bluuebunny/crossref_metadata_2025 huggingface dataset:
Potato (Solanum tuberosum L.) Varieties Improvement in Kerinci, Jambi
Authors: Izhar Lutfi , Edi Syafri
Published: February 2022

Potato is the main vegetable commodity cultivated by farmers in Kerinci Regency and has been supported by appropriate agro-ecosystems, the availability of land areas, labor and market opportunities as well as government endowment. In general, farmers in every season have not fully implemented cultivation technology recommendations. This paper aims to describe the growth and productivity improvement of potato varieties in Kerinci, Jambi. The activity was carried out in Tanjung Bunga Village, Kayu Aro District, Kerinci Region during wet season 2018, involving 3 cooperative farmers and a land area of 0.25 ha which was planted with two varieties namely Granola and Medians. The results showed that the Medians variety gave a higher number of tubers than the Granola variety, but a large number of tubers was obtained from the Granola variety. Therefore, the Granola variety provided a heavier yield of 17.08 kg or equivalent to 22.775.5 kg/ha, while the Medians was only 12.50 kg or 17.862.25 kg/ha. This study was also found three main pests that occurred ie, leaf-miner fly, armyworm, and tuber-miner, whereas late blight disease was caused by Phytophthora infestans simultaneously infecting both varieties. However, conducting the demonstration plots in this season, the Granola variety was more resistant to disease than the Medians variety.
Research of fermentation processes of protein substrates by consortiums of lactic acid bacteria
Authors: Kitaevskaya S V , Ponomarev V Y , Sh Yunusov E
Published: February 2022

The paper presents data on the assessment of the biotechnological activity of new consortiums of lactic acid bacteria Lactobacillus with the proteolytic activity. A comparative assessment of the biotechnological use of previously isolated strains of lactic acid bacteria and their combinations using methods that are highly effective in the technology of fermented food products is carried out. Biotechnological properties were studied on various food objects and substrates of animal and plant origin with a high protein content. As a result of the studies, consortiums of lactic acid bacteria, they can be recommended for inclusion in the composition of starter cultures for the production of functional products.
Mechanical and tribological behavior of friction stir processed AZ61/egg shell powder/WS2 Hybrid surface composite
Authors: Hariprasad V , Megalingam A
Published: February 2022

Egg Shell Powder (ESP) and Tungsten Disulphide (WS2) are reinforced on AZ61 magnesium alloy through Friction Stir Process (FSP). The average particle size of ESP and WS2 are 45 μm and 10 μm, respectively. The ESP and WS2 mixed at different weight percentage (80/20, 70/30, 50/50, 30/70 and 20/80). Initially, equally spaced cylindrical holes are drilled on AZ61 alloy and then reinforcement mixture is filled in the holes using a flat head tool to secure the reinforcements. FSP tool pin with threaded profile is used to perform the friction stir process at tool rotation speed of 1000 rpm, 7 kN of axial load and 5 mm minute−1 tool transfers speed. From the micro and macro optical images, the defect free FSPed composite is obtained for the reinforcement combination of AZ61/80ESP/20WS2. The mechanical, tribological and corrosion tests are conducted on FSPed AZ61/80ESP/20WS2 composite and AZ61 base alloy according to ASTM standards. Microhardness increased twice in the nugget zone of FSPed AZ61/80ESP/20WS2 composite compared to the AZ61 base alloy because of grain refinement. The ultimate tensile strength of FSPed AZ61/80ESP/20WS2 composite increased up to 8.3% compared to AZ61 base alloy and showed ductile behaviour during the fracture. Dry wear tests conducted at three different sliding velocities (0.83, 1.7 and 2.5 m s−1) and three different loads (5 N, 10 N and 15 N) by keeping the sliding distance as 1500 m. The results showed an improvement in wear resistance of FSPed AZ61/80ESP/20WS2 composite up to 35% compared to the AZ61 base alloy. SEM images revealed that the wear mechanism changes from adhesive to abrasive under high operating conditions. The results of electrochemical corrosion test revealed that the corrosion rate of the FSPed AZ61/80ESP/20WS2 composite reduced significantly at the nugget zone because of grain refinement and reinforcement addition.
Zinc titanates nanopowders: synthesis and characterization
Authors: Gabal M A , Angari Y M Al
Published: February 2022

