bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATIENT DECISION MAKING ABOUT UTILIZATION OF TREATMENT AND MANAGEMENT METHODS: TOWARD ENHANCED PROMOTION OF PREVENTIVE SELF-MANAGEMENT FOR ULCERATIVE COLITIS
Authors: DuBois Kelli , Blake Christine , Rudisill Caroline , Harrison Sayward , Hebert James 
Published: January 2024

Abstract

BACKGROUND
Living with Ulcerative Colitis (UC) is accompanied by physical and psychosocial burdens that significantly detract from quality of life. To accommodate, individuals employ multiple treatment and management methods to mitigate gastrointestinal (GI) disease symptoms, reduce pharmaceutical dependence, and respond to the daily challenges of living with UC. This study examines why and how patients choose to utilize treatment and management methods, with emphasis on patient perspectives and experiences.

METHODS
Adults living with UC for at least 5 years, who had experienced at least one disease flare, were recruited to participate in individual, semi-structured qualitative interviews (N=21). Verbatim transcripts were thematically analyzed using emergent coding with Nvivo12®.

RESULTS
Decision making about the use of treatment and management methods was shaped by participants’ sources of information, attitudes toward self-management, and personal motivations. Participants rarely expressed feelings of personal responsibility for the unpredictable course of illness. However, some believed that they could, to varying degrees, take charge of their UC experience. A few individuals described an active approach to managing their illness through self-adjusting treatment methods, health behavior change, and self-advocacy towards satisfaction with treatment options and enhanced patient-provider communication. The poor quality of life associated with the daily burden of living with UC emerged as a primary motive for exploration and utilization of treatment and management methods. Participants drew conclusions about diet’s impact on disease activity by observation of immediate GI symptoms. While most patients aimed to mitigate UC symptoms by taking medications, reducing stress, and avoiding perceived ‘trigger’ foods, participants reported primarily utilizing treatment and management methods as reactive responses to flares instead of as preventive measures against disease activity and disease progression.

DISCUSSION
Results provide insight into patient decision making and may inform individualized patient care, improve patient-provider communication, and guide interdisciplinary efforts to support self-management among patients with UC. Findings highlight a need for greater focus on promoting preventive self-management lifestyle behaviors to protect against disease activity and progressive impairment. This research supports the promotion of disease prevention and self-management both inside and outside of the clinical setting.
YOUTUBE AND INFLAMMATORY BOWEL DISEASE, A 10-YEAR UPDATE
Authors: Jain Varun , Gilman Christy Ann , Figueroa Esteban 
Published: January 2024

Abstract

INTRODUCTION
As the prevalence of inflammatory bowel disease (IBD) continues to rise, patients are turning to social media, notably YouTube®, for IBD information. This content has transformed since Mukewar et. al’s 2013 analysis of the top YouTube® videos about IBD. Furthermore, patient-desired information is now better understood, including 1) IBD treatment pros and cons, 2) self-advocacy, 3) IBD health tips, 4) IBD coping strategies, and 5) education on patient experiences. We analyzed YouTube® IBD videos to assess their informational quality and ability to address patient-desired attributes.

METHODS
Using the query “inflammatory bowel disease OR IBD,” we reviewed the top 50 English YouTube® IBD videos under 20 minutes. We gathered video metadata and assessed informational quality using the Patient Educational Video Score for Inflammatory Bowel Disease (PEVIS-IBD score) designed by Mukewar et al. with disease and treatment advancement updates. Possible scores ranged from 0 to 28. Patient-desired attribute count was noted per video. One-way ANOVA was done to test statistical significance.

RESULTS
49/50 videos remain accessible. 35% focus on Crohn’s Disease, 30% on Ulcerative Colitis, and 35% on both. Most videos were MD/RN education (17, 35%), patient stories (14, 29%), and hospital/physician-produced IBD explainers (11, 22%). Only 18 (37%) had YouTube® Health Source Accreditation.
MD/RN education videos ranked highest on PEVIS-IBD (13.47). Patient stories ranked lowest (7.57). 24/49 discussed at least one patient-desired attribute, with half of these covering three or more. MD/RN education videos did not address any attributes. Figure 1 shows detailed information about each category of video.

