bluuebunny/crossref_metadata_2025_split huggingface dataset:
INFLAMMATORY BOWEL DISEASE CLASSIFICATION USING THE GUT MICROBIOME: A BENCHMARK OF MICROBIAL DATA ANALYSIS METHODS
Authors: Kubinski Ryszard , Djamen Jean , Zhanabaev Timur , Martin Ryan 
Published: January 2021

Abstract
The prevalence of inflammatory bowel disease (IBD) is increasing throughout the developed world. For the newly diagnosed, the time between the appearance of symptoms and diagnosis can take months, involving invasive procedures. There is an urgent need to develop a simple, low cost, accurate and non-invasive diagnostic test.
With decreasing costs of next-generation sequencing, many studies have compared IBD gut microbiomes to healthy controls, successfully identifying bacterial biomarkers for IBD. Unfortunately, a majority of these studies utilize machine learning and statistical methods on either single or low-sample size datasets. This results in the creation of disease classification models that have a high level of overfitting and therefore minimal clinical application to new patient cohorts. There are several data preprocessing methods available for data normalization and reduction of cohort specific signals (batch reduction) which can address this lack of cross-dataset performance. With an abundance of potential methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (combination of data preprocessing and model) for microbiome-based IBD diagnostic tools.
We used a collection of 12 IBD-associated North American microbiome datasets (~4000 samples) to benchmark several machine learning pipelines. Raw sequencing data was processed, collapsed at the OTU or Genus level and merged using QIIME2. Datasets were then normalized using either sum-scaling or log based methods and batch reduction was performed using either zero-centering or Empirical Bayes’ approaches. Performance of pipelines was evaluated using binary accuracy, AUC, F1 metric and MCC score. Generalizability of pipelines was evaluated using leave one out cross validation, where data from one study was left out of the training set and tested upon. The best performing and most generalizable pipeline included a Random Forest model paired with centered log ratio based normalization and batch reduction via an Empirical Bayes’ based approach. This combination, along with others, showed equivalent or higher performance to that of more complex models involving deep neural networks (DNNs). In addition to benchmarking our pipelines, we also explore their limitations, such as the tendency of zero-centered batch reduction to rely on balanced data as input or the tendency of Empirical Bayes’ based methods to introduce artificial signals into data, evidencing certain methods as poor tools for clinical use.
To our knowledge, this is the first comprehensive benchmark of data preprocessing and machine learning methods for microbiome-based disease classification of IBD. These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.
IMPROVING PATIENT PARTICIPATION IN LONGITUDINAL RESEARCH: AN INNOVATIVE PATIENT-LED PATIENT-ORIENTED QUALITATIVE RESEARCH PROJECT TO UNDERSTAND THE MOTIVATIONS AND BARRIERS TO GETTING AND STAYING INVOLVED IN THE IMAGINE SPOR STUDY
Authors: Zelinsky Sandra , Daley Kimberlee , Neary Emma , Mason Kate , Bellissimo Gail , DeNino Alysia , MacKean Gail , Fernandes Aida , Moayyedi Paul , Marshall Deborah 
Published: January 2021

Abstract

Background
The Inflammation, Microbiome, & Alimentation, Gastro-Intestinal & Neuropsychiatric Effects (IMAGINE) Strategy for Patient-Oriented Research (SPOR) Network is conducting a large longitudinal research study to investigate the interactions between inflammation, microbiome, diet, and mental health in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This study aims to recruit 2000 patients with Crohn’s disease, 2000 with ulcerative colitis, 2000 with IBS, and 2000 healthy controls. Each subject is assessed annually for 4 years and is asked to submit blood, urine, and stool samples, and complete online questionnaires on their health status. Given the ambitious recruitment target, a group of IMAGINE Patient Research Partners (PRPs) led a qualitative study to better understand the motivations and barriers of healthy controls to participating in this study to inform more effective recruitment and retention strategies.

Methods
This study has been co-led, co-designed, and executed by IMAGINE’s PRPs with support from academic researchers. PRPs were trained in qualitative research, co-designed the interview guide, and developed a semi-structured interview guide. Qualitative semi-structured interviews were conducted by 7 PRPs and were recorded electronically. All of the interviews were transcribed by a PRP, a trained medical transcriptionist. Five PRPs conducted data analysis and coded the interview content into common themes.

