bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher levels of bodily pain in people with long‐term type 1 diabetes: associations with quality of life, depressive symptoms, fatigue and glycaemic control – the Dialong study
Authors: Molvær A. K. , Iversen M. M. , Igland J. , Peyrot M. , Tell G. S. , Holte K. B. , Berg T. J. 
Published: May 2020

AbstractAimsTo compare reported level of bodily pain, overall and health‐related quality of life (QoL), depression and fatigue in people with long‐term type 1 diabetes vs. a comparison group without diabetes. Further, to examine the associations of total bodily pain with QoL, depression, fatigue and glycaemic control in the diabetes group.MethodsCross‐sectional study of 104 (76% of eligible) people with type 1 diabetes of ≥ 45 years’ duration attending the Norwegian Diabetes Centre and 75 persons without diabetes who completed questionnaires measuring bodily pain (RAND‐36 bodily pain domain), shoulder pain (Shoulder Pain and Disability Index), hand pain (Australian/Canadian Osteoarthritis Hand Index), overall QoL (World Health Organization Quality of Life – BREF), health‐related QoL (RAND‐36), diabetes‐specific QoL (Audit of Diabetes‐Dependent Quality of Life; only diabetes group), depression (Patient Health Questionnaire) and fatigue (Fatigue questionnaire). For people with type 1 diabetes, possible associations between the bodily pain domain (lower scores indicate higher levels of bodily pain) and other questionnaire scores, were measured with regression coefficients (B) per 10‐unit increase in bodily pain score from linear regression.ResultsThe diabetes group reported higher levels of bodily (P = 0.003), shoulder and hand pain (P < 0.001) than the comparison group. In the diabetes group, bodily pain was associated with lower overall and diabetes‐specific QoL [B (95% confidence intervals)]: 0.2 (0.1, 0.2) and 0.2 (0.1, 0.3); higher levels of depression −1.0 (−1.3, −0.7) and total fatigue −1.5 (−1.9, −1.2); and worse glycaemic control HbA1c (mmol/mol; %) −0.8 (−1.5, −0.1); −0.1 (−0.1, −0.01).ConclusionsPeople with long‐term type 1 diabetes experience a high level of bodily pain compared with a comparison group. Total bodily pain was associated with worse QoL and glycaemic control.
Prevalence of diabetes and impaired fasting glucose in Poland in 2005–2014: results of the WOBASZ surveys
Authors: Rutkowski M. , Wojciechowska A. , Śmigielski W. , Drygas W. , Piwońska A. , Pająk A. , Tykarski A. , Kozakiewicz K. , Waśniewska M. K , Zdrojewski T. 
Published: May 2020

AbstractAimsTo evaluate the prevalence of diabetes and impaired fasting glucose in Poland in 2013–2014 and to determine the temporal trends between 2003–2005 and 2013–2014.MethodsA questionnaire survey was conducted in a representative sample of Polish adults, complemented by anthropometric and fasting plasma glucose measurements. The research was part of the national cross‐sectional WOBASZ study. Diabetes was assessed as self‐reported or screened (fasting plasma glucose level ≥ 7 mmol/l, based on one blood sample).ResultsIn the years 2013–2014 among 5694 participants aged 20–74 years, 6.0% (95% CI 5.4–6.6) reported a previous diagnosis of diabetes (5.8% in women and 6.2% in men). In addition, 2.4% of the participants (95% CI 2.0–2.8) without a previous diagnosis of diabetes (1.8% of women and 3.1% of men) had a fasting blood glucose level ≥7.0 mmol/l in a single measurement. In a single measurement, 18.4% of the participants (95% CI 17.4–19.4; 13.2% of women and 23.8% of men) had impaired fasting glucose. The prevalence of dysglycaemia in the WOBASZ II study was significantly higher compared to the WOBASZ I study findings from 2003–2005, increased from 6.6% to 8.4% for diabetes and from 9.3% to 18.4% for impaired fasting glucose (after age and sex standardization to the 2013 Polish population).ConclusionsThe prevalence of diabetes in Poland is similar to that observed in other European populations and has increased significantly over the last decade.
Implementation of the Endocrine Society clinical practice guidelines for gestational diabetes mellitus to a knowledge tool
Authors: Korvesi Vasiliki M. , Chouvarda Ioanna , Mastorakos George , Goulis Dimitrios G. 
Published: May 2020

AbstractBackgroundDespite the production of clinical practice guidelines (CPGs) in many medical areas, their use is not sufficiently adopted in clinical practice. Incorporation of CPGs in knowledge tools (KnowT) or decision support systems (DSS) for routine use can improve healthcare providers' compliance to CPGs.Materials and methodsClinical practice guidelines for gestational diabetes mellitus (GDM) were searched for, collected and compared. The CPG that met pre‐specified criteria ([a] published by a European or American organization between 2010 and 2018, [b] being developed a systematic way and [c] having statements of “level of evidence” and “strength of recommendation”) was chosen for implementation (Endocrine Society, 2013). Its recommendations were deconstructed, re‐organized and reconstructed as an algorithm (in the form of a flowchart), which was integrated into a KnowT. Content completeness and evaluation of CPG by the Guideline Implementability Appraisal tool (GLIA) were performed as well. The primary objective was the development of a clinical algorithm in the field of GDM and its integration into a KnowT. The secondary objective was to demonstrate the completeness of the CPG content and evaluate its implementability in the KnowT.ResultsEndocrine Society 2013 CPG was restructured as a flowchart, and a KnowT was constructed with the use of the “Openlabyrinth” software. The completeness of the content was confirmed, and GLIA appraisal demonstrated its implementability.ConclusionEndocrine Society 2013 CPG for GDM is a complete set of recommendations. Its structure makes possible the design of a clinical algorithm and its implementation into a KnowT.
Natural variation of root lesion nematode antagonism in the biocontrol fungus Clonostachys rosea and identification of biocontrol factors through genome‐wide association mapping
Authors: Iqbal Mudassir , Broberg Martin , Haarith Deepak , Broberg Anders , Bushley Kathryn E. , Brandström Durling Mikael , Viketoft Maria , Funck Jensen Dan , Dubey Mukesh , Karlsson Magnus 
Published: May 2020

AbstractBiological control is a promising approach to reduce plant diseases caused by nematodes to ensure high productivity in agricultural production. Large‐scale analyses of genetic variation in fungal species used for biocontrol can generate knowledge regarding interaction mechanisms that can improve efficacy of biocontrol applications. In this study, we performed a genome‐wide association study (GWAS) for in vitro antagonism against the root lesion nematode Pratylenchus penetrans in 53 previously genome re‐sequenced strains of the biocontrol fungus Clonostachys rosea. Nematode mortality in C. rosea potato dextrose broth (PDB) culture filtrates was highly variable and showed continuous variation (p < .001) between strains, indicating a polygenic inheritance. Twenty‐one strains produced culture filtrates with higher (p ≤ .05) nematode mortality compared with the PDB control treatment, while ten strains lowered (p ≤ .05) the mortality. The difference in in vitro antagonism against P. penetrans correlated with antagonism against the soybean cyst nematode Heterodera glycines, indicating lack of host specificity in C. rosea. An empirical Bayesian multiple hypothesis testing approach identified 279 single nucleotide polymorphism markers significantly (local false sign rate < 10–10) associated with the trait. Genes present in the genomic regions associated with nematicidal activity included several membrane transporters, a chitinase and genes encoding proteins predicted to biosynthesize secondary metabolites. Gene deletion strains of the predicted nonribosomal peptide synthetase genes nps4 and nps5 were generated and showed increased (p ≤ .001) fungal growth and conidiation rates compared to the wild type. Deletion strains also exhibited reduced (p < .001) nematicidal activity and reduced (p ≤ .05) biocontrol efficacy against nematode root disease and against fusarium foot rot on wheat. In summary, we show that the GWAS approach can be used to identify biocontrol factors in C. rosea, specifically the putative nonribosomal peptide synthetases NPS4 and NPS5.
Abemaciclib sensitizes HPV‐negative cervical cancer to chemotherapy via specifically suppressing CDK4/6‐Rb‐E2F and mTOR pathways
Authors: Liu Yuan , Zhao Runsheng , Fang Shanshan , Li Quan , Jin Yiqiang , Liu Bo 
Published: May 2020

ABSTRACTCervical cancer is the second most common malignancy in women, and the novel therapeutic treatment is needed. Abemaciclib is a FDA‐approved drug for breast cancer treatment. In this work, we identified that abemaciclib has potent anti‐cervical cancer activity. We demonstrate that abemaciclib is the most effective drug against human papillomavirus (HPV)‐negative cervical cancer cells compared to ribociclib and palbociclib, with its IC50 at nanomolar concentration range. This is achieved by the inhibition of proliferation and induction of apoptosis, through specifically suppressing CDK4/6‐Rb‐E2F and mTOR pathways by abemaciclib in HPV‐negative cervical cancer cells. Of note, the combination of abemaciclib with paclitaxel and cisplatin at sublethal concentration results in much greater efficacy than chemotherapy alone. In addition, we confirm the efficacy of abemaciclib and its combination with paclitaxel or cisplatin at the doses that are not toxic to mice in HPV‐negative cervical cancer xenograft mouse model. Interestingly, we show that abemaciclib and other CDK4/6 inhibitors are not effective in targeting HPV‐positive cervical cancer cells, and this is likely to be associated with the high p16 and low Rb expression in HPV‐positive cervical cancer cells. Our work is the first to provide the preclinical evidence to demonstrate the potential of abemaciclib for the treatment of HPV‐negative cervical cancer. The mechanism analysis highlights the therapeutic value of inhibiting CDK4/6 in HPV‐negative but not HPV‐positive cervical cancer.
Peptidomimetic‐based identification of FDA‐approved compounds inhibiting IRE1 activity
Authors: Doultsinos Dimitrios , Carlesso Antonio , Chintha Chetan , Paton James C. , Paton Adrienne W. , Samali Afshin , Chevet Eric , Eriksson Leif A. 
Published: May 2020

Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein‐folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA‐approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard‐of‐care chemotherapy temozolomide (TMZ).
Mouse model systems of autism spectrum disorder: Replicability and informatics signature
Authors: Kabitzke Patricia , Morales Diana , He Dansha , Cox Kimberly , Sutphen Jane , Thiede Lucinda , Sabath Emily , Hanania Taleen , Biemans Barbara , Brunner Daniela 
Published: May 2020

AbstractPhenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter‐ and intra‐laboratory replicability, particularly in behavioral domains such as social and cognitive function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies of five genetic mouse model systems of ASD. To assess the intra‐laboratory robustness of previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three‐yearlong effort using informatics techniques to assess commonalities and differences. Our results showed high intra‐laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle but pivotal differences in testing conditions, housing enrichment, or background strains and less so on the variability of the behavioral phenotypes. The overall informatics analysis suggests that in our behavioral assays we can separate the set of tested mouse model system into two main classes that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept.
Effect of Fremanezumab Monthly and Quarterly Doses on Efficacy Responses
Authors: Fiedler‐Kelly Jill , Passarell Julie , Ludwig Elizabeth , Levi Micha , Cohen‐Barak Orit 
Published: May 2020

ObjectiveExposure‐response (E‐R) models were developed to provide a description of the time‐course of treatment effect for monthly and quarterly dosing regimens of fremanezumab.BackgroundFremanezumab is a monoclonal antibody for preventive treatment of episodic migraine (EM) and chronic migraine (CM). In phase 2b and 3 clinical studies of fremanezumab, significant reductions in migraine and headache days and other clinical endpoints were observed for patients with EM and patients with CM. Development of E‐R models relating individual‐specific measures of drug exposure to clinical endpoints provides a more granular understanding of the expected effects of different doses on therapeutic outcomes by accounting for variability in pharmacokinetic (PK) properties.MethodsData from 2 phase 2b and 2 phase 3 studies of adults with EM or CM were used. Individual exposures were calculated from a population PK model and related to monthly migraine days in EM and moderate‐severe (M/S) headache days in CM. Model‐based stochastic simulations were performed to compare predicted responses for the various treatment regimens.ResultsThe effect of average fremanezumab concentration compared to placebo on the reduction in migraine days and M/S headache days was predicted by the models to be similar for 225 mg monthly and 675 mg once quarterly over time for both EM and CM patients. Both regimens were associated with better response than placebo. A similar percent of EM and CM responders was predicted across the range of observed body weights.ConclusionsExposure‐response evaluations showed that both monthly (225 mg) and quarterly (675 mg) fremanezumab dosing regimens were appropriate in achieving clinical benefit in adult patients with EM or CM.
Multiple methods of assessing nectar foraging conditions indicate peak foraging difficulty in late season
Authors: Garbuzov Mihail , Balfour Nicholas J. , Shackleton Kyle , Al Toufailia Hasan , Scandian Luciano , Ratnieks Francis L. W. 
Published: May 2020

Abstract
One of the major challenges faced by pollinators worldwide is the reduction in their food supply, nectar, and pollen. Given the considerable seasonal variation in the abundance of both floral resources and flower‐visiting insects, conservation initiatives aiming to help pollinators through floral resource supplementation could increase their impacts by targeting periods when the foraging conditions are most difficult. Direct assessment of foraging conditions, however, is extremely labour‐intensive.
Here, we compared eight practical measures expected to reflect the foraging difficulty for nectar in the environment. Five measures involved Apis mellifera – an indicator species for the flower‐visitor guild due to its generalist, energetically optimal, and long‐distance foraging habit. These included (i) visitation at feeders with a range of sucrose concentrations, (ii) guarding and (iii) fighting levels at hive entrances, (iv) rates of hive weight changes, and (v) foraging distances encoded in waggle dances. The other measures were (vi–viii) counts of flower‐visiting insects in relation to the rate of nectar sugar secretion in three plant species attractive to flower‐visiting insects.
There was considerable, although not complete agreement among the eight measures. Eleven of 28 pairwise correlations were statistically significant. Guarding and fighting correlated with most (five) other measures. We conclude that seven of the eight measures could be potentially useful in gauging seasonal patterns in local foraging conditions, which could help guide targeted conservation initiatives. Assessment of guarding and fighting levels at A. mellifera hive entrances is recommended, as these correlated significantly with most other measures and are easy to obtain in practice.
Mutational landscape of severe combined immunodeficiency patients from Turkey
Authors: Firtina Sinem , Yin Ng Yuk , Hatirnaz Ng Ozden , Kiykim Ayca , Aydiner Elif , Nepesov Serdar , Camcioglu Yildiz , Sayar Esra H. , Reisli Ismail , Torun Selda H. , Cogurlu Tuba , Uygun Dilara , Simsek Isil E. , Kaya Aysenur , Cipe Funda , Cagdas Deniz , Yucel Esra , Cekic Sukru , Uygun Vedat , Baris Safa , Ozen Ahmet , Ozbek Ugur , Sayitoglu Muge 
Published: May 2020

AbstractSevere combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next‐generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon‐based targeted NGS panel, which contained 18 most common SCID‐related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease‐causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom‐made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK− SCID). Incidence of autosomal‐recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom‐made sequencing panel was able to identify and confirm the previously known and novel disease‐causing variants with high accuracy.
New Venture Survival: A Review and Extension
Authors: Soto‐Simeone Aracely , Sirén Charlotta , Antretter Torben 
Published: May 2020

AbstractThis paper provides an evaluative overview of the new venture survival literature. Since Stinchcombe's primary attempt to explain the mortality rates of new ventures, different research fields, including entrepreneurship, management and sociology, have devoted considerable attention to the antecedents of new venture survival. Despite this lively research commitment, a comprehensive review of the literature on new venture survival – as one of the most essential performance measures for new ventures – is missing. Covering 54 years of research, this paper provides an overview of the factors affecting new venture survival and highlights important methodological aspects in this research field. The review concludes by discussing opportunities for future research.
Resisting Bare Life: Civil Solidarity and the Hunt for Illegalized Migrants
Authors: Vandevoordt Robin 
Published: May 2020

AbstractWhile European governments have pursued illegalized migrants for decades, the techniques through which they do so have taken a more radical turn since 2015. Focusing on the particular case of Belgium, this paper documents how its Federal government has increasingly tried to “police” migrants into the European refugee regime, while migrants and citizens have continued to resist these efforts through a series of “political” actions. Drawing on ethnographic work with the Brussels‐based Citizen Platform for the Support of Refugees, I pursue two aims: first, I demonstrate how the Belgian state has consciously produced a humanitarian crisis as part of a broader “politics of exhaustion”; and second, I explore the specific forms and types of humanitarian action that emerge from citizens’ response to these policies. I do so by describing three moments in which these opposing logics of policing and politicization conjure.
Hallmarks of NLRP3 inflammasome activation are observed in organotypic hippocampal slice culture
Authors: Hoyle Christopher , Redondo‐Castro Elena , Cook James , Tzeng Te‐Chen , Allan Stuart M. , Brough David , Lemarchand Eloise 
Published: May 2020

SummaryMicroglial inflammation driven by the NACHT, LRR and PYD domain‐containing protein 3 (NLRP3) inflammasome contributes to brain disease and is a therapeutic target. Most mechanistic studies on NLRP3 activation use two‐dimensional pure microglial cell culture systems. Here we studied the activation of the NLRP3 inflammasome in organotypic hippocampal slices, which allowed us to investigate microglial NLRP3 activation in a three‐dimensional, complex tissue architecture. Toll‐like receptor 2 and 4 activation primed microglial inflammasome responses in hippocampal slices by increasing NLRP3 and interleukin‐1β expression. Nigericin‐induced NLRP3 inflammasome activation was dynamically visualized in microglia through ASC speck formation. Downstream caspase‐1 activation, gasdermin D cleavage, pyroptotic cell death and interleukin‐1β release were also detected, and these findings were consistent when using different NLRP3 stimuli such as ATP and imiquimod. NLRP3 inflammasome pathway inhibitors were effective in organotypic hippocampal slices. Hence, we have highlighted organotypic hippocampal slice culture as a valuable ex vivo tool to allow the future study of NLRP3 inflammasomes in a representative tissue section, aiding the discovery of further mechanistic insights and drug development.