bluuebunny/crossref_metadata_2025 huggingface dataset:
P563 Comparison of long-term outcomes of infliximab with adalimumab in biologic naïve patients with Crohn’s disease: a tertiary referral center 13-year experience
Authors: Yuksel I , Durak M B , Kilic V , Kivrakoglu F , Kosar K , Erdogan C , Alkan A
Published: May 2021

Background

The comparative efficacy and safety of infliximab (IFX) and adalimumab (ADA) have shown variable results in biologic-naïve patients with Crohn’s disease (CD). Thus, long-term comparisons between IFX and ADA with or without immunomodulator therapies are still needed.

The purpose of this study was to evaluate the long-term clinical effectiveness and safety profile of IFX compared to ADA in biologic-naïve patients with CD.

Methods

Data of all adult CD patients treated with IFX or ADA as their first biologic agent was collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related major abdominal surgery, steroid use and serious infections leading to treatment cessation.

Results

Out of 224 biologic-naïve patients with CD, 101 started IFX first (median age at onset: 38.12 years, 61.4% male) and 123 started ADA first (median age at onset: 30.2 years, 64.2% male).

Median disease duration was 6.94 years (IQR: 3.82–12.17) and 6.91 years (IQR: 3.94–10.95) for IFX and ADA, respectively, of whom 33% and 37.4% had active smokers, 10.9% and 13.4% had family history of inflammatory bowel disease (IBD) 22.8% and 19.5% had perianal disease, 43.6% and 43.9 had prior major abdominal surgery and 52.6% and 49.6% had extraintestinal manifestations.

There were no significant differences between the two groups with respect to the age at onset of tumor necrosis factor antagonist, gender, smoking status, family history of IBD, perianal disease, prior major abdominal surgery, extraintestinal manifestations, prior immunomodulator (Thiopurine or Methotrexate) or steroid usage, all laboratory test results and Crohn’s Disease Activity Index (CDAI) score at baseline (p>0.05).

Overall, the median follow-up time was 2.81 and 3.55 years after starting the first IFX and ADA group, respectively. There were no significant differences in the rate of steroid use (4% IFX vs. 10.6% ADA p=0.109), CD-related hospitalization (13.9% IFX vs. 22.8% ADA p=0.127), CD-related major abdominal surgery (9.9% IFX vs. 13% ADA p=0.608) and serious infections leading to treatment cessation (1% IFX vs 0.8% ADA p>0.999) between IFX and ADA. These outcomes were similar in patients treated with IFX or ADA monotherapy or in combination with an immunomodulator.

Conclusion

In this retrospective observational tertiary referral center study, we observed that there was no significant difference in long-term effectiveness and safety of infliximab and adalimumab in biologic-naïve patients with CD.
P573 Comparative effectiveness of second-line biological therapies for Ulcerative colitis and Crohn’s disease in patients with prior failure of anti-tumour necrosis factor treatment
Authors: Hyun H K , Yu J , Kang E A , Park J , Park S J , Park J J , Kim T I , Kim W H , Cheon J H
Published: May 2021

Background

Therapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn’s disease (CD) are lacking.

Methods

Patients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy.

Results

A total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC : 37; CD : 28), ustekinumab (CD : 16), or tofacitinib (UC : 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients.

Conclusion

After prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients showed similarities in terms of the efficacy in inducing and maintaining a clinical response.
P585 IBD Reference and Biosimilar adalimumab CroSS over Study (iBaSS): a mixed methods clinical trial of patients transitioning between originator and biosimilar adalimumab. Qualitative findings from an interim analysis presenting the patient perspective
Authors: Young D , Latter S , Harvey J , Addison J , Freudensprung U , Cummings F
Published: May 2021

Background

iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adults with Crohn’s disease. 112 participants have been recruited from patients attending the IBD clinic for routine treatment. Eligibility criteria included mHBI < 8, stable on Humira™ or Imraldi™ with no expectation to discontinue or adjust adalimumab (ADA) dosing in the study period. The pragmatic study design mimics the optimal care pathway of patients transitioning between originator and biosimilar ADA, allowing all participants to experience both. Such transitions are part of routine clinical practice but with little understanding of the patient perspective. As part of iBaSS we capture the patient perspective and experience of transition, with the aim of informing future practice.

Methods

Purposive sampling was used to capture a wide range of perspectives from a subset of the participants treated with the originator ADA at enrolment. Interviews were semi-structured, using open-ended questions, facilitated by a topic guide developed with reference to published literature. Interviews were recorded, transcribed and analysed using thematic analysis. Thirty five participants were interviewed.

Results

Five themes were identified: (1) understanding and awareness of biosimilars, (2) motivation to undertake transition, (3) initial concerns, (4) reassuring factors and (5) reflection of experience.

