bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rate‐dependent aberrancy and cardiac resynchronization therapy
Authors: Haseeb Sohaib , Gul Enes Elvin 
Published: August 2020

AbstractLeft bundle branch block (LBBB) can result in significant dyssynchrony in left ventricular (LV) contraction, ultimately leading to cardiac remodeling. LBBB can be rate dependent and may appear with LV systolic dysfunction. Cardiac resynchronization therapy (CRT) has been demonstrated to improve hemodynamics as well as clinical symptoms in patients with LBBB. We describe the case of a 57‐year‐old man who underwent CRT implantation due to exertional dyspnea, rate‐dependent LBBB, and impaired left LV systolic function.
Behind the scene: Paracetamol hypersensitivity in children
Authors: Sipahi Cimen Sevgi , Yucel Esra , Ozceker Deniz , Suleyman Ayse , Hizli Demirkale Zeynep , Sayili Ugurcan , Guler Nermin , Ozdemir Cevdet , Tamay Zeynep Ulker 
Published: August 2020

AbstractBackgroundParacetamol, a non‐steroidal anti‐inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity.MethodsSixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX‐1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross‐intolerance hypersensitivity. A subsequent OCT with a selective COX‐2 inhibitor was performed in those cross‐intolerant patients to find out a safe alternative drug.ResultsSixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross‐intolerant after OCT with a COX‐1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross‐intolerant patients, a safe alternative non‐steroidal anti‐inflammatory drug was identified after an OCT with a selective COX‐2 inhibitor.ConclusionOCT stands as the gold‐standard procedure in verifying the diagnosis of patients with paracetamol‐induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.
Liver failure and x‐linked immunodeficiency type 47
Authors: Gumm Alexis J. , Basel Donald G. , Thakrar Pooja , Suchi Mariko , Telega Grzegorz 
Published: August 2020

AbstractPatients with defects in the ATP6AP1 gene have rarely been described. ATP6AP1‐related disorders are a subtype of CDG, which result in enzyme deficiencies affecting multiple organ systems ranging from mild to life‐threatening. Of the 13 patients described, all had hepatopathy, but this is the first case to be successfully transplanted. We describe two brothers who developed hyperbilirubinemia shortly after birth and progressed to liver failure, case 1 by 12 months of age, with successful transplant 2 years later, and case 2 by 4 months of age, who passed away while awaiting liver transplant. Both boys were found to have a new variant in the ATP6AP1 gene: c.932/p.Leu311Gln. Although the identified ATP6AP1 gene variant was classified as unknown significance at the time, both children's phenotypes fit with what has been described for ATP6AP1‐related disorders. Therefore, this result appears to have been diagnostic for both boys. This rare type of CDG, X‐linked immunodeficiency type 47 (OMIM #300972), particularly in patients who progress to liver failure requiring transplant, should be included on the differential of liver failure in infants and toddlers, and its gene should be added to the diagnostic workup for such cases.
Calcineurin inhibitor (CNI)‐associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery
Authors: Ume Adaku C. , Pugh Jennifer M. , Kemp Michael G. , Williams Clintoria R. 
Published: August 2020

AbstractThe use of the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus remains a cornerstone in post‐transplantation immunosuppression. Although these immunosuppressive agents have revolutionized the field of transplantation medicine, its increased skin cancer risk poses a major concern. A key contributor to this phenomenon is a reduced capacity to repair DNA damage caused by exposure to ultraviolet (UV) wavelengths of sunlight. CNIs decrease DNA repair by mechanisms that remain to be fully explored. Though CsA is known to decrease the abundance of key DNA repair enzymes, less is known about how tacrolimus yields this effect. CNIs hold the capacity to inhibit both of the main catalytic calcineurin isoforms (CnAα and CnAβ). However, it is unknown which isoform regulates UV‐induced DNA repair, which is the focus of this review. It is with hope that this insight spurs investigative efforts that conclusively addresses these gaps in knowledge. Additionally, this research also raises the possibility that newer CNIs can be developed that effectively blunt the immune response while mitigating the incidence of skin cancers with immunosuppression.
ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica
Authors: Guan Fei , Zhang Chongyang , Jiang Chunjie , Jacques Muziazia Lupemba , Bai Yang , Lu Shengjun , Liu Wenqi , Lei Jiahui 
Published: August 2020

