bluuebunny/crossref_metadata_2025 huggingface dataset:
DIFFERENTIALLY EXPRESSED GENE SIGNATURES OF ULCERATIVE COLITIS DETERMINE NOVEL REGULATORS AND PREDICT RESPONSE TO BIOLOGIC THERAPY
Authors: Penrose Harrison , Toraih Eman , Ruiz Emmanuelle , Iftikhar Rida , Collins Morgan , Kandil Emad , Savkovic Suzana
Published: January 2021

Disease heterogenicity among Ulcerative colitis (UC) patients and their variable responses to therapy is not well understood. Previously, using publicly available transcriptomes from colonic tissue of UC patients, we demonstrated the immune cell landscape and pathways that are common and distinct among patients and for non-responders to biologic therapy. Here, we AIM to determine differentially expressed gene signatures specific to inflamed UC tissue and for non-responders to biologic anti-TNFa and anti-a4b7 therapy in large patient cohorts. Methods: Transcriptomes from 210 UC patient samples from inflamed and matched uninflamed tissue (GSE4183, GSE14580, GSE38713, GSE107593) and from UC patients prior to and while receiving anti-TNFa (infliximab) and anti-a4b7 integrin (vedolizumab) (GSE12251, GSE73661) treatment were analyzed. Generating and analyzing differentially expressed genes (DEGs), transcriptional signatures, and hierarchical clustering were performed using the limma Bioconductor R package and Cluster3/JavaTree software. Disease/function analysis was performed by Ingenuity Pathway Analysis (IPA) and predicting outcomes to therapy by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). Transcripts were validated in primary UC tissue samples using qPCR. Results: In three UC cohorts, we identified a specific transcriptional signature of 100 DEGs (UC100) common among patients (Figure 1A-D). The UC100 signature was validated in an independent cohort, demonstrating the ability to distinctly separate inflamed from matched uninflamed transcriptomes (p=4.65e-08). The UC100 DEGs encode protein involved in inflammation, immunity, antimicrobial response, growth, cellular movement, metabolism (lipid, amino acid), and energy production. Among them are many DEGs with unexamined roles in UC, including PCK1, HMGCS2, ACAT1, HCAR3, LPCAT1, and LIPG. Their differential expression was further validated in primary UC tissue by qPCR. Moreover, we identified twenty DEGs in UC patients resistant to anti-TNFa and anti-a4b7 therapy (UCR20) (Figure 2A-C). The UC20R DEGs encode protein involved in inflammation, immune cell trafficking, antimicrobial responses, lipid metabolism, and mitochondrial dysfunction. Four of the top DEGs predicted resistance to both therapies with a sensitivity of 73.3% and specificity 85.7%; AUC for IGFBP5: 0.86±0.008, p=0.008; STC1: 0.83±0.09, p=0.015; VNN2: 0.81±0,10, p=0.022; and SELE: 0.77±0.11, p=0.045. Conclusion: This study demonstrates differentially expressed genes in UC common across cohorts and those with predictive power to biologic therapy outcome. This provides a platform for development of more precise diagnostic tools and personally tailored therapeutic regimens for UC patients.
REGULATION OF HUMAN INTESTINAL ORGANOID REACTIVE OXYGEN SPECIES PRODUCTION AND MITOCHONDRIAL FUNCTION BY DUOX2 GENETIC VARIATION AND MICROBIAL PRODUCTS
Authors: Jurickova Ingrid , Novak Elizabeth , Angerman Elizabeth , Bonkowski Erin , Mollen Kevin , Denson Lee
Published: January 2021

Introduction

The DUOX2 intestinal epithelial NADPH oxidase is upregulated in Crohn’s Disease (CD), and DUOX2 mutations are associated with increased CD risk. Oxidative stress and loss of mitochondrial function disrupt the intestinal barrier promoting inflammatory responses to commensals. The relative impact of DUOX2 mutations and microbial products in this regard is poorly understood.

Hypothesis

We hypothesized that DUOX2 genetic variation would be associated with differences in cellular reactive oxygen species (ROS) production and mitochondrial function in a Human Intestinal Organoid (HIO) model system.

Methods

Induced pluripotent stem cell lines derived from pediatric CD patients with and without combined DUOX2 missense mutations(R701Q, P982A, and H678R) were used to generate wild type (WT) and DUOX2mut HIOs. Reactive oxygen species (ROS) production was measured using the two-color ROS-ID® Total ROS/Superoxide detection kit, and the mitochondrial membrane potential (MMP) was measured using JC1 staining by flow cytometry in HIO EpCAM+ epithelial cells and CD90+ stromal cells. Expression of inflammatory and mitochondrial genes which varied with DUOX2 mutation carriage in CD patent ileal biopsies was measured by RT-PCR. HIO mitochondrial complex I and II activity was measured using an Oroboros respirometer.

