bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancellation mechanism of dark matter direct detection in Higgs-portal and vector-portal models
Authors: Cai Chengfeng , Zeng Yu-Pan , Zhang Hong-Hao
Published: January 2022

Abstract

We present two alternative proofs for the cancellation mechanism in the U(1) symmetric pseudo-Nambu-Goldstone-Boson Dark Matter (pNGB DM) model. They help us to have a better understanding of the mechanism from multi-angle, and inspire us to propose some interesting generalizations. In the first proof, we revisit the non-linear representation method and rephrase the argument with the interaction eigenstates. In this picture, the phase mode (DM) can only have a trilinear interaction with a derivative-squared acting on the radial mode when the DM is on-shell. Thus, the DM-quark scattering generated by a mass mixing between the radial mode and the Higgs boson vanishes in the limit of zero-momentum transfer. Using the same method, we can easily generalize the model to an SO(N) model with general soft-breaking structures. In particular, we study the soft-breaking cubic terms and identify those terms which preserve the cancellation mechanism for the DM candidate. In our discussion of the second method, we find that the cancellation relies on the special structure of mass terms and interactions of the mediators. This condition can be straightforwardly generalized to the vector-portal models. We provide two examples of the vector-portal case where the first one is an SU(2)L × U(1)Y × U(1)X model and the second one is an SU(2)L × U(1)Y × U(1)B−L × U(1)X model. In the first model the vector mediators are the Zμ boson and a new U(1)X gauge boson Xν, while in the second model the mediators are the U(1)B−L and U(1)X gauge bosons. The cancellation mechanism works in both models when there are no generic kinetic mixing terms for the gauge bosons. Once the generic kinetic mixing terms are included, the first model requires a fine-tuning of the mixing parameter to avoid the stringent direct detection bound, while the second model can naturally circumvent it.
The Log of Gravity at 15
Authors: Santos Silva J. M. C. , Tenreyro Silvana
Published: January 2022

We review the contribution of “The Log of Gravity” (Santos Silva and Tenreyro, Rev Econ Stat 88:641–658, 2006), summarize the main results in the ensuing literature, and provide a brief review of the state-of-the-art in the estimation of gravity equations and other constant-elasticity models.
The Alberta moving beyond breast cancer (AMBER) cohort study: baseline description of the full cohort
Authors: Friedenreich Christine M. , Vallance Jeff K. , McNeely Margaret L. , Culos-Reed S. Nicole , Matthews Charles E. , Bell Gordon J. , Mackey John R. , Kopciuk Karen A. , Dickau Leanne , Wang Qinggang , Cook Diane , Wharton Stephanie , McNeil Jessica , Ryder-Burbidge Charlotte , Morielli Andria R. , Courneya Kerry S.
Published: January 2022

Purpose

The Alberta Moving Beyond Breast Cancer (AMBER) Study is an ongoing prospective cohort study investigating how direct measures of physical activity (PA), sedentary behavior (SB), and health-related fitness (HRF) are associated with survival after breast cancer.

Methods

Women in Alberta with newly diagnosed stage I (≥ T1c) to IIIc breast cancer were recruited between 2012 and 2019. Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak); upper and lower body muscular strength and endurance; dual-X-ray absorptiometry to measure body composition; and questionnaires to measure self-reported PA and SB.

Results

At baseline, the 1528 participants’ mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%.

