bluuebunny/crossref_metadata_2025 huggingface dataset:
Burden of Schizophrenia or Psychosis-Related Symptoms in Adults Undergoing Substance Abuse Evaluation
Authors: Trudeau Kimberlee J. , Burtner Joanna , Villapiano Albert J. , Jones Megan , Butler Stephen F. , Joshi Kruti
Published: June 2018

This study evaluated the biopsychosocial characteristics of adults undergoing substance abuse evaluation with potential schizophrenia/psychotic disorder, or possible schizophrenia/psychosis-like symptoms, compared with those with no schizophrenia/psychosis-like symptoms. A cross-sectional, observational study examined 170,201 adults, aged 18 to 30, who completed the Addiction Severity Index–Multimedia Version (ASI-MV). Approximately 10% were classified as having possible schizophrenia/psychosis-like symptoms or potential schizophrenia/psychotic disorder. These patients were more likely to exhibit moderate to extreme severity on employment, medical, legal, substance use, social, and psychiatric status than nonsymptomatic patients. The potential schizophrenia or psychotic disorder cohort was also more likely to have ever experienced physical abuse (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 4.12–4.48) and/or sexual abuse (OR = 4.32, 95% CI = 4.15–4.51) versus the no schizophrenia/psychosis-like symptoms cohort. Findings support a recommendation for routine screening for mental health issues, particularly schizophrenia/psychosis-like symptoms, for adults entering substance use disorder treatment settings. This may increase the likelihood of appropriate and earlier intervention.
Family and Personality Predictors of Clinical Depression and Anxiety in Emerging Adults
Authors: Mitkovic Voncina Marija , Kosutic Zeljka , Pesic Danilo , Todorovic Dejan , Peulic Aleksandar , Lazarevic Milica , Rakovic Dobroslavic Ivana , Djuric Mina , Bradic Zagorka , Pejovic Milovancevic Milica , Gotlib Dorothy , Lecic Tosevski Dusica
Published: June 2018

There is an ongoing debate on the relationship between depression and anxiety, but data on similarities and differences in their predictor profiles are scarce. The aim of our study was to compare family and personality predictors of these disorders among 220 “emerging adults.” As such, two clinical groups with noncomorbid depressive and anxiety disorders, and one healthy control group were assessed by sociodemographic questionnaires, Structured Clinical Interview for DSM-IV Disorders and NEO Personality Inventory, Revised. We found significant overlap in family and personality risk profiles, with increasing effect size for predictors common to anxiety and depression when the categories “no disorder–anxiety disorder–depressive disorder” were considered as existing along a continuum. Among the contributing factors we assessed, family psychiatric history, family structure and conflicts with parents were more significant than personality traits. Our study indicates that emerging adults may be more vulnerable to depression than anxiety in the presence of family and personality risk factors.
Alterations in Mitochondrial Function in Blood Cells Obtained From Patients With Sepsis Presenting to an Emergency Department
Authors: Jang David H. , Orloski Clinton J. , Owiredu Shawn , Shofer Frances S. , Greenwood John C. , Eckmann David M.
Published: June 2018

Objective:

Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis.

Design:

Prospective observational study.

Setting:

Single site tertiary academic emergency department.

Subjects:

We enrolled a total of 48 subjects in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls.

Interventions:

Peripheral blood mononuclear cells were measured with high-resolution respirometry (OROBOROS O2K).

Measurements and Main Results:

The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 29 years old, respectively. In the Sepsis group, the median 1st 24-h SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared with 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared with the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared with the other group. There were no age-related differences in respiration between the Older and Younger control group.

Conclusions:

Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.
The comparative genomics of Bifidobacterium callitrichos reflects dietary carbohydrate utilization within the common marmoset gut
Authors: Albert Korin , Rani Asha , Sela David A.
Published: June 2018

Bifidobacterium is a diverse genus of anaerobic, saccharolytic bacteria that colonize many animals, notably humans and other mammals. The presence of these bacteria in the gastrointestinal tract represents a potential coevolution between the gut microbiome and its mammalian host mediated by diet. To study the relationship between bifidobacterial gut symbionts and host nutrition, we analyzed the genome of two bifidobacteria strains isolated from the feces of a common marmoset (Callithrix jacchus), a primate species studied for its ability to subsist on host-indigestible carbohydrates. Whole genome sequencing identified these isolates as unique strains of Bifidobacterium callitrichos. All three strains, including these isolates and the previously described type strain, contain genes that may enable utilization of marmoset dietary substrates. These include genes predicted to contribute to galactose, arabinose, and trehalose metabolic pathways. In addition, significant genomic differences between strains suggest that bifidobacteria possess distinct roles in carbohydrate metabolism within the same host. Thus, bifidobacteria utilize dietary components specific to their host, both humans and non-human primates alike. Comparative genomics suggests conservation of possible coevolutionary relationships within the primate clade.
Spt6 is required for the fidelity of promoter selection
Authors: Doris Stephen M. , Chuang James , Viktorovskaya Olga , Murawska Magdalena , Spatt Dan , Stirling Churchman L. , Winston Fred
Published: June 2018

