bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker
Authors: Koraishy Farrukh M. , Salas Joanne , Neylan Thomas C. , Cohen Beth E. , Schnurr Paula P. , Clouston Sean , Scherrer Jeffrey F.
Published: October 2019

Background

Inflammation is known to be associated with posttraumatic stress disorder. It is not known if total white blood cell count, a routinely checked inflammatory marker, is associated with posttraumatic stress disorder symptom trajectories using medical record data.

Methods

We used latent class growth analysis to identify three-year posttraumatic stress disorder symptom trajectories using posttraumatic stress disorder (PTSD) Checklist (PCL) scores. The outcome for each patient was maximum white blood cell count from index posttraumatic stress disorder diagnosis to last PCL . Using linear regression analysis, we then calculated and compared the average white blood cell count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression, and other comorbid inflammatory conditions.

Results

Patients were 40.2 (SD ± 13.5) years of age, 83.7% males and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: “moderate-large decrease,” “moderate-severe-slight decrease,” and “severe-persistent.” In adjusted analyses, “severe-persistent” versus “moderate-large decrease” had significantly higher white blood cell count (B = 0.64; 95%CI = 0.18, 1.09; p = .006). Although non-significant, “moderate-severe-slight decrease” versus “moderate-large decrease” also had a higher white blood cell count (B = 0.42; 95% CI: −0.02, 0.86; p = .061).

Conclusion

Persistently severe posttraumatic stress disorder is associated with a higher white blood cell count than improving posttraumatic stress disorder. White blood cell appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases.
Meeting Report From the 2019 “Organelle Zone” Symposium in Osaka, Japan
Authors: Levine Tim P. , Perez Franck , Saheki Yasunori , von Blume Julia
Published: October 2019

On May 29, 2019, at the Osaka University Hospital, Japan, the “Organelle Zones” research grant group (see http://organellezone.org/english/ ) organized a 1 day symposium for its own members and four guest speakers, with about 60 attendees. The research group studies three different ways in which regions within organelles carry out functions distinct from other parts of the organelle. Work at this suborganellar level is increasingly recognized as an important aspect of cell biology. The group’s projects are divided into these themes with 9 Principal Investigators and 18 Coinvestigators over 5 years. The symposium followed a similar meeting in 2018 and had four speakers from within the consortium as well as the external speakers. The talks were divided into three sessions, each showcasing one way of subcompartmentalizing organelles into zones.
Strengthen the European collaborative environmental research to meet European policy goals for achieving a sustainable, non-toxic environment
Authors: Brack Werner , Ait-Aissa Selim , Backhaus Thomas , Birk Sebastian , Barceló Damià , Burgess Rob , Cousins Ian , Dulio Valeria , Escher Beate I. , Focks Andreas , van Gils Jos , Ginebreda Antoni , Hering Daniel , Hewitt L. Mark , Hilscherová Klára , Hollender Juliane , Hollert Henner , Köck Marianne , Kortenkamp Andreas , de Alda Miren López , Müller Christin , Posthuma Leo , Schüürmann Gerrit , Schymanski Emma , Segner Helmut , Sleeuwaert Frank , Slobodnik Jaroslav , Teodorovic Ivana , Umbuzeiro Gisela , Voulvoulis Nick , van Wezel Annemarie , Altenburger Rolf
Published: October 2019

To meet the United Nations (UN) sustainable development goals and the European Union (EU) strategy for a non-toxic environment, water resources and ecosystems management require cost-efficient solutions for prevailing complex contamination and multiple stressor exposures. For the protection of water resources under global change conditions, specific research needs for prediction, monitoring, assessment and abatement of multiple stressors emerge with respect to maintaining human needs, biodiversity, and ecosystem services. Collaborative European research seems an ideal instrument to mobilize the required transdisciplinary scientific support and tackle the large-scale dimension and develop options required for implementation of European policies. Calls for research on minimizing society’s chemical footprints in the water–food–energy–security nexus are required. European research should be complemented with targeted national scientific funding to address specific transformation pathways and support the evaluation, demonstration and implementation of novel approaches on regional scales. The foreseeable pressure developments due to demographic, economic and climate changes require solution-oriented thinking, focusing on the assessment of sustainable abatement options and transformation pathways rather than on status evaluation. Stakeholder involvement is a key success factor in collaborative projects as it allows capturing added value, to address other levels of complexity, and find smarter solutions by synthesizing scientific evidence, integrating governance issues, and addressing transition pathways. This increases the chances of closing the value chain by implementing novel solutions. For the water quality topic, the interacting European collaborative projects SOLUTIONS, MARS and GLOBAQUA and the NORMAN network provide best practice examples for successful applied collaborative research including multi-stakeholder involvement. They provided innovative conceptual, modelling and instrumental options for future monitoring and management of chemical mixtures and multiple stressors in European water resources. Advancement of EU water framework directive-related policies has therefore become an option.
Establish data infrastructure to compile and exchange environmental screening data on a European scale
Authors: Slobodnik Jaroslav , Hollender Juliane , Schulze Tobias , Schymanski Emma L. , Brack Werner
Published: October 2019

