bluuebunny/crossref_metadata_2025 huggingface dataset:
Vision oder Utopie? Junge Ideen für die Zukunft Europas
Authors: Augustin Friederike , Schubert Jana
Published: August 2019

Although most of the first-time voters and young citizens of the European Union (EU) share a positive attitude towards the EU, less than 30 percent cast their votes in the European elections of 2014. Against this backdrop, this year’s European election campaigns particularly focused on young people aged 15 to 24. In that sense, the youth participation project #EngagEU aimed at motivating young people to vote in the European elections 2019 and at empowering them to formulate concrete political demands. Summarised in the manifesto “Young Ideas for the Future of Europe”, their ideas were presented to the public as well as to Federal President Frank-Walter Steinmeier on 30 April 2019 at the #1stYoung Ci⁠tizens’Convention organised by the Institut für Europäische Politik and discussed with young can­di­da⁠tes for the European elections. Technology-based solutions to combat climate change and an independent monitoring capacity for EU values and democratic principles are concrete demands that political decision-makers might take up in the aftermath of the European elections.
Zukunftsszenarien und Reformoptionen für die Europäische Union: vom Weißbuch der Kommission zu einer flexibleren Arbeitsmethode
Authors: Calliess Christian
Published: August 2019

Tackling the ongoing European ‘polycrisis’ has been complicated by the lack of a consensus between the Member States and among European citizens about the role they want the European Union (EU) to play, its tasks and its future. A Union that has become more diverse due to enlargement now has to deepen in areas that are highly sensitive domestically. Against the backdrop of the scenarios presented in the European Commission’s White Paper on the Future of Europe the author argues for a more flexible working method of the EU. This method should be based on more efficiency by focusing on political priorities and implementing a new concept of cooperative enforcement together with a common understanding of subsidiarity. Where no consensus can be reached greater flexibility and - in the long run - a new architecture of the EU should allow for pioneer groups to move ahead and to lead by positive example.
The Netherlands selling submarines to Taiwan: how to judge government action?
Authors: RUSMAN Paul
Published: August 2019

The Dutch sale of major weapons to Taiwan in 1980 ran counter to the Netherlands’ recent recognition of the People’s Republic of China as the sole representative of China. This led to a rupture of diplomatic relations, an outcome seemingly unexpected in spite of the Dutch Foreign Ministry’s strong opposition to the deal. A few years later a new government composed of the same parties turned down a follow-up order. Why did the Dutch government sail so close to the wind and what made it change course? Such questions are tackled using approaches from international relations theory, such as politico-military strategy, good judgment in foreign policy, and (international) political economy. Yet in this case the analyst cannot be satisfied with easy explanations. Might not a fruitful angle be to consider the Netherlands as a highly competent but small state, driven by the high stakes involved to explore to the limit what little manoeuvring room it had vis-a-vis China?
Conference Circuit: Becoming a leader on campus
Authors: Mech Terrence F.
Published: August 2019

Conference Circuit: Becoming a leader on campus
Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial
Authors: Schuurhuizen Claudia S.E.W. , Braamse Annemarie M.J. , Beekman Aartjan T.F. , Cuijpers Pim , van der Linden Mecheline H.M. , Hoogendoorn Adriaan W. , Berkhof Hans , Sommeijer Dirkje W. , Lustig Vera , Vrijaldenhoven Suzan , Bloemendal Haiko J. , van Groeningen Cees J. , van Zweeden Annette A. , van der Vorst Maurice J.D.L. , Rietbroek Ron , Tromp-van Driel Cathrien S. , Wymenga Machteld N.W. , van der Linden Peter W. , Beeker Aart , Polee Marco B. , Batman Erdogan , Los Maartje , van Bochove Aart , Brakenhoff Jan A.C. , Konings Inge R.H.M. , Verheul Henk M.W. , Dekker Joost
Published: August 2019

Background: This study evaluated the effectiveness of a screening and stepped care program (the TES program) in reducing psychological distress compared with care as usual (CAU) in patients with metastatic colorectal cancer starting with first-line systemic palliative treatment. Patients and Methods: In this cluster randomized trial, 16 hospitals were assigned to the TES program or CAU. Patients in the TES arm were screened for psychological distress with the Hospital Anxiety and Depression Scale and the Distress Thermometer/Problem List (at baseline and 10 and 18 weeks). Stepped care was offered to patients with distress or expressed needs, and it consisted of watchful waiting, guided self-help, face-to-face problem-solving therapy, or referral to specialized mental healthcare. The primary outcome was change in psychological distress over time, and secondary outcomes were quality of life, satisfaction with care, and recognition and referral of distressed patients by clinicians. Linear mixed models and effect sizes were used to evaluate differences. Results: A total of 349 patients were randomized; 184 received the TES program and 165 received CAU. In the TES arm, 60.3% of the patients screened positive for psychological distress, 26.1% of which entered the stepped care program (14.7% used only watchful waiting and 11.4% used at least one of the other treatment steps). The observed low use of the TES program led us to pursue a futility analysis, which showed a small conditional power and therefore resulted in halted recruitment for this study. No difference was seen in change in psychological distress over time between the 2 groups (effect size, −0.16; 95% CI, −0.35 to 0.03; P>.05). The TES group reported higher satisfaction with the received treatment and better cognitive quality of life (all P<.05). Conclusions: As a result of the low use of stepped care, a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer did not improve psychological distress. Our results suggest that enhanced evaluation of psychosocial concerns may improve aspects of patient well-being.
Towards a quantitative model of epidemics during conflicts
Authors: Banerjee Soumya
Published: August 2019

