bluuebunny/crossref_metadata_2025_split huggingface dataset:
A238 ALTERED GUT MICROBIOME COMPOSITION AND FUNCTION ARE ASSOCIATED WITH GUT BARRIER DYSFUNCTION IN HEALTHY RELATIVES OF CROHN’S DISEASE PATIENTS
Authors: Leibovitzh H , Lee S , Xue M , Raygoza Garay J , Hernandez-Rocha C , Madsen K , Meddings J , Guttmen D S , Espin Garcia O , Goethel A , Griffiths A , Moayyedi P , Huynh H Q , Jacobson K , Mack D R , Abreu M , Bernstein C N , Marshall J , Turner D , Xu W , Turpin W , Croitoru K 
Published: February 2022

Abstract

Background
The gut microbiome may play a role in gut barrier homeostasis including epithelial barrier function, but data are scarce and limited to animal studies

Aims
To assess if alterations in gut microbiome are associated with gut barrier function

Methods
We utilized the Genetic Environmental Microbial (CCC GEM) cohort of healthy first-degree relatives (FDRs) of Crohn’s disease (CD) patients. Gut barrier function was assessed using the ratio of urinary fractional excretion of lactulose to mannitol (LMR). Stool bacterial DNA was extracted and sequenced for the V4 hypervariable region of the 16S rRNA gene using MiSeq and processed using QIIME2. Microbial functions were imputed using PICRUSt2. The cohort was divided into a North American discovery cohort (n=2,472) and non-North American external validation cohort (n=655). LMR&gt;0.025 was defined as abnormal. LMR-microbiome associations were assessed using multivariable regression model and Random Forest (RF) classifier algorithm. q&lt;0.05 was considered significant when multiple tests were performed

Results
The median age of the entire cohort was 17.0 years [IQR 12.0; 24.0], 52.6% were females and 25.4% had LMR&gt;0.025. In the discovery cohort, subjects with LMR&gt;0.025 had markedly reduced alpha diversity (Chao1 index, estimate= -0.0037, p=4.0e-04) and altered beta diversity (Bray-Curtis dissimilarity index, PERMANOVA: pseudo-F statistic = 2.99, p=1.0e-03). We identified eight bacterial genera and 52 microbial pathways associated with LMR&gt;0.025 (q&lt;0.05). Four genera (decreased Adlercreutzia [odds ratio(OR)=0.74, 95% confidence interval (CI) 0.6–0.91], Clostridia-UCG-014 [OR=0.71, 95%CI 0.59–0.86], and Clostridium-sensu-stricto-1 [OR=0.75, 95%CI 0.61–0.92] and increased Colidextribacter [OR=1.65, 95%CI 1.2–2.26]) and eight pathways (including decreased biosynthesis of glutamate [OR=0.4, 95%CI 0.21–0.74], tryptophan [OR=0.06, 95%CI 0.01–0.27] and threonine [OR=0.038, 95%CI 0.003–0.41]) were replicated. Bacterial community composition was associated with gut barrier homeostasis as defined by the RF analysis (p= 1.4e-6)

Conclusions
Gut microbiome community and pathways are associated with gut barrier function. These findings may identify potential microbial targets to modulate barrier function
Submitted on behalf of the CCC-GEM Consortium

Funding Agencies
CCC, CIHRCrohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III; The Leona M. and Harry B. Helmsley Charitable Trust; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases
A243 HISTAMINE H1-RECEPTOR ANTAGONISTS SUPPRESS THE HYPEREXCITABILITY OF NOCICEPTIVE NEURONS EXPOSED TO IBS-C PATIENT STOOL SUPERNATANTS
Authors: Neary E , Jiménez-Vargas N N , Lomax A E , Reed D E , Vanner S 
Published: February 2022

Abstract

Background
Abdominal pain is the primary cause of morbidity in many chronic GI disorders such as IBS, but the molecular mechanisms contributing to pain signaling are unclear. Stool supernatants from patients with diarrhea-predominant IBS increase the excitability of DRG neurons compared to supernatants from healthy controls, suggesting that mediators in the stool may sensitize nociceptors. Additionally, histamine has been implicated as a mediator of hypersensitivity in IBS patients. However, it is unclear if stool supernatants from constipation-predominant IBS (IBS-C) patients affect the excitability of DRG neurons. Furthermore, it is unknown if specific neuro-mediators in stool such as histamine impact the excitability of nociceptive neurons in this subgroup of IBS patients.

