bluuebunny/crossref_metadata_2025 huggingface dataset:
P538 The reliability of patient performed fecal calprotectin testing
Authors: Crouwel F , Dijkhuis L E J L , Duijvestein M , Buiter H J C , De Boer N K , Hamer H M
Published: May 2021

Background

For measurement of fecal calprotectin (FC) a stool sample is sent to the laboratory, where calprotectin is extracted and determined. With the CALiaGold (CG) tube, especially designed for home sampling, this labor-intensive extraction procedure in the laboratory can be bypassed. Furthermore, the home-use of this buffer containing extraction device can potentially prevent FC degradation. We aimed to determine the reliability of patient performed FC extraction, to assess whether degradation during transport can be prevented and to determine its usability by patients.

Methods

In this prospective cross-sectional observational study, 4 CG tubes and 2 regular tubes were filled from the same bowel movement by patients with inflammatory bowel disease. Half of the tubes were directly frozen, others were sent to the laboratory by mail. Four more CG tubes were filled at the laboratory; 2 from the native sample sent by mail and 2 from the directly frozen native sample. The FC levels were measured by a particle enhanced turbidimetric immunoassay. The directly frozen tubes were used for the comparison between patient and analyst performed extractions, while the tubes sent by regular mail were used to determine FC stability during transport. The usability was assessed with a questionnaire.

Results

Fifty-three patients were included. No significant difference was found in patient performed extractions compared to analyst performed extractions in samples with FC levels <200 µg/g. However, in samples with FC levels ≥200 µg/g patient performed extractions were significantly lower (p=0.014). When patients were divided in 3 groups (i.e. FC levels <50ug/g, 50–200 µg/g and >200 µg/g), the resulting Cohen’s kappa coefficient was 0.787 (95% CI: 0.646–0.928), reflecting a substantial agreement between patient and analyst performed extraction. A median FC increase of 28.6% was found in the native samples after one freeze-thaw cycle, potentially explaining the higher FC levels in the analyst performed extractions from the directly frozen native sample.

Patients sampling imprecision was higher (p<0.01, median CV 17%) compared to the analyst (median CV 8%). Higher FC levels were found in the CG tubes sent by mail compared to native samples, reflecting less FC degradation. The questionnaire revealed that 62% of patients preferred the CG tube and 8% the conventional tube.

Conclusion

Patient performed FC extraction is a realistic alternative sampling method, especially since the freeze-thaw process in the native samples may have led to higher values in the analyst performed extractions. Moreover, usage may prevent FC degradation during transport and patients prefer the use of the extraction device.
P549 Changing Lanes: Switching Therapies in Inflammatory Bowel Disease, An Observational Study
Authors: Mc Gettigan N , Leung E , Harhen A , Anderson E , McMahon S , Walshe M , Keohane J , Sengupta S
Published: May 2021

Background

Switching between therapies in inflammatory bowel disease (IBD) is common and a paucity of data exists regarding the optimal switching strategy. A number of new drug therapies have recently emerged for the treatment of IBD. Failure of biologic and small molecule therapies occur regularly, prompting the need for a treatment switch. Our aim is to review trends amongst our patients who switched biologic/small molecule therapy to identify high risk characteristics and to look for predictor variables which may reduce the need to switch in the future.

Methods

This is a 4 year retrospective observational study of IBD patients who underwent a therapy switch. Patients were identified from a prospectively maintained IBD database of 141 patients. Patient demographics, treatment history, disease history, biomarkers (within 3 months of switch) and endoscopy results were reviewed. Minitab17 was used for statistical analysis.

Results

Switching of biologic therapy was observed in 39 patients (28%); 21 (54%) were male; mean age was 42.8Y. Of these, 21 (53.9%) had Crohn’s disease (CD), 17 (44%) had ulcerative colitis (UC) and 1 patient had indeterminate colitis. Mean disease duration at time of switch was 78 months. 82% (n=14/17) of UC patients had pancolitis. 43% (n=9/21) of CD patients had a previous intestinal resection. The most common initial therapy was Adalimumab 46% (n=18) (Fig1) with the most common switch to IFX 36% (n=14) (Fig2). Primary LOR occurred in 28% (n=11) and secondary LOR in 44% (n=17), the remainder switched due to infusion reaction/adverse effects (n=10) and clinical remission (n=1). Mean CRP was 13.68 (95% CI: 7.28, 20.09), mean FCP was 874 (95% CI: 418, 1329), mean mayo score was 1.88 (95% CI: 1.37, 2.39), mean SES CD score was 5.79 (95% CI: 3.24, 8.33). Median IFX level was 0.8ug/ml (IQR 0.4, 9.7), 37.5% (n=6/16) of the patients on IFX developed ADAs to IFX. Median Adalimumab level was 5.2ug/ml (IQR 1.4, 13.5) and 11% (n=2/18) developed ADAs to Adalimumab. A significant negative correlation was found between FCP and IFX level using Spearman rank correlation -0.822, p = 0.01. 39% (n=15) were on an immunomodulator, no significant association was found between immunomodulator therapy and primary/secondary LOR, p= 0.67 and p= 0.63. 28% (n=11) were admitted with an IBD flare in the 1st year post switch and 13% (n=5) underwent intestinal resection. 8 (21%) subsequently switched to a 3rd biologic agent.

