bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adalimumab‐induced platelet antibodies resulting in severe thrombocytopenia
Authors: Boiten Henk‐Jan , Amini Sufia , Wolfhagen Frank H. J. , Westerweel Peter E. 
Published: February 2021

Anti‐tumour necrosis factor‐α (TNFα) agents are effective in diseases including Crohn's disease but may cause cytopenias. The mechanisms involved in anti‐TNFα agent‐induced thrombocytopenia are scarce. We report a 73‐year‐old male with Crohn's disease for which he currently used adalimumab, an anti‐TNFα agent. He had received mesalazine and infliximab before the treatment of adalimumab. No comorbidities were present. Routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24 × 109/L), after which adalimumab was discontinued. Bleeding symptoms included cutaneous haematomas and mild epistaxis. Direct monoclonal antibody‐specific immobilization of platelet antigens revealed autoantibodies specific to glycoprotein IIb/IIIa and glycoprotein V platelet receptors. There was no bone marrow suppression. Other causes of the thrombocytopenia were ruled out. The platelet count normalized after adalimumab discontinuation. No further interventions were required. Monitoring thrombocyte levels after initiating anti‐TNFα agents is recommended, which could lead to prevention of this potentially fatal phenomenon.
Determination and estimation of optimal quarantine duration for infectious diseases with application to data analysis of COVID‐19
Authors: Wang Ruoyu , Wang Qihua 
Published: February 2021

AbstractQuarantine measure is a commonly used nonpharmaceutical intervention during the outbreak of infectious diseases. A key problem for implementing quarantine measure is to determine the duration of the quarantine. Different from the existing methods that determine a constant quarantine duration for everyone, we develop an individualized quarantine rule that suggests different quarantine durations for individuals with different characteristics. The proposed quarantine rule is optimal in the sense that it minimizes the average quarantine duration of uninfected people with the constraint that the probability of symptom presentation for infected people attains the given value closing to 1. The optimal solution for the quarantine duration is obtained and estimated by some statistical methods with application to analyzing COVID‐19 data.
IL‐17‐induced inflammation modulates the mPGES‐1/PPAR‐γ pathway in monocytes/macrophages
Authors: Raucci Federica , Saviano Anella , Casillo Gian Marco , Guerra‐Rodriguez Miguel , Mansour Adel Abo , Piccolo Marialuisa , Ferraro Maria Grazia , Panza Elisabetta , Vellecco Valentina , Irace Carlo , Caso Francesco , Scarpa Raffaele , Mascolo Nicola , Alfaifi Mohammed , Iqbal Asif Jilani , Maione Francesco 
Published: February 2021

Background and PurposeRecent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal PGE2 synthase (mPGES) and PPAR‐γ expression are modulated by a variety of inflammatory factors and stimuli. Considering that very little is known about the biological effects promoted by IL‐17 in the context of mPGES‐1/PPAR‐γ modulation, we sought to investigate the contribution of this unique cytokine on this integrated pathway during the onset of inflammation.Experimental ApproachWe evaluated effects of PF 9184 (mPGES‐1 inhibitor) and troglitazone (PPAR‐γ agonist) in vitro, using the mouse macrophage cell line J774A.1. In vivo, the dorsal air pouch model in CD1 mice was used, and inflammatory infiltrates were analysed by flow cytometry. Locally produced cyto‐chemokines and PGs were assessed using elisa assays. Western blots were also employed to determine the activity of various enzymes involved in downstream signalling pathways.Key ResultsPF 9184 and troglitazone, in a time‐ and dose‐dependent manner, modulated leukocyte infiltration, myeloperoxidase activity, and the expression of COX‐2/mPGES‐1, NF‐кB/IкB‐α, and mPTGDS‐1/PPAR‐γ, induced by IL‐17. Moreover, both PF 9184 and troglitazone modulated PG (PGE2, PGD2, and PGJ2) production, the expression of different pro‐inflammatory cyto‐chemokines, and the recruitment of inflammatory monocytes, in response to IL‐17.Conclusions and ImplicationsOur data suggest that IL‐17 may constitute a specific modulator of inflammatory monocytes during later phases of the inflammatory response. The results of this study show, for the first time, that the IL‐17/mPGES‐1/PPAR‐γ pathway could represent a potential therapeutic target for inflammatory‐based and immune‐mediated diseases.LINKED ARTICLESThis article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc
Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation
Authors: Takasawa Kei , Miyakawa Yuichi , Saito Yoko , Adachi Eriko , Shidei Tsunanori , Sutani Akito , Gau Maki , Nakagawa Ryuichi , Taki Atsuko , Kashimada Kenichi , Morio Tomohiro 
Published: February 2021

