Publications by authors named "Sandeep K Gupta"

151 Publications

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

J Pediatr Gastroenterol Nutr 2021 Sep;73(3):325-328

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children.

Objectives: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children.

Methods: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models.

Results: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy.

Conclusion: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).
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http://dx.doi.org/10.1097/MPG.0000000000003178DOI Listing
September 2021

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

J Allergy Clin Immunol 2021 Jul 6. Epub 2021 Jul 6.

Inform Diagnostics, Irving, Tex; Department of Pathology, Baylor College of Medicine, Houston, Tex.

Background: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Methods: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists.

Results: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life.

Conclusions: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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http://dx.doi.org/10.1016/j.jaci.2021.07.001DOI Listing
July 2021

Manuscript Review at the Journal of Pediatric Gastroenterology and Nutrition: The Impact of Reviewers on Editor Decisions.

J Pediatr Gastroenterol Nutr 2021 Jun 24. Epub 2021 Jun 24.

University of Illinois College of Medicine at Peoria, Peoria, IL University of Geneva, Geneva, Switzerland University of California San Francisco, San Francisco, CA Community Health Network, Indianapolis, IN Indiana University School of Medicine, Indianapolis, IN.

Objective: Given the importance of scholarly work in academic medicine, better understanding of the manuscript review process (MRP) is useful for authors, reviewers, and editorial boards. We aim to describe the MRP at the Journal of Pediatric Gastroenterology and Nutrition (JPGN), assess the correlation between editor decisions and reviewer recommendations, and provide transparency to this process.

Methods: All manuscripts submitted in 2018 to JPGN were included in this analysis. Data included reviewers' manuscript scores and recommendations, time spent on each review by reviewers, the editor's rating of the reviewers' reviews, the editor's first decision, and final outcome. Data were collated using the JPGN manuscript submission website, Editorial Manager.

Results: 1023 manuscripts were submitted to JPGN in 2018 and included in this analysis. Of these, 486 manuscripts had at least two peer reviewers. The recommendations of the two reviewers were in agreement 43% of the time. Intra-class correlation (ICC) between the two reviewers suggests moderate agreement (ICC = 0.40). When both reviewers agreed to Not Reject (289/486), the editor agreed in 93% of cases (269/289). When both reviewers agreed to Reject (55/486), the editor agreed 100% of the time (55/55). The reviewers disagreed in about one-third of submissions (142/486), and the editor recommended to Reject in two-thirds of these cases (95/142). Overall, inter-reviewer agreement strongly correlated with the editor's initial decision (p < 0.001).

Conclusions: The editor most often agreed with reviewers' assessments when there was concordance between the two reviewers' recommendations. About a third of peer reviews result in discordant recommendations between the two reviewers.
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http://dx.doi.org/10.1097/MPG.0000000000003208DOI Listing
June 2021

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms Following Dilation in Adults With Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2021 May 29. Epub 2021 May 29.

Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, Colorado.

Background & Aims: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and eosinophils per high-power field (eos/hpf).

Methods: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers OMEGA observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf.

Results: Among 100 patients (n = 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (rho = 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (rho = -0.38; P = .157 for ≤1 y and rho = 0.02; P = .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P = .183) and 0.78 (P = .494), respectively. Dilation modified the association between symptoms and eos/hpf (P = .005 and P = .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively).

Conclusions: In nondilated EoE adults, eos/hpf correlates modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.
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http://dx.doi.org/10.1016/j.cgh.2021.05.049DOI Listing
May 2021

Merging Pincer Motifs and Potential Metal-Metal Cooperativity in Cobalt Dinitrogen Chemistry: Efficient Catalytic Silylation of N to N(SiMe ).

Angew Chem Int Ed Engl 2021 Jun 19;60(26):14480-14487. Epub 2021 May 19.

Universität Göttingen, Institut für Anorganische Chemie, Tammannstrasse 4, 37077, Göttingen, Germany.