Opinions expressed were often heterogeneous, but commonly-occurring experiences were also identified. Prior awareness of biosimilars and knowledge of the biosimilar concept was low indicating a disparity between healthcare professionals and patients. Patients accept a biosimilar transition to minimise drug expenditure. Prior to undertaking biosimilar transition away from the brand they had experienced, efficacy and adverse effects were common concerns for patients. Trust in the healthcare team is critical to patient acceptance of biosimilars and important reassurances include a point of contact, education about biosimilars and specific monitoring. When reflecting on the experience, participants noted little subjective difference in efficacy or tolerability (although 22 participants specifically mentioned injection pain) following brand transition and the majority feel comfortable with future transition to another ADA biosimilar. Injection experience is important in patient satisfaction.

Conclusion

While biosimilars have driven a reduction in drug acquisition costs, the majority of patients have little knowledge and some concerns about transitioning to a biosimilar but accept the principles and can be reassured. The wide-ranging views elucidated suggest that a tailored, patient-centred approach is key to successful implementation.
P594 Utilisation of anti-TNF agents in phlegmonous Crohn’s disease: an Australian tertiary referral centre experience
Authors: Chiu L , Digby-Bell J , Seah J , Melton S , Taylor K , Sparrow M
Published: May 2021

Background

Phlegmonous Crohn’s disease (CD) is a complication of penetrating disease where traditional management was surgical. There are a paucity of studies evaluating its medical management. The aim of our single-centre, retrospective case series was to evaluate the efficacy and safety of anti-TNF therapy in managing phlegmonous CD.

Methods

Cases were identified through searching patient records for CT, MRI and intestinal ultrasound reports containing the words “Crohn’s” and “phlegmon”. Patients were included if found to have CD-related phlegmon subsequently started on anti-TNF. Patients were excluded if they were already on an anti-TNF at diagnosis, or underwent surgery prior to starting anti-TNF. Electronic review of patient records was undertaken to determine demographics, current medication, length of disease and surgery.

Results

Of the 66 cases identified, 11 fulfilled inclusion criteria. 2 cases required surgery at 38 and 197 days post-phlegmon diagnosis, both of which had earlier ceased anti-TNF due to failed trial and severe depression respectively. 4 patients discontinued anti-TNF during follow up: 1 experienced severe anaphylaxis, 1 failed anti-TNF trial, and 2 ceased due to personal preference (severe depression, concern about adverse effects). 8 of 10 had complete resolution of the phlegmon with 1 patient awaiting imaging 6 months post-phlegmon diagnosis.

Conclusion

9 of 11 of our patient cohort avoided surgery after starting anti-TNF therapy for phlegmonous CD, out to a median follow up of 20 months. Our findings suggest anti-TNFs are generally well tolerated, and early commencement may be effective in preventing surgical intervention.
P605 Development and validation of an objective disability index for Inflammatory Bowel Disease patients (ODIBD)
Authors: Melcarne L , Vergara Gómez M , Villoria Ferrer A , Brunet Mas E , Garcìa Iglesias P , Llovet Soto L , Dosal Galguera A , Monllor Nunell T , Alforcea Alcaraz S , Calvet Calvo X
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) can be a cause of disability. To date, the scores that evaluate disability in IBD patient use mainly subjective criteria. The aim of this study was to develop and validate an index of disability in IBD based on objective, measurable criteria.

Methods

IBD patients from the Catalan and Spanish Crohn and Colitis Associations volunteered to fulfill an online self-administered survey. Demographic, clinical, and therapeutic variables were collected. They also informed on whether they have a recognized disability and whether they receive a work disability pension.

Patients were divided into a training and validation set. In the training set, different multivariate analyses were carried out to evaluate objective variables related to having a recognized work disability, a general disability or a moderate or severe degree of disability.

The score was elaborated with the statistically or clinically significant variables present in the multivariate analyses.

The ROC curves for predicting general and work disability were calculated.

Results

981 valid surveys were included. Sixty six percent of the patients were women, mean age was 40.9 years and 59.3% had Crohn’s disease. Of these patients, 85 (9.1%) had a recognized work disability and 429 (45.9%) had a degree of recognized general disability. The results of the multivariate analyses are shown in table 1.

Eight variables were selected to develop the inflammatory bowel disease objective work disability index (ODIBD) (table 2). Each variable was scored one point to calculate the final index.

The AUROC of the index in the training group was 0.76 for work disability and 0.71 for general disability. The AUROC of the index in the validation group was 0.83 for work disability and 0.67 for general disability (fig1).

Conclusion

The ODIBD may be useful score to objectively assess of work disability in patients with IBD.
P607 The Faroese IBD Study: Update on incidence from 2015–2020 and prevalence from 1960–2020
Authors: Nielsen K R , Midjord J , Hammer T , Lophaven S , Burisch J
Published: May 2021

Background

Previous reports have found that the Faroe Islands has the highest reported incidence of inflammatory bowel disease (IBD) in the world.1,2 The purpose of this study was to update our previous work on the IBD incidence from 1960–20142 with data up until 2020 and to describe the prevalence of IBD over 60 years.