Epidemics may both contribute to and arise as a result of conflict. The effects of conflict on infectious diseases are complex and there have been confounding observations of both increase and decrease in disease outbreaks during and after conflicts. However there is no unified mathematical model that explains all these counter-intuitive observations. There is an urgent need for a quantitative framework for modelling conflicts and epidemics. We introduce a set of mathematical models to understand the role of conflicts in epidemics. Our mathematical framework has the potential to explain the counterintuitive observations and the complex role of human conflicts in epidemics. Our work suggests that aid and peacekeeping organizations should take an integrated approach that combines public health measures, socio-economic development, and peacekeeping in the conflict zone. Our approach exemplifies the role of non-linear thinking in complex systems like human societies. We view our work as a step towards a quantitative model of disease spread in conflicts.
DigestiFlow - reproducible demultiplexing for the single cell era
Authors: Holtgrewe Manuel , Nieminen Mikko , Messerschmidt Clemens , Beule Dieter
Published: August 2019

Summary. Managing raw sequencing data and conversion into sequences (demultiplexing) remains a challenging topic for groups running sequencing devices. They face many challenges in such efforts and solutions range from manual management of spreadsheets to very complex and customized LIMS systems handling much more than just sequencing raw data. In this manuscript, we describe the software package DigestiFlow that focuses on the management of Illumina flow cell sample sheets and raw data. Namely, it allows for automated extraction of flow cell raw data information, management of sample sheets, and the automated (and thus reproducible) demultiplexing of Illumina base calls data.

Availability and Implementation. The software is available under the MIT license at https://github.com/bihealth/digestiflow-server. The client and demux software components are available via Bioconda.
Allogenic stem cell transplant in a patient with classical Kaposi's sarcoma
Authors: Barchas Richard
Published: August 2019

A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.
Developing a global occupational health and safety management system model for Japanese companies
Authors: Kajiki Shigeyuki , Mori Koji , Kobayashi Yuichi , Hiraoka Kou , Fukai Nanae , Uehara Masamichi , Adi Nuri Purwito , Nakanishi Shigemoto
Published: August 2019

Objectives

To develop and validate a global occupational health and safety management system (OHSMS) model for Japanese companies.

Methods

In cooperation with a Japanese company, we established a research team and gathered information on occupational health and safety (OHS) practices in nine countries where the target company operated manufacturing sites. We then developed a model hypothesis via research team meeting. The model hypothesis was introduced to local factories in Indonesia and Thailand as trial sites. We evaluated the roles of the company headquarters, the implementation process, and any improvements in OHS practices at the sites. Based on the results, a global OHSMS model was formalized for global introduction.

Results

The model consisted of both headquarters and site roles. These roles were well-functioning, and OHS at the sites improved. Two issues concerning the functioning of the headquarters were identified: the need to establish a reporting system to the headquarters and the need to support the improvement of specialized human resources. By improving the model hypothesis to address these issues, the model was formalized for global introduction.

Conclusions

The global OHSMS model was based on the use of methods and specialized human resources relevant to each region and their common objectives, as well as evaluation indicators based on the minimum requirements of the company headquarters. To verify the effectiveness of this model, the experiment should be extended to other countries.
Safety and Tolerability of Thrombin Inhibition in Scleroderma‐Associated Interstitial Lung Disease
Authors: Silver R. M. , Wilson D. A. , Akter T. , Atanelishvili I. , Huggins J. T. , Kajdasz K. , Highland K. B. , Nietert P. J. , Bogatkevich G. S.
Published: August 2019

Objective

Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) (scleroderma) and the leading cause of scleroderma‐related deaths. There exists an unmet need for a new drug therapy for ILD‐complicated SSc. Substantial evidence supports an important role for thrombin in the pathogenesis of SSc‐associated ILD (hereafter SSc‐ILD), and targeting thrombin with a direct thrombin inhibitor could prove to be a novel and effective treatment strategy. As a first step toward designing a clinical trial to test the efficacy of thrombin inhibition in SSc‐ILD, we conducted this study to test the safety and tolerability of dabigatran in patients with SSc‐ILD.

Methods

We performed a prospective, single‐center, open‐label treatment trial with the direct thrombin inhibitor, dabigatran, in patients with SSc‐ILD. Any patient with a history of gastrointestinal hemorrhage or gastric antral vascular ectasia was excluded. Blood monitoring was performed monthly, and patient‐reported outcomes, pulmonary function tests, and skin scores were obtained at baseline and at 3‐ and 6‐month visits. Bronchoscopy with bronchoalveolar lavage (BAL) was performed at baseline and at 6 months for measurement of lung thrombin activity.