Zinc titanates nanopowders viz.; Zn2TiO4, ZnTi3O8 and ZnTiO3 were synthesized through the thermal decomposition course of ZnC2O4.2H2O-TiO2 precursors mixture (1:1 mole ratio), prepared via a new co-precipitation method up to 900 °C. Thermogravimetric measurement (TG) was utilized to characterize the precursors mixture decomposition while x-ray diffraction (XRD), Fourier transform infra-red (FT-IR) were used to characterize the decomposition products as well as the phase transitions at different temperatures. XRD revealed the starting of titanates formation at 700 °C via detecting Zn2TiO4 along with ZnO and TiO2 (anatase) diffraction peaks. By increasing the calcination temperature to 800 °C, the ZnO content vanished with the appearing of Zn2Ti3O8 besides ZnTi2O4 and impurities of TiO2 (anatase). Finally at 900 °C, the Zn2Ti3O8 content was decomposed into ZnTiO3. Nitrogen adsorption-desorption isotherm of the calcined precursors mixture at 900 °C indicated low specific surface area of 7.1 m2 g−1 in accordance with the agglomeration nature estimated via transmission electron microscopy (TEM) study. The conductivity measurements showed semiconducting behavior of the prepared titanates with ferroelectric transition in the range 200 °C–308 °C. The obtained low dielectric value suggests the uses of present titanates as a co-fired ceramic or resonator ceramics.
Roadmap on Machine learning in electronic structure
Authors: Kulik H J , Hammerschmidt T , Schmidt J , Botti S , Marques M A L , Boley M , Scheffler M , Todorović M , Rinke P , Oses C , Smolyanyuk A , Curtarolo S , Tkatchenko A , Bartók A P , Manzhos S , Ihara M , Carrington T , Behler J , Isayev O , Veit M , Grisafi A , Nigam J , Ceriotti M , Schütt K T , Westermayr J , Gastegger M , Maurer R J , Kalita B , Burke K , Nagai R , Akashi R , Sugino O , Hermann J , Noé F , Pilati S , Draxl C , Kuban M , Rigamonti S , Scheidgen M , Esters M , Hicks D , Toher C , Balachandran P V , Tamblyn I , Whitelam S , Bellinger C , Ghiringhelli L M
Published: February 2022

In recent years, we have been witnessing a paradigm shift in computational materials science. In fact, traditional methods, mostly developed in the second half of the XXth century, are being complemented, extended, and sometimes even completely replaced by faster, simpler, and often more accurate approaches. The new approaches, that we collectively label by machine learning, have their origins in the fields of informatics and artificial intelligence, but are making rapid inroads in all other branches of science. With this in mind, this Roadmap article, consisting of multiple contributions from experts across the field, discusses the use of machine learning in materials science, and share perspectives on current and future challenges in problems as diverse as the prediction of materials properties, the construction of force-fields, the development of exchange correlation functionals for density-functional theory, the solution of the many-body problem, and more. In spite of the already numerous and exciting success stories, we are just at the beginning of a long path that will reshape materials science for the many challenges of the XXIth century.
A descriptive report of the rapid implementation of automated MRC-ICU calculations in the EMR of an academic medical center
Authors: Webb Andrew J , Rowe Sandra , Newsome Andrea Sikora
Published: February 2022

Purpose

Numerous clinical scoring tools exist for a variety of patient populations and disease states, but few tools provide information specifically designed for use by critical care pharmacists. The medication regimen complexity–intensive care unit (MRC-ICU) score was designed to provide high-level information about the complexity of critically ill patients’ medication regimens for use by critical care pharmacists. To date, implementation of this score in the electronic medical record (EMR) has not been reported.

Using an agile project management framework, the MRC-ICU score was rapidly implemented into an academic medical center’s EMR. The score is automatically calculated for all critically ill patients and is available for critical care pharmacists to triage patient review in their individual workflow. Reporting capabilities of the score also allow for granular complexity trending over time and between units, supplementing other objective measures of pharmacist workload.

Conclusion

The MRC-ICU score can be quickly implemented into the EMR for pharmacist use in real time. Future investigations into how pharmacists utilize this information and how to harness reporting capabilities for pharmacist workload assessment are warranted.
Network medicine in ovarian cancer: topological properties to drug discovery
Authors: Chirom Keilash , Malik Md Zubbair , Mangangcha Irengbam Rocky , Somvanshi Pallavi , Singh R K Brojen
Published: February 2022

Network medicine provides network theoretical tools, methods and properties to study underlying laws governing human interactome to identify disease states and disease complexity leading to drug discovery. Within this framework, we investigated the topological properties of ovarian cancer network (OCN) and the roles of hubs to understand OCN organization to address disease states and complexity. The OCN constructed from the experimentally verified genes exhibits fractal nature in the topological properties with deeply rooted functional communities indicating self-organizing behavior. The network properties at all levels of organization obey one parameter scaling law which lacks centrality lethality rule. We showed that $\langle k\rangle $ can be taken as a scaling parameter, where, power law exponent can be estimated from the ratio of network diameters. The betweenness centrality $C_B$ shows two distinct behaviors one shown by high degree hubs and the other by segregated low degree nodes. The $C_B$ power law exponent is found to connect the exponents of distributions of high and low degree nodes. OCN showed the absence of rich-club formation which leads to the missing of a number of attractors in the network causing formation of weakly tied diverse functional modules to keep optimal network efficiency. In OCN, provincial and connector hubs, which includes identified key regulators, take major responsibility to keep the OCN integrity and organization. Further, most of the key regulators are found to be over expressed and positively correlated with immune infiltrates. Finally, few potential drugs are identified related to the key regulators.
The clinical effectiveness and safety of using epidermal growth factor, fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing: a systematic review and meta-analysis
Authors: Wei Yating , Li Jiangfeng , Huang Yao , Lei Xun , Zhang Lijun , Yin Meifang , Deng Jiawen , Wang Xiaoyan , Fu Xiaobing , Wu Jun
Published: February 2022

Background

Promoting wound healing is crucial to restore the vital barrier function of injured skin. Growth factor products including epidermal growth factor (EGF), fibroblast growth factor (FGF) and granulocyte-macrophage colony stimulating factor (GM-CSF) have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds. This has resulted in a lack of guidelines and standards for proper application regimes. Therefore, this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes.