Using a pyrazolate-bridged dinucleating ligand that provides two proximate pincer-type PNN binding sites ("two-in-one pincer"), different synthetic routes have been developed towards its dicobalt(I) complex 2 that features a twice deprotonated ligand backbone and two weakly activated terminal N substrate ligands directed into the bimetallic pocket. Protonation of 2 is shown to occur at the ligand scaffold and to trigger conversion to a tetracobalt(I) complex 4 with two end-on μ -bridging N ; in THF 4 is labile and undergoes temperature-dependent N /triflate ligand exchange. These pyrazolate-based systems combine the potential of exhibiting both metal-metal and metal-ligand cooperativity, viz. two concepts that have emerged as promising design motifs for molecular N fixation catalysts. Complex 2 serves as an efficient (pre)catalyst for the reductive silylation of N into N(SiMe ) (using KC and Me SiCl), yielding up to 240 equiv N(SiMe ) per catalyst.
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http://dx.doi.org/10.1002/anie.202101387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251579PMC
June 2021

A System-Driven Taxonomy of Attacks and Defenses in Adversarial Machine Learning.

IEEE Trans Emerg Top Comput Intell 2020 Aug 25;4(4):450-467. Epub 2020 May 25.

IMPACT lab (http://impact.asu.edu/), CIDSE, Arizona State University, Tempe, Arizona, USA, 85281.

Machine Learning (ML) algorithms, specifically supervised learning, are widely used in modern real-world applications, which utilize Computational Intelligence (CI) as their core technology, such as autonomous vehicles, assistive robots, and biometric systems. Attacks that cause misclassifications or mispredictions can lead to erroneous decisions resulting in unreliable operations. Designing robust ML with the ability to provide reliable results in the presence of such attacks has become a top priority in the field of adversarial machine learning. An essential characteristic for rapid development of robust ML is an arms race between attack and defense strategists. However, an important prerequisite for the arms race is access to a well-defined system model so that experiments can be repeated by independent researchers. This paper proposes a fine-grained system-driven taxonomy to specify ML applications and adversarial system models in an unambiguous manner such that independent researchers can replicate experiments and escalate the arms race to develop more evolved and robust ML applications. The paper provides taxonomies for: 1) the dataset, 2) the ML architecture, 3) the adversary's knowledge, capability, and goal, 4) adversary's strategy, and 5) the defense response. In addition, the relationships among these models and taxonomies are analyzed by proposing an adversarial machine learning cycle. The provided models and taxonomies are merged to form a comprehensive system-driven taxonomy, which represents the arms race between the ML applications and adversaries in recent years. The taxonomies encode best practices in the field and help evaluate and compare the contributions of research works and reveals gaps in the field.
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http://dx.doi.org/10.1109/tetci.2020.2968933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971418PMC
August 2020

Changes to Pediatric Gastroenterology Practice During the COVID-19 Pandemic and Lessons Learned: An International Survey of Division and Group Heads.

Gastroenterology 2021 Sep 4;161(3):1052-1055. Epub 2021 Mar 4.

Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, The Hospital for Sick Children, Department of Paediatrics and the Wilson Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.02.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093127PMC
September 2021

Clinical Practice Survey of Repeat Endoscopy in Pediatric Inflammatory Bowel Disease in North America.

J Pediatr Gastroenterol Nutr 2021 07;73(1):61-66

Division of Pediatric Gastroenterology, Columbia University Medical Center, New York, NY.

Objectives: Endoscopic remission has become a standard treatment target in inflammatory bowel disease (IBD). It is unclear how widely this practice has been adopted amongst pediatric gastroenterology providers. This study determines the frequency of repeat endoscopy in pediatric IBD and evaluates for predictive baseline characteristics of providers.

Methods: We developed a cross-sectional survey, which was distributed via 3 national email listservs to pediatric gastroenterology providers. We obtained baseline characteristics of respondents and assessed motivations and barriers for the practice of repeat endoscopy compared with none.

Results: Two hundred and thirty-eight unique respondents completed the online survey. Response rate was 11% (238 of 2300 possible participants). The majority practice in an academic setting (77%) and reported participation in ImproveCareNow (63%). Overall, 65% of respondents perform repeat endoscopy to assess for endoscopic remission in pediatric IBD as part of routine clinical practice. Fifty-six percent reported repeat endoscopy as individuals in the absence of a departmental protocol. "Symptoms are not sufficient to follow IBD patients" was reported by 82% of those who repeat endoscopy; conversely, "I perform endoscopy based on clinical, biomarker, and/or imaging trends" was reported by 81% of those who do not repeat endoscopy. The establishment of a pediatric-specific guideline was most commonly reported to change current practice, based on rank-order scoring.