Results
A total of 27 interviews (13 male and 14 female) were conducted. Participants ranged from 20–75 years old. The top four themes of key motivators to study participation that emerged were Convenience, Experience, Communication, and Compensation. The interview participants identified Convenience as being low time commitment, the flexibility of scheduling, multiple recruitment locations, or using a courier for collecting samples. The Experience category reflects the desire to stay involved if their experience is relaxed, hassle-free, and fun, with emphasis on the study being well-organized. Participants stressed the importance of Communication such as reminders, annual updates, and newsletters. Compensation was important to some participants such as gift cards, parking reimbursement, or non-monetary items such as thank you cards and tokens of appreciation.

Conclusions
This study was co-created by PRPs who were actively involved throughout all stages of the project. The results from this patient-led study will help inform adaptations to recruitment and retention strategies for the national IMAGINE SPOR study.
“ADULTING” WITH IBD: A NOVEL, VIRTUAL INFLAMMATORY BOWEL DISEASE TRANSITION PROGRAM FOR TEENS AND CAREGIVERS
Authors: Stellway Jacklyn , Waschmann Malika , Lin Henry , Harris Michael 
Published: January 2021

Abstract
Introduction: Rates of newly diagnosed inflammatory bowel disease (IBD) in pediatric patients increased by 133% from 2007–2016. With the rise comes an increase in patients ultimately transitioning from pediatric to adult GI care. While pediatric care is family-centered and multi-disciplinary adult care is patient-centered with expectation for autonomy. However, less than 15% of patients are fully responsible for their IBD care by late adolescents. The transition period is marked by adverse health outcomes including decreased compliance and increased disease activity and hospitalization. Our data recognized up to 74% of IBD youth reported not having discussed transition at home or with their GI providers, and a desire to receive information in person. Without guidance from the GI team patients may not have adequate time to plan for successful transition.
Methods: A one-day 3.5-hour transition preparedness workshop was developed to address the demonstrated need in a pediatric GI clinic. Recruitment letters were distributed to 134 IBD youth ages 15–19. Eighteen consenting participants completed measures prior to and following the workshop (at 3 and 12 months). Assessment tools included previously validated self- and parent-reports: Patient Health Questionnaire-8, General Anxiety Disorder-7), Transition Readiness Assessment Questionnaire, IBD Self Efficacy Scale; and Helping for Health Inventory.
Results: While the workshop was designed for in person the pandemic required shift to virtual had strengths and potential drawbacks. Youth across 300 miles were able to attend, as well as IBD young adult peers sharing their personal transition experiences. It is hypothesized pre-workshop data will demonstrate low levels of transition readiness and IBD self-efficacy, with increases in 3- and 12-month post-workshop data. Transition readiness is also presumed to correlate with measures of IBD self-efficacy and miscarried helping by parents. We will present program effectiveness data with factors known to both facilitate and obstruct successful transition from pediatric to adult IBD care.
Conclusion: There remains a paucity of literature evaluating the efficacy of IBD transition programs. This research informs such programs by evaluating the efficacy of a one-day virtual workshop on skill development and knowledge. Assessment data and follow up after transition to adult care will provide important information to guide development of evidence-based transition planning for IBD patients.
PERFORMANCE CHARACTERISTICS OF A FRET-BASED IMMUNOASSAY FOR QUANTITATION OF ADALIMUMAB ON A POINT-OF-CARE INSTRUMENT SYSTEM
Authors: Ong Edgar , Huang Ruo , Kirkland Richard , Hale Michael , Mimms Larry 
Published: January 2021

Abstract

Introduction
A fast (&lt;5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassay was developed for the quantitative detection of adalimumab (ADL) and biosimilars for use in therapeutic drug monitoring using only 20 µL of fingerstick whole blood or serum at the point-of-care. The Procise ADL assay and the ProciseDx analyzer are CE-marked. Studies were performed to characterize analytical performance of the Procise ADL assay on the ProciseDx analyzer.

