bluuebunny/crossref_metadata_2025 huggingface dataset:
FullMeSH: improving large-scale MeSH indexing with full text
Authors: Dai Suyang , You Ronghui , Lu Zhiyong , Huang Xiaodi , Mamitsuka Hiroshi , Zhu Shanfeng
Published: October 2019

Motivation

With the rapidly growing biomedical literature, automatically indexing biomedical articles by Medical Subject Heading (MeSH), namely MeSH indexing, has become increasingly important for facilitating hypothesis generation and knowledge discovery. Over the past years, many large-scale MeSH indexing approaches have been proposed, such as Medical Text Indexer, MeSHLabeler, DeepMeSH and MeSHProbeNet