Aims
To evaluate whether IBS-C stool supernatants induce nociceptive signaling in DRG neurons compared to healthy control (HC) stool supernatants.
If so, to evaluate the role of histamine 1 (H1) receptors in DRG neuron nociceptive signaling initiated by mediators in IBS-C stool supernatants.

Methods
IBS-C (n=5) and HC (n=2) patient stool was collected, filtered, and dissolved with Krebs solution in a 1:8 (g/v) dilution. Dorsal root ganglion (DRG) neurons from C57BL/6 mice were incubated with HC or IBS-C stool supernatant for 30 minutes. To evaluate whether histamine in stool supernatants can sensitize H1 receptors on nociceptors, DRG neurons were pre-incubated with the H1-receptor antagonist pyrilamine (1μM, 30 min) before stool supernatants. Changes in DRG neuronal excitability were recorded using perforated patch-clamp techniques to measure the rheobase (minimum input current needed to elicit an action potential) and the resting membrane potential (RMP).

Results
In neurons incubated with IBS-C stool supernatants (n=28) the rheobase decreased (63%) compared to healthy controls (78 ± 13.7 pA; n=6). This effect was reversed in DRG neurons pre-incubated with the H1 receptor antagonist, pyrilamine, (n=26) (77 ± 5.9 pA, p&lt;0.001) compared to neurons incubated with IBS-C supernatant alone (50 ± 5.13 pA; n=28). No changes were found in the RMP. The data were analyzed with the non-parametric Kruskal-Wallis test.

Conclusions
IBS-C stool supernatants increase the excitability of DRG neurons compared to HC. Furthermore, the H1-receptor antagonist pyrilamine inhibits the neuronal hyperexcitability evoked by mediators in IBS-C patient stool. These findings suggest that the neuroactive metabolite histamine may contribute to visceral pain experienced by patients with IBS-C. Further studies are needed to examine whether similar signaling to nociceptive neurons by stool supernatants occurs in other subtypes of IBS.

Funding Agencies
CAG, CIHR
A247 MEDITATION AND YOGA FOR IRRITABLE BOWEL SYNDROME (MY-IBS): A RANDOMIZED CONTROLLED TRIAL
Authors: D’Silva A , Marshall D , Rajagopalan V , Nasser Y , Vallance J , Raman M 
Published: February 2022

Abstract

Background
When delivered in person, yoga is effective in managing Irritable Bowel Syndrome (IBS) symptoms. However, research is needed to determine the feasibility and effectiveness of yoga as a therapeutic option when delivered virtually.

Aims
The aim was to explore the feasibility and effectiveness of a yoga program, delivered virtually, for patients with IBS. We hypothesized the program would be feasible and effective in improving outcomes in the intervention group compared to the control group.

Methods
Adults diagnosed with IBS were randomized to receive either a Hatha yoga intervention or to an advice-only control group. The intervention consisted of facilitator-led weekly online classes for eight weeks delivered using Microsoft Office Teams and daily home practice. Yoga sessions included sequential delivery of postures, chanting, breathing exercises, and meditation over four weeks, with integrated practice over the final four weeks. Feasibility was evaluated with recruitment and attrition rates, adherence, and safety. The primary outcome was severity of IBS symptoms (IBS-Symptom Severity Score, IBS-SSS). Secondary outcomes included anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), and stress (Perceived Stress Scale) assessed at baseline and eight weeks. Unadjusted and adjusted analysis of variance (and covariance) models compared baseline and post-intervention data between groups using intent to treat analysis.