Results

Of 15 patients with SSc‐ILD, 14 completed 6 months of treatment with dabigatran at 75 mg taken orally twice daily. Adverse events were uncommon and usually mild or unrelated to the study medication. No serious adverse event was observed. Dabigatran was well tolerated, and we observed no significant gastrointestinal, pulmonary, or other safety issues or intolerability. BAL fluid thrombin activity decreased or remained stable in 13 of 14 (92.8%) subjects.

Conclusion

Dabigatran appears to be safe and well tolerated in patients with SSc‐ILD. A larger randomized controlled trial to test the efficacy of direct thrombin inhibition with dabigatran can be considered.
Upconversion Luminescence Sandwich Assay For Detection of Influenza H7 Subtype
Authors: Tsang Ming‐Kiu , Wong Yuen‐Ting , Tsoi Tik‐Hung , Wong Wing‐Tak , Hao Jianhua
Published: August 2019

With large anti‐Stokes shifts and background‐free signals, upconversion luminescent (UCL) screening assays have been a promising method to reduce the transmission of influenza epidemic, which can critically alleviate the disease burden and extra annual deaths. In this work, a luminescent resonance energy transfer sandwich assay is developed, which utilizes core–shell upconversion nanoparticles and gold nanoparticles as the donor and acceptor, respectively. The influenza H7 gene of H7N9 virus is used as the target for optimization of the assay. Importantly, the hybridization time of the assay is ≈40 min and the specificity test indicates the probes are specific toward the H7 target. The limit of detection of the system is ≈134 × 10−12 m (≈3.22 × 1010 molecules). Moreover, the assay is tested with the use of polymerase chain reaction validated samples from human isolates. The results are promising for implanting future on‐site rapid influenza screening application.
Switching between Crystallization from the Glassy and the Undercooled Liquid Phase in Phase Change Material Ge2Sb2Te5
Authors: Pries Julian , Wei Shuai , Wuttig Matthias , Lucas Pierre
Published: August 2019

Controlling crystallization kinetics is key to overcome the temperature–time dilemma in phase change materials employed for data storage. While the amorphous phase must be preserved for more than 10 years at slightly above room temperature to ensure data integrity, it has to crystallize on a timescale of several nanoseconds following a moderate temperature increase to near 2/3 Tm to compete with other memory devices such as dynamic random access memory (DRAM). Here, a calorimetric demonstration that this striking variation in kinetics involves crystallization occurring either from the glassy or from the undercooled liquid state is provided. Measurements of crystallization kinetics of Ge2Sb2Te5 with heating rates spanning over six orders of magnitude reveal a fourfold decrease in Kissinger activation energy for crystallization upon the glass transition. This enables rapid crystallization above the glass transition temperature Tg. Moreover, highly unusual for glass‐forming systems, crystallization at conventional heating rates is observed more than 50 °C below Tg, where the atomic mobility should be vanishingly small.
Safe, Metal‐Free, and Direct Synthesis of Dialkyl Acylmethylidenehydrazine‐1,1‐dicarboxylates from Dimethylsulfoxonium Acylmethylides and Dialkyl Azodicarboxylates
Authors: Zhou Bingnan , Dong Jun , Xu Jiaxi
Published: August 2019

N‐Acylhydrazones are versatile electrophiles for the synthesis of nitrogen‐containing compounds. Dialkyl acylmethylidenehydrazine‐1,1‐dicarboxylates are a class of N‐acylhydrazones and were prepared efficiently from dimethylsulfoxonium acylmethylides and dialkyl azodicarboxylates. The reaction is temperature‐controlled, generating tetraalkyl 3,6‐diacyl‐1,2,4,5‐tetrazinane‐1,2,4,5‐tetracarboxylates as major products accompanied by dialkyl acylmethylidenehydrazine‐1,1‐dicarboxylates as byproducts at low temperature, or dialkyl acylmethylidenehydrazine‐1,1‐dicarboxylates only at high temperature. The current direct synthetic method is a safe and transition‐metal‐free route for the synthesis of dialkyl acylmethylidenehydrazine‐1,1‐dicarboxylates.

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Value of supplementing vitamin C to the triple therapy on the eradication rates ofHelicobacter pyloriinfection
Authors: El Shahawy Mohamed S. , El Metwaly Ibrahim , Shady Zakarya M.
Published: August 2019