AbstractBackgroundThe most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8. Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by genetic form, particularly biallelic mutations in KATP channel genes. A few reports indicated marked clinical heterogeneity in siblings with identical biallelic mutations in ABCC8. The clinical heterogeneity in biallelic KATP CHI was speculated to be caused by epigenetic and environmental factors or related to differences in splicing factor machinery.ObjectiveTo elucidate the clinical pathophysiology, especially heterogeneity, among three cases with CHI caused by a homogenous novel mutation.Patients and MethodsWe report a case series that includes two siblings and one unrelated individual with CHI caused by a homogenous 1‐bp deletion around the splice acceptor site at the exon 35 mutation of ABCC8, which exhibited markedly distinct phenotypes. To assess the effect of the mutation on splicing, we performed digital droplet polymerase chain reaction (ddPCR) on normal pancreas tissue and a patient’s lymphocytes.ResultsddPCR of ABCC8 cDNA revealed that expression of exon 35 and its upstream and downstream regions did not differ. These data suggested that clinical heterogeneity may not be caused by differences in splicing factor machinery.ConclusionThe phenotypic variation in homozygotes could not be explained by splicing abnormalities. Though early genetic diagnosis of KATP CHI could contribute to selecting appropriate therapeutic options, more deliberate selection of therapeutic options in diffuse CHI due to biallelic ABCC8 mutations may be required.
A phase I, nonrandomized controlled trial demonstrating the novel technique of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy utilizing warm humidified carbon dioxide insufflation
Authors: Garrett Celine , Steffens Daniel , Ansari Nabila , Koh Cherry 
Published: February 2021

AbstractAimThe aim of this work was to report on the safety and feasibility of warm humidified CO2 (WHCO2) insufflation during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodTen consecutive patients with histologically confirmed peritoneal cancer were enrolled in this phase I pilot nonrandomized controlled trial. They were alternately assigned to CRS and HIPEC with WHCO2 versus standard procedure. WHCO2 was delivered at 10 L/min, a pressure of 4.5 bar, 37ºC and 98% relative humidity during CRS using the HumiGardTM system. HIPEC was performed with an open abdomen using the Coliseum technique at 42ºC for 60 min. All patients were admitted to the intensive care unit and commenced on total parenteral nutrition postoperatively. Surface and core temperatures were measured every 30 min using an infrared camera and nasopharyngeal probe, respectively. Clinicopathological, intra‐ and postoperative details were collated between groups, and median surface and core temperatures were statistically compared.ResultsSurface and core temperatures were generally higher in the WHCO2 group. Core temperature at 120 and 180 min was significantly higher in the WHCO2 versus the non‐WHCO2 group (p = 0.028 and 0.008, respectively). There was a significant linear relationship between core and surface temperature at 30, 60, 90, 120, 150 and 180 min (p = 0.033, 0.004, 0.007, 0.021, 0.009 and 0.006, respectively). The peritoneal cancer index was lower but the estimated blood loss was higher in the non‐WHCO2 than the WHCO2 group.ConclusionWHCO2 in CRS and HIPEC appears to be safe and feasible. An appropriately powered phase II trial will be required to determine if WHCO2 is associated with improved intra‐ and postoperative outcomes.
Histopathology of chronic spontaneous urticaria with occasional bruising lesions is not significantly different from urticaria with typical wheals
Authors: Batista Mariana , Calado Rebeca , Gil Francisco , Cardoso José C. , Tellechea Oscar , Gonçalo Margarida 
Published: February 2021