Conclusion

We have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.
Assessing the Kinematic GPS Positioning Performance Under the Effect of Strong Ionospheric Disturbance Over China and Adjacent Areas During the Magnetic Storm
Authors: Geng Wei , Huang Wengeng , Liu Guoqi , Liu Siqing , Luo Binxian
Published: January 2022

The geomagnetic storm caused numerous disturbances of the ionosphere, particularly, plasma irregularities, which can affect the accuracy of Global Positioning System (GPS) positioning. This study quantifies the impacts of the ionospheric disturbance on GPS precise point positioning (PPP) solutions during extreme space weather events by taking advantage of 260 GPS stations in China. The results show that the average positioning error in China increased significantly during the ionospheric disturbance on 08 Sep 2017. By comparing the kinematic GPS‐PPP (3‐D) error distribution map and the ROTI index map, it is found that the ionospheric irregularities are one of the main reasons for degrading the GPS positioning accuracy. The statistical analysis results show that when the ionospheric scintillation index S4 is greater than 0.4, the average kinematic GPS‐PPP error calculated by the station is higher than 0.8 m.
Defect engineered SnO2 nanoparticles enable strong CO2 chemisorption toward efficient electroconversion to formate
Authors: Ning Baoxing , Liu Miaomiao , Hu Yanjie , Jiang Hao , Li Chunzhong
Published: January 2022

The ultrahigh oxygen vacancy content enhances the conductivity and CO2 chemisorption of SnO2 nanoparticles for an efficient conversion of CO2 into formate.
Pd(ii)/Lewis acid catalyzed regioselective olefination of indole with dioxygen
Authors: Tan Chen , Jiang Hongwu , Zeng Miao , Li Kaiwen , Chen Zhuqi , Yin Guochuan
Published: January 2022

Pd(ii)/Lewis acid can catalyze indole olefination faster with electron-rich olefins than with electron-deficient ones, and dioxygen is employed as the sole oxidant.
Reliability and validity of an indoor local positioning system for measuring external load in ice hockey players
Authors: Gamble Alexander S. D. , Bigg Jessica L. , Pignanelli Christopher , Nyman Danielle L. E. , Burr Jamie F. , Spriet Lawrence L.
Published: January 2022

This study determined the reliability and validity of a Kinexon local positioning system (LPS) for measuring external load in ice hockey players during an on‐ice session. Fourteen ice hockey players (25.1 y, 78.6 kg, 176.9 cm) wore two LPS sensors to examine the inter‐sensor reliability of the LPS during an on‐ice session, and LPS speed and acceleration were measured during 40 m linear on‐ice sprints and compared to a previously validated robotic sprint device to examine LPS accuracy. The coefficient of variation (CV), standard error of measurement (SEM), and intra‐class correlation coefficient (ICC) were calculated for each LPS measure. Pearson's correlations, simple linear regressions, and Bland–Altman plots were used to test the agreement and relationship between the two systems. Statistical significance was determined at p < 0.05. The majority of LPS measures were reliable (CV < 10% and ICC > 0.9) when comparing the two sensors worn by each player. Peak speed, speed at 5 m, and 0‐5 m acceleration were all comparable to those reported by the robotic sprint device, with nearly perfect (peak speed and 0–5 m acceleration) and very large (speed at 5 m) magnitudes of correlation and mean biases <0.5 km/hr for speed measures and <0.01 m/s2 for acceleration. The present results demonstrate that the Kinexon LPS is reliable and accurate for investigating on‐ice external load in ice hockey players when sensors are consistently secured on the back of the players’ shoulder pads.
EFFICACY OF BIOLOGIC DRUGS IN SHORT-DURATION VERSUS LONG-DURATION INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND INDVIDUAL-PATIENT-DATA METANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Ben-Horin Shomron , Novack Lena , Mao Ren , Guo Jing , Zhao Yue , Sergienko Ruslan , Zhang Jian , Kobayashi Taku , Hibi Toshihumi , Chowers Yehuda , Peyrin-Biroulet Laurent , Colombel Jean-Frederic , Kaplan Gilaad , Chen Min-Hu
Published: January 2022

BACKGROUND

Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may associate with higher efficacy, especially in Crohn’s disease (CD).

METHODS

A systematic review and individual-patient-data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (Oct 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction-of-remission in patients with short-duration (≤18months) versus long-duration disease (>18months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients’ characteristics on the primary outcome. Study PROSPERO registration: CRD42018041961.