Methods
Analytical testing was performed by spiking known amounts of ADL into negative serum and whole blood specimens. Analytical sensitivity was determined using limiting concentrations of ADL. Linearity was determined by testing ADL across the assay range. Hook effect was assessed at ADL concentrations beyond levels expected to be found within a patient. Testing of assay precision, cross-reactivity and potential interfering substances, and biosimilars was performed. The Procise ADL assay was also compared head-to-head with another CE-marked assay: LISA-TRACKER adalimumab ELISA test (Theradiag, France). The accuracy of the Procise ADL assay is established through calibrators and controls traceable to the WHO 1st International Standard for Adalimumab (NIBSC code: 17/236).

Results
The Procise ADL assay shows a Limit of Blank, Limit of Detection, and Lower Limit of Quantitation (LLoQ) of 0.1, 0.2, and 0.6 µg/mL in serum and 0.5, 0.9, and 1.3 µg/mL in whole blood, respectively. The linear assay range was determined to be 1.3 to 51.5 µg/mL in serum and whole blood. No hook effect was observed at an ADL concentration of 200 µg/mL as the value reported as “&gt;ULoQ”. Assay precision testing across 10 days with multiple runs and reagent lots showed an intra-assay coefficient of variation (CV) of 2.8%, an inter-assay CV of ≤1.5%, and a total CV of 3.5%. The presence of potentially interfering/cross-reacting substances showed minimal impact on assay specificity with %bias within ±7.4% of control. Testing of biosimilars (adalimumab-atto and adalimumab-xxxx) showed good recovery. A good correlation to the Theradiag adalimumab ELISA was obtained for both serum (slope=0.94; r=0.99) and whole blood (slope=1.13; r=0.98) samples (Figure 1).

Conclusion
Results indicate that the Procise ADL assay is sensitive, specific, and precise yielding results within 5 minutes from both whole blood and serum without the operator needing to specify sample type. Additionally, it shows good correlation to a comparator assay that takes several hours and sample manipulation to yield results. This makes the Procise ADL assay ideal for obtaining fast and accurate ADL quantitation, thus allowing for immediate drug level dosing decisions to be made by the physician during patient treatment.
BIOLOGICS BEFORE SURGERY FOR IBD: ARE THEY ASSOCIATED WITH POST-OPERATIVE INFECTIOUS COMPLICATIONS? RESULTS FROM THE NATIONAL SURGICAL QUALITY IMPROVEMENT PROGRAM INFLAMMATORY BOWEL DISEASE COLLABORATIVE IN &gt;1500 PATIENTS
Authors: Holubar Stefan , Eisenstein Samuel , Bordeianou Liliana , Jia Xue , Hull Tracy , Hyman Neil , Lee Edward , Messaris Evangelos , Ramamoorthy Sonia , Saraidaridis Julia , Scow Jeffrey , Shaffer Virginia , Smith Radhika , Steinhagen Randolph 
Published: January 2021

Abstract

Background
We aimed to utilize the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Inflammatory Bowel Disease (IBD) Collaborative, which includes disease-specific variables, to assess the association between preoperative biologic exposure and post-operative infectious complications in the largest cohort reported to date.

Methods
Data was obtained from ten IBD centers from 2017 - 2018. Univariate and multivariate analyses were performed, with any biologic use within 60-days of surgery as the primary predictor, adjusting for diagnosis, chronic steroid use, immunomodulator (IMM) use, ostomy construction, anemia, malnutrition, operative length, emergency surgery, and other variables with p&lt;0.05 from the univariate analysis. The primary endpoint was any (composite) infectious complication, and the secondary endpoint was any (composite) surgical site infection.