Methods

We searched PubMed/Medline (1980–2020), Cochrane Library (1980–2020), Cochrane CENTRAL (from establishment to 2020), ClinicalTrials.gov (from establishment to 2020), Chinese Journal Full-text Database (CNKI, 1994–2020), China Biology Medicine disc (CBM, 1978–2019), Chinese Scientific Journal Database (VIP, 1989–2020) and Wanfang Database (WFDATA, 1980–2019). Randomized controlled trials (RCTs), quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included.

Results

A total of 7573 papers were identified through database searching; 229 papers including 281 studies were kept after final screening. Administering growth factors significantly shortened the healing time of acute skin wounds, including superficial burn injuries [mean difference (MD) = −3.02; 95% confidence interval (CI):−3.31 ~ −2.74; p < 0.00001], deep burn injuries (MD = −5.63; 95% CI:−7.10 ~ −4.17; p < 0.00001), traumata and surgical wounds (MD = −4.50; 95% CI:−5.55 ~ −3.44; p < 0.00001). Growth factors increased the healing rate of acute skin wounds and decreased scar scores. The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group.

Conclusions

The studied growth factors not only are effective and safe for managing acute skin wounds, but also accelerate their healing with no severe adverse reactions.
Improved immunogenicity following the third dose of BNT162b2 mRNA vaccine in heart transplant recipients
Authors: Shaul Aviv Avraham , Itzhaki Ben Zadok Osnat , Ben-Avraham Binyamin , Yaari Vicky , Barsheshet Alon , Levi Amos , Ben Zvi Haim , Eliakim Raz Noa , Abed Galia , Abuhazira Miriam , Abu Akel Mahmood , Mats Israel , Barac Yaron D , Aravot Dan , Kornowski Ran , Ben-Gal Tuvia
Published: February 2022

OBJECTIVES

The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients.

METHODS

This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14–28 days after the third dose. Titres above 50 U/ml were interpreted positive.

RESULTS

We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58–70]. At baseline, the median of 27 days (IQR 13–42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4–130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7–6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre.

CONCLUSIONS

Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.
Barley: a potential cereal for producing healthy and functional foods
Authors: Geng La , Li Mengdi , Zhang Guoping , Ye Lingzhen
Published: February 2022

Barley is the fourth largest cereal crop in the world. It is mainly used for feeding, beer production and food. Barley is receiving more attention from both agricultural and food scientists because of its special chemical composition and health benefits. In comparison with other cereal crops, including wheat, rice and maize, barley grains are rich in dietary fiber (such as β-glucan) and tocols, which are beneficial to human health. It is well proved that diets rich in those chemicals can provide protection against hypertension, cardiovascular disease, and diabetes. Barley has been widely recognized to have great potential as a healthy or functional food. In this review, we present information about studies on the physical structure of the barley grain and the distribution of its main chemical components, nutrient and functional composition of barley grain and their health benefits, and the approaches of improving and utilizing the nutrient and functional chemicals in barley grain. With the development of processing technologies, functional components in barley grains, especially β-glucan, can be efficiently extracted and concentrated. Moreover, nutrient and functional components in barley grains can be efficiently improved by precise breeding and agronomic approaches. The review highlights the great potential of barley used as healthy and functional foods, and may be instructive for better utilization of barley in food processing.
Role status and status-saving behaviour in world politics: the ASEAN case
Authors: He Kai , Feng Huiyun
Published: February 2022

Most research on status in international politics focuses on a state's ‘trait status’, defined by valued attributes that a state possesses, but ignores the importance of ‘role status’, which is constituted through state interactions and competent practices in world politics. By integrating prospect theory and role status scholarship, this article introduces a ‘status-saving’ argument to shed light on how states adopt risk-acceptant strategies to salvage the decline in their role status in world politics. We test the status-saving argument by examining the ASEAN states’ bold community-building efforts in the early 2000s, especially the adoption of the ASEAN Charter in 2007. We argue that both the economic and political conditions of ASEAN were far from mature enough to pursue such an institutionalization and legalization endeavour. The perceived decline of international role status after the 1998 Asian financial crisis, however, encouraged the ASEAN states to take this ‘great leap forward’ behaviour towards regional integration, which has placed ASEAN's long-term status and internal unity in a more risky and vulnerable position. We conclude that pursuing role status is another way for states, especially rising powers, to seek status in a deference hierarchy. Dominant powers should consider accommodating the pursuit of role status by rising powers and encourage ‘do-goodism’ in world politics.
Quasisteady models for weld temperatures in fused filament fabrication
Authors: Edwards D A
Published: February 2022

During fused filament fabrication (FFF), strands of hot extruded polymer are layered onto a cooler substrate. The bond strength between layers is related to the weld temperature at the polymer/substrate interface, and hence understanding temperature evolution is of keen interest. A series of increasingly sophisticated models is presented: a standard heat equation, an unsteady fin equation and a fin equation with a heat-loss jump condition. Each is analytically tractable and uses a quasisteady approximation for the temperature in the growing substrate. The jump condition introduces the complication of a non-self-adjoint problem, but fits the experimental data very well.
A6 MECHANISMS UNDERLYING GUT DYSFUNCTION FOLLOWING C. DIFFICILE INFECTION AND IMPLICATIONS FOR TREATMENT
Authors: Saqib Z , BAI X , De Palma G , Hynes A , Surette M , Bercik P , Collins S M
Published: February 2022