Conclusions: A majority of representative providers repeat endoscopy to assess for endoscopic remission in pediatric IBD. Fewer years in practice favored repeating endoscopy. The need for North American pediatric guidelines with pediatric-specific evidence to support the long-term benefits of endoscopic remission are highlighted in this study.
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http://dx.doi.org/10.1097/MPG.0000000000003100DOI Listing
July 2021

Recombinase polymerase amplification assay combined with a dipstick-readout for rapid detection of Mycoplasma ovipneumoniae infections.

PLoS One 2021 4;16(2):e0246573. Epub 2021 Feb 4.

Animal Health, AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Palmerston North, New Zealand.

Mycoplasma ovipneumoniae infects both sheep and goats causing pneumonia resulting in considerable economic losses worldwide. Current diagnosis methods such as bacteriological culture, serology, and PCR are time consuming and require sophisticated laboratory setups. Here we report the development of two rapid, specific and sensitive assays; an isothermal DNA amplification using recombinase polymerase amplification (RPA) and a real-time PCR for the detection of M. ovipneumoniae. The target for both assays is a specific region of gene WP_069098309.1, which encodes a hypothetical protein and is conserved in the genome sequences of ten publicly available M. ovipneumoniae strains. The RPA assay performed well at 39°C for 20 min and was combined with a lateral flow dipstick (RPA-LFD) for easy visualization of the amplicons. The detection limit of the RPA-LFD assay was nine genome copies of M. ovipneumoniae per reaction and was comparable to sensitivity of the real-time PCR assay. Both assays showed no cross-reaction with 38 other ovine and caprine pathogenic microorganisms and two parasites of ruminants, demonstrating a high degree of specificity. The assays were validated using bronchoalveolar lavage fluid and nasal swab samples collected from sheep. The positive rate of RPA-LFD (97.4%) was higher than the real-time PCR (95.8%) with DNA as a template purified from the clinical samples. The RPA assay was significantly better at detecting M. ovipneumoniae in clinical samples compared to the real-time PCR when DNA extraction was omitted (50% and 34.4% positive rate for RPA-LFD and real-time PCR respectively). The RPA-LFD developed here allows easy and rapid detection of M. ovipneumoniae infection without DNA extraction, suggesting its potential as a point-of-care test for field settings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246573PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861559PMC
August 2021

Gastrointestinal Food Allergies and Intolerances.

Gastroenterol Clin North Am 2021 03;50(1):41-57

Community Health Network, 6626 E 75th Street, Suite 400, Indianapolis, IN 46250, USA; Section of Pediatric Gastroenterology, Hepatology, Nutrition, Riley Hospital for Children at IU Health, Indiana University School of Medicine, ROC 4210, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA. Electronic address:

Adverse reactions to food include immune-mediated food allergies, celiac disease, and nonimmune-mediated food intolerances. Differentiating between these many disorders is important to guide us toward appropriate testing and management. Double-blind placebo-controlled food challenges are the gold standard for food allergy diagnosis but are difficult and time-consuming. In place of this, strong clinical history, other supportive tests, and oral food challenges are helpful. Some commonly available tests for food allergy and intolerances lack sufficient evidence for efficacy. Food intolerance diagnosis is largely based on history and supported by symptom improvement with appropriate dietary manipulation.
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http://dx.doi.org/10.1016/j.gtc.2020.10.006DOI Listing
March 2021

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

J Pediatr Gastroenterol Nutr 2021 05;72(5):718-722

Department of Bioengineering.

Abstract: Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.
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http://dx.doi.org/10.1097/MPG.0000000000003032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048378PMC
May 2021

Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice.

Sci Rep 2020 12 18;10(1):22289. Epub 2020 Dec 18.

Grasslands Research Centre, AgResearch, Hopkirk Research Institute, Private Bag 11008, Palmerston North, 4442, New Zealand.

Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bovine tuberculosis diagnostic tests. Here, we report the development of a protein-particle-based vaccine containing MAP antigens Ag85A-SOD-Ag85B-74F as a fusion ('MAP fusion protein particle'). The fusion antigen displayed on protein particles was identified using mass spectrometry. Surface exposure and accessibility of the fusion antigen was confirmed by flow cytometry and ELISA. The MAP fusion protein particle vaccine induced strong antigen-specific T-cell immune responses in mice, as indicated by increased cytokine (IFN-γ and IL-17A) and costimulatory signals (CD40 and CD86) in these animals. Following MAP-challenge, a significant reduction in bacterial burden was observed in multiple organs of the mice vaccinated with the MAP fusion protein particle vaccine compared with the PBS group. The reduction in severity of MAP infection conferred by the MAP fusion protein particle vaccine was similar to that of Silirum and recombinant protein vaccines. Overall, the results provide evidence that MAP antigens can be engineered as a protein particulate vaccine capable of inducing immunity against MAP infection. This utility offers an attractive platform for production of low-cost particulate vaccines against other intracellular pathogens.
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http://dx.doi.org/10.1038/s41598-020-79407-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749150PMC
December 2020

The World is One Family.

Authors:
Sandeep K Gupta

J Pediatr Gastroenterol Nutr 2021 01;72(1)

Academic Affairs/Community Health Network, Indianapolis, IN; and Section of Pediatric Gastroenterology, Hepatology, Nutrition, Riley Hospital for Children/Indiana University School of Medicine, Indianapolis, IN.

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http://dx.doi.org/10.1097/MPG.0000000000002989DOI Listing
January 2021

Enhancing the barrier height for Yb(III) single-ion magnets by modulating axial ligand fields.

Chem Commun (Camb) 2020 Oct;56(79):11879-11882

Department of Chemistry, Indian Institute of Technology Bombay, Mumbai-400076, India.

The effect of systematic modification of the axial ligand field X on Ueff values in Yb(iii)-based SIMs, [Yb(Ph3PO)4X2]X' (X, X' = NO3 (1), OTf (2) and X = I/Br/Cl; X' = I3 (3)), whose equatorial Ph3PO ligation remains unchanged, has been investigated. Combined magnetic studies coupled with ab initio calculations reveal weakening of the axial ligand fields leading to the increase in the energy barrier, apart from suggesting the operation of different relaxation pathways.
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http://dx.doi.org/10.1039/d0cc01370fDOI Listing
October 2020

Short Communication: Oral Administration of Heat-killed KB290 in Combination with Retinoic Acid Provides Protection against Influenza Virus Infection in Mice.

Nutrients 2020 Sep 24;12(10). Epub 2020 Sep 24.

AgResearch Ltd., Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand.

Influenza virus type A (IAV) is a seasonal acute respiratory disease virus with severe symptoms, and an effective preventive measure is required. Despite many reports describing the potentially protective effects of lactic acid bacteria, few studies have investigated the effects of nutritional supplement combinations. This study reports the effect of the combined intake of heat-killed KB290 (KB290) and vitamin A (VA) on mice challenged with a sublethal dose of IAV. For 2 weeks, five groups of mice were fed either placebo, KB290, VA, or a combination of KB290 and VA (KB290+VA). After subsequent IAV challenge, bodyweight and general health were monitored for up to 2 weeks. Viral titres were determined in the lungs of animal subgroups euthanised at days 3, 7, and 14 after IAV challenge. A significant loss was observed in the bodyweights of IAV-infected animals from day 1 post-IAV challenge, whereas the mice fed KB290+VA did not lose any weight after IAV infection, indicating successful protection from the infection. Additionally, mice in the KB290+VA group showed the highest reduction in lung viral titres. In conclusion, the combination of KB290 and VA could be a useful food supplement relevant for protection against seasonal influenza virus infection in humans.
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http://dx.doi.org/10.3390/nu12102925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600661PMC
September 2020

Cyclic (Alkyl)(Amino)Carbene-Stabilized Aluminum and Gallium Radicals Based on Amidinate Scaffolds.

Inorg Chem 2020 Aug 3;59(16):11253-11258. Epub 2020 Aug 3.

Institut für Anorganische Chemie, Universität Göttingen, Tammannstrasse 4, Göttingen 37077, Germany.

