bluuebunny/crossref_metadata_2025_split huggingface dataset:
MACHINE LEARNING-BASED PREDICTION OF GEBOES SCORE AND HISTOLOGIC IMPROVEMENT AND REMISSION THRESHOLDS IN ULCERATIVE COLITIS
Authors: Shanis Zahil , Padigela Harshith , Sucipto Kathleen , Shamshoian John , Li Jin , Walker Andrew , Fahy Darren , Lin Mary , Montalto Mike , Beck Andrew , Mehta Jimish , Wapinski Ilan , Khosla Archit , Pokkalla Harsha , Najdawi Fedaa , Jayson Christina 
Published: January 2023

Abstract

BACKGROUND
Histology is emerging as a key therapeutic endpoint for ulcerative colitis driven by associations between histologic response and long-term outcomes. However, existing scoring systems are subjective and consequently have variable inter- and intra-reader variability. Geboes scoring is a well-established system for ulcerative colitis histologic assessment that has previously been used to define thresholds for histo-endoscopic mucosal improvement (Geboes Score ≤3.1, together with Mayo score 0 or 1) and histologic remission (Geboes Score &lt;2). Here we report the first machine learning (ML)-based prediction of the Geboes Score, and Geboes Score-derived thresholds of histologic improvement and remission, directly from whole slide images (WSI) of hematoxylin and eosin (H&E)-stained mucosal biopsies.

METHODS
3,148 WSI were scored by three expert gastrointestinal pathologists and the median consensus score was used to determine the Geboes score for each slide as ground truth. ML models were trained on median consensus scores to predict the Geboes score and subscores for each slide. Model performance vs. pathologist median consensus score was measured using accuracy and the F1 score, which accounts for both false positive and false negative errors.

RESULTS
The ML-based model performance, measured against median consensus scores of three pathologists, showed strong performance at predicting overall Geboes Score, with a quadratic kappa of 0.89. The model was also able to predict both histologic improvement and histologic remission with high accuracy. For predicting histological improvement as defined by a Geboes Score of ≤3.1, the model showed accuracy of 0.92 and F1 score of 0.92 (Figure 1). For predicting histological remission as defined by a Geboes Score of &lt; 2, the model showed accuracy of 0.91 and F1 score of 0.89 (Figure 2).

CONCLUSIONS
We report a ML-based approach for predicting Geboes score and Geboes score-based key thresholds of histologic improvement and histologic remission. Model predictions show high accuracy compared to median consensus pathologist scores. This approach may enable standardized, reproducible and accurate prediction of these clinically relevant thresholds to better measure histologic disease activity and treatment response in clinical trials.
METHODS TO DERIVE A CROHN'S DISEASE ACTIVITY INDEX FROM ELECTRONIC HEALTH RECORDS DATA
Authors: Swenson Anna , Womack Katherine , Quinn Meaghan , Curhan Gary 
Published: January 2023

Abstract

BACKGROUND
The Crohn’s Disease Activity Index (CDAI) is currently the gold-standard for measuring disease activity in Crohn’s disease (CD) patients. It is the most commonly used outcome measure in clinical trials, however, due to the burden of completion, it is infrequently used in routine care. Real world data, including electronic health records (EHR), are useful for studying longitudinal disease and treatment outcomes in the real world, but most EHR databases do not include CDAI. Building off the methods presented by Rudrapatna et al. 2021, we calculated a derived CDAI using data elements available in EHRs.

METHODS
Data were derived from the OM1 PremiOM UC Dataset (OM1, Boston, MA), a multisource real-world database with linked healthcare claims and EHR data on US patients with CD (2013-present). Weight, body temperature and hematocrit were sourced from structured vital signs and laboratory data. Ideal body weight was calculated from height and gender using the Devine formula. Extraintestinal manifestations/complications were evaluated based on the presence or absence of ICD diagnosis codes for each condition. Abdominal mass was abstracted from clinical notes. Number of stools in the past 7 days, average daily abdominal pain, and general well being were extrapolated from single-day measures extracted from clinical notes rather than based on 7-day diaries. Each component value was multiplied by the weights outlined in Best et al. 1976. Components recorded within 4 months were added to calculate a derived CDAI. Multiple CDAIs could be calculated for each patient over time, but each component was allowed to contribute to only one CDAI score.

