bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota shape ‘inflamm-ageing’ cytokines and account for age-dependent decline in DNA damage repair
Authors: Guedj Avital , Volman Yael , Geiger-Maor Anat , Bolik Julia , Schumacher Neele , Künzel Sven , Baines John F , Nevo Yuval , Elgavish Sharona , Galun Eithan , Amsalem Hagai , Schmidt-Arras Dirk , Rachmilewitz Jacob 
Published: October 2019

ObjectiveFailing to properly repair damaged DNA drives the ageing process. Furthermore, age-related inflammation contributes to the manifestation of ageing. Recently, we demonstrated that the efficiency of repair of diethylnitrosamine (DEN)-induced double-strand breaks (DSBs) rapidly declines with age. We therefore hypothesised that with age, the decline in DNA damage repair stems from age-related inflammation.DesignWe used DEN-induced DNA damage in mouse livers and compared the efficiency of their resolution in different ages and following various permutations aimed at manipulating the liver age-related inflammation.ResultsWe found that age-related deregulation of innate immunity was linked to altered gut microbiota. Consequently, antibiotic treatment, MyD88 ablation or germ-free mice had reduced cytokine expression and improved DSBs rejoining in 6-month-old mice. In contrast, feeding young mice with a high-fat diet enhanced inflammation and facilitated the decline in DSBs repair. This latter effect was reversed by antibiotic treatment. Kupffer cell replenishment or their inactivation with gadolinium chloride reduced proinflammatory cytokine expression and reversed the decline in DSBs repair. The addition of proinflammatory cytokines ablated DSBs rejoining mediated by macrophage-derived heparin-binding epidermal growth factor-like growth factor.ConclusionsTaken together, our results reveal a previously unrecognised link between commensal bacteria-induced inflammation that results in age-dependent decline in DNA damage repair. Importantly, the present study support the notion of a cell non-autonomous mechanism for age-related decline in DNA damage repair that is based on the presence of ‘inflamm-ageing’ cytokines in the tissue microenvironment, rather than an intrinsic cellular deficiency in the DNA repair machinery.
Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype
Authors: Li Hao-Ran , Qiu Bai-Quan , Gao Jian , Jin Chun , Jiang Jia-Hao , Ding Jian-Yong 
Published: October 2019

AimsTo unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC.MethodsImmunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods.ResultsElevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate.ConclusionsOur study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.
What can public health do for the welfare state? Occupational health could be an answer
Authors: Benavides Fernando G , Serra Consol , Delclos George L 
Published: October 2019

BackgroundThe welfare state has a long history of uncertain future. Nonetheless, health indicators of people living in countries with a more universal and generous welfare state remain better than those living under less generous and more individualist welfare regimes. In this essay, we reflect on how occupational health, as part of public health, can contribute to the sustainability of the welfare state.MethodsOver the course of the political and social transformations of the State, from single guarantor of security to assuming civil and social rights, the practice of public health has added, to its original objectives related to the control of epidemics of contagious diseases, the promotion of health and the reduction of inequalities in health. In the context of the 2030 Agenda of Sustainable Development Goals, there is a great opportunity to expand the welfare state through public health policies.ResultsOn the other hand, the welfare state is only possible when persons are employed in the formal sector. Through their taxes, workers and employers support the welfare state. Occupational health, by preventing injury and illness, and promoting the health of working people, can contribute significantly to the existence of decent work and a quality labour market.ConclusionThe mission of occupational health is to help people enjoy a healthy and prolonged working life, as a critical component of human well-being.
Increasing knowledge in IGF1R defects: lessons from 35 new patients
Authors: Giabicani Eloïse , Willems Marjolaine , Steunou Virginie , Chantot-Bastaraud Sandra , Thibaud Nathalie , Abi Habib Walid , Azzi Salah , Lam Bich , Bérard Laurence , Bony-Trifunovic Hélène , Brachet Cécile , Brischoux-Boucher Elise , Caldagues Emmanuelle , Coutant Regis , Cuvelier Marie-Laure , Gelwane Georges , Guemas Isabelle , Houang Muriel , Isidor Bertrand , Jeandel Claire , Lespinasse James , Naud-Saudreau Catherine , Jesuran-Perelroizen Monique , Perrin Laurence , Piard Juliette , Sechter Claire , Souchon Pierre-François , Storey Caroline , Thomas Domitille , Le Bouc Yves , Rossignol Sylvie , Netchine Irène , Brioude Frédéric 
Published: October 2019

