bluuebunny/crossref_metadata_2025_split huggingface dataset:
Editorial: improving precision of iron deficiency diagnosis in inflammatory bowel disease
Authors: Detlie Trond Espen , Jahnsen Jørgen 
Published: June 2020

LINKED CONTENTThis article is linked to Daude et al papers. To view these articles, visit https://doi.org/10.1111/apt.15739 and https://doi.org/10.1111/apt.15832.
Editorial: gut microbiota profile in patients with autoimmune hepatitis—a clue for adjunctive probiotic therapy? Authors' reply
Authors: Liwinski Timur , Schramm Christoph 
Published: June 2020

LINKED CONTENTThis article is linked to Liwinski et al and Granito et al papers. To view these articles, visit https://doi.org/10.1111/apt.15754 and https://doi.org/10.1111/apt.15795.
Editorial: no man’s oesophagus is an island—authors' reply
Authors: Woo Matthew , Andrews Christopher N. 
Published: June 2020

LINKED CONTENTThis article is linked to Woo and Andrews and Ravi and Katzka papers. To view these articles, visit https://doi.org/10.1111/apt.15758 and https://doi.org/10.1111/apt.15799.
Editorial: PNPLA3 genotype and liver diseases–more than non‐alcoholic fatty liver disease. Authors' reply
Authors: Mederacke Young‐Seon , Mederacke Ingmar 
Published: June 2020

LINKED CONTENTThis article is linked to Mederacke et al and Huang and Chuang papers. To view these articles, visit https://doi.org/10.1111/apt.15722 and https://doi.org/10.1111/apt.15788.
The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma
Authors: Li Jiayi , Shi Chaoji , Zhou Rong , Han Yong , Xu Shengming , Ma Hailong , Zhang Zhiyuan 
Published: June 2020

AbstractReceptor tyrosine kinases (RTKs) and Yes‐associated protein (YAP) are critical driving factors in tumors. Currently, the regulation of RTKs in the Hippo‐YAP pathway has been recognized as an important issue. However, the relationship between AXL, one of the RTKs, and YAP in head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, the crosstalk between AXL and YAP was thoroughly investigated in vitro and in vivo. We determined that there was a positive correlation between AXL and YAP in the HNSCC tissue samples and the Cancer Genome Atlas (TCGA) dataset, and high co‐expression was associated with poor prognosis. Inhibiting YAP decreased AXL expression in HNSCC cells, while YAP overexpression increased AXL. Moreover, ectopic expression of AXL reversed tumor suppressor phenotypes mediated by YAP silencing. This reversal effect was also confirmed in vivo. In addition, AXL overexpression and Gas6, a ligand of AXL, stimulated YAP dephosphorylation, nuclear translocation, and target gene transcription. AXL inhibition decreased YAP dephosphorylation and nuclear translocation. Mechanistically, Gas6 induced a competitive binding to phosphorylated signal transducers and activators of transcription 3 (STAT3) with large tumor suppressor kinase 1 (LATS1) and inhibited the Hippo pathway. This study revealed a novel non‐transcriptional effect of STAT3 in Gas6/AXL‐induced YAP activity, suggesting that STAT3 acted as a critical “molecular switch” during the mutual promotion between AXL and YAP, which might be a promising therapeutic target in HNSCC.
TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity
Authors: Dasouki M , Jabr A , AlDakheel G , Elbadaoui F , Alazami A M , Al-Saud B , Arnaout R , Aldhekri H , Alotaibi I , Al-Mousa H , Hawwari A 
Published: June 2020