Background

Recent evidence suggests an increasing prevalence of gut dysfunction following C. difficile infection (CDI). The accompanying prolonged antibiotic (AB) exposure likely contributes to chronic gut dysfunction and our ability to induce gut dysfunction in germ free (GF) mice colonized with microbiota from a patient with severe slow transit post CDI (PCDI) supports this notion (10.1093/jcag/gwz047.117). Furthermore, we were able to restore gut function following fecal microbial transfer from healthy murine donors. Our studies have implicated a role for macrophages in the destruction of the Interstitial Cell of Cajal (ICC) network underlying slow colonic transit in the humanized mouse model. These findings prompted us to evaluate microbiota-directed therapy in normalising gut function in this model.

Aims

1)To investigate whether dietary psyllium rescues the development of slow colonic transit (SCT) through modulating host function via microbiota mediated immune mechanisms; and 2)To evaluate the mechanisms underlying the beneficial effects of psyllium

Methods

GF mice were colonized with either microbiota from the PCDI patient or healthy control (HC) for 3 weeks following which PCDI mice were treated with either a control diet or a 15% psyllium diet (PSY). Colonic motility was assessed before and after the diet intervention using the bead expulsion test. Stool samples were collected for microbial profiling, and short and branched-chain fatty acids (SCFA/BCFA) analysis. Colonic muscle layers encompassing myenteric plexus (MP) were collected for gene expression analysis and to evaluate activated macrophages and ICC degeneration using immunohistochemistry.

Results

Microbiota from a PCDI patient induced a SCT phenotype in GF mice (n=13) as compared to mice colonized with HC microbiota (p=0.0002). Psyllium rescued this SCT phenotype in mice (PCDI(n=7) vs.PSY(n=6):p=0.0014). The psyllium-induced rescue was accompanied by normalization of the ICC network and morphological alterations in infiltrating macrophages. This was supported by changes in immune-related gene expression in the MP including CD11b, NOS, Myd88, Mapk1 and NF-κB. Additionally, bacterial composition was different between PCDI and PSY group (p=0.003). SCFAs like acetic and propionic acid were increased, while BCFA like isobutyric and isovaleric acid were decreased following PSY treatment. These alterations in SCFA/BCFA were supported by fluctuations in specific bacteria like Butyricimonas, Phascolarctobacterium and Allistipes.

Conclusions

Our results provide evidence that chronic gut dysfunction following CDI and AB exposure is microbiota-driven. Furthermore, microbiota-directed therapy using psyllium could serve as a novel therapeutic strategy to normalize gut function via microbiota-mediated restoration of immune homeostasis in these patients.

Funding Agencies

W. Garfield Weston Foundation
A10 EARLY LIFE SENSITIZATION TO GLUTEN INDUCES SUSTAINED IMMUNOPATHOLOGY IN DR3-DQ2 MICE
Authors: Godbout J , Wulczynski M , Galipeau H J , Constante M , Ribeiro T , Sloboda D , Verdu E
Published: February 2022

Background

Celiac disease (CeD) is an autoimmune T-cell mediated enteropathy, triggered by gluten, a group of proteins found in wheat, barley, and rye. The defined role of gluten as a dietary trigger, necessary genes (HLA-DQ2 and/or DQ8), and tissue transglutaminase (TG2) as the autoantigen together, are unique features of CeD. Although CeD onset can occur at any age, first dietary introduction of gluten during infancy is a critical window of exposure, especially in infants homozygous for the HLA DQ2.5 allele. While adult sensitization studies have been recently performed in DR3-DQ2 mice, the consequences of early life gluten sensitization timing remain unexplored.

Aims

Our aim was to characterize gluten-immunopathology and CeD-specific serology in specific pathogen free (SPF) DR3-DQ2 transgenic mice sensitized to gluten, 1 week before weaning.

Methods

Seven-week-old SPF DR3-DQ2 transgenic mice, kept on a gluten-free diet (GFD), were paired for breeding. At post-natal day 3, pups were standardized to 4 per litter (n=2 male, n=2 female) to ensure equal nutrition across litters. At 14 days of age, pups were sensitized with pepsin-trypsin digested gliadin and cholera toxin (CT) three times in one week (n=15). At 21 days of age, pups were weaned and placed either on a gluten-containing diet (n=7), (equivalent of 20g/d of gluten in a human diet -high dose-) or an isocaloric GFD (n=8) until 10 weeks of age. Non-sensitized controls (n=7) received only CT and were kept on the GFD. At sacrifice, serum was collected for anti-TG2 and anti-gliadin antibodies (AGA). Jejunal tissue was collected for histological analysis using villus-to-crypt (V/C) ratios and CD3+ intraepithelial lymphocytes (IEL) counts.

Results

Gluten-sensitized mice placed on a gluten-containing diet post-weaning had lower V/C ratios and higher CD3+ IEL counts compared with controls (p<0.01). Pre-weaning sensitized mice that were kept on a GFD post-weaning had sustained decreases in V/C ratios and higher CD3+ IEL counts (p<0.01). Out of 15 sensitized mice, 7 developed positive anti-gliadin IgA (p=0.02) and 4 had positive anti-TG2 IgA antibodies (p=0.01) in intestinal contents, irrespective of gluten in the diet. None of the controls had detectable AGA or anti-TG2 antibodies.