Methods

All cases of Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) diagnosed between 1960 to 2020, including all age groups and year of death, were retrieved from the Medical Centre at the National Hospital of the Faroe Islands. Diagnoses were ascertained according to the Copenhagen Diagnostic Criteria. Population data from 1960–2020 were retrieved from Statistics Denmark and Statistics Faroe Islands. Point prevalence rates (per 100,000) were estimated as all IBD patients alive and living in the Faroe Islands by the end of 1960, 1970, 1980, 1990, 2000, 2010 and 2020, divided by the Faroese population (end of year).

Results

232 individuals have been diagnosed with IBD during the past 6 years in the Faroe Islands: 29 (12%) with CD, 111 (48%) with UC and 92 (40%) with IBDU, resulting in an increased age-standardised IBD incidence rate (European Standard Population, ESP) from 74 per 100,000 person-years (py) in 2010–14 to 80 in 2015–20. Figure 1 illustrates the updated IBD incidence rate integrated with results from our previous study.2 The point prevalence rate of IBD was 5,8 cases per 100,000 persons in 1960; 46,6 in 1970; 133,9 in 1980; 325,4 in 1990; 610,7 in 2000; 925,1 in 2010 and 1407,9 cases per 100,000 in 2020, corresponding to 1,4% of the Faroese population living with IBD in 2020 compared to 0,6% in 2000.

Conclusion

The increasing incidence of IBD from 2015–2020 is mainly driven by IBDU, accounting for 40% of all cases and has increased from 21 per 100,000 (ESP) in 2010–14 to 32 in 2015–2020. The age-standardised incidence rate of CD remains unchanged compared to our previous study, at 10 per 100,000 (ESP), while the incidence of UC has decreased from 44 to 39 per 100,000 (ESP). The prevalence of IBD has increased radically in accordance with the increasing incidence. Further investigations into the high proportion of IBDU and causes of the observed IBD pattern is currently ongoing.

1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2018;390:2769–78.et al.

2. The Faroese IBD Study: Incidence of Inflammatory Bowel Diseases Across 54 Years of Population-based Data. J Crohns Colitis 2016;10:934–42.
P615 Does smoking really influence the development and the outcomes of Inflammatory Bowel Disease in Asian population? Results from the Taiwanese patients
Authors: Chen B C , Weng M T , Chang C H , Huang L Y , Wei S C
Published: May 2021

Background

Smoking has been reported to be associated with increased risk of Crohn’s disease (CD) and protect against ulcerative colitis (UC) from the Western population. However, the association are not well studied and there is no report about smoking and disease outcomes in the Asian population. This study is to clarify the influence of smoking in the development and disease outcomes of inflammatory bowel disease (IBD) in Asian population.

Methods

This case-controlled study was conducted by cross section chart review for smoking status as well as clinical characteristics of IBD patients at the National Taiwan University Hospital (NTUH). Age, sex, co-morbidities (hypertension, diabetes, and hyperlipidemia) matched non-IBD control were identified by using the database from the National Health Interview Survey of Taiwan, with 4 to 1 ratio for IBD patients. Clinical characteristics including disease phenotype, medication usage, times of admissions, times of emergency room (ER) visits, surgery, development of new cancer, survival status, endoscopic severity, laboratory data were retrieved and analyzed.

Results

A total of 700 IBD patients (UC: 412; CD: 378) diagnosed from January 1963 to 2020 were identified and analyzed for the influence of smoking to outcomes. The median follow-up time of UC and CD was 104 and 85 months, respectively. Among them, 575 patients (UC: 297, CD: 278) with complete information of comorbidities and aged from 12 to 64 years old were enrolled for smocking prevalence analysis. The prevalence of smoking was significantly lower in UC compared to the matched control (20.88% vs 30.39%, p = 0.0003), but there was no difference between CD and the matched control (19.78% vs 22.12%, p = 0.595). UC smokers were associated with less times of admission (1.56 vs. 2.46, p = 0.017), but higher rate of new cancer development (16% vs. 6.67%, p = 0.01), and mortality (16% vs. 4.91%, p = 0.001), when compared to the non-smokers. CD smokers tended to have disease located in terminal ileum (L1) and ileocolon (L3) (p = 0.0067), higher rate of stricturing (B2) and penetrating (B3) disease (p = 0.0328), higher risk of surgery (60.32% vs. 38.27%, p = 0.001) than the non-smokers, but no difference on mortality.