AbstractAimsThe Schistosoma japonicum (S japonicum)‐infected ApoE gene deficiency (ApoE−/−) mice were used to determine effect of ApoE on hepatic immunopathology.MethodsMurine activities and appetite, body weight, and ratio of liver weight to its body weight (Hepatic mass index, HMI) were observed. Worm load and liver egg burden were evaluated as the infection intensity. Number and size of liver egg granulomas and serum levels of alanine aminotransferase (ALT) were investigated. We analysed hepatic fibrosis by markers of fibrosis in tissue, detected hepatic Th17 and Treg frequency by flow cytometry, and measured hepatic expressions of RORγt, Foxp3, IL‐17A and TGF‐β1 via qPCR. Lipid metabolism was determined by serum levels of cholesterol (TC) and triglyceride (TG) as well as hepatic Oil red O staining.ResultsIn the infected ApoE−/− mice, the increased infection intensity aggravated the hepatic immunopathology (evidenced by increased HMI, elevated egg granulomas and increased ALT levels) and fibrosis (increased hepatic collagen deposition). ApoE deficiency resulted in significantly elevated ratio of hepatic Th17/Treg and higher serum levels of TC and TG, along with higher level of hepatic Oil red O staining.ConclusionsApoE deficiency promotes hepatic pathology and fibrosis by exacerbating Th17/Treg imbalance and altering lipid metabolism in murine schistosomiasis japonica.
A molecular epidemiology study reveals the presence of identical genotypes on grapevines and ground cover weeds and the existence of separate genetic groups in a Botrytis cinerea population
Authors: Toffolatti Silvia L. , Maddalena Giuliana , Marcianò Demetrio , Passera Alessandro , Quaglino Fabio 
Published: August 2020

AbstractBotrytis cinerea, the grey mould agent, is one of the most important pathogens of grapevine, due to the great yield losses caused and the economic costs related to disease control. Ground cover plants are assumed to have a role in the complex epidemiology of the pathogen, even if no information on the genetic variability of the strains is available. In this study, a molecular epidemiology approach, based on the comparative analysis of the nucleotide sequences of multiple genes (ITS1‐ITS2, G3PDH, NEP1, NEP2, BC‐hch, and sdhB), was used to evaluate whether B. cinerea isolated from herbaceous species contributes to grey mould diffusion on grapevines. From 330 samples collected in two vineyards in Lombardy, Italy, 63 B. cinerea strains were isolated from tissues of grapevine with symptoms (50 strains) and spontaneous ground cover plants (13 strains). Capsella bursa‐pastoris, Cardamine impatiens, Lamium purpureum, and Crepis tectorum were identified as novel B. cinerea hosts. Sequence analysis and phylogeny showed that the same genotypes were present on both grapevines and herbaceous plants, with no fitness (estimated from growth and sporulation on potato dextrose agar) or pathogenicity (on grapevine leaves and berries, and tomato leaves) penalties. This confirms that ground cover plants can be a source of inoculum for B. cinerea on grapevine. Moreover, phylogenetic analysis of the BC‐hch gene allowed the identification of two genetically distinct clusters, characterized by vegetative incompatibility and different distributions of the mating types, fitness, and pathogenicity. Therefore, B. cinerea seems to be composed of two diverging subpopulations that do not differ for host specialization.
Testing the top‐down contingent capture of attention for abrupt‐onset cues: Evidence from cue‐elicited N2pc
Authors: Goller Florian , Schoeberl Tobias , Ansorge Ulrich 
Published: August 2020

AbstractMany studies using N2pc as a marker of attentional capture have demonstrated top‐down contingent capture for salient color singletons: Among all salient cues that are not predictive of the target location, only cues similar to searched‐for target features, and thus, matching to the top‐down attentional control settings capture attention. This is reflected in matching cue's elicitation of an N2pc and a cueing effect in behavior, and the absence of the corresponding effects for non‐matching cues (with features dissimilar to that of the searched‐for targets). Yet, with abrupt‐onset cues, corresponding evidence is missing, inviting speculations about the potential of abrupt‐onset cues to capture attention followed by quick suppression within the target displays. Here, we used two types of abrupt‐onset cues to test if capture by such cues also adheres to the contingent‐capture principle: matching abrupt‐onset cues with a color similar to the top‐down control settings and non‐matching abrupt‐onset cues with a color different from all searched‐for targets. With the help of these cues, top‐down contingent capture was supported. Only matching abrupt‐onset cues elicited an N2pc and a behavioral cueing effect. Depending on the exact side conditions, non‐matching cues either elicited no N2pc or a PD (i.e., evidence of active suppression). Results are discussed against the background of competing theories on attention capture by abrupt‐onset cues.
The role of shelf morphology on storm‐bed variability and stratigraphic architecture, Lower Cretaceous, Svalbard
Authors: Grundvåg Sten‐Andreas , Jelby Mads E. , Olaussen Snorre , Śliwińska Kasia K. 
Published: August 2020

