bluuebunny/crossref_metadata_2025 huggingface dataset:
P599 Perspectives on disease- and treatment-related issues encountered by patients with Inflammatory Bowel Disease: a qualitative concept mapping study
Authors: Risager Christensen K , Steenholdt C , Skougaard M , Ainsworth M A , Brynskov J , Buhl S , Kristensen L E , Schjødt Jørgensen T
Published: May 2021

Background

Therapeutic options for inflammatory bowel diseases (IBD) have documented effect on hard endpoints such as clinical and endoscopic remission. However, little is still known about issues that are of concern and importance to patients. This study aimed to explore, and rate, the importance of treatment- and disease-related issues and concerns experienced by patients with Crohn’s disease (CD) and ulcerative colitis (UC) by a state-of-the art qualitative approach.

Methods

Concept Mapping (CM) is a validated qualitative method, widely used to identify and organize disease- and treatment-related issues. In 8 CM workshops each with 3–4 participating patients, patients’ statements were elicited through a nominal group technique and organized using themes. The statements were visualized by multidimensional scaling, and cluster analysis was used to retrieve clusters organized by themes. The result was validated by patients, and further rated in terms of clinical importance. Then, thematic analyses were performed to generate a conceptual model of disease-related issues and concerns.

Results

In all, 13 CD and 13 UC patients participated of whom 7 (53%) and 3 (23%) were in clinical remission. There were 8 (62%) and 9 (69%) females, median disease duration of 17 years (IQR 12–20) and 11 years (5–15) respectively. In each disease group, 12 (92%) received biologics and 1 (8%) thiopurine, median age was 42 years (38–50). In the CD and UC workshops, 335 and 408 statements were generated, respectively, resulting in 10 CD and 11 UC clusters. The 5 highest rated clusters from each disease group along with generic clusters are shown in the Figure 1ab. Three clusters were rated to be “very important” (mean ≥ 4) for CD (Positive attitude, Acceptance and recognition, and Personal experiences living with CD), and 1 cluster for UC (Take responsibility and control over your own life). In the above-mentioned clusters, statements rated as of great importance (median= 5) were scattered as follows for CD 6/15 (40%), 10/35 (29%) and 12/30 (40%), respectively; and for UC 27/62 (44%)). In addition, UC patients also rated statements about efficacy of medication, and concerns and consequences high. CD patients created 26 (8%) (median=4) and UC 10 (2.5%) (median=4.5) symptoms specific statements scattered in different clusters.

Conclusion

The majority of the core concepts found in this study originated from patients’ perspectives focused on personomics, rather than from conventional patient reported outcomes such as bowel symptoms. Some core concepts differed across diseases, but most were independent of disease type. These data offer new knowledge to guide selection of clinically relevant and value-based treatment outcomes for IBD patients.
P620 Pivoting in a pandemic: The impact of COVID-19 on the provision of care for patients with Inflammatory Bowel Disease – A retrospective study
Authors: Malhi G , Chambers J , Minhas G , Mikail M , Khanna R , Wilson A
Published: May 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, also known as COVID-19, initially began in a small cluster of patients in Wuhan, China and was declared a worldwide pandemic in March of 2020. Since the onset of the pandemic, the focus of many healthcare systems has shifted toward limiting non-essential visits to the hospital in order to prioritize and allocate resources toward treating those affected by COVID-19. While the effect of COVID-19 has been felt amongst many patient populations, those with Inflammatory Bowel Disease (IBD) have been particularly impacted. We aimed to determine how changes to the provision of IBD care due to the COVID-19 pandemic has affected IBD patients.

Methods

A retrospective cohort study was carried out in patients with an IBD diagnosis comparing patients admitted to two tertiary care centres affiliated with Western University in London, Canada between March 17 and August 31 2019 (2019 cohort or pre-pandemic), to patients admitted between March 17 and August 31 2020 (2020 cohort or pandemic). Patients were reviewed to assess any differences in care utilization and IBD-related outcomes such as hospitalization, need for surgery, length of stay in hospital and in-patient drug therapy during the defined time periods.

Results

A total of 863 patients were reviewed in 2019, and 554 in 2020. Of those, 184 (CD, n= 125; UC, n= 59) and 172 (CD, n= 109; UC, n= 62) encounters met the inclusion criteria for 2019 and 2020 respectively. Patient demographics were similar between 2019 and 2020 cohort with the exception of age (2019, mean age = 44.76 years ± 16.78; 2020, mean age=50.36 years ± 17.82, p=0.002). The length of stay in hospital was shorter in 2020 (6.88 days vs 9.63, p=0.045). Significantly fewer patients were initiated on Infliximab in hospital in 2020 (2020, 3.50 per month; 2019, 6.83 per month, p=0.001). Fewer in-patient surgeries were performed in 2020 (2019, 76; 2020, 57; p=0.112).