RESULTS

We obtained data from five biologics drug manufacturers and included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab or vedolizumab (6,168 CD, 3,227 UC patients). In CD, induction-of-remission rates were higher in pooled placebo and active arms’ patients with short-disease duration≤18 months (41.4%, 244/589) compared with disease-duration>18months (29.8%, 852/2857, meta-analytically estimated OR=1.33, 95%CI:1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction-of-remission, was not different in short-duration disease ≤18 months (n= 589, OR 1.47, 95%CI:1.01-2.15) compared with longer disease-duration (n=2857, OR 1.43, 95%CI:1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cut-offs and when modelled for individual-patients’ co-variates, including prior anti-TNFs exposure. In exploratory post-hoc analysis comparing patients with colonic-CD (L2) versus small-bowel L1 CD (and excluding ileo-colonic L3 disease) the OR for induction-of-remission in long-duration disease>18months compared with short-duration disease was 0.62 for small-bowel CD (95%CI: 0.42; 0.91) but was not significant in pooled colonic CD population (OR=0.94, 95%CI: 0.66; 1.34)

CONCLUSION

This Individual patient level meta-analysis of multiple biologics’ clinical trials found there a higher rate of induction-of-remission in early CD for both biologics and placebo, resulting in a treatment-to-placebo effect ratio which is similar across different disease durations. No such relationships between disease-duration and outcomes is found in UC.

Rate of remission induction by duration of disease at initiation of treatment. The dots denote proportion of an outcome averaged per the respective year.
ADDITIVE EFFECT OF PROBIOTICS ON 5-AMINOSALICYLIC ACID THERAPY IN PATIENT WITH ULCERATIVE COLITIS
Authors: Kim Minjun
Published: January 2022

BACKGROUND AND AIMS

In patients with ulcerative colitis (UC), Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, data regarding the ability of EcN to increase health-related quality of life or induce remission, compared with placebo, remain scarce. We investigated the efficacy of EcN as an add-on therapy for UC.

METHODS

We conducted a multicentre, double-blind, randomised, placebo-controlled study in patients with mild-to-moderate UC. Overall, 133 eligible patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks, and inflammatory bowel disease questionnaire (IBDQ) scores, clinical remission, and response rate were compared.

RESULTS

In total, 58 and 60 patients in the EcN and placebo groups, respectively, completed the study. EcN was not superior to placebo in increasing the IBDQ scores (30 [51.7%] vs. 31 [51.7%], respectively; per-protocol, P= 1.0; intention-to-treat, P= 0.86). However, a significantly lower number of patients in the EcN group exhibited a decreased IBDQ score than those in the placebo group (1 [1.7%] vs. 8 [13.3%], respectively; per-protocol, P= 0.03; intention-to-treat, P= 0.02). Compared with the placebo group, a significantly high number of patients in the EcN group exhibited clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], respectively; P= 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], respectively; P= 0.03).

CONCLUSIONS

EcN is safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remissions in patients with mild-to-moderate UC.
SELECTIVELY IMPROVEMENT OF THE RESPONSE OF IMMUNE CELLS TO OPPORTUNISTIC MICROORGANISMS: AN INNOVATIVE PROPOSAL FOR IBD FROM AN ANCIENT GRAIN
Authors: Segura Sergio Pumarola
Published: January 2022

BACKGROUND

Inflammatory Bowel Disease (IBD) results from an unbalanced immune response to the gut microbiome. There is a lack of proposals that integrate and may balance the multiple factors (Immunity, microbiome and diet) that together condition the onset and evolution of the disease. D-fagomine is a small molecule, naturally present in buckwheat grain. It Is a monosaccharide mimetic showing glycosidase enzyme inhibition properties. Clinical studies have shown its efficacy to control postprandial glycemic response. Subsequent research “in vitro” had also shown D-fagomine to inhibit the fimbriae adhesion and biofilm formation of some proteobacteria, including ie E. coli or Salmonella.