Results

Epithelial ROS production was reduced in DUOX2mut HIO under basal conditions; this difference was not observed following pyocyanin stimulation (Fig. 1A). A profound suppression of epithelial ROS production was observed following butyrate treatment. Butyrate did not alter stromal cell ROS production. Under these conditions, induction of ROS by pyocyanin was abrogated in WT, but not DUOX2mut HIO epithelial cells (Fig. 1B). Butyrate increased expression of core genes regulating the mitochondrial respiratory chain and DNA synthesis (COX5B, NDUFA1, POLG2, SLC25A27) and HIF1A implicated in barrier function, independent of genotype (p<0.05). The epithelial and stromal cell mitochondrial membrane potential (MMP) (Fig. 2A), and HIO mitochondrial complex I activity (Fig. 2B), were reduced in DUOX2mut HIO under basal conditions. This was specific, as mitochondrial complex II activity did not vary with DUOX2 genotype.

Conclusions

We confirmed epithelial effects of DUOX2 genotype and butyrate exposure on ROS production in the HIO model system. Genotype dependent effects on basal ROS production were largely abrogated by the microbial products pyocyanin and butyrate, although butyrate inhibition of pyocyanin induced ROS production was dependent on intact DUOX2 function. Data suggest a previously unanticipated effect of DUOX2 genetic variation on the epithelial and stromal cell MMP and cellular respiration. This may have implications for mechanisms by which DUOX2 regulates barrier function and inflammatory responses to commensals in CD.
EVALUATING THE ROLE OF GOBLET CELL ASSOCIATED ANTIGEN PASSAGES (GAPS) IN THE DEVELOPMENT OF MUCOSAL IMMUNE TOLERANCE IN THE CFTR KO INTESTINE
Authors: Young Sarah , McDonald Keely , Newberry Rodney , Clarke Lane
Published: January 2021

Greater than 70,000 individuals worldwide are living with the monogenetic disease cystic fibrosis (CF). The development of chronic intestinal inflammation, with clinical signs resembling inflammatory bowel disease-like conditions, is a common yet poorly understood occurrence in CF patients. This inflammation is typically neutrophilic in human and animal models with a heightened basal pro-inflammatory cytokine release. Prior research utilizing intestinal organoids (enteroids) cultured from Cftr knockout mice has shown that goblet cells in the CF mouse intestine demonstrate defective clearance of mucin granules and abnormal mucus retention. Goblet cell-associated antigen passages (GAPs), located in the small intestine and colon, deliver intraluminal antigens to antigen-presenting dendritic cells in the submucosa. This mechanism serves as an important step in the development and maintenance of tolerogenic dendritic cell populations expressing receptors to luminal antigens with involvement of regulatory T cell activation and release of IL-10. We hypothesized that mucus plugging of goblet cells in the CF intestine leads to defective GAP formation and a consequent decrease in the expansion of tolerogenic dendritic cells. To test this hypothesis, Cftrtm1Unc (Cftr KO) and wild type (WT) sex-matched littermate pairs (n=2) maintained on a commercially available liquid diet (Peptamen®) were anesthetized with ketamine/xylazine for a laparotomy to inject a luminal fluorescent 10kD dextran dye into the mid-jejunum. After 30 min, the mice were euthanized with CO2, and the intestine was collected for immunofluorescent staining to evaluate GAP formation. In the WT intestine, the dextran dye was observed within goblet cells outlined by CK18 immunofluorescence, a goblet cell marker. Punctate dextran dye was observed in the submucosa, suggestive of dendritic cell uptake. In contrast, the Cftr KO mice demonstrated defective GAP formation, i.e., without dye penetration of goblet cells, and the lack of punctate dextran fluorescence in the submucosa. To evaluate the population of tolerogenic dendritic cells, small intestinal segments from Cftr KO-WT sex-matched littermate pairs (3-female and 2-male pairs) were collected for FACS sorting of submucosal CD103+ (tolerogenic) and CD103- (pro-inflammatory) dendritic cells. The WT mice had a significantly higher population of CD103+ tolerogenic dendritic cells compared to the CF mice (WT: 20.5+/-2, CF: 9.2+/-3, P < 0.006). A trend towards an increase in CD103- dendritic cells was seen in the CF intestine. In summary, the CF mice were found to have defective intraluminal antigen transfer through the GAP pathway and a significant decrease in tolerogenic dendritic cells in the intestine.
VALIDATION OF HPTM-001, A HUMANIZED CANDIDATE THERAPEUTIC ANTIBODY FOR PROMOTING MUCOSAL WOUND HEALING IN IBD
Authors: Liang Tony , Presta Leonard , Brazil Jennifer , Parkos Charles , Cheng Jennifer
Published: January 2021

A hallmark of the clinical course of patients with Inflammatory Bowel Disease (IBD) is poorly healing erosions and ulcers in the intestinal mucosa. Despite the adverse clinical consequences of non-healing mucosal wounds in IBD, current front-line therapies that selectively target mucosal wound healing are not available.