Neutral, mononuclear aluminum and gallium radicals, stabilized by cyclic (alkyl)(amino)carbene (cAAC), were synthesized. LMCl upon reduction with KC in the presence of cAAC afforded the radicals LMCl(cAAC), where L = PhC(NBu) and M = Al (), Ga (). The radicals were characterized by X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and mass spectrometry. EPR, SQUID measurement, and computational calculations confirmed paramagnetism of the radicals with unpaired spin mainly on cAAC.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01913DOI Listing
August 2020

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases.

J Pediatr Gastroenterol Nutr 2020 10;71(4):524-529

Department of Pediatrics, Cincinnati Children's Hospital Medical Center.

Objectives: Clinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE.

Methods: We conducted a cross-sectional study of contact registry data collected from 2015 to 2018. Statistical comparisons were made using chi-square (categorical measures) and the Mann-Whitney U test (continuous measures). Multivariable analyses were used to evaluate associations between treatment and feelings of isolation.

Results: Of the 715 reporting an EGID diagnosis (n = 525 EoE; n = 190 non-EoE EGID), a higher proportion of those with a non-EoE EGID reported more frequent specific and nonspecific gastrointestinal symptoms, including nausea, abdominal pain, diarrhea, constipation, and bloating (P < 0.01 for all). Participants with a non-EoE EGID were more likely to report higher frequency of fatigue, isolation, and deep muscle or joint pain (P < 0.01 for all). Specific food elimination and elemental formula treatments were associated with increased odds of more frequent (at least weekly) feelings of isolation for participants with EoE (adjusted odds rtaio [aOR]: 2.4; 95% confidence interval [CI]: 1.5--4.1 for specific food elimination and adjusted OR: 1.9; 95% CI: 1.2--3.3 for elemental formula).

Conclusions: Significant differences exist in the symptoms and comorbidities experienced between those with EoE versus non-EoE EGIDs. Additional investigation is needed to elucidate the factors that may contribute to the high disease burden of these poorly understood conditions.
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http://dx.doi.org/10.1097/MPG.0000000000002817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574400PMC
October 2020

Eosinophilic esophagitis: current status and future directions.

Pediatr Res 2020 09 21;88(3):345-347. Epub 2020 Jan 21.

Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria/Children's Hospital of Illinois, 530 NE Glen Oak Avenue North Building, Room 6646, Peoria, IL, USA.

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http://dx.doi.org/10.1038/s41390-020-0770-4DOI Listing
September 2020

High-Pressure Crystallographic and Magnetic Studies of Pseudo- Symmetric Dy(III) and Ho(III) Single-Molecule Magnets.

Inorg Chem 2020 Jan 12;59(1):717-729. Epub 2019 Dec 12.

Department of Chemistry , Aarhus University , Langelandsgade 140 , 8000 Aarhus C , Denmark.

Single-ion magnets based on lanthanide ions in pseudo- symmetry have gained much attention in recent years as they are reported to possess a large blocking temperature and a large barrier for magnetization reversal. Magneto-structural correlations reveal that the axial O-Ln-O angle is an important parameter to control the barrier, and while it can be fine-tuned by chemical modification, an alternative would be to utilize hydrostatic pressure. Herein, we report the crystal structures and static magnetic properties of two air-stable isostructural lanthanide SIMs under applied pressures. The complexes exhibit pseudo- symmetry around the Ln(III)-ion (Ln = Dy or Ho), which coordinates to five equatorial water molecules and two large neutral phosphonic diamide ligands along the axial direction. High-pressure single-crystal X-ray diffraction experiments revealed two phase-transitions and an increasing deviation from -symmetry between ambient pressure and 3.6 GPa. High-pressure direct-current magnetic measurements of the Dy(III) compound showed large steps in the hysteresis loops near zero field, indicative of quantum tunneling of magnetization (QTM). These steps grow in size with increasing pressure, suggesting that QTM becomes progressively more active, which correlates well with the pressure-induced increased overall deviation from pseudo- symmetry and decreasing axial O-Dy-O angle. A strong temperature dependence of the step size is seen at 0.3 GPa, which shows that the SMM character persists even at this pressure. To understand the origin of significant variation in the tunneling probability upon pressure, we performed a range of calculations based on the CASSCF/RASSI-SO/SINGLE_ANISO method on both Dy and Ho complexes. From the energies and magnetic anisotropy of the sublevels, we find a complex variation of the energy barrier with pressure, and using a constructed geometrical parameter, , taking into account changes in both bond angles and distances, we link the magnetic properties to the first coordination sphere of the molecules.
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http://dx.doi.org/10.1021/acs.inorgchem.9b02962DOI Listing
January 2020

Future therapies for eosinophilic gastrointestinal disorders.