Results
Sixty-five participants participated (32 treatment, 33 control). The mean age was 44.2±14.1 years and 91% identified as female. Participants had been living with IBS for 11.7±11 years. Fifteen participants were lost to follow-up (20% attrition rate). Participants attended on average 5.9±1.7 out of a possible 8 sessions (74% adherence) and accumulated 1,187±545 minutes in daily practice over eight weeks. No adverse events were reported. The groups did not differ at baseline (P&gt;0.05). From baseline to post intervention, unadjusted ANOVA models indicated the yoga program was not statistically superior to the control group for IBS-symptoms (-17.5 points; 95% CI -62.6 to 27.6; P = 0.440), anxiety (-0.91 points; 95% CI -2.47 to 0.64; P = 0.245) and stress (-0.65 points; 95% CI -1.73 to 0.44; P = 0.239). Significant differences between groups were seen for depression (-1.82 points; 95% CI -3.49 to -0.15; P = 0.033). A second model considered relevant covariates including age, comorbidities, and years since diagnosis (i.e., ANCOVA), and the results were similar to the unadjusted model.

Conclusions
Our virtual Hatha yoga and mediation program was feasible, and participants showed improvement in their depression scores. However, they did not experience a significant improvement in their IBS symptoms, anxiety, or stress, perhaps due to the short timeframe of the intervention.

Funding Agencies
None
A251 USE OF INDIRECT CALORIMETRY TESTING TO DIRECT NUTRITION SUPPORT IN CRITICALLY ILL PATIENTS WITH GASTROINTESTINAL CONDITIONS
Authors: Russell L , Janisse N , Jones G , Karachi T , Serrano P E , ApSimon M , Armstrong D , Pinto-Sanchez M I 
Published: February 2022

Abstract

Background
Indirect calorimetry (IC), which measures oxygen uptake and carbon dioxide output, determines energy expenditure (EE) more precisely than predictive equations in critically ill patients. It is unknown whether the use of IC affects energy provision in critically ill patients with gastrointestinal (GI) conditions that affect absorption and digestion

Aims
To (1) compare IC and predictive equations for determining energy needs and (2) evaluate whether IC results affect changes in nutrition support in critically ill patients with GI conditions.

Methods
In a prospective, observational study, IC was performed for 25 to 55 mins in critically ill patients admitted to intensive care or clinical wards at 2 tertiary-care hospitals in Hamilton, Ontario between Feb 2018 to Sept 2021. EE measured by IC was compared to EE determined by a predictive equation (25 kcal/kg) or the Harris-Benedict (HB) formula. A change in energy provision was defined as a change of &gt;10% directed by IC. Continuous data are expressed as means and standard deviation (SD), and categorical data as a proportion of patients. The Mann Whitney U Test (SPSSv26) was used to compare GI and non-GI populations.

Results
Of 296 IC tests in 229 patients, 39 of them were in 30 GI patients (11 female; mean age 62 yrs; SD 19). Admission GI diagnoses were pancreatitis (33%), liver disease (20%), Crohn’s disease/ autoimmune enteropathy (20%), post-bowel resection (10%), chronic abdominal pain (10%), and cholangitis (7%). The predictive formula underestimated EE in 67% of GI patients (mean deficit 503 kcal/day) compared to IC, corresponding to a mean deficit of 25% of patients’ energy needs. The HB formula underestimated EE in 73% of patients (mean deficit 652 kcal/day), a mean deficit of 28% of patients’ energy needs compared to IC. Pancreatitis was the majority diagnosis (75% of the predictive equation; 50% HB) among patients with the highest deficit (&gt;30%) in energy needs when compared to IC. There were no significant differences in the rates of underestimation of energy needs based on predictive and HB formulas between the GI and non-GI patients or between luminal GI and non-luminal GI conditions. After IC, 63% of tests led to changes in energy provisions in GI patients; most requiring an increase in energy provisions (53%).