Conclusion

The most common therapy switch was within Anti-TNF drug class, mean CRP and FCP were raised at the time of switch and a significant number of patients were admitted in the year post switch with an IBD flare. Pancolitis in UC and previous intestinal surgery in CD were common characteristics of those who switched.
P553 Factors related to steroid consumption in IBD patients: Evidence from a multicenter Study
Authors: Barkan R , Shpoker L , Abboud R , Nafrin S , Ganon M , Ilsar T , Volf T , Markovitch L , Saban M , Kagan I
Published: May 2021

Background

Steroids are frequently used to induce remission in inflammatory bowel disease (IBD) but should not be used as maintenance treatment. Understanding the factors related to steroid consumption is essential in order to avoid over prescription of these drugs.

Methods

A cross-sectional study was conducted between 2019 and 2020 in six medical centers in Israel. Data was collected using a structured self-administered tool containing the following: socio demographic and clinical characteristics, knowledge of side effects and complications of steroid treatment, self-care and compliance with medical instructions, Steroid Assessment Tool (SAT) and objective physiological measures.

Results

The study included 402 IBD patients; 262 patients with Crohn’s disease (CD) (66%) and 135 patients with ulcerative colitis (UC) (34%). Most of the patients reported being monitored in the IBD unit in the medical centers (87.7%). A quarter of the patients (n=88) had been prescribed systemic steroids over the previous year, and 20 (23%) received 3 or more prescriptions for systemic steroids over the preceding year. Likewise, over 20% of patients were on systemic steroid therapy for over 4 months in the preceding year. Those patients were mostly men and ultra-orthodox. Patients with UC were prescribed steroids more often than CD patients. Knowledge levels regarding appropriate steroid consumption were significantly higher among women (F=40.24, p<.001) and lower among ultra-orthodox patients (X2=6.43, p<.05). Although most of the patients (85.9%) were routinely treated by gastroenterologist, the majority (80%) choose to visit the general practitioner when their disease had flared up.

Conclusion

Several factors were found to be related to inappropriateness use of steroids in IBD patients. Thus, tailored intervention for specific population should be developed to ensure that steroids are used correctly and that their side effects are minimized. Also, infrastructure and alignment of an integrated health care delivery system, with multidisciplinary team may provide the optimal environment for care coordination, especially during disease flare.
P569 Online education significantly improved gastroenterologists’ knowledge of management strategies and treatment options for ulcerative colitis
Authors: Bell E , Calle M
Published: May 2021

Background

Ulcerative colitis (UC) is a challenging condition for gastroenterologists to manage. With the rapid evolution of the treatment landscape and more stringent goals for therapy, many physicians may struggle to stay abreast of current best practice in UC management.

We assessed whether online continuous medical education (CME) can improve gastroenterologists’ knowledge of management strategies and treatment options for UC.

Methods

Gastroenterologists participated in an online CME activity entitled ‘Key Considerations for Treatment Success in Patients With UC’. This was a 45-minute segmented video activity with accompanying slides. Questions were developed to address each of the educational objectives for the activity. Educational effect was assessed using a repeated-pair design, pre-/post-assessment. A Chi-square test of independence determined if a statistically significant improvement (5% significance level, P<.05) existed in the number of correct responses between the pre-test and post-test scores. Cramer’s V estimated the effect size of the education (<.06, modest impact; .06-.15, noticeable impact; .16-.26, considerable impact; >.26, extensive impact). The activity launched on 16 May 2019 with data collection through 11 September 2019.

Results

A total of 1173 gastroenterologists participated in the activity. Of those, 171 completed both pre- and post-questions, providing a set of linked learner data for analysis.

The results showed:

• Significant improvement in average percentage of correct responses, rising from 47% at baseline to 77% post-activity (P<.001) and extensive educational impact (Cramer’s V=.260)

• The percentage of gastroenterologists (n=171) answering all 3 questions correctly more than tripled, from 13% pre-activity to 41% post-activity

• Significant improvements in knowledge of UC pathogenesis, treatment targets according to STRIDE recommendations, and which drug targets IL-12 and IL-23 (P<.001 for all 3 questions)

• 38% of gastroenterologists reported increased confidence in selecting an appropriate therapy for a patient with UC

Conclusion

Online education significantly improved gastroenterologists’ knowledge of management strategies and treatment options in UC which should support them in achieving successful outcomes for their patients. However, there remains a notable gap in knowledge of the STRIDE recommendations and in confidence regarding treatment selection. These results suggest that gastroenterologists would benefit from additional education to reinforce their knowledge of UC management strategies and improve their confidence in translating these principles into clinical practice.
P636 The natural history of COVID-19 in patients with IBD: A nationwide study by the Hellenic Society for the Study of IBD
Authors: Bamias G , Kokkotis G , Christodoulou D , Delis V , Gatopoulou A , Giouleme O , Kalantzis C , Kapsoritakis A , Karatzas P , Karmiris K , Katsanos K , Kevrekidou P , Mathou N , Michalopoulos G , Michopoulos S , Papaconstantinou I , Polymeros D , Potamianos S , Poulopoulos G , Protopappas A , Soufleris K , Theodoropoulou A , Triantafillidis J K , Triantafyllou K , Tsiolakidou G , Tsironi E , Tzouvala M , Viazis N , Zacharopoulou E , Zampeli E , Papatheodoridis G , Mantzaris G J
Published: May 2021

Background

COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to the frequent administration of immune-modifying treatments.