Spt6 is a conserved factor that controls transcription and chromatin structure across the genome. Although Spt6 is viewed as an elongation factor,spt6mutations inSaccharomyces cerevisiaeallow elevated levels of transcripts from within coding regions, suggesting that Spt6 also controls initiation. To address the requirements for Spt6 in transcription and chromatin structure, we have combined four genome-wide approaches. Our results demonstrate that Spt6 represses transcription initiation at thousands of intragenic promoters. We characterize these intragenic promoters, and find sequence features conserved with genic promoters. Finally, we show that Spt6 also regulates transcription initiation at most genic promoters and propose a model of initiation-site competition to account for this. Together, our results demonstrate that Spt6 controls the fidelity of transcription initiation throughout the genome and reveal the magnitude of the potential for expressing alternative genetic information via intragenic promoters.
Non-invasive prenatal testing as a valuable source of population specific allelic frequencies
Authors: Budis J , Gazdarica J , Radvanszky J , Harsanyova M , Gazdaricova I , Strieskova L , Frno R , Duris F , Minarik G , Sekelska M , Szemes T
Published: June 2018

Low-coverage massively parallel genome sequencing for non-invasive prenatal testing (NIPT) of common aneuploidies is one of the most rapidly adopted and relatively low-cost DNA tests. Since aggregation of reads from a large number of samples allows overcoming the problems of extremely low coverage of individual samples, we describe the possible re-use of the data generated during NIPT testing for genome scale population specific frequency determination of small DNA variants, requiring no additional costs except of those for the NIPT test itself. We applied our method to a data set comprising of 1,548 original NIPT test results and evaluated the findings on different levels, from in silico population frequency comparisons up to wet lab validation analyses using a gold-standard method. The revealed high reliability of variant calling and allelic frequency determinations suggest that these NIPT data could serve as valuable alternatives to large scale population studies even for smaller countries around the world.
An adaptive fully discontinuous Galerkin level set method for incompressible multiphase flows
Authors: Karakus Ali , Warburton Tim , Aksel Mehmet Haluk , Sert Cuneyt
Published: June 2018

Purpose

This study aims to focus on the development of a high-order discontinuous Galerkin method for the solution of unsteady, incompressible, multiphase flows with level set interface formulation.

Design/methodology/approach

Nodal discontinuous Galerkin discretization is used for incompressible Navier–Stokes, level set advection and reinitialization equations on adaptive unstructured elements. Implicit systems arising from the semi-explicit time discretization of the flow equations are solved with a p-multigrid preconditioned conjugate gradient method, which minimizes the memory requirements and increases overall run-time performance. Computations are localized mostly near the interface location to reduce computational cost without sacrificing the accuracy.

Findings

The proposed method allows to capture interface topology accurately in simulating wide range of flow regimes with high density/viscosity ratios and offers good mass conservation even in relatively coarse grids, while keeping the simplicity of the level set interface modeling. Efficiency, local high-order accuracy and mass conservation of the method are confirmed through distinct numerical test cases of sloshing, dam break and Rayleigh–Taylor instability.

Originality/value

A fully discontinuous Galerkin, high-order, adaptive method on unstructured grids is introduced where flow and interface equations are solved in discontinuous space.
An empirical assessment of current accounts sustainability for major South Asian economies
Authors: Shastri Shruti , Giri A.K. , Mohapatra Geetilaxmi
Published: June 2018

Purpose

The purpose of this paper is to assess the sustainability of current accounts for five major South Asian economies, namely, India, Pakistan, Bangladesh, Sri Lanka and Nepal, for the period 1985–2016.

Design/methodology/approach

The study employs the intertemporal solvency model of Hakkio and Rush (1991) and Husted (1992). Autoregressive Distributed Lag bounds test, Gregory and Hansen’s test and Carrion-i-Silvestre and Sanso’s test are used to assess the cointegration between current account inflows and outflows. The coefficients of long-run relationship are obtained using dynamic ordinary least squares. Besides the econometric investigation, the study also examines some other indicators such as the composition of current account, size of external debt, etc., to shed further light on the sustainability of current accounts.

Findings

The study finds support for the long-run relationship between the current account outflows and inflows for all the countries. The estimates of slope coefficient indicate strong sustainability in case of India, Bangladesh and Nepal, whereas weak sustainability holds for Sri Lanka and Pakistan underscoring the need for policy interventions. In a comparative perspective, the current accounts in India, Nepal and Bangladesh conform more to a sustainable behavior in terms of the size of deficits, external debt stock and compliance to the intertemporal budget constraint.

Originality/value

The study employs econometric techniques allowing for structural breaks in the assessment of current account sustainability. Besides using the intertemporal model, the study also examines factors such as composition of current accounts, size of external debts, etc., to evaluate sustainability.
Escape the “Hockey stick” trap: five potent strategic moves that spur growth
Authors: Leavy Brian
Published: June 2018

Purpose

This interview with the authors of Strategy – Beyond the Hockey Stick offers their insights into a major problem which has bedevilled the strategy process in too many companies over the years - the combination of bold but delusional “hockey-stick” forecasts and timid strategic moves – a coupling that severely limits the impact of any strategy.

