bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positioning biologics in the management of moderate to severe Crohn's disease
Authors: Hashash Jana G. , Mourad Fadi H. 
Published: March 2021

Purpose of review
Since there is a lack of head-to-head randomized controlled trials, little direction is provided from guidelines on the positioning of biologics for the treatment of Crohn's disease (CD). This review utilizes comparative effectiveness and safety results from real-world data and network meta-analyses to inform clinical practice for positioning of biological therapies in the treatment of moderate-to-severe CD.

Recent findings
We summarize the results of studies pertaining to the identification of predictors for response to biologics in CD. Recently published studies about the management of moderate-to-severe CD are discussed and a positioning algorithm is proposed for the therapeutic approach of these patients.

Summary
Different classes of biologics are comparable with regards to safety and almost similar in effectiveness in the management of CD. There are certain clinical scenarios in which one biologic is more effective than another. For instance, patients with a more aggressive disease phenotype such as fistulizing disease would benefit from infliximab over other biologics, whereas in older patients at a higher risk for infectious complications, it may be more appropriate to use ustekinumab or vedolizumab over the anti-tumor necrosis factor (TNF) agents. More data pertaining to identifying predictors of response to the different available therapies and head-to-head comparison trials are needed to personalize our therapeutic approach of CD patients.
Women RISE
Authors: Zimbro Kathie S. , Maduro Ralitsa S. , Haimani Olivia F. , Hahn Donna S. , Morgan Merri K. 
Published: March 2021

Background:
The Women RISE program, educating women and health care providers along with technology support, may reduce opioid use.

Local Problem:
Opioid use presented health concerns for women in Virginia's Central Shenandoah Valley.

Methods:
We evaluated the impact of Women RISE on self-management of chronic pain and opioid use, provider prescribing practices, and opioid reduction within our community.

Interventions:
We implemented the Chronic Pain Self-Management Program (CPSMP), educated women and providers, and streamlined access to the Prescription Management Program. Opioid best practice alerts informed providers about their prescribing practices.

Results:
The CPSMP was beneficial in improving women's coping skills, knowledge about opioid use, and overall quality of life. Opioid prescriptions were reduced 34%. We also reduced unneeded opioid analgesics within our community.

Conclusions:
Women were better able to manage chronic pain and stressors impacting opioid misuse. Opioid prescribing practices improved, limiting opioid availability in our community.
An Integrative Review of the Barriers and Facilitators to Nurse Engagement in Quality Improvement in the Clinical Practice Setting
Authors: Alexander Catherine C. , Tschannen Dana , Hays Deana , Clouse Morgan , Zellefrow Cindy , Amer Kim Siarkowski , Lambert-Davis Jacquelyn , Watson Tressa Honaas , Tovar Elizabeth G. , Milner Kerry A. 
Published: March 2021

Background:
Nurse engagement in quality improvement (QI) improves health care quality and outcomes but is typically low in clinical settings.

Purpose:
An integrative review was conducted to identify facilitators and barriers of nurse engagement in QI.

Methods:
This integrative review was conducted using an electronic search of databases with search terms specific to nursing engagement in QI. The Johns Hopkins Nursing Evidence-Based Practice Evidence Level and Quality Guide was used to rate quality and level of evidence.

Results:
Nine articles met the criteria for review. Top barriers were leadership, education and training, resource constraints, data, culture, and time. Top facilitators were leadership, education and training, culture, mentors, and champions.

Conclusion:
High-quality literature exploring barriers and facilitators of nurse engagement in QI is lacking. Research is needed to examine the degree to which these barriers and facilitators impact engagement and how they can be addressed to increase it.
Development and Implementation of a Brief Healthcare Professional Support Program Based in Gratitude, Mindfulness, Self-compassion, and Empathy
Authors: Victorson David , Sauer Christina , Horowitz Bruriah , Wolf-Beadle Julie 
Published: March 2021

OBJECTIVE
To highlight the development, implementation, and initial findings of a brief healthcare professional support program called “GRACE.”

BACKGROUND
Healthcare professionals face significant work-related stressors that when left unmanaged can negatively affect their overall well-being and contribute to burnout.

METHODS
Over a 2-year period, the GRACE program was delivered to 8 clinical units at a midsized southwestern hospital. Questionnaires were administered at baseline and 1 month.