Conclusion

In Asian IBD population, smoking is a protective factor for UC occurrence and associated with lower hospitalization rate but more cancer and higher mortality. In contrast, smoking has no effect for CD occurrence and mortality but related to more aggressive behavior which resulted in higher surgical rate.
Estimating Perceptual Range of Female Monarch Butterflies (Danaus plexippus) to Potted Vegetative Common Milkweed (Asclepias syriaca) and Blooming Nectar Resources
Authors: Fisher Kelsey E , Bradbury Steven P
Published: May 2021

Habitat loss in the summer breeding range contributes to eastern North American monarch (Lepidoptera: Nymphalidae) population decline. Habitat restoration efforts include increasing native prairie plants for adult forage and milkweed (Asclepias spp.) for oviposition and larval development. As the monarch is a vagile species, habitat establishment at a grain that matches the monarch perceptual range will facilitate efficient movement, decrease fitness costs of dispersal, and increase oviposition. We released 188 experimental monarch females 5, 25, 50, and 75 m downwind from potted milkweed and blooming forbs in 4–32 ha sod fields. Perceptual range was estimated from monarchs that flew towards and landed on the milkweed and forbs. Flight patterns of 49 non-experimental monarchs that landed on the resources were also observed. In our experimental, resource-devoid setting, wind-facilitated movement occurred most frequently. Monarchs performed direct displacement as evidenced by shallow turn angles and similarity of Euclidian and total distances traveled. We hypothesize similar monarch flight behavior when traveling over other resource-devoid areas, such as crop fields. Although the majority of experimental monarchs flew downwind, eight experimental and 49 non-experimental monarchs were observed flying upwind toward, and landing on, the potted resources from distances ranging from 3 to 125 m (mean = 30.98 m, median = 25 m, mode = 25 m). A conservative estimate of the perceptual range is 125 m, as longer distances cannot be precluded; however, the majority of observations were ≤50 m. Our findings suggest establishing habitat patches ~ 50 m apart would create functional connectivity across fragmented agricultural landscapes.
Response to Anti-α4β7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline
Authors: Gazouli Maria , Dovrolis Nikolas , Bourdakou Marilena M , Gizis Michalis , Kokkotis Georgios , Kolios George , Michalopoulos Georgios , Michopoulos Spyridon , Papaconstantinou Ioannis , Tzouvala Maria , Viazis Nikos , Xourafas Vasilleios , Zacharopoulou Eirini , Zampeli Evanthia , Mantzaris Gerasimos , Papatheodoridis George , Bamias Giorgos
Published: May 2021

Background

Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4β7, vedolizumab, in patients with active ulcerative colitis (UC).

Methods

Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly.

Results

In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a “core” mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade.

Conclusions

Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.
Foretelling the Flex—Vertebral Shape Predicts Behavior and Ecology of Fishes
Authors: Donatelli Cassandra M , Roberts Alexus S , Scott Eric , DeSmith Kylene , Summers Dexter , Abu-Bader Layanne , Baxter Dana , Standen Emily M , Porter Marianne E , Summers Adam P , Tytell Eric D
Published: May 2021

Synopsis

One key evolutionary innovation that separates vertebrates from invertebrates is the notochord, a central element that provides the stiffness needed for powerful movements. Later, the notochord was further stiffened by the vertebrae, cartilaginous, and bony elements, surrounding the notochord. The ancestral notochord is retained in modern vertebrates as intervertebral material, but we know little about its mechanical interactions with surrounding vertebrae. In this study, the internal shape of the vertebrae—where this material is found—was quantified in 16 species of fishes with various body shapes, swimming modes, and habitats. We used micro-computed tomography to measure the internal shape. We then created and mechanically tested physical models of intervertebral joints. We also mechanically tested actual vertebrae of five species. Material testing shows that internal morphology of the centrum significantly affects bending and torsional stiffness. Finally, we performed swimming trials to gather kinematic data. Combining these data, we created a model that uses internal vertebral morphology to make predictions about swimming kinematics and mechanics. We used linear discriminant analysis (LDA) to assess the relationship between vertebral shape and our categorical traits. The analysis revealed that internal vertebral morphology is sufficient to predict habitat, body shape, and swimming mode in our fishes. This model can also be used to make predictions about swimming in fishes not easily studied in the laboratory, such as deep sea and extinct species, allowing the development of hypotheses about their natural behavior.
Impact of preoperative antithrombotic therapy in patients undergoing elective isolated coronary artery bypass grafting
Authors: van Steenbergen Gijs J , van Straten Albert H M , Kabak Serhat , van Veghel Dennis , Dekker Lukas , Soliman-Hamad Mohamed A
Published: May 2021

OBJECTIVES

The objective of this retrospective study was to assess differences in clinical outcomes between patients on acetylsalicylic acid (ASA) monotherapy and patients on other antithrombotic (AT) regimens undergoing elective coronary artery bypass grafting (CABG).

METHODS

Patients who underwent elective isolated CABG between 2017 and 2019 at the Catharina Hospital Eindhoven were eligible for this study. The primary end points were re-exploration for bleeding and postoperative blood product transfusion. Secondary end points included 30-day mortality, in-hospital stroke, in-hospital myocardial infarction and duration of hospitalization. Propensity matching was used to compare outcomes of the main study groups (ASA vs other AT therapy) and subgroups of AT therapy (guideline adherence vs non-adherence).