Design/methodology/approach

The McKinsey authors examined publicly available information on the world’s 2,393 largest companies, and plotted their average annual economic profit

Findings

They found that the curve is extremely steep at the both ends: those in the top quintile average some 30 times as much economic profit as those in the middle three quintiles.

Practical implications

One of the biggest pitfalls in the strategy process is this very human propensity for bold forecasts and timid actions. Strategy requires confronting uncertainly head-on by embracing the notion of probability by calibrating the odds of a strategy succeeding, building in explicit trigger points to re-examine decisions as we learn more. 10;

Originality/value

What has been largely missing from the literature is a study of the average-to-top transition based on an extensive data set, one that encompasses a greater range of performance profiles and average-to-top transition trajectories. This is the knowledge gap that Strategy Beyond the Hockey Stick: People, Probabilities, and Big Moves to Beat the Odds fills.
The GRK2 Promoter Is Regulated by Early‐Growth Response Transcription Factor EGR‐1
Authors: Klenke Stefanie , Engler Andrea , Ecker Daniel , Ochsenfarth Crista , Danowski Nina , Peters Jürgen , Siffert Winfried , Frey Ulrich H.
Published: June 2018

The G‐protein‐coupled receptor kinase 2 (GRK2) plays a major role in cardiovascular diseases, and its expression is increased in heart failure. However, only little is known about factors being involved in up‐regulation of GRK2 expression through transcriptional regulation of its promoter. Since the transcription factor early‐growth response 1 (EGR‐1) is also up‐regulated in patients with heart failure, we tested the hypothesis that EGR‐1 regulates GRK2 transcription. Stimulation of immortalized rat cardiomyocytes (H9c2) with phorbol 12‐myristate 13‐acetate (PMA) resulted in up‐regulation of Egr‐1 and subsequently of Grk2 mRNA expression, with maximum Grk2 expression (p = 0.008) 5 hr after PMA stimulation and being abolished by actinomycin D, indicating a transcriptional mechanism. To identify naturally occurring variants affecting promoter transcriptional activity, we identified a novel G(‐43)A polymorphism (rs182084609), which surrounded a putative EGR‐1‐binding site. While the minor A allele frequency was rare (0.02), this variant was used to explore regulation by EGR‐1 and promoter construct with altered alleles at nt‐43 were subjected of reporter assays in human embryonic kidney cells (Hek293). Here, EGR‐1 over‐expression resulted in a more than twofold increase in GRK2 promoter activity but only in the presence of the G‐allele (p = 0.04). In electrophoretic mobility shift assays, EGR‐1 over‐expression resulted in a specific binding of transcription factors only to the G oligonucleotide. Finally, EGR‐1 over‐expression resulted in increased GRK2 mRNA expression (p = 0.03). We identified EGR‐1 as a regulator of GRK2 transcription. Suppression of GRK2 expression by inhibition of EGR‐1 binding to GRK2 might be a promising approach to mitigate adrenergic desensitization.
Case of immune‐mediated necrotizing myopathy associated with anti‐signal recognition particle antibodies: Dramatic improvement after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy for intravascular large B‐cell lymphoma
Authors: Komiya Hiroyasu , Hagihara Maki , Tanaka Kenichi , Tada Mikiko , Joki Hideto , Koyano Shigeru , Doi Hiroshi , Nishino Ichizo , Takeuchi Hideyuki , Tanaka Fumiaki
Published: June 2018

Immune‐mediated necrotizing myopathy associated with anti‐signal recognition particle antibodies (anti‐SRP myopathy) is representative of several subtypes of necrotizing immune‐mediated myopathy, and is characterized by rapidly progressive proximal muscle weakness, dysphagia and poor responsiveness to conventional immunosuppressive therapies. We report a 71‐year‐old man who developed anti‐SRP myopathy followed by malignant lymphoma, and whose condition dramatically improved with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy. He showed progressive proximal muscle weakness with severe dysphagia, and was diagnosed with anti‐SRP myopathy by antibody tests and pathological examination. He was treated with conventional immunosuppressive therapies, specifically corticosteroids, intravenous immunoglobulin and tacrolimus; however, none of these therapies were effective. Two months after starting tacrolimus, the patient developed intravascular large B‐cell lymphoma, which was suspected to be an iatrogenic immunodeficiency‐associated lymphoproliferative disorder. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy resulted in not only complete remission of lymphoma, but also dramatic improvement of anti‐SRP myopathy. The present case suggests that rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy is a potential treatment for anti‐SRP myopathy.
Healing criteria: How should an episode of benign paroxistic positional vertigo of posterior semicircular canal′s resolution be defined? Prospective observational study
Authors: Guerra‐Jiménez G. , Domènech‐Vadillo E. , Álvarez‐Morujo de Sande M.G. , González‐Aguado R. , Galera‐Ruiz H. , Morales Angulo C. , Martín‐Mateos A.J. , Figuerola‐Massana E. , Ramos‐Macías Á. , Domínguez‐Durán E.
Published: June 2018

Objectives

To compare the outcome of the Epley maneuver (EM) in benign paroxysmal positional vertigo of the posterior canal (CSP‐BPPV) depending on the definition used for recovery.