RESULTS
Program participants were 36 years old on average, female (81%), and White (68%) and mostly employed as nurses (66%). Attendees reported increased knowledge, understanding, and confidence and found the program to be acceptable. One month after training, participants demonstrated significant improvements in self-compassion. Medical units that received GRACE training saw significantly greater increases in patient satisfaction scores compared with units that did not receive training.

CONCLUSIONS
The GRACE program was feasible and acceptable to deliver, and initial proof-of-concept evidence was supported.
T2 Hepatocellular Carcinoma Exception Policies That Prolong Waiting Time Improve the Use of Evidence-based Treatment Practices
Authors: Durkin Claire , Kaplan David E. , Bittermann Therese 
Published: March 2021

Background.
A United Network for Organ Sharing policy change in 2015 created a 6-mo delay in the receipt of T2 hepatocellular carcinoma exception points. It was hypothesized that the policy changed locoregional therapy (LRT) practices and explant findings because of longer expected waiting time.

Methods.
Patients transplanted with a first T2 hepatocellular carcinoma exception application between January 1, 2010 and December 31, 2014 (prepolicy; N = 6562), and those between August 10, 2015 and December 2, 2019 (postpolicy; N = 2345), were descriptively compared using data from United Network for Organ Sharing.

Results.
Median time from first application to transplantation was more homogenous across the US postpolicy, due to greater absolute increases in Regions 3, 6, 10, and 11 (>120 d). During waitlisting, postpolicy candidates received more LRT overall (P < 0.001), with more notable increases in previously short-wait regions. Postpolicy explants were overall more likely to have ≥1 tumor with complete necrosis (23.9 versus 18.4%; P < 0.001) and less likely have ≥1 tumor with no necrosis (32.6% versus 38.5%; P < 0.001). Significant geographic variability in explant treatment response was observed prepolicy with recipients in previously short-wait regions having more frequent tumor viability at transplant. Postpolicy, there were no differences in the prevalence of recipients with ≥1 tumor with 100% or 0% necrosis across regions (P = 0.9 and 0.2, respectively).

Conclusions.
The 2015 T2 exception policy has led to reduced geographic variability in the use of pretransplant LRT and in less frequent tumor viability on explant for recipients in previously short-waiting times.
Ex Situ Arterial Reconstruction During Normothermic Perfusion of the Liver
Authors: Nasralla David , Lembach Hanns , Mergental Hynek , Mirza Darius , Friend Peter , Muiesan Paolo , Perera MTPR 
Published: March 2021

Background.
Aberrant hepatic arterial anatomy may be seen in up to 30% of liver grafts, and reconstruction prolongs the cold ischemic time or the arterialization times. If normothermic machine preservation (NMP) is used to preserve liver grafts, the presence of aberrant arterial anatomy poses a challenge. Dual arterial cannulation is a temporary solution to enable effective perfusion, until optimal circumstances are met for arterial reconstruction, without compromising ischemia time. To date the technical and logistical feasibility of arterial reconstruction ex situ and during NMP has not been reported.

Methods.
Series of 5 cases from the Consortium for Organ Preservation in Europe randomized controlled trial in which grafts with arterial anatomic variations were reconstructed while organs were perfused on NMP.

Results.
One donor after cardiac death and 4 donor after brain death livers with arterial anatomical variations reconstructed while on NMP were included. All patients survived transplantation, spending 1–7 d in intensive care unit and discharged home after 5–15 d. None of the cases developed early allograft dysfunction or any early technical complications. At follow-up, there were no late hepatic artery thrombosis, stenosis, or any other vascular–related complication. Four of 5 patients underwent magnetic resonance cholangiopancreatography at 6 mo with no evidence of ischemic cholangiopathy.

Conclusions.
The case series described above suggests that ex vivo arterial reconstruction surgery on liver grafts while on board the NMP device is feasible, safe, and effective.
Need for Pretransplant Midodrine Does Not Negatively Impact Simultaneous Liver-kidney Transplant Outcomes
Authors: Barman Pranab M. , King Lindsay Y. , Berg Carl L. , Parish Alice , Niedzwiecki Donna , Barbas Andrew S. , McElroy Lisa , Patel Yuval A. 
Published: March 2021

Background.
Midodrine is often needed pretransplant to improve hemodynamics in simultaneous liver-kidney transplant candidates. Previous research has shown that patients requiring midodrine before kidney transplant alone have increased posttransplant risk for delayed allograft function, graft failure, and death. However, the impact of pretransplant midodrine use on outcomes after simultaneous liver-kidney transplant is unknown.