BackgroundThe type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro.MethodsDNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients.ResultsWe detected 21 IGF1R defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of IGF1R. Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation.ConclusionWe report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS.
Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia
Authors: Verdura Edgard , Fons Carme , Schlüter Agatha , Ruiz Montserrat , Fourcade Stéphane , Casasnovas Carlos , Castellano Antonio , Pujol Aurora 
Published: October 2019

BackgroundSince 1994, over 50 families affected by the episodic ataxia type 1 disease spectrum have been described with mutations in KCNA1, encoding the voltage-gated K+ channel subunit Kv1.1. All of these mutations are either transmitted in an autosomal-dominant mode or found as de novo events.MethodsA patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing (WES). A candidate variant was tested using cellular assays and patch-clamp recordings.ResultsWES revealed a homozygous variant (p.Val368Leu) in KCNA1, involving a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Functional analysis showed that mutant protein alone failed to produce functional channels in homozygous state, while coexpression with wild-type produced no effects on K+ currents, similar to wild-type protein alone. Treatment with oxcarbazepine, a sodium channel blocker, proved effective in controlling seizures.ConclusionThis newly identified variant is the first to be reported to act in a recessive mode of inheritance in KCNA1. These findings serve as a cautionary tale for the diagnosis of channelopathies, in which an unreported phenotypic presentation or mode of inheritance for the variant of interest can hinder the identification of causative variants and adequate treatment choice.
Original research: Second IVIg course in Guillain-Barré syndrome with poor prognosis: the non-randomised ISID study
Authors: Verboon Christine , van den Berg Bianca , Cornblath David R , Venema Esmee , Gorson Kenneth C , Lunn Michael P , Lingsma Hester , Van den Bergh Peter , Harbo Thomas , Bateman Kathleen , Pereon Yann , Sindrup Søren H , Kusunoki Susumu , Miller James , Islam Zhahirul , Hartung Hans-Peter , Chavada Govindsinh , Jacobs Bart C , Hughes Richard A C , van Doorn Pieter A 
Published: October 2019

ObjectiveTo compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses.MethodsFrom the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared those treated with one IVIg course to those treated with two IVIg courses. The primary endpoint, the GBS disability scale at 4 weeks, was assessed with multivariable ordinal regression.ResultsOf 237 eligible patients, 199 patients received a single IVIg course. Twenty patients received an ‘early’ second IVIg course (1–2 weeks after start of the first IVIg course) and 18 patients a ‘late’ second IVIg course (2–4 weeks after start of IVIg). At baseline and 1 week, those receiving two IVIg courses were more disabled than those receiving one course. Compared with the one course group, the adjusted OR for a better GBS disability score at 4 weeks was 0.70 (95%CI 0.16 to 3.04) for the early group and 0.66 (95%CI 0.18 to 2.50) for the late group. The secondary endpoints were not in favour of a second IVIg course.ConclusionsThis observational study did not show better outcomes after a second IVIg course in GBS with poor prognosis. The study was limited by small numbers and baseline imbalances. Lack of improvement was likely an incentive to start a second IVIg course. A prospective randomised trial is needed to evaluate whether a second IVIg course improves outcome in GBS.
Incidence of surgical site infection in dogs undergoing soft tissue surgery: risk factors and economic impact
Authors: Espinel‐Rupérez Jorge , Martín‐Ríos Maria Dolores , Salazar Veronica , Baquero‐Artigao Maria Rosario , Ortiz‐Díez Gustavo 
Published: October 2019

ObjectivesTo determine (1) the incidence of surgical site infection (SSI) in patients undergoing soft tissue surgery at a veterinary teaching hospital and to study (2) and describe the main risk factors associated with SSI and (3) assess the economic impact of SSI.DesignProspective cohort study.SettingVeterinary teaching hospital.Participants184 dogs undergoing soft tissue surgery during a 12‐month period (October 2013 to September 2014).Primary outcome measureSurgical site infection.ResultsOut of the 184 patients analysed, SSI was diagnosed in 16 (8.7 per cent) patients, 13 (81.3 per cent) were classified as superficial incisional infection, 2 (12.5 per cent) as deep incisional infection and 1 (6.3 per cent) as organ/space infection. The administration of steroidal anti‐inflammatory drugs (P=0.028), preoperative hyperglycaemia (P=0.015), surgical times longer than 60 minutes (P=0.013), urinary catheterisation (P=0.037) and wrong use of the Elizabethan collar (P=0.025) were identified as risk factors. Total costs increased 74.4 per cent, with an increase in postsurgical costs of 142.2 per cent.ConclusionsThe incidence of SSI was higher than the incidence reported in other published studies, although they were within expected ranges when a surveillance system was implemented. This incidence correlated with an increase in costs. Additionally new important risk factors for its development were detected.
Longitudinal study describing time to Salmonella seroconversion in piglets on three farrow‐to‐finish farms
Authors: Cevallos‐Almeida Maria , Fablet Christelle , Houdayer Catherine , Dorenlor Virginie , Eono Florent , Denis Martine , Kerouanton Annaëlle 
Published: October 2019