Robust techniques based on liquid (LC) and gas chromatography (GC) coupled with high-resolution mass spectrometry (HR-MS) enable sensitive screening, identification, and (semi)quantification of thousands of substances in a single sample. Recent progress in computational sciences has enabled archiving and processing of HR-MS ‘big data’ at the routine level. As a result, community-based databases containing thousands of environmental pollutants are rapidly growing and large databases of substances with unique identifiers allowing for inter-comparison at the global scale have become available. A data-archiving infrastructure is proposed, allowing for retrospective screening of HR-MS data, which will help define the ‘chemical universe’ of organic substances and enable prioritisation of toxicants causing adverse environmental effects at the local, river basin, and national and European scale in support of the European water and chemicals management policy.
Prioritisation of water pollutants: the EU Project SOLUTIONS proposes a methodological framework for the integration of mixture risk assessments into prioritisation procedures under the European Water Framework Directive
Authors: Faust Michael , Backhaus Thomas , Altenburger Rolf , Dulio Valeria , van Gils Jos , Ginebreda Antoni , Kortenkamp Andreas , Munthe John , Posthuma Leo , Slobodnik Jaroslav , Tollefsen Knut Erik , van Wezel Annemarie , Brack Werner
Published: October 2019

Current prioritisation procedures under the EU Water Framework Directive (WFD) do not account for risks from chemical mixtures. SOLUTIONS proposes a multiple-lines-of-evidence approach to tackle the problem effectively. The approach merges all available evidence from co-exposure modelling, chemical monitoring, effect-based monitoring, and ecological monitoring. Full implementation of the proposed methodology requires changes in the legal text in adaptation to scientific progress.
Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial
Authors: Pedersen Lene Rørholm , Olsen Rasmus Huan , Anholm Christian , Astrup Arne , Eugen-Olsen Jesper , Fenger Mogens , Simonsen Lene , Walzem Rosemary L. , Haugaard Steen Bendix , Prescott Eva
Published: October 2019

Background

Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD.

Methods

Seventy CAD patients, BMI 28–40 kg/m2 and age 45–75 years were randomised to (1) 12 weeks’ aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks’ AIT twice weekly or (2) a low energy diet (LED) (800–1000 kcal/day) for 8–10 weeks followed by 40 weeks’ weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis.

Results

Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (− 8.4; − 6.1) and waist circumference by 6.6 cm (− 7.7; − 5.5) compared to 1.7 kg (− 0.7; − 2.6) and 3.3 cm (− 5.1; − 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change.

Conclusions

Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients.

Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).
Extracellular and macropinocytosis internalized ATP work together to induce epithelial–mesenchymal transition and other early metastatic activities in lung cancer
Authors: Cao Yanyang , Wang Xuan , Li Yunsheng , Evers Maria , Zhang Haiyun , Chen Xiaozhuo
Published: October 2019

Background

Extracellular ATP (eATP) was shown to induce epithelial–mesenchymal transition (EMT), a very important early process in metastasis, in cancer cells via purinergic receptor signaling. However, the exact induction mechanisms are far from fully known. We previously described that eATP is internalized by cancer cells in vitro and in vivo by macropinocytosis in human non-small cell lung cancer A549 and other cancer cells, drastically elevates intracellular ATP levels, enhances cell proliferation and resistance to anticancer drugs. In this study, we tested the hypothesis that eATP and macropinocytosis-internalized eATP also induces EMT and other early steps of metastasis.

Methods

Floating cells, fencing, and transwell assays were used to show that ATP induces cell detachment, new colony formation, migration and invasion in human A549 and other lung cancer cells. Western blots were used to detect ATP-induced changes in EMT-related proteins; Confocal microscopy was used to demonstrate ATP-induced metastasis-related cell morphological changes. Inhibitors and siRNA knockdowns were used to determine P2X7’s involvement in the ATP-induced EMT. CRISPR–Cas9 knockout of the SNX5 gene was used to identify macropinocytosis’ roles in EMT and cancer cell growth both in vitro and in vivo. Student t-test and one-way ANOVA were used to determine statistical significance, P < 0.05 was considered significant.