AbstractThe dominance of isotropic hummocky cross‐stratification, recording deposition solely by oscillatory flows, in many ancient storm‐dominated shoreface–shelf successions is enigmatic. Based on conventional sedimentological investigations, this study shows that storm deposits in three different and stratigraphically separated siliciclastic sediment wedges within the Lower Cretaceous succession in Svalbard record various depositional processes and principally contrasting sequence stratigraphic architectures. The lower wedge is characterized by low, but comparatively steeper, depositional dips than the middle and upper wedges, and records a change from storm‐dominated offshore transition – lower shoreface to storm‐dominated prodelta – distal delta front deposits. The occurrence of anisotropic hummocky cross‐stratification sandstone beds, scour‐and‐fill features of possible hyperpycnal‐flow origin, and wave‐modified turbidites within this part of the wedge suggests that the proximity to a fluvio‐deltaic system influenced the observed storm‐bed variability. The mudstone‐dominated part of the lower wedge records offshore shelf deposition below storm‐wave base. In the middle wedge, scours, gutter casts and anisotropic hummocky cross‐stratified storm beds occur in inferred distal settings in association with bathymetric steps situated across the platform break of retrogradationally stacked parasequences. These steps gave rise to localized, steeper‐gradient depositional dips which promoted the generation of basinward‐directed flows that occasionally scoured into the underlying seafloor. Storm‐wave and tidal current interaction promoted the development and migration of large‐scale, compound bedforms and smaller‐scale hummocky bedforms preserved as anisotropic hummocky cross‐stratification. The upper wedge consists of thick, seaward‐stepping successions of isotropic hummocky cross‐stratification‐bearing sandstone beds attributed to progradation across a shallow, gently dipping ramp‐type shelf. The associated distal facies are characterized by abundant lenticular, wave ripple cross‐laminated sandstone, suggesting that the basin floor was predominantly positioned above, but near, storm‐wave base. Consequently, shelf morphology and physiography, and the nature of the feeder system (for example, proximity to deltaic systems) are inferred to exert some control on storm‐bed variability and the resulting stratigraphic architecture.
A model to predict SARS‐CoV‐2 infection based on the first three‐month surveillance data in Brazil
Authors: Diaz‐Quijano Fredi A. , da Silva José M. N. , Ganem Fabiana , Oliveira Silvano , Vesga‐Varela Andrea L. , Croda Julio 
Published: August 2020

AbstractObjectiveCOVID‐19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS‐CoV‐2 infection in suspected patients reported to the Brazilian surveillance system.MethodsWe analysed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who travelled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation.ResultsWe described 1468 COVID‐19 cases (confirmed by RT‐PCR) and 4271 patients with other illnesses. With a data subset including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41–96.67%) for the diagnosis of COVID‐19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51–97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%).ConclusionWe obtained a model suitable for the clinical diagnosis of COVID‐19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modelling epidemiological trends.
Subclinical bacteriuria and surgical site infections in dogs with cranial cruciate ligament disease
Authors: Garcia Cheslymar , Benitez Marian E. , Grant David C. , Barry Sabrina L. 
Published: August 2020

AbstractObjectiveTo determine the prevalence of subclinical bacteriuria (SBU) in dogs with cranial cruciate ligament (CCL) disease, the clinical variables and clinicopathologic data associated with SBU, and the incidence of surgical site infections (SSI) in dogs with and without SBU.Study designProspective, clinical cohort study.AnimalsOne hundred fifty‐five dogs with CCL disease.MethodsDogs had a urinalysis, sediment examination, and aerobic urine culture performed. Age, breed, sex, body weight, body condition score, clinical history, and physical examination findings were recorded. Dogs with SBU were not treated for bacteriuria or with postoperative antibiotics. Standard perioperative antimicrobials were provided for all dogs. Dogs that received nonsteroidal anti‐inflammatory drugs were not excluded. Dogs that underwent an osteotomy were followed for at least 1 year to determine incidence of SSI. Outcomes and variables associated with SBU were assessed.ResultsIn 155 dogs with CCL disease, the prevalence of SBU was 6.5%, and SBU occurred exclusively in female dogs (11.4%). The incidence of SSI was 22.3% (25/112). Two of six dogs with SBU and 23/106 dogs without SBU developed SSI. Organisms isolated from SSI were different from those isolated from urine.ConclusionThe prevalence of SBU in dogs with CCL disease was similar to that in other studies in which SBU was evaluated in various populations of dogs.Clinical significanceScreening for and treatment of SBU may not be beneficial prior to tibial osteotomy for CCL disease. Additional studies are required to determine whether dogs with SBU have a greater risk of SSI.
Tetraspanin‐7 regulation of L‐type voltage‐dependent calcium channels controls pancreatic β‐cell insulin secretion
Authors: Dickerson Matthew T. , Dadi Prasanna K. , Butterworth Regan B. , Nakhe Arya Y. , Graff Sarah M. , Zaborska Karolina E. , Schaub Charles M. , Jacobson David A. 
Published: August 2020