Design

Multicenter observational prospective study.

Setting

Otoneurology Units of 5 tertiary reference hospitals.

Participants

All patients presenting with unilateral CSP‐BPPV assisted for 1‐year period.

Exclusion criteria

Spontaneous nystagmus, positive McClure‐Pagnini maneuver, positive bilateral Dix‐Hallpike maneuver (DHM), positive DHM for vertigo but negative for nystagmus and atypical nystagmus.

Main outcome measures

Response to EM was measured after 7 days in 3 different outcomes: disappearance of nystagmus during the DHM in the follow‐up visit, disappearance of vertigo during the DHM and general status (GS) during daily life activities.

Results

264 patients were recruited (68 male/166 female, mean age 62 years). After the EM, nystagmus disappeared in 67% of them, vertigo in 54% and 36% were asymptomatic in their daily life. These outcomes were strongly correlated, but they were not concordant in a clinically significant group of cases; only the 26% of patients met all of them. The healing process follows the next sequence: negativization of positional nystagmus, then disappearance of positional vertigo and, finally, the improvement of GS during daily life activities.

Conclusion

Nowadays, healing criteria for the resolution of an PSC‐BPPV episode have not been specifically defined yet. Provided that other otoneurological disorders have been ruled out, the next resolution criterion is proposed: absence of nystagmus and specifically during control DHM and disappearance of symptoms during daily life activities.
Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress
Authors: Weber Matthew A. , Graack Eric T. , Scholl Jamie L. , Renner Kenneth J. , Forster Gina L. , Watt Michael J.
Published: June 2018

Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague‐Dawley rats exposed to social defeat in mid‐adolescence (P35‐39) show impaired working memory in adulthood (P56‐70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter‐mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor‐mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction. Control and previously defeated rats did not differ in either DOPA accumulation following amino acid decarboxylase inhibition (NSD‐1015 100 mg/kg ip.) or total/phosphorylated tyrosine hydroxylase protein expression, suggesting dopamine synthesis in the adult mPFC is not altered by adolescent defeat. However, exposure to adolescent defeat caused greater decreases in extracellular dopamine release (measured using in vivo chronoamperometry) in the adult mPFC upon local infusion of the D2 receptor agonist quinpirole (3 nM), implying greater D2 autoreceptor function. Equally enhanced D2 autoreceptor‐mediated inhibition of dopamine release is seen in the adolescent (P40 or P49) mPFC, which declines in control rats by adulthood. However, this developmental decrease in autoreceptor function is absent following adolescent defeat, suggesting retention of an adolescent‐like phenotype into adulthood. Current and previous findings indicate adolescent defeat decreases extracellular dopamine availability in the adult mPFC via both enhanced inhibition of dopamine release and increased dopamine clearance, which may be viable targets for improving treatment of cognitive deficits seen in neuropsychiatric disorders promoted by adolescent stress.
Activity‐dependent vs. neurotrophic modulation of acetylcholine receptor expression: Evidence from rat soleus and extensor digitorum longus muscles confirms the exclusive role of activity
Authors: Buffelli Mario , Tognana Enrico , Cangiano Alberto , Busetto Giuseppe
Published: June 2018

Evoked electrical muscle activity suppresses the transcription of mRNAs for acetylcholine receptors in extrajunctional myonuclei. Muscle denervation or disuse releases such inhibition and extrajunctional receptors appear. However, in soleus muscles paralysed with nerve‐applied tetrodotoxin, a restricted perijunctional region has been described where myonuclei remain inhibited, a finding attributed to nerve‐derived trophic factor(s). Here, we reinvestigate extrajunctional acetylcholine receptor expression in soleus and extensor digitorum longus muscles up to 90 days after denervation or up to 20 days of disuse, to clarify the role of trophic factors, if any. The perijunctional region of soleus muscles strongly expressed acetylcholine receptors during the first 2–3 weeks of denervation. After 2–3 months, this expression had disappeared. No perijunctional expression was seen after paralysis by tetrodotoxin or botulinum toxin A. In contrast, the extensor digitorum longus never displayed suppressed perijunctional acetylcholine receptor expression after any treatment, suggesting that it is an intrinsic property of soleus muscles. Soleus denervation only transiently removed the suppression, and its presence in long‐term denervated soleus muscles contradicts any contribution from nerve‐derived trophic factor(s). In conclusion, our results confirm that evoked electrical activity is the physiological factor controlling the expression of acetylcholine receptors in the entire extrajunctional membrane of skeletal muscles.
Topical silver and gold nanoparticles complexed with Cornus mas suppress inflammation in human psoriasis plaques by inhibiting NF‐κB activity
Authors: Crisan Diana , Scharffetter‐Kochanek Karin , Crisan Maria , Schatz Susanne , Hainzl Adelheid , Olenic Liliana , Filip Adriana , Schneider Lars A. , Sindrilaru Anca
Published: June 2018

