bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome‐wide association study reveals the locus responsible for microtia in Valle del Belice sheep breed
Authors: Mastrangelo S. , Sottile G. , Sutera A. M. , Di Gerlando R. , Tolone M. , Moscarelli A. , Sardina M. T. , Portolano B. 
Published: August 2018

SummaryMicrotia is a congenital deformity of the outer ear with phenotypes varying from a small auricle to total absence (anotia). The genetic basis is still poorly understood, and very few studies have been performed in sheep. Valle del Belice sheep is a breed showing microtia. The aim of this study was to identify the potential genomic regions involved in microtia in sheep. A total of 40 individuals, 20 with microtia and 20 normal, were genotyped with the Illumina OvineSNP50 BeadChip. The comparison among the results from a genome‐wide association study, Fisher's exact test and FST analysis revealed a single strong association signal: rs419889303 on chromosome 1, located within intron 3 of the CLRN1 gene. Our study suggests for the first time that this novel candidate gene is responsible for microtia in sheep. Additional analysis based on the sequencing would help confirm our findings and allow for the proposal of a precise genetic basis for microtia in sheep.
Comparison of cellular localisation of the Ca2+‐binding proteins calbindin, calretinin and parvalbumin in the retina of four different Macaca species
Authors: Roski Christian , Langrock Christiane , Körber Nicole , Habermann Gunnar , Buse Eberhard , Reichenbach Andreas , Pannicke Thomas , Francke Mike 
Published: August 2018

AbstractCa2+‐binding proteins are differentially expressed in the nervous system; their functional role often remains unclear. This immunohistochemical study aimed at characterising and comparing the expression pattern of the Ca2+‐binding proteins calbindin (Calb), calretinin (Calr) and parvalbumin (Parv) in the retina of four species of macaque monkeys: Macaca fascicularis (cynomolgus macaque), M. mulatta (rhesus macaque), M. thibetana (Tibetan macaque) and M. fuscata (Japanese macaque). Calb was found in cone photoreceptors and in a subset of bipolar cells. Calr was expressed in a subpopulation of amacrine cells. Parv was present in horizontal and ganglion cells. In addition, Müller cells were stained using antibodies against the specific marker cellular retinaldehyde‐binding protein (CRALBP). Immunostainings were used for calculation of the density of different cell populations. The expression pattern was similar between the examined species and between retinal regions.
Genotype–phenotype correlation and the size of microdeletion or microduplication of 7q11.23 region in patients with Williams‐Beuren syndrome
Authors: Ghaffari Mahsa , Tahmasebi Birgani Maryam , Kariminejad Roxana , Saberi Alihossein 
Published: August 2018

AbstractWilliams‐Beuren syndrome (WBS) is a chromosomal microdeletion syndrome with variable phenotypic features such as supravalvular aortic stenosis (SVAS), facial appearance characteristics, growth retardation, and infantile hypercalcemia. This study aimed to detect the 7q11.23 microdeletion in 10 patients with early clinical diagnosis of WBS using fluorescent in situ hybridization or array comparative genomic hybridization. As an alternative method, multiplex ligation‐dependent probe amplification (MLPA) was used to confirm this microdeletion. Clinical features were also compared with detected genotypes. To reveal the parental origin of deletion, four polymorphic markers (D7S1870, D7S489, D7S613, and D7S2476) were used. The deletion had maternal origin in 80% and paternal origin in 20% of the cases. From 10 patients with early clinical diagnosis of the WBS, 3 patients presented with atypical phenotypes such as infantile hypocalcemia, normal IQ, and normal facial characterization, but the sizes of their deletions seemed to be almost similar to other cases. Regarding such observation, we suggest that the phenotypic variations of WBS are influenced not only by the deletion size and involving genes but also by the breakpoint regions and probably epigenetic effects. However, further research is required to explore the effect of such parameters on phenotypic features.
Patterns of opioid use during initial buprenorphine/naloxone treatment in relation to changes in opioid management laws in Kentucky
Authors: Dhanda Anjali , O'Connor Stephen S. , McGuire Heather , Knox Ellen , Ruth Erika 
Published: August 2018