Methods.
We performed a retrospective study of all adult (age ≥18 y) simultaneous liver-kidney transplant recipients from a single academic transplant center from February 1, 2002, to June 30, 2019.

Results.
Sixty-four simultaneous liver-kidney transplants were performed in our institution during this time period, of which, 43 were not on midodrine before transplant, 17 were on midodrine alone, and 4 were on intravenous (IV) vasopressor therapy. Despite the midodrine group having a higher MELD-Na at listing, higher MELD-Na at transplant, and being older, there were no significant differences in key outcomes including delayed renal allograft function, estimated glomerular filtration rate at transplant discharge, and estimated glomerular filtration rate at 1 y after transplant compared with the nonmidodrine group. There was no significant difference in graft failure or survival at last follow-up.

Conclusions.
Our study suggests that need for pretransplant midodrine should not be a barrier to simultaneous liver-kidney transplant.
A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation
Authors: Aggarwal Avin , Te Helen S. , Verna Elizabeth C. , Desai Archita P. 
Published: March 2021

Background.
Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT.

Methods.
We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries.

Results.
Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific “cutoff” values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol.

Conclusions.
Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.
A Program of Research to Evaluate the Impact of Deceased Organ Donation Legislative Reform in Nova Scotia: The LEADDR Program
Authors: Weiss Matthew J. , Krmpotic Kristina , Cyr Tim , Dhanani Sonny , Dieudé Mélanie , Dirk Jade S. , Hartell David , Isenor Cynthia , James Lee , Lucas Amanda , Patriquin Chelsea , Simpson Christy , Sullivan Victoria L. , Tennankore Karthik K. , Thurlow Jennifer , Urquhart Robin , Vorster Hans , Beed Stephen D. 
Published: March 2021

Background.
This is the first time deemed consent, where the entire population of a jurisdiction is considered to have consented for donation unless they have registered otherwise, will be implemented in North America. While relatively common in other regions of the world—notably Western Europe—it is uncertain how this practice will influence deceased donation practices and attitudes in Canada.

Methods.
We describe a Health Canada funded program of research that will evaluate the implementation process and full impact of the deceased organ donation legislation and the health system transformation in Nova Scotia that includes opt-out consent.

Results.
There is a need to evaluate the impact of these changes to inform not only Nova Scotia and Atlantic Canada, but also other provincial, national, and international stakeholders.

Conclusions.
We establish a rigorous academic framework that we will use to evaluate this significant health system transformation.
Epigenetic drift association with cancer risk and survival, and modification by sex
Authors: Yu Chenglong , Wong Ee Ming , Joo Jihoon Eric , Hodge Allison M. , Makalic Enes , Schmidt Daniel , Buchanan Daniel D. , Severi Gianluca , Hopper John L. , English Dallas R. , Giles Graham G. , Southey Melissa C. , Dugué Pierre-Antoine 
Published: March 2021

AbstractTo investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case-control studies of colorectal (N=835), gastric (N=170), kidney (N=143), lung (N=332), prostate (N=869) and urothelial (N=428) cancers, and mature B-cell lymphoma (N=438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls) - replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios [HR]), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates (GS summary data) for these CpGs were 94%, 86% and 91%, respectively. Significant signals for cancer risk and survival were identified at some individual age-related CpGs. There was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Two CpGs overlapping TMEM49 and ARX genes were associated with survival of overall (HR=0.91, P=7.7×10−4) and colorectal (HR=1.52, P=1.8×10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.Simple SummaryAgeing is the strongest cancer risk factor, and men and women exhibit disparate risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift might contribute to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 3,215 matched case-control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis.
Genetic variability associated withOAS1expression in myeloid cells increases the risk of Alzheimer’s disease and severe COVID-19 outcomes
Authors: Magusali Naciye , Graham Andrew C. , Piers Thomas M. , Panichnantakul Pantila , Yaman Umran , Shoai Maryam , Reynolds Regina H. , Botia Juan A. , Brookes Keeley J. , Guetta-Baranes Tamar , Bellou Eftychia , Bayram Sevinc , Sokolova Dimitra , Ryten Mina , Frigerio Carlo Sala , Escott-Price Valentina , Morgan Kevin , Pocock Jennifer M. , Hardy John , Salih Dervis A. 
Published: March 2021