Several clinical studies have shown that higher prevalence ofHelicobacter pyloriinfection is associated with low vitamin C (Vit C) level in serum. The aim of this study was to assess the effect of supplementation of Vit C on the eradication rates of clarithromycin‐based triple therapy forH. pyloriinfection. This study included 100 patients diagnosed withH. pylorigastritis using magnifying narrow‐band imaging endoscopy supported by stool antigen test. Patients were divided into two groups: Patients in group A (n = 50) received amoxicillin, clarithromycin, and esomeprazole for 2 weeks while patients in group B (n = 50) received Vit C for 4 weeks, in addition to amoxicillin, clarithromycin, and esomeprazole for 2 weeks. The eradication rates were assessed using per‐protocol (PP) and intention‐to‐treat (ITT) analysis. Our results revealed that, eradication was achieved in 31 (70.45%) of 44 patients by PP and 31 (62.%) of 50 by ITT analysis in group A, while in group B, eradication was achieved in 34 (73.91%) of 46 patients by PP and 34 (68%) of 50 by ITT analysis. However, when Vit C supplementation was added to the clarithromycin‐based triple therapy it was observed that there were no statistically significant differences between groups A and B (P= .663 in ITT analysis andP= .727 in PP analysis).Our results demonstrated that supplementing Vit C to clarithromycin‐based triple therapy did not provide an additional advantage for achieving significantly higher eradication rates forH. pylori‐related chronic gastritis and most likely to be preventive rather than curative.
Tunable Hydrogen Release from Amine–Boranes via their Insertion into Functional Polystyrenes
Authors: Ledoux Audrey , Brunet Juliette , Raynaud Jean , Lacôte Emmanuel
Published: August 2019

Polystyrene‐g‐boramine random copolymers are dihydrogen reservoirs with tunable dehydrogenation temperatures, which can be adjusted by selecting the boramine content in the copolymers. They display a unique dihydrogen thermal release profile, which is a direct consequence of the insertion of the amine–boranes in a polymeric scaffold, and not from a direct modification of the electronics or sterics of the amine–borane function. Finally, the mixture of polystyrene‐g‐boramines with conventional NH3‐BH3 (borazane) allows for a direct access to organic/inorganic hybrid dihydrogen reservoirs with a maximal H2 loading of 8 wt %. These exhibit a dehydrogenation temperature lower than that of either the borazane or the polystyrene‐g‐boramines taken separately.
Bridging Crystal Engineering and Drug Discovery by Utilizing Intermolecular Interactions and Molecular Shapes in Crystals
Authors: Spackman Peter R. , Yu Li‐Juan , Morton Craig J. , Parker Michael W. , Bond Charles S. , Spackman Mark A. , Jayatilaka Dylan , Thomas Sajesh P.
Published: August 2019

Most structure‐based drug discovery methods utilize crystal structures of receptor proteins. Crystal engineering, on the other hand, utilizes the wealth of chemical information inherent in small‐molecule crystal structures in the Cambridge Structural Database (CSD). We show that the interaction surfaces and shapes of molecules in experimentally determined small‐molecule crystal structures can serve as effective tools in drug discovery. Our description of the shape and interaction propensities of molecules in their crystal structures can be used to screen them for specific binding compatibility with protein targets, as demonstrated through the high‐throughput profiling of around 138 000 small‐molecule structures in the CSD and a series of drug–protein crystal structures. Electron‐density‐based intermolecular boundary surfaces in small‐molecule crystal structures and in target‐protein pockets are utilized to identify potential ligand molecules from the CSD based on 3D shape and intermolecular interaction matching.
Copper‐catalyzed one‐pot coupling reactions of aldehydes (ketones), tosylhydrazide and 2‐amino(benzo)thiazoles: An efficient strategy for the synthesis of N‐alkylated (benzo)thiazoles
Authors: Xie Zengyang , Chen Ruijiao , Ma Mingfang , Kong Lingdong , Liu Jun , Wang Cunde
Published: August 2019

An efficient and practical C–N bond formation methodology for the synthesis of N‐alkylated (benzo)thiazoles was developed, via the copper‐catalyzed one‐pot two‐step reactions of 2‐amino(benzo)thiazoles and aldehydes (ketones) with tosylhydrazide. This cross‐coupling reaction proceeded smoothly and tolerated a broad range of functional groups (46 examples). A variety of functionalized N‐alkylated (benzo)thiazoles were obtained in moderate to high yields. Notably, gram‐scale synthesis of fanetizole (anti‐inflammatory drug) was also realized through this protocol.
Cationic organotin cluster [t‐Bu2Sn(OH)(H2O)]22+2OTf−‐catalyzed one‐pot three‐component syntheses of 5‐substituted 1H‐tetrazoles and 2,4,6‐triarylpyridines in water
Authors: Wang Hongshe , Zhao Weixing , Du Juan , Wei Fenyan , Chen Qi , Wang Xiaomei
Published: August 2019

The cationic organotin cluster [t‐Bu2Sn(OH)(H2O)]22+2OTf− is easy to prepare and stable in air. The catalytic activity of [t‐Bu2Sn(OH)(H2O)]22+2OTf− as a neutral organotin Lewis acid catalyst is probed through the one‐pot three‐component syntheses of 5‐substituted 1H‐tetrazoles from aldehydes, hydroxylamine hydrochloride and sodium azide, and of 2,4,6‐triarylpyridines from aromatic aldehydes, substituted acetophenones and ammonium acetate. The reactions proceed well in the presence of 1 mol% of [t‐Bu2Sn(OH)(H2O)]22+2OTf− in water and provide the corresponding 5‐substituted 1H‐tetrazoles and 2,4,6‐triarylpyridines in good to excellent yields. The method reported has several advantages such as the catalyst being neutral, low catalyst loading and use of water as a green solvent.
Retardation of Crystallization through the Addition of Dairy Phospholipids
Authors: Cooper Zachary , Simons Casey , Martini Silvana
Published: August 2019