Conclusion

Preliminary data demonstrate during the COVID-19 pandemic there was a significant reduction in the length of stay for patients with IBD as well as fewer patients initiated on infliximab while in hospital. There was also a decrease in the number of surgeries performed in 2020. These differences may reflect an effort to minimize contact between patients and health care facilities as well as reduce the introduction of further immunosuppression. Further research will be to determine whether if more ER visits became hospitalizations and any delays in appointment times or endoscopies, or compliance issues with medications may have led to these aforementioned outcomes.
P632 Is the gender or age of the physician key to a good physician-patient with Inflammatory Bowel Disease relationship?
Authors: García Mateo S , Martínez-Domínguez S J , Gargallo-Puyuelo C J , Gomollón García F
Published: May 2021

Background

The importance of good patient-physician relationship in chronic diseases, including Inflammatory Bowel Disease (IBD), is well stablished. Empathy has become one of the most important researches items in terms of patient-physician relationship because it is positive influence on the quality of care.

The aim of the study was to assess the level of IBD specialist physician′s empathy as perceived by their patients and if it varies according to the age and gender of the patient and the physician.

Methods

This is a national cross-sectional study. Recruitment was conducted between July and November of 2020 by sending a voluntary online survey to IBD patients who take part of Spanish association of patients with IBD (ACCU España). The survey included CARE (Consultation and Relational Empathy) scale (maximum score 50 points and minimum 10 points).

Results

Five hundred sixty one responses to the survey were received. After applying exclusion criteria, 536 patients were included in the analysis. Total median score of CARE scale was 44.50 (IQR 31.25–50.00), that reflects a very good punctuation. Most of the patients (531 (99.1%)) considered the contents of the questionnaire to be an important issue. Analyzing CARE scale scores of cases in which the sex of patient and physician were the same compared who did not, no statistically significant differences were found. No differences were found either, comparing punctuation of CARE scale based on patient-physician age ranges as is shown in Table 1.

n (%): Absolute frequency (percentage). *Median (IQR). **Univariate analysis performed with U Mann-Whitney test or Kruskal-Wallis

Conclusion

Spanish IBD patients have a great IBD specialist empathy perception, which is the key to a good patient-physician relationship, and this fact is not influenced by age or gender of patients or physicians.
P688 Association of Akkermansia muciniphila with a healthy gut microbiome
Authors: Ellul S , Rausch P , PIsani A , Bang C , Ellul P , Franke A
Published: May 2021

Background

Comprehensive knowledge of the types and ratios of microbes present in the healthy gastrointestinal human gut is required before any study is attempted to alter the microbiome to treat one condition. Akkermansia muciniphila, a mucin-degrading bacterium, belonging to the phylum Verrucomicrobia, has been inversely associated with inflammation and diabetes whilst it has been internationally proposed as one of the contributors for maintaining a healthy gut and glucose homeostasis. Studies noted that higher amounts of this microorganism in the gut microbiota was linked to a metabolically healthier lifestyle; therefore, linking an interaction between the gut bacterial richness and abundance of A. muciniphila. This organism was noted to improve the gut barrier using its outer membrane protein Amuc 1100, which seems to interact with Toll-like receptor 2, whilst potentially adhering to intestinal epithelial cells, leading its role in balancing the human immunological homeostasis whilst strengthening the monolayer integrity of the wall.

The aim of this study was to assess if there is any difference in the presence of Akkermansia muciniphila between IBD patients and controls.

Methods

Faecal microbiota from newly diagnosed treatment naïve IBD patients and controls were analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq.

Results

100 patients with IBD and 97 controls were recruited. Forty-one different ASVs were identified from our cohort, all of which being differentially abundant between the different health conditions present. From these, 20 ASVs such as ASV-14 G-Alistipes uncl., and ASV 20-Akkermansia muciniphila, were found to be more abundant in healthy individuals than in IBD patients. There was no dietary association.

Conclusion

In this study Akkermansia muciniphila was significantly found in higher amount in the healthy control population than in the IBD cohort. The potential role of repopulating the gut bacteria with Akkermansia muciniphila needs to be investigated as to reduce the burden of disease, medications prescribed and the clinical outcome.
Age-replacement policy for items described by stochastic degradation with dependent increments
Authors: Cha Ji Hwan , Finkelstein Maxim , Levitin Gregory
Published: May 2021

We consider a hybrid preventive maintenance policy. As in the classic model of age-replacement, a system is replaced either on failure or on reaching a predetermined age T. Additionally, it can be replaced on reaching a predetermined level of deterioration at some intermediate time in [0,T). We use a transformed gamma process with dependent increments to model the deterioration. A failure of an item occurs when this process reaches a predetermined deterministic level. We show that the proposed policy outperforms the classical one, that is, it achieves a lower value of the long-run cost rate. A detailed numerical illustration is presented and sensitivity analysis for the main parameters of the model is performed. The work in the paper makes an important contribution to maintenance modelling because dependent increments can better represent deterioration of a real system.
Haemosporidian prevalence and community composition vary little across a chickadee hybrid zone
Authors: Rice Ari A , Curry Robert L , Weckstein Jason D
Published: May 2021

Within animal hybrid zones, parasites may determine competitive outcomes between host species and thus affect hybridization dynamics. We addressed this hypothesis by evaluating haemosporidian prevalence and community composition in a rapidly moving hybrid zone between Black-capped Chickadees (Poecile atricapillus) and Carolina Chickadees (P. carolinensis). Using molecular methods, we screened for haemosporidians in multiple chickadee populations across the hybrid zone and investigated whether parasite prevalence varied as a function of admixture among these birds. We identified 36 parasite lineages from 3 haemosporidian genera (Plasmodium, Haemoproteus, and Leucocytozoon) but found no genera or lineages more likely to infect any particular chickadee taxon. Instead, haemosporidian prevalence varied across sites and seasons: Leucocytozoon was more prevalent during chickadees’ breeding season, whereas Haemoproteus prevalence peaked during nonbreeding periods. Leucocytozoon infected proportionally fewer birds at the leading edge of the hybrid zone than near its center. However, haemosporidian communities were similar among chickadee populations, and evidence for parasite exchanges between chickadee taxa was lacking. These results underscore the complexity of bird–parasite relationships and suggest that haemosporidians are unlikely to play a major role in the ongoing movement of this hybrid zone.
Medical neglect in Ontario: Implications for health care provision
Authors: Allan Kate , Joh-Carnella Nicolette , Fallon Barbara , Vandermorris Ashley , Houston Emmaline
Published: May 2021

Objectives

This study explores child welfare investigations for medical neglect in Ontario, Canada, focusing on household, family and child characteristics of such investigations and factors associated with substantiated victimization.

Methods

This analysis used data from the Ontario Incidence Study of Reported Child Abuse and Neglect 2018. Bivariate analyses compared medical neglect with other neglect investigations to create a profile of medical neglect investigations in Ontario, and a binary logistic regression determined which case characteristics were associated with substantiation of medical neglect.

Results

Compared with other neglect investigations, medical neglect investigations were more likely to involve children less than 1 year old and caregivers under 21 years old, households that had run out of money in the past 6 months for basic necessities, primary caregivers with few social supports, mental health issues or drug/solvent abuse concerns, and children with at least one functioning concern. Medical neglect investigations in which the primary caregiver had few social supports were almost four times more likely to be substantiated (OR=3.698, P<0.05).

Conclusions

While the public’s perception of medical neglect tends to focus on parental refusal of treatment due to philosophical/religious beliefs, this Ontario sample indicates that medical neglect is often driven by financial constraints and a lack of social support. Implications for health care providers within a universal health care system are discussed.
Expression Patterns and Functional Characterization of Arabidopsis Galactose Oxidase-Like Genes Suggest Specialized Roles for Galactose Oxidases in Plants
Authors: Šola Krešimir , Dean Gillian H , Li Yi , Lohmann Julia , Movahedan Mahsa , Gilchrist Erin J , Adams Keith L , Haughn George W
Published: May 2021

Galactose oxidases (GalOxs) are well-known enzymes that have been identified in several fungal species and characterized using structural and enzymatic approaches. However, until very recently, almost no information on their biological functions was available. The Arabidopsis (Arabidopsis thaliana) gene ruby particles in mucilage (RUBY) encodes a putative plant GalOx that is required for pectin cross-linking through modification of galactose (Gal) side chains and promotes cell–cell adhesion between seed coat epidermal cells. RUBY is one member of a family of seven putative GalOxs encoded in the Arabidopsis genome. To examine the function(s) of GalOxs in plants, we studied the remaining six galactose oxidase-like (GOXL) proteins. Like RUBY, four of these proteins (GOXL1, GOXL3, GOXL5 and GOXL6) were found to localize primarily to the apoplast, while GOXL2 and GOXL4 were found primarily in the cytoplasm. Complementation and GalOx assay data suggested that GOXL1, GOXL3 and possibly GOXL6 have similar biochemical activity to RUBY, whereas GOXL5 only weakly complemented and GOXL2 and GOXL4 showed no activity. Members of this protein family separated into four distinct clades prior to the divergence of the angiosperms. There have been recent duplications in Brassicaceae resulting in two closely related pairs of genes that have either retained similarity in expression (GOXL1 and GOXL6) or show expression divergence (GOXL3 and RUBY). Mutant phenotypes were not detected when these genes were disrupted, but their expression patterns suggest that these proteins may function in tissues that require mechanical reinforcements in the absence of lignification.
Apparent total tract nutrient digestibility and metabolizable energy estimation in commercial fresh and extruded dry kibble dog foods
Authors: Tanprasertsuk Jirayu , Perry LeeAnn M , Tate Devon E , Honaker Ryan W , Shmalberg Justin
Published: May 2021

Commercial fresh cooked foods have started gaining popularity among American dog owners in recent years. However, nutrient digestibility and the estimation of metabolizable energy (ME) of commercial fresh dog foods remain inadequately understood, even though both measures are critical to provide the intended calories for the target animal. In this preliminary study, different cohorts of normal-weight dogs were fed one of five test diets of comparable macronutrient composition: a chicken-based extruded dry kibble diet (n = 12), and chicken- (n = 12), beef- (n = 6), pork- (n = 6), or turkey-based fresh food (n = 6) for 10 d. Daily food intake and fecal characteristics were recorded, and fecal samples were collected for nutrient analysis. Despite comparable dry matter (DM) and caloric intakes between the two chicken-based diets, the fresh diet led to lower defecation frequency (1.2 ± 0.2 vs. 1.7 ± 0.5 times/d, adjusted P < 0.001), lower fecal DM (24 ± 8 vs. 47 ± 10 g/d, adjusted P < 0.001), and lower fecal calories (92 ± 31 vs. 189 ± 43 kcal/d, adjusted P < 0.001) than the kibble diet. The apparent total tract digestibility of DM, protein, fat, nitrogen-free extract, and calories of the kibble diet were all significantly lower than any of the fresh diets (adjusted P < 0.001 for all). Measured ME per food DM in all of the fresh diets, except the pork-based recipe, was significantly higher than that of the kibble diet (adjusted P < 0.001 for all). For the kibble diet, the modified Atwater calculation underestimated the ME and the NRC 2006 calculation was the most accurate predictor of ME. The standard Atwater calculation performed best for the two fresh diets that had the highest fat content (chicken, beef) and the NRC 2006 calculation performed best for the fresh diet that had the highest protein content (pork). ME of the turkey-based diet was equally overestimated and underestimated with the standard Atwater and NRC 2006 methods, respectively. We propose that commercial and home-prepared fresh diets should be assessed using standard Atwater factors as commonly done in human nutrition, or preferably for commercial products, by direct measurement in conforming feeding trials.
Brain Plasticity Reflects Specialized Cognitive Development Induced by Musical Training
Authors: Choi Uk-Su , Sung Yul-Wan , Ogawa Seiji
Published: May 2021

Learning a musical instrument requires a long period of training and might induce structural and functional changes in the brain. Previous studies have shown brain plasticity resulting from training with a musical instrument. However, these studies did not distinguish the effects on brain plasticity of specific musical instruments as they examined the brain of musicians who had learned a single musical instrument/genre and did not control for confounding factors, such as common or interactive effects involved in music training. To address this research gap, the present work investigated musicians who had experience with both a piano and a wind instrument, for example, flute, trumpet, clarinet etc. By examining the difference between the 2 musical instruments in the same subject, we avoided the effects common to all musical instruments and the confounding factors. Therefore, we identified several high-tier brain areas displaying a brain plasticity specific to each musical instrument. Our findings show that learning a musical instrument might result in the development of high cognitive functions reflecting the skills/abilities unique to the instrument played.
Taking a Rational Approach to a Reported Antibiotic Allergy
Authors: Berghuis Dagmar , Lambregts Merel M.C. , de Boer Mark G.J.
Published: May 2021

Up to 10% of hospitalized patients have an antibiotic allergy label in their medical file, most frequently concerning penicillins. However, the vast majority of reported allergies to antibiotics does not represent a “true” allergy but are due to drug intolerance, idiosyncratic reactions or symptoms of the concurrent infectious disease. Since antibiotic allergy labels result in deviation from first-choice antimicrobial therapy, tackling the issue of incorrect antibiotic allergy labelling, already at young age, is a core element of antibiotic stewardship. In this article, we describe the structured approach to the patient with a presumed antibiotic allergy with emphasis on key elements of allergy-specific history taking and the limited risk of cross-allergic reactions between beta-lactam subclasses.
Pheochromocytomas and paragangliomas
Authors: Yen Kevin , Lodish Maya
Published: May 2021

Purpose of review

Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in the diagnosis and management of pediatric PPGLs.

Recent findings

The vast majority of pediatric PPGLs have an associated germline mutation, making genetic studies imperative in the work up of these tumors. Somatostatin receptor-based imaging modalities such as 68Ga-DOTATATE and 64Cu-DOTATATE are shown to have the greatest sensitivity in pediatric PPGLs. Peptide receptor radionuclide therapies (PRRTs) such as 177Lu-DOTATATE are shown to have efficacy for treating PPGLs.

Genetics play an important role in pediatric PPGLs. Advances in somatostatin receptor-based technology have led to use of 68Ga-DOTATATE and 64Cu-DOTATATE as preferred imaging modalities. While surgery remains the mainstay for management of PPGLs, PRRT is emerging as a treatment option for PPGLs
Cross-cultural Validation of the Full Range Test of Visual Motor Integration Used with Children in Four Arab Countries
Authors: Emam Mahmoud Mohamed , Al-Attiyah Asma A. , Alhuwilah Amthal , Awed Huda Shaaban , Omara Ehab
Published: May 2021

SIGNIFICANCE

Arab countries have a shortage of culturally sensitive psychoeducational assessments. Tests of visual-motor integration are low in their linguistic demands, yet they are not culture-free.

PURPOSE

The aim of this study was to explore the psychometric properties and the validation of the Full Range Test of Visual Motor Integration (FRTVMI) across four Arabic speaking countries, namely, Sultanate of Oman, Kuwait, Qatar, and the Kingdom of Saudi Arabia (n = 2318).

METHODS

The FRTVMI was administered to 2318 children from four Gulf countries. Criterion measures included the Reading Observation Scale and the achievement scores in reading. All raw data obtained for the FRTVMI were analyzed using the Statistical Package for Social Sciences and R package (version 3.5.1, 2018). Construct validity was examined using confirmatory factor analysis. The internal consistency, test-retest reliability, and interrater reliability of FRTVMI were also examined.

RESULTS

The means for Cronbach α, intraclass correlation, and test-retest reliability across the four countries were 0.87, 0.87, and 0.90, respectively. Spearman ρ correlation between FRTVMI scores and Reading Observation Scale scores ranged between 0.16 and 0.51 across the four countries and were 0.57, 0.43, and 0.45 for male and female participants and the entire sample, respectively. The Spearman ρ correlations between FRTVMI scores and reading achievement scores ranged between 0.15 and 0.20 across the four countries and were 0.27, 0.29, and 0.26 for male and female participants and the entire sample, respectively. The modified model indices showed that the FRTVMI was adequate for use in the four countries and for both male and female participants. The reliability estimates for the test were high, whereas the concurrent validity estimates were moderate.

CONCLUSIONS

The unidimensionality of the test should be taken with caution, as we found some indication for the multidimensionality of the test factor structure. Implications for cross-cultural assessment are discussed.
Analysis of Data Use Registers published by health data custodians in the UK
Authors: Karrar Nada , Khan Shahriar Kabir , Manohar Sinduja , Quattroni Paola , Seymour David , Varma Susheel
Published: May 2021

Transparency of how health and social care data is used by researchers is crucial to building public trust. We define “data use registers” as a public record of data an organisation has shared with other individuals or organisations for the purpose of research, innovation and service evaluation, and are used by some data custodians across the United Kingdom to increase transparency of data use. They typically contain information about the type of data being shared, the purpose, date of approval and name of organisation or individual using (or receiving) the data. However, information published lacks standardisation across organisations. Registers do not yet have a consistent approach and are often incomplete, updated infrequently and not accessible to the public. In this paper, we present an empirical analysis of existing data use registers in the UK and investigate accessibility, content, format and frequency of updates across health data organisations. This analysis will inform future recommendations for a data use register standard that will be published by the UK Health Data Research Alliance.
Identifying dysregulated immune cell subsets following critical volumetric muscle loss with pseudo-time trajectories
Authors: Hymel Lauren A. , Anderson Shannon E. , Turner Thomas C. , York William Y. , Lim Hong Seo , Qiu Peng , Jang Young C. , Willett Nick J. , Botchwey Edward A.
Published: May 2021

Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis techniques to elucidate the cellular players underlying a functional or pathological outcome as a result of subcritical or critical VML in the murine quadriceps, respectively. We found that critical VML presented with a sustained presence of M2-like and CD206hiLy6Chi ‘hybrid’ macrophages whereas subcritical defects resolved these populations. These macrophage subsets may contribute to fibrogenesis in critical VML, especially in the presence of TGF-β. Furthermore, several T cell populations were significantly elevated in critical VML compared to subcritical injuries. Specifically, there was a significant increase of CD127+ T cells at days 3 and 7, and upregulated CD127 expression may indicate aberrant IL-7 signaling in critical VML. These results demonstrate a dysregulated immune response in critical VML that is unable to resolve the chronic inflammatory state and transition to a pro-regenerative microenvironment. These data provide important insights into potential therapeutic strategies which could reduce the immune cell burden and pro-fibrotic signaling characteristic of VML.
Brain capillary obstruction as a novel mechanism of anti-CD19 CAR T cell neurotoxicity
Authors: Faulhaber Lila D , Hartsuyker Kendra Jae , Phuong Anthea Q , Cho Yeheun , Mand Katie K , Harper Stuart D , Olson Aaron K , Garden Gwenn A , Shih Andy Y , Gust Juliane
Published: May 2021

Immunotherapy for hematologic malignancies with CD19-directed CAR T cells is associated with neurotoxicity in about 40% of patients. Systemic cytokine release syndrome, endothelial activation, and disruption of endothelial integrity have all been associated with neurotoxicity, but it remains unclear how these mechanisms interact and how they lead to neurologic dysfunction. We developed a syngeneic mouse model which manifests systemic cytokine release and behavioral abnormalities within 3-5 days after infusion of high-dose murine CD19-CAR T cells. Histologic examination revealed widespread brain hemorrhages, diffuse extravascular IgG deposition, loss of capillary pericyte coverage and increased prevalence of string capillaries. In vivo two-photon imaging of blood flow revealed plugging of >10% of capillaries by leukocytes, associated with regions of localized hypoxia. These data reveal capillary obstruction and associated brain hypoxia and microvascular decline as a potential basis for neurotoxicity during CD19-CAR T cell treatment in humans, which may be amenable to therapeutic interventions.
A comparison of shear- and compression-induced mechanotransduction in SW1353 chondrocytes
Authors: Welhaven Hope D. , McCutchen Carley N. , June Ronald K.
Published: May 2021

Mechanotransduction is a biological phenomenon where mechanical stimuli are converted to biochemical responses. A model system for studying mechanotransduction are the chondrocytes of articular cartilage. Breakdown of this tissue results in decreased mobility, increased pain, and reduced quality of life. Either disuse or overloading can disrupt cartilage homeostasis, but physiological cyclical loading promotes cartilage homeostasis. To model this, we exposed SW1353 cells to cyclical mechanical stimuli, shear and compression, for different durations of time (15 and 30 min). By utilizing liquid chromatography-mass spectroscopy (LC-MS), metabolomic profiles were generated detailing metabolite features and biological pathways that are altered in response to mechanical stimulation. In total, 1,457 metabolite features were detected. Statistical analyses identified several pathways of interest. Taken together, differences between experimental groups were associated with inflammatory pathways, lipid metabolism, beta-oxidation, central energy metabolism, and amino acid production. These findings expand our understanding of chondrocyte mechanotransduction under varying loading conditions and time periods.
Cause-specific student absenteeism monitoring in K-12 schools for detection of increased influenza activity in the surrounding community - Dane County, Wisconsin, 2014-2020
Authors: Temte Jonathan L. , Barlow Shari , Goss Maureen , Temte Emily , Schemmel Amber , Bell Cristalyne , Reisdorf Erik , Shult Peter , Wedig Mary , Haupt Thomas , Conway James H. , Gangnon Ronald , Uzicanin Amra
Published: May 2021

Background

Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.

Materials and Methods

Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.

Findings

Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.

Discussion

Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.
Attentional brain rhythms during prolonged cognitive activity
Authors: Gaillard C. , De Sousa C. , Amengual J. , Loriette C. , Ziane C. , Hadj Hassen S. Ben , Di Bello F. , Hamed S. Ben
Published: May 2021

As routine and lower demand cognitive tasks are taken over by automated assistive systems, human operators are increasingly required to sustain cognitive demand over long periods of time. This has been reported to have long term adverse effects on cardiovascular and mental health. However, it remains unclear whether prolonged cognitive activity results in a monotonic decrease in the efficiency of the recruited brain processes, or whether the brain is able to sustain functions over time spans of one hour and more. Here, we show that during working sessions of one hour or more, contrary to the prediction of a monotonic decline, behavioral performance in both humans and non-human primates consistently fluctuates between periods of optimal and suboptimal performance at a very slow rhythm ofcirca5 cycles per hour. These fluctuations are observed in both high attentional (in non-human primates) and low attentional (in humans) demand conditions. They coincide with fluctuations in pupil diameter, indicating underlying changes in arousal and information-processing load. Accordingly, we show that these rhythmic behavioral fluctuations correlate, at the neurophysiological level, with fluctuations in the informational attention orientation and perception processing capacity of prefrontal neuronal populations. We further identify specific markers of these fluctuations in LFP power, LFP coherence and spike-field coherence, pointing towards long-range rhythmic modulatory inputs to the prefrontal cortex rather than a local prefrontal origin. These results shed light on the resilience of brain mechanisms to sustained effort and have direct implications on how to optimize high cognitive demand working and learning environments.
Climate change and the complex dynamics of green spruce aphid–spruce plantation interactions
Authors: Thornley John H. M. , Newman Jonathan A.
Published: May 2021

Aphids can have a significant impact on the growth and commercial yield of spruce plantations. Here we develop a mechanistic deterministic mathematical model for the dynamics of the green spruce aphid (Elatobium abietumWalker) growing on Sitka spruce (Picea sitchensis(Bong.) Carr.). These grow in a northern British climate in managed plantations, with planting, thinning and a 60-year rotation. Aphid infestation rarely kills the tree but can reduce growth by up to 55%. We used the Edinburgh Forest Model (efm) to simulate spruce tree growth. The aphid sub-model is described in detail in an appendix. The only environmental variable which impacts immediately on aphid dynamics is air temperature which varies diurnally and seasonally. The efm variables that are directly significant for the aphid are leaf area and phloem nitrogen and carbon. Aphid population predictions include dying out, annual, biennual and other complex patterns, including chaos. Predicted impacts on plantation yield of managed forests can be large and variable, as has been observed; they are also much affected by temperature, CO2concentration and other climate variables. However increased CO2concentration appears to ameliorate the severity of the effects of increasing temperatures coupled to worsening aphid infestations on plantation yield.
Confounds of using theunc-58selection marker highlights the importance of genotyping co-CRISPR genes
Authors: Rawsthorne-Manning Helena , Calahorro Fernando , Izquierdo Patricia Gonzalez , Holden-Dye Lindy , O’Connor Vincent , Dillon James
Published: May 2021

Multiple advances have been made to increase the efficiency of CRISPR/Cas9 editing using the model genetic organismCaenorhabditis elegans(C. elegans). Here we report on the use of co-CRISPR ‘marker’ genes: worms in which co-CRISPR events have occurred have overt, visible phenotypes which facilitates the selection of worms that harbour CRISPR events in the target gene. Mutation in the co-CRISPR gene is then removed by outcrossing to wild type but this can be challenging if the CRISPR and co-CRISPR gene are hard to segregate. However, outcrossing can be avoided by selecting worms of wild type appearance from a ‘jackpot’ brood. These are broods in which a high proportion of the progeny of a single injected worm display the co-CRISPR phenotype suggesting high CRISPR efficiency. This can deliver worms that harbour the desired mutation in the target gene locus without the co-CRISPR mutation. We have successfully generated a discrete mutation in theC. elegans nlg-1gene using this method. However, in the process of sequencing to authenticate editing in thenlg-1gene we discovered genomic rearrangements that arise at the co-CRISPR geneunc-58that by visual observation were phenotypically silent but nonetheless resulted in a significant reduction in motility scored by thrashing behaviour. This highlights that careful consideration of the hidden consequences of co-CRISPR mediated genetic changes should be taken before downstream analysis of gene function. Given this, we suggest sequencing of co-CRISPR genes following CRISPR procedures that utilise phenotypic selection as part of the pipeline.
Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2
Authors: Tillinghast Jordan , Bowser Darren , Lee Kenneth Pak Kin
Published: May 2021

Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile onset Parkinson’s disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analogue or to spermine in the presence of phosphomimetics determined by electron cryo-microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2’s architecture establishes physical principles underlying selective polyamine transport and anticipates a “pump-channel” intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2’s potential in neuroprotective therapy.

Highlights

Structures of the Parkinson’s disease-associated polyamine transporter ATP13A2

Structures of three transport cycle intermediates reveal the gating mechanism

Architecture of the polyamine binding site reveals mechanisms for ion selectivity

The polyamine binding site’s location anticipates an ion channel-like mechanism
Regional Differences in Brain Plasticity and Behaviour as a Function of Sex and Enrichment Type: Oxytocin Matters
Authors: Faraji Jamshid , Lotfi Hamid , Moharrerie Alireza , Jafari S. Yaghoob , Soltanpour Nasrin , Tamannaiee Rosa , Marjani Kameran , Roudaki Shabnam , Naseri Farhad , Moeeini Reza , Metz Gerlinde A.S.
Published: May 2021

The early environment is critical to brain development, but the relative contribution of physical vs. social stimulation is unclear. Here, we investigated in male and female rats the response to early physical and social environmental enrichment in relation to oxytocin (OT) and brain-derived neurotrophic factor (BDNF) expression. The findings show that males and females respond differently to prolonged sensorimotor stimulation from postnatal day 21-110 in terms of functional, structural and molecular changes in the hippocampus vs. medial prefrontal cortex (mPFC). Physical enrichment promoted motor and cognitive functions and hippocampal BDNF mRNA and protein expression in both sexes. Combined physical and social enrichment, however, promoted functional and structural gain predominantly in females. These changes were accompanied by elevated plasma oxytocin (OT) levels and BDNF mRNA expression in the mPFC while the hippocampus was not affected. Administration of an OT antagonist in females blocked the beneficial effects of enrichment and led to reduced cortical BDNF signaling. These findings suggest that an OT-based mechanism selectively stimulates a region-specific BDNF response which is dependent on the type of experience.
A novel class of human milk oligosaccharides based on 6’- galactosyllactose and containing N-acetylglucosamine branches extended by oligogalactoses
Authors: Hanisch Franz-Georg , Kunz Clemens
Published: May 2021

Human milk oligosaccharides (HMOs) have attracted much attention in recent years not only as a prebiotic factor, but in particular as an essential component in infant nutrition related to their impact in innate immunity. The backbone structures of complex HMOs generally contain single or repetitive lacto-N-biose (type 1) or lactosamine (type 2) units in either linear or branched chains extending from a lactose core. While all known branched structures originate from 3,6-substitution of the lactosyl core galactose, we here describe a new class of HMOs that tentatively branch at terminal galactose of 6’-galactosyllactose. Another novel feature of this class of HMOs was found in linear oligo-galactosyl chains linked to one of the N-acetylglucosamine (GlcNAc) branches. The novel structures exhibit general formulas with hexose vs. hexosamine contents of 5/2 to 8/2 and can be designated as high-galactose (HG)-HMOs. In addition, up to three fucosyl residues are linked to the octa- to dodecasaccharides, which were detected in two human milk samples from Lewis blood group defined donors. Structural analyses of methylated glycans and their alditols comprised MALDI mass spectrometry, ESI-(CID)MS and linkage analyses by GC-MS of the derived partially methylated alditol acetates. Enzymatic degradation by application of β1-3,4-specific galactosidase supported the presence of terminal galactose linked β1−6 to one of the two GlcNAc branches.
Polarization effects of X-ray monochromators modeled using dynamical scattering theory
Authors: Mendenhall Marcus H. , Black David , Windover Donald , Cline James P.
Published: May 2021

The difference in the diffracted intensity of the σ- and π-polarized components of an X-ray beam in powder diffraction has generally been treated according to equations based on dipole scattering, also known as kinematic X-ray scattering. Although this treatment is correct for powders and post-sample analyzers known to be of high mosaicity, it does not apply to systems configured with nearly perfect crystal incident-beam monochromators. Equations are presented for the polarization effect, based on dynamical diffraction theory applied to the monochromator crystal. The intensity of the π component relative to the σ component then becomes approximately proportional to |cos  2θm| rather than to cos22θm, where θm is the Bragg diffraction angle of the monochromator crystal. This changes the predicted intensities of X-ray powder diffraction patterns produced on instruments with incident-beam monochromators, especially in the regions far from 2θ = 90° in the powder pattern. Experimental data, based on well known standard reference materials, are presented, confirming that the dynamical polarization correction is required when a Ge 111 incident-beam monochromator is used. The dynamical correction is absent as an option in the Rietveld analysis codes with which the authors are familiar.
New developments in institutional research on performance measurement and management in the public sector
Authors: Modell Sven
Published: May 2021

Purpose

This paper reviews and reflects on institutional research on performance measurement and management (PMM) in the public sector emerging over the past decade and discusses potential extensions of this body of research.

Design/methodology/approach

The paper takes the form of a reflective review with an emphasis on how institutional theory has been used in PMM research in the public sector.

Findings

Although institutional research on PMM in the public sector has continued to grow over the past decade, much of this research still pays relatively one-sided attention to the influence of pre-existing institutions on PMM practices and has left the constitutive effects of such practices under-researched. In order to address this shortcoming and nurture research that pays more equal attention to the institutional effects on and of PMM practices, a research agenda based on dialogue with the sociology of valuation and valuation studies is outlined. Such research is arguably well-suited for examining emerging themes in the public sector accounting and management literatures centred on the publicness of public service provision and notions of organisational hybridity.

Research limitations/implications

The paper offers a starting point for research that can provide a more holistic and dynamic perspective on how PMM practices are implicated in the shaping of institutional fields over time.

Originality/value

The paper continues to advance an established research agenda in the public sector accounting and management literatures whilst suggesting ways of extending this research agenda.
Treatment options for DOCK8 deficiency‐related severe dermatitis
Authors: Ollech Ayelet , Mashiah Jacob , Lev Atar , Simon Amos J. , Somech Raz , Adam Etai , Barzilai Aviv , Hagin David , Greenberger Shoshana
Published: May 2021

Background

Cutaneous manifestations of dedicator of cytokinesis 8 gene (DOCK8) deficiency, a combined type of T and B cell immunodeficiency, previously designated as autosomal recessive hyper IgE syndrome, includes dermatitis and skin infections. There are limited treatment options for dermatitis related to the syndrome.

Objective

To describe a cohort of patients with DOCK8 deficiency with a focus on the treatment of their cutaneous manifestations.

Methods

A retrospective study on all children with the genetic diagnosis of DOCK8 deficiency treated at the Sheba Medical Center between 1/1/2003 and 1/1/2021 was preformed. Collected data included: demographic features, family history, laboratory, genetic testing, skin manifestations, treatment, and disease course. Description of two cases of severe recalcitrant dermatitis treated with dupilumab is detailed.

Results

Nine children with a genetic diagnosis of DOCK8 deficiency were included, of whom six were girls (66%) with a median age of 8.5 (±2.2 SD) years. The median age at diagnosis was 2.8 (±2.6 SD) years. Six patients were born to consanguineous parents. Five out of six patients who received hematopoietic stem cell transplantation (HSCT) had a complete response, and one was recently transplanted. Of note, two patients, while awaiting HSCT, were treated with dupilumab for their severe dermatitis resulting in a marked improvement of the cutaneous manifestations and pruritus.

Conclusions

Hematopoietic stem cell transplantation is the gold standard and most effective therapy for patients with DOCK8 deficiency. Dupilumab, a biological therapy indicated for atopic dermatitis and other Th2 derived dermatoses, is an excellent option for dermatitis in patients with DOCK8 deficiency and can be used as a bridge before HSCT. Larger studies are needed to confirm this observation.