Results
A total of 1,562 patients were included, of which 832 (53%) were not exposed to biologics, and 730 (47%) were exposed to biologics before surgery. The biologics group had more preoperative weight loss, lower albumin, more systemic sepsis, more IMM and steroid use, and more had Crohn’s disease (all p&lt;0.001). The biologics group were also more likely to receive a new ostomy and to have a colectomy (vs. proctectomy or small bowel procedure), and fewer had elective surgery (all p&lt;0.001). On univariate analysis (Table 1), compared with no biologic exposure, biologic exposure was not associated with any infectious complications, any surgical site infections, anastomotic leak after colectomy, or other post-operative outcomes, but was associated with increased rate of anastomotic leak after proctectomy (n=423), 6.7% vs. 1.9%, p=0.02. With respect to the primary and secondary outcomes, the results of the multivariate analyses are shown in Table 2. Biologics were shown not to be associated with any infectious complication (OR 0.88, 95%CI 0.54 – 1.42) or any surgical site infection (OR 0.77, 95% CI 0.46 – 1.28), while Crohn’s disease was associated with any infectious complications (OR 2.11 95% CI 1.12 – 4, p=0.02).

Conclusions
In the largest nationally representative retrospective cohort to date, we found that biologics exposure within 60-days of surgery for IBD, using well-validated methodology and after vigorous adjustment for disease- and surgery-specific covariates, was not associated with post-operative infectious or surgical site infectious complications.
Sverdrup meets Lambert: analytical solution for Sverdrup’s critical depth
Authors: Kovač Žarko , Platt Trevor , Sathyendranath Shubha 
Published: January 2021

AbstractIn his 1953 paper, Harald Sverdrup argued that the development of a spring bloom in the ocean depends on the juxtaposition of two depth horizons: the mixed-layer depth and the critical depth. Mixed-layer depth shallower than the critical depth favours phytoplankton growth in the layer and vice versa. However, mathematically, Sverdrup left the problem unsolved in the form of a transcendental equation. In spite of the high number of citations that this paper has garnered, the solution to this equation has not been found, until now. In this work, we present an analytical solution for the critical depth, as originally defined by Sverdrup. The paper opens with the definition of the critical depth and the description of the Lambert W function. The analytical solution for critical depth follows. Sverdrup’s original model is extended to include the effect of light attenuation by phytoplankton and the analytical solution for steady-state biomass in the mixed layer is derived. The expression for mixed-layer production at steady state is also presented. Two novel variants of the critical depth are defined: the optically uncoupled critical depth and the optically coupled critical depth. It is demonstrated that at steady state the optically coupled critical depth equals the mixed-layer depth and that the irradiance at the base of the mixed layer equals the irradiance at the optically uncoupled critical depth. Competitive exclusion is demonstrated to hold and the optically uncoupled critical depth is linked to the critical light intensity in multi-species competition. Finally, a conservation principle for the critical depth is found.
Professional regulatory entanglement: the curious case of project management in Italy
Authors: Sabini Luca , Paton Steve 
Published: January 2021

AbstractGrowth in the internationalization of economic activity has favoured an increase in institutional control at a supranational level. A typical example of such institutions that wield this control is corporate professions such as Project Management (PM). Attempting to replicate the successful strategies of the collegial professions but embracing advantages presented by global markets, corporate professions is confronted by the dilemma of how to reconcile the demands of stakeholders at both national and global levels. This research investigates an international corporate profession, PM, and its development within Italy using a historical case study. Results shows an increase in the number of regulations faced by international corporate professions as they attempt to satisfy a number of different institutions (and their competing agendas) while attempting to colonize a national context. This we define as ‘professional regulatory entanglement’. It concludes that what was once a simple bargain involving two actors, the state and the profession, with a long established, commonly agreed and mutually beneficial agenda is now a much more complex system involving multiple actors and a number of competing agendas and this results in the homogenization of professional practice across the globe.
The International Court of Justice
Authors: Simma Bruno 
Published: January 2021

Abstract
This chapter evaluates the International Court of Justice, which is one of the United Nation’s principal Charter bodies, and its principal judicial organ. As such, it hears cases brought by states against others and can render advisory opinions sought by certain organs of the UN and international organizations authorised to do so, both of which bear on a wide range of international legal issues. The ICJ is not specifically a human rights body, but its jurisprudence may have, indeed has had, an impact on international human rights law. The chapter then looks at the interpretation and application of human rights by the ICJ. It also assesses the linkage of the Court and human rights, identifying two phases in the engagement of the Court with human rights matters.
The Commission on the Status of Women
Authors: Kabasakal Arat Zehra F 
Published: January 2021