RESULTS

A total of 1068 patients were included: 710 patients on ASA monotherapy and 358 patients on other AT regimens. In the 256 matched patients in the main study groups, using AT regimens other than ASA monotherapy was associated with increased risk of re-exploration for bleeding [6.6% vs 2.0%, P = 0.017; odds ratio (OR) 3.57 (1.29–9.83)] and increased use of blood products [37.5% vs 20.3%, P < 0.001; OR 2.35 (1.58–3.49)]. In 122 matched subgroup patients, non-adherence was associated with an increased risk of re-exploration [10.7% vs 3.3%, P = 0.044; OR 3.52 (1.11–11.12)] and increased blood product use [51.6% vs 25.4%, P < 0.001; OR 3.13 (1.83–5.38)]. Secondary end points were not significantly different among the main study groups and subgroups.

CONCLUSIONS

Preoperative use of AT therapy other than ASA monotherapy in patients who elected CABG was associated with the increased postoperative use of blood products and risk of re-exploration for bleeding; this finding was even more pronounced in non-guideline-adherent patients.
Task-Dependent Effects of SKF83959 on Operant Behaviors Associated With Distinct Changes of CaMKII Signaling in Striatal Subareas
Authors: Liu Pei-Pei , Chao Chih-Chang , Liao Ruey-Ming
Published: May 2021

Background

SKF83959, an atypical dopamine (DA) D1 receptor agonist, has been used to test the functions of DA-related receptor complexes in vitro, but little is known about its impact on conditioned behavior. The present study examined the effects of SKF83959 on operant behaviors and assayed the neurochemical mechanisms involved.

Methods

Male rats were trained and maintained on either a fixed-interval 30-second (FI30) schedule or a differential reinforcement of low-rate response 10-second (DRL10) schedule of reinforcement. After drug treatment tests, western blotting assayed the protein expressions of the calcium-/calmodulin-dependent protein kinase II (CaMKII) and the transcription factor cyclic AMP response element binding protein (CREB) in tissues collected from 4 selected DA-related areas.

Results

SKF83959 disrupted the performance of FI30 and DRL10 behaviors in a dose-dependent manner by reducing the total number of responses in varying magnitudes. Moreover, the distinct profiles of the behavior altered by the drug were manifested by analyzing qualitative and quantitative measures on both tasks. Western-blot results showed that phospho-CaMKII levels decreased in the nucleus accumbens and the dorsal striatum of the drug-treated FI30 and DRL10 subjects, respectively, compared with their vehicle controls. The phospho-CREB levels decreased in the nucleus accumbens and the hippocampus of drug-treated FI30 subjects but increased in the nucleus accumbens of drug-treated DRL10 subjects.

Conclusions

Our results provide important insight into the neuropsychopharmacology of SKF83959, indicating that the drug-altered operant behavior is task dependent and related to regional-dependent changes of CaMKII-CREB signaling in the mesocorticolimbic DA systems.
Path Dependence in Disability
Authors: Agarwal Neha , Kohler Hans-Peter , Mani Subha
Published: May 2021

The average prevalence of disability in most African countries is 10%, but for many it exceeds the global disability prevalence rate of 15%. The extent to which this disability capturing functional and activity limitations results in permanent job loss, lowered lifetime income and assets, in part, depends upon the extent to which the onset of limitations becomes permanent. In this paper, we use five rounds of longitudinal data from rural Malawi, a low-income African country with high prevalence of disability, to examine path dependence in activity limitations. We estimate a dynamic linear panel data model where the coefficient on the one-period lagged health outcome captures path dependence in limitations. Our preferred Arellano–Bover estimates show that males experience partial persistence in both the incidence and intensity of severe limitations and no persistence in other limitations. Females, on the other hand, exhibit no persistence in any type of limitations. Our findings have important policy implications for computing the long-term costs associated with onset of activity limitations as these costs can be moderated by the recovery exhibited in these limitations.
A novel application of SMART on FHIR architecture for interoperable and scalable integration of patient-reported outcome data with electronic health records
Authors: Wesley Deliya B , Blumenthal Joseph , Shah Shrenikkumar , Littlejohn Robin A , Pruitt Zoe , Dixit Ram , Hsiao Chun-Ju , Dymek Christine , Ratwani Raj M
Published: May 2021

Objective

Despite a proliferation of applications (apps) to conveniently collect patient-reported outcomes (PROs) from patients, PRO data are yet to be seamlessly integrated with electronic health records (EHRs) in a way that improves interoperability and scalability. We applied the newly created PRO standards from the Office of the National Coordinator for Health Information Technology to facilitate the collection and integration of standardized PRO data. A novel multitiered architecture was created to enable seamless integration of PRO data via Substitutable Medical Apps and Reusable Technologies on Fast Healthcare Interoperability Resources apps and scaled to different EHR platforms in multiple ambulatory settings.

Materials and Methods

We used a standards-based approach to deploy 2 apps that source and surface PRO data in real-time for provider use within the EHR and which rely on PRO assessments from an external center to streamline app and EHR integration.

