bluuebunny/crossref_metadata_2025_split huggingface dataset:
A QUALITATIVE STUDY EXPLORING MEANINGFUL IMPROVEMENT IN BOWEL URGENCY AMONG ADULTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
Authors: Newton Louise , Guobyte Aiste , McFadden Shehan , Symonds Tara , Delbecque Laure , Donaldson Jill , Naegeli April 
Published: January 2022

Abstract

BACKGROUND
Ulcerative Colitis (UC) is a chronic disease with periods of relapse and remission. Bowel urgency, the sudden or immediate need for a bowel movement, is one of the most bothersome symptoms experienced by patients with UC. This study explored how patients define urgency severity and what would be a meaningful improvement based on a numeric rating scale (NRS).

METHODS
In-depth interviews were conducted in the United States with 19 adults with clinician-confirmed moderate to severe UC. Participants were asked to define levels of bowel urgency severity using an 11-point NRS (where 0 = no urgency and 10 = worst possible urgency) and to describe what would be a meaningful improvement based on how this change would impact their daily life. Interviews were audio-recorded, transcribed, and coded using thematic coding in NVivo.

RESULTS
Mild bowel urgency was described as ranging between 0 to 3 on the 11-point scale by most UC patients (n=16, 84%). Mild was described as “almost normal” or “normal urgency” (n=6, 32%) and being able to make it to the bathroom with ease (n=5, 25%). Most participants (n=15, 79%) rated moderate urgency between 4 to 6 on the 11-point scale. At this level, participants commented that they would need to ensure they are close to a bathroom (n=7, 37%). Finally, ratings for severe urgency clustered between 6 to 8 (n=7, 37%) and 8 to 10 (n=12, 63%). Severe bowel urgency was described as an immediate or uncontrollable need (n=8, 42%) which impacts their ability to leave the home (n=7, 37%). When asked about what change on the urgency NRS would be meaningful, n=10 (53%) participants reported that a 1-point change would be meaningful, with most stating that any change was an improvement. Participants commented that a 1-point change would reflect improved emotional well-being and greater confidence to leave the home. In contrast, 9 (47%) participants wanted improvements of more than 1-point change; 5 (26%) indicated that a 2-point improvement was required to consider the change meaningful and 4 (21%) felt a 3-point change or more was needed. With this greater level of change, participants described having a significant improvement in urgency, with less frequent urges and improved emotional well-being.

CONCLUSION
This qualitative study revealed that UC patients largely agreed regarding ratings of ‘mild’ and ‘moderate’ bowel urgency on an 11-point severity scale. ‘Severe’ bowel urgency was split between two ranges suggesting the existence of ‘very severe’ bowel urgency. In addition, the majority of UC patients perceived a 1 or 2-point reduction on the urgency NRS as a meaningful change in their lives.
IDENTIFYING BARRIERS TO HEALTH MAINTENANCE IN MEDICALLY-UNDERSERVED PATIENTS WITH IBD: A QUALITATIVE STUDY
Authors: Belton Juanita , Sanfratello Natalie , Gaitan Erika , LeBron Alana , Wasan Sharmeel , White Julie , Moss Alan 
Published: January 2022

Abstract

BACKGROUND
Disparities in adherence to health maintenance recommendations have been well-documented in patients with IBD. Solutions to address these issues remain under-described or evaluated. We sought to engage at-risk patients with IBD for a qualitative assessment of their barriers to health maintenance targets. The goal of this endeavor is to inform the design of interventions to address these disparities in practice.

METHODS
Boston University School of Medicine (BUSM) and the Crohn’s and Colitis Program at Boston Medical Center (BMC), in partnership with Health Resources in Action (HRiA), conducted focus groups with medically underserved patients with inflammatory bowel disease (IBD), and interviews with IBD providers between April-July of 2021. Four focus groups were conducted virtually in English (n=3) and Spanish (=1) with IBD patients (n=11) receiving care at BMC’s Crohn’s and Colitis Program. Enrollees were selected based on criteria for being ‘at-risk’ for health maintenance non-adherence; defined as insured by MassHealth or a Boston Medical Center Accountable Care Organization (ACO) and who have outstanding health maintenance needs (i.e., lacking a documented flu shot in the past 2 years). In addition, two interviews were conducted with clinical providers serving patients with IBD. Qualitative analyses were conducted with NVivo (NVivo qualitative data analysis Software; QSR International Pty Ltd. Version 12). Transcripts were double coded by two analysts based upon a mutually agreed upon codebook and differences were reconciled through discussion until a consensus was reached (average kappa=0.96). Key themes were identified by discussion frequency and intensity.