ORIGINAL AIM

The aim of the study was to confirm the effects of D-fagomine on the adhesion to human gut mucosa using adherent-invasive E coli (AIEC) that is a microorganism usually linked to IBD.

METHOD

Ex vivo human resected colonic mucosa was cultured (4 h) with AIEC inoculum and D-fagomine at different range of doses (0-5000 ppm). The amount of E. coli in tissue and supernatant was quantified, measuring also TNF-alfa and LDH.

RESULTS

It was confirmed the inhibition of AIEC adhesion to the colonic mucosa in a direct dose-response relationship. Totally unexpected, D-fagomine was found to modulate TNF-alfa in an apparent double sigmoid curve with the max activity in the range of 50 ppm (Figure 1). This curve corresponds to an activator of the innate immune cells with mechanism related to complement activation, (ie mannose, betaglucan). Finally D-fagomine was helping the mucosa to detect and overcome the evasion mechanism of AIEC at the range of 50 ppm. Additional studies were considered necessary to confirm these results with different models.

ADDED AIM

The novel aim was to assess the human immune cell response (other than colonic mucosa) in the dose range of 50 ppm D-fagomine in front of different microorganisms able to evade the human immune system.

ADDED METHOD

Ex vivo human blood was cultured with D-fagomine (50 ppm) and the correspondent inoculum of different models: bacteria = E. coli (AIEC) and fungus = Blastomyces sp. TNF-alfa was quantified.

ADDED RESULTS

D-fagomine, at 50 ppm, stimulates TNF-alfa response of human immune cells against AIEC and also Blastomyces (Figure 2). Both models give coherent results, and confirm that D-fagomine at the range of 50 ppm improves the capacity of the innate immune cells to detect human opportunistic microorganisms.

CONCLUSIONS

Our results have shown for the first time D-fagomine helping human immune cells to develop a more efficient immune response to better control the presence of opportunistic microorganisms. This is of great interest in IBD and also synergic with D-fagomine activity of delaying the release of sugars from diet to the gut, reducing then the negative effects of a Western Diet to humans and also to its microbiome.
COMPLICATIONS OF MYOCARDITIS IN INFLAMMATORY BOWEL DISEASE (IBD): A POPULATION-BASED COMPARATIVE STUDY BETWEEN ULCERATIVE COLITIS AND CROHN’S DISEASE
Authors: Dasu Neethi , Khalid Yaser , Blair Brian , Chhoun Christopher , Joo Lucy
Published: January 2022

INTRODUCTION

Cardiac Complications are common in IBD. Myocarditis is a serious extraintestinal manifestation associated with inflammatory bowel disease. The aim of this study is to investigate the complications associated with myocarditis in patients who have IBD (Ulcerative Colitis vs Crohn’s Disease) patients.

METHODS

Methods Data was extracted from the National Inpatient Sample (NIS) 2016-2019 Database. The NIS was searched for hospitalizations for adult patients with myocarditis as a principal discharge diagnosis who had Ulcerative Colitis (UC) versus those with Crohn’s Disease (CD) as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis. Characteristics and complications of myocarditis were compared between UC and CD.

RESULTS

A total of 874,285 hospitalized patients aged ≥18 years had IBD, of which 563,700 (64.48%) had UC and 310,585 (35.52%) had CD. Myocarditis was present in 250 (0.03%) patients; 100 UC (0.34%) and 150 CD (0.52%). Overall prevalence of myocarditis was 18.87 per 100,000 hospitalizations for IBD patients. Prevalence was 23.22 in UC (Mean age 48.5 ± 2.1 years p<0.001, 56% women p<0.001, 76% Caucasian p<0.001) and 11.55 in CD (Mean age 39.5± 1.42 years, p<0.001; 37% women, p<0.001; 72% Caucasian, p <0.001) per 100,000 hospitalizations respectively (p<0.001). Annual incidence of myocarditis was rising for UC over a 5-year period per 100,000 hospitalizations (13.6 in 2016, 25.1 in 2019, ptrend = 0.04) and for CD (10.3 in 2016, 13.4 in 2019, ptrend = 0.03). In patients with myocarditis, UC patients had lesser in-hospital mortality (3.4% % vs. 5.2 %, p< 0.001), AKI (5.3% vs. 13.4%, p< 0.001), congestive heart failure (14.5% vs. 33.2%, p<0.001) and cardiogenic shock (4.3% vs. 8.7%, p<0.001) compared to CD. Atrial fibrillation was the most common arrhythmia in both UC and CD (6.1% vs. 6.2%, p = 0.968). Ventricular fibrillation was higher in CD (3.4% vs. 1.1%, p<0.001).