RESULTS
Among 13,159 CD patients, only 12 had a CDAI recorded in their notes. After applying the algorithm, we were able to calculate a derived CDAI for 1,378 patients. 489 patients had &gt; 1 score derived. Figure 1 shows the distribution of derived CDAIs. Patients with a derived CDAI were younger and a higher proportion were treated with biologics and corticosteroids than those who could not have a CDAI calculated (Table 1).

CONCLUSIONS
A derived CDAI can be calculated from data that may be routinely recorded in EHRs. Efforts to standardize the collection of CDAI components in EHRs would further increase the availability of derived CDAIs. Further work to validate these derived scores against a gold standard and to replicate the findings in other real-world datasets should be considered. Validation was not feasible in this dataset due to the lack of recorded CDAIs. Derived CDAIs could potentially be used to study longitudinal changes in disease status and treatment effectiveness in settings where observed CDAIs are unavailable.
ILEOSTOMY AND RISK OF ACUTE KIDNEY INJURY IN PATIENTS WITH CROHN'S DISEASE
Authors: Abomhya Ahmed , Ayaz Salman , Haider Salman 
Published: January 2023

Abstract

BACKGROUND
Chron's disease is an inflammatory disorder that can involve any part of GI tract but most commonly involves the small intestine. Many of the patients with Cohn’s disease end up requiring surgery, and the 10-year risk of requiring surgery is estimated to be around 50%. The most common type of surgery in patients with Crohn’s disease is ileocecal resection. More than 40,000 ileostomies are formed annually in the United States. Up to 15% of patients who receive ileostomy experience a de novo or community-onset AKI within 90 days. Oral rehydration with iso-osmolar fluids is the mainstay of outpatient management. Both hypotonic fluids, and hypertonic fluids can cause a net flow of fluid into the bowel lumen increasing the ostomy output. We aimed to study the risk of AKI within 30 days in CD patients after an ileostomy procedure.

METHODS
We collected data from the Healthcare Cost and Utilization Project- (HCUP) Nationwide Readmission Database- 2016- 2018. CD patients were identified and those who received an ileostomy procedure were identified using ICD-10 and PCS-10 codes respectively. Median and IQR were used to describe Continuous variables, and proportions were used with categorical variables. Comparison between groups was performed by Mann Whitney test for continuous variables and the Chi-Square test for Categorical variables.

RESULTS
We identified 214,622 index hospitalizations with CD, 3,789 of whom received an ileostomy procedure. Of those who received ileostomy, 2.1% were readmitted within 30 days for a primary diagnosis of AKI while 2.9% had 30-day readmission with a secondary diagnosis of AKI. CD patients admitted for AKI after ileostomy had a median length of stay of 14 days (IQR: 8-24). CD patients who received ileostomy had a higher rate of 30-day admission for AKI (2.1% vs. 0.3%, P &lt;0.001) and a higher rate of 30-day readmission with a secondary diagnosis of AKI (2.9% vs. 1.5%, P &lt;0.001) compared to CD patients who didn’t receive ileostomy during the index hospitalization. CD patients who received an ileostomy procedure and were readmitted for AKI within 30 days had an average cost of hospitalization of $140,544 (IQR: $85,072 - $242,059). CD patients admitted for AKI within 30 days after an ileostomy were older (59, IQR: 48-69 vs. 47, IQR: 33-61, P &lt;0.001) compared to those who didn’t have a 30day readmission for AKI respectively.

CONCLUSION
In a nationwide cohort of patients hospitalized with Crohn’s disease, patients who received ileostomy had a significant risk of AKI within 30-days. The development of AKI was associated with significant morbidity, hospital readmission, and elevated costs of hospitalization. Further studies are needed to investigate novel measures to decrease the risk of AKI in this patient population.
PREDICTORS OF DEVELOPING MULTIPLE EXTRA-INTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE
Authors: Alizadeh Madeline , Motwani Kiran , Cross Raymond 
Published: January 2023