Background and ObjectivesThere is limited information on the most commonly used opioid reported at the time of presentation for treatment with buprenorphine/naloxone and the extent to which state policy may impact type of opioid use reported.MethodsRetrospective study, total N = of 595 from four different medical locations from January 1, 2009 to July 1, 2016 that provided buprenorphine/naloxone treatment in Louisville, Kentucky. Study aims included identifying the most commonly used opioid at the time of treatment before and after the creation of a state‐wide opioid prescribing surveillance system (ie, the 2012 House Bill 1 [HB1]), and determine the extent to which clinical setting, sex, age, and insurance type impacted type of opioid reported during the intake appointment.ResultsNon‐heroin opioid use decreased in the academic and private practice settings following passage of HB1, while heroin use increased in all three settings. After controlling for clinical setting and demographic characteristics, there was a significant increase in patients who reported using heroin (vs. non‐heroin opioid) (RR = 25.00, p ≤ .001, CI = 12.08–51.73) and a significant increase in patients who reported using opioid agonists (vs. non‐heroin opioid) (RR = 6.56, p ≤ .001, CI = 4.10–10.50) following enactment of HB1.Discussion and ConclusionsAfter the passage of HB1, there was a significant increase in patients reporting heroin use and opioid agonists compared to non‐heroin opioids when presenting for treatment.Significant SignificanceThere has been a notable shift in the opioid epidemic, which is evident in the outpatient treatment settings. (Am J Addict 2018;27:560–566)
Associated factors of widespread pattern of dermatitis among patch test population: 12‐Year retrospective study
Authors: Boonchai Waranya , Maneeprasopchoke Pitchaya , Chaweekulrat Pichanee , Kasemsarn Pranee 
Published: August 2018

AbstractBackground/ObjectiveWidespread dermatitis is often associated with diagnostic and therapeutic challenges. Multiple factors influence this widespread pattern of dermatitis. We aim to study the associated factors in patch‐tested patients who presented with widespread pattern of dermatitis.MethodThis retrospective, case–control study was conducted on patients with dermatitis who were patch tested during January 2005 to December 2016. The demographic data, patient and family histories, diagnoses, and patch test findings were recorded and analyzed.ResultsOf the 3201 included patients, 645 (20.2%) had widespread pattern of dermatitis. Being male, age >60, and history of either atopic dermatitis (AD) or metal allergy were significantly associated with the widespread dermatitis pattern. A multivariate analysis demonstrated that preservatives were the significant offending allergens, especially methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and methylisothiazolinone (MI) alone.ConclusionWidespread pattern of dermatitis is associated with gender, age, underlying atopic dermatitis and a history of metal allergy. Preservatives are the significant offending allergens of widespread dermatitis, especially MCI/MI, and MI alone. A thorough history taking and patch testing, including preservatives, are necessary to determine the cause of widespread pattern of dermatitis.
Exhaled breath condensate volatilome allows sensitive diagnosis of persistent asthma
Authors: Cavaleiro Rufo João , Paciência Inês , Mendes Francisca Castro , Farraia Mariana , Rodolfo Ana , Silva Diana , de Oliveira Fernandes Eduardo , Delgado Luís , Moreira André 
Published: August 2018