Results

eATP potently induces expression of matrix metallopeptidases (MMPs), and detachment, EMT, migration, and invasion of lung cancer cells. The induction was independent of TGF-β and semi-independent of P2X7 activation. eATP performs these functions not only extracellularly, but also intracellularly after being macropinocytically internalized to further enhance P2X7-mediated EMT, filopodia formation and other early steps of metastasis. The knockout of macropinocytosis-associated SNX5 gene significantly reduces macropinocytosis, slows down tumor growth, and changes tumor morphology in nude mice.

Conclusions

Collectively, these results show that eATP's functions in these processes not only from outside of cancer cells but also inside after being macropinocytotically internalized. These findings shed light on eATP’s initiator and effector roles in almost every step in early metastasis, which calls for rethinking and rebalancing energy equations of intracellular biochemical reactions and the Warburg effect, and identifies eATP and macropinocytosis as novel targets for potentially slowing down EMT and preventing metastasis.
Bio-efficacy and wash resistance of MAGNet long-lasting insecticidal net against wild populations of Anopheles funestus in experimental huts in Muheza, Tanzania
Authors: Kweka Eliningaya J. , Tungu Patrick K. , Mahande Aneth M. , Mazigo Humphrey D. , Sayumwe Subira , Msangi Shandala , Lyaruu Lucile , Waweru John , Kisinza William , Wangai James
Published: October 2019

Background

The decline in malaria cases and vectors is major milestone in fighting against malaria. The efficacy of MAGNet long-lasting insecticidal nets (MAGNet LLIN), an alpha-cypermethrin incorporated long-lasting net, with the target dose ± 25% of 5.8 g active ingredient (AI)/kg (4.35–7.25 g AI/kg) was evaluated in six veranda-trap experimental huts in Muheza, Tanzania against freely flying wild population of Anopheles funestus.

Methods

MAGNet LLINs were tested against wild, free-flying, host-seeking An. funestus mosquitoes over a period of 6 weeks (total of 36 nights in the huts). MAGNet LLIN efficacy was determined in terms of mosquito mortality, blood-feeding inhibition, deterrence, induced exiting, personal protection, and insecticidal killing over 20 washes according to WHO standardized procedures. Efficacy was compared with reference to a WHOPES recommended approved LLINs (DuraNet) and to a net conventionally treated (CTN) treated with alpha-cypermethrin at WHO-recommended dose and washed to just before cut-off point. The efficacy of MAGNet was evaluated in experimental huts against wild, free-flying, pyrethroid-resistant An. funestus. The WHO-susceptibility method was used to detect resistance in wild Anopheles exposed to 0.75% permethrin. Mosquito mortality, blood-feeding inhibition and personal protection were compared between untreated nets and standard LLINs. Blood-feeding rates were recorded and compared between the 20 times washed; blood-feeding rates between 20 times washed MAGNet LLIN and 20 times washed WHOPES-approved piperonyl butoxide (PBO)/pyrethroid were not statistically different (p > 0.05).

Results

The results have evidently shown that MAGNet LLIN provides similar blood-feeding inhibition, exophily, mortality, and deterrence to the standard approved LLIN, thus meeting the WHOPES criteria for blood feeding. The significantly high feeding inhibition and personal protection over pyrethroid-resistant An. funestus recorded by both unwashed and 20 times washed MAGNet compared to the unwashed DuraNet, the WHOPES-approved standard pyrethroid-only LLIN provides proof of MAGNet meeting Phase II WHOPES criteria for a LLIN.

Conclusion

Based on this study, MAGNet has been shown to have a promising impact on protection when 20 times washed against a highly resistant population of An. funestus.
Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study
Authors: Ding Xian-Fei , Li Jin-Bo , Liang Huo-Yan , Wang Zong-Yu , Jiao Ting-Ting , Liu Zhuang , Yi Liang , Bian Wei-Shuai , Wang Shu-Peng , Zhu Xi , Sun Tong-Wen
Published: October 2019

Background

To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and laboratory parameters.

Methods

A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission.

Results

All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count.

Conclusions

This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.
Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology
Authors: Frecer Vladimir , Iarossi Giancarlo , Salvetti Anna Paola , Maltese Paolo Enrico , Delledonne Giulia , Oldani Marta , Staurenghi Giovanni , Falsini Benedetto , Minnella Angelo Maria , Ziccardi Lucia , Magli Adriano , Colombo Leonardo , D’Esposito Fabiana , Miertus Jan , Viola Francesco , Attanasio Marcella , Maggio Emilia , Bertelli Matteo
Published: October 2019

Background

Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium.

Methods

Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands.

Results

Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants.