BackgroundPigs are frequently colonised with Salmonella enterica, and this constitutes a major risk for human salmonellosis. The infection can be assessed by the serological response of pigs to S enterica. A longitudinal study was undertaken on‐farm to correctly describe this serological response and investigate factors associated with age at Salmonella seroconversion.MethodsThree pig farms and in each farm three successive batches were considered. Per batch, 40 piglets were selected at random from 10 sows (four piglets per sow). Blood was sampled from sows one week after farrowing and from piglets at weeks 1, 6, 10, 14, 18 and 22 and at the slaughterhouse. Salmonella antibodies were detected in serum using a commercial ELISA test. Factors related to farm characteristics, batch management system, porcine reproductive and respiratory syndrome infection, and sows’ Salmonella serological status were recorded to assess their effect on age at seroconversion.ResultsAt week 1 after farrowing, 96.5 per cent of the sows had antibodies against Salmonella. The serological results of piglets at weeks 1 and 6 only were positively correlated with those of the sows. The average age at Salmonella seroconversion was 137±2.2 days (confidence interval at 95 per cent). The first seroconversions occurred from weeks 10 to 14, but most of the pigs (54.6 per cent) were seropositive at the end of the fattening period, with variations between farms and batches (28.9–75.7 per cent). Herd/farm was significantly associated with age at seroconversion.ConclusionThis longitudinal study allowed the authors to follow precisely the evolution of Salmonella seroconversion from maternity to slaughterhouse and confirm the relationship between the seroconversion of sows and serology of their piglets. Moreover, factors related to farm practices and management as a whole are more influential than individual factors (at the pig level) on age at Salmonella seroconversion.
Axions are blind to anomalies
Authors: Quevillon Jérémie , Smith Christopher 
Published: October 2019

Abstract
The axion couplings to SM gauge bosons are derived in various models, and shown to always arise entirely from non-anomalous fermion loops. They are thus independent of the anomaly structure of the model. This fact is without consequence for vector gauge interactions like QCD and QED, but has a major impact for chiral gauge theories. For example, in the DFSZ axion model, the couplings of axions to electroweak gauge bosons do not follow the pattern expected from chiral anomalies, as we prove by an explicit calculation. The reason for this mismatch is traced back to triangle Feynman diagrams sensitive to the anomalous breaking of the vector Ward identity, and is ultimately related to the conservation of baryon and lepton numbers. Though our analyses are entirely done for true axion models, this observation could have important consequences for axion-like particle searches.
Noncardiac Versus Cardiac Mortality in Heart Failure With Preserved, Midrange, and Reduced Ejection Fraction
Authors: Vergaro Giuseppe , Ghionzoli Nicolò , Innocenti Lisa , Taddei Claudia , Giannoni Alberto , Valleggi Alessandro , Borrelli Chiara , Senni Michele , Passino Claudio , Emdin Michele 
Published: October 2019

Background

A thorough analysis of noncardiac determinants of mortality in heart failure (
HF
) is missing. Furthermore, evidence conflicts on the outcome of patients with
HF
and no or mild systolic dysfunction. We aimed to investigate the prevalence of noncardiac and cardiac causes of death in a cohort of chronic
HF
patients, covering the whole spectrum of systolic function.

Methods and Results

We enrolled 2791 stable
HF
patients, classified into HF with reduced ejection fraction (
HF
r
EF
; left ventricular ejection fraction [EF] <40%), HR with midrange EF (
HF
mr
EF
; left ventricular
EF
41–49%), or HF with preserved
EF
(
HF
p
EF
; left ventricular
EF
≥50%), and followed up for all‐cause, cardiac, and noncardiac mortality (adjudicated as due to cancer, sepsis, respiratory disease, renal disease, or other causes). Over follow‐up of 39 months, adjusted mortality was lower in
HF
p
EF
and
HF
mr
EF
versus
HF
r
EF
(hazard ratio: 0.75 [95%
CI,
0.67–0.84],
P
<0.001 for
HF
p
EF
; hazard ratio: 0.78 [95%
CI
, 0.63–0.96],
P
=0.017 for
HF
mr
EF
).
HF
r
EF
had the highest rates of cardiac death, whereas noncardiac mortality was similar across left ventricular
EF
categories. Noncardiac causes accounted for 62% of deaths in
HF
p
EF
, 54% in
HF
mr
EF
and 35% in
HF
r
EF
; cancer was twice as frequent as a cause of death in
HF
p
EF
and
HF
mr
EF
versus
HF
r
EF
. Yearly rates of noncardiac death exceeded those of cardiac death since the beginning of follow‐up in
HF
p
EF
and
HF
mr
EF
.