Recent studies revealed an association between colonic inflammation and aberrant glycosylation of epithelial CD44v6. Under conditions of inflammation, epithelial CD44v6 was shown to be decorated with the terminal glycan sialyl Lewis A. Importantly, targeting sialylated Lewis glycans on CD44v6 with a murine antibody GM35 was shown to promote mucosal wound healing in cell lines and in biopsy based wounding assays as well as dextran sodium sulfate (DSS) induced murine colitis models.

We sequenced CDRs from GM35 and produced a humanized antibody. Eight candidate human IgG1 clones were produced and screened. hPTM-001.4772 was selected from the eight candidates based on glycan affinity and selectivity compared to GM35. In vitro wound healing studies revealed that PTM-001.4772 was as effective as GM35 in promoting repair of scratch wounds with human intestinal epithelial cells. Furthermore, intraperitoneal injection of mice with hPTM-001.4772 during induction of DSS colitis resulted in reduced weight loss compared to control IgG. These results suggest that hPTM-001.4772 is well-positioned as a unique potential candidate therapeutic for IBD that can be used to selectively promote healing of mucosal wounds and ulcers.
INCIDENCE AND RISK FACTORS FOR NEOPLASIA IN INFLAMMATORY BOWEL DISEASE
Authors: Garcia Joana Lemos , Rosa Isadora , Moleiro Joana , da Silva João Pereira , Pereira António Dias
Published: January 2021

Introduction and goals

Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia due to IBD itself or its therapy. The aim of this study was to evaluate the incidence of malignant neoplasia in IBD patients in a portuguese hospital, the associated risk factors and the therapy adjustments made.

Methods

Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological center during 2015–2020 were included. Demographic and clinical data were registered.

Results

A total of 318 patients were included: female n=175(55.0%), age at diagnosis=37.24(±15,28)years-old, Crohn’s disease (CD) n=168(52.8%), Primary Sclerosing Cholangitis n=7, family history of cancer n=12, previous diagnosis of neoplasia n=23(7.2%), smokers n=49 (15.4%). A total of 42 cancers were diagnosed in 36 patients (11.3%) - median of 12.0(IQR=8.0–21.0) years after IBD diagnosis. Most affected organs: skin (n=15 in 11 patients; melanoma=1), colon and rectum (n=8 in 6 patients), prostate (n=4), breast (n=3) and anal canal (n=2). In those with non-melanoma skin cancer, 6 patients were under active treatment with azathioprine and 2 had stopped it for more than two years. In both univariate/multivariate analysis, the occurrence of neoplasia was associated with tobacco exposure (p=0.0.29/p=0.004), age (p<0.001/p=0,003) and IBD duration (p=0.001/p=0.017). There was no association with IBD therapy. In 9 cases, the cancer treatment was different because of the IBD (type of surgery n=6, drugs used n=2, radiotherapy not used n=1); IBD treatment was changed in 9 patients; clinical remission was lost in 1 patient in whom azathioprine treatment was halted after cancer. In the last follow-up, 3 patients remained with active oncological disease and 5 had died, 3 of which with active cancer. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p=0.003) and positively with salicylates use (p=0.016) and IBD remission before cancer diagnosis (p=0.008). In the multivariate analysis, the statistical significance was lost. Overall survival was lower in smokers with or without neoplasia (p<0.001) and in those who developped cancer (p=0.003).

Conclusion

In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, age and tobacco exposure were risk factors for the development of neoplasia. Tobacco is globally associated with lower survival rates and may be associated with a lower cure/remission rate, while salicylates and IBD remission may have a beneficial effect.
RISK OF ADVERSE OUTCOMES IN HOSPITALIZED PATIENTS WITH AUTOIMMUNE DISEASE AND COVID-19: A MATCHED COHORT STUDY FROM NEW YORK CITY
Authors: Faye Adam , Lee Kate , Laszkowska Monika , Kim Judith , Blackett John , McKenney Anna , Krigel Anna , Giles Jon , Wang Runsheng , Bernstein Elana , Green Peter , Krishnareddy Suneeta , Hur Chin , Lebwohl Benjamin
Published: January 2021

Objective

To examine the impact of autoimmune disease on the composite outcome of intensive care unit admission, intubation, or death, from COVID-19 in hospitalized patients.

Methods

Retrospective cohort study of 186 patients hospitalized with COVID-19 between March 1st–April 15th, 2020 at New York-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with autoimmune disease and 124 age- and sex- matched controls. The primary outcome was a composite of intensive care unit admission, intubation, and death, with secondary outcome assessing time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between autoimmune disease and clinical outcomes.