AbstractBackgroundChronic spontaneous urticaria (CSU) may occasionally exhibit long‐lasting lesions with bruising, usually considered a hallmark of urticarial vasculitis (UV). Histopathology of these chronic urticarial lesions has not been extensively studied.MethodsSkin biopsies from patients with anti‐H1 resistant CSU were evaluated for several parameters (edema, location, intensity, and cell composition of the inflammatory infiltrate, and abnormalities in the blood vessels).ResultsWe studied 45 patients (37 female/8 male, mean age 49.3 years) with CSU, 60% of whom with occasional bruising lesions and 3 patients with hypocomplementemic UV. Histopathology in CSU showed mainly perivascular and interstitial inflammatory infiltrate (91.1%), including eosinophils (80%), neutrophils (77.8%), and lymphocytes (71.1%), vasodilatation (88.9%), intravascular neutrophils (95.6%), dermal edema (51.1%), swelling of endothelial cells (51.1%), and minor and rare fibrinoid necrosis and karyorrhexis (6.7%). Significant karyorrhexis and frank fibrinoid necrosis were observed, respectively, in two and three cases of UV. In patients with occasional bruising, mast cells occurred in fewer cases whereas eosinophils were more frequent, but no statistically significant difference was found for other parameters.ConclusionsHistopathological findings were not significantly different between CSU with or without bruising lesions. Bruising may be associated with more severe forms of CSU with no histopathological signature, although UV cannot be completely excluded based on histopathology.
Follikulotropismus bei Lentigo maligna und Lentigo‐maligna‐Melanom im Kopf‐Hals‐Bereich
Authors: Dika Emi , Lambertini Martina , Patrizi Annalisa , Misciali Cosimo , Scarfì Federica , Pellacani Giovanni , Mandel Victor Desmond , Tullio Francesca Di , Stanganelli Ignazio , Chester Johanna , Kaleci Shaniko , Massi Daniela , De Giorgi Vincenzo , Cinotti Elisa , Rubegni Pietro , Perrot Jean Luc , Farnetani Francesca 
Published: February 2021

ZusammenfassungHintergrundLentigo maligna (LM) und das Lentigo maligna‐Melanom (LMM) sind Histotypen des Melanoms, die in Hautarealen mit kumulativer Schädigung durch Sonneneinstrahlung entstehen. Atypische Melanozyten in den Haarfollikeln (Follikulotropismus) sind ein typisches Merkmal von LM/LMM. Die Bedeutung dieses Phänomens ist noch nicht vollständig aufgeklärt. Bei LM könnte es jedoch mit dem Ansprechen auf die Behandlung und beim LMM mit der Progression korrelieren.ZielDiese retrospektive Multicenterstudie hat das Ziel, dermatoskopische Merkmale im Zusammenhang mit Follikulotropismus bei LM/LMM zu identifizieren.Patienten und MethodenWir haben insgesamt 25 Fälle von LM und 73 Fälle von LMM analysiert, die in den Jahren 2005–2014 an den Melanomzentren der Universitäten Bologna, Modena, Florenz und Siena in Italien sowie der Universität Nizza in Frankreich diagnostiziert wurden.ErgebnisseGraue Kreisformationen (44 %) deuteten auf einen Befall auf der Ebene des Isthmus/Bulbus hin; bei LM‐Läsionen am Infundibulum fehlten sie völlig (p= 0,041). In der Gruppe der LMM deuteten hell/dunkelbraune Pseudonetzwerke und hellbraune strukturlose Bereiche auf eine diffuse Verteilung maligner Melanozyten in den follikulären Einheiten hin (p< 0,001 bzw. p= 0,001), während graue Kreisformationen auf eine fokale oder diffuse Verteilung schließen ließen (p< 0,001).SchlussfolgerungenEin besseres Verständnis der Ausbreitung maligner Melanozyten kann Ärzten bei der Entscheidung helfen, ob die Läsion radikal exzidiert oder in dem am stärksten invasiven Anteil (mit potenziellem Follikulotropismus) biopsiert werden soll.
Atopic skin diathesis rather than atopic dermatitis is associated with specific contact allergies
Authors: Forkel Susann , Cevik Naciye , Schill Tillmann , Worm Margitta , Mahler Vera , Weisshaar Elke , Vieluf Dieter , Pfützner Wolfgang , Löffler Harald , Schön Michael P. , Geier Johannes , Buhl Timo 
Published: February 2021