FINDINGS
Key themes that emerged from these comprehensive discussions regarding barriers to patients completing their health maintenance requirements included: lack of culturally appropriate education and information in the patients’ primary languages, specifically patients cited that they had not received information regarding the connection between their IBD and required vaccinations. Also, living with IBD can be stressful, stigmatizing, and isolating, and more mental health supports are needed through ways of integrated care, mental health resources, and support groups. Patients recommended integrating holistic approaches to IBD care and management, including diet/nutrition, exercise, and managing stress Furthermore, other themes that emerged included: insights into patients dealing with chronic pain; medical management is a critical component to preventing flare ups, yet numerous barriers to accessing care exist;. Findings from this process are intended to inform a 12-month quality improvement (QI) initiative within BMC’s Crohn’s and Colitis Program with the ultimate goal of improving patient care.
STIGMA INTERNALIZATION IN NON-WHITE PATIENTS WITH IBD AND ITS RELATIONSHIP WITH PATIENT OUTCOMES
Authors: Veracruz Nicolette , Taft Tiffany 
Published: January 2022

Abstract

INTRODUCTION
Disease-related stigmatization is present in patients with IBD and includes internalization of discriminatory attitudes or behaviors. Prior studies show IBD-related stigma is associated with worse clinical outcomes. However, this has not been well-studied in underrepresented racial and ethnic minority populations (URM). The aim of the current study is to evaluate levels of internalized stigma in URM IBD patients and its relationship with the health-related quality of life (HRQoL) domains of anxiety, depression, fatigue, sleep disturbance, social functioning, and pain interference.

METHODS
Adult patients 18+ recruited via social media and researchmatch.org website completed an anonymous online survey: demographics, disease information, Harvey Bradshaw Index (HBI) or simple clinical colitis activity index (SCCAI) with &gt;4 = active IBD, NIH-PROMIS QoL module (anxiety, depression, fatigue, sleep disturbance, pain interreference, social function), and the Internalized Stigma for Mental Illness scale (ISMI) (“mental illness” replaced with “IBD”). High internalized stigma on ISMI is weighted average &gt; 2.50 on both the total score and each subscale (Alienation, Social Withdrawal, Discrimination, Stereotype Endorsement, Stigma Resistance). Independent samples t-Test, Pearson’s correlation, and hierarchical linear regression statistics were used.

RESULTS
90 participants: 50% UC, 79% female, 66% South/Southeast Asian, 10% Hispanic, Age (Mean±SD))=34.8±9.8 years. 52% had active IBD (5.77±4.22) with “biologic” medications most used (38.9%). 27% reported high levels of internalized stigma: 54% reported alienation, 39% social withdrawal, 27% discrimination, 3% stereotype endorsement; 19% reported stigma resistance. No differences by age, IBD type, gender, race, or ethnicity. Patients with active IBD reported more internalized stigma (2.33±0.44 vs. 2.10±0.38, p=.008). Internalized stigma was significantly correlated with all patient outcomes: anxiety r=0.595, depression r=0.620, fatigue r=0.356, sleep disturbance r=0.328, pain interference r=0.421, and social function r= -0.566 (all p&lt;.01). When controlling for HBI/SCCAI score, internalized stigma was a larger predictor of anxiety (β=.560, p&lt;.001), depression (β=.567, p&lt;.001), sleep disturbance (β=.272, p=.010), and social function (β= -.341, p=.003) than symptom severity, and smaller but significant predictor of fatigue (β=.255, p=.006) and pain interference (β=.308, p&lt;.001).

CONCLUSION
Stigma internalization is prevalent in URM IBD patients, with alienation and social withdrawal most reported. Stigma was associated with negative outcomes, and is possibly a stronger predictor of HRQoL in IBD than the disease activity of IBD itself. Further research with larger cohorts and more diverse populations is needed in order to further elucidate the role of disease stigma in URM IBD patient experiences.
ANTI-SARS-COV-2 VACCINATION AND ANTIBODY RESPONSE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE ON IMMUNE-MODIFYING THERAPY. PROSPECTIVE SINGLE TERTIARY CENTER STUDY ON 602 IBD PATIENTS
Authors: Cerna Karin , Duricova Dana , Lukas Martin , Machkova Nadezda , Hruba Veronika , Lukas Milan 
Published: January 2022

Abstract

BACKGROUND AND AIM
Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease of 2019 (COVID-19), thus data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We have conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414 and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and the magnitude of seroconversion, to assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and to analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD.

METHODS
The study included 602 IBD patients and 168 immunocompetent health-care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination, and 8 weeks after the end of vaccination.