Summary
Primary immune deficiency (PID) disorders are clinically and molecularly heterogeneous diseases. T cell receptor excision circles (TRECs) and κ (kappa)-deleting excision circles (KRECs) are markers of T and B cell development, respectively. They are useful tools to assess T and B cell function and immune reconstitution and have been used for newborn screening for severe combined immunodeficiency disease (SCID) and agammaglobulinemia, respectively. Their profiles in several genetically confirmed PIDs are still lacking. The objective of this study was to determine TREC and KREC genomic profiling among various molecularly confirmed PIDs. We used real-time–quantitative polymerase chain reaction (RT–qPCR)-based triplex analysis of TRECs, KRECs and β-actin (ACTB) in whole blood genomic DNA isolated from 108 patients with molecularly confirmed PIDs. All agammaglobulinemia patients had low KREC counts. All SCIDs and Omenn syndrome patients secondary to mutations in RAG1, RAG2, DCLRE1C and NHEJ1 had low TREC and KREC counts. JAK3-deficient patients had normal KREC and the TREC count was influenced by the type of mutation. Early-onset ADA patients had low TREC and KREC counts. Four patients with zeta-chain-associated protein kinase 70 (ZAP70) had low TREC. All purine nucleoside phosphorylase (PNP) patients had low TREC. Combined immunodeficiency (CID) patients secondary to AK2, PTPRC, CD247, DCLREC1 and STAT1 had normal TREC and KREC counts. Most patients with ataxia–telangiectasia (AT) patients had low TREC and KREC, while most DOCK8-deficient patients had low TRECs only. Two of five patients with Wiskott–Aldrich syndrome (WAS) had low TREC counts as well as one patient each with bare lymphocyte syndrome (BLS) and chronic granulomatous disease. All patients with Griscelli disease, Chediak–Higashi syndrome, hyper-immunoglobulin (Ig)M syndrome and IFNGR2 had normal TREC and KREC counts. These data suggest that, in addition to classical SCID and agammaglobulinemia, TREC/KREC assay may identify ZAP70 patients and secondary target PIDs, including dedicator of cytokinesis 8 (DOCK8) deficiency, AT and some individuals with WAS and BLS.
Ashen History: Narrating the Fire at the Origin of Modern Singapore
Authors: Loh Kah Seng 
Published: June 2020

AbstractOral histories of former squatters trace the origins of modern Singapore to its largest and historically most important fire at Bukit Ho Swee on 25 May 1961. The inferno not only razed an urban kampong, it also set the stage for the government to transform Singapore into an organized public housing state of governable citizen‐workers. The storytellers’ ashen histories highlight the grey area colored by the memory of the inferno; they straddle national and local history, and reveal the price of citizenship in Singapore. The narratives of the kampong tell us much about people’s mobility, community, and modernity—they were far from inert, as the state depicted them. Where the state was transfixed on high modernism in the form of organized public housing blocks, the squatters were willing to accept different typologies of housing and ways of life. Their narratives of, and alternatively silence on, possible arson outline the social worlds of the squatters in the past but also underline the ambivalent position of socialized citizens today, straddling and mediating between their own narratives and that of the state.
The effect of the number of active electrode poles during tined lead placement on long‐term efficacy of sacral neuromodulation in patients with faecal incontinence
Authors: Assmann R. , Breukink S. O. , Caubergh S. A. P. , Stassen L. P. S. , van Kuijk S. M. J. , Melenhorst J. 
Published: June 2020

AbstractAimThere is an ongoing debate as to whether or not the efficacy of sacral neuromodulation (SNM) is optimized by maximizing the total number of active electrode poles (AEPs) during lead placement because there are more programming options. However, this is at the cost of increased operating time. The aims of this study were to establish if a higher number of AEPs improves SNM efficacy during the trial period and after permanent implantable pulse generator (IPG) placement and if there is there a correlation between number of AEPs and battery life of the first placed IPG.MethodThis was a single centre retrospective cohort study of new patients with faecal incontinence who underwent SNM between 2000 and 2018. Exclusion criteria were sphincter defect > 30%, rectocele/enterocele Grade 3 or higher and incomplete records.ResultsIn all, 288/456 (63%) patients (women 91%; mean age 58.5 ± 11.7 years) were eligible for analysis. The number of AEPs during lead placement was two (n = 42, 14.5%), three (n = 82, 28.5%) and four (n = 164, 57%). There was no association between the number of AEPs during tined lead placement and long‐term efficacy. Neither the success rate of the trial phase nor the battery life after first placed IPG was influenced by the number of AEPs.ConclusionIn this study, the number of AEPs does not seem to influence long‐term efficacy of SNM success rate during the trial phase or the battery life of the first placed IPG. However, we also suggest that at the very least there should be two AEPs at lead placement.
Prioritizing road‐kill mitigation areas: A spatially explicit national‐scale model for an elusive carnivore
Authors: Russo Luca F. , Barrientos Rafael , Fabrizio Mauro , Di Febbraro Mirko , Loy Anna 
Published: June 2020