Conclusions

Using this computational approach, we designed a method for estimating BCVA progression in patients with BEST1 variants.
A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma
Authors: Krishnan Anitha , Kocab Andrew J. , Zacks David N. , Marshak-Rothstein Ann , Gregory-Ksander Meredith
Published: October 2019

Background

Glaucoma is a complex, multifactorial disease where apoptosis, microglia activation, and inflammation have been linked to the death of retinal ganglion cells (RGCs) and axon degeneration. We demonstrated previously that FasL-Fas signaling was required for axon degeneration and death of RGCs in chronic and inducible mouse models of glaucoma and that Fas activation triggered RGC apoptosis, glial activation, and inflammation. Here, we investigated whether targeting the Fas receptor with a small peptide antagonist, ONL1204, has anti-inflammatory and neuroprotective effects in a microbead-induced mouse model of glaucoma.

Methods

Intracameral injection of microbeads was used to elevate intraocular pressure (IOP) in Fas-deficient (Faslpr) mice and WT C57BL/6J mice that received an intravitreal injection of the Fas inhibitor, ONL1204 (2 μg/1 μl) (or vehicle only), on day 0 or day 7 after microbead injection. The IOP was monitored by rebound tonometry, and at 28 days post-microbead injection, Brn3a-stained RGCs and paraphenylenediamine (PPD)-stained axons were analyzed. The effects of ONL1204 on retinal microglia activation and the expression of inflammatory genes were analyzed by immunostaining of retinal flatmounts and quantitative PCR (qPCR).

Results

Rebound tonometry showed equivalent elevation of IOP in all groups of microbead-injected mice. At 28 days post-microbead injection, the RGC and axon counts from microbead-injected Faslprmice were equivalent to saline-injected (no IOP elevation) controls. Treatment with ONL1204 also significantly reduced RGC death and loss of axons in microbead-injected WT mice when compared to vehicle-treated controls, even when administered after IOP elevation. Confocal analysis of Iba1-stained retinal flatmounts and qPCR demonstrated that ONL1204 also abrogated microglia activation and inhibited the induction of multiple genes implicated in glaucoma, including cytokines and chemokines (GFAP, Caspase-8, TNFα, IL-1β, IL-6, IL-18, MIP-1α, MIP-1β, MIP-2, MCPI, and IP10), components of the complement cascade (C3, C1Q), Toll-like receptor pathway (TLR4), and inflammasome pathway (NLRP3).

Conclusions

These results serve as proof-of-principal that the small peptide inhibitor of the Fas receptor, ONL1204, can provide robust neuroprotection in an inducible mouse model of glaucoma, even when administered after IOP elevation. Moreover, Fas signaling contributes to the pathogenesis of glaucoma through activation of both apoptotic and inflammatory pathways.
Social anxiety disorder and emotion regulation problems in adolescents
Authors: Sackl-Pammer Petra , Jahn Rebecca , Özlü-Erkilic Zeliha , Pollak Eva , Ohmann Susanne , Schwarzenberg Julia , Plener Paul , Akkaya-Kalayci Türkan
Published: October 2019

Background

Social anxiety disorder (SAD) in adolescents may be associated with the use of maladaptive emotion regulation (ER) strategies. The present study examined the use of maladaptive and adaptive ER strategies in adolescents with SAD.

Methods

30 adolescents with SAD (CLIN) and 36 healthy adolescents for the control group (CON) aged between 11 and 16 years were assessed with the standardized questionnaires PHOKI (Phobiefragebogen für Kinder und Jugendliche) for self-reported fears as well as FEEL-KJ (Fragebogen zur Erhebung der Emotionsregulation bei Kindern und Jugendlichen) for different emotion regulation strategies.

Results

Compared to controls, adolescents with SAD used adaptive ER strategies significantly less often, but made use of maladaptive ER strategies significantly more often. There was a significant positive correlation between maladaptive ER and social anxiety in adolescents. Examining group differences of single ER strategy use, the CLIN and CON differed significantly in the use of the adaptive ER strategy reappraisal with CLIN reporting less use of reappraisal than CON. Group differences regarding the maladaptive ER strategies withdrawal and rumination, as well as the adaptive ER strategy problem-solving were found present, with CLIN reporting more use of withdrawal and rumination and less use of problem-solving than CON.

Conclusions

Promoting adaptive emotion regulation should be a central component of psychotherapy (cognitive behavioral therapy-CBT) for social anxiety in adolescents from the beginning of the therapy process. These findings provide rationale for special therapy programs concentrating on the establishment of different adaptive ER strategies (including reappraisal). As an increased use of maladaptive ER may be associated with SAD in adolescents, it may be paramount to focus on reduction of maladaptive ER (for example withdrawal and rumination) from the beginning of the psychotherapy process. Incorporating more ER components into psychotherapy (CBT) could increase the treatment efficacy. Further investigations of the patterns of emotion regulation in specific anxiety groups like SAD in adolescents is needed to continue to optimize the psychotherapy (CBT) concept.
Metformin paradoxically worsens insulin resistance in SHORT syndrome
Authors: Lewandowski Krzysztof C. , Dąbrowska Katarzyna , Brzozowska Maria , Kawalec Joanna , Lewiński Andrzej
Published: October 2019

Background

SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available.