Results

Patients with autoimmune disease were more likely to have at least one comorbidity (25.8% vs. 12.9%, p=0.03), take chronic immunosuppressive medications (66.1% vs. 4.0%, p<0.01), and have had a solid organ transplant (16.1% vs. 1.6%, p<0.01). There were no significant differences in intensive care unit admission (14.2% vs. 19.4%, p=0.44), intubation (14.2% vs. 17.7%, p=0.62) or death (17.5% vs. 14.5%, p=0.77). On multivariable analysis, patients with autoimmune disease were not at an increased risk for a composite outcome of intensive care unit admission, intubation, or death (adjOR 0.79, 95%CI 0.37–1.67). On Cox regression, autoimmune disease was not associated with in-hospital mortality (adjHR 0.73, 95%CI 0.33–1.63).

Conclusion

Among patients hospitalized with COVID-19, individuals with autoimmune disease did not have an increased risk of a composite outcome of intensive care unit admission, intubation, or death.

Kaplan-Meier curve examining death, stratified by the presence or absence of autoimmune disease in all 186 patients, with 16 patients censored as of 4/29/2020
RECENT APPROACHES FOR SMOKING CESSATION IN CROHN’S DISEASE: A QUALITATIVE REVIEW
Authors: Moon Jooyoung , Moon Hanna
Published: January 2021

Background

The clinical practice guideline for Crohn’s disease (CD) management strongly recommends the avoidance and cessation of smoking. However, no standardized smoking cessation (SC) program exists for CD patients. Results from a nationwide survey among U.S. gastroenterologists have shown that SC counseling occurs irregularly and that almost half are not comfortable discussing SC strategies with their patients. These findings suggest that systematization and improvements in approaches for SC are necessary. This study aimed to provide a comprehensive review on recent developments and recommendations in SC care for CD patients.

Methods

A systematic literature review was conducted using PubMed, Google Scholar, and Web of Science databases for articles published from years 2016 to 2020. Two researchers independently screened and reviewed data. Inclusion criteria included peer-reviewed, published scientific articles written in the English language that examined SC in CD patients. Only studies with adults (≥18 years old) and those with more than 10 subjects were included. No geographic limitations were applied. A total of 12 articles met our inclusion criteria.

Results

CD patients were found to have a significantly lower rate of SC when compared to the average population. Initial diagnosis of CD served as a strong motivator to quit, suggesting that SC education and intervention should begin on the first visit. Other significant positive predictors for SC in previous smokers included male gender, older age, and higher BMI. Adoption of a standardized program with a systematized process of questioning, documenting, and educating patients on SC resulted in an increase in discussion of SC strategies. Studies which expressed concerns regarding the deleterious effects of passive smoking on CD suggested that SC counseling be more broadly applied to include a patient’s cohabitants. For those who require more intervention, addiction medicine consultation has been shown to reduce smoking use by a substantial margin of 27%. In order to increase the success of SC, a recent trial has taken a personalized approach that involves measuring an individual’s nicotine metabolite ratio to recommend a matching medication. Results have been promising with high rates of satisfaction of 85%.

Conclusions

Gastroenterologists should provide SC counseling more often and on a more regular basis, especially for patients who receive an initial diagnosis of CD. As existing SC strategies have limitations, new approaches are being actively explored, but further studies are desperately needed. Development of standardized and personalized SC programs should be considered so that SC counseling can become a routine and integral part of care for CD patients.
TELEMEDICINE IN IBD: GOOD TRUST FROM OUTPATIENTS DURING THE COVID-19 PANDEMIC IN MILAN (LOMBARDY)
Authors: Costantino Andrea , Noviello Daniele , Mazza Stefano , Berté Roberto , Vecchi Maurizio , Caprioli Flavio
Published: January 2021

Background and Aim

During the recent COVID-19 pandemic, telemedicine has enabled many IBD patients worldwide to get access to remote assistance. Some positive reports on the use of telemedicine among patients and healthcare providers have been published1-4, but a patient’s trust perspective is not available yet.

The aim of our study was to verify IBD patients’ trust in telemedicine. This study was approved by our local Ethics Committee.

Material and Methods

At our Gastroenterology Unit in Milan (Italy), 123 video-consultations were delivered to IBD patients with mild or moderate disease, in place of follow-up visits scheduled but not provided during the general lockdown (March-April 2020).

Video-calling solutions from Google (Hangouts or Meet) or Microsoft Teams were used according to the patient’s preference.

The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire.5

The primary endpoint was expressed as a >75% percentage of patients giving a score of at least 4 out of 5 in a Likert Scale for three selected key statements: “I can trust video-consultation”, “I can trust that possible problems with the telemedicine service will be solved properly” and “I feel at ease when working with this website”.

The questionnaire was formulated through the EUSurvey platform, widely used for clinical research questionnaires in Europe.

Results

One-hundred-fifteen (93.4%) video-consultations were performed out of the 123 scheduled. Among the 115 consultations, 100 questionnaires were completed (86.9%). The primary endpoint of trust in the telemedicine service was achieved in 95%, 90% and 84% of patients for the three selected key statements about the trust in the telemedicine service, its capability to solve clinical problems and its ease to use.

While clinical outcomes were beyond our intentions, we reported no drugs withdrawal in this cohort nor major events.