AbstractAimRoads impact wildlife in different ways, among which road mortality has been the most studied. Budgets in conservation biology are usually small, and macroecological approaches have been employed in recent years as the first steps towards guiding management. Carnivores are particularly vulnerable to mortality on roads due to their elevated ecological needs (low population density, often low fecundity and relatively large home ranges). Our aim was to develop a ranking methodology to prioritize specific areas for road‐kill mitigation.LocationContinental Italy.MethodsWe studied 271 occurrences of live polecats (Mustela putorius) and 212 polecat road‐kill sites. We used the former to generate a species distribution model and the latter to identify the variables that determined the road‐kill risk. Habitat suitability was derived from a spatial distribution model that combined the polecat occurrence data with a set of environmental variables. Prey availability was derived from the combination of suitability maps of 26 prey species. We used generalized linear modelling to identify the set of variables that best explained the occurrence of road‐kills. The variables included in the best performing model were combined to produce the road risk map and to identify the areas with the highest densities of road sections with highest risk.ResultsRoad‐kills were positively associated with the road sections with higher broad‐leaved forest coverage. The number of casualties was found to be higher than expected on the national and provincial roads and lower than expected on the local roads.Main conclusionsThis approach allowed us to identify the 10 × 10 km cells where mitigation actions to prevent road‐kills should be prioritized. As mitigation actions (wildlife passage construction, fencing) are expensive, measures should be prioritized on the specific high‐risk road sections inside these selected cells, avoiding generalized mitigation plans.
Speech in children with cerebral palsy
Authors: Mei Cristina , Reilly Sheena , Bickerton Molly , Mensah Fiona , Turner Samantha , Kumaranayagam Dhanooshini , Pennington Lindsay , Reddihough Dinah , Morgan Angela T. 
Published: June 2020

AimTo examine the frequency, characteristics, and factors associated with speech delay and disorder in a community sample of children with cerebral palsy (CP).MethodParticipants were 84 children (37 females, 47 males; aged between 4y 11mo–6y 6mo) with CP identified through a population‐based registry. Speech and oromotor function were systematically evaluated to provide a differential diagnosis of articulation, phonological, and motor speech disorders.ResultsIn total, 82% (69/84) of participants had delayed or disordered speech production, including minimally verbal presentations (n=20). Verbal participants (n=64) presented with dysarthria (78%), articulation delay or disorder (54%), phonological delay or disorder (43%), features of childhood apraxia of speech (CAS) (17%), or mixed presentations across these conditions. Speech intelligibility was poorest in those with dysarthria and features of CAS. Speech delay or disorder in verbal participants was associated with language impairment (p=0.002) and reduced health‐related quality of life (p=0.04) (Fisher’s exact test). Poorer speech accuracy (i.e. lower percentage consonants correct) correlated with greater impairments in both language (p<0.001) and oromotor function (p<0.001) (Spearman’s test).InterpretationThe speech profile of children with CP is characterized by impairment at multiple levels of speech production (phonetic, cognitive‐linguistic, neuromuscular execution, and high‐level planning/programming), highlighting the importance of a personalized differential diagnosis informing targeted treatment.
Genetic predisposition in metabolic‐dysfunction‐associated fatty liver disease and cardiovascular outcomes—Systematic review
Authors: Ismaiel Abdulrahman , Dumitrascu Dan L. 
Published: June 2020