Abstract
This chapter describes the Commission on the Status of Women (CSW), which was the first international organ ever created to promote women’s rights and equality. The status of women has been on the agenda of the United Nations since its inception and typically addressed as an issue of discrimination in relation to human rights. As the UN’s work on human rights has evolved and expanded, so have its apparatuses and activities on the advancement of women’s rights and status. The CSW played a key role in drafting declarations and treaties that promote women’s rights, organizing world conferences on women, the development of other UN agencies that address women’s issues, and monitoring and evaluating the attention given to women by other agencies. The chapter examines and discusses the CSW’s operational structure, changing agenda, major accomplishments, the difficulties encountered by the Commission, and the controversies surrounding both its work and the UN approach to women’s issues.
The Human Rights Committee
Authors: Hennebel Ludovic 
Published: January 2021

Abstract
This chapter discusses the United Nations Human Rights Committee, which is in charge of the supervision of a major human rights treaty within the UN machinery, the International Covenant on Civil and Political Rights (ICCPR). This was adopted in 1966 and came into force in 1976. The Human Rights Committee enjoys a peculiar position in the international human rights architecture. It has been labelled ‘as one of the most active and innovative’ bodies among the UN institutions involved in human rights monitoring, considering that it is in charge of one of the two covenants which, together with the Universal Declaration, are sometimes presented as the ‘International Bill of Rights’ and covers the broadest subject-jurisdiction matter. At the same time, the Committee and its work remain overlooked and quite obscure even for most human rights lawyers and certainly for a lay audience. The chapter assesses the Committee’s mechanisms and work.
The Committee on Economic, Social and Cultural Rights
Authors: Alston Philip 
Published: January 2021

Abstract
This chapter evaluates the Committee on Economic, Social and Cultural Rights. The Committee has devoted, and seems likely to continue to devote, much of its energies to streamlining and refining procedures and to laying the foundations upon which a serious effort can be made to promote respect for economic, social and cultural rights. In many respects, the Committee has confronted problems which are common to all of the treaty bodies. In other respects, however, the challenges that confront it and the context in which it must work are significantly different from those of the other committees. Among the many factors that tend to distinguish its task are: the lack of conceptual clarity of many of the norms reflected in the Covenant on Economic, Social and Cultural Rights; the ambivalence of most governments towards economic, social and cultural rights; and the absence of national institutions specifically committed to the promotion of economic rights qua rights.
The High Commissioner for Human Rights
Authors: Clapham Andrew 
Published: January 2021

Abstract
This chapter discusses the Office of the United Nations High Commissioner for Human Rights. The High Commissioner’s Office is much more than the secretariat of the Human Rights Council and the other UN human rights bodies. The High Commissioner’s Office conducts fact-finding, engages with governments, develops policies for the UN system as a whole, monitors situations around the world, and the High Commissioner himself or herself often speaks out to condemn policies and practices. Inevitably this means suggesting a course of action for the member states and other parts of the UN system that those actors may be resistant to. The chapter then outlines the development of the Office and highlights some of the achievements while pointing to the obstacles that any High Commissioner has to overcome.
Human Rights Co-Ordination Within the UN System
Authors: Minet Georges 
Published: January 2021

Abstract
This concluding chapter looks at human rights co-ordination within the UN system. For a long time, human rights in the United Nations tended to be treated as a special domain, one which might be of growing importance, but which did not necessarily need to be a consistent focus of the entire UN machinery. The importance of co-ordination and coherence for human rights promotion, however, has steadily become clearer, as the perception has grown that the human rights ‘issue area’ cannot be successfully dealt with in a vacuum or in isolation. The focus here, accordingly, is on the relationship of human rights to various relevant parts of the UN system—‘inter-regime’ co-ordination—rather than on co-ordination among human rights activities undertaken by the various members of the UN family of institutions—‘intra-regime’ co-ordination. It is the former aspect of co-ordination that has proved to be most problematic and had achieved the least progress until the recent period.