Conclusion

Our results showed that during the COVID-19 pandemic most of our IBD patients accepted to receive a video-consultation in spite of the traditional in-person visit and trusted the video-consultation.

References:

1. Bezzio C. et al. Gut 2020;69:1213–1217

2. George L.A., Raymond K. Current Gastroenterology Reports (2020) 22: 12

3. Lees C. W. et al. Gastroenterology 2020; 2020 May 28

4. Allocca M et al. Clin Gastroenterol Hepatol 2020;18:1882–1883

5. Velsen, L. V. et al, H. Int. J. Med. Inform 2017;97:52–58.
ANALYSIS OF ONLINE INFORMATION ON SUPPORT GROUP MEETINGS FOR CROHN’S DISEASE PATIENTS
Authors: Moon Jooyoung , Moon Hanna
Published: January 2021

Background

In 2018, the American College of Gastroenterology published guidelines for Crohn’s disease management that emphasized the importance of addressing the patient’s quality of life (QOL). Due to the unique challenges that they face, afflicted patients and their families benefit from support groups that provide psychosocial support. Hospitals have traditionally preferred in-person support group meetings, but there has recently been a great increase in the need for online meetings amidst the COVID-19 pandemic. With increasing usage of the Internet for health advice and assistance, it is important to assess the availability of information on support groups online.

Methods

Two independent investigators queried the terms “Crohn’s support group” using the Google search engine. The first 100 websites were analyzed and categorized into either informational websites (IW) or professional websites (PW) depending on their association. The mode of support group meetings was categorized as either online or in-person. Websites that included outdated events, were inaccessible, did not specify the mode of meeting, required additional contact, or were irrelevant were excluded. Statistical analyses were performed using the chi-squared test of independence with significance level at p<0.05.

Results

A total of 56 websites (33 IW, 23 PW) met our inclusion criteria. IW offered online meetings more often than PW (60.6% and 39.1%, respectively; p=0.11). In contrast, PW offered in-person meetings more often than IW (73.9% and 69.7%, respectively; p=0.73). Excluded websites (30 IW, 14 PW) were further analyzed for their reason for elimination. For IW, the most frequent causes of exclusion in descending order were as follows: irrelevance (30.0%), outdated (26.7%), inaccessible (20.0%), did not specify the mode of meeting (13.3%), and redirected for further information (10.0%). Listing of outdated sessions was the most common reason for exclusion of PW from the study (57.1%), and the proportion was significantly higher than IW (26.7%) (p=0.01).

Conclusion

Crohn’s disease patients face unique challenges that require special attention. Support groups are an important means of alleviating stress, depression, and anxiety in order to improve their QOL. Yet, due to the COVID-19 social distancing policies, many are refrained from participating in in-person sessions. This study illustrates that more online support group meetings are needed and that professional websites should improve on making regular updates for future meeting sessions.
PATIENTS’ JOURNEY THROUGH INFLAMMATORY BOWEL DISEASE (IBD): A QUALITATIVE STUDY
Authors: Omprakash Tina Aswani , Reilly Norelle , Bhagwakar Jan , Carrell Jeanette , Woodburn Kristina , Breyer Abby , Close Frances , Wong Gabriel
Published: January 2021

Background

Inflammatory bowel disease (IBD) is a debilitating intestinal condition, manifesting as Crohn’s disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC). The patient experience is impacted by a lack of awareness from other stakeholders despite growing global disease prevalence. To gain deeper insight of the patient experience, promote quality care, and enhance quality of life, we performed a qualitative study of the patient journey starting from pre-diagnosis through treatment.

Methods

U.S. patients with IBD were recruited via UC/CD support groups and organizations, social media platforms, blog followers, and personal networks. Participants were screened via an emailed survey and asked to self-identify as medically diagnosed on the basis of reported diagnostic testing. Interviews were conducted by qualitative researchers by phone or web conferencing. Open-ended questions were developed to support and gather information about our learning objectives—primarily, our desire to understand the unique experiences of UC/CD patients in their journey from symptom onset through diagnosis, treatment and maintenance (e.g. “Upon diagnosis, what were your immediate thoughts about the condition?”). This qualitative data were analyzed using Human-Centered Design methodology, including patient typologies (personas), forced temporal zoom (journey maps), forced semantic zoom (stakeholder system mapping), and affinity mapping for pattern recognition of unmet needs.

Results

A total of 32 patients were interviewed: N=17 CD patients, N=13 UC patients and N=2 IC patients. The interviewed population reflected regional, demographic, and disease-related diversity (Table 1). Five unique, mutually exclusive journeys were identified to understand and classify patient experiences: (1) Journey of Independence, (2) Journey of Acceptance, (3) Journey of Recognition, (4) Journey of Passion and (5) Journey of Determination (Figure 1). Patients with IBD expressed a need for increased awareness, education, and training for providers to shorten the path to diagnosis. Mental health support was found to be a critical gap in care, particularly for major treatment decisions (e.g., surgery). The inclusion of emotional support into the treatment paradigm was perceived as essential to long-term wellness. Patient attitudes and self-advocacy varied on their individual journeys; understanding these journeys may accelerate time to diagnosis and treatment.