New biomaterials based on nanoparticles (NPs) carrying polyphenols‐rich extracts (Cornus mas) recently showed promising anti‐inflammatory activity in psoriasis. We aimed to understand how topically delivered silver and gold nanoparticles complexed with Cornus mas (Ag‐NPs‐CM, Au‐NPs‐CM) modulate inflammation in psoriasis at cellular and molecular level. The impact on psoriatic inflammation was assessed in vitro on pro‐inflammatory macrophages, by clinical score, high‐frequency ultrasonography and immunohistology of psoriasis plaques treated with Ag‐NPs‐CM, Au‐NPs‐CM or control. Incubation of pro‐inflammatory macrophages with nanoparticles significantly decreased the release of NO, IL‐12 and TNF‐α. Immunofluorescence confirmed that nanoparticles significantly reduced CD68‐positive macrophages and their IL‐12 and TNF‐α production in human psoriasis plaques. NPs‐CM appear to repress NF‐κB activation in macrophages, inhibiting the production of pro‐inflammatory factors with causal role in psoriasis. Ag and Au NPs‐CM represent a novel nanoparticle‐based “green” technology which may provide an efficient tool for modern psoriasis therapy, circumventing immunosuppression‐related side effects of biologicals.
DNA methylation profiles of immune response‐related genes in apical periodontitis
Authors: Wichnieski C. , Maheshwari K. , Souza L. C. , Nieves F. , Tartari T. , Garlet G. P. , Carneiro E. , Letra A. , Silva R. M.
Published: June 2018

Aim

To investigate the DNA methylation profiles of immune response‐related genes in apical periodontitis (AP) lesions.

Methodology

The methylation profiles on the cytosine‐phosphate‐guanine (CpG) regions of 22 gene promoters involved in inflammation and autoimmunity were assessed in 60 human AP lesions and 24 healthy periodontal ligaments (controls) using a pathway‐specific real‐time polymerase chain reaction array (EpiTect® Methyl Signature PCR Array Human Inflammatory Response). Differentially methylated genes were subsequently assessed for their mRNA expression. Data analyses (One‐way anova, Tukey's multiple comparisons tests and Mann–Whitney tests) were performed using GraphPad Prism 6 software. P values ≤ 0.05 were considered statistically significant.

Results

Significant DNA hypermethylation was observed for CXCL3 and FADD gene promoters in AP lesions when compared to control tissues (P < 0.001) and among other genes (P < 0.05). In contrast, IL12B and IL4R were associated with significant hypomethylation in comparison to other genes (P < 0.05). IL12B, IL4R, CXCL3 and FADD had differential mRNA expression in AP lesions and controls (P < 0.001).

Conclusions

Differential methylation profiles of immune response‐related genes, such as FADD, CXCL3, IL12B and IL4R, may have an influence on individual AP susceptibility and patient treatment outcomes, through their potential contributions to altered expression of disease‐relevant genes. Methylation and/or genetic variations in additional genes may also contribute to the dynamics of AP development and should be considered in future studies.
Safety and efficacy of topical cantharidin for the treatment of pediatric molluscum contagiosum: a prospective, randomized, double‐blind, placebo‐controlled pilot trial
Authors: Guzman Anthony K. , Schairer David O. , Garelik Jessica L. , Cohen Steven R.
Published: June 2018

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6‐week, randomized, double‐blind, placebo‐controlled trial with subsequent open‐label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety‐four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post‐treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P = 0.0065). The mean (SD) lesion count change from baseline was −5.1 (12.2) in the placebo only arm; the mean change (SD) was −17.4 (12.8) in the cantharidin only arm (P = 0.0033) and −15.9 (11.6) in the cantharidin with occlusion arm (P = 0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well‐tolerated and associated with the resolution of MC.
EOCENE AND OLIGO‐MIOCENE SOURCE ROCKS IN THE RIONI AND KURA BASINS OF GEORGIA: DEPOSITIONAL ENVIRONMENT AND PETROLEUM POTENTIAL
Authors: Pupp M. , Bechtel A. , Ćorić S. , Gratzer R. , Rustamov J. , Sachsenhofer R. F.
Published: June 2018

For over a century, oil has been produced in Georgia from oilfields located in the foreland basins between the Greater and Lesser Caucasus foldbelts. To date, little information on the associated source rocks has been available. In this context, this paper presents a study of 380 samples of Eocene (Kuma Formation) and Oligocene to Lower Miocene (Maikop Group) source rocks from three outcrop sections in the Rioni and Kura Basins. The Kuma Formation in the Rioni Basin is composed of fully‐marine marls and is about 40 m thick. At the Martivili and Khobi sections, the formation is thermally immature and has an average TOC of 3.2 wt%. The hydrogen indices (HI) of 300–600 mg HC/g TOC indicate that the organic matter is oil‐prone Type II kerogen. The oil generation potential is between 1.0 and 2.4 t HC/m2, and the Kuma Formation is therefore interpreted as a prolific source rock.