DISCUSSION
Our study shows a shift in IBD YouTube videos, with ⅓ of the top 50 videos being MD/RN education, a previously undescribed segment. Despite high PEVIS-IBD scores reflecting high-quality factual content, all of these videos lack patient-desired attributes, signaling a need for research to ascertain their value to patients.
Of the patient-centric videos (32, excluding MD/RN education), 75% discussed at least one desired attribute, with half discussing 3 or more. Patient story videos had the highest attribute count, but low PEVIS-IBD scores, highlighting an opportunity for videos that simultaneously feature patient stories and facts about IBD.
Only 37% of videos had YouTube® Health Source Accreditation, with videos from reputable organizations like the Crohn's and Colitis Foundation lacking this tag. Medical societies should be aware of this feature and ensure their channels are properly accredited.

Figure 1 Analysis of key video metadata by category.

Reference
Mukewar S, et al. YouTube and inflammatory bowel disease. J Crohns Colitis. 2013;7(5):392-402.
MICROBIAL REPRESENTATION ASSOCIATION WITH LEVEL OF SHORT CHAIN FATTY ACIDS IN SMALL BOWEL
Authors: Xu Linda , Yang Fan , Riethoven Jean-Jack , Izard Jacques 
Published: January 2024

Abstract

BACKGROUND
Small bowel microbiome and associated postbiotics understanding is still in its infancy.
In intestinal bowel disease treatment, surgical interventions leading to an ostomy are often the last resort. The ileostomates and the colostomates lack the whole or part of the colonic function, respectively. In these populations, fecal effluents represent aspects of the small bowel microbial communities and associated small molecules not available in traditional stool collections.

METHODS
We completed a cross-sectional collection of samples from participants with digestive resections were recruited including 26 ileostomates and 23 colostomates. Additionally, 22 individuals with unaltered digestive tracts were enrolled for a total of 71 participants. Stool were self-collected in transport and storage medium. Identification and quantitation of short chain fatty acids were performed using LC MS/MS equipped with a C18 reversed phase UHPLC column. Concentrations for acetic, propionic, butyric, isobutyric, valeric, 2-methylbutyric, isovaleric, and hexanoic acid were obtained. Analysis of covariance (ANCOVA) was used to evaluate the difference in the mean SCFA concentration across the groups. Microbial membership identification was performed using 16 rDNA sequencing for a subset of 59 samples. A table of amplicon sequence variants (ASV) counts per sample was derived using the dada2 R package. Kruskal-Wallis and Post-hoc test Dunn with Benjamini-Hochberg multiple test correction were used to compare the abundance of bacteria producing and utilizing specific short chain fatty acids between the three groups.

RESULTS
For the eight measured short chain fatty acids, all were significantly decreased in ileostomates compared to colostomates and control group (p &lt; 0.001). We observed significant positive correlations between microbial metabolite producers and corresponding metabolites for propionic acid, butyric acid, isobutyric acid, and isovaleric acid. For example, at the level of the population, a positive correlation was found between the abundance of butyric acid microbial producers and the butyric acid level (R=0.5, p = 7.3e-05). Conversely, a significant negative correlation between levels of acetate producers and fecal acetic acid was found in the whole population.

CONCLUSION
The presence of a partial colon, in colostomate, did not drastically alter the detection of the different short chain fatty acids compared to the individuals with an intact colon. In contrast the absence of a colon was associated with a significant drop in level of detected postbiotics. These findings underline the biogeographical distribution of both the microbiome and small molecules along the digestive tract.
DIFFERENTIAL MORTALITY OUTCOMES AMONG DIFFERENT CLASSES OF DRUGS IN ELDERLY PATIENTS WITH ULCERATIVE COLITIS USING A MULTI-CENTER RESEARCH NETWORK
Authors: Chaaban Lara , Giorgianni Francesca , Melia Joanna 
Published: January 2024

Abstract

BACKGROUND
Several medical therapies exist for ulcerative colitis (UC) including 5-aminosalicylates (5-ASAs), immunomodulators (IMM), biologics and Janus Kinase (JAK) inhibitors that aim to induce and sustain both clinical and endoscopic remission of UC. Selection of treatment is dictated by disease severity and patient characteristics and preference. Long-term differences in mortality risk among these therapies is unknown. The aim of this study is to compare 10-year mortality among older adult UC patients exposed to different treatment regimens.