AbstractBackgroundThe diagnosis and phenotyping of paediatric asthma are particularly complex due to the lack of currently available sensitive diagnostic tools. This often results in uncertainties associated with inhaled steroid therapy prescription. Therefore, this study aimed to investigate whether volatile organic compounds measured in exhaled breath condensate can be used as biomarkers for asthma diagnosis in the paediatric population.MethodsA total of 64 participants, aged 6‐18 years, were recruited on a random basis during visits to an outpatient allergy clinic and to a juvenile football team training session. Lung function, airway reversibility and skin prick tests were performed. Exhaled breath condensate samples were collected, and breathprints were assessed using an electronic nose. Information on medical diagnosis of asthma, rhinitis and atopic dermatitis was retrieved for each participant. A hierarchical cluster model based on the volatilome profiles was then created.ResultsA two‐cluster exhaled volatile organic compound‐based hierarchical model was able to significantly discriminate individuals with asthma from those without the disease (AUC = 0.81 [0.69‐0.93], P < 0.001). Individuals who had persistent asthma and were prescribed corticosteroid therapy by the physician were also significantly distinguished in the model (AUC = 0.81 [0.70‐0.92], P < 0.001). Despite being less specific, the method showed higher overall accuracy, sensitivity and AUC values when compared to spirometry with bronchodilation.ConclusionsAnalysis of the exhaled breath condensate volatilome allowed the distinction of paediatric individuals with a medical diagnosis of asthma, identifying those in need of corticosteroid therapy.
Artemisia pollen allergy in China: Component‐resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization
Authors: Gao Zhongshan , Fu Wan‐Yi , Sun Yuemei , Gao Biyuan , Wang Hui‐Ying , Liu Meiling , Luo Fang‐Mei , Zhou Xiang , Jin Jing , Zhao Lan , Wu Shandong , Liu Yi , Wu Lingying , Wang Xuefeng , Tang Ning‐Bo , Guo Bao‐Hua , Feng Yan , Zhou Jian Ying , Gadermaier Gabriele , Ferreira Fatima , Versteeg Serge A. , van Ree Ronald 
Published: August 2018

AbstractBackgroundArtemisia pollen allergy is a major cause of asthma in Northern China. Possible associations between IgE responses to Artemisia allergen components and clinical phenotypes have not yet been evaluated. This study was to establish sensitization patterns of four Artemisia allergens and possible associations with demographic characteristics and clinical phenotypes in three areas of China.MethodsTwo hundred and forty patients allergic to Artemisia pollen were examined, 178 from Shanxi and 30 from Shandong Provinces in Northern China, and 32 from Yunnan Province in Southwestern China. Allergic asthma, rhinitis, conjunctivitis, and eczema symptoms were diagnosed. All patients’ sera were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7.ResultsThe frequency of sensitization and the IgE levels of the four components in Artemisia allergic patients from Southwestern China were significantly lower than in those from the North. Art v 1 and Art an 7 were the most frequently recognized allergens (84% and 87%, respectively), followed by Art v 3 (66%) and Art ar 2 (48%). Patients from Northern China were more likely to have allergic asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of allergic asthma, in which co‐sensitization to three major allergens Art v 1, Art v 3, and Art an 7 is prominent.ConclusionsComponent‐resolved diagnosis of Chinese Artemisia pollen‐allergic patients helps assess the potential risk of mugwort‐associated allergic asthma.
FARMERS’ WILLINGNESS TO INVEST IN NEW COOPERATIVE INSTRUMENTS: A CHOICE EXPERIMENT
Authors: ALHO Eeva 
Published: August 2018

ABSTRACTGlobalization of agricultural markets put pressures on producer cooperatives to invest in expansion and growth to safeguard their competitiveness. Availability of capital is limited if farmers do not have incentives to increase their capital contribution. Cooperative literature recognizes the residual rights, transferability, and the appreciation potential of the investment as the potential solutions for the problems that may impede cooperative investments. The objective of this study is to understand farmer preferences regarding investment attributes and the potential for attracting investment capital from members and non‐members. We employ a choice experiment method to test new cooperative investment instruments. The data consist of a questionnaire conducted with 406 Finnish dairy farmers. Random parameter latent class logit model is used in the estimation of the data. The results indicate that most of the respondents regard the new investment instruments positively. However, farmers prefer restricting ownership rights to members. Incentives for members to participate in financing cooperative growth could be designed with capital‐based residual rights, mechanisms for transferability and for the appreciation of firm value. Estimation that considered choice difficulty improved model fit, which highlights the need to address respondent burden also in future studies of hypothetical investments in order to produce unbiased estimates.
Hypochromatic large urothelial cells in urine cytology are indicative of high grade urothelial carcinoma
Authors: Pierconti Francesco , Martini Maurizio , Straccia Patrizia , Fiorentino Vincenzo , Musarra Teresa , Larocca Luigi Maria , Lopez‐Beltran Antonio 
Published: August 2018