Conclusions
The use of IC to accurately measure EE led to changes in energy provisions in critically ill GI patients. Preventing over- and underfeeding with the implementation of IC to guide nutrition has the potential to improve outcomes in critically ill patients with gastrointestinal conditions.

Funding Agencies
None
A257 PANCREATIC CANCER TREATMENT AND END OF LIFE OUTCOMES: A POPULATION BASED COHORT STUDY
Authors: Khan R , Salim M , Tanuseputro P , Hsu A , Coburn N , Talarico R , James P 
Published: February 2022

Abstract

Background
Patients with pancreatic cancer face challenging decisions regarding treatment choices following their diagnosis and often lack data on end-of-life (EOL) outcomes. Without the available information, older patients may be undertreated, dying earlier than they would have with treatment, while others may be overtreated and exposed to aggressive measures with harmful side effects.

Aims
To describe survival and EOL outcomes among pancreatic cancer patients based on index cancer treatment, disease stage, and patient characteristics.

Methods
We conducted a population based cohort study in Ontario, Canada of patients who died from April 2010 to December 2017 and were diagnosed with pancreatic cancer prior to death. We used administrative databases to collect data on demographics, baseline health status, treatments, and outcomes. The primary exposure was index cancer treatment (no treatment, radiation, chemotherapy alone, surgery alone, and surgery with chemotherapy). The primary outcomes were mortality, health care encounters per 30 days in the last six months of life, and palliative care visits per 30 days within the last six months of life. Secondary outcomes were location of death (institution vs. community), hospitalization within the last 30 days of life, and receipt of chemotherapy within the last 30 days of life. We estimated the association between the exposure and outcomes using multivariable models, adjusting for demographics, comorbidities, and cancer stage. Hazard ratios, adjusted mean differences, and odds ratios were reported with 95% confidence intervals.

Results
Our cohort included 9950 adults with a median age at diagnosis of 78. 56% received no index treatment, 5% underwent radiation, 27% underwent chemotherapy alone, 7% underwent surgery alone, and 6% underwent surgery and chemotherapy. In the multivariable regression (Table and Figure), radiation, chemotherapy alone, surgery alone, and surgery with chemotherapy were all associated with decreased mortality and fewer healthcare encounters. All groups except radiation were associated with fewer palliative care visits. All treatment groups were associated with lower odds of institutional death and hospitalization within the last 30 days of life, and higher odds of chemotherapy within the last 30 days of life.

Conclusions
Our data, the first to provide EOL outcome estimates based on index cancer treatment, can help patients make initial treatment decisions after a diagnosis of pancreatic cancer.
Multivariable regression analyses predicting primary and secondary outcomes

Association between index cancer treatment and primary outcomes.

Funding Agencies
CIHR
A258 ROSAI-DORFMAN0-DESTOMBES DISEASE: A RARE CAUSE OF OBSTRUCTIVE JAUNDICE
Authors: Akhtar D , Donaldson M A , Akhtar N H , Owen D , Gan S 
Published: February 2022

Abstract

Background
Rosai-Dorfman-Destombes Disease (RDD) is rare histiocytic disorder that is most frequently seen in children and young adults. Gastrointestinal involvement is reported in &lt;1% of cases and typically involves the small bowel and colon. Pancreatic and hepatic involvement has been previously reported but is extremely rare.

Aims
To describe a case of obstructive jaundice in the setting of a very rare histiocytic disorder known as RDD.