Abstract
Extraintestinal Manifestations (EIMs) of Inflammatory Bowel Diseases (IBD) are a frequent feature of disease, occurring in 25-40% of patients with IBD. While associations with IBD type, gender, and age at diagnosis are known, less is known about the associations between different EIMs and which patients are most likely to develop more than 1 EIM. The goal of our study was to better characterize which patients may be at higher risk of developing multiple EIMs.
METHODS: A retrospective review of patients enrolled in the Study of Prospective Adult Research Cohort with IBD (SPARC IBD) registry was performed and demographics, clinical data, and patient-reported outcomes were analyzed. A total of 1,202 patients with data available on EIMs were included, where EIMs included IBD-associated arthropathy, ocular complications including uveitis/iritis, primary sclerosing cholangitis, erythema nodosum, pyoderma gangrenosum, and thrombotic complications. Welch’s t-test and Fisher’s exact test were used to assess differences among continuous and categorical variables between those with versus without EIMs, as well as for comparisons between individual EIM groups.
RESULTS: Three hundred forty-seven patients with at least 1 EIM were identified, compared to 855 patients without any EIMs. Two hundred eight four patients were identified as having 1 EIM, 54 patients had 2 EIMs, and 9 patients had 3 EIMs. Patients with Crohn’s disease and women were more likely to have 2 or more EIMs (p-value = 0.00517 and 0.000285, respectively). Patients with ocular manifestations were likeliest to have at least 2 EIMs (with 27/37 or 73.0% having multiple), while those with pyoderma gangrenosum and IBD associated arthritis were least likely to have additional EIMs (p-value = 0.000500). Further, no patients with PSC developed pyoderma gangrenosum (Fisher’s multiple comparison p-value = 0.00187). Most patients with 3 EIMs had IBD-associated arthritis and/or erythema nodosum (88% having each), while only 1 patient (11%) with 3 EIMs had PSC (p-value = 0.00161).
CONCLUSION: Women and patients with Crohn’s disease are more likely to develop multiple EIMs and patients with ocular EIMs are more likely to have another EIM. Understanding how individual EIMs relate to one another can be used to better identify patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.
SEPSIS IN THE SETTINGS OF INFLAMMATORY BOWEL DISEASE: STUDYING THE OUTCOMES OF OVER EIGHT-MILLION PATIENTS
Authors: Aldiabat Mohammad , Kilani Yassine , Aljabiri Yazan , Al-bashabsheh Abdel-qader 
Published: January 2023

Abstract

BACKGROUND
Inflammatory bowel disease (IBD) is associated with increased risk of infections, attributed to the nature of the disease itself, and the use of immunosuppressive agents in these patients as well. However, the impact of IBD on patients with sepsis is poorly studied. In this analysis, authors aim to investigate the outcomes of sepsis in patients with IBD.

METHODS
This is an analysis of the National Inpatient Sample Database of the years 2016 to 2019. Using ICD-10 codes, authors identified patients who were admitted with a principal diagnosis of sepsis and those with history of Crohn’s disease (CD) and ulcerative colitis (UC). Primary outcome was mortality difference AND risk of sepsis-related complications. Secondary outcomes included length of stay and charge of care. Multivariate logistic analysis was performed using Stata/BE 17.0. Baseline patients and facilities characteristics were incorporated into the analysis. Data was considered statistically significant if p-value was &lt;0.05.

RESULTS
Among a total number of 8,403,578 patients who were admitted for sepsis and included in the study, 61390 (0.73%) and 47504 (0.56%) had a history of CD and UC, respectively. When compared to general population, adjusted odds ratio for mortality were lower in patients with CD than in UC (OR 1.01, p&lt;0.001, 95% CI 0.74 – 0.87 vs OR 0.81, p=0.758, 95% CI 0.93 – 1.09). Increased risk of septic shock observed in UC-sepsis group more than in CD-sepsis group (OR 1.28, p&lt;0.001, 95% CI 1.21 – 1.34 vs OR 1.08, p=0.001, 95% CI 1.03 – 1.13), acute kidney injury (UC OR 1.18, p&lt;0.001, 95% CI 1.13 – 1.23, CD OR 1.11, p&lt;0.001, 95% CI 1.06 – 1.15) and non-variceal upper GI bleeding (UC OR 1.64, 95% CI 1.50 – 1.79, p&lt;0.001vs CD OR 1.15, 95% CI 1.04 – 1.27, p=0.004). Both groups had prolonged length of stay, more prolonged with UC (UC Coefficient 1.04 days, 95% CI 0.85 – 1.24, p&lt;0.001, vs CD Coefficient 0.67, 95% CI 0.51 – 0.82, p&lt;0.001) and in charge of care (UC Coefficient 13505$, 95% CI 10561 – 16449, p&lt;0.001 vs CD Coefficient 5855$, 95% CI 3251 – 8189, p&lt;0.001) when compared to admitted sepsis patients without prior history of IBD.