In this study, we have examined 67 cytology specimens from patients from 2014 to 2016. The ratio man to women was 4:1 with a median age of 75 years (range: 55–87 years). Thin‐Prep processed urinary cytology specimens demonstrated large urothelial cells, with cytologic features of malignancy, thus including hypochromatic nuclei with occasional peripherally accentuated chromatin rim. The cytological diagnosis of High Grade Urothelial Carcinoma (HGUC) was made in 55 patients while 12 specimens were classified as Atypical Urothelial Cells (AUC). This cases represent the 15% of the HGUC and the 4% of the AUC cases diagnosed in our department between 2016 to 2018. Of note, is the fact that in AUC cases, hypochromatic irregular urothelial cells were the only type of cells with malignant features observed in the specimen, and therefore, according to the Paris System criteria, the absence of nuclear hyperchromasia precludes a diagnosis of suspicious high grade urothelial carcinoma (SHGUC) or High Grade Urothelial Carcinoma (HGUC). Subsequent biopsy diagnosis of high grade urothelial carcinoma confirmed the cytological diagnosis of HGUC in 55 patients but also in all 12 patients with a AUC cytologic diagnosis. Our study series support the hypothesis that malignant urothelial cells with hypochromatic nuclei seen in urine cytologic specimens can be diagnostic for HGUC based on their very large nuclei, high nuclear cytoplasmatic ratio (N/C) >0.7, irregular nuclear outlines and coarse (frequently peripheral) chromatin in the absence of hyperchromasia.
Lisinopril‐associated bullous pemphigoid in an elderly woman: a case report of a rare adverse drug reaction
Authors: Ballout Rami A. , Musharrafieh Umayya , Khattar Joe 
Published: August 2018

An 87‐year‐old woman with a long‐standing history of hypertension, hypothyroidism and diabetes presented to us with scaly and pruritic vesicles of an erythematous base and crusted surface of 2‐month duration. They first appeared on her abdomen and gradually spread to her lower back, thighs, before spreading to her upper and lower limbs. Her lesions were non‐painful, aggravated by sun exposure only, and sparing mucous membranes. Nikolsky sign was positive with no discernible fluid‐filled bullae. History was remarkable only for a doubling of her Lisinopril dosage 2 months prior to the appearance of her lesions, with no other potential environmental and/or drug triggers recognizable on history taking. In light of the appearance of her lesions after her Lisinopril dose escalation, in the absence of any other discernible triggers, an adverse drug reaction (ADR) was entertained, yielding a corresponding Naranjo ADR probability score of 7. Particularly, drug‐induced pemphigus foliaceus was initially suspected given her clinical presentation and the morphology and distribution of her lesions. However, her skin biopsy altered our diagnosis to drug‐induced bullous pemphigoid (BP) instead, making this the second case reported to date on Lisinopril‐induced BP, and the first to report a dose–response variant of this adverse reaction.
Safety, tolerability, pharmacokinetics and pharmacokinetic‐pharmacodynamic modelling of the novel H4 receptor inhibitor SENS‐111 using a modified caloric test in healthy subjects
Authors: Venail Frédéric , Attali Pierre , Wersinger Eric , Gomeni Roberto , Poli Sonia , Schmerber Sebastien 
Published: August 2018

AimA Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H4 receptor antagonist SENS‐111, an oral small molecule.MethodsOne hundred healthy subjects were randomized in a placebo‐controlled, double‐blind study evaluating single‐ascending doses (SAD; 100–500 mg) and multiple‐ascending doses (MAD; 50–150 mg day−1, 4 days; 200–250 mg day−1, 7 days). Effects of SENS‐111 on nystagmus and vertigo induced by modified caloric tests were measured in the MAD studies. Population PK and PK/PD models were developed using a nonlinear mixed‐effects approach.ResultsSENS‐111 was well tolerated with mild to moderate events. No sedation was reported. A maximal tolerated dose was not reached. Dose‐proportional increases in concentrations were seen up to 200 mg and more than dose‐proportional thereafter, with mean half‐life between 24 and 56 h. The caloric test induced mild but measurable vertigo and nystagmus with large intra/inter‐individual variation for all parameters. SENS‐111 did not significantly impact nystagmus but significantly improved latency of vertigo appearance/disappearance, duration and European Evaluation of Vertigo questionnaire parameters vs. baseline. A two‐compartment model with first‐order absorption, distribution and elimination best fit the data. PK/PD indirect modelling applied to vertigo duration and latency of appearance indicated maximum activity between 100 and 500 ng ml−1 plasma concentrations, corresponding to 100 and 200 mg day−1, which are appropriate for clinical efficacy evaluations in vestibular diseases.ConclusionsSENS‐111 is a well‐tolerated first‐in‐class H4 receptor antagonist with acceptable PK for oral daily dosing. PK/PD modelling determined plasma concentrations and doses for efficacy studies in patients with vertigo symptoms.
Yes‐associated protein mediates angiotensin II‐induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling
Authors: Lin Maohuan , Yuan Woliang , Su Zizhuo , Lin Caina , Huang Tucheng , Chen Yangxin , Wang Jingfeng 
Published: August 2018