Methods

We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via the unbiased reporting of all cases that were registered during the first and second waves of the pandemic. Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnosis of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies were analysed against adverse outcomes (hospitalization, ICU admission, and death).

Results

We identified 80 patients with IBD who were diagnosed with COVID-19 during the study period (male:65%; median age=44 [IQR=26] years; CD:62.5%). Adverse outcomes were reported in 16 patients (20%), including 3 ICU admissions (3.75%) and 2 deaths (2.5%). Negative prognostic factors for adverse outcomes included age, Body Mass Index, and hypertension, as well as dyspnoea, fatigue and abdominal pain at presentation. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable course COVID-19. Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous medications.

Conclusion

Patients with IBD who developed COVID-19 had a benign course with adverse outcomes being scarce. Treatment with biologics had a beneficial effect, supporting the continuation of therapy during the pandemic.
P649 Ulcerative Colitis Narrative Japanese survey: Identifying gaps between patient and healthcare professional perspectives on communication and disease management to optimise patient care
Authors: Watanabe K , Gardiner S , Arai S
Published: May 2021

Background

The Ulcerative Colitis (UC) Narrative is a global initiative examining perspectives on multiple aspects of UC via 2 related surveys (1 patient [pt]-based and 1 healthcare professional [HCP]-based), with the aim of improving understanding of the impact of UC and identifying gaps in optimal care. We present survey responses from pts and HCPs in Japan, a subanalysis of the global UC Narrative.

Methods

Surveys were conducted by The Harris Poll between Nov 2017 and Jan 2018. Pts (≥18 years of age) met the following criteria: had a diagnosis of UC (confirmed by endoscopy), had not had a colectomy, had taken prescription UC medication beyond 5-aminosalicylates, and had visited a gastroenterologist/internist in the previous year. HCPs were required to see ≥5 pts with UC per month, and ≥10% of their current pts had to be taking a biologic for their UC. Self-reported treatment history was used as a proxy for disease severity, and >80% of pt respondents were required to have moderate to severe UC.

Results

210 pts and 151 HCPs in Japan responded. The mean age of pts with UC was 44.3 (standard deviation 11.6; median 44) years, and 73% were male. Most (85%) pts were satisfied with their communication with their HCP. HCPs slightly underestimated pt satisfaction, believing that, on average, 71% of their pts were satisfied. However, most pts (65%) and HCPs (82%) wished for more discussion about goals for managing or treating UC. Most (83%) pts said they were honest with their HCP when discussing their experiences with UC, although almost half (45%) said they regretted not telling their HCP more; most (75%) HCPs felt that their pts were being honest with them. Over half (55%) of pts said they were hesitant to tell their HCP if they did not take their medication exactly as prescribed; however, most (79%) HCPs believed that >50% of their pts adhered to treatment. HCPs underestimated the importance of toileting accidents to pts (28% vs 54%), and overestimated the importance of mucosal healing (59% vs 29%) (Figure 1). Some pts had misconceptions about treatment: only 69% knew that it was not OK to stop taking UC medications once they felt better, only 76% knew that it was not OK to keep using steroids as a long-term maintenance medication, and only 60% knew that it was possible for their body to stop responding to biologics (Figure 2). Most (71%) HCPs believed that pt advocacy organisations are important, but only recommended them to 26% of pts; only 38% of pts had interacted with one.

Conclusion

There was a high level of concordance in responses between pts in Japan and their HCPs; however, this survey revealed several gaps between pt and HCP perspectives. Consequently, the importance of pt-HCP communication in treat-to-target strategies remains.
P653 Rheumatic extraintestinal manifestations in ulcerative colitis : Prevalence and predictive factors
Authors: Mtir M , Cherif D , Kchir H , Hassine H , Maamouri N
Published: May 2021

Background

Ulcerative colitis (UC) are an inflammatory condition affecting the gastrointestinal tract. They are considered as chronic disease with complex genetic, immune and environmental components. UC are not exclusive to the gastrointestinal system as they have been identified to be associated with extraintestinal manifestations (EIM) that encompass every other organ in the human body including musculoskeletal system.

The aim of this study was to evaluate the prevalence and predictive factors of rheumatic EIM among patients with UC.

Methods

We carried out a retrospective study from January 2000 to December 2018 including all patients with UC. A complete rheumatologic examination, osteodensitometry,lumbosacral and sacroiliac X-rays were performed.The variables retrospectively analyzed were: gender, age,habits, location and extension of the disease, biochemical markers, other EIM, and previous immunosuppressive therapy. We investigated associations between rheumatic manifestations and clinical and biological criteria.

Results

Seventy eight patients were included in our study with an average age of 47,56 years [24–85 years]. Sex ratio M/F 0,85.

Rheumatic manifestations of any type were present in 42,3%(33 of 78). Peripheral arthritis were observed in 3,8%. Axial involvement including sacroiliitis (SI), with or without spondylitis was noticed in 8,97%. Bone mineral loss was present in 25,6% with 13 cases of osteopenia and 7 cases of osteoporosis. Three patients (3,8%) had an association of SI and osteoporosis. No cases of enthesopathy have been reported.

