractPredicting therapeutic responses in cancer patients is a major challenge in the field of precision medicine due to high inter- and intra-tumor heterogeneity. Most drug response models need to be improved in terms of accuracy, and there is limited research to assess therapeutic responses of particular tumor types. Here, we developed a novel method DROEG (Drug Response based on Omics and Essential Genes) for prediction of drug response in tumor cell lines by integrating genomic, transcriptomic and methylomic data along with CRISPR essential genes, and revealed that the incorporation of tumor proliferation essential genes can improve drug sensitivity prediction. Concisely, DROEG integrates literature-based and statistics-based methods to select features and uses Support Vector Regression for model construction. We demonstrate that DROEG outperforms most state-of-the-art algorithms by both qualitative (prediction accuracy for drug-sensitive/resistant) and quantitative (Pearson correlation coefficient between the predicted and actual IC50) evaluation in Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopedia datasets. In addition, DROEG is further applied to the pan-gastrointestinal tumor with high prevalence and mortality as a case study at both cell line and clinical levels to evaluate the model efficacy and discover potential prognostic biomarkers in Cisplatin and Epirubicin treatment. Interestingly, the CRISPR essential gene information is found to be the most important contributor to enhance the accuracy of the DROEG model. To our knowledge, this is the first study to integrate essential genes with multi-omics data to improve cancer drug response prediction and provide insights into personalized precision treatment.
Let’s pluck the daisy: dissection as a tool to explore the diversity of Asteraceae capitula
Authors: Fu Lin , Palazzesi Luis , Pellicer Jaume , Balant Manica , Christenhusz Maarten J M , Pegoraro Luca , Pérez-Lorenzo Iván , Leitch Ilia J , Hidalgo Oriane 
Published: January 2023

AbstractAsteraceae, the daisy family, are one of the most diverse families of angiosperms and are predominant in many ecosystems, including grasslands, deserts, savannas and high-elevation mountains. They are characterized by a peculiar inflorescence, the capitulum, which mimics a flower, but is actually made up of many tightly grouped florets. The capitulum is considered a key character underpinning the impressive evolutionary success of the family, and it plays a pivotal role in the economic importance of the family, given that many species are cultivated for their capitulum for agricultural and horticultural purposes. However, to date, there is still no comprehensive understanding of the extent of the morphological diversity of capitula across lineages of Asteraceae. This is mainly due to a lack of appropriate tools for describing such a complex and condensed structure. To address the problem, we present a protocol for characterizing the full diversity of capitula from any lineage of Asteraceae. This involves making a whole dissection of a capitulum from fresh material; it is simple and cost-effective and requires relatively easy-to-transport equipment meaning that it can be done during fieldwork.
Standardized cotton swab sampling with nested quantitative polymerase chain reaction is effective for diagnosing ordinary scabies
Authors: Chung Hyun Chul , Chun Eun Ji , Kim Joon Ki , Kim Sang Seok , Kim Chul Woo 
Published: January 2023

Abstract

Background
Low sensitivity of the PCR assay for diagnosing scabies has been noted because of the difficulty in obtaining tissue containing Sarcoptes scabiei DNA.

Aim
To evaluate nested real-time quantitative PCR (nRT-qPCR) with nonexpert-dependent standardized cotton swab sampling (CSW) as a tool for diagnosing scabies.

Methods
All patients underwent dermoscopic and microscopic examination (MS) with scraped sampling (Sc). Patient samples were acquired with a single, dry swab rubbed across the flexor areas of both wrists as well as the eight interdigital spaces and on any suspected scabies lesions. nRT-qPCRs were performed with Sc and CSW samples.

Results
Out of 125 patients with suspected scabies, 120 patients were sampled, and 57 were positive (positive with: MS n = 53; nRT-qPCR with Sc n = 52; nRT-qPCR with CSW n = 46) and 63 were negative for scabies. The sensitivities of these tests were 93.0%, 91.2% and 80.7%, respectively, which were not different statistically (P &gt; 0.05). However, upon subsequent monitoring after treatment, the sensitivity of nRT-qPCR with CSW was only 36.6%, which was significantly lower than 83.0% for MS and 92.7% for nRT-qPCR with Sc (P &lt; 0.001). The obtained sequences showed 97%–100% homology with scabies sequences deposited in GenBank.