Key points
Tetraspanin (TSPAN) proteins regulate many biological processes, including intracellular calcium (Ca2+) handling. TSPAN‐7 is enriched in pancreatic islet cells; however, the function of islet TSPAN‐7 has not been identified.
Here, we characterize how β‐cell TSPAN‐7 regulates Ca2+ handling and hormone secretion. We find that TSPAN‐7 reduces β‐cell glucose‐stimulated Ca2+ entry, slows Ca2+ oscillation frequency and decreases glucose‐stimulated insulin secretion.
TSPAN‐7 controls β‐cell function through a direct interaction with L‐type voltage‐dependent Ca2+ channels (CaV1.2 and CaV1.3), which reduces channel Ca2+ conductance. TSPAN‐7 slows activation of CaV1.2 and accelerates recovery from voltage‐dependent inactivation; TSPAN‐7 also slows CaV1.3 inactivation kinetics.
These findings strongly implicate TSPAN‐7 as a key regulator in determining the set‐point of glucose‐stimulated Ca2+ influx and insulin secretion.
AbstractGlucose‐stimulated insulin secretion (GSIS) is regulated by calcium (Ca2+) entry into pancreatic β‐cells through voltage‐dependent Ca2+ (CaV) channels. Tetraspanin (TSPAN) transmembrane proteins control Ca2+ handling, and thus they may also modulate GSIS. TSPAN‐7 is the most abundant islet TSPAN and immunostaining of mouse and human pancreatic slices shows that TSPAN‐7 is highly expressed in β‐ and α‐cells; however, the function of islet TSPAN‐7 has not been determined. Here, we show that TSPAN‐7 knockdown (KD) increases glucose‐stimulated Ca2+ influx into mouse and human β‐cells. Additionally, mouse β‐cell Ca2+ oscillation frequency was accelerated by TSPAN‐7 KD. Because TSPAN‐7 KD also enhanced Ca2+ entry when membrane potential was clamped with depolarization, the effect of TSPAN‐7 on CaV channel activity was examined. TSPAN‐7 KD enhanced L‐type CaV currents in mouse and human β‐cells. Conversely, heterologous expression of TSPAN‐7 with CaV1.2 and CaV1.3 L‐type CaV channels decreased CaV currents and reduced Ca2+ influx through both channels. This was presumably the result of a direct interaction of TSPAN‐7 and L‐type CaV channels because TSPAN‐7 coimmunoprecipitated with both CaV1.2 and CaV1.3 from primary human β‐cells and from a heterologous expression system. Finally, TSPAN‐7 KD in human β‐cells increased basal (5.6 mM glucose) and stimulated (45 mM KCl + 14 mM glucose) insulin secretion. These findings strongly suggest that TSPAN‐7 modulation of β‐cell L‐type CaV channels is a key determinant of β‐cell glucose‐stimulated Ca2+ entry and thus the set‐point of GSIS.
COVID-19 in children: analysis of the first pandemic peak in England
Authors: Ladhani Shamez N , Amin-Chowdhury Zahin , Davies Hannah G , Aiano Felicity , Hayden Iain , Lacy Joanne , Sinnathamby Mary , de Lusignan Simon , Demirjian Alicia , Whittaker Heather , Andrews Nick , Zambon Maria , Hopkins Susan , Ramsay Mary Elizabeth 
Published: August 2020

ObjectivesTo assess disease trends, testing practices, community surveillance, case-fatality and excess deaths in children as compared with adults during the first pandemic peak in England.SettingEngland.ParticipantsChildren with COVID-19 between January and May 2020.Main outcome measuresTrends in confirmed COVID-19 cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity rates in children compared with adults; community prevalence of SARS-CoV-2 in children with acute respiratory infection (ARI) compared with adults, case-fatality rate in children with confirmed COVID-19 and excess childhood deaths compared with the previous 5 years.ResultsChildren represented 1.1% (1,408/129,704) of SARS-CoV-2 positive cases between 16 January 2020 and 3 May 2020. In total, 540 305 people were tested for SARS-COV-2 and 129,704 (24.0%) were positive. In children aged <16 years, 35,200 tests were performed and 1408 (4.0%) were positive for SARS-CoV-2, compared to 19.1%–34.9% adults. Childhood cases increased from mid-March and peaked on 11 April before declining. Among 2,961 individuals presenting with ARI in primary care, 351 were children and 10 (2.8%) were positive compared with 9.3%–45.5% in adults. Eight children died and four (case-fatality rate, 0.3%; 95% CI 0.07% to 0.7%) were due to COVID-19. We found no evidence of excess mortality in children.ConclusionsChildren accounted for a very small proportion of confirmed cases despite the large numbers of children tested. SARS-CoV-2 positivity was low even in children with ARI. Our findings provide further evidence against the role of children in infection and transmission of SARS-CoV-2.