Otherwise, univariate and multivariate logistic regression methods testing for each predictor and their possible association with rheumatic manifestations among UC had shown a decreased risk for rheumatic manifestations with an age over 40 years (p=0,018), an hepatobiliary disorders such as the presence of hepatic cytolysis (p=0,034) and cholestasis (p=0,017) , the coexistence of dermatologic EIM (p=0,048).

Forms complicated with an acute severe ulcerative colitis are likely to be correlated with rheumatologic manifestations (p=0,039) but location and extension of the disease had not shown any significant association.

And finally, patients who underwent systemic corticosteroid treatment were highly associated with a decreased risk for rheumatic manifestations (p=0,044).

Conclusion

Predictive factors involved in the occurrence of rheumatic manifestations are: an advanced age, presence of other EIM, severe forms and the use of steroid. Regular screening for EIM and early use of biological therapies may prevent the development of musculoskeletal involvement . Medical care for patients with UC should be multidisciplinary involving the coordination between rheumatologists and gastroenterologists .
P665 Cardiovascular risk profile in chronic auto-inflammatory diseases: a cross-sectional single center study
Authors: Sleutjes J A M , Roeters van Lennep J E , Verploegh P J P , van Doorn M B A , Vis M , van der Woude C J , de Vries A C
Published: May 2021

Background

Chronic auto-inflammatory diseases are associated with an increased risk of arterial and venous cardiovascular diseases (CVD). Pathogenesis may be related to chronic inflammation and/or traditional CVD risk factors. We aimed to assess the prevalence of CVD and cardiovascular risk profile in inflammatory bowel disease (IBD), psoriasis (PSO) and spondylarthropathies (SpA).

Methods

This is a single center cross-sectional study at the depts. of Gastroenterology, Dermatology and Rheumatology. Patients ≥18 years underwent body measurements (blood pressure (BP), BMI, waist and hip circumference), laboratory analysis (plasma glucose, lipid spectrum) and completed a cardiovascular questionnaire (e.g. history of CVD, medication use). Multivariate linear and logistic regression models corrected for age and sex were applied to identify differences between groups.. Sensitivity analyses were performed excluding patients taking statins or anti hypertensive drugs. Within groups, association between lipid levels and clinical disease activity was assessed by stratification, and with CRP levels by Pearson correlation test.

Results

A total of 668 patients were included (335 males (50%), median age 47 years: 459 IBD (69%), 106 PSO (16%) and 103 SpA patients (15%). (Table 1) The prevalence of venous thromboembolisms was 6%, heart failure 3% and arterial CVD 8%. IBD patients had lower BMI, systolic BP, TC and LDL-c levels, and lower odds ratio of having diabetes, overweight and hypercholesterolemia, as compared to PSO and SpA, but a higher odds ratio of having VTE. (Table 2) These results were independent of statin of anti hypertensive drug use. All groups showed a trend towards higher levels of TC, HDL-c and LDL-c during disease remission as compared to active disease (Figure 1) Overall, TC and LDL-c levels were inversely correlated with CRP (R -.145, p=.002 and R -.111, p=.016); within groups a significant association was only observed in IBD. (Table 3, Figure 2)

Conclusion

IBD patients have a more favorable cardiovascular risk profile, as compared to PSO and SpA. Screening and early intervention for CVD risk factors requires different strategies for each population.
Role of pharmacogenomics in T-cell hypersensitivity drug reactions
Authors: Hertzman Rebecca J. , Deshpande Pooja , Gibson Andrew , Phillips Elizabeth J.
Published: May 2021

Purpose of review

An update of the pharmacogenetic risk factors associated with T-cell-mediated delayed hypersensitivity reactions.

Recent findings

Recent HLA associations relevant to our understanding of immunopathogenesis and clinical practice include HLA-B∗13:01 with co-trimoxazole-induced SCAR, and HLA-A∗32:01 with vancomycin-DRESS, for which an extended HLA class II haplotype is implicated in glycopeptide antibiotic cross-reactivity. Hypoactive variants of ERAP1, an enzyme-trimming peptide prior to HLA loading, are now associated with protection from abacavir-hypersensitivity in HLA-B∗57:01+ patients, and single-cell sequencing has defined the skin-restricted expansion of a single, public and drug-reactive dominant TCR across patients with HLA-B∗15:02-restricted carbamazepine-induced SJS/TEN. More recent strategies for the use of HLA and other risk factors may include risk-stratification, early diagnosis, and diagnosis in addition to screening.

HLA is necessary but insufficient as a risk factor for the development of most T-cell-mediated reactions. Newly emerged genetic and ecological risk factors, combined with HLA-restricted response, align with underlying immunopathogenesis and drive towards enhanced strategies to improve positive-predictive and negative-predictive values. With large population-matched cohorts, genetic studies typically focus on populations that have been readily accessible to research studies, but it is now imperative to address similar risk in globally relevant and understudied populations.
Recent advances in understanding the adaptive evolution of metabolic genes and traits
Authors: Yang Shuang , Ye Kaixiong
Published: May 2021

Purpose of review

This review summarizes the recent advances in understanding the adaptive evolution of metabolic genes and traits, providing insights into gene-diet interactions in human evolution and health.