Methods

We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea.

Results

She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4.52. Extended Oral Glucose Tolerance Test was performed and showed severe IR. She was then started on metformin 850 mg twice a day, and had repeated OGTT. This showed dramatic worsening of glucose tolerance (e.g. glucose 96 mg/dl versus 187 mg/dl and 68 mg/dl versus 204 mg/dl at 120 and 150 min of OGTT, respectively). This was accompanied by a massive increase of already high insulin concentrations (e.g. from 488.6 to > 1000 µIU/ml, and from 246.8 to > 1000 µIU/ml at 120 and 150 min of OGTT, respectively). Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 µIU/ml versus 100.6 µIU/ml without metformin).

Conclusions

Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Hence, metformin treatment might be potentially harmful in these patients. Though, the precise cause of such profound and paradoxical worsening of glucose tolerance post metformin remains unknown, SHORT syndrome might prove to be an interesting model to study the mechanism(s) of metformin action.
Global existence of weak solution for the compressible Navier–Stokes–Poisson system with density-dependent viscosity
Authors: Cui Meiying , Song Wenjing
Published: October 2019

In this paper, we are concerned with the existence of global weak solutions to the compressible Navier–Stokes–Poisson equations with the non-flat doping profile when the viscosity coefficients are density-dependent, the data are large and spherically symmetric, and we focus on the case where those coefficients vanish in vacuum. We construct a suitable approximate system and consider it in annular regions between two balls. The global solutions are obtained as limits of such approximate solutions. Our proofs are mainly based on the energy and entropy estimates.
Random attractors for the stochastic coupled suspension bridge equations of Kirchhoff type
Authors: Xu Ling , Huang Jianhua , Ma Qiaozhen
Published: October 2019

This paper is devoted to the dynamical behavior of stochastic coupled suspension bridge equations of Kirchhoff type. For the deterministic cases, there are many classical results such as existence and uniqueness of a solution and long-term behavior of solutions. To the best of our knowledge, the existence of random attractors for the stochastic coupled suspension bridge equations of Kirchhoff type is not yet considered. We intend to investigate these problems. We first obtain the dissipativeness of a solution in higher-energy spaces$H^{3}(U)\times H_{0}^{1}(U)\times (H^{2}(U)\cap H_{0}^{1}(U))\times H_{0}^{1}(U)$H3(U)×H01(U)×(H2(U)∩H01(U))×H01(U). This implies that the random dynamical system generated by the equation has a random attractor in$(H^{2}(U)\cap H_{0}^{1}(U))\times L^{2}(U) \times H_{0}^{1}(U)\times L^{2}(U)$(H2(U)∩H01(U))×L2(U)×H01(U)×L2(U), which is a tempered random set in the space in$H^{3}(U)\times H_{0}^{1}(U)\times (H^{2}(U)\cap H_{0} ^{1}(U))\times H_{0}^{1}(U)$H3(U)×H01(U)×(H2(U)∩H01(U))×H01(U).
Pathological transition as the arising mechanism for drug resistance in lung cancer
Authors: Chen Yueqing , Tang Waiying Yvonne , Tong Xinyuan , Ji Hongbin
Published: October 2019

Despite the tremendous efforts for improving therapeutics of lung cancer patients, its prognosis remains disappointing. This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insufficient development of effective therapeutics in clinic. Based on the current progresses of lung cancer research, we classify drug resistance mechanisms into three different levels: molecular, cellular and pathological level. All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic. Our understanding on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis. In this review, we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.
Evaluation of Lymphadenopathy and Suspected Lymphoma in a Lymphoma Rapid Diagnosis Clinic
Authors: Nixon Shannon , Bezverbnaya Ksenia , Maganti Manjula , Gullane Patrick , Reedijk Michael , Kuruvilla John , Prica Anca , Kridel Robert , Kukreti Vishal , Bennett Sabrina , Rogalla Patrik , Delabie Jan , Pintilie Melania , Crump Michael
Published: October 2019

PURPOSE:

Lymphomas often present a diagnostic challenge, and for some a delay in diagnosis can negatively influence outcomes of therapy. We established a nurse practitioner–led lymphoma rapid diagnosis clinic (LRDC) with the goal of reducing wait times to definitive diagnosis. We examined the initial 30-month experience of the LRDC, and results were compared with time periods before implementation of the clinic to determine program impact.