RESULTS
Of IBD patients, 82.2% were receiving biological treatment: most of them were treated TNF-alpha inhibitors (48.5%) and just under half of them with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The post-vaccine seropositivity rate among IBD patients and controls was 97.8% versus 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared to two other vaccines (p &lt; 0.0001) and to control ChAdOx1 nCoV-19 recipients (p = 0.01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. TNF-alpha inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with the lower post-vaccination antibody response ( p &lt;0.0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and eight weeks after its completion.

CONCLUSION
Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNFa inhibitors with concomitant immunomodulators and show priority of mRNA vaccines in this specific group of patients.
COVID-19 INFECTIONS IN VACCINATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE: OUTCOMES AND RISK FACTORS FOR SEVERE DISEASE
Authors: Spiera Emily , Ganjian Danielle , Zhang Xian , Brenner Erica , Agrawal Manasi , Colombel Jean-Frederic , Kappelman Michael , Kornbluth Asher , Ungaro Ryan 
Published: January 2022

Abstract

BACKGROUND
There are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population.

METHODS
Data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death.

RESULTS
Among 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids.

CONCLUSION
In patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.
EARLY VERSUS DELAYED INITIATION OF VEDOLIZUMAB IN ULCERATIVE COLITIS: TREATMENT RESPONSE IN THE REAL WORLD (RALEE)
Authors: Cleveland Noa , Candela Ninfa , Carter John , Kuharic Maja , Qian Joyce , Tang Lily , Turpin Robin , Rubin David 
Published: January 2022

Abstract

BACKGROUND
Pivotal trials in ulcerative colitis (UC) have indicated that earlier intervention with a biologic is associated with greater likelihood of treatment response. However, in real-world clinical practice, patients with newly diagnosed UC are often prescribed conventional therapies, such as immunomodulators (IM), corticosteroids (CS), and/or 5-aminosalicylates (5-ASA) before biologic treatment, which may result in suboptimal clinical outcomes and high costs. RALEE is an observational study investigating the impact of early versus delayed initiation of vedolizumab (VDZ) on clinical and economic outcomes in patients with inflammatory bowel disease, using administrative data sets. Here, we report the impact on treatment response in patients with UC.

METHODS
Using the MarketScan Commercial Claims and Encounters database and the MarketScan Medicare Supplemental database, we identified adult patients diagnosed with UC between 2017 and 2018 who had ≥ 1 claim for VDZ and continuous enrollment for ≥ 12 months before and after their initial UC diagnosis. Patients were excluded if they received VDZ, anti-tumor necrosis factor therapy, or other biologic therapy in the 12 months before their initial UC diagnosis. Five post-diagnosis treatment pathways were predefined: (1) EARLY VDZ, VDZ within 30 days of initial UC diagnosis; (2) DELAYED VDZ 1, IM (not 5-ASA) before VDZ; (3) DELAYED VDZ 2, CS with IM before VDZ; (4) DELAYED VDZ 3, 5-ASA with CS before VDZ; or (5) DELAYED VDZ 4, 5-ASA with CS and IM before VDZ. Response was defined as no occurrence of the following events within 60 days after VDZ initiation: new concomitant use of CS, inflammatory bowel disease-related surgery, increased administration of VDZ, VDZ treatment discontinuation, or treatment switch. Response was evaluated with logistic regression (backwards selection) with EARLY VDZ as the reference group.

RESULTS
We identified 136,315 patients with UC, of whom 1,342 received VDZ and met the selection criteria. The median age of patients was 43 years; 51.0% of patients were male and 96.4% were commercially insured. The proportion of patients with response to VDZ was higher for EARLY VDZ (88.8%) than any of the DELAYED VDZ treatment pathways (70.1–79.8%) (Figure 1). Delayed initiation of VDZ (DELAYED VDZ 1, 2, and 4) was associated with a significantly lower likelihood of response than EARLY VDZ (Figure 2).

CONCLUSION
This analysis demonstrates that patients with UC are more likely to respond to therapy if initiated on VDZ within 30 days of diagnosis than if initiation is delayed by use of IM, CS, and/or 5-ASA. These findings are consistent with clinical guidelines that recommend use of VDZ for induction of remission in patients with moderately to severely active UC. Further analyses of remission, healthcare resource utilization, and associated direct medical costs are underway.
Deep learning based on multi-omics integration identifies potential therapeutic targets in breast cancer
Authors: Pan Xingxin , Burgman Brandon , Sahni Nidhi , Yi S. Stephen 
Published: January 2022