Recent findings

The rapid accumulation of ancient DNA across time and geography illuminates unprecedented details of some well-established examples of genetic adaptation to diet, such as the LCT and FADS genes. Novel cases of thrifty genes were identified, especially a microRNA at the LCT locus that controls energy expenditure and glucose homeostasis, connecting the historical adaptation to present-day metabolic disorders. A new example of gene–diet–microbiota interactions was established among the AMY1 copy number, starchy diets, and resistant-starch-digesting Ruminococcus. The explosion of genome-wide association studies in large cohorts unravels the present-day health implications of historically adaptive genetic variants. It also enables studies into the polygenic adaptation of metabolic traits, revealing intriguing adaptive signals for increased bone mineral density, blood pressure, and risk of type 2 diabetes, but decreased body mass index and HbA1c.

The rapid accumulation of ancient and modern DNA has fueled the characterization of novel and existing cases of genetic adaptation. However, transferring these evolutionary insights into genome-informed precision nutrition requires extensive mechanistic studies and genotype-aware clinical trials.
Genetic diversity of the pathogenic banana Fusarium wilt in northern Viet Nam
Authors: Thi Loan Le , Mertens Arne , Vu Dang Toan , Vu Dang Tuong , Le Anh Minh Pham , Duc Huy Nguyen , de Backer Sander , Swennen Rony , Vandelook Filip , Panis Bart , Amalfi Mario , Decock Cony , Gomes Sofia I.F. , Merckx Vincent S.F.T. , Janssens Steven B.
Published: May 2021

Fusarium is one of the most important fungal genera of plant pathogens that affect the cultivation of a wide range of crops. Agricultural losses caused by Fusarium oxysporum f. sp. cubense (Foc) have a direct effect on the income, subsistence and nourishment of thousands of smallholder farmers worldwide. In addition, also commercial growers are strongly affected. For Viet Nam, predictions on the impact of Foc for the future are dramatic with an estimated loss in banana production area of 8% within the next 5 years and up to 71% within the next 25 years. In the current study we applied a combined morphological - molecular approach to assess the taxonomic identity and phylogenetic position of the different Foc isolates that were collected in northern Viet Nam. In addition, we aim to estimate the proportion of the different Fusarium races that are infecting bananas in northern Viet Nam. The morphology of the isolates was investigated by growing the collected Fusarium isolates on four distinct nutritious media (PDA, SNA, CLA, and OMA). Molecular phylogenetic relationships were inferred by sequencing partial rpb1, rpb2 and tef1a genes and adding the obtained sequences into a large phylogenetic framework. The present study showed that Foc Race 1 is the most common strain in northern Viet Nam, causing 74% of all the infections. A more in-depth molecular characterization shows that of the Foc Race 1 infections, 92% are caused by Fusarium tardichlamydosporum and 8% by F. duoseptatum. Compared to Foc Race 1, Foc TR4 (represented by F. odoratissimum) account for only 10.5% of the Fusarium wilting in northern Viet Nam demonstrating that Foc TR4 is not yet a dominant strain in the region. Foc Race 2 infections of Vietnamese bananas also account for 10.5% of the Fusarium wilting in northern Viet Nam. One of the isolates cultured from diseased bananas collected in northern Viet Nam was phylogenetically not positioned within the F. oxysporum species complex (FOSC), but in contrast fell within the Fusarium fujikuroi species complex (FFSC). As a result, it is possible that a new pathogen for bananas has been found. Besides being present on several ABB ‘Tay banana’, Foc Race 1 was also found as pathogen on wild Musa lutea, showing the importance of wild bananas as possible sink for Foc.
DYNLL1 mis-splicing is associated with replicative genome instability in SF3B1 mutant cells
Authors: Tam Annie S , Tsai Shuhe , Chang Emily Yun-Chia , Mathew Veena , Shanks Alynn , Docking T. Roderick , Kumar Arun , Bernard Delphine G , Karsan Aly , Stirling Peter C
Published: May 2021

Genome instability is a hallmark of cancer that arises through a panoply of mechanisms driven by oncogene and tumour-suppressor gene mutations. Oncogenic mutations in the core splicing factor SF3B1 have been linked to genome instability. Since SF3B1 mutations alter the selection of thousands of 3' splice sites affecting genes across biological pathways, it is not entirely clear how they might drive genome instability. Here we confirm that while R-loop formation and associated replication stress may account for some of the SF3B1-mutant genome instability, a mechanism involving changes in gene expression also contributes. An SF3B1-H662Q mutant cell line mis-splices the 5'UTR of the DNA repair regulator DYNLL1, leading to higher DYNLL1 protein levels, mis-regulation of DNA repair pathway choice and PARP inhibitor sensitivity. Reduction of DYNLL1 protein in these cells restores genome stability. Together these data highlight how SF3B1 mutations can alter cancer hallmarks through subtle changes to the transcriptome.
High-pressure and environment effects in selenourea and its labile crystal field around molecules
Authors: Roszak Kinga , Katrusiak Andrzej
Published: May 2021