METHODS
Using TriNetX, a multicenter research database, elderly patients with UC who are 65 years or older were identified using ICD-10 code for ulcerative colitis(K51) on the Research Network, accessed on September 26th, 2023. Cohorts were subdivided according to exclusive different lines of therapy as shown in table 1: 5-ASAs, IMM, Biologics, and JAK inhibitors. Advanced therapy included the latter three classes of drugs whereas simple therapy included 5-ASA agents. Comparison of 10-year mortality profiles was done for advanced therapy and each different therapeutic class in reference to simple therapy (5-ASAs). Analyses were performed on a built-in statistical software on TriNetX.

RESULTS
When comparing advanced therapy to simple amino-salicylate-based therapies, elderly patients demonstrated higher 10-year mortality with advanced therapy (13.5% vs 12.4%, OR=1.10, 95 % CI [1.13,1.29], p=0.017) as shown in table 2. When breaking down the classes of advanced therapies, immunomodulators had the highest risk of mortality as compared to simple therapy ( 19.1% vs 12.4%, 1.67 95%CI [1.52, 1.84], p&lt;0.0001). However, biologic therapies had a lower mortality risk when compared to simple therapy (9.3% vs 12.4%, OR=0.73, 95% CI [0.64, 0.83], p&lt;0.0001). Further data are needed to assess the mortality risk of JAK inhibitors as they were recently approved for ulcerative colitis and 10-year mortality risk could not be examined.

CONCLUSION
Among the different drug classes, immunomodulators were significantly associated with higher 10-year mortality risk compared to simple therapy whereas biologic therapies had the lowest mortality risk.

Table 1 Lines of Therapy

Table 2 Characteristics and Mortality Outcome of Patients on Different Lines of Therapy
SAFETY OF ANTI-TUMOR NECROSIS FACTOR AGENTS COMPARED TO USTEKINUMAB AND VEDOLIZUMAB IN ELDERLY PATIENTS WITH ULCERATIVE COLITIS
Authors: Chaaban Lara , Huang Jane , Melia Joanna 
Published: January 2024

Abstract

BACKGROUND
Common first-line treatments for ulcerative colitis (UC) currently include anti-tumor necrosis factor (anti-TNF) agents, ustekinumab (interleukin-12/interleukin-23 receptor antagonist), and vedolizumab (integrin antagonist). However, there are safety concerns when prescribing biologic therapies to elderly patients. While these medications have all demonstrated general efficacy and safety in UC, this study aims to examine the long-term comparative safety of anti-TNF agents with vedolizumab and ustekinumab in elderly patients with UC.

METHODS
The Research Network on TriNetX database was accessed on September 26, 2023, to identify patients at least 65 old who were diagnosed with UC: the first cohort included patients prescribed anti-TNF agents (included adalimumab, certolizumab pegol, golimumab, and infliximab) and the second cohort included patients prescribed either vedolizumab or ustekinumab. Primary outcomes included mortality, corticosteroid use, subsequent colectomy, colon cancer, infections, and all-cause hospitalizations within 10 years after matching for age, sex, and race. All analyses were performed in real-time using built-in statistical algorithms on TriNetX.

RESULTS
After matching cohorts, 1,075 elderly patients with UC patients were included in each cohort as shown in table 1. Patients who were prescribed anti-TNF therapy had a significantly increased 10-year risk of mortality (10.7%) compared to patients on either vedolizumab or ustekinumab therapy (5.77%) (OR 1.96, 95% CI [1.42, 2.7], p &lt;0.0001). Corticosteroid use was higher in the anti-TNF cohort (40.6% vs 34.9%, p= 0.007). There were no significant differences between the two cohorts when comparing the need for colectomy (3.26% vs 2.23%, p = 0.15) or colorectal cancer occurrence (1.67% vs 2.05%, p=0.52) within 10 years. However, the anti-TNF cohort had a higher risk of all-cause hospitalization (32.5 % vs 22%, p=&lt;0.0001), respiratory tract infections (18.4% vs 14.5%, p=0.015), and urinary tract infections (10.4% vs 7%, p=0.005).

CONCLUSION
In elderly patients with UC, ustekinumab or vedolizumab are safer treatment options compared to anti-TNF therapy.