The objective of this work was to identify the effects that milk phospholipids (PL) have on crystallization of anhydrous milk fat (AMF). Three mixtures were prepared by adding 0%, 0.01%, and 0.1% PL to AMF. Each mixture was crystallized for 90 min at 24, 26, and 28 °C. The solid fat content was measured as a function of time and fitted to the Avrami equation. Melting point, thermal behavior, viscoelastic properties, and crystal morphology were all measured at 90 min. All assays were repeated, as well as hardness, after being stored at 5 °C for 48 hours. Samples containing PL showed slower crystallization as concentration increased especially at higher temperatures (26 and 28 °C). The addition of PL caused a difference in crystal morphology resulting in visibly larger crystals at 90 min. The elasticity and hardness at 90 min were influenced by the addition of PL at 24 °C with lower values obtained in samples with PL compared to the AMF alone. No differences in hardness nor in elasticity was observed for samples crystallized at 26 and 28 °C. A decrease in melting enthalpy was observed in samples with PL indicating a reduction in crystallization at all temperatures, which was supported by crystal morphology.
Knockdown of arylalkylamine N‐acetyltransferase‐like 2 in Drosophila melanogaster
Authors: Anderson Ryan L. , Wallis Dylan J. , Aguirre Alexander , Holliday Dean , Merkler David J.
Published: August 2019

Drosophila melanogaster produces fatty acid amides, and thus, provides a model to unravel the pathways for their biosynthesis. We previously demonstrated that arylalkylamine N‐acetyltransferase‐like 2 (AANATL2) from D. melanogaster will catalyze the formation of long‐chain N‐acylserotonins and N‐acyldopamines in vitro. Generating silencing RNA via the UAS/GAL4 bipartite approach for targeted gene expression effectively decreased the endogenous levels of the AANATL2 transcripts in D. melanogaster, as shown by reverse transcription quantitative polymerase chain reaction. Consistent with these data, western blot analysis of the offspring of the AANATL2 knockdown flies using an anti‐AANATL2 antibody revealed a significant reduction in the expression of the AANATL2 protein. Reduced expression of AANATL2 decreased the cellular levels of N‐palmitoyldopamine (PALDA), providing strong evidence that AANATL2 is responsible for the biosynthesis of PALDA in vivo. This is the first time that the expression of an AANAT has been reduced in D. melanogaster to link one of these enzymes to the in vivo production of an N‐acylarylalkylamide.
Decade‐long X‐ray observations of HESS J0632+057
Authors: Malyshev Denys , Chernyakova Maria , Santangelo Andrea , Pühlhofer Gerd
Published: August 2019

We present the results of a decade of X‐ray observations of the gamma ray loud binary HESS J0632+057 and interpret the available broadband data in view of the system geometry and emission mechanisms. We have performed an analysis of all X‐ray data available to date from Swift, XMM‐Newton, Chandra, NuSTAR, and Suzaku. We refine the orbital period of the system to be days (95% c.l.), consistent with previous studies but measured with significantly better accuracy. We report on a hydrogen column density and spectral slope variation along the orbit. We argue that the observed variability can be explained within an “inclined disk” model in which the orbit of the compact object is inclined to the disk of the Be star. We show that the observed X‐ray to TeV emissions can originate from a broken cut‐off power‐law population of electrons and describe a way in which future X‐ray/TeV observations can distinguish between the proposed model and the alternative flip‐flop emission scenario of this system.
Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study
Authors: Benachenhou Sérine , Etcheverry Antoine , Galarneau Luc , Dubé Jean , Çaku Artuela
Published: August 2019

Autism spectrum disorder (ASD) has been associated with low cholesterol levels in a limited number of studies. However, the prevalence of hypocholesterolemia as well as the degree of association with ASD remains to be elucidated. We therefore sought to investigate the lipid profiles of a group of French‐Canadian ASD individuals. The medical records of 79 ASD individuals and 79 age and gender‐matched healthy controls were retrospectively reviewed. The fasting lipid profiles including total cholesterol (TC), high‐density lipoprotein, triglycerides, and low‐density lipoprotein were extracted for individuals of both groups along with the following clinical data: anthropometric measurements, medication use and associated disorders. Lipid parameters were compared to age and gender‐based normative population and categorized in centile groups. The prevalence of hypocholesterolemia was revealed to be more than threefold higher in ASD individuals as compared to the general population (23%; P = 0.005). The 25th centile was determined as a potential TC threshold that could best predict the ASD (odds ratio [OR] = 3.04; 95% confidence interval [CI]: 1.58–6.65; P < 0.001). This study identified specific ASD comorbidities associated with hypocholesterolemia: TC levels below the 10th centile were associated with a higher rate of ASD‐associated intellectual disability (OR = 3.33; 95% CI: 1.26–8.00) and anxiety/depression (OR = 4.74; 95% CI: 1.40–15.73). Overall, these results support a potential association between hypocholesterolemia and ASD occurrence. Application of this study to larger populations is urging to provide more extensive data that may further elucidate the association between hypocholesterolemia and ASD. Autism Res 2019, 12: 1860–1869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Association of autism spectrum disorder (ASD) with abnormally low levels of cholesterol (hypocholesterolemia) has been documented before. These studies were incomplete, and the conclusion remains speculative. Here, we reviewed the medical records of 79 French‐Canadian ASD individuals and compared their total cholesterol (TC) levels to healthy individuals matched for age and gender. We observed four times more hypocholesterolemia in ASD than in the general population. Furthermore, low TC in ASD was associated with higher rates of ASD‐associated intellectual disability and anxiety/depression. Our results support an association between hypocholesterolemia and ASD and open novel opportunities for the diagnosis and treatment of specific forms of ASD.
The role of motivation and volition in economic decisions: Evidence from eye movements and pupillometry
Authors: Ludwig Jonas , Jaudas Alexander , Achtziger Anja
Published: August 2019