Conclusions

Pre-weaning gluten sensitization of DR3-DQ2 mice induced prolonged gluten immunopathology that did not reverse after 5 weeks on a GFD. Our results indicate that young DR3-DQ2 mice are susceptible to gluten sensitization, with sustained immunopathology, suggesting a critical window of vulnerability in familial carriers of DQ2.5. This novel model will be useful to investigate environmental cofactors at the first time of gluten introduction to the diet.

Funding Agencies

CIHR
A28 RESPONSE RATE OF VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEOIBD) PATIENTS TO ANTI-TNF TREATMENT IS HIGHER THAN PREVIOUSLY REPORTED, BUT HIGHER DOSING IS REQUIRED-A LARGE TERTIARY SINGLE CENTER EXPERIENCE
Authors: Eindor A , Meleady L , Jacobson K
Published: February 2022

Background

Very early onset inflammatory bowel disease (VEOIBD) patients are known to have special disease characteristics. Limited data is available regarding biologic use and long-term outcomes in VEOIBD patients.

Aims

We aimed to assess long-term outcomes and time to progression to biologic treatment in VEOIBD patients. Secondary aim was to determine Infliximab prescribing practice during the course of treatment.

Methods

We retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics, symptoms at diagnosis, disease location and severity were documented. Data on biologic treatment at initiation and during follow up including type of biologic, dosing and response were collected. Kaplan Meier curves were used to assess the number of years to progression to biologic treatment and the parameters influencing commencement. Infliximab dosing and intervals were recorded for all patients treated with Infliximab during induction, after one year and at last follow up.

Results

89 patients with VEOIBD were diagnosed during the study period. Median age at diagnosis was 3.8 years (IQR 2.6–5.1), 45.3% had Crohn’s disease (CD) and 62.8% were males. Median duration of follow up was 6.39 years (IQR 3.71–10.55). Biologic treatment was started on 39.5% of patients and 7.1% underwent surgery. In patients with CD, the addition of perianal fistulizing disease or stricturing disease was associated with more rapid progression to biologic treatment (p=0.024, p=0.038, respectively). In patients with UC, disease severity (p=0.017) was associated with early initiation of a biologic. The median Infliximab dose at one year was 10 mg/kg (IQR 7.5–11) with median dose interval of 4 weeks (IQR 4–6). At the time of the last follow up, 18 patients (72%) maintained treated with Infliximab and had a median dose of 9 mg/kg per dose (IQR 8.1–10) and a median dose interval of 4.5 weeks (IQR 4–6). Clinical remission was reported in 61.8% of patients on their first biologic agent at the last follow up.

Conclusions

Factors influencing earlier progression to biologics were disease severity and disease behaviour. The response rate was higher than previously reported and might be due to higher Infliximab dosing with shorter infusion intervals than standard dosing.

Funding Agencies

None
A36 NON-PSYCHOTROPIC PHYTOCANNABINOIDS ATTENUATE VISCERAL HYPERSENSITIVITY IN DEXTRAN SULFATE SODIUM (DSS)-INDUCED COLITIS
Authors: Svendsen K , Defaye M , Sharkey K A , Altier C
Published: February 2022

Background

The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are complex chronic diseases that affect an increasing proportion of the population. Abdominal pain is a major clinical symptom, but current treatments are limited and a source of frustration for patients, many of whom seek alternatives such as cannabis. Cannabis contains many compounds with therapeutic potential that do not have the prohibitive psychotropic effects of tetrahydrocannabinol. These non-psychotropic cannabinoids (npCBs) have a variety of effects including analgesia and anti-inflammatory actions and show potentiating effects when administered in combination. The range of actions of these compounds potentially allows for their development as novel therapeutics for treatment of pain in IBD.

Aims

To investigate the analgesic effects of cannabichromene (CBC), cannabidiol (CBD), cannabidivarin (CBDV), and cannabigerol (CBG), individually and in combination, in the treatment of colitis-evoked visceral hypersensitivity.

Methods

The analgesic effects of the npCBs were investigated in an acute dextran sodium sulfate model of colitis. Abdominal pain was quantified by electromyographic recordings of the reflexive contraction of the external oblique muscles in response to colorectal distension. Activation of the spinal cord was assessed using immunohistochemistry for the neuronal activity marker c-Fos in neurons of the spinal dorsal horn.

Results

CBD reduced pain responses in the functional assay and spinal cord c-Fos activity in a dose-dependent manner. A single intraperitoneal injection of 10 mg/kg, 30 minutes prior to application of the noxious stimulus, reduced pain responses to the level of non-DSS treated control animals. CBDV, and CBG were found to be ineffective in either assay at doses of 1, 5, and 10 mg/kg.

Conclusions

These results suggest CBD may be a promising therapeutic agent in the treatment of colitis–induced visceral hypersensitivity with rapid translational value due to the legalization of cannabis and rapidly growing cannabis industry in Canada. Additionally, CBDV, CBC, and CBG will be further investigated for their analgesic effects and any potentiating effects from administration of multiple npCBs examined.