Methods
Case Report

Results
A 59-year old previously healthy male of Asian descent presented with obstructive jaundice. Initial imaging demonstrated intra and extrahepatic biliary duct dilation with concurrent diffuse enlargement of the pancreas compatible with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed with stenting and biopsy. ERCP demonstrated a distal common bile duct stricture with biopsies suggestive of low grade reactive changes and inflammation. Subsequent endoscopic ultrasound (EUS) guided biopsy of the pancreas showed active and chronic inflammation, necrosis, and atrophic pancreatic tissue, with no definitive evidence of autoimmune pancreatitis (Figure 1). Ca-19-9 and IgG4 were normal. He was treated with a course of prednisone and responded well, with repeat CT imaging showing almost complete resolution of the previously demonstrated pancreatic changes. A diagnosis of autoimmune pancreatitis was made. He re-presented 6-months later, however, with fatigue and repeat imaging now displayed lymphadenopathy in the neck, chest, and abdomen, and a bulky pancreatic head with associated hepatomegaly. Lymph node excisional biopsy confirmed the diagnosis of RDD with the presence of scattered histiocytic cells showing emperipolesis with a low number of IgG4 positive cells (Figure 1). The patient was promptly initiated on prednisone and rituximab and has since then had excellent clinical response.

Conclusions
RDD is a rare non-Langerhans cell histiocytosis of unknown etiology that has a prevalence of 1:200 000. RDD clinically presents with painless bilateral cervical lymphadenopathy and can manifest with both nodal and extra nodal involvement. The most common sites of extra nodal disease are the skin and central nervous system, but rarely, can also present with pancreatic involvement. The use of fine needle guided biopsy in diagnosing RDD with extra nodal disease can be limited by low yield, sclerotic tissue, or non-diagnostic findings. For this reason, RDD with pancreatic involvement can masquerade as autoimmune pancreatitis, pancreatic malignancy and IgG4-related disease.This case report raises awareness about RDD with pancreatic and biliary involvement, a rare entity, that can present with obstructive jaundice.

Figure 1: Histological sections of lymph node(left) with hystiocytic cells showing emperipolesis(arrow) and pancreas(right) showing active and chronic inflamation, necrosis and atrophy

Funding Agencies
None
A three-stage hybrid clustering system for diagnosing children with primary headache disorder
Authors: Simić Svetlana , Sakač Slađana , Banković Zorana , Villar José R , Calvo-Rolle José Luis , Simić Svetislav D , Simić Dragan 
Published: February 2022

AbstractHeadache disorders can be considered as the predominant neurological condition. In the field of neurological diseases, migraine was estimated to cost a total of €27 billion per year for the loss through reduced work productivity in the European Community. Medical data and information in turn provide knowledge based on which physicians make scientific decisions for diagnosis and treatments. It is, therefore, very useful to create diagnostic tools to help physicians make better decisions. This paper is focused on a new hybrid clustering system combining analytic hierarchy process and weighted fuzzy c-means clustering method for diagnosing children with primary headache disorder. The proposed three-stage hybrid diagnosing system is tested on data set collected from hospitalized children in the Clinical Centre of Vojvodina, Novi Sad, Serbia.
Two-stage treatment of idiopathic scoliosis using the LSZ growing system with a 10-year follow-up: a case report
Authors: Sampiev M T , Zagorodniy N V , Lysenko I S , Dubinin I P , CHemurzieva K H M 
Published: February 2022

Abstract
A clinical case of an 11-year-old patient with idiopathic scoliosis treatment using the LSZ growing system. The main thoracic curve was 88°, with a lumbar curve of 52°. The patient was at Risser stage 3. At the first stage, posterior correction and instrumentation (T1-L5) of the deformity using the LSZ growing system were performed. Residual deformity of the spine was 15°. At a follow-up, the spine grew by 5 cm. As the second stage of surgical treatment, this system was removed and replaced with selective instrumentation at T4-T12. The patient was followed up for 10 years. On the control radiographs of the spine in the standing position in 2021, adequate correction is preserved. That described technique allowed to ultimately perform selective definitive instrumentation, preserving near full range of movement in the lumbar spine. Further studies are needed to determine the effectiveness of the described approach.
Spectroscopic observations of V455 Andromedae superoutburst in 2007: The most exotic spectral features in dwarf nova outbursts
Authors: Tampo Yusuke , Nogami Daisaku , Kato Taichi , Ayani Kazuya , Naito Hiroyuki , Narita Norio , Fujii Mitsugu , Hashimoto Osamu , Kinugasa Kenzo , Honda Satoshi , Takahashi Hidenori , Narusawa Shin-ya , Sakamoto Makoto , Imada Akira 
Published: February 2022