AbstractGenome-wide association studies of late-onset Alzheimer’s disease (AD) have highlighted the importance of variants associated with genes expressed by the innate immune system in determining risk for AD. Recently, we and others have shown that genes associated with variants that confer risk for AD are significantly enriched in transcriptional networks expressed by amyloid-responsive microglia. This allowed us to predict new risk genes for AD, including the interferon-responsive oligoadenylate synthetase 1 (OAS1). However, the function ofOAS1within microglia and its genetic pathway are not known. Using genotyping from 1,313 individuals with sporadic AD and 1,234 control individuals, we confirm that theOAS1variant, rs1131454, is associated with increased risk for AD and decreasedOAS1expression. Moreover, we note that the same locus was recently associated with critical illness in response to COVID-19, linking variants that are associated with AD and a severe response to COVID-19. By analysing single-cell RNA-sequencing (scRNA-seq) data of isolated microglia fromAPPNL-G-Fknock-in and wild-type C57BL/6J mice, we identify a transcriptional network that is significantly upregulated with age and amyloid deposition, and contains the mouse orthologueOas1a, providing evidence thatOas1aplays an age-dependent function in the innate immune system. We identify a similar interferon-related transcriptional network containingOAS1by analysing scRNA-seq data from human microglia isolated from individuals with AD. Finally, using human iPSC-derived microglial cells (h-iPSC-Mg), we see thatOAS1is required to limit the pro-inflammatory response of microglia. When stimulated with interferon-gamma (IFN-γ), we note that cells with lowerOAS1expression show an exaggerated pro-inflammatory response, with increased expression and secretion of TNF-α. Collectively, our data support a link between genetic risk for AD and susceptibility to critical illness with COVID-19 centred onOAS1and interferon signalling, a finding with potential implications for future treatments of both AD and COVID-19, and the development of biomarkers to track disease progression.
Default Mode Network spatial configuration varies across task domains
Authors: Mancuso Lorenzo , Cavuoti-Cabanillas Sara , Liloia Donato , Manuello Jordi , Buzi Giulia , Duca Sergio , Cauda Franco , Costa Tommaso 
Published: March 2021

AbstractRecent developments in network neuroscience suggest reconsidering what we thought we knew about the Default Mode Network (DMN). Although this network has always been seen as unitary and associated with the resting state, a new deconstructive line of research is pointing out that the DMN could be divided into multiple subsystems supporting different functions. By now, it is well known that the DMN is not only deactivated by tasks, but also involved in affective, mnestic, and social paradigms, among others. Nonetheless, it is starting to become clear that the array of activities in which it is involved, might also be extended to more extrinsic functions. The present meta-analytic study is meant to push this boundary a bit further. The BrainMap database was searched for all experimental paradigms activating the DMN, and their activation maps were then computed. An additional map of task-induced deactivations was also created. A Multidimensional Scaling indicated that such maps could be arranged along an anatomo-psychological gradient, which goes from midline core activations, associated with the most internal functions, to the involvement of lateral cortices in more external tasks. Further investigations suggested that such extrinsic mode is especially related to reward, semantic, and emotional functions. However, an important finding was that the variability of task-induced DMN anatomic redistribution was hard to recapitulate, as none of the maps, or any linear combination of them, could represent the whole space of its dynamical reconfiguration. Altogether, our findings suggest that the DMN may be characterized by a richer functional diversity and a more spatial complexity than previously suggested.
An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease
Authors: Palanski Brad A. , Weng Nielson , Zhang Lichao , Hilmer Andrew J. , Fall Lalla A. , Swaminathan Kavya , Jabri Bana , Sousa Carolina , Fernandez-Becker Nielsen Q. , Khosla Chaitan , Elias Joshua E. 
Published: March 2021

ABSTRACTCeliac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we developed a novel liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detected 679 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes.