bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID‐19 and Ethnic Inequalities in England and Wales*
Authors: Platt Lucinda , Warwick Ross 
Published: June 2020

AbstractThe economic and public health crisis created by the COVID‐19 pandemic has exposed existing inequalities between ethnic groups in England and Wales, as well as creating new ones. We draw on current mortality and case data, alongside pre‐crisis labour force data, to investigate the relative vulnerability of different ethnic groups to adverse health and economic impacts. After accounting for differences in population structure and regional concentration, we show that most minority groups suffered excess mortality compared with the white British majority group. Differences in underlying health conditions such as diabetes may play a role; so too may occupational exposure to the virus, given the very different labour market profiles of ethnic groups. Distinctive patterns of occupational concentration also highlight the vulnerability of some groups to the economic consequences of social distancing measures, with Bangladeshi and Pakistani men particularly likely to be employed in occupations directly affected by the UK's ‘lockdown’. We show that differences in household structures and inequalities in access to savings mean that a number of minority groups are also less able to weather short‐term shocks to their income. Documenting these immediate consequences of the crisis reveals the potential for inequalities to become entrenched in the longer term.
The influence of human resource practices on perceived work ability and the preferred retirement age: A latent growth modelling approach
Authors: Pak Karen , Kooij Dorien T. A. M. , De Lange Annet H. , van den Heuvel Swenneke , Van Veldhoven Marc J. P. M. 
Published: June 2020

AbstractOrganisations are challenged to extend working lives of older workers. However, there is little empirical evidence available on how organisations should do this. This study aims to fill this gap by testing the effect of Human Resource (HR) practices on perceived work ability and the preferred retirement age. Based on the Conversation of Resources theory, we expected that the use of HR practices has a positive effect on perceived work ability and preferred retirement age. We have conducted latent growth curve modelling to test our hypotheses amongst 12,444 employees aged 45 and older at four time points. The results indicate that developmental practices are positively related to work ability, whereas maintenance practices are negatively related to work ability and the preferred retirement age. Accommodative practices are negatively related to the intercepts of both outcomes but not to the slopes, whereas utilisation practices are not related to the outcomes at all.
IL17F rs763780 single nucleotide polymorphism is associated with asthma after bronchiolitis in infancy
Authors: Holster Annukka , Teräsjärvi Johanna , Barkoff Alex‐Mikael , Lauhkonen Eero , Törmänen Sari , Helminen Merja , Korppi Matti , He Qiushui , Nuolivirta Kirsi 
Published: June 2020

AbstractAimInterleukin‐17F (IL‐17F) is involved with asthma. The aim of this study was to evaluate the association of IL17F polymorphisms with childhood asthma after bronchiolitis in infancy.MethodsWe invited 166 children who were hospitalised for bronchiolitis at younger than 6 months of age to follow‐up visits at 5‐7 years and 11‐13 years of ages. Asthma and allergy diagnoses, asthma‐presumptive symptoms and use of inhaled corticosteroids (ICSs) were registered. Blood samples were available for IL17F rs763780 (T/C), rs11465553 (C/T) and rs7741835 (C/T) determinations in 165 cases.ResultsThe presence of IL17F rs11465553 and rs7741835 variations showed no significant associations with any asthma or allergy outcome at either 5‐7 years or 11‐13 years of ages. Instead, children with the variant IL17F rs763780 genotype had used more often ICSs between the follow‐up visits from 5‐7 to 11‐13 years (adjusted OR 3.58) than those with the wild genotype. Children with the variant IL17F rs763780 genotype reported more often doctor‐diagnosed atopic dermatitis (adjusted OR 2.71) at 11‐13 years of age than those with the wild genotype.ConclusionThis prospective long‐term follow‐up study provided preliminary evidence on the association of the IL17F rs763780 polymorphism with asthma at school age after bronchiolitis in infancy.
Bayes‐based dosing of infliximab in inflammatory bowel diseases: Short‐term efficacy
Authors: Santacana Juncosa Eugènia , Rodríguez‐Alonso Lorena , Padullés Zamora Ariadna , Guardiola Jordi , Rodríguez‐Moranta Francisco , Serra Nilsson Katja , Bas Minguet Jordi , Morandeira Rego Francisco , Colom Codina Helena , Padullés Zamora Núria 
Published: June 2020

AimsTherapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de‐intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real‐world dataset of patients suffering from inflammatory bowel disease.MethodsWe performed a single‐centre prospective study with one‐group pre‐test/post‐test design in 108 adult inflammatory bowel disease patients treated with model‐based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey‐Bradshaw index and partial Mayo) and inflammatory biomarkers per patient.ResultsThe initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de‐intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103–160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P < .0001) and the median infliximab trough concentrations increased from 3.21 (0.99–5.45) to 5.13 mg/L (3.57–6.53) (P < .0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de‐intensification cohort, no patients experienced an increase in the Harvey‐Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of >5 mg/L.ConclusionIn our cohort of inflammatory bowel disease patients, Bayes‐based optimized dosing improved the short‐term efficacy of infliximab treatment.
Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database
Authors: Cutroneo Paola Maria , Isgrò Valentina , Ientile Valentina , Santarpia Mariacarmela , Ferlazzo Guido , Fontana Andrea , Carrega Paolo , Matarangolo Elena , Barnaba Simona , Spina Edoardo , Trifirò Gianluca 
Published: June 2020

AimsTo provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italian spontaneous adverse drug reaction (ADR) reporting system.MethodsWe selected all ADR reports attributed to ipilimumab (CTLA‐4 inhibitor), nivolumab, pembrolizumab, atezolizumab (PD‐1/PD‐L1 inhibitors) from the Italian spontaneous reporting system (2011–2018). Descriptive analyses of reports for ICIs have been conducted. Time to onset of adverse effects was stratified by system organ class. Reporting odds ratio was used as measure of ADR reporting disproportionality. ICI‐related ADR reports were compared with 2 reference groups, i.e. all other suspected drugs or all other antineoplastic agents.ResultsOverall, 2217 (0.7%) reports were related to ICIs (nivolumab: 72.2% of those reports; ipilimumab: 14.3%; pembrolizumab: 10.3%; and atezolizumab: 3.5%). ICI‐related ADR reports mostly involved males (65%) and median age was 67 (interquartile range 59–73) years. Serious reports accounted for 48.8%. Frequencies of endocrine, general, hepatobiliary, metabolism, musculoskeletal, respiratory disorders, infections and neoplasms were significantly higher for ICIs than for all other drugs (P < .001). Except for infections, similar results emerged through comparison with other anticancer drugs. Colitis, hypophysitis and skin disorders were more frequently reported for anti‐CTLA‐4 drugs than PD‐1/PD‐L1 ICIs, and the opposite for musculoskeletal effects, pneumonia, and thyroid dysfunctions. ICIs were disproportionally associated also with less known risks, e.g. ischaemic heart disease, cardiac failure and optic nerve disorders.ConclusionThe most frequently reported safety issues were probably immune‐related adverse events including general, gastrointestinal and respiratory disorders. Potentially emerging safety signals, such as ischaemic heart disease and cardiac failure, requiring further investigation were detected.
A lesson from a saboteur: High‐MW kininogen impact in coronavirus‐induced disease 2019
Authors: Colarusso Chiara , Terlizzi Michela , Pinto Aldo , Sorrentino Rosalinda 
Published: June 2020

The newly identified coronavirus SARS‐CoV‐2 that spread from China is causing the pandemic COVID‐19 with a fatality rate from 5‐15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS‐CoV‐2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS‐CoV‐2 main protease (Mpro). Once bound to ACE2 and the other two proteases in concert they allow the virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 as its binding to by the virus increases bradykinin and its metabolites, which facilitate inflammation in the lung (causing cough and fever), coagulation and the complement system. These three systems are involved in angioedema, cardiovascular dysfunction and sepsis, pathologies which occur in COVID‐19 patients. Thus, we propose that blocking the kallikrein–kinin system with lanadelumab, approved for hereditary angioedema, will prevent facilitation of these 3 systems.Linked ArticlesThis article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Circular RNA LPAR3 sponges microRNA‐198 to facilitate esophageal cancer migration, invasion, and metastasis
Authors: Shi Yijun , Fang Na , Li Yadong , Guo Zizhang , Jiang Wei , He Yaozhou , Ma Zijian , Chen Yijiang 
Published: June 2020

AbstractIn this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT‐PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)‐198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR‐198‐MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer.
Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation
Authors: Nagasaki‐Maeoka Eri , Ikeda Kazuhiro , Takayama Ken‐ichi , Hirano Takayuki , Ishizuka Yoshiaki , Koshinaga Tsugumichi , Tsukune Naoya , Takayama Tadateru , Inoue Satoshi , Fujiwara Kyoko 
Published: June 2020

AbstractNeuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system, and accounts for approximately 15% of all pediatric cancer‐related deaths. As the 5‐y survival rate of patients with high‐risk NB is <50%, novel therapeutic strategies for NB patients are urgently required. Nonaethylene glycol mono(′4‐iodo‐4‐biphenyl)ester (9bw) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria. Although 9bw shows remarkable inhibition of tumor cell growth, the underlying mechanisms remain unclear. Here, we examined the efficacy of 9bw on human NB‐derived cells, and investigated the molecular mechanisms underlying the cytotoxic effects of 9bw on these cells. Our results indicated that 9bw induced cell death in NB cells by decreasing the production of ATP. Metabolome analysis and measurement of oxygen consumption indicated that 9bw markedly suppressed oxidative phosphorylation (OXPHOS). Further analyses indicated that 9bw inhibited the activity of mitochondrial respiratory complex I. Moreover, we showed that 9bw inhibited growth of NB in vivo. Based on the results of the present study, 9bw is a good candidate as a novel agent for treatment of NB.
Western Canadian producers’ attitudes towards wheat breeding funding
Authors: Galushko Viktoriya , Çule Monika , Gray Richard 
Published: June 2020

AbstractIn 2017, the federal government initiated national consultations for two new crop royalty systems that could be used to support additional crop breeding. In this study, we examine wheat growers’ attitudes towards breeding research and assess their inclination to contribute more to wheat variety development through checkoffs or enhanced royalties. We report a random effect probit estimation for a survey of 877 western Canadian wheat producers that took place from November 2018 to January 2019. We found at least 26% of survey respondents were willing to pay more to support additional wheat breeding. However, this support is contingent on the model for revenue collection and where additional revenue is invested. Producers generally favored increased checkoffs over enhanced royalty collection. Among the royalty options presented, the farm saved seed royalties mechanism had less support than the simpler to implement end‐point royalties mechanism. We also found support is much higher if new royalty mechanisms are used to support university or government programs versus private breeding programs. This result suggests developing widespread producer support for enhanced royalty collection may require broader commitments for funding, ownership, and control of crop breeding programs.
Role of pericyte‐derived SENP1 in neuronal injury after brain ischemia
Authors: Sun Meiling , Chen Xiang , Yin Yi‐Xuan , Gao Yinping , Zhang Li , Chen Boqian , Ji Yin , Fukunaga Kohji , Han Feng , Lu Ying‐Mei 
Published: June 2020

AbstractAimsSUMOylation is a posttranslational modification related to multiple human diseases. SUMOylation can be reversed by classes of proteases known as the sentrin/SUMO‐specific proteases (SENPs). In the present study, we investigate the potential role of SENP1 in pericytes in the brain ischemia.MethodsPericyte‐specific deletion of senp1 mice (Cspg4‐Cre; senp1f/f) were used for brain function and neuronal damage evaluation following brain ischemia. The cerebral blood vessels of diameter, velocity, and flux were performed in living mice by two‐photon laser scanning microscopy (TPLSM). Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of pericyte‐specific SENP1 in the pathological process of brain ischemia. A coculture model of HBVPs and HBMECs mimicked the BBB in vitro and was used to evaluate BBB integrity after glucose deprivation.ResultsOur results showed that senp1‐specific deletion in pericytes did not affect the motor function and cognitive function of mice. However, the pericyte‐specific deletion of senp1 aggravated the infarct size and motor deficit following focal brain ischemia. Consistently, the TPLSM data demonstrated that SENP1 deletion in pericytes accelerated thrombosis formation in brain microvessels. We also found that pericyte‐specific deletion of senp1 exaggerated the neuronal damage significantly following brain ischemia in mice. Moreover, SENP1 knockdown in pericytes could activate the apoptosis signaling and disrupt the barrier integrity in vitro coculture model.ConclusionsOur findings revealed that targeting SENP1 in pericytes may represent a novel therapeutic strategy for neurovascular protection in stroke.
Performance ofSclerodermus brevicornis,a parasitoid of invasive longhorn beetles, when reared on rice moth larvae
Authors: Abdi Mohamed Khadar , Jucker Costanza , De Marchi Beatrice , Hardy Ian C.W. , Lupi Daniela 
Published: June 2020

AbstractBiological control efficiency can be improved by developing effective mass‐rearing systems to produce large numbers of high‐quality parasitoids. This study explored an alternative host for rearingSclerodermus brevicornis(Kieffer) (Hymenoptera: Bethylidae), a potential biocontrol agent for the suppression of exotic and invasive wood‐boring longhorn beetle (Coleoptera: Cerambycidae) populations in the European agroforestry ecosystems. We tested larvae of the rice moth,Corcyra cephalonicaStainton (Lepidoptera: Pyralidae), as host for the parasitoid. We quantified the probability and timing of host attack and parasitism as well as reproductive success, offspring production, and the characteristics of adult offspring. AsS. brevicornisis a quasi‐social species (multiple females, communally produced offspring broods), we also explored the effects of varying the number of females to which individual hosts were presented, with the aim of determining the optimal female‐to‐host ratio. As time to host attack can be a limiting factor inS. brevicornisrearing protocols, we tested the use of adult females of another bethylid species,Goniozus legneriGordh, to paralyseC. cephalonicalarvae prior to presentation. We identified the conditions within our experiment that maximized offspring production per host and offspring production per adult female parasitoid. We found thatC. cephalonicais suitable as a factitious host and, as it is considerably more straightforward for laboratory rearing than cerambycid species, it is a good candidate for adoption by futureS. brevicornismass‐rearing and release programmes.
The value of screening biopsies in light‐chain (AL) and transthyretin (ATTR) amyloidosis
Authors: Cohen Oliver C. , Sharpley Faye , Gilbertson Janet A. , Wechalekar Ashutosh D. , Sachchithanantham Sajitha , Mahmood Shameem , Whelan Carol J. , Martinez‐Naharro Ana , Fontana Marianna , Lachmann Helen J. , Hawkins Philip N. , Gillmore Julian D. 
Published: June 2020

AbstractIntroductionSystemic amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low‐risk approach to diagnosis.Objectives and MethodsAll patients with systemic AL and ATTR amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006‐2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement.ResultsDiagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) amyloidosis, respectively, was 73.2% and 27.3% for AFA (P< .001), 59.7% and 42.2% for BM (P< .001), and 74.6% and 44.6% for GI biopsy (P< .001). ATTR amyloid deposits were detected in 35.4% BMs and 33.3% of GI biopsies when AFA did not demonstrate amyloid. In AL amyloidosis, sensitivity of combined AFA and BM biopsy in AL amyloidosis was 82.9%. There was a strong association between whole body amyloid burden and sensitivity of each screening biopsy method. The diagnostic sensitivity of screening biopsies ranged from 80.0% to 90.5% for patients with a large amyloid load on 123I‐SAP scintigraphy in comparison with 53.9%‐79.0% in those with no visceral amyloid visible on imaging.ConclusionPerforming both AFA and BM biopsy should be considered in suspected AL amyloidosis to substantially reduce the clinical risk associated with critical organ biopsy. The sensitivity of screening biopsies in ATTR amyloidosis is poor.
Perioperative management for patients with von Willebrand disease: Defining the optimal approach
Authors: Miesbach Wolfgang 
Published: June 2020

Abstractvon Willebrand disease (VWD) is the most common inherited bleeding disorder characterised by a quantitative or qualitative deficiency in von Willebrand factor (VWF). During invasive surgical procedures, patients with VWD require additional treatment to maintain haemostasis; however, due to the complexity of VWD, there is a lack of consensus on the optimal management. In the perioperative period, patients are usually treated with VWF and factor FVIII (FVIII)‐containing concentrates to provide an immediate haemostatic response to prevent excessive bleeding during both elective and emergency surgery. With the introduction of recombinant VWF (rVWF), there is a need for guidance on the use of the various VWF products in the perioperative period for all types of patients and surgeries. This review provides an overview of the current evidence for the surgical management of patients with VWD and, summarises the optimal treatment approach during the perioperative period, and highlights key unanswered questions and the research needed to address the evidence gaps.
P. F. Strawson was neither an externalist nor an internalist about moral responsibility
Authors: De Mesel Benjamin 
Published: June 2020

AbstractInternalism about moral responsibility is the view that moral responsibility is determined primarily by an agent's mental states; externalism is the view that moral responsibility is determined primarily by an agent's overt behaviour and by circumstances external to the agent. In a series of papers, Michelle Ciurria has argued that most if not all current accounts of moral responsibility, including Strawsonian ones, are internalist. Ciurria defends externalism against these accounts, and she argues that, in contrast to his contemporary followers, P.F. Strawson himself was an externalist. I believe that Ciurria's reading of Strawson is problematic. The aim of this paper is to elucidate Strawson's position with regard to the internalism‐externalism issue against the background of Ciurria's reading of him. I conclude that Strawson was neither an internalist nor an externalist about moral responsibility. I draw extensively upon the whole body of Strawson's work, much of which is sadly neglected in discussions of ‘Freedom and Resentment’, although it illuminates many of the issues discussed there.