Results

The apps were developed to enable patients to answer validated assessments (eg, a Patient-Reported Outcomes Measurement Information System including using a Computer Adaptive Test format). Both apps were developed to populate the EHR in real time using the Health Level Seven FHIR standard allowing providers to view patients’ data during the clinical encounter. The process of implementing this architecture with 2 different apps across 18 ambulatory care sites and 3 different EHR platforms is described.

Conclusion

Our approach and solution proved feasible, secure, and time- and resource-efficient. We offer actionable guidance for this technology to be scaled and adapted to promote adoption in diverse ambulatory care settings and across different EHRs.
Characterizing Herbivory by European Earwigs (Dermaptera: Forficulidae) on Navel Orange Fruit with Comparison to Forktailed Bush Katydid (Orthoptera: Tettigoniidae) Herbivory
Authors: Kahl Hanna M , Mueller Tobias G , Cass Bodil N , Xi Xinqiang , Cluff Emma , Grafton-Cardwell Elizabeth E , Rosenheim Jay A
Published: May 2021

In establishing Integrated Pest Management (IPM) plans for understudied pests, it is crucial to understand the nature of their herbivory and resulting damage. European earwig (Forficula auricularia L.; Dermaptera: Forficulidae) densities are increasing in citrus orchards in Central California. Field observations suggest that earwigs feed on young, developing citrus fruit, but this hypothesis had not been examined with formal experimentation. Forktailed bush katydid nymphs (Scudderia furcata Brunner von Wattenwyl; Orthoptera: Tettigoniidae) are well-known citrus herbivores that feed on young citrus fruit, and it is possible that earwig damage may be misdiagnosed as katydid damage. Here we report findings from two field experiments in navel oranges (Citrus sinensis (L.) Osbeck; Sapindales: Rutaceae) that together tested: (1) whether earwigs damage young citrus fruit; (2) whether the amount of damage earwigs generate differs across developmental stage or sex of adult earwigs; (3) the window of time during which fruit are most sensitive to earwig damage; (4) whether damaged fruit are retained to harvest; and (5) the resulting damage morphology caused by earwigs relative to katydids. Earwigs, particularly nymphs, chewed deep holes in young citrus fruit from 0 to 3 wk after petal fall. Fruit damaged by earwigs were retained and exhibited scars at harvest. The morphology and distribution of scars on mature fruit only subtly differed between earwigs and katydids. This study establishes that earwigs can be direct pests in mature navel orange trees by generating scars on fruit and likely contribute to fruit quality downgrades.
PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway
Authors: Huang Bangliang , Xiong Xin , Zhang Linlin , Liu Xiufei , Wang Yuren , Gong Xiaoli , Sang Qian , Lu Yongling , Qu Hua , Zheng Hongting , Zheng Yi
Published: May 2021

The activity of proteinase is reported to correlate with the development and progression of nonalcoholic fatty liver disease (NAFLD). Puromycin-sensitive aminopeptidase (PSA/NPEPPS) is an integral nontransmembrane enzyme that functions to catalyze the cleavage of amino acids near the N-terminus of polypeptides. A previous study suggested that this enzyme acts as a regulator of neuropeptide activity; however, the metabolic function of this enzyme in the liver has not been explored. Here, we identified the novel role of PSA in hepatic lipid metabolism. Specifically, PSA expression was lower in fatty livers from NAFLD patients and mice (HFD, ob/ob, and db/db). PSA knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation through enhanced lipogenesis and attenuated fatty acid β-oxidation. Moreover, PSA mediated activation of the master regulator of antioxidant response, nuclear factor erythroid 2-related factor 2 (NRF2), by stabilizing NRF2 protein expression, which further induced downstream antioxidant enzymes to protect the liver from oxidative stress and lipid overload. Accordingly, liver-specific PSA overexpression attenuated hepatic lipid accumulation and steatosis in ob/ob mice. Furthermore, in human liver tissue samples, decreased PSA expression correlated with the progression of NAFLD. Overall, our findings suggest that PSA is a pivotal regulator of hepatic lipid metabolism and its antioxidant function occurs by suppressing NRF2 ubiquitination. Moreover, PSA may be a potential biomarker and therapeutic target for treating NAFLD.
Repellency of p-Anisaldehyde Against Musca domestica (Diptera: Muscidae) in the Laboratory
Authors: Showler Allan T , Harlien Jessica L
Published: May 2021

The house fly, Musca domestica L. (Diptera: Muscidae), is a nuisance pest often associated with livestock production, and it can also mechanically transmit the causal agents of human and veterinary diseases. We found that a 0.5% concentration of p-anisaldehyde, produced by many plants consumed by humans, repelled adult M. domestica in static air olfactometer tubes under laboratory conditions for ≥24 h, but by 48 h the repellent activity had worn off. Repellency, however, was not observed in response to 0.5% p-anisaldehyde that had been exposed to sunlight radiation lamps for 2 h. When p-anisaldehyde was aged in darkness for 48 h, it showed strong initial repellency for <1 h. The repellent action of 0.5% p-anisaldehyde was sufficient to keep adult M. domestica from landing on three different food sources when the botanical substance was misted onto the food sources, and when it was placed in proximity to, but not in contact with, the food sources. Extension of p-anisaldehyde’s repellent action using solvents other than acetone is discussed.
Barley transcription factor HvNLP2 mediates nitrate signaling and affects nitrogen use efficiency
Authors: Gao Yangyang , Quan Shuxuan , Lyu Bo , Tian Tian , Liu Zhiguang , Nie Zhentian , Qi Shengdong , Jia Jingbo , Shu Jing , Groot Edwin , Wu Jiajie , Wang Yong
Published: May 2021