CONCLUSION
Patient admitted with sepsis have worse outcomes in the settings of inflammatory bowel diseases, represented by higher risk septic shock, acute kidney injury, non-variceal upper GI bleeding, prolonged length of stay and increased charge of care. These outcomes noticed to be more severe in sepsis patients with ulcerative colitis than those with Crohn’s disease. Clinicians and intensivist should be aware of the high risk associated with inflammatory bowel disease in sepsis patients, especially in those with ulcerative colitis.
DEMOCRATIC DELIBERATION TO ASSESS VETERAN PREFERENCES FOR BIOSIMILAR MEDICATION SWITCHING FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE IN A RESOURCE CONSCIOUS SETTING
Authors: Ryan Kerry , Hou Jason , Baker Jessica , Krenz Christopher , Waljee Akbar , De Vries Raymond 
Published: January 2023

Abstract

BACKGROUND
To optimize care while being resource conscious, the Veterans Health Administration (VHA) must develop equitable policies that incorporate Veterans’ values and beliefs. Switching patients with Inflammatory Bowel Disease (IBD) from biologic medications (originators) to less expensive biosimilars offers the opportunity to explore potential policies. Unlike originators, the FDA did not require disease-specific randomized controlled trials for approval of biosimilars, creating provider and patient concerns about the safety of switching to these medications. Deliberative democratic (DD) methods allow us to assess Veteran views of switching programs, a necessary step in creating equitable policy approaches.

METHODS
We carried out two 2-day sessions with Veterans from the Ann Arbor VA (n=17) and Houston VA (n=12). Deliberation began with education about IBD, use of biologics (including biosimilars), and related implementation challenges. Participants engaged in facilitated small group discussions designed to 1) identify Veterans views about biosimilar switching and their preferences for informing Veterans about switching, and 2) evaluate responses to five approaches for switching: (a) “status quo”–switching policies vary by VHA facility, (b) “sickest last”–Veterans with the most severe IBD are switched last, (c) “opt-out”–Veterans may opt-out of switching, (d) “next appointment”–Veterans are switched at their next appointment, and (e) “lottery”–patients are switched based on random selection. Participants ranked options (1=most preferred, 5=least preferred) and proposed modifications to these approaches. Participants completed pre- and post-DD session surveys. Discussion transcripts were analyzed using qualitative methods.

RESULTS
Participant demographics are in Table 1. Most Veterans sessions preferred the “sickest last” (mean rank: 1.8, standard deviation: 0.9) or “opt-out” (2.4,1.4) approaches over the “status quo” (3.1,1.0) or “lottery” (4.6,0.9); preferences did not significantly change after deliberation (Figure 1). Preferences reflected Veterans’ concerns about the risk of switching to biosimilars for the most vulnerable Veterans and their strong preference for information and transparency around biosimilar switching. Participants emphasized the importance of informed choice, prioritizing based on health status, personalization, and shared decision-making (e.g., treatment should be geared to individual patient in discussion with their provider).

CONCLUSION
DD methods are effective for soliciting Veterans' opinions and preferences for health policies. Veterans favored policies that provided information and control, promoted shared decision-making, and reduced risk to vulnerable patients. Incorporating patient preferences and insights is critical when implementing health policies in the VHA and other resource-limited settings.
EPITHELIAL CELLS OF ULCERATIVE COLITIS PATIENTS REQUIRE NORMAL LEVELS OF MITOCHONDRIA AND BETA-CATENIN TO UTILIZE BUTYRATE METABOLISM AND PROMOTE ULCER HEALING
Authors: Erinkitola Iyabo , Abomhya Ahmed , Hassan Syed Adeel , Conder Evan , Rosenau Kian , Kapur Neeraj , Goretsky Tatiana , Barrett Terrence 
Published: January 2023

Abstract

BACKGROUND
Under normal conditions butyrate produced by obligate anaerobes (e.g. firmicutes) provides the dominant energy source for colonocytes via β-oxidation and the tricarboxylic acid cycle. Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) characterized by reduced butyrate metabolism and intestinal epithelial cell (IEC) mitochondria (needed for β-oxidation). Given that nonhealing ulcers in UC are associated with reduced crypt fissioning and branching, we asked whether there was a relationship between mitochondrial deficiency and butyrate-induced crypt branching using colonoid cultures grown from human biopsies.