AbstractBackgroundDespite the demonstrated increased cardiovascular (CV) risk associated with metabolic‐dysfunction‐associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C > T near membrane‐bound O‐acyltransferase domain‐containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C > T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD.Materials and MethodsAn electronic search on PubMed, Embase and Cochrane Library for articles published till 23 March 2020 was systematically performed. Articles were screened, and data extracted from eligible studies by two reviewers independently.ResultsStudies conducted on adults with MAFLD involving European, Hispanic and African American populations evaluating rs641738 reported reduced hepatic expression of MBOAT7, increased hepatic fat content, severity of MAFLD, susceptibility to develop NASH, advanced fibrosis and HCC in adults. However, most articles involving Asian individuals contradicted these findings. Studies involving obese children associated rs641738 with increased plasma alanine aminotransferase (ALT) levels, while its association with MAFLD remains inconsistent. The rs641738 variant was assessed as a MAFLD susceptibility gene in coronary artery disease (CAD) reporting neutral effects.ConclusionsDespite inconclusive results in Asian populations, rs641738C > T near MBOAT7 is associated with increased hepatic fat, MAFLD severity, susceptibility to develop NASH, advanced fibrosis and HCC in adults from Caucasian, Hispanic and African American ethnicities with MAFLD, as well as elevated ALT levels in children, while exerting neutral effects in CAD.
Effect of temperature on reproduction, development, and phenotypic plasticity ofDrosophila suzukiiin Brazil
Authors: Schlesener Daniele C.H. , Wollmann Jutiane , Krüger Alexandra P. , Martins Liliane N. , Teixeira Cristiano M. , Bernardi Daniel , Garcia Flavio R.M. 
Published: June 2020

AbstractTemperature is a determining factor for the development and establishment potential of insect pests. The present study describes the impact of temperature (13, 18, 23, 25, 28, 30, and 33 °C) on the life cycle parameters and phenotypic plasticity of South American populations ofDrosophila suzukii(Matsumura) (Diptera: Drosophilidae) in the laboratory. Secondary objectives were to determine the lower thermal threshold and thermal constant to estimate the number of annual generations of the insect in small‐fruit‐producing regions in Brazil. The highest egg‐to‐adult survival was recorded at 23 and 25 °C. At 30 and 33 °C, no emergence ofD. suzukiiwas observed. The egg‐to‐adult development time was shortest at 25 and 28 °C (ca. 10 days). The net reproductive rate (R0), and the intrinsic rate of population increase (rm) were highest at 23 and 25 °C. In contrast, temperatures of 13 and 28 °C generated largest and smallest body sizes, respectively, and caused reductions of 99 and 93% in R0. The estimated lower thermal threshold was 7.8 °C for egg‐to‐adult survival. The estimated thermal constant was 185.8 degree days, and the estimated annual number of generations ofD. suzukiiranged from 17.1 in cold regions to 27.2 in warm regions. The results of the present study are important for understandingD. suzukiioccurrence in the field, contributing to more informed and precise pest management.
Favorable COVID‐19 course despite significant comorbidities in a ruxolitinib‐treated patient with primary myelofibrosis
Authors: Koschmieder Steffen , Jost Edgar , Cornelissen Christian , Müller Tobias , Schulze‐Hagen Maximilian , Bickenbach Johannes , Marx Gernot , Kleines Michael , Marx Nikolaus , Brümmendorf Tim H. , Dreher Michael 
Published: June 2020

AbstractCOVID‐19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID‐19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental “cytokine storm”, such as Janus‐activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55‐yo patient with proven COVID‐19 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in‐label for co‐existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID‐19. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient´s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS‐CoV‐2 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID‐19 pneumonia, preventing cytokine storm and ARDS.
Serum soluble ST2 is a potential long‐term prognostic biomarker for transient ischaemic attack and ischaemic stroke
Authors: Tian X. , Guo Y. , Wang X. , Pei L. , Wang X. , Wu J. , Sun S. , Li Y. , Ning M. , Buonanno F. S. , Xu Y. , Song B. 
Published: June 2020