SummaryBackgroundThe association of atopic dermatitis (AD) and allergic contact dermatitis has been a matter of considerable uncertainty. Study results range from lack of any association to increased sensitization for multiple allergens, but fail to identify consistent allergen associations.ObjectiveWe studied a large patch test cohort of patients stratified by their atopic skin diathesis using the Erlangen Atopy Score (EAS), independent of active skin disease.MethodsRetrospective multi‐center data analysis from five departments of dermatology in Germany with 4,509 patients. Patients were grouped as “no atopic skin diathesis” (n = 2,165) and “atopic skin diathesis” (n = 1,743), according to EAS.ResultsSignificantly more individuals with atopic skin diathesis showed at least one positive patch test reaction to the baseline series compared to individuals without atopic skin diathesis (49.1 % vs. 38.3 %). In logistic regression analyses, atopic skin diathesis was associated with a significantly higher risk of sensitization to methylchloroisothiazolinone/methylisothiazolinone (OR 2.383) and methylisothiazolinone (OR 1.891), thiuram mix (OR 1.614), as well as nickel (OR 1.530), cobalt (OR 1.683), and chromium (OR 2.089).ConclusionsAtopic skin diathesis proved to be the most important intrinsic risk factor for contact sensitization to few, specific allergens. Past or present AD was a less relevant variable.
Genetic variation analyses indicate conserved SARS‐CoV‐2–host interaction and varied genetic adaptation in immune response factors in modern human evolution
Authors: Lee Ji‐Won , Lee In‐Hee , Sato Takanori , Kong Sek Won , Iimura Tadahiro 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a pandemic as of early 2020. Upon infection, SARS‐CoV‐2 attaches to its receptor, that is, angiotensin‐converting enzyme 2 (ACE2), on the surface of host cells and is then internalized into host cells via enzymatic machineries. This subsequently stimulates immune response factors. Since the host immune response and severity of COVID‐19 vary among individuals, genetic risk factors for severe COVID‐19 cases have been investigated. Our research group recently conducted a survey of genetic variants among SARS‐CoV‐2‐interacting molecules across populations, noting near absence of difference in allele frequency spectrum between populations in these genes. Recent genome‐wide association studies have identified genetic risk factors for severe COVID‐19 cases in a segment of chromosome 3 that involves six genes encoding three immune‐regulatory chemokine receptors and another three molecules. The risk haplotype seemed to be inherited from Neanderthals, suggesting genetic adaptation against pathogens in modern human evolution. Therefore, SARS‐CoV‐2 uses highly conserved molecules as its virion interaction, whereas its immune response appears to be genetically biased in individuals to some extent. We herein review the molecular process of SARS‐CoV‐2 infection as well as our further survey of genetic variants of its related immune effectors. We also discuss aspects of modern human evolution.
Being, belonging, and borders: Scandinavian creation theology as political theology
Authors: Gerle Elisabeth 
Published: February 2021