Conclusions

Noncardiac death is a major determinant of outcome in stable
HF
, exceeding cardiac‐related mortality in
HF
p
EF
and
HF
mr
HF
. Comorbidities should be regarded as main therapeutic targets and objects of dedicated quality improvement initiatives, especially in patients with no or mild systolic dysfunction.
Unlocking the Arctic’s Resources Equitably: Using a Law-and-Science Approach to Fix the Beaufort Sea Boundary
Authors: Bekker Pieter , van de Poll Robert 
Published: October 2019

Abstract
This article analyses the unresolved maritime boundary situated in Arctic waters in the Beaufort Sea, between Canada and the United States through an integrated law-and-science approach incorporating new imagery technology. Resolving the Canada-United States disagreement over the Beaufort Sea boundary based on modern geo-scientific technology and the three-step delimitation methodology developed in the jurisprudence of international courts and tribunals could serve as a catalyst for the peaceful and equitable resolution of all other unresolved boundaries in the Arctic Ocean. This includes the boundaries involving Russia, which can claim more than 40 per cent of the Arctic shoreline. Given that the United States is not a party to the United Nations Convention on the Law of the Sea, this article focuses on mechanisms available to Canada and the United States under general international law and by applying ‘best law’ and ‘best science’.
Range sizes of groundwater amphipods (Crustacea) are not smaller than range sizes of surface amphipods: a case study from Iran
Authors: Esmaeili-Rineh Somayeh , Mamaghani-Shishvan Mahmoud , Fišer Cene , Akmali Vahid , Najafi Nargess 
Published: October 2019

The connectivity of groundwater aquifers is lower compared to surface waters. Consequently, groundwater species are expected to have smaller distributional ranges than their surface relatives. Molecular taxonomy, however, unveiled that many species comprise complexes of morphologically cryptic species, with geographically restricted distributional ranges in subterranean as well as in surface waters. Hence, the range sizes of surface and groundwater species might be more similar in size than hitherto thought. We tested this hypothesis by comparing the range size of surface amphipods of the genus Gammarus and subterranean amphipods of the genus Niphargus in Iran. We re-analyzed the taxonomic structure of both genera using two unilocus species delimitation methods applied to a fragment of the COI mitochondrial marker, to identify molecular operational taxonomic units (MOTUs), and assessed the maximum linear extent (MLE) of the ranges of MOTUs from both genera. Genus Gammarus comprised 44–58 MOTUs while genus Niphargus comprised 20–22 MOTUs. The MLEs of the two genera were not significantly different, regardless the delimitation method applied. The results remained unchanged also after exclusion of single site MOTUs. We tentatively conclude that in this case there is no evidence to consider that groundwater species are geographically more restricted than surface species.
Caregiver Experiences of Care Coordination for Recently Discharged Patients: A Qualitative Metasynthesis
Authors: Callister Catherine , Jones Jacqueline , Schroeder Shara , Breathett Khadijah , Dollar Blythe , Sanghvi Urvi Jhaveri , Harnke Ben , Lum Hillary D. , Jones Christine D. 
Published: October 2019

Caregivers of patients often provide key support for patients after hospitalization. This qualitative metasynthesis describes caregiver perspectives about care coordination for patients discharged from the hospital. A literature search of Ovid Medline and CINAHL completed on May 23, 2018, identified 1,546 studies. Twelve articles were included in the final metasynthesis. Caregiver perspectives about care coordination were compiled into overall themes. A subanalysis of studies in which patients were discharged with home health services was completed. Five main themes emerged related to caregiver perspectives on care coordination after hospitalization: (a) Suboptimal access to clinicians after discharge, (b) Feeling disregarded by clinicians, (c) Need for information and training at discharge, (d) Overwhelming responsibilities to manage appointments and medications, and (e) Need for emotional support. Findings from this metasynthesis suggest the need for clinicians to engage with caregivers to provide support, training, and communication after hospital discharge.