METHODS:

All patients referred to LRDC with suspicion of lymphoma from June 1, 2015 to Nov 30, 2017 were evaluated. Time from initial consultation to diagnosis was compared with patients diagnosed at our center with lymphoma in 2008 and 2012. Patient symptoms and relevant laboratory/imaging findings were collected to identify patterns of presentation and predictive factors for benign diagnoses.

RESULTS:

Of the 126 patients evaluated, 66 (52%) had confirmation of lymphoma diagnosis. Median time to lymphoma diagnosis was 16 days for patients assessed in LRDC and 28 days for historical controls ( P < .001). By univariable analysis, lymph node size greater than 3.4 cm and presence of mediastinal or abdominal adenopathy increased the likelihood of a diagnosis of malignancy, whereas younger age, being a nonsmoker, and prior rheumatologic condition were associated with a nonmalignant diagnosis. In multivariable analysis, lymph node size, age, and prior rheumatologic diagnosis remained significant.

CONCLUSION:

Establishing a nurse practitioner–led LRDC was effective in shortening time to diagnosis of lymphoma. Younger age, smaller lymph node size, and prior rheumatologic disorder reduced the likelihood of a cancer diagnosis in our patient population.
Spherical spindle shape promotes perpendicular cortical orientation by preventing isometric cortical pulling on both spindle poles during C. elegans female meiosis
Authors: Vargas Elizabeth , McNally Karen P. , Cortes Daniel B. , Panzica Michelle T. , Danlasky Brennan , Li Qianyan , Maddox Amy Shaub , McNally Francis J.
Published: October 2019

Meiotic spindles are positioned perpendicular to the oocyte cortex to facilitate segregation of chromosomes into a large egg and a tiny polar body. In C. elegans, spindles are initially ellipsoid and parallel to the cortex before shortening to a near spherical shape with flattened poles and then rotating to the perpendicular orientation by dynein-driven cortical pulling. The mechanistic connection between spindle shape and rotation has remained elusive. Here we used three different genetic backgrounds to manipulate spindle shape without eliminating dynein-dependent movement or dynein localization. Ellipsoid spindles with flattened or pointed poles became trapped in either a diagonal or a parallel orientation. Mathematical models that recapitulated the shape dependence of rotation indicated that the lower viscous drag experienced by spherical spindles prevented recapture of the cortex by astral microtubules emanating from the pole pivoting away from the cortex. In addition, maximizing contact between pole dynein and cortical dynein stabilizes flattened poles in a perpendicular orientation and spindle rigidity prevents spindle bending that can lock both poles at the cortex. Spindle shape can thus promote perpendicular orientation by three distinct mechanisms.
Muscle-selective RUNX3 dependence of sensorimotor circuit development
Authors: Wang Yiqiao , Wu Haohao , Zelenin Pavel , Fontanet Paula , Wanderoy Simone , Petitpré Charles , Comai Glenda , Bellardita Carmelo , Xue-Franzén Yongtao , Huettl Rosa-Eva , Huber Brosamle Andrea , Tajbakhsh Shahragim , Kiehn Ole , Ernfors Patrik , Deliagina Tatiana G. , Lallemend François , Hadjab Saida
Published: October 2019

The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet, the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 controls also the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin-3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator critical for specifying a generic PSN type identity after neurogenesis, is later regulated by target muscle-derived signal to contribute to the specialized aspects of the sensorimotor connection selectivity.
Concerted metabolic shift in early forebrain alters the CSF proteome and depends on cMYC downregulation for mitochondrial maturation
Authors: Fame Ryann M. , Shannon Morgan L. , Chau Kevin F. , Head Joshua P. , Lehtinen Maria K.
Published: October 2019

Massive, coordinated cellular changes accompany the transition of central nervous system (CNS) progenitors from forebrain neurectodermal cells to specified neuroepithelial cells. We previously found that c-MYC regulates the changing ribosomal and proteostatic landscapes in mouse forebrain precursors at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure; NTC) (Chau et al., 2018). Here we demonstrate parallel coordinated transcriptional changes in metabolic machinery during this same stage of forebrain specification. Progenitors showed striking mitochondrial structural changes transitioning from glycolytic cristae at E8.5, to more traditional mitochondria at E10.5. Accordingly, glucose usage shifted in progenitors such that E8.5 progenitors relied on glycolysis, and after NTC increasingly used oxidative phosphorylation. This metabolic shift was matched by changes in surrounding amniotic and cerebrospinal fluid proteomes. Importantly, these mitochondrial morphological shifts depend on c-MYC downregulation. Together, our findings demonstrate metabolic shifting accompanies dynamic organelle and proteostatic remodeling of progenitor cells during the earliest stages of forebrain development.
The Invisible Hand of the Government: Moral Suasion during the European Sovereign Debt Crisis
Authors: Ongena Steven , Popov Alexander , Van Horen Neeltje
Published: October 2019