METHODS
IECs from biopsies taken from active and uninvolved areas of the same UC patient were grown in colonoid cultures. After the second passage, the colonoids with crypt branching were quantified. In separate studies, we modeled mitochondrial deficiency by shRNA knockdown of transcription mitochondrial factor A (Tfam) in human colonoids, a gene responsible for mitochondrial DNA stability and transcription. Both shControl and shTfam colonoids were treated with 5mM of Na-butyrate overnight. NCM460 cells were also treated with 5mM of butyrate overnight, and both ATP levels and TCF/LEF (b-catenin transcriptional activity) were examined.

RESULTS
Colonoids from active UC segments demonstrated 27% less crypt branching than uninvolved areas. These areas also displayed reduced mitochondria complex levels by WB of IEC. To directly examine the role of mitochondria in these effects, crypt branching was examined in shTFAM-treated colonoids where crypt branching levels were 31% less than shCont-treated colonoids (Fig. 1). Butyrate treatment of both shCont and shTfam colonoids increased crypt formation by 11% and 8%, respectively compared to untreated groups. In addition, butyrate increased levels of ATP by 55% and b-catenin transcriptional activity (TCF-LEF) by &gt;600%.

CONCLUSION
This data was consistent with the notion that the failure to heal ulceration in UC patients involves both 1) reduction in butyrate availability from the microbiome (ie reduced stimulation) and 2) reduced mitochondria needed to metabolize butyrate. Upon effective anti-inflammatory treatment, we believe butyrate levels and IEC mitochondrial metabolism increase which contributes to IEC b-catenin signaling and enhanced crypt fissioning/branching needed for effective ulcer healing. We believe this data provide a potential mechanism for how enhanced mitochondrial function contributes to ulcer healing in IBD.
PROBIOTIC BIFIDOBACTERIUM AND A NEW GENERATION POSTBIOTIC: ALGINIC ACID
Authors: Bozkurt Hüseyin 
Published: January 2023

Abstract

AIMS OF THE STUDY
According to International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus (2019),Postbiotics are defined as a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. Postbiotic Alginic acid, also called algin, is a naturally occurring, edible exopolysaccharide found in brown algae. Alginic acid and its Na/Ca salt form of Alginate show the capability in water-binding, water-retention water, and immense swelling and gelation, which could act as a protective barrier via promoting biofilm formation on the bacterial cell surfaces. Alginic acid is a potent inducer of Th1 pathway.We aimed to analyze the Postbiotic alginate formed by the human intestinal beneficial bacteria, bifidobacteria,by degrading sodium alginate.

METHODS
In these study, which were designed in Yildiz Technical University / Istanbul, Biohybrid films were produced by using both Bifidobacterium animalis subsp.lactis BB-12 probiotic strain and Bifidobacterium infantis in combination with sodium alginate (SA), which demonstrates biocompatibility and facilitated gelation properties in aeorobic atmospheric condition were considered as bifidobacterial surfactan source.

RESULTS
In biohybrid biofilm study(1), based on the spectroscopic and mechanical analysis, it was found that mechanical strength increased in films produced by adding Bifidobacterium infantis in SA while this increase was relatively lower as compared to those containing Bifidobacterium animalis subsp. lactis BB-12 as crosslinking ratio increases. Besides, bacteria contained in bio-hybrid films increased the percentage of amorphous zone of SA in SA/bacteria films, which reduced the crystallinity ratio. This indicated that crystalline chains contained in the structure of SA are degraded by probiotic bifidobacteria(Fig.1)

CONCLUSIONS
This is the first study that Biohybrid biosurfactan that contains Bifidobacterium infantis, Bifidobacterium animalis subsp. lactis BB-12 and SA structures coated medical/nonmedical devices and sets can be a pioneering approach to reduce carbon emissions, as well as to prevent secondary infections and increase device protection. Also, It paved the way for the postbiotic use of alginic acid/Alginate by probiotic Bifidobacteria.