Plants have evolved complex mechanisms to adapt to the changing nitrogen levels in the environment. In Arabidopsis, more than a dozen nitrate signaling regulatory genes have been characterized, including the NODULE INCEPTION-LIKE PROTEIN (AtNLP) genes, which play essential roles in nitrate signaling. However, whether NLP genes in the Triticeae crops are involved in nitrate regulation and nitrogen use efficiency (NUE) remains unknown. Here, we isolated a barley (Hordeum vulgare L.) mutant, hvnlp2-1, from a TILLING (Targeting Local Lesions IN Genomes) population and constructed two RNAi lines, hvnlp2-2 and hvnlp2-3, to study the function of HvNLP2. The expression of the nitrate-responsive genes was substantially inhibited after nitrate treatment in the hvnlp2 mutants, indicating that HvNLP2 controls nitrate signaling. Nitrate content was significantly higher in the hvnlp2 mutants, which may result from the decreased assimilation of nitrogen caused by reduced nitrate reductase activity and expression of nitrate assimilatory genes. HvNLP2 is localized to the nucleus in the presence of nitrate. Further investigation showed that HvNLP2 binds to and activates the nitrate-responsive cis-elements. Moreover, hvnlp2 exhibited reduced biomass, seed yield, and NUE. Therefore, HvNLP2 controls nitrate signaling and plays an important role in NUE.
Epigenetic regulation of temperature responses: past successes and future challenges
Authors: Pandey Saurabh Prakash , Benstein Ruben M , Wang Yanwei , Schmid Markus
Published: May 2021

In contrast to animals, plants cannot avoid unfavorable temperature conditions. Instead, plants have evolved intricate signaling pathways that enable them to perceive and respond to temperature. General acclimation processes that prepare the plant to respond to stressful heat and cold usually occur throughout the whole plant. More specific temperature responses, however, are limited to certain tissues or cell types. While global responses are amenable to epigenomic analyses, responses that are highly localized are more problematic as the chromatin in question is not easily accessible. Here we review current knowledge of the epigenetic regulation of FLOWERING LOCUS C and FLOWERING LOCUS T as examples of temperature-responsive flowering time regulator genes that are expressed broadly throughout the plants and in specific cell types, respectively. While this work has undoubtedly been extremely successful, we reason that future analyses would benefit from higher spatiotemporal resolution. We conclude by reviewing methods and successful applications of tissue- and cell type-specific epigenomic analyses and provide a brief outlook on future single-cell epigenomics.
Plastid NDH Pseudogenization and Gene Loss in a Recently Derived Lineage from the Largest Hemiparasitic Plant Genus Pedicularis (Orobanchaceae)
Authors: Li Xin , Yang Jun-Bo , Wang Hong , Song Yu , Corlett Richard T , Yao Xin , Li De-Zhu , Yu Wen-Bin
Published: May 2021

The plastid genome (plastome) is highly conserved in both gene order and content and has a lower mutation rate than the nuclear genome. However, the plastome is more variable in heterotrophic plants. To date, most such studies have investigated just a few species or only holoheterotrophic groups, and few have examined plastome evolution in recently derived lineages at an early stage of transition from autotrophy to heterotrophy. In this study, we investigated the evolutionary dynamics of plastomes in the monophyletic and recently derived Pedicularis sect. Cyathophora (Orobanchaceae). We obtained 22 new plastomes, 13 from the six recognized species of section Cyathophora, six from hemiparasitic relatives and three from autotrophic relatives. Comparative analyses of gene content, plastome structure and selection pressure showed dramatic differences among species in section Cyathophora and in Pedicularis as a whole. In comparison with autotrophic relatives and other Pedicularis spp., we found that the inverted repeat (IR) region in section Cyathophora had expansions to the small single-copy region, with a large expansion event and two independent contraction events. Moreover, NA(D)H dehydrogenase, accD and ccsA have lost function multiple times, with the function of accD being replaced by nuclear copies of an accD-like gene in Pedicularis spp. The ccsA and ndhG genes may have evolved under selection in association with IR expansion/contraction events. This study is the first to report high plastome variation in a recently derived lineage of hemiparasitic plants and therefore provides evidence for plastome evolution in the transition from autotrophy to heterotrophy.
COVID-19 vaccination certificate (CVC) for ASEAN: the way forward?
Authors: Corpuz Jeff Clyde G
Published: May 2021