Abstract
We present our spectroscopic observations of V455 Andromedae during the 2007 superoutburst. Our observations cover this superoutburst from around the optical peak of the outburst to the post-superoutburst stage. During the early superhump phase, the emission lines of the Balmer series, He i, He ii, Bowen blend, and C iv/N iv blend were detected. The He ii 4686 line exhibited a double-peaked emission profile, where Balmer emission lines were single-peaked, which is unexpected from its high inclination. In the ordinary superhump phase, the Balmer series transitioned to double-peaked emission profiles, and high-ionization lines were significantly weakened. These transitions of the line profiles should be related to the structural transformation of the accretion disk, as expected between the early and ordinary superhump transition in the thermal–tidal instability model. The Doppler map of Hα during the early superhump phase exhibits a compact blob centered at the primary white dwarf. In analogy to SW Sex-type cataclysmic variables, this feature could emerge from the disk wind and/or the mass accretion column on to the magnetized white dwarf. The Doppler map of He ii 4686 Å is dominated by the ring-like structure and imposed two flaring regions with the velocity of ∼300 km s−1, which is too slow for a Keplerian accretion disk. The phase of the flaring regions was coincident with the inner spiral arm structure identified during the early superhump phase. Our disk wind model with the enhanced emission from the wind component launched from the inner arm structure successfully reproduced the observed properties of He ii 4686 Å. Therefore, V455 And is the first case in dwarf nova outbursts where the presence of the disk wind is inferred from an optical spectrum.
Detection of nitrogen and oxygen in a galaxy at the end of reionization
Authors: Tadaki Ken-ichi , Tsujita Akiyoshi , Tamura Yoichi , Kohno Kotaro , Hatsukade Bunyo , Iono Daisuke , Lee Minju M , Matsuda Yuichi , Michiyama Tomonari , Nagao Tohru , Nakanishi Kouichiro , Nishimura Yuri , Saito Toshiki , Umehata Hideki , Zavala Jorge 
Published: February 2022

Abstract
We present observations of [N ii] 205 μm, [O iii] 88 μm, and dust emission in a strongly-lensed, submillimeter galaxy (SMG) at z = 6.0, G09.83808, with the Atacama Large Millimeter/submillimeter Array (ALMA). Both [N ii] and [O iii] line emissions are detected at &gt;12σ in the ${0{^{\prime \prime}_{.}}8}$-resolution maps. Lens modeling indicates that the spatial distribution of the dust continuum emission is well characterized by a compact disk with an effective radius of 0.64 ± 0.02 kpc and a high infrared surface brightness of ΣIR = (1.8 ± 0.3) × 1012 L⊙ kpc−2. This result supports that G09.83808 is the progenitor of compact quiescent galaxies at z ∼ 4, where the majority of its stars are expected to be formed through a strong and short burst of star formation. G09.83808 and other lensed SMGs show a decreasing trend in the [N ii] line to infrared luminosity ratio with increasing continuum flux density ratio between 63 and 158 μm, as seen in local luminous infrared galaxies (LIRGs). The decreasing trend can be reproduced by photoionization models with increasing ionization parameters. Furthermore, by combining the [N ii]/[O iii] luminosity ratio with far-infrared continuum flux density ratio in G09.83808, we infer that the gas phase metallicity is already Z ≈ 0.5–0.7 Z⊙. G09.83808 is likely one of the earliest galaxies that has been chemically enriched at the end of reionization.