Conclusion
CSW with nRT-qPCR shows sensitivity close to MS with scraping performed by experts for diagnosing scabies in an outpatient setting, but not for post-treatment monitoring. CSW with nRT-qPCR may be useful for physicians unfamiliar with a traditional diagnostic method, and for screening an outbreak in community facilities.
OP12 Does early initiation of biologics change the natural history of IBD? a nationwide study from the epi-IIRN
Authors: Focht G , Lujan R , Atia O , Greenfeld S , Kariv R , Loewenberg Weisband Y , Lederman N , Matz E , Dotan I , Turner D 
Published: January 2023

Abstract

Background
Studies have reported conflicting findings regarding the effect of timing of biologics initiation on disease course, often affected by selection and referral biases. In this nationwide cohort study we aimed to explore whether early initiation of biologics is associated with better disease outcomes in CD and UC.

Methods
Data of patients diagnosed with IBD in the epi-IIRN cohort from 2005 to 2020 were retrieved from 4 Israeli Health-Maintenance-Organizations covering 98% of the population.The primary analysis was time to steroid-dependency and IBD-related surgery. To control for confounding by indication in which the severity of disease could account both for the timing of biologics and risk of disease outcomes,we compared treatment strategies using the cloning,censoring and weighting method to emulate a target trial. Inverse probability of treatment weights were fitted per patient to adjust by weighting for time varying confounding and selection bias.Survival probabilities(POS) were estimated and compared at 10 years post diagnosis for each strategy through weighted non-parametric Kaplan-Meier estimators. The 95%CIs for survival probabilities were calculated using non-parametric bootstrap with 500 replicates.

Results
Of the 34,375 patients diagnosed with IBD, 7,452(39%) CD patients and 2,235(15%) UC patients received biologics and included in the analysis. In total,1,139 CD and 206 UC patients received biologics during the first three months after diagnosis,2,108 CD and 450 UC during the 3-12 month period,1,161 CD and 396 UC during 1-2 year period,and 719 CD and 271 UC during 2-3 years post diagnosis. Patients who initiated biologics after 3 years post diagnosis were excluded as they were not considered early biologics initiation.In CD,at 10 years post diagnosis there was a significant but modest decrease in IBD-related surgeries when initiating biologics prior to 3 months compared to the other periods (POS:0-3 months 0.75[CI 0.71- 0.79] vs 2-3 year 0.7[CI 0.66-0.73] ;p&lt;0.05).The same observation with a larger effect, was apparent for steroid-dependency (POS:0-3 months 0.78[CI 0.75-0.82] vs 2-3 year 0.69[CI 0.66-0.71]; p&lt;0.001)(Fig 1). In UC, no significant differences in colectomy rate at 10 years was observed between the treatment periods (POS:0-3 months 0.92[CI 0.87-0.97] vs. 2-3 years 0.94[CI 0.91-0.98];p=0.42). On the other hand, a significant decrease was apparent for steroid-dependency (POS:0-3 months 0.78[CI 0.75-0.82] vs 2-3 year 0.69[CI 0.66-0.71];p&lt;0.001)(Fig 2).

Conclusion
Our study showed a slight advantage to earlier initiation of biologics,as reflected by longer time to IBD-related surgery and steroid-dependency in CD.In UC, the effect of early biologics was minor and was only apparent for steroid dependency in UC.
OP23 Asymptomatic inflammatory bowel disease diagnosed during the colorectal cancer population screening in Catalonia
Authors: Brunet E , Selva A , Bas-Cutrina F , Brujats A , Caballol B , Gomez B , Gonzalez C , Busquets D , Monfort D , Vera D P , Maristany E , Cirera G , Torres G , Castro-Poceiro J , Lopez J , Gonzalez-Gonzalez L , Marquez-Mosquera L , Gallach M , Esteve M , Tremosa G , Torra S , Robles V , Rodríguez-Lago I , Calvet X 
Published: January 2023

Abstract

Background
Background: It has been postulated that early treatment of inflammatory bowel disease (IBD) is associated with a better long-term response. In Catalonia, the early detection program for colorectal cancer (EDPCRC) has been active since 2010, and was extended to the entire Catalan territory in 2015. The aim of this study is to describe the natural history of IBD asymptomatic diagnosed through the EDPCRC in Catalonia.