Economic decisions usually involve high stakes, real consequences, and some degree of personal risk. This article explores the impact of motivational and volitional states on economic decision processes in an incentivized lottery choice task. We investigated the patterns of decision time, choice, information search, and pupil dilation dependent on an experimental manipulation of motivation and volition, that is, the deliberative and the implemental mindset. The results indicated that choice preferences in economic decisions were robust and remained unaffected by motivational and volitional states, but decision processes were notably impacted. Decision makers in a deliberative state of mind searched for information more extensively and made slower decisions than the baseline. The implemental mindset was associated with more attention paid to the probability attributes of the gambles relative to the deliberative mindset. Furthermore, we observed that gamble outcomes that entailed no win at all (i.e., zero outcomes) played an important role for information search. These outcomes were largely disregarded in terms of predecisional information search but elicited pupillary responses similar to very high outcome lotteries. These results inform the current debate about the zero effect in risky choice. We also discuss the potential of eye‐tracking studies of risky choice to dissolve ambiguities concerning the contributions of effort and arousal to modulating pupillary response. Implications for theoretical advances in decision research are discussed.
National risk prediction model for perioperative mortality in non-cardiac surgery
Authors: Campbell D , Boyle L , Soakell-Ho M , Hider P , Wilson L , Koea J , Merry A F , Frampton C , Short T G
Published: August 2019

Background

Many multivariable models to calculate mortality risk after surgery are limited by insufficient sample size at development or by application to cohorts distinct from derivation populations. The aims of this study were to validate the Surgical Outcome Risk Tool (SORT) for a New Zealand population and to develop an extended NZRISK model to calculate 1-month, 1-year and 2-year mortality after non-cardiac surgery.

Methods

Data from the New Zealand National Minimum Data Set for patients having surgery between January 2013 and December 2014 were used to validate SORT. A random 75 per cent split of the data was used to develop the NZRISK model, which was validated in the other 25 per cent of the data set.

Results

External validation of SORT in the 360 140 patients who underwent surgery in the study period showed good discrimination (area under the receiver operating characteristic curve (AUROC) value of 0·906) but poor calibration (McFadden's pseudo-R2 0·137, calibration slope 5·32), indicating it was invalid in this national surgical population. Internal validation of the NZRISK model, which incorporates sex and ethnicity in addition to the variables used in SORT for 1-month, 1-year and 2-year outcomes, demonstrated excellent discrimination with AUROC values of 0·921, 0·904 and 0·895 respectively, and excellent calibration (McFadden's pseudo-R2 0·275, 0·308 and 0·312 respectively). Calibration slopes were 1·12, 1·02 and 1·02 respectively.

Conclusion

The SORT performed poorly in this national population. However, inclusion of sex and ethnicity in the NZRISK model improved performance. Calculation of mortality risk beyond 30 days after surgery adds to the utility of this tool for shared decision-making.
Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases
Authors: Wang X-Y , Zhang R , Wang Z , Geng Y , Lin J , Ma K , Zuo J-L , Lu L , Zhang J-B , Zhu W-W , Chen J-H
Published: August 2019

Background

Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta-analysis was undertaken to evaluate its prognostic value.

Methods

References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease-free survival after hepatic resection between patients with CRLM originating from right- or left-sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this.

Results

The final analysis included 21 953 patients from 45 study cohorts. Compared with left-sided primary tumour location, right-sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease-free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right-sided primary tumour location on overall survival was more prominent in the non-Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01).

Conclusion

This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.
Nationwide study of appendicitis in children
Authors: Omling E , Salö M , Saluja S , Bergbrant S , Olsson L , Persson A , Björk J , Hagander L
Published: August 2019

Background

Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease.

Methods

A nationwide cohort study of all paediatric appendicitis cases in Sweden, 2001–2014, was undertaken, including incidence of disease in different population strata, with trends over time. The risk of complicated disease was determined by regression methods, with travel time as the primary exposure and individual-level socioeconomic determinants as independent variables.