Conclusion

Better understanding of patient journeys can help healthcare providers improve their approach to patient care and coordination.
Pneumococcal Carriage in Burkina Faso After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results From 2 Cross-sectional Population-Based Surveys
Authors: Kaboré Lassané , Adebanjo Tolulope , Njanpop-Lafourcade Berthe Marie , Ouangraoua Soumeya , Tarbangdo Felix T , Meda Bertrand , Velusamy Srinivasan , Bicaba Brice , Aké Flavien , McGee Lesley , Yaro Seydou , Betsem Edouard , Gervaix Alain , Gessner Bradford D , Whitney Cynthia G , Moïsi Jennifer C , Van Beneden Chris A
Published: January 2021

Background

Burkina Faso, a country in Africa’s meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction.

Methods

We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey.

Results

We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%–35.9%; P = .03); among carriers aged 1–4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%–40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed.

Conclusion

Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.
Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis
Authors: Long Richard , Lau Angela , Egedahl Mary Lou , Paulsen Catherine , Heffernan Courtney , Edwards Brett , Cooper Ryan
Published: January 2021

Background

Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown.

Methods

We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982–2001 and 2002–2019. The proportion of MDR tuberculosis among migrants arriving from high MDR (HMDR) tuberculosis burden countries during these 2 periods was used to estimate the proportion of cases due to immigration versus change in proportion in the country of birth. Epidemiologic, spatiotemporal, and drug resistance pattern data were used to confirm local transmission.

Results

Fifty-two of 3514 (1.48%) foreign-born culture-positive tuberculosis patients had MDR tuberculosis: 8 (0.6%) in 1982–2001 and 44 (2.0%) in 2002–2019. Between time periods, the proportion of MDR tuberculosis among migrants with tuberculosis from HMDR tuberculosis countries increased from 1.11% to 3.62%, P = .003; 31.6% attributable to recent immigration and 68.4% to a higher proportion of MDR tuberculosis in cases arrived from HMDR tuberculosis countries. No cases of MDR tuberculosis were attributable to local transmission.

Conclusions

In stark contrast to HMDR tuberculosis countries, local transmission plays no important role in the occurrence of MDR tuberculosis in Canada. Improved tuberculosis programming in HMDR tuberculosis countries is urgently needed.
Human-centered development of an electronic health record-embedded, interactive information visualization in the emergency department using fast healthcare interoperability resources
Authors: Thayer Jeritt G , Ferro Daria F , Miller Jeffrey M , Karavite Dean , Grundmeier Robert W , Utidjian Levon , Zorc Joseph J
Published: January 2021

Objective

Develop and evaluate an interactive information visualization embedded within the electronic health record (EHR) by following human-centered design (HCD) processes and leveraging modern health information exchange standards.

Materials and Methods

We applied an HCD process to develop a Fast Healthcare Interoperability Resources (FHIR) application that displays a patient’s asthma history to clinicians in a pediatric emergency department. We performed a preimplementation comparative system evaluation to measure time on task, number of screens, information retrieval accuracy, cognitive load, user satisfaction, and perceived utility and usefulness. Application usage and system functionality were assessed using application logs and a postimplementation survey of end users.

Results

Usability testing of the Asthma Timeline Application demonstrated a statistically significant reduction in time on task (P < .001), number of screens (P < .001), and cognitive load (P < .001) for clinicians when compared to base EHR functionality. Postimplementation evaluation demonstrated reliable functionality and high user satisfaction.

Discussion

Following HCD processes to develop an application in the context of clinical operations/quality improvement is feasible. Our work also highlights the potential benefits and challenges associated with using internationally recognized data exchange standards as currently implemented.

Conclusion

Compared to standard EHR functionality, our visualization increased clinician efficiency when reviewing the charts of pediatric asthma patients. Application development efforts in an operational context should leverage existing health information exchange standards, such as FHIR, and evidence-based mixed methods approaches.
Population Genomic Analyses Confirm Male-Biased Mutation Rates in Snakes
Authors: Schield Drew R , Perry Blair W , Nikolakis Zachary L , Mackessy Stephen P , Castoe Todd A
Published: January 2021