Table 1 Demographics and Comparative 10-year Outcomes of Elderly Patients with UC.
REAL-WORLD RATE AND MAGNITUDE OF DOSE ESCALATION WITH BIOLOGICS IN PATIENTS WITH CROHN’S DISEASE
Authors: Gorritz Magdaliz , Tuly Rifat , Sun Kainan , Creveling Thomas , Moses Richard , Fisher Deborah , Bires Nicholas , Chan Wai Man Maria , Johnson Nate , Hull Michael , Upadhyay Navneet 
Published: January 2024

Abstract

INTRODUCTION
Advanced therapies (ATs), such as adalimumab (ADA), infliximab (INF), vedolizumab (VED), and ustekinumab (UST), referred to as biologics, are regularly used to treat moderate-to-severe Crohn’s disease (CD). Loss of response is a common problem with biologics in CD and one solution is to increase dose of biologics, affecting the cost of CD management. Assessing real-world dosing with biologics is important to inform the estimated treatment cost. The objective of this study was to assess the rate and magnitude of dose escalation with biologics in treatment of CD.

METHODS
This retrospective cohort study identified adult American patients in the IQVIA PharMetrics® Plus database who were diagnosed with CD and started an AT for CD between 01 Jan 2015 and 31 May 2021. Index date was the start date of a qualifying AT. Patients had ≥12 months of continuous pre- and post-index enrollment in a health plan, no claims for AT during the pre-index period, and no autoimmune diseases or indeterminate colitis. Rate and magnitude of dose escalation were assessed from the start of maintenance phase with AT until the end of follow-up period. Dose escalation was measured in first-line (1L) and second-line (2L) settings and defined as an increase in average dose ≥20% than expected dosing per FDA label during follow-up period after maintenance dose was reached. Dose escalations of ≥50% and ≥100% were also measured.

RESULTS
The study identified 7,353 CD patients starting an AT (1L setting) (median age, 38 years; 51.4% female; median follow-up, 28.5 [18.6-43.0] months), and 1,608 (21.9%) patients who received treatment with AT in a 2L setting. More patients reached maintenance dose in a 1L setting (89.4% [INF] to 93.8% [ADA]) than in a 2L setting (77.4% [INF] to 90.3% [UST]). The rate of dose escalation in patients who reached maintenance dose was 21.1% [ADA], 19.2% [IFX], 29.3% [VED], 49.5% [UST] in a 1L setting, vs 23.8% [ADA], 21.9% [IFX], 25.1% [VED], 52.0% [UST], respectively, in a 2L setting (Figure 1). The frequency of dose escalation ≥50% varied for different therapies, 13.8% [ADA], 6.1% [IFX], 19.1% [VED], and 40.0% [UST] in a 1L setting vs 15.3% [ADA], 9.0% [IFX], 17.6% [VED], and 42.3% [UST] in a 2L setting (Figure 2). Dose escalation ≥100% was uncommon with both 1L therapies (0.6% [ADA] to 10.1% [VED]) and 2L therapies (0% [ADA] to 7.7% [VED]).

CONCLUSIONS
A meaningful percentage of Crohn’s disease patients treated with adalimumab, infliximab, vedolizumab, or ustekinumab had dose escalation regardless of line of treatment. Understanding the impact of these utilization patterns may inform real-world cost management.

Figure 1 Rate of dose escalation with advanced therapies in Crohn’s disease

Figure 2 Magnitude of dose escalation with advanced therapies in Crohn’s disease
Host Transcriptional Meta-signatures Reveal Diagnostic Biomarkers for Plasmodium falciparum Malaria
Authors: Silva Nágila Isleide , Souza Pedro Felipe Loyola , Silva Bárbara Fernandes , Fonseca Simone Gonçalves , Gardinassi Luiz Gustavo 
Published: January 2024

Abstract

Background
Transcriptomics has been used to evaluate immune responses during malaria in diverse cohorts worldwide. However, the high heterogeneity of cohorts and poor generalization of transcriptional signatures reported in each study limit their potential clinical applications.

Methods
We compiled 28 public data sets containing 1556 whole-blood or peripheral blood mononuclear cell transcriptome samples. We estimated effect sizes with Hedge's g value and the DerSimonian-Laird random-effects model for meta-analyses of uncomplicated malaria. Random forest models identified gene signatures that discriminate malaria from bacterial infections or malaria severity. Parasitological, hematological, immunological, and metabolomics data were used for validation.

Results
We identified 3 gene signatures: the uncomplicated Malaria Meta-Signature, which discriminates Plasmodium falciparum malaria from uninfected controls; the Malaria or Bacteria Signature, which distinguishes malaria from sepsis and enteric fever; and the cerebral Malaria Meta-Signature, which characterizes individuals with cerebral malaria. These signatures correlate with clinical hallmark features of malaria. Blood transcription modules indicate immune regulation by glucocorticoids, whereas cell development and adhesion are associated with cerebral malaria.

Conclusions
Transcriptional meta-signatures reflecting immune cell responses provide potential biomarkers for translational innovation and suggest critical roles for metabolic regulators of inflammation during malaria.
Trading Sovereignty for Self-Determination
Authors: Beall Katherine M 
Published: January 2024

Abstract
Weak or dependent states, especially those with histories of colonial and imperial domination, have traditionally been among the strongest advocates for strict institutionalization and observance of the norm of non-interference. These states are vulnerable to international pressure, and they have sought to limit this pressure by “jealously” guarding their sovereignty. Yet, after decades of advocating for strict non-interference, many have begun to delegate extensive interventionist authority to their regional organizations. What explains this change? I explore this question in the case of the decision by Latin American leaders to compromise on non-interference by delegating authority to enforce human rights to the Organization of American States. I argue that they were motivated by attempts to maintain self-determination and resist the imposition of authority. In making this argument, I extend the definition of self-determination to incorporate self-determination over international rules. I show that existing explanations for this development that emphasize norm diffusion or democratization cannot account for important dynamics. These findings offer evidence that the expansion of regionalism in the Global South has been, in part, a subtle strategy to mitigate the undesirable effects of hierarchy and to create an international system based on respect for self-determination.
A novel glycine-rich peptide fromZophobas atratus, coleoptericin B, targets bacterial membrane and protects againstKlebsiella pneumoniae-induced mastitis in mice
Authors: Wang Xue , Li Shuxian , Du Mengze , Liu Ning , Shan Qiang , Zou Yunjing , Wang Jiufeng , Zhu Yaohong 
Published: January 2024

AbstractObjectivesThe growing occurrence of bacterial resistance has spawned the development of novel antimicrobial agents. Antimicrobial peptides, a class of small molecules with antimicrobial activity, have been regarded as the ideal alternatives to antibiotics.MethodsIn this study, we amplified a new type of Zophobas atratus coleoptericin (denoted coleoptericin B) through rapid amplification of cDNA ends (RACE) PCR and expressed recombinant Z. atratus coleoptericin B (rZA-col B) by prokaryotic expression. Subsequently, we evaluated the antimicrobial effect and biocompatibility of rZA-col B in vivo, investigated its antimicrobial mechanism, and assessed its therapeutic effect in a murine model of mastitis caused by MDR Klebsiella pneumoniae.ResultsThe in vivo studies demonstrated that rZA-col B possesses broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. It exhibited less than 1.5% haemolysis and 10% cytotoxicity, even at a concentration of 128 μM. Additionally, rZA-col B had a minimal risk of inducing drug resistance. Furthermore, rZA-col B could disrupt the integrity of bacterial membranes, induce membrane permeabilization and ultimately lead to bacterial death. Importantly, rZA-col B also alleviated mastitis caused by MDR K. pneumoniae in a murine model by enhancing bacterial clearance, reducing neutrophil infiltration, decreasing TNF-α and IL-1β expression, and protecting the mammary barrier.ConclusionsrZA-col B may be a promising antibacterial agent to combat MDR bacterial infection.
Improving reporting standards for phenotyping algorithm in biomedical research: 5 fundamental dimensions
Authors: Wei Wei-Qi , Rowley Robb , Wood Angela , MacArthur Jacqueline , Embi Peter J , Denaxas Spiros 
Published: January 2024

Abstract

Introduction
Phenotyping algorithms enable the interpretation of complex health data and definition of clinically relevant phenotypes; they have become crucial in biomedical research. However, the lack of standardization and transparency inhibits the cross-comparison of findings among different studies, limits large scale meta-analyses, confuses the research community, and prevents the reuse of algorithms, which results in duplication of efforts and the waste of valuable resources.

Recommendations
Here, we propose five independent fundamental dimensions of phenotyping algorithms—complexity, performance, efficiency, implementability, and maintenance—through which researchers can describe, measure, and deploy any algorithms efficiently and effectively. These dimensions must be considered in the context of explicit use cases and transparent methods to ensure that they do not reflect unexpected biases or exacerbate inequities.