The Maikop Group in the Rioni Basin was studied at the Martvili section, where it is thermally immature. The Oligocene succession is divided by calcareous shales deposited during the Solenovian Event (at the onset of nannoplankton zone NP23) into Pshekhian and Solenovian‐to‐Kalmykian intervals. The Pshekhian interval (NP21‐22) is over 60 m thick and comprises a marly lower part and a shale‐rich upper part, and contains high quantities (average 2.7 wt% TOC) of Type II‐III kerogen (average HI: 278 mg HC/g TOC). The overlying largely carbonate‐free shale succession, 424 m thick, is less organic matter ‐rich (∼2.0 %TOC) and contains dominantly Type III kerogen (average HI: 140 mg HC/g TOC). In total, the Maikop Group has a generation potential of about 4 t HC/m2, a value which is higher than in most other sub‐basins in the Eastern Paratethys. Because the Rioni Basin continues westwards into the Black Sea, these results are relevant for future exploration in the eastern part of the Black Sea Basin.

The Maikop Group in the western Kura Basin in the Tbilisi area is over 3500 m thick and includes numerous sandstone beds. Because of the great thickness of the Maikop Group and the presence of about 3 km of overburden, which was removed during Miocene to Recent unroofing, potential source rocks in the Eocene to Lower Oligocene succession have reached oil window maturities but their hydrocarbon potential is low.
ORGANIC GEOCHEMICAL EVALUATION OF POTENTIAL CENOZOIC SOURCE ROCKS IN THE MOGHAN BASIN, NW IRAN: IMPLICATIONS FOR HYDROCARBON EXPLORATION
Authors: Mirshahani M. , Bahrami H. , Rashidi M. , Tarhandeh E. , Khani B.
Published: June 2018

A detailed organic geochemical evaluation of potential source rock samples (n = 350) collected from outcrops and wells in the Cenozoic Moghan Basin, NW Iran, was undertaken using whole rock (Rock‐Eval pyrolysis, organic petrography) and extract (GC and GC‐MS) analyses. The studied intervals consist of Eocene to Miocene shale/sandstone successions interpreted to have been deposited in nearshore marine conditions. Three potential source rock intervals were investigated: the Salm Aghaji Formation (lower Middle Eocene), the lower member of the Ojagheshlagh Formation (upper Middle Eocene), and the Ziveh Formation (Oligo‐Miocene). The results were used to evaluate the samples' petroleum potential and thermal maturity.

A range of maturity parameters indicate that these source rocks are in the early oil generation window in the study area, and outcrop samples are less mature than subsurface samples. Rock‐Eval Tmaxvalues for the outcrop and subsurface samples range from 410–442 °C and 438–445 °C, respectively. At a regional scale, there is an eastwards increase in thermal maturity which reaches the main oil window (ca. 3000 m) in the east of the Moghan Basin, as indicated by both VRomeasurements and maturity‐sensitive biomarkers. Fair to moderate TOC contents (averaging 0.72, 0.99 and 0.78 wt.%) were recorded respectively for the Salm Aghaji, Ojagheshlagh and Ziveh Formations. Average HI values of less than 200 mg HC/g TOC (131, 178 and 104 respectively for the three formations) indicate the dominance of Type III kerogen. This is consistent with detailed molecular parameters which show a dominance of C29steranes over C27and C28homologues. These observations are interpreted to indicate a nearshore marine depositional environment with an abundant terrigenous organic matter input. However, HI values of several samples fall into the range of 250 to 650 mg HC/g TOC showing the local presence of Type II kerogen. Thus the geochemistry and maturity results from this study suggest that shale‐rich intervals in the Salm Aghaji, Ojagheshlagh and Ziveh Formations may be potential source rocks for the oil shows which have been recorded in wells in the Moghan Basin.
Effect of vitamin E supplementation in milk replacer and Shiga toxoid vaccination on serum α‐tocopherol, performance, haematology and blood chemistry in male Holstein calves
Authors: Schmidt Nadine , Luhmann Tim , Hüther Liane , Meyer Ulrich , Barth Stefanie A. , Geue Lutz , Menge Christian , Frahm Jana , Dänicke Sven
Published: June 2018

Vitamin E (vit E), an essential antioxidant for maintaining the stability of biological membranes and the function of the immune system, is considered to support adaptive immune responses and performance in cattle. The principal virulence factor of Shiga toxin (Stx)‐producingEscherichia coli(STEC), the eponymous Stx, modulates cellular immune responses in cattle, the primarySTECreservoir. Active and passive immunization of calves with Shiga toxoids (rStxMUT) was recently shown to reduce theSTECshedding. Here, we examined the influence of vit E on calves' serum α‐tocopherol, performance, haematology, blood chemistry and its interaction withrStxMUTimmunization. Data from calves having received passive (colostrum from immunized cows) and active (intramuscularly at 5th and 8th weeks of life) vaccination withrStxMUT(n = 24) were compared to unvaccinated controls (n = 24; fed with low anti‐Stx colostrum, placebo injected). For each vaccination group, data were analysed according to the level of vit E supplementation offered by milk replacer (188 IU all‐rac‐α‐tocopheryl acetate daily [VitEM] vs. 354 IU [VitEH]). An increase by 79% in daily vit E supplementation led to slightly higher serum α‐tocopherol level and earlier concentrate intake at the beginning of the experiment without significant differences in live weight gain, haematology, blood chemistry parameters and peripheralCD4+andCD8+T‐cell subpopulations.rStxMUTvaccination modulated theCD4+/CD8+ratio irrespective of vit E supplementation but decreased concentrate intake in VitEHin a time‐dependent manner. Results of our study indicate that an increase in daily vit E supplementation vastly fails to exert effects on laboratory parameters and growth performance. However, observed interactive effects of vit E supply and vaccination on the regulation of feed intake deserves further attention.
The Arabidopsis USL1 controls multiple aspects of development by affecting late endosome morphology
Authors: Yuan Rongrong , Lan Jingqiu , Fang Yuxing , Yu Hao , Zhang Jinzhe , Huang Jiaying , Qin Genji
Published: June 2018