Background and purposeSoluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke.MethodsPatients within 24 h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all‐cause death within 90 days and 1 year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards.ResultsAmong the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31–28.84) ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43–18.51) for poor outcome within 90 days and 3.00 (1.29–6.97) at 1 year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37–106.6%, P = 0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08–5.18%, P = 0.043) at 90 days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74–74.61%, P = 0.013) at 1 year.ConclusionsIncreased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90 days and 1 year, suggesting that serum sST2 may be a potential long‐term prognostic biomarker for TIA/ischaemic stroke.
Zebrafish model of posttraumatic epilepsy
Authors: Cho Sung‐Joon , Park Eugene , Telliyan Tamar , Baker Andrew , Reid Aylin Y. 
Published: June 2020

AbstractObjectivePosttraumatic epilepsy (PTE) is defined as recurrent and unprovoked seizures occurring >1 week after traumatic brain injury (TBI). Animal studies of PTE are lengthy and expensive. In this study, we developed a cost‐effective PTE animal model using zebrafish to bridge the gap between in vitro studies and low‐throughput animal studies.MethodsWe used two different sets of parameters (G1 and G2) to induce closed‐head TBI in adult zebrafish using pulsed high‐intensity focused ultrasound. Injured fish and naive controls were evaluated for behavioral deficits and spontaneous behavioral seizure activity up to 21 days postinjury (DPI). We also assessed behavioral seizure susceptibility to a subconvulsive dose of pentylenetetrazole (PTZ; 2.5 mmol·L–1) and recorded electrophysiological signals to confirm seizure activity up to 40 DPI. In addition, we investigated injury‐related changes in the blood‐brain barrier and expression levels of various proteins altered in rodent and human TBI.ResultsThe G2 parameters resulted in a more severe TBI, with a mortality rate of 25%, as well as motor dysfunction and heightened anxiety persisting at 21 DPI. One hundred percent of the G2 group showed spontaneous myocloniclike behavior, and 80% demonstrated tonic‐clonic–like behavioral seizures by 21 DPI. Such activities were not detected in the naive group. After the application of 2.5 mmol·L–1 PTZ, 100% of injured zebrafish had cloniclike seizures at 21 DPI, versus 30% of the naive group. We also demonstrated electrographic seizure activity at 40 DPI, which was not detected in the naive controls. Lastly, we observed acute blood‐brain barrier dysfunction and increased levels of HMGB1 and ratios of phosphorylated/total Akt and tau through 21 DPI.SignificanceTogether, the results indicate that severe TBI in the adult zebrafish leads to similar behavioral and physiological changes to those of more traditional models, including the development of PTE, and suggest this may be a useful model that can accelerate research in TBI/PTE.
Surgical treatment of a mammary gland comedocarcinoma in an Arabian mare: Post‐operative management, and histopathological and immunohistochemical features
Authors: Sabiza S. , Rezaie A. , Naddaf H. , Sajjadi Dezfouli M. , Kaamyab Niya M. 
Published: June 2020

SummaryA lactating 20‐year‐old, brown, Arabian mare, weighing about 300 kg, presented for bleeding from one teat and severe swelling of the entire mammary gland. The mare had untreated mastitis 10 months before. Consequently, a gangrenous teat developed after chronic bloody and purulent discharges. The teat was removed surgically by the field veterinarian. At that time, the mammary gland increased in size. Bloody and purulent discharges restarted 10 days previously. Under general anaesthesia, the entire mammary gland was removed. Comedocarcinoma was diagnosed by histopathological assessment. Immunohistochemical staining was performed for pan‐cytokeratin and vimentin. Microscopic examination of immunohistochemical stained slides revealed expression of pan‐cytokeratin. In conclusion, this report describes clinical, macroscopic, histopathological and immunohistochemical characteristics of comedocarcinoma that did not metastasise to regional lymph nodes. Reports in the field of equine oncology contribute to improved general knowledge in equine medicine, contributing to better diagnosis and treatment.