CONCLUSION

Interestingly, Myocarditis was associated with higher mortality, higher cardiac complications and was more prevalent in patients with CD compared to UC. Further randomized controlled trials are necessary to determine the mechanisms between IBD and cardiovascular diseases and to study the disparity between UC and CD. This study further illustrates the importance of successful management of IBD in order to reduce disease activity and cardiovascular risk factors.
NOD2 PROMOTES HOST DEFENSE AND RECOVERY INDUCING MACROPHAGE-MEDIATED INNATE LYMPHOID CELLS TYPE 3 ACTIVATION FOLLOWING FUNGAL INFECTION IN EXPERIMENTAL COLITIS
Authors: McAndrew Morgan , Havran Hannah , Di Martino Luca , Ghannoum Mahmoud , Pizarro Theresa , De Salvo Carlo
Published: January 2022

Recent studies have documented the complexity of the intestinal fungal community (‘mycobiome’) in mice, and clinical and experimental observations have shown that the mycobiome influences both gut health and disease, e.g., inflammatory bowel disease (IBD). In fact, prior studies have shown that Crohn’s disease (CD) patients, compared to healthy controls, harbor higher levels of intestinal Candida tropicalis (Ct), which is the major fungal species detected in the colons of colitic mice after DSS challenge. More recently, Debaryomyces hansenii (also known as Candida famata) has been found in intestinal wounds of mice and inflamed mucosal tissues of CD patients. Moreover, proteins encoded by genes within IBD susceptibility loci, such as the pattern recognition receptor (PRR), NOD2, are known not only to recognize bacterial components, but also a fungal cell wall element, chitin. In fact, the role of PRRs in regulating immunity against intestinal fungi, and how fungi influence IBD remains poorly defined. We challenged DSS colitic WT and Nod2-/- mice with Ct 2 days before DSS administration and subsequently on day (d)0, 3 and 6. Our data confirms previous studies that Ct challenge does not exacerbate colitis in DSS-treated C57BL/6 wildtype (WT) mice, however, Ct-infected Nod2-/- mice possess a higher fungal burden and exhibit worse colitis symptoms, such as weight loss, decreased stool consistency, and presence of blood in stools, vs. Ct-infected WT mice, indicating an essential and protective role for NOD2 during colitis recovery after Ct challenge. Our results also show that Ct-infected Nod2-/- mice display a marked reduction in colonic Il22 and Il17, which are cytokines previously reported to be important in maintaining epithelial barrier integrity during DSS colitis, These data were confirmed in colons of Ct infected DSS challenged, ileitis-prone SAMP1/YitFc (SAMP) mice that were deficient in NOD2. Moreover, Our in vitro data show, a decrease in Il1b and Il23 in bone marrow-derived macrophages from SAMP Nod2-/- mice compared to WT after 2h of exposure to chitin. IL-17+ innate lymphoid cells (ILCs) are also known to control fungal burden during opportunistic fungal infections, and interestingly, our findings indicate that Ct infection of Nod2-/- vs. WT mice results in a decreased frequency of mesenteric lymph node–derived type 3 ILCs (ILC3s), suggesting that delay in fungal clearance and recovery in Nod2-/- mice may be due to the inability to mount protective type 3 immune responses. Taken together, the data so far collected suggests that NOD2 is essential to maintain gut mycobiome homeostasis and drives protective innate immune responses, via a macrophage-mediated ILC3 recruitment and IL-17 mechanism, by preventing the overgrowth of opportunistic fungi that may contribute to chronic intestinal inflammation, such as that observed in CD.
TRENDS IN ADMISSIONS, OUTCOMES AND FINANCIAL BURDEN OFC. DIFFICILE INFECTION RELATED HOSPITALIZATIONS AMONG INFLAMMATORY BOWEL DISEASE PATIENTS: A NATIONWIDE ANALYSIS
Authors: Tahir Muhammad Waqas , Tariq Raseen , Tahir Zoya , Zaheer Arsalan , Khanna Sahil
Published: January 2022