Methods
Methods: Observational, longitudinal and retrospective study of patients with IBD detected in the EDPCRC with a positive faecal immunological test in 21 centers in Catalonia between 2010 and 2019. Data was collected from the clinical histories.

Results
Results: 237 patients were identified; 35 patients had symptoms before endoscopy and were excluded from the study, finally 200 patients were diagnosed with asymptomatic IBD during the EDPCRC; 109 ulcerative colitis (54.5%), 63 Crohn’s disease (31.5%) and 28 unclassifiable colitis (14%). 35.5% were women (n=71) with an average age of 60 years (range 49-79). Of the asymptomatic, 40.5% developed symptoms (n=81), being diarrhea the most frequent (n=45; 55.6%). The median time to first symptom was 368 days. Treatment was prescribed in 74.5% (n=149) of the patients. Mesalazine was the most frequently prescribed drug (n=130). The main reason for prescribing it was endoscopic activity (n=107), followed by the appearance of symptoms (n=39) and the biochemical activity (n=9). Only 19 patients (9.5%) required biological treatment (5 infliximab, 10 adalimumab, 2 vedolizumab and 2 ustekinumab). 4 patients (2%) required surgery.

Conclusion
Conclusion: Less than half of patients diagnosed with IBD at a preclinical stage develop symptoms after the first year of follow-up. Only 9.5% require biological treatment and 2% surgery. Three-quarters of patients are prescribed treatment; the most used was mesalazine.
OP30 Human umbilical cord mesenchymal stem cells derived exosomes alleviate Ulcerative Colitis by inhibiting macrophage ferroptosis via miR-23b-3p/Nrf2 pathway
Authors: Liu L , Zhao J , Ye Y , Feng Z , Wang X , Cao X 
Published: January 2023

Abstract

Background
Human umbilical cord mesenchymal stem cell derived exosomes (HucMSC-Exo) have broad application prospects in treatment of various disease, including ulcerative colitis (UC). Macrophages can trigger intestinal mucosal inflammation thereby participating in the onset and development of UC. As a newly discovered iron-dependent cell death pathway, ferroptosis has also been found accompanied by inflammatory response in recent studies. We speculated that there could be relationship between macrophage ferroptosis and inflammatory response in UC. Furthermore, the role of macrophage ferroptosis in the process of HucMSC-Exo alleviating UC remains undefined. This study aims to explore the therapeutic effect and mechanism of HucMSC-Exo on UC by regulating macrophage ferroptosis.

Methods
The gene expression of ferroptosis-related proteins was assessed in colon samples from healthy controls and UC patients to explore the relationship between ferroptosis and UC. In vivo, colitis was induced by dextran sulfate sodium in mice. HucMSC-Exo was administered intravenously to estimate its curative effect, and its gut homing was evaluated by animal live imaging analysis. In vitro, HucMSC-Exo were cocultured with ferroptosis inducer RSL3-treated bone marrow-derived macrophages (BMDMs), RAW264.7 cell line, followed by examining the effect of HucMSC-Exo. Transfection of microRNA mimics and gene knockdown were used to confirm the role of miR-23b-3p in HucMSC-Exo regulating of macrophage ferroptosis.

Results
Compared with healthy individuals, ferroptosis may be involved in the mucosal inflammation of UC patients. HucMSC-Exo were found to successfully target damaged colon tissues in vivo. HucMSC-Exo treatment significantly improved the pathological damage of colon tissue, increased the expression of glutathione peroxidase 4 (GPX4), while markedly decreasing the levels of iron and lipid ROS, and reducing the secretion of interleukin (IL)-1β and IL-6, and then relieved macrophage ferroptosis to alleviate murine colitis. In vitro experiments showed that HucMSC-Exo could be effectively absorbed by macrophages and rescued RSL3-induced ferroptosis, which was consistent with the effect of ferrostatin-1, a ferroptosis-specifific inhibitor. Mechanismly, HucMSC-exo could inhibit macrophage ferroptosis by delivering its highly expressed miR-23b-3p to activate Nrf2 pathway. Additionally, the protection of HucMSC-exo for UC was attenuated by decreasing the expression of miR-23b-3p or inhibiting Nrf2 pathway.