Funding Agencies

Alberta Innovates
A44 PGC1-α INHIBITION WORSENS DSS-INDUCED COLITIS IN MICE
Authors: Oliveira Ponce J P , Lopes F
Published: February 2022

Background

Inflammatory bowel diseases (IBD) represent a wide range of gastrointestinal diseases that are characterized by chronic inflammation of the gastrointestinal tract (GIT). Affecting more than 6 million individuals globally, the most prevalent forms of IBD are Ulcerative colitis (UC), characterized by inflammation and ulceration of the colon and rectum, and Crohn’s disease (CD), characterized by inflammation of several areas of the GIT. Due to the morbidity and occasionally mortality arising from IBD, as well as its increasing global prevalence, the search for novel treatments and cures for IBD presents great importance. Loss of immune tolerance significantly contributes to the inflammatory patterns observed in IBD patients. Dendritic Cells (DCs), key antigen-presenting cells, are important mediators of tolerance in the gut when polarized to tolerogenic DCs (tolDCs). The phenotype of tolDCs has been shown to directly depend on their intracellular metabolism, mostly by adopting mitochondrial oxidative phosphorylation. Peroxisome proliferator-activated receptor-gamma coactivator (PGC)1-α is a transcription coactivator that plays a crucial role in mediating cellular energy metabolism. Evidence shows that activation of PGC1-α stimulates mitochondrial biogenesis and promotes oxidative metabolism in a variety of biological processes.

Aims

The aim of this project was to evaluate whether activation or inhibition of PGC1-α impacts inflammatory response in DSS-induced colitic in mice. We hypothesize that the PGC1-α pharmacological activator ZLN005 would ameliorate colitis as a result of tolDC polarization. On other hand, the PGC1-α pharmacological inhibitor SR18292 would increase inflammatory responses and decrease tolerance.

Methods

C57/b6 mice received DSS in drinking water for 5 days, followed by 3 days of tap water. Mice were treated with vehicle, ZLN005 (10 mg/kg), or SR18292 treatment (25 mg/kg) for the 3 days of drinking tap water. Under necropsy, colitis was assessed by disease activity score (DAS), colon length, weight change, myeloperoxidase (MPO) activity assay, histopathology score, and cytokines by ELISA. Intestinal tolerance was accessed by evaluating T cells polarization to Treg, TH1, TH2, or TH17 by qPCR of the transcription factors Foxp3 (Treg), Tbx21 (TH1), Gata3 (TH2), and Rorγt (TH17) expressed in the colon.

Results

Our results demonstrated that ZLN005 did not alter the inflammatory response induced by DSS, gauged by MPO assay, DAS, and histopathology, suggesting that ZLN005 was ineffective in polarizing tolDCs. However, we observed a worsening of inflammatory conditions with treatment with SR18292 with a decrease in IL-10 levels and increased MPO values, potentially stemming from the loss of tolDCs and intestinal tolerance.

Conclusions

PGC1-α inhibition worsens inflammatory response in DSS-induced colitis potentially by inhibiting tolDC polarization and loss of intestinal tolerance.

Funding Agencies

None
A45 INFLIXIMAB IN COMBINATION WITH AN IMMUNOMODULATOR IS ASSOCIATED WITH AN ATTENUATED ANTIBODY RESPONSE TO BNT162B2 SARS-COV-2 VACCINE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: Lawrence S , Shire Z , Reicherz F , Lavoie P , Jacobson K
Published: February 2022

Background

Adult data have shown that Infliximab (IFX) impairs the antibody response to a single dose of the mRNA-BNT162b2 SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). The true impact of IFX on SARS-CoV-2 vaccine efficacy in pediatric IBD (PIBD) patients is unknown.

Aims

To evaluate the humoral immune response to the BNT162b2 SARS-CoV-2 in PIBD patients treated with anti-tumor necrosis factor (TNF) therapy.

Methods

PIBD patients treated with anti-TNF therapy either alone or in combination with an immunomodulator, who received at least one dose of the BNT162b2 SARS-CoV-2 vaccine, were prospectively enrolled from 1st June 2021 at BC Children’s Hospital. Serum antibody levels for [spike (S) protein and receptor-binding domain (RBD)] were determined at baseline and 28 days after their first and second vaccine doses. Antibody responses were assessed using multiplex serology IgG assay against four SARS-CoV-2 antigens: S-protein, RBD, N-terminal domain (NTD) and N-protein using the SARS-CoV-2 Panel 2 (Meso Scale Diagnostics).

Results

Forty-two PIBD patients received a single dose of BNT162b2 (median age 14.5yrs (IQR 14–16); 43% female; 79% crohn’s disease, 21%, ulcerative colitis). Of those on IFX monotherapy (43%), both S-protein and RBD antibody concentrations 28 days post BNT162b2 were comparable to healthy adult controls (n=20, median age: 36yrs (IQR 29–40); 65% female) who had received one dose of BNT162b2 (p = 0.07) [Figure 1]. In PIBD patients on IFX in combination with either azathioprine or methotrexate (57%) both S-protein and RBD antibody concentrations were significantly lower than controls after 1 dose of BNT162b2 (p = 0.0003) [Figure 1].

In the PIBD cohort (n=27) who received 2 doses of BNT162b2 vaccine (median age 14yrs (IQR 14–16);41% female;63% crohn’s disease, 37% ulcerative colitis; median interval between doses 56 days (IQR 22–105)), there was no difference in antibody response after 2 doses compared to healthy adult controls (n=14, median age: 44 years (IQR 36–51); 29% female) whether they were on IFX monotherapy (41%) or in combination with an immunomodulator (59%) [Figure 1].