Ambient-pressure trigonal phase α of selenourea SeC(NH2)2 is noncentrosymmetric, with high Z′ = 9. Under high pressure it undergoes several intriguing transformations, depending on the pressure-transmitting medium and the compression or recrystallization process. In glycerine or oil, α-SeC(NH2)2 transforms into phase β at 0.21 GPa; however in water, phase α initially increases its volume and can be compressed to 0.30 GPa due to the formation of α-SeC(NH2)2·xH2O. The single crystals of α-SeC(NH2)2 and of its partial hydrate α-SeC(NH2)2·xH2O are shattered by pressure-induced transitions. Single crystals of phase β-SeC(NH2)2 were in situ grown in a diamond-anvil cell and studied by X-ray diffraction. The monoclinic phase β is centrosymmetric, with Z′ = 2. It is stable to 3.20 GPa at least, but it cannot be recovered at ambient conditions due to strongly strained NH...Se hydrogen bonds. No hydrogen-bonding motifs present in the urea structures have been found in selenourea phases α and β.
Resolution of a bent-crystal spectrometer for X-ray free-electron laser pulses: diamond versus silicon
Authors: Kaganer Vladimir M. , Petrov Ilia , Samoylova Liubov
Published: May 2021

The resolution function of a spectrometer based on a strongly bent single crystal (bending radius of 10 cm or less) is evaluated. It is shown that the resolution is controlled by two parameters: (i) the ratio of the lattice spacing of the chosen reflection to the crystal thickness and (ii) a single parameter comprising crystal thickness, its bending radius, distance to a detector, and anisotropic elastic constants of the chosen crystal. The results allow the optimization of the parameters of bent-crystal spectrometers for the hard X-ray free-electron laser sources.
Exploring push and pull factors for talent development and retention: implications for practice
Authors: Mutanga Justine , Kaisara Godwin , Yakobi Khulekani , Atiku Sulaiman Olusegun
Published: May 2021

Purpose

This study explores some of the key push and pull factors to consider in talent development and retention of competent employees by businesses operating in Namibia.

Design/methodology/approach

The participants in this study comprised of randomly selected white-collar employees in Namibia. The study adopted a qualitative research approach, utilizing online focus groups to gain insights related to white-collar labor turnover and retention. Thematic content analysis was employed during the data reduction process.

Findings

The findings revealed specific push and pull factors for consideration in developing talent retention strategies in contemporary business organizations.

Originality/value

Most of the extant literature on white-collar retention and labor turnover is based on Western contexts. The findings of this study contribute to the available literature by providing a perspective from the developing world, specifically, Namibia.
Coproducing digital archives with 2SLGBTQ+ Atlantic Canadian youth amidst the COVID-19 pandemic
Authors: Burkholder Casey , MacEntee Katie , Mandrona April , Thorpe Amelia , Pride/Swell Pride/Swell
Published: May 2021

Purpose

The authors explore the coproduction of a digital archive with 50 2SLGBTQ+ youth across Atlantic Canada during the COVID-19 pandemic in order to catalyze broader public participation in understanding 2SLGBTQ+ youth-led activism in this place and time through art production.

Design/methodology/approach

Through a mail-based participatory visual research project and an examination of collage, zines and DIY facemasks, the authors highlight how the production, sharing and archiving of youth-produced art adds to methodological discussions of exhibiting and digital archiving with 2SLGBTQ+ youth as a form of activist intervention.

Findings

In reflexively examining the cocuration of art through social media and project website, the authors argue that coproducing digital archives is an important part of knowledge mobilization. Also, the authors consider how the work has been interacted with by a broader public, so far in an exclusively celebratory manner and note the benefits and challenges of this type of engagement to the youth and to the understandings of 2SLGBTQ+ youth archives.

Originality/value

The authors suggest that these modes of engaging in participatory visual research at a distance offer original contributions in relation to how participation can be understood in a digital and mail-based project. The authors see participant control of how to share works within digital archives as a contribution to the understanding of people's capacity to negotiate and take ownership of these spaces. These strategies are participant-centered and suggest ways that archiving can be made more accessible, especially when working with communities who are socially marginalized or otherwise excluded from the archival process.
Electrosonic statecraft
Authors: VANDERMEULEN IAN
Published: May 2021

On a radio show operated by Morocco's National Broadcasting Service, listeners call in to recite the Qur’ān on air and receive critical commentary on their performance from the show's hosts. The show, called Learn Recitation of the Qur’ān, is linked politically and discursively to Morocco's broader “recitational revival” (ṣaḥwa tajwīdīyya) and to its concerns with a distinct “Moroccan” variant of Qur’ānic recitational practice. The show's on‐air pedagogical encounter is ultimately mediated by a confluence of technologies, built space, and discursive authority in the “backstage” space of the radio station's studio—producing what I call electrosonic statecraft. Yet this form of statecraft is ultimately caught between guiding the individual pedagogical progress of its subjects and expanding its community of reciters. This forces subjects to endure forms of “latency,” meaning technological interruptions or participatory deferrals that delay their pedagogical progress, rendering a “perfect” recitation, and perhaps the state itself, seemingly imminent yet always just beyond reach. [radio, media, sound, technology, statecraft, Qur’ān, Islam, Morocco]
Ruins for the future
Authors: LITTLEJOHN ANDREW
Published: May 2021