Results

Some 38 939 children with appendicitis were identified. Of these, 16·8 per cent had complicated disease, and the estimated risk of paediatric appendicitis by age 18 years was 2·5 per cent. Travel time to the treating hospital was not associated with complicated disease (adjusted odds ratio (OR) 1·00 (95 per cent c.i. 0·96 to 1·05) per 30-min increase; P = 0·934). Level of education (P = 0·177) and family income (P = 0·120) were not independently associated with increased risk of complicated disease. Parental unemployment (adjusted OR 1·17, 95 per cent c.i. 1·05 to 1·32; P = 0·006) and having parents born outside Sweden (1 parent born in Sweden: adjusted OR 1·12, 1·01 to 1·25; both parents born outside Sweden: adjusted OR 1·32, 1·18 to 1·47; P < 0·001) were associated with an increased risk of complicated appendicitis.

Conclusion

Every sixth child diagnosed with appendicitis in Sweden has a more complicated course of disease. Geographical distance to the surgical facility was not a risk factor for complicated appendicitis.
Population-based study of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ
Authors: Keymeulen K B I M , Geurts S M E , Lobbes M B I , Heuts E M , Duijm L E M , Kooreman L F S , Voogd A C , Tjan-Heijnen V C G
Published: August 2019

Background

Determinants of the use of breast MRI in patients with ductal carcinoma in situ (DCIS) in the Netherlands were studied, and whether using MRI influenced the rates of positive resection margins and mastectomies.

Methods

All women aged less than 75 years, and diagnosed with DCIS between 2011 and 2015, were identified from the Netherlands Cancer Registry. Multivariable logistic regression analyses were performed, adjusting for incidence year, age, hospital type, DCIS grade and multifocality.

Results

Breast MRI was performed in 2382 of 10 415 DCIS cases (22·9 per cent). In multivariable analysis, patients aged less than 50 years, those with high- or intermediate-grade DCIS and patients with multifocal disease were significantly more likely to have preoperative MRI. Patients undergoing MRI were more likely to have a mastectomy, either as first surgical treatment or following breast-conserving surgery (BCS) in the event of positive margins (odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33). The risk of positive surgical margins after BCS was similar for those with versus without MRI. The secondary mastectomy rate after BCS was higher in patients who had MRI, especially in women aged less than 50 years (OR 1·94, 1·31 to 2·89). All findings were similar for low- and intermediate/high-grade DCIS.

Conclusion

Adding MRI to conventional breast imaging did not improve surgical outcome in patients diagnosed with primary DCIS. The likelihood of undergoing a mastectomy was twice as high in the MRI group, and no reduction in the risk of margin involvement was observed after BCS.
Germline mismatch repair gene variants analyzed by universal sequencing in Japanese cancer patients
Authors: Kiyozumi Yoshimi , Matsubayashi Hiroyuki , Horiuchi Yasue , Higashigawa Satomi , Oishi Takuma , Abe Masato , Ohnami Sumiko , Urakami Kenichi , Nagashima Takeshi , Kusuhara Masatoshi , Miyake Hidehiko , Yamaguchi Ken
Published: August 2019

Background

Lynch syndrome (LS) is the commonest inherited cancer syndrome caused by pathogenic variants of germline DNA mismatch repair (g.MMR) genes. Genome‐wide sequencing is now increasingly applied for tumor characterization, but not for g.MMR. The aim of this study was to evaluate the incidence and pathogenicity of g.MMR variants in Japanese cancer patients.

Methods

Four g.MMR genes (MLH1, MSH2, MSH6, and PMS2) were analyzed by next generation sequencing in 1058 cancer patients (614 male, 444 female; mean age 65.6 years) without past diagnosis of LS. The g.MMR variant pathogenicity was classified based on the ClinVar 2015 database. Tumor MMR immunohistochemistry, microsatellite instability (MSI), and BRAF sequencing were also investigated in specific cases.

Results

Overall, 46 g.MMR variants were detected in 167 (15.8%) patients, 17 likely benign variants in 119 patients, 24 variants of uncertain significance (VUSs) in 68 patients, two likely pathogenic variants in two patients, and three pathogenic variants in three (0.3%) patients. The three pathogenic variants included two colorectal cancers with MLH1 loss and high MSI and one endometrial cancer with MSH6 loss and microsatellite stability. Two likely pathogenic variants were shifted to VUSs by ClinVar (2018). One colon cancer with a likely benign variant demonstrated MLH1 loss and BRAF mutation, but other nonpathogenic variants showed sustained MMR and microsatellite stability.

Conclusions

Universal sequencing of g.MMR genes demonstrated sundry benign variants, but only a small proportion of cancer patients had pathogenic variants. Pathogenicity evaluation using the ClinVar database agreed with MSI, MMR immunohistochemistry, and BRAF sequencing.
Prolonged postoperative ileus in gastric surgery: Is there any difference between laparoscopic and open surgery?
Authors: Liang Wenquan , Li Jiyang , Zhang Wang , Liu Jie , Li Mingsen , Gao Yunhe , Wang Ning , Cui Jianxin , Zhang Kecheng , Xi Hongqing , Wei Bo , Chen Lin
Published: August 2019

Background

Prolonged postoperative ileus (PPOI) is a common complication after abdominal surgery, but data about risk factors of PPOI for patients with gastric cancer are rare. We sought to investigate the impact of laparoscopic versus open surgery for PPOI after gastric cancer surgery.