Conclusions

We provide evidence of an attenuated antibody response in PIBD patients on IFX in combination with an immunomodulator after a single dose of BNT162b2. However, our data show a robust antibody response in PIBD patients, despite their infliximab treatment, after two doses of BNT162b2 vaccine. Our results are consistent with adult IBD data and highlight the importance of administering the second vaccine dose to achieve protection in this vulnerable patient population. Long-term follow-up to assess longevity of vaccine protection is warranted.

Funding Agencies

None
A51 ROLE OF GUT MICROBIOTA IN THE EPISODIC NATURE OF SYMPTOMS IN IRRITABLE BOWEL SYNDROME
Authors: Mohan V , Pinto-Sanchez M I , Nardelli A , Borojevic R , De Palma G , Collins S M , Bercik P
Published: February 2022

Background

Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder with likely heterogenous pathophysiology, multiple symptoms, and comorbidities. Growing evidence shows that the gut microbiota composition and function are altered in IBS patients. However, identifying the critical drivers of clinical expression remains challenging due to the episodic occurrence of IBS symptoms, the inherent variability in composition of gut microbiota across individuals, and high sensitivity of gut microbiota to dietary and environmental cues.

Aims

To identify whether changes in gut microbiota composition accompany or, predict the occurrence of symptoms.

Methods

28 IBS patients (IBS-D n=20, IBS-C n=8) and 10 healthy controls (HC) were followed longitudinally for 25 weeks, collecting stool samples, and recording their symptoms weekly. Stool microbiota profiles were assessed by 16S rRNA gene sequencing using Illumina platform. The sequences were preprocessed, filtered, and annotated using DADA2 and phyloseq pipelines; statistical analyses were performed using FactomineR and microbiomeanalyst packages in R. Statistical significance was set at p<0.05.

Results

Multifactorial analysis of clinical data classified 950 samples in 6 clusters. Distribution of samples among the clusters was based on Bristol stool scale defining symptomatic periods (scores <3 and >4 indicating abnormal stool) and asymptomatic periods (scores 3 or 4), with several gut and mood symptoms varying significantly between the two categories. IBS-D patients, but not IBS-C patients presented with changes in symptoms severity, such as pain, diarrhea, constipation, and anxiety during the symptomatic periods. Depression scores were, however, higher in IBS-C compared to IBS-D patients. In contrast, immune makers such as fecal b-defensin-2 and calprotectin were higher during asymptomatic periods in IBS-D, but not in IBS-C patients. Bacterial diversity profiles differed among IBS patients (IBS-D and IBS-C) and HC, namely Shannon index and Bray-Curtis distance, but they did not change significantly between the symptomatic and asymptomatic periods within each subtype. Despite this, several bacterial taxa unique to each cluster were identified using linear mixed models.

Conclusions

Our results demonstrate the need to study patterns of co-occurrence of IBS symptoms and their severity during symptomatic and asymptomatic periods to better understand the role of identified bacterial taxa in the symptom generation. Identifying their temporal changes and cross-feeding patterns in individual patients will shed light on the underlying mechanistic role of gut microbiota in IBS, which might be otherwise obscured by group generalizations.

Funding Agencies

CIHR
A64 THE DIETARY FIBRE RHAMNOGALACTURONAN PROMOTES INTESTINAL EPITHELIAL CELL MIGRATION THROUGH THE NF-κB SIGNALING PATHWAY
Authors: Baggio C H , Shang J , Nascimento A , Cipriani T , MacNaughton W
Published: February 2022

Background

Damaged intestinal epithelial barrier is characteristic of inflammatory bowel diseases (IBD) and mucosal healing is the primary goal for IBD treatment. We previously showed the direct beneficial effects of rhamnogalacturonan (RGal), a polysaccharide isolated from the plant Acmella oleracea, on intestinal epithelial barrier function with participation of TLR4 and PKC activation. We also observed that RGal accelerates wound healing in human colonic epithelial Caco-2 cells. RNAseq data and pathway analysis have indicated the involvement of the canonical nuclear factor kB (NF-kB) signaling pathway.

Aims

We hypothesize that RGal increases intestinal epithelial wound healing through NF-kB signaling pathway.

Methods

Caco-2 cells monolayers were scratched and treated with vehicle (media or 0.5% DMSO in media) or RGal (1000 mg/ml) for 48 h. Wound healing was assessed using the IncuCyte live cell imaging system. Proliferation and apoptosis of cells were evaluated using EdU and TUNEL assays, respectively. Inhibitors were added at the same time (transcription inhibitor Actinomycin D, 5 mg/ml) or 1 h (NF-kB inhibitors Bay 11–7082 and JSH-23, 10 and 20 mM, respectively, or COX-2 inhibitor NS-398, 20 mM) before RGal treatment. Unwounded Caco-2 monolayers treated with RGal (1000 mg/ml) were collected for Western blotting for COX-2 protein.