The polar transport of auxin controls many aspects of plant development. However, the molecular mechanisms underlying auxin tranport regulation remain to be further elucidated.

We identified a mutant named as usl1 (unflattened and small leaves) in a genetic screen in Arabidopsis thaliana. The usl1 displayed multiple aspects of developmental defects in leaves, embryogenesis, cotyledons, silique phyllotaxy and lateral roots in addition to abnormal leaves. USL1 encodes a protein orthologous to the yeast vacuolar protein sorting (Vps) 38p and human UV RADIATION RESISTANCE‐ASSOCIATED GENE (UVRAG). Cell biology, Co‐IP/MS and yeast two‐hybrid were used to identify the function of USL1.

USL1 colocalizes at the subcellular level with VPS29, a key factor of the retromer complex that controls auxin transport. The morphology of the VPS29‐associated late endosomes (LE) is altered from small dots in the wild‐type to aberrant enlarged circles in the usl1 mutants. The usl1 mutant synergistically interacts with vps29. We also found that USL1 forms a complex with AtVPS30 and AtVPS34.

We propose that USL1 controls multiple aspects of plant development by affecting late endosome morphology and by regulating the PIN1 polarity. Our findings provide a new layer of the understanding on the mechanisms of plant development regulation.
A novel balloon technique to induce intra‐abdominal hypertension and its effects on cardiovascular parameters in a conscious dog model
Authors: Jang Min , Son Won‐gyun , Jo Sang‐min , Kim Hyunseok , Shin Chi Won , Lee Inhyung
Published: June 2018

Objective

To evaluate a new balloon technique to induce intra‐abdominal hypertension (IAH) and abdominal compartment syndrome in a conscious dog model, and to evaluate the effect of intra‐abdominal pressure (IAP) on cardiovascular, respiratory, and arterial blood gas values in conscious dogs with IAH.

Design

Prospective, experimental study.

Setting

University‐based small animal research facility.

Animals

Six healthy Beagle dogs, 4 males, and 2 females.

Interventions

A new balloon device designed for this study using a Foley urethral catheter and latex balloon was placed in the abdominal cavity. Consecutive measurements of IAP were made by measuring the intravesicular pressure. The abdomen was inflated with air to IAPs of 10, 15, 20, and 25 mm Hg. Heart rate, respiratory rate, systolic arterial blood pressure, and arterial blood gases were evaluated at baseline and at 15, 30, 45, 60, 120, 240, and 300 minutes after IAP increase.

Measurements and Main Results

The air insufflated into the intra‐abdominal balloon device significantly increased the IAP and led to sustained IAH. The respiratory rate increased significantly (P< 0.05) when IAP was increased to 15, 20, and 25 mm Hg. Although heart rate, systolic arterial blood pressure, PaO2, and PaCO2did not show statistically significant differences between baseline and posttreatment values over time, the dogs with increased IAP showed a distended abdomen and apparent discomfort, and 4/6 (67%) vomited. After measurement of IAP, air was removed. There were no adverse effects noted after removal of the balloon device.

Conclusion

The balloon device was successfully insufflated and led to sustained IAH in conscious dogs. This balloon technique does not require general anesthesia for instillation or removal of gas after installment. An acute IAP increase in normal conscious dogs induced discomfort, vomiting, and increased respiratory effort.
The Relationship Between Quality of Life and Attitudes Toward Barriers in the Leisure Time of Physical Education Students of Adıyaman University
Authors: Yetiş Ümit
Published: June 2018

The purpose of this study was to investigate the relationship between quality of life and attitudes toward barriers to leisure time in Adiyaman University of Physical Education in Turkey. The study also examined the differences in quality of life and attitudes toward barriers to the leisure time of Adiyaman University students in Turkey. A standard questionnaire (ÜNİVERSİTE YAŞAM KALİTESİ ÖLÇEĞİ) was used to measure the quality of life students. The standard questionnaire (BOŞ ZAMAN ENGELLERİ ÖLÇEĞİ) was used to measure the attitude to the barriers to leisure time of students. Reliability of the questionnaires was evaluated using Cronbach's alpha test, the quality of life questionnaire of students was 0.82 and the leisure barrier questionnaire was 0.79. The questionnaires were distributed among the statistical sample (181 students of Adiyaman University of Physical Education in Turkey). The results showed that there is a significant negative relationship between quality of life and attitudes towards the obstacles in leisure time of the Adiyaman University of Physical Education students in Turkey. The correlation coefficient between two variables was 0.63. Also, there was a significant difference in the quality of life and attitudes toward barriers to leisure time among Adiyaman Universidad students in Turkey. Male students had a higher quality of life, and female students had more obstacles in spending their leisure time.
Learning to extract a large inter-aural level difference in lag clicks
Authors: Nilsson Mats E.
Published: June 2018