In 2011 a tsunami over 20 meters high struck Japan's northeastern coastline. Along with causing close to 20,000 deaths, it destroyed many buildings, leaving behind a landscape of ruins. In the years since the disaster, various groups in Japan have interpreted these ruins as a way to work through “what went wrong.” Some pointed to local officials’ failure to properly prepare for the disaster, as well as the form of economic development that they had promoted. Others, however, particularly state officials, argued that the ruins of failed development reveal something that can be used to stimulate economic recovery and legitimize further development. Ironically, these groups mobilized the debris of “progress” to advance progress itself, complicating theories of recent ruins as “counter‐sites.” This shows that actors can construct and leverage the truth content of ruins in support of the very ideologies and processes that caused their ruination in the first place. [3.11, disaster, governance, materiality, modernity, ruination, Japan]
Reply to the comment of Schollnberger on ‘Subsidence analysis of salt tectonics‐driven carbonate minibasins’ (Northern Calcareous Alps, Austria), published on Basin Research 2020; 00: 1– 23 doi:10.1111/bre.12500
Authors: Strauss Philipp , Granado Pablo , Muñoz Josep Anton
Published: May 2021

The subsidence analysis study presented by Strauss et al. (Basin Research, 2020, doi: 10.1111/bre.12500) for Triassic carbonate platforms located in the eastern Northern Calcareous Alps shows that salt expulsion allowed for the growth of thick isolated depocenters (>1.5 km) at rates faster than that tectonic subsidence alone can provide. In this answer to a comment by Schollnberger (Basin Research, 2021, doi: 10.1111/bre.12549) we discuss in detail the rationale behind our subsidence model and the assessment of the initial salt thickness. Excellent biostratigraphic control as well as precise knowledge of paleo‐bathymetry for most of the sedimentary record allowed to setup the subsidence model with well‐defined boundary conditions.
Ut primatum habeant: the early medieval church in Dalmatia and the Aquileian strategy
Authors: Prozorov Vadim
Published: May 2021

In the ninth century, the church of Rome, having lost power in the Balkans in the iconoclastic period, struggled to maintain control over the eastern Adriatic coast, which was divided between the Byzantine and Frankish empires. The Dalmatian church hierarchy strived to preserve the integrity of their province under the authority of the archbishop of Spalatum, but was challenged by the bishop of Nona from the Slavic Duchy of the Croats, who claimed the metropolitan status for himself. Their conflict was resolved at the Councils of Spalatum in 925 and 928. The article re‐examines the ninth‐ and tenth‐century context for the councils, and suggests parallels between the Dalmatian case and the earlier debate between Cividale and Grado over metropolitan authority in the province of Aquileia. It demonstrates that the Dalmatian church may have followed an Aquileian precedent.
On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice
Authors: Pulles Astrid E. , van Vulpen Lize F. D. , Coeleveld Katja , Mastbergen Simon C. , Schutgens Roger E. G. , Lafeber Floris P. J. G.
Published: May 2021

Introduction

Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease‐modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A previous study in haemophilic mice demonstrated that treatment with the iron chelator deferasirox (DFX) 8 weeks before joint bleed induction, attenuated cartilage damage upon blood exposure. However, in haemophilia patients this approach is not opportune given the unpredictable occurrence of hemarthroses.

Aim

To evaluate the effectiveness of on‐demand DFX treatment, initiated immediately after joint bleed induction.

Methods

A joint bleed was induced in 66 factor VIII‐deficient mice by infra‐patellar needle puncture. Mice were randomly assigned to treatment with either placebo (drinking water) or DFX (dissolved in drinking water) throughout the study. Five weeks after joint bleed induction, inflammation and cartilage damage were assessed histologically. Joints of ten bleed naive haemophilic mice served as controls.

Results

A joint bleed resulted in significant inflammation and cartilage damage in the blood‐exposed joint compared with those of control animals, in both the placebo and DFX group (all p = <.05). No differences in tibiofemoral or patellar inflammation (p = .305 and p = .787, respectively) nor cartilage damage (p = .265 and p = .802, respectively) were found between the blood‐exposed joints of both treatment groups.

Conclusion

On‐demand treatment with DFX does not prevent joint damage following blood exposure in haemophilic mice. DFX seems unable to reach the joint in time to exert its effect before the irreversible harmful process is initiated.
Estimation of neutrophil activation marker in lichen planus patients
Authors: Khattab Fathia M. , Ghonaim Rania , Samir Mai A.
Published: May 2021

Background

Lichen planus disease is a chronic inflammatory disorder of mucosal and cutaneous tissues, and its etiology and pathogenesis are unclear. Cytokines have a significant role in the beginning, the maintenance of inflammatory and intercellular crosstalk.

Aim

We assessed serum levels of neutrophil activation marker (calprotectin) in patients with cutaneous lichen planus with different subtypes and made a comparison with healthy individuals.

Materials and Method

Peripheral blood samples of 30 cases with lichen planus were compared with 30 healthy individuals. Serum samples were prepared from LP patients, using a commercial ELISA kit, and calprotectin level was measured in each serum sample.

Results

The serum level of calprotectin was significantly raised in LP cases compared with control (141.34 ± 17.47 ng/ml versus 40.03 ± 1.54 ng/ml respectively; p < 0.001). No correlation was recorded among of serum of calprotectin and patients’ ages, sex, disease period, and the existence or strength of pruritus. But a strong positive correlation was present between the coexistence of oral lesions and the number of locations.