Results

In the wound healing assay, RGal at a concentration of 1000 µg/ml enhanced wound healing by 12.5% at 48 h compared to control group, under 10% serum conditions. Neither proliferation nor apoptosis were involved in the RGal effect on wound healing, suggesting the response was due solely to cell migration. Actinomycin D (5 mg/ml), Bay 11–7082 (10 mM) or JSH-23 (20 mM) treatment significantly reversed the effect of RGal on wound healing, showing that the response was transcriptionally dependent and involved NF-kB signaling. Treatment of cells with NS-398 (20 mM) also reversed the effect of RGal on wound healing. COX-2 protein expression was significantly increased at 6 and 12 h after RGal addition to Caco-2 monolayers.

Conclusions

These data suggest that the plant-based polysaccharide RGal increases intestinal epithelial cell wound healing by increasing cell migration. The RGal effect is dependent on the activation of the transcription factor NF-kB and downstream COX-2 protein expression and activity. Our findings show a novel mechanism of action of RGal in wound healing that could help in the resolution of intestinal inflammation and mucosal healing.

Funding Agencies

NSERC
A82 DELIVERY OF AMBULATORY CARE DURING THE COVID-19 PANDEMIC IN THE DIVISION OF DIGESTIVE CARE & ENDOSCOPY, HALIFAX, NS
Authors: Francheville J , Koto P , Peltekian K
Published: February 2022

Background

The COVID-19 pandemic has placed the Canadian healthcare system under substantial strain requiring rapid and systemic changes to healthcare delivery in gastroenterology ambulatory care, including a shift to providing synchronous clinical visits virtually. It is important to describe and evaluate the impact of this care delivery change on patients, providers and the healthcare system in order to improve the quality of virtual care in the future.

Aims

As part of a larger quality improvement initiative, the aim of this project was to better understand the health system impact of the shift from in-person to virtual care delivery in the Division of Digestive Care & Endoscopy in Halifax, NS.

Methods

Using a before-and-after observational study design, outpatient encounters from January-March 2020 (Pre-COVID) were compared to encounters after the pandemic restrictions began April-June 2020 (COVID-Impacted). The primary objective was to compare the proportion of synchronous clinic encounters in the gastroenterology ambulatory space conducted virtually before versus after pandemic restrictions were implemented. Secondary objectives were to determine whether patient, disease, or provider-specific factors were associated with virtual care visits or changed with the implementation of pandemic restrictions. Endoscopic encounters were excluded. Descriptive statistics were used to compare patient and encounter characteristics in the Pre-COVID and COVID-Impacted periods. Multiple logistic regression modeling was used to evaluate the association between patient and provider characteristics and use of virtual care delivery. Unadjusted and adjusted odds ratio with associated 95% CI were estimated.

Results

A total of 4,923 unique patients (60.1% Pre-COVID and 39.9% in the COVID-Impacted period) and 6,659 encounters were identified. The proportion of synchronous clinical visits conducted virtually increased after February 2020, increasing from 25% (Pre-COVID) to 91% (COVID-Impacted). The Pre-COVID versus COVID-Impacted periods also differed with respect to median patient age (56 vs. 59, P = 0.000), mean proximity to the hospital (40km vs. 48km, P = 0.007) and proportion of new consults deemed urgent (9.8% vs. 20.0%, P = 0.000). Patients with family physicians, return visits, and patient age greater than 65 years were associated with the use of synchronous virtual care visits.

Conclusions

This project details the abrupt and significant disruption in in-person ambulatory, non-endoscopic digestive care and the dramatic uptake in virtual care delivery as a result of COVID-19 restrictions in Halifax, NS. Future research will explore virtual care use as pandemic restrictions ease to inform how virtual care is integrated into post-pandemic practice to guide new standards of care.

Funding Agencies

None
A83 BEST PRACTICES FOR THE PROVISION OF VIRTUAL CARE IN IBD AND BEYOND: A SYSTEMATIC REVIEW OF CURRENT GUIDELINES
Authors: Anvari S , Neumark S , Jangra R , Sandre A , Pasumarthi K , Xenodemetropoulos T
Published: February 2022

Background

Telemedicine has emerged as a feasible adjunct to in-person care in multiple clinical contexts, including inflammatory bowel disease (IBD), and its role has expanded in the context of the COVID-19 pandemic. However, there exists a general paucity of information surrounding best practice recommendations for conducting specialty or disease-specific virtual care.

Aims

The purpose of this study was to systematically review existing best practice guidelines for conducting telemedicine encounters, both in general and specific to patients with IBD.

Methods

A systematic review of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) of existing guidelines for the provision of virtual care was performed. Data was synthesized using the Synthesis Without Meta-Analysis (SWiM) guideline, and the AGREE II tool was used to evaluate quality of evidence

Results

A total of 60 studies providing guidance for virtual care encounters were included; 52% of these were published during the COVID-19 pandemic. No gastroenterology-specific guidelines were found. The majority (95%) of provider guidelines specified a type of virtual encounter to which their guidelines applied. Of included studies, 65% provided guidance regarding confidentiality/security, 58% discussed technology/setup, and 56% commented on patient consent. 31 studies also provided guidance to patients or caregivers. Overall guideline quality was poor.

Conclusions

General best practices for successful telemedicine encounters include ensuring confidentiality and consent, preparation prior to a visit, and clear patient communication. Future studies should aim to objectively assess the efficacy of existing clinician practices in order to further optimize the provision of virtual care for specific populations, such as patients with IBD.

Funding Agencies

None