Conclusion
HucMSC-Exo could activate Nrf2 antioxidant pathway and abrogate macrophage ferroptosis by delivering miR-23b-3p and ultimately ameliorate colitis.
OP31 High fat diet exacerbates colitis through microbial metabolite deoxycholic acids induced-ferroptosis
Authors: Wang C , Gu Y , Cao H 
Published: January 2023

Abstract

Background
High-fat diet (HFD) is closely related to the occurrence and development of IBD, which increases the level of deoxycholic acid (DCA). DCA-treated mice showed pro-inflammatory cell infiltration and colonic inflammation. Ferroptosis, a newly recognized form of cell death characterized by iron overload and the generation of reactive oxygen species (ROS) has recently been observed in colitis. Whether DCA affects ferroptosis and whether it contributes to colitis has not been explored.

Methods
Twenty-four Female C57BL/6 mice were randomly divided into 4 groups: control group, DCA group, DSS group, and DSS plus DCA group. Real-time PCR and Western blotting were used to detect the transcription and protein expression of ferroptosis-related genes. RNA sequencing was used to analyze the changes of differential genes in the intestinal tissue of mice treated with DCA. Transmission electron microscope was employed to observed the changes of intestinal epithelial cell morphology and intracellular mitochondria. Finally, the binding force between DCA and HIF-2α was calculated by molecular dynamics to explore the structural biological basis of the interaction between DCA and HIF-2α, and screen innovative drugs.

Results
We found that DCA exacerbated the disease activity index, histological damage and cell death in mice with colitis. In vivo, ferroptosis KEGG pathway was enriched by RNA sequencing in colonic tissues. DCA treatment significantly induced ferroptosis in DSS-induced mice, as evidenced by iron overload, ROS and MDA production, accompanied by decreased expression of GPX4 and increased expression of ACSL4. Transmission electron microscopy also confirmed the occurrence of ferroptosis in colonic tissues. In vitro, DCA induced ferroptosis were also observed in IEC-6 cells and Caco-2 cells under the combined treatment of Lipopolysaccharide (LPS). Interestingly, RNA sequencing revealed that the expression levels of the apical iron divalent metal transporter-1 (DMT1) were significantly upregulated in DCA treated-mice with colitis. DMT1 is a direct target gene of hypoxia inducible factor (HIF)-2α. We also found that DCA could increase the level of DMT1 and HIF-2α in the intestinal epithelial cell lines. Pharmacological inhibition of HIF-2α significantly inhibited the expression of DMT1 and blocked the promotion of ferroptosis by DCA. These data provide a mechanistic basis for the widely reported link between ferroptosis and colitis risk.

Conclusion
Taken together, these findings suggest that DCA aggravates colitis through the induction of ferroptosis in the HIF2α-DMT1 signaling pathway and provides a new perspective for UC prevention in the future.
OP38 Modulation of the septin cytoskeleton ameliorates intestinal fibrogenesis
Authors: Naydenov N , Le T H N , Lechuga Villarauz S , Elias M , West G , Czarnecki D , Plesec T , Ivanov A , Rieder F 
Published: January 2023

Abstract

Background
Fibrosis-induced intestinal strictures leading to obstruction are a common and serious complication of Crohn’s disease (CD) with currently no available specific anti-fibrotic therapies. Cytoskeletal dynamics in mesenchymal cells are associated with organ fibrogenesis. Septin filaments are a novel cytoskeletal element, but the functional role of septins in regulating intestinal inflammation and fibrosis remain unknown. We examined the involvement of the septin cytoskeleton in modulating fibrogenic signaling in intestinal fibrogenesis in vitro and in vivo.

Methods
Expression of different septins in human intestinal resection tissues, primary human intestinal myofibroblasts (HIMF) and immortalized colonic myofibroblast (CCD 18co cells) were examined by real-time PCR and immunoblotting. Functional inhibition of the septin cytoskeleton was achieved using siRNA for septin 7 and the cell-permeable small molecule forchlorfenuron (FCF). Migration and proliferation of HIMF were examined by wound healing and thymidine incorporation assays, respectively. Levels of secreted cytokines were measured using cytometric bead array. Roles of septins in the development intestinal fibrosis in vivo was studied using a chronic DSS colitis model in mice with administration of FCF or vehicle.