Methods

A retrospective cohort study was conducted using a registry database consecutively collected from June 2016 to March 2017. PPOI was defined as no bowel function persisting for more than 4 days. Univariate analysis and multiple logistic regression models were performed to investigate risk factors, and stratified analysis was carried out to examine the primary association at different levels of a potential confounding factor.

Results

A total of 162 patients composed of 63 patients undergoing laparotomy and 99 patients undergoing laparoscopy were enrolled and PPOI was observed in 32 (19.75%) patients. Risk factors significantly correlated with PPOI were as follows: open surgery, older age, late surgical pathologic staging, postoperative use of opioid analgesic, low level of postoperative albumin and serum potassium. Compared to open surgery, the laparoscopic surgery was a strong protective factor for PPOI after adjusting related variables (OR = 0.17, CI: 0.05‐0.52, P = .002). There was an interaction between surgical methods and the postoperative WBC level (P for interaction = .007). In the two group stratified analysis of WBC, laparoscopic surgery had a significant lower risk of PPOI than open group for the patients with WBC counts above the middle level in crude or adjusted models. This result remained significantly in the three group stratified analysis for the patients with WBC counts in the middle and or high tertile groups.

Conclusions

PPOI is a common postoperative complication of patients after gastrectomy. Laparoscopic surgery is associated with decreased risk of PPOI in gastric surgery. Patients who underwent open surgery and presented with high level of WBC should be cautious with PPOI.
PTTG1 is involved in TNF‐α‐related hepatocellular carcinoma via the induction of c‐myc
Authors: Lin Xianyi , Yang Yidong , Guo Yunwei , Liu Huiling , Jiang Jie , Zheng Fengping , Wu Bin
Published: August 2019

Hepatocellular carcinoma (HCC) is a malignant disease caused by a variety of factors. However, the genomic and molecular aberrations in HCC are largely unknown. Herein, pituitary tumor transforming gene 1 (PTTG1) was discovered as a potential inflammation‐related oncogene in HCC, and its functions and molecular mechanisms were investigated. mRNA expression microarray, real‐time polymerase chain reaction (PCR), immunohistochemistry, and western blotting analyses revealed that PTTG1 is upregulated in HCC. Further in vitro and in vivo studies indicated that the proinflammatory cytokine tumor necrosis factor‐α (TNF‐α) induces PTTG1 expression, and PTTG1 was found to upregulate c‐myc, a well‐known oncogene. Downregulation of PTTG1 reduced c‐myc and proliferating cell nuclear antigen (PCNA) expression and inhibited cell proliferation. Interestingly, inhibition of c‐myc by 10058‐F4 did not affect PTTG1, which suggests that PTTG1 regulates c‐myc expression. Furthermore, PTTG1 expression levels are inversely correlated with HCC patient survival, indicating an independent prognostic biomarker for patients with HCC. Our data demonstrate that PTTG1 is involved in TNF‐α‐related HCC via c‐myc induction and that PTTG1 may be a potential therapeutic target for HCC.
Covalent versus Noncovalent Binding of Ruthenium η6‐p‐Cymene Complexes to Zinc‐Finger Protein NCp7
Authors: Sheng Yaping , Hou Zhuanghao , Cui Shiyong , Cao Kaiming , Yuan Siming , Sun Mei , Kljun Jakob , Huang Guangming , Turel Iztok , Liu Yangzhong
Published: August 2019

Ruthenium–arene complexes are a unique class of organometallic compounds that have been shown to have prominent therapeutic potencies. Here, we have investigated the interactions of Ru‐cymene complexes with a zinc‐finger protein NCp7, aiming to understand the effects of various ligands on the reaction. Five different binding modes were observed on selected Ru‐complexes. Ru‐cymene complex can bind to proteins through either noncovalent binding alone or through a combination of covalent and noncovalent binding modes. Moreover, the noncovalent interaction can promote the coordination of RuII to NCp7, resulting synergistic effects of the different ligands. The binding of Ru(Cym) complexes leads to dysfunction of NCp7 through zinc‐ejection and structural perturbation. These results indicate that the reactivity of Ru‐complexes can be modulated by ligands through different approaches, which could be closely correlated to their different therapeutic effects.
Strategies for Bioelectrochemical CO2 Reduction
Authors: Yuan Mengwei , Kummer Matthew J. , Minteer Shelley D.
Published: August 2019

Atmospheric CO2 is a cheap and abundant source of carbon for synthetic applications. However, the stability of CO2 makes its conversion to other carbon compounds difficult and has prompted the extensive development of CO2 reduction catalysts. Bioelectrocatalysts are generally more selective, highly efficient, can operate under mild conditions, and use electricity as the sole reducing agent. Improving the communication between an electrode and a bioelectrocatalyst remains a significant area of development. Through the examples of CO2 reduction catalyzed by electroactive enzymes and whole cells, recent advancements in this area are compared and contrasted.