Using proprietary data on banks’ monthly securities holdings, we show that during the European sovereign debt crisis, domestic banks in fiscally stressed countries were considerably more likely than foreign banks to increase their holdings of domestic sovereign bonds during months when the government needed to roll over a relatively large amount of maturing debt. This result cannot be explained by risk shifting, carry trading, or regulatory compliance. Domestic banks that received government support, are small, or with weaker balance sheets were particularly susceptible to “moral suasion,” while governance of banks played less of a role. (JEL D72, E62, G21, G28, H11, H63).
Monopoly Power and Endogenous Product Variety: Distortions and Remedies
Authors: Bilbiie Florin O. , Ghironi Fabio , Melitz Marc J.
Published: October 2019

The inefficiencies related to endogenous product creation and variety under monopolistic competition are two-fold: one static—the mis-alignment between consumers and producers regarding the value of a new variety; and one dynamic—time variation in markups. When production factors (labor and physical capital ) are elastic and traded in competitive markets, further distortions appear. Appropriate taxation schemes can restore optimality if they preserve entry incentives. Quantitatively, the welfare costs of each distortion by itself amounts to 2 to 5 percent of consumption. But their overall cost when jointly present is greatly magnified, and generates up to a 25 percent welfare loss. (JEL D21, D43, H21, H25, H32, L13)
Some Evidence on Secular Drivers of US Safe Real Rates
Authors: Lunsford Kurt G. , West Kenneth D.
Published: October 2019

We study long-run correlations between safe real interest rates in the United States and over 30 variables that have been hypothesized to influence real rates. The list of variables is motivated by an intertermporal IS equation, by models of aggregate savings and investment, and by reduced-form studies. We use annual data, mostly from 1890 to 2016. We find that safe real interest rates are correlated as expected with demographic measures. For example, the long-run correlation with labor force hours growth is positive, which is consistent with overlapping generations models. For another example, the long-run correlation with the proportion of 40 to 64 year-olds in the population is negative. This is consistent with standard theory where middle-aged workers are high savers who drive down real interest rates. In contrast to standard theory, we do not find productivity to be positively correlated with real rates. Most other variables have a mixed relationship with the real rate, with long-run correlations that are statistically or economically large in some samples and by some measures but not in others. (JEL E21, E22, E24, E43, E52)
Multiparametric MRI in differentiation between muscle invasive and non-muscle invasive urinary bladder cancer with vesical imaging reporting and data system (VI-RADS) application
Authors: Makboul Marwa , Farghaly Shimaa , Abdelkawi Islam F.
Published: October 2019

Objective:

To evaluate role of multiparametric MRI (mp-MRI) in differentiation between invasive and non-invasive bladder cancer and accuracy of vesical imaging reporting and data system (VI-RADS) score.

Methods and materials:

50 patients diagnosed as cancer bladder were enrolled in this study, mp-MRI including conventional (T  1 weighted imaging and high resolution T  2 weighted imaging) and functional sequences (diffusion-weighted imaging and dynamic contrast enhanced-MRI) were done, all data were regrouped to evaluate the accuracy of each separate sequence and mp-MRI in distinguishing non-muscle invasive from muscle-invasive tumors, with VI-RADS score application and comparison with pathological findings, then interobserver agreement for detection of muscle invasion according to mp-MRI and VI-RADS scoring system findings was calculated.

Results:

Diagnostic accuracy of mp-MRI in differentiation between muscle invasive and non-muscle invasive bladder cancer was (84%) with highest sensitivity (78%), very good agreement between mp-MRI and histopathological data (k = 0.87), and highest area under curve (AUC) reaching 0.83, dynamic contrast enhanced-MRI sequence showed the highest accuracy in muscle invasion detection by (88%), with highest AUC 0.83. Diagnostic accuracy of VI-RADS score in detection of muscle invasion was 84%, with specificity and negative predictive value of 88% and AUC was 0.83. Interobserver agreement was strong as regard diagnostic performance of mp-MRI and VI-RADS scoring for detection of muscle invasion reaching (K = 0.82, p < 0.001) and (K = 0.87, p < 0.001) respectively.

Conclusion:

mp-MRI is considered as comprehensive and effective tool for determination of muscle invasion in cases of urinary bladder cancer. Also VI-RADS scoring system can accurately differentiate between invasive and non-invasive bladder cancer.