AbstractObjectivesYes‐associated protein (YAP) has been reported to regulate cell proliferation and differentiation. We aimed to characterize the role of YAP in angiotensin II (Ang II)‐induced hypertensive vascular remodelling (HVR) and vascular smooth muscle cells (VSMCs) phenotypic modulation and to explore the underlying mechanisms.Materials and methodsAn HVR rat model was established by continuous Ang II infusion for 2 weeks. Western blotting, qRT‐PCR, and confocal microscopy were conducted to assess YAP expression. YAP‐shRNA interfering plasmid and adenovirus were constructed to knock down YAP. We used cell proliferation and migration assays, accompanied by pathway inhibitors, to evaluate the biological function and underlying mechanisms.ResultsAng II upregulated YAP expression in the media of carotid artery; however, in vivo YAP silencing significantly mitigated HVR, independent of the blood pressure level. Ang II upregulated YAP expression and promoted YAP nuclear accumulation in a dose‐ and time‐dependent manner in rat VSMCs. YAP knockdown ameliorated Ang II‐induced VSMCs phenotypic modulation. The regulation of YAP by Ang II could be blocked by pretreatment with angiotensin receptor type 1 antagonist losartan or F‐actin depolymerizing agent latrunculin B but not the AT2R antagonist PD 123319. Disrupting the YAP‐TEA domain (TEAD) interaction with verteporfin inhibited Ang II‐induced VSMCs phenotypic modulation.ConclusionsYes‐associated protein mediated angiotensin II‐induced VSMCs phenotypic modulation and vascular remodelling. YAP is a potential therapeutic target for HVR beyond blood pressure control.
Immunohistochemical expression of melanocytic and myofibroblastic markers and their molecular correlation in atypical fibroxanthomas and pleomorphic dermal sarcomas
Authors: Helbig Doris , Mauch Cornelia , Buettner Reinhard , Quaas Alexander 
Published: August 2018

BackgroundAtypical fibroxanthomas (AFXs) and pleomorphic dermal sarcomas (PDSs) are UV‐induced pleomorphic skin tumors with a non‐specific immunoprofile. For that reason, exclusion of other dedifferentiated tumor entities by immunohistochemistry is still mandatory to avoid misdiagnosis.MethodsWe determined the expression frequency of several melanocytic and myofibroblastic markers investigating 50 AFXs and PDSs.. Next‐generation‐sequencing (NGS) was performed in microphthalmia‐associated transcription factor (MiTF)‐expressing cases.ResultsWe identified one MiTF‐expressing AFX and PDS, and two PDSs harboring single S100‐positive dendritic cells whereas Melan A, HMB45, and SOX10 were negative. Calponin was moderately expressed by tumor giant cells in one PDS whereas h‐caldesmon, desmin, and myogenin were not expressed in any of the AFXs or PDSs. The MiTF‐positive AFX presented CDKN2A, OXA1L, and PDGFRA mutations whereas the PDS harbored a typical TP53 mutation. Both patients have not shown any tumor progression over the last 16 and 30 months.ConclusionRarely, AFX and PDS express the melanocytic marker MiTF and/or the myofibroblastic marker calponin. In doubtful cases, using a panel of immunohistochemical markers helps to avoid misdiagnosis.