Results
All septin genes were expressed in intestinal tissues with a predominant expression of septin 7. Pro-fibrotic transforming growth factor-β1 (TGFβ1) triggered HIMF activation manifested by the increased production of ECM proteins such as fibronectin and collagen 1 and enhanced expression of the myofibroblast markers α-smooth muscle actin, L-caldesmon and tropomyosin. Septin 7 knockdown resulted in loss of other septin proteins thereby disrupting the entire septin cytoskeleton. Either pharmacological, or genetic disruption of the septin cytoskeleton reversed the effect of TGFβ1 by attenuating production of ECM proteins and reducing expression of myofibroblast markers. Interestingly, these effects were only found on protein level and were not due to changes in gene expression, suggesting inhibition of their expression at a post-transcriptional level. Moreover, pharmacological or genetic disruptions of the septin cytoskeleton resulted in reduced migration, and attenuated cytokine secretion by activated myofibroblasts. FCF administration did not affect intestinal inflammation, but decreased the fibrosis score during chronic DSS colitis in mice.

Conclusion
Our data highlights the septin cytoskeleton as a novel regulator of intestinal myofibroblast activation and function. This for the first time implicates the cytoskeleton as an active participant in intestinal fibrosis and as a potential novel target for the development of anti-fibrotic therapies in IBD patients.
DOP19 Incidence and initial disease presentation of inflammatory bowel diseases in Denmark: findings from a Copenhagen IBD Inception Cohort Study (IBD Prognosis Study)
Authors: Attauabi M , Madsen G R , Wewer A V , Bendtsen F , Jakobsen C , Dorn-Rasmussen M , Malham M , Theede K , Bjerrum J T , Boysen T , Seidelin J B , Burisch J 
Published: January 2023

Abstract

Background
The increasing incidence of inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC), Crohn’s disease (CD), and unclassified IBD (IBD-U), in Denmark requires close surveillance. Therefore, we aimed to investigate their current incidence and initial disease presentation in a population-based inception cohort.

Methods
IBD Prognosis Study is an ongoing prospective population-based inception cohort of patients diagnosed with UC, CD, or IBD-U between May 1st, 2021, and May 1st, 2023, according to the Copenhagen IBD Criteria within the well-defined geographical uptake area of Hvidovre University Hospital and Herlev University Hospital. This area has a catchment population of 1,050,000, corresponding to ~20% of the Danish population. The incidence rate is defined as the number of new cases between May 1st, 2021, and October 31st, 2022, divided by the total number of 100,000 inhabitants covered in included sites per year during the same period. For the incidence calculations, pediatric-onset of IBD was defined as age &lt; 19 years at diagnosis. However, for the clinical description, for the clinical presentation, the cut-off was &lt;18 years.

Results
As of October 31, 2022, a total of 219, 134, and 24 patients with adult-onset UC, CD, and unclassified IBD (IBD-U), respectively, has been included, corresponding to incidence rates of 13.9, 8.5, and 1.5 per 100,000 adults per year. Further, 11, 16, and two patients with pediatric-onset UC, CD, and IBD-U were included, corresponding to 3.6, 6.3, and 0.7 per 100,000 pediatric cases per year. Demographics and initial disease presentation are presented in Tables 1-2, initial disease burden and treatment patterns in Tables 3-4.

Conclusion: The preliminary data from the ongoing prospective population-based cohort, IBD Prognosis Study, indicate that the incidence rates of adult-onset IBD appear stabilized, while that of pediatric-onset CD is increasing, when compared with data from before 2010.1,2
The study is ongoing and includes extensive and continuous examinations, including endoscopy, intestinal ultrasound investigations, magnetic resonance imaging of the small intestine and biliary and pancreatic ducts, patient-reported measures, and biobanking. As such, the cohort is expected to deliver essential knowledge on the mechanisms for the unpredictable course of IBD.3
References:
1. Vind I et al. Am J Gastroenterol. 2006; doi:10.1111/j.1572-0241.2006.00552.x
2. Jakobsen C et al. Inflamm Bowel Dis. 2011; doi:10.1002/ibd.21654
3. Attauabi M et al. BMJ Open. 2022; doi:10.1136/bmjopen-2021-055779