AbstractDesire for life and protecting lives has come to the fore during the pandemic. Borders have been closed to stop the spread of Covid‐19. The virus does not respect borders, yet physical distance is crucial. Three things have become clear. One is the level of uncertainty about which measures are most efficient. The other is that the neo‐liberal philosophy with “just in time” deliveries on a global market has made everyone vulnerable and invited national protectionism rather than collaboration. A third insight is that the lack of borders between wild and tame animals and human beings is connected to the emergence of the virus itself, where rain forests are exploited for short sighted profit. In the midst of this, a cry for Being, for Life, and Human Flourishing, can be heard as an underlying drumbeat. In relation to this I ponder Being in relation to Belonging and to Borders. I first describe a political landscape where neo‐nationalist, and neo‐atheist, claims for belonging, have emerged all over the world, and hence emphasized strong borders between different people, but not for capital. Secondly, I draw on resources from Scandinavian Creation Theology, especially Grundtvig, Aulén, and Wingren to paint a planetary vision with porous borders, beyond patriarchy, populism, and protectionism. In the long run there is no opting out of the planetary vulnerability. I launch the term eschatological creation theology for a creation theology that allows creation to be inspired by the Kin‐dom to come with righteousness and life in abundance.
Unusual presentations of cardiac rupture during COVID‐19 pandemic
Authors: Allende Norberto Gustavo , Santos Ramiro , Sokn Fernando Jose , Merino Sabrina Andrea , Accastello Gerardo Maximiliano , Medina Juan Carlos , Isquierdo Ignacio Nicolas , Rapallo Carlos Alberto 
Published: February 2021

AbstractThe Covid‐19 pandemia has many other undesirable consequences apart of virus infection. Less people is hospitalized due to acute coronary syndrome and the delay to seek medical attention has increased. Patients with ST segment elevation myocardial infarction arrive at the hospital too late to be timely treated and we have recently seen mechanical complications that were more frequent in the past decades before the use of reperfusion strategies. In this report we describe the presentation, evolution and detailed imaging evaluation of two patients with unusual presentations of cardiac rupture: left ventricular pseudoaneurysm and left ventricular intramyocardial dissecting hematoma.
Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice
Authors: Wu Jing , Fan Zhen , Zhao Yuxing , Chen Qiunan , Xiao Qian 
Published: February 2021

AbstractDiabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans‐4‐[4‐(3‐adamantan‐1‐y1‐ureido)‐cyclohexyloxy]‐benzoic acid (t‐AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t‐AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein‐95 (PSD95) and N‐methyl‐d‐aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline‐rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.
Reintroducing extirpated herbivores could partially reverse the late Quaternary decline of large and grazing species
Authors: Schowanek Simon D. , Davis Matt , Lundgren Erick J. , Middleton Owen , Rowan John , Pedersen Rasmus Ø. , Ramp Daniel , Sandom Christopher J. , Svenning Jens‐Christian 
Published: February 2021

AbstractAimReinstating large, native herbivores is an essential component of ecological restoration efforts, as these taxa can be important drivers of ecological processes. However, many herbivore species have gone globally or regionally extinct during the last 50,000 years, leaving simplified herbivore assemblages and trophically downgraded ecosystems. Here, we discuss to what extent trophic rewilding can undo these changes by reinstating native herbivores.LocationGlobal.Time periodWe report functional trait changes from the Late Pleistocene to the present, and estimated trait changes under future scenarios.Major taxa studiedWild, large (≥ 10 kg), terrestrial, mammalian herbivores.MethodsWe use a functional trait dataset containing all late Quaternary large herbivores ≥ 10 kg to look at changes in the body mass and diet composition of herbivore assemblages, a proxy for species’ ecological effects. First, we assess how these traits have changed from the Late Pleistocene to the present. Next, we quantify how the current body mass and diet composition would change if all extant, wild herbivores were restored to their native ranges (and if no functional replacements were used), exploring scenarios with different baselines.ResultsDefaunation has primarily removed large and grazing herbivores. Reinstating extant herbivores across their native ranges would reverse these changes, especially when reinstating them to their prehistoric distributions. It would partially restore herbivore body mass and diet composition to pre‐anthropogenic conditions. However, in the absence of complementary interventions (e.g., introducing functional replacements), many herbivore assemblages would remain down‐sized and browser dominated, relative to pre‐anthropogenic conditions.Main conclusionsMany terrestrial herbivore assemblages—and hence ecosystems—would remain trophically downgraded, even after bringing back all extant, native herbivores. Therefore, complementary interventions would be required to achieve complete functional restoration. Nevertheless, our findings suggest that reintroducing the remaining native herbivores would diversify the herbivory and disturbances of herbivore assemblages.