INTRODUCTION

Inflammatory bowel disease (IBD) patients with colonic involvement are known to have microbiome changes which may increase their risk of C. difficile infection (CDI). We conducted an analysis to describe the implications of CDI on hospitalized IBD patients.

METHODS

We used the National Inpatient Sample database from 2007 through 2018, to identify patients admitted with primary or secondary diagnosis of IBD using the ICD-9 or ICD-10 codes. We identified CDI as well as colectomy using diagnostic codes. We identified trends in nationwide estimates for annual admissions, age at admission, length of stay (LOS), in-patient mortality, Elixhauser comorbidity index and total hospital charge (adjusted for inflation). We used the Cochran-Armitage test for trend significance.

RESULTS

Between 2007 and 2018, there were an estimated total of 3,728,348 admissions with IBD, of which 161,744 patients had CDI (4.3%). Median age at admission was 52 years, with 56.7% females. There was a rising trend of CDI among IBD patients, from 2.9% in 2007 to a peak of 5.4% in 2015 with a decline towards the end of study period at 4.4% in 2018. Mean score for Elixhauser comorbidity index increased from 4.6 to 7.4 (p-trend <0.05) for non-CDI subgroup and from 9.9 to 11.4 (p-trend <0.05) for CDI subgroup during the study period.

The median LOS was 4 days for patients without CDI vs 6 days with CDI. Trend in LOS was stable for patients without CDI but decreased from 8 days to 5 days over the 12-year study period for patients with CDI (p-trend <0.05). Overall, among patients with IBD, the risk of colectomy was 5.3%. Risk was higher in CDI subgroup (7.3% vs 5.2%, RR 1.41, 95% CI 1.39 - 1.44).

The overall mortality among IBD patients was 1.6% with no significant trend observed over time. All cause in-hospital mortality was significantly higher among patients with concomitant CDI (6.8%) vs without CDI (1.4%) (RR 4.99, 95% CI 4.89 - 5.10). Within CDI subgroup, there was a trend of decrease in mortality from 7-11% in the beginning of the study, to about 3-3.5% towards the end of the study period (p-trend <0.05).

After adjusting for inflation, there was a significant increase in charges among both subgroups: increased from $28,575 in 2007 to $68,614 in 2018 (p-trend <0.005) for non-CDI subgroup and from $57,987 in 2007 to $95,799 in 2018 (p-trend <0.005) for CDI subgroup. Overall charges were significantly higher for CDI subgroup.

CONCLUSION

The incidence of CDI in IBD patients increased over the study period with stability towards the latter half. Hospitalized IBD patients with concomitant CDI have a higher comorbidity index, a longer length of stay, a higher risk of colectomy and an increased risk of mortality when compared to those without CDI. Total hospitalization charges are also significantly higher with CDI subgroup and have been increasing overtime.
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

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

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

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 >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 > 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<.01). When controlling for HBI/SCCAI score, internalized stigma was a larger predictor of anxiety (β=.560, p<.001), depression (β=.567, p<.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<.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

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 < 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 <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

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

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

Effective 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

Individual 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

Chemotherapy 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.