Conclusion

Calprotectin can be used as a marker of Lichen planus severity and progression. Calprotectin may play a role in the pathogenesis of LP.
A unique disaster response in aged residential dementia care: Can the experience inform future care models?
Authors: Moir Chris , Lesa Raewyn , Ritchie Lorraine
Published: May 2021

Aims and Objectives

To understand how staff who chose to live‐in with residents in a level 3 dementia care unit perceived the experience, in particular, their perceptions of how residing on site affected resident well‐being.

Background

COVID‐19 has been especially devastating in aged residential care (ARC) facilities. In March 2020, when the threat became realised in New Zealand, one residential dementia care facility implemented a unique response to the imminent threat of COVID‐19. Eight staff members made the decision to live on site during the lockdown, ensuring residents’ risk of contracting the virus was significantly reduced as carers would not go outside of the facility.

Design

A qualitative descriptive inquiry.

Methods

Seven staff who chose to live‐in, and the facility manager, participated in semi‐structured, face‐to‐face interviews at the ARC. Audio‐recorded interviews were transcribed verbatim and analysed using a thematic analysis approach. COREQ guidelines were adhered to in the reporting of this study.

Results

An overarching motif which emerged from the findings was the articulation of an ‘all in this together’ attitude which fostered feelings of camaraderie and collaboration which enhanced the experience for staff individually, and as a group. Themes identified were as follows: (a) A ‘safe’ but challenging choice, (b) Benefits for the staff and (c) Positive outcomes for the residents.

Conclusion

This crisis inadvertently brought about an enhanced ‘dementia‐friendly’, person‐centred communal environment.

Relevance to clinical practice

This study identified themes that deepen our understanding of caring for vulnerable populations during a pandemic and beyond. Given the success of this ‘live‐in’ innovation, consideration must be given to applying these findings more generally when planning care models for best outcomes for residents receiving rest home level dementia care. How we care for people in disaster situations reflects the heart of the caring workforce, but such innovation may be extended to usual care where indicated.
Influence of patterns of neonatal transfers on breastfeeding outcomes
Authors: Sinclair Lynn , Spence Kaye , Galea Claire ,   NSW Neonatal Clinical Nurse Consultant Network and NICUs
Published: May 2021

Aim

To investigate/evaluate the impact of hospital transfers on breastfeeding outcomes for infants requiring neonatal intensive care and to explore approaches to supporting lactation and breastfeeding.

Methods

A national study of two cohorts of infants admitted to the nine neonatal intensive care units (NICUs) in New South Wales (NSW) Australia using data sourced from a prospectively collected NICUS data collection.

Results

A total of 7829 infants were admitted to the nine NICUs in NSW for two 18‐month cohorts (2012/2013 and 2015/2016) and were included in the study. These infants experienced 17 238 transfers to 107 different hospitals during the study period. Multiple transfers and low gestational age were independently associated with lower breastfeeding rates at hospital discharge across both cohorts. Extremely preterm infants and those with the greatest number of hospital transfers are least likely to be breastfed at time of discharge. Breastfeeding rates remained unchanged over time. The level of lactation support varied across NICUs.

Conclusion

This study highlights the challenges of establishing and maintaining breastfeeding for infants requiring intensive care who have had multiple hospital transfers for continuing or specialist care. There is wide variation in lactation support across facilities. The importance of a consistent approach, education programmes and the provision of appropriate lactation support is emphasised.
The persistence of inequality across Indian states: A time series approach
Authors: Bandyopadhyay Sanghamitra
Published: May 2021

There is a growing literature on the importance of persistent regional inequalities in developing countries, with evidence that the lack of convergence in incomes across regions is associated with a rise in conflict and social unrest. However, there is a relative paucity of literature on the stochastic characteristics of gross domestic product at the sub‐national level. In this paper we identify new stochastic properties of Indian states' gross domestic product between 1960 and 2019 using a fractional stochastic convergence approach. We test for fractional stochastic convergence in relative incomes in order to identify high persistence and mean reversion. Interval estimates of the largest autoregressive coefficient for the relative incomes of Indian states are wide, thus including many alternatives that are persistent. Interval estimates of the half‐life of relative income shocks suggest that in several cases shocks die out within 0–10 years. Finally, we estimate a fractionally integrated model and obtain mixed evidence of mean reversion and non‐stationarity, with six out of 16 states experiencing mean reversion. These results are highly encouraging and contradict earlier studies which show long‐term divergence and polarization of regional incomes across Indian states, and are thus of great relevance to policy‐makers.
THE USE OF FERROMAGNETIC AMORPHOUS MATERIALS 5BDSR IN HIGH-FREQUENCY OVERVOLTAGE PROTECTION DEVICES
Authors: Korobeynikov Sergey , Loman Valentin
Published: May 2021

The paper discusses the prospects of using nanocrystalline amorphous materials in the electric power industry. In particular, in the field of protection of electric power equipment of substations from high-frequency pulses. The effectiveness of using such materials to activate the anomalous skin effect in multilayer conductors is shown. The resulting conductors increase their resistance at lightning frequencies, thereby making it possible to create devices that effectively suppress high-frequency pulses. The authors give an example of a protective frequency-dependent device using nanocrystalline ferromagnetic material and the results of its use in trial operation. The paper shows the results of comparing round and flat frequency-dependent conductors.