Ann Allergy Asthma Immunol 2020 03 26;124(3):219-226. Epub 2019 Nov 26.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Illinois and the University of Illinois College of Medicine, Peoria, Illinois. Electronic address:

Objective: To review novel therapeutics in development for treatment of eosinophilic gastrointestinal disorders (EGIDs).

Data Sources: Clinical trial data (clinicaltrials.gov) and literature search on PubMed.

Study Selections: Studies on treatment and clinical trials in EGIDs were included in this review.

Results: During the past decade, significant progress has been made in understanding disease mechanisms in EGIDs. As a result, a variety of novel therapeutics have been developed for treatment of these disorders. Several monoclonal antibodies against targets, including interleukin (IL) 4, IL-5, IL-13, integrins, and siglec-8, have shown promise in early trials. Novel formulations of corticosteroids are also in development.

Conclusion: The field of EGID research has advanced rapidly, and disease-modifying therapeutics are closer to clinical application.
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http://dx.doi.org/10.1016/j.anai.2019.11.018DOI Listing
March 2020

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders.

Dig Dis Sci 2020 07 26;65(7):2024-2035. Epub 2019 Nov 26.

Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, CB #7080, Chapel Hill, NC, 27599, USA.

Background: Little is known about the endoscopic and histologic findings of non-esophageal eosinophilic gastrointestinal diseases (EGID).

Aim: To characterize the presenting endoscopic and histologic findings in patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at diagnosis and 6 months after initiating the treatment.

Methods: We conducted a retrospective cohort study at 6 US centers associated with the Consortium of Eosinophilic Gastrointestinal Researchers. Data abstracted included demographics, endoscopic findings, tissue eosinophil counts, and associated histologic findings at diagnosis and, when available, after initial treatment.

Results: Of 373 subjects (317 children and 56 adults), 142 had EG, 123 EGE, and 108 EC. Normal endoscopic appearance was the most common finding across all EGIDs (62% of subjects). Baseline tissue eosinophil counts were quantified in 105 (74%) EG, 36 (29%) EGE, and 80 (74%) EC subjects. The mean peak gastric eosinophil count across all sites was 87 eos/hpf for EG and 78 eos/hpf for EGE. The mean peak colonic eosinophil count for EC subjects was 76 eos/hpf (range 10-500). Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized. Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings.

Conclusions: In this large cohort, normal appearance was the most common endoscopic finding, emphasizing the importance of biopsy, regardless of endoscopic appearance. Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible.
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http://dx.doi.org/10.1007/s10620-019-05961-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315780PMC
July 2020

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

J Allergy Clin Immunol 2020 01 16;145(1):255-269. Epub 2019 Nov 16.

Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address:

Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools.

Objective: We aimed to develop tissue- and blood-based diagnostic platforms for EG.

Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels.

Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001).

Conclusion: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.
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http://dx.doi.org/10.1016/j.jaci.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949389PMC
January 2020

Adrenal Insufficiency in Children With Eosinophilic Esophagitis Treated With Topical Corticosteroids.

J Pediatr Gastroenterol Nutr 2020 03;70(3):324-329

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Illinois College of Medicine/Children's Hospital of Illinois, Peoria, IL.

Objectives: The aim of the study was to identify practices of gastroenterologists screening for adrenal insufficiency (AI) and report prevalence of AI in children with eosinophilic esophagitis (EoE) treated with topical corticosteroids (TCS); compare serum dehydroepiandrosterone sulfate (DHEA-S) levels to morning serum cortisol (MSC) levels as screening tool for AI.

Methods: A multipart study was conducted. In part 1, a survey about screening practices for AI in children with EoE on TCS was sent to gastroenterologists belonging to a PedsGI listserv and to EoE consortia. In part 2, children with EoE on TCS for ≥6 months were prospectively screened for AI with MSC levels. For subjects with a MSC level of <10 μg/dL, a repeat MSC level and/or confirmatory adrenocorticotropic hormone (ACTH) stimulation testing was offered. AI was defined by peak serum cortisol level <18 μg/dL. In part 3, DHEA-S levels were drawn with MSC levels.