The emergence of coronavirus disease-2019 (COVID-19) pandemic has stimulated governments to an extensive discussion on the necessity of COVID-19 vaccination certificate (CVC) to help monitor and manage the rollout of vaccinations and revive the economy. A recent correspondence highlighted the ethical issues concerning COVID-19 diagnostic test results and vaccination certificates. This paper highlights the potential benefits and harms of implementing CVC in the ASEAN region.
Collectivism is associated with enhanced neural response to socially salient errors among adolescents
Authors: Rapp Amy M , Grammer Jennie K , Tan Patricia Z , Gehring William J , Chavira Denise A , Miller Gregory A
Published: May 2021

The perceived salience of errors can be influenced by individual-level motivational factors. Specifically, those who endorse a high degree of collectivism, a cultural value that emphasizes prioritization of interpersonal relationships, may find errors occurring in a social context to be more aversive than individuals who endorse collectivism to a lesser degree, resulting in upregulation of a neural correlate of error-monitoring, the error-related negativity (ERN). This study aimed to identify cultural variation in neural response to errors occurring in a social context in a sample of diverse adolescents. It was predicted that greater collectivism would be associated with enhanced neural response to errors occurring as part of a team. Participants were 95 Latinx (n = 35), Asian American (n = 20) and non-Latinx White (n = 40) adolescents (ages 13–17) who completed a go/no-go task while continuous electroencephalogram was recorded. The task included social (team) and non-social (individual) conditions. ERN was quantified using mean amplitude measures. Regression models demonstrated that collectivism modulated neural response to errors occurring in a social context, an effect that was most robust for Latinx adolescents. Understanding cultural variation in neural sensitivity to social context could inform understanding of both normative and maladaptive processes associated with self-regulation.
Pilgrim’s Progress: The Landscape of the NHS Hospital, 1948–70
Authors: DeVane Ed
Published: May 2021

This article argues the politics of land-use was fundamental to the challenges of realizing Britain’s welfare state. It makes this case through a focus on efforts to plan and design new hospitals in the National Health Service (NHS) between 1948 and 1970. It pays particular attention to the Pilgrim Hospital in Boston, Lincolnshire which serves as an exemplar of a sort of politics that has been largely overlooked due to an overemphasis on central government. At the Pilgrim, a private landowner claimed inadequate consultation had produced a hospital proposal that was counter to local opinion, resulting in their farmstead being preserved within the grounds of a modern tower-on-podium facility. Working back from this aesthetic compromise, the significance of the landscaped hospital is introduced and situated within patterns of NHS land transactions and conflicts over site acquisition. This analysis re-orientates historical research to better reflect the decentralized nature of post-war planning in Britain. It does so by demonstrating how the welfare state internalized the criticisms of wider publics and powerful existing cultural and economic frameworks. These necessary processes formed the real groundwork for state modernization.
Comparison of Perioperative Complications in Anterior Decompression With Fusion and Posterior Decompression With Fusion for Cervical Spondylotic Myelopathy
Authors: Morishita Shingo , Yoshii Toshitaka , Inose Hiroyuki , Hirai Takashi , Yuasa Masato , Matsukura Yu , Ogawa Takahisa , Fushimi Kiyohide , Okawa Atsushi , Fujiwara Takeo
Published: May 2021

Study Design:

A retrospective cohort study with a national inpatient database.

Objective:

This study aimed to research the perioperative complication rates of cervical spondylotic myelopathy (CSM) patients who underwent anterior decompression with fusion (ADF) and posterior decompression with fusion (PDF) using a large national inpatient database and propensity score matching (PSM) analysis.

Summary of Background Data:

There are several ways to successfully achieve surgical spinal decompression in CSM patients; however, evidence of the systemic complications and reoperation rates in ADF and PDF is lacking.

Materials and Methods:

We identified patients who were hospitalized for CSM and underwent either ADF or PDF from 2010 to 2016 using the Japanese Diagnosis Procedure Combination database. In the ADF and PDF groups, we compared postoperative complications (systemic and local), medical costs during hospitalization, and mortality before and after PSM. In addition, multivariate regression analysis was performed to identify risk factors for perioperative systemic complications.

Results:

A total of 1013 matched pairs were made after PSM. More perioperative systemic complications were detected in the ADF group than in the PDF group (at least 1 complication: ADF vs. PDF: 15.2% vs. 12.0%, P=0.038), especially for respiratory failure (1.4% vs. 0.4%, P=0.018), pneumonia (1.9% vs. 0.5%, P=0.004), and dysphagia (3.0% vs. 1.1%, P=0.003). The costs were ~$8000 higher (P<0.001) and the length of hospital stay was almost 5 days longer (P<0.001) in the PDF group. The risk factors for perioperative systemic complications in ADF were high age, low body mass index, and preoperative respiratory disease, and the factors in PDF were high body mass index and preoperative renal disease.

Conclusion:

More systemic complications, especially respiratory events, were more frequently observed in the ADF group, while the medical costs were higher and the hospital stay was longer in the PDF group.

Level of Evidence:

Level III.