Advances in knowledge:

The VI-RADS system was recently suggested for the uniform evaluation of muscle invasion in cancer bladder by mp-MRI. In this paper, we applied this system to 50 cases to evaluate its ease and compared the results with the histopathological findings for evaluation of its accuracy.
Intervenções Regulatórias, Volatilidade e Contágio: Uma Análise VIRF
Authors: Bragança Gabriel Godofredo Fiuza de , Pessoa Marcelo de Sales , Rocha Katia
Published: October 2019

Este artigo examina como intervenções regulatórias podem afetar o risco de mercado de empresas de eletricidade e de telecomunicações negociadas na BM&FBOVESPA. O artigo utiliza um modelo GARCH (Generalized AutoRegressive Conditional Heteroskedasticity) bivariado para analisar o impacto de duas intervenções regulatórias em 2012: a primeira tomada pela Agência Nacional de Telecomunicações (ANATEL); a segunda, pela Agência Nacional de Energia Elétrica (ANEEL), na volatilidade e covariância do índice de ações pertencentes a esses setores. Neste artigo, adota-se também a função de resposta impulso desenvolvida por Hafner & Herwartz (2006) para estimar a persistência desses efeitos. Os resultados revelam que o impacto da intervenção regulatória na volatilidade do setor de energia elétrica foi significativo, duradouro e contaminou o setor de telecomunicações. Além disso, mostram que o efeito da intervenção regulatória no risco do setor de telecomunicações foi pequeno.
Private Equity e Venture Capital no Brasil: uma Análise de sua Evolução
Authors: Carvalho Antonio Gledson , Gallucci Netto Humberto , Sampaio Joelson
Published: October 2019

Este artigo analisa as principais idiossincrasias dos investimentos em Private Equity e Venture Capital no Brasil e sua evolução entre 2004 e 2009. As principais idiossincrasias são: participação de limited partners no processo de investimento, a inexistência de leverage buyouts, o controle compartilhado das empresas investidas e o uso de direitos especiais para compensar a falta de controle total. As principais mudanças observadas recentemente são: o aumento de investimentos em private equity ante a venture capital, eficiência dos gestores no processo de seleção das empresas investidas, uso dos painéis de arbitragem na resolução de conflitos e na participação de limited partners no processo de investimento.
Os Fatores Determinantes do Pagamento de Dividendos: o Efeito do Obrigatório Mínimo Legal e Contratual nas Empresas Brasileiras
Authors: Vancin Daniel Francisco , Procianoy Jairo Laser
Published: October 2019

Este estudo busca identificar os efeitos do dividendo obrigatório mínimo legal e contratual nos fatores determinantes das companhias listadas na BM&FBovespa a pagar dividendos, demonstrando que a metodologia proposta representa um avanço na busca destes determinantes, espelhando a realidade do desejo efetivo de pagar. Para alcançar este objetivo foi construído um modelo tobit com variáveis instrumentais, segregando a amostra em três grupos: a Amostra Completa, grupo ACIMA e grupo MÍNIMO. No total, foram analisadas 1531 distribuições de dividendos no período de 2007 a 2013. Verificou-se a existência de fortes evidências empíricas que as empresas pagantes de dividendos acima do obrigatório legal e contratual apresentam fatores determinantes diferentes daquelas que pagam apenas este. Dessa forma, a existência de empresas na amostra que pagam apenas o dividendo obrigatório influencia nos coeficientes da regressão quando olhamos todos os grupos de forma conjunta, acarretando vieses importantes para a pesquisa de determinantes de dividendos no Brasil. Isto porque as empresas que pagam acima do obrigatório legal e contratual são as reais tomadoras da decisão de pagar dividendos, visto que empresas que pagam apenas o obrigatório simplesmente cumprem a legislação.
Análise de integração financeira entre o mercado acionário brasileiro e o argentino: Uma abordagem dinâmica
Authors: Pontuschka Martin , Perlin Marcelo Scherer
Published: October 2019

Neste artigo buscamos verificar a dinâmica da integração financeira entre as séries temporais do índice acionário brasileiro e argentino. Para isto, estimamos um modelo de estado de espaço através do filtro de Kalman, que permite a observação da dinâmica da integração financeira ao longo do tempo. Seguimos a proposta de Haldane e Hall (1991), que sugerem um modelo de espaço de estado para observar convergência entre diferentes séries temporais. Ao estimar o modelo conseguimos observar momentos de convergência e momentos de divergência entre o mercado acionário brasileiro e o argentino ao longo dos anos entre 1987 e 2014. Uma importante evidência foi a observação de divergência entre os índices acionários regionais em momentos de crise nos mercados internacionais. Ou seja, nos momentos de maior estresse nos mercados financeiros, o índice acionário brasileiro apresentou maior convergência em relação aos mercados internacionais do que em relação ao mercado argentino. Esta evidência está de acordo com Manning (2002), o qual verificou o mesmo efeito nos mercados acionários asiáticos durante a crise de 1997.