Results: Seven percent (16/238) of gastroenterologists screened for AI. Providers in EoE consortia were more likely to screen than nonconsortia providers [9/21(43%) vs 7/217(3%); P = 0.0001]. Thirty-seven children were prospectively screened for AI, and 51% (19/37) had a low MSC level. Ten patients had a low-dose ACTH stimulation test (LDST) after 1 or more low MSC levels. Five percent (2/37) of patients were diagnosed with AI. DHEA-S and MSC levels had a moderate correlation (rs = 0.44, P = 0.03).

Conclusions: Gastroenterologists belonging to EoE consortia were more likely to screen for AI. Prevalence of AI in our prospective cohort was 5%. DHEA-S has a moderate correlation with MSC levels, but more data is required to assess utility as a screening tool for AI.
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http://dx.doi.org/10.1097/MPG.0000000000002537DOI Listing
March 2020

A single-ion single-electron cerrous magnet.

Dalton Trans 2019 Nov 12;48(42):15928-15935. Epub 2019 Sep 12.

Department of Chemistry, Indian Institute of Technology Bombay, Mumbai-400076, India.

Herein, we present monometallic Ln(iii) complexes [LLn(NO)] [where Ln = Ce (1) and La (2)] assembled from a simple reaction of the respective lanthanide nitrate hydrate and a bulky phosphonic diamide BuPO(NHPr) ligand (L), where complex 1 behaves as a single-ion single-electron magnet under a small applied magnetic field. The Ce(iii) ion occupies a nine-coordinate distorted muffin-like coordination environment. The combination of direct and Raman process dominates the relaxation dynamics in 1 under the applied dc field. The low-temperature measurements performed with oriented crystals on a micro-SQUID setup exhibits strong tunnelling at zero-field, consistent with the theoretical results where strong mixing of the ground state with higher excited m levels is detected and also throws additional insights on the relaxation dynamics of 1. Ab initio calculations have been performed to understand the origin of anisotropy and models have been proposed for future directions.
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http://dx.doi.org/10.1039/c9dt03052bDOI Listing
November 2019

How to Advance Research, Education, and Training in the Study of Rare Diseases.

Gastroenterology 2019 10 8;157(4):917-921. Epub 2019 Aug 8.

Department of Pediatrics and Internal Medicine, Division of Pediatric Gastroenterology/Hepatology/Nutrition, University of Illinois College of Medicine/Children's Hospital of Illinois, Peoria, Illinois. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2019.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034804PMC
October 2019

Hitherto unknown eight-connected frameworks formed from ABO metal organophosphate heterocubanes.

Chem Commun (Camb) 2019 Jul 21;55(55):7994-7997. Epub 2019 Jun 21.

Department of Chemistry, IIT Bombay, Powai, Mumbai-400076, India.

Modulation of a functional group on the distal part of a phosphate ester has been prudently exploited to selectively switch between the formation of D4R SBUs and 3-D framework structures. While amino substitution at the para-position of an aryl phosphate results in the isolation of tetra-amino functionalized discrete D4R zinc phosphate or its 4-connected 3-D framework, the introduction of an acetylamino substituent leads to a single-step assembly of a rare eight-connected 3-D framework solid.
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http://dx.doi.org/10.1039/c9cc01893jDOI Listing
July 2019

Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium.

Am J Gastroenterol 2019 06;114(6):984-994

Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Objectives: The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC.

Methods: In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses.

Results: Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements.

Conclusions: In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.
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http://dx.doi.org/10.14309/ajg.0000000000000228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554065PMC
June 2019

Bacillus coagulans Unique IS2 in Constipation: A Double-Blind, Placebo-Controlled Study.

Probiotics Antimicrob Proteins 2020 06;12(2):335-342

Department of Paediatrics, KRM Hospital and Research Centre, First Floor, Room No. 01 3/92-93 Vijayant Khand, Lucknow, Uttar Pradesh, 226010, India.