Male-biased mutation rates occur in a diverse array of organisms. The ratio of male-to-female mutation rate may have major ramifications for evolution across the genome, and for sex-linked genes in particular. In ZW species, the Z chromosome is carried by males two-thirds of the time, leading to the prediction that male-biased mutation rates will have a disproportionate effect on the evolution of Z-linked genes relative to autosomes and the W chromosome. Colubroid snakes (including colubrids, elapids, and viperids) have ZW sex determination, yet male-biased mutation rates have not been well studied in this group. Here we analyze a population genomic dataset from rattlesnakes to quantify genetic variation within and genetic divergence between species. We use a new method for unbiased estimation of population genetic summary statistics to compare variation between the Z chromosome and autosomes and to calculate net nucleotide differentiation between species. We find evidence for a 2.03-fold greater mutation rate in male rattlesnakes relative to females, corresponding to an average μZ/μA ratio of 1.1. Our results from snakes are quantitatively similar to birds, suggesting that male-biased mutation rates may be a common feature across vertebrate lineages with ZW sex determination.
National Human Rights Institutions in Post-Conflict Settings: An Evolving Research Agenda?
Authors: Molloy Sean
Published: January 2021

The potential contributions that National Human Rights Institutions (NHRIs) can make in post-conflict settings has drawn increased attention from academics and practitioners alike. For some, NHRIs can assume positive roles assisting not only in the protection and promotion of human rights but also in peacebuilding and transitional justice processes. Conversely, scholars identify a spectrum of potential obstacles that may hinder the translation of this potential into practice. Others assess that NHRIs can even hamper efforts to transition from conflict to peace. Existing literature identifies a number of factors that determine the contributions that NHRIs can make in conflict-affected settings. These include the institutional design of an NHRI, the degree of autonomy from the government, and the level of expertise needed to navigate the post-conflict landscape. This article considers a number of mechanisms and avenues available that could help NHRIs to navigate post-conflict transitions. Specifically, the article examines the potential impact of peace agreements that include provisions on NHRIs; post-conflict guidelines developed for NHRIs operating in conflict-affected settings; and various accountability-based mechanisms that monitor NHRIs and post-conflict governments on an ongoing basis. After considering how these options could support the positive contributions that NHRIs make to peace, the article will argue that more questions than answers arise. By identifying these uncertainties, however, the discussion helps illuminate important gaps in the literature, pointing to the need for a more comprehensive and integrated research agenda on NHRIs in post-conflict contexts.
Brothers, Workers or Syrians? The Politics of Naming in Lebanese Municipalities
Authors: Mourad Lama
Published: January 2021

Displaced Syrians in Lebanon face a multitude of legal, social and political categories that operate together to structure their lives and opportunities. One important site of juxtaposition of these various categories can be found in the area of municipal governance, namely in the form of bannered discriminatory curfews that line the public squares of many of Lebanon’s urban neighbourhood, towns and villages. The various named ‘targets’ of these curfews—whether foreigners, Syrians, displaced, labourers, brothers or the disembodied ‘motorbike’ (a class marker in this context)—instantiate the complexity of issues of Syrian belonging in this context. This article examines these categories through their historical, political and social dimensions, and through the lived experience of Syrians who encounter, negotiate and—at times—resist them. Building on over a year of fieldwork in Lebanon from October 2015 to December 2016, this article relies on a diverse set of sources, including ethnographic observation, documents and interviews with a wide array of actors including Lebanese citizens and displaced Syrians, mayors and municipal police officers, as well as lawyers, journalists, aid workers and central government officials.
s.Four New Challenges, 16 International Trade, Public Health, and Human Rights
Authors: Chuang-Feng Wu , Chien-Huei Wu
Published: January 2021

This chapter explores how to navigate health-related human rights in the trade and public health complex by tracing the intersection of international trade and public health and examining the role of international trade in global health law. An intrinsic tension exists between international trade, public health, and human rights in this globalizing world. Even though growing global interconnectedness has generated economic growth and information sharing, it is also characterized by threats—to access to medicine, commercialization of health care, and widening health inequality. Although this tension was well recognized in the development of the World Trade Organization, it has become much more complicated in recent decades. By addressing critical questions surrounding trade and public health, examining the transformation of risks into opportunities through global efforts, it will be possible to investigate possible venues to resolve trade and public health tensions in light of human rights.
The General Assembly
Authors: Clapham Andrew
Published: January 2021

This chapter examines the General Assembly, which is the United Nations’ main deliberative organ. To the extent that it reflects the will of the majority of the UN members, it has some influence on the organization’s general direction. It is the organ generally mandated to discuss and make recommendations on any question within the scope of the UN Charter, and it is specifically asked to initiate studies and make recommendations to promote, among other things, human rights. However, the General Assembly is an assembly of state representatives. This political composition can make it difficult to find agreement on which human rights deserve promotion, and which states, or rather which governments, should be singled out for censure. Nevertheless, the General Assembly has developed the international law and universal standards which underpin the world of human rights protection, improved the United Nation’s institutional machinery, and authorized some important human rights-related field operations and investigative mandates.
The Permanent Forum on Indigenous Issues
Authors: Heyward Madeleine
Published: January 2021