AbstractEffective and precise classification of breast cancer patients for their disease risks is critical to improve early diagnosis and patient survival. In the recent past, a significant amount of multi-omics data derived from cancer patients has emerged. However, a robust framework for integrating multi-omics data to subgroup cancer patients and predict survival prognosis is still lacking. In addition, effective therapeutic targets for treating breast cancer patients with poor prognoses are in dire need. To begin to resolve this difficulty, we developed and optimized a sophisticated deep learning-based model in breast cancer that can accurately stratify patients based on their prognosis. We built a survival-associated predictive framework integrating transcription profile, miRNA expression, somatic mutations, copy number variation, DNA methylation and protein expression. This framework achieved promising performance in distinguishing high-risk breast cancer patients from those with good prognoses. Furthermore, we constructed multiple fully connected neural networks that are trained on prioritized multi-omics signatures or even only potential single-omics signatures, based on our customized scoring system. Together, the landmark multi-omics signatures we identified may serve as potential therapeutic targets in breast cancer.
Task-related changes in aperiodic activity are related to visual working memory capacity independent of event-related potentials and alpha oscillations
Authors: Virtue-Griffiths Sian , Fornito Alex , Thompson Sarah , Biabani Mana , Tiego Jeggan , Thapa Tribikram , Rogasch Nigel C 
Published: January 2022

AbstractIndividual differences in visual working memory capacity are related to slow-wave event-related potentials (ERPs) and suppression of alpha-band oscillatory power measured during the delay period of memory tasks using electroencephalography (EEG). However, recent evidence suggests that changes in the non-oscillatory, aperiodic features of the EEG signal may also contribute to working memory performance. We assessed several features of task-related changes in aperiodic activity including the spatial distribution, the effect of memory load, and the relationship between memory capacity, slow-wave ERPs, and alpha suppression. Eighty-four healthy individuals performed a continuous recall working memory task consisting of 2, 4 or 6 coloured squares while EEG was recorded. Aperiodic activity during a baseline and delay period was quantified by fitting a model to the background of the EEG power spectra using the FOOOF toolbox, which returned parameters describing the slope (exponent) and broadband offset of the spectra. The aperiodic exponent decreased (i.e., slope flattened) over lateral parieto-occipital electrodes but increased (i.e., slope steepened) over fronto-central electrodes during the delay period, whereas the offset decreased over parieto-occipital electrodes. These task-related changes in aperiodic activity were not altered by memory load. Larger increases in the aperiodic exponent were associated with higher working memory capacity measured from both the EEG task and a separate battery of complex span tasks, and this relationship was independent of slow-wave ERPs and alpha suppression. Our findings suggest that task-related changes in aperiodic activity during working memory are region specific and reflect an independent neural mechanism important for general working memory ability.
mTOR is a Major Determinant of Chemosensitivity
Authors: Liu Yuanhui , Azizian Nancy G. , Sullivan Delaney K. , Li Yulin 
Published: January 2022

ABSTRACTChemotherapy can eradicate a majority of cancer cells. However, a small population of tumor cells often survives drug treatments through genetic and/or non-genetic mechanisms, leading to tumor recurrence. Here we report a reversible chemoresistance phenotype regulated by the mTOR pathway. Through a genome-wide CRISPR knockout library screen in pancreatic cancer cells treated with chemotherapeutic agents, we have identified mTOR pathway as a prominent determinant of chemosensitivity. Pharmacological suppression of mTOR activity in cancer cells from diverse tissue origins leads to the persistence of a reversibly resistant population, which is otherwise eliminated by chemotherapeutic agents. Conversely, activation of mTOR pathway increases chemosensitivity in vitro and in vivo and predicts better survival among various human cancers. Persister cells display a senescence phenotype. Inhibition of mTOR does not induce cellular senescence per se, but rather promotes the survival of senescent cells through regulation of autophagy and G2/M cell cycle arrest, as revealed by a small molecule chemical library screen. Thus, mTOR plays a causal yet paradoxical role in regulating chemosensitivity; inhibition of the mTOR pathway, while suppressing tumor expansion, facilitates the development of a reversible drug-tolerant senescence state.
A horizon for haptic perception
Authors: Miller Luke E. , Jarto Felix , Medendorp W. Pieter 
Published: January 2022

AbstractThe spatial limits of sensory acquisition (its sensory horizon) is a fundamental property of any sensorimotor system. In the present study, we sought to determine the sensory horizon for the human haptic modality. At first blush, it seems obvious that the haptic system is bounded by the space where the body can interact with the environment (e.g., the arm span). However, the human somatosensory system is exquisitely tuned to sensing with tools—blind-cane navigation being a classic example of this. The horizon of haptic perception therefore extends beyond body space, but to what extent is unknown. We first used neuromechanical modelling to determine the theoretical horizon, which we pinpointed as six meters. We then used a psychophysical localization paradigm to behaviorally confirm that humans can haptically localize objects using a six-meter rod. This finding underscores the incredibly flexibility of the brain’s sensorimotor representations, as they can be adapted to sense with an object many times longer than the user’s own body.