Functional constipation has a high prevalence in both adults and children affecting quality of life. Evidence suggests that probiotics can reduce the symptoms of constipation. As the effects of probiotics are strain specific, the efficacy of Bacillus coagulans Unique IS2 in the treatment of functional constipation in adults was evaluated. Subjects (n = 100) diagnosed with functional constipation were supplemented with either B. coagulans Unique IS2 (2 billion CFU) or placebo capsules once daily for 4 weeks. Subjects were evaluated for treatment success (defined as three or more spontaneous stools per week), stool consistency, difficulty of defecation, defecation and abdominal pain. By the end of the fourth week, there was a statistically significant (p < 0.001) increase in number of bowel movements in the probiotic treated group as compared to placebo. Ninety eight percent of subjects in the probiotic group achieved normal stool consistency as compared to placebo (74%). Moreover, there was relief from symptoms of incomplete evacuation, painful defecation and abdominal pain associated with constipation in probiotic treated group as compared to placebo. In conclusion, B. coagulans Unique IS2 significantly decreased the symptoms of constipation indicating effectiveness of the strain in the treatment of constipation.Trial registration: CTRI/2017/11/010539.
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http://dx.doi.org/10.1007/s12602-019-09542-9DOI Listing
June 2020

Eosinophilic Esophagitis-A Primer for Otolaryngologists.

JAMA Otolaryngol Head Neck Surg 2019 04;145(4):373-380

Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Peoria.

Importance: Eosinophilic esophagitis (EoE) is a chronic, inflammatory condition of the esophagus. Prevalence of EoE is on the rise and, owing to its associated extragastrointestinal manifestations and comorbidities, otolaryngologists are increasingly encountering this condition in their practice.

Observations: Symptoms of EoE are vague and vary greatly based on patient's age. The gastrointestinal symptoms include dysphagia, food impaction, feeding difficulties, symptoms mimicking gastroesophageal reflux, abdominal pain, vomiting, and failure to thrive. Several otolaryngologic symptoms are associated with EoE including rhinosinusitis, chronic cough, recurrent croup, hoarseness, and other aerodigestive symptoms refractory to gastroesophageal reflux therapy. Eosinophilic esophagitis is also frequently associated with other atopic conditions, such as asthma, eczema, and food allergies. The diagnosis is made on endoscopy with biopsies that reveal eosinophil-predominant esophageal inflammation. There are 3 major treatment approaches to EoE, commonly referred to as the 3 Ds: diet, drugs, and dilation. Untreated inflammation of esophagus from EoE can result in irreversible structural damage to the esophagus, leading to fibrosis, strictures, and impaired esophageal function.

Conclusions And Relevance: Eosinophilic esophagitis is now a fairly prevalent condition with considerable morbidity. Otolaryngologists should be familiar with the various clinical presentations of this condition in different age groups. Early diagnosis and treatment of this condition is a key for avoiding or postponing its complications.
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http://dx.doi.org/10.1001/jamaoto.2018.4177DOI Listing
April 2019

A Conceptual Approach to Understanding Treatment Response in Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2019 10 30;17(11):2149-2160. Epub 2019 Jan 30.

Division of Pediatric Gastroenterology, University of Illinois College of Medicine, Peoria, IL.

While the diagnosis and initial treatment of eosinophilic esophagitis are becoming more standardized, there are still major gaps in knowledge related to measuring treatment response. One such question centers on how to measure treatment response and what treatment endpoints should be. This impacts not only patient care and engagement in decision-making, but also the field of drug development. In addition, studies so far have use a myriad of treatment endpoints including over a dozen histologic endpoint criteria. This review will discuss the various stakeholders involved in assessment of treatment endpoints of a complex condition, including patients, practitioners and regulatory agencies, and the care settings in which treatment response is assessed, including routine clinical care, clinical trials, and observational studies. Potential parameters or treatment endpoints such as histology, symptoms, patient-reported outcomes, endoscopy, and biomarkers are discussed along with associated challenges and opportunities. A framework on how to define treatment outcomes is discussed and a conceptual approach treatment response is proposed. This takes into account histology, symptoms, and endoscopic findings and harnesses existing, validated tools. It includes definitions of nonresponse, complete normalization, and a graded response category between these 2 extremes, and also permits flexibility and latitude for modifications as newer knowledge emerges. In addition, ways to position the pediatric population in these endeavors are discussed as are future research directions.
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http://dx.doi.org/10.1016/j.cgh.2019.01.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667323PMC
October 2019
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