This chapter explores the Permanent Forum on Indigenous Issues (PFII), which is the first permanent UN body in which state and non-state nominees hold equal status. The PFII is primarily a product of increasing recognition within the UN system of the need for more focused attention to protect and promote indigenous peoples’ rights—full accommodation of indigenous rights within existing human rights mechanisms and instruments ‘remains elusive’, and indigenous individuals and communities across the world continue to experience significant discrimination and social and economic disadvantage. Since the adoption in 2007 of the UN Declaration on the Rights of Indigenous Peoples, the first comprehensive and generally applicable international instrument on indigenous rights, the PFII has taken an increasingly rights-based approach across its mandate. The chapter then considers the PFII’s institutional landscape and its strengths and weaknesses as a protector and promoter of human rights, with a focus on implementation of the Declaration.
The Committee on the Elimination of Racial Discrimination (CERD)
Authors: Thornberry Patrick
Published: January 2021

This chapter studies the Committee on the Elimination of Racial Discrimination (CERD), the oldest of the monitoring bodies of the UN ‘core’ treaties. Preceded by a Declaration on the Elimination of All Forms of Racial Discrimination in 1963, the International Convention on the Elimination of all Forms of Racial Discrimination (ICERD) was adopted by the UN General Assembly on 21 December 1965 and entered into force on 4 January 1969. CERD oversees the implementation of the Convention. The chapter evaluates how CERD has worked to deliver its mandate, where it has innovated, and where it has been able to draw upon the wider human rights acquis to ground its positions, and where it may have struggled to deliver. It focuses on a number of issues around the core principles: discrimination and the grounds thereof; special measures; segregation; and the problem of addressing hate speech.
Sources and Principles of Islamic Law
Authors: Eisenberg David M
Published: January 2021

This chapter examines the sources and principles of Islamic law. A broad understanding of the sources and principles of Islamic law is prerequisite to an examination of the legal foundations of Islamic finance. Islamic law comprises a complex and vast body of doctrine that has taken shape in extremely varied circumstances for well over a millennium as part and parcel of an evolutionary process still vigorously underway. The chapter then describes the technical terminology employed by Muslim jurists across the entire field of Islamic law. All the technical terminology is in Arabic but exact or rough equivalents can be found in other legal systems. The chapter also looks at the legal concepts relevant to Islamic finance from a historical perspective as the point of departure for an exposition of the Islamic law of contract, for which they provide the conceptual underpinnings.
Islamic Financial Institutions
Authors: Henderson Andrew
Published: January 2021

This chapter discusses Islamic Finance Institutions (IFIs), which are established on the principle that there should be no separation between temporal and religious matters. Compliance with the Shari’a is in theory the governing law for all aspects of a practising Muslim's life, including financial and business transactions. Recognizing that, under the Shari’a, money does not have a time-value separate from the value of goods that are exchanged through the use of money, IFIs embrace the principle of sharing profit and loss and reject interest as a cost for accepting and lending money. Within these constraints, IFIs offer various services, including: (a) Islamic commercial banking; (b) Islamic wealth and asset management; (c) Islamic insurance; and (d) social services, where the IFI makes loans. In practice, a firm will offer Islamic financial services either as a full IFI, whereby its entire business is dedicated to offering Shari’a-compliant services and products, or through an ‘Islamic Window’, whereby a part of the firm's business is dedicated to offering Shari’a-compliant services and products. In either case, the firm will appoint a Shari’a Supervisory Board (SSB) entrusted with the duty of directing, reviewing, and supervising the firm's activities to ensure compliance with the Shari’a.
Murabaha and Tawarruq
Authors: Nethercott Craig R
Published: January 2021

This chapter focuses on the murabaha structure, which is probably the most commonly used Islamic finance structure in modern Islamic banking. The simplicity of structure in its current application has promoted its use as a popular and flexible Islamic financing instrument. Indeed, the use of the murabaha has been extended beyond a widespread application as a standalone instrument to a composite component of Sukuk issuance in modern application. The murabaha contract is understood within the Islamic tradition to have a pre-Islamic origin evidenced in pre-Islamic literature and characterized as a fiduciary contract with the objective to assist less knowledgeable buyers in the determination of the fair price of unfamiliar goods. Today, murabaha is commonly used as a mode of finance, in its variant structures, for the acquisition of assets, commodities, and goods in the ordinary course of trade. The structure is also used as a corporate finance tool for working capital and liquidity management. The chapter then considers commodity murabaha (tawarruq) and its application.
Sukuk
Authors: Hanif Atif , Johansen Julian , Richardson Edana
Published: January 2021

This chapter focuses on the sukuk market, which represents one of the more high-profile elements of the Islamic finance industry. Over the last two decades, the sukuk market has been a key driver behind the growth of Islamic finance globally, with the state of the sukuk market often seen as a barometer for the health of the wider Islamic finance market. However, the sukuk industry has also had its own specific hurdles to overcome. Internal scepticism, a multitude of complex structures, and legislative restrictions have all contributed to the current shape of the sukuk market. While this market may never challenge the conventional debt capital markets in terms of size or accessibility, it remains a key aspect of the Islamic finance industry generally and offers an important Shari’a-compliant resource for issuers and investors.