Many blind people learn to use sound reflections to localize objects. However, precedence-effect research has reported evidence both for and against the possibility to improve lateralization of lag clicks preceded by lead clicks. This training study used stimuli more relevant to human echolocation than did previous training studies. One participant, the author, practiced lateralizing a lag-click inter-aural level difference (ILD) of 10 dB for 60 days, with performance measured in the lag–lead peak amplitude ratio at threshold. Clear improvements were observed at interclick intervals of 2–18 ms, suggesting that extracting a large lag-click ILD may improve with practice.
Differential Cortical Control of Chest Wall Muscles During Pressure- and Volume-Related Expiratory Tasks and the Effects of Acute Expiratory Threshold Loading
Authors: Boliek Carol A. , Bakhtiari Reyhaneh , Pedersen Lauren , Esch Julia R. , Cummine Jacqueline
Published: June 2018

We examined whether or not coherence between chest wall intercostal and oblique muscles changed as a function of lung volume excursion, alveolar pressure, and muscular demand. We also assessed the effects of acute expiratory threshold loading (ETL) on chest wall muscular control. A total of 15 healthy adults (7 males; average age = 28 years) completed maximum performance and ETL tasks. Chest wall surface electromyographic and kinematic recordings were made. Participants also performed a session of acute ETL. We showed that corticomuscular control of the chest wall varied as a function of lung volume excursion and muscular effort. Acute ETL had some effect on respiratory kinematics but not coherence.
Basal channels drive active surface hydrology and transverse ice shelf fracture
Authors: Dow Christine F. , Lee Won Sang , Greenbaum Jamin S. , Greene Chad A. , Blankenship Donald D. , Poinar Kristin , Forrest Alexander L. , Young Duncan A. , Zappa Christopher J.
Published: June 2018

Ice shelf basal channels cause transverse fractures that can be exacerbated by surface rivers, culminating in calving.
X chromosome protects against bladder cancer in females via aKDM6A-dependent epigenetic mechanism
Authors: Kaneko Satoshi , Li Xue
Published: June 2018

Why are men more likely than women to have cancer? We report that the genetic inequality is an independent intrinsic cause.
Nanoscale momentum-resolved vibrational spectroscopy
Authors: Hage Fredrik S. , Nicholls Rebecca J. , Yates Jonathan R. , McCulloch Dougal G. , Lovejoy Tracy C. , Dellby Niklas , Krivanek Ondrej L. , Refson Keith , Ramasse Quentin M.
Published: June 2018

A widely applicable method for accessing phonon dispersions of materials at high spatial resolution is demonstrated.
Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis
Authors: Viktorova Ekaterina G. , Khattar Sunil K. , Kouiavskaia Diana , Laassri Majid , Zagorodnyaya Tatiana , Dragunsky Eugenia , Samal Siba , Chumakov Konstantin , Belov George A.
Published: June 2018

A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced
in vivo
, in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.
Association of LACC1, CEBPB-PTPN1, RIPK2 and ADO-EGR2 with ocular Behcet’s disease in a Chinese Han population
Authors: Wu Pengcheng , Du Liping , Hou Shengping , Su Guannan , Yang Lu , Hu Jiayue , Deng Jing , Cao Qingfeng , Yuan Gangxiang , Zhou Chunjiang , Kijlstra Aize , Yang Peizeng
Published: June 2018

Background

An Immunochip study recently identified the association of a number of new genetic loci with Behcet’s disease (BD).

Objective

To confirm the association between new genetic loci reported in an Immunochip study and BD in a Han Chinese population.

Methods

A two-stage association study was carried out in 1238 patients with BD and 1458 healthy controls. Twenty-two candidate single nucleotide polymorphisms (SNPs) were selected for genotyping by iPLEXGold genotyping or TaqMan SNP assays and a meta-analysis was performed for significantly associated markers.

Results

The results showed that four SNPs (LACC1/rs9316059, CEBPB-PTPN1/rs913678, ADO-EGR2/rs224127 and RIPK2/rs10094579) were associated with BD in an allelic association test (rs9316059 T allele: pc=4.95×10−8, OR=0.687; rs913678 C allele: pc=3.01×10−4, OR=1.297; rs224127 A allele: pc=3.77×10−4, OR=1.274; rs10094579 A allele: pc=6.93×10−4, OR=1.302). For four SNPs tested by meta-analysis, the association with BD was strengthened and all exceeded genome-wide significance (rs9316059: p=2.96×10−16; rs913678: p=2.09×10−16; rs224127: p=5.28×10−13; rs10094579: p=9.21×10−11).

Conclusions

Our findings confirmed the association of four loci (LACC1, CEBPB-PTPN1, ADO-EGR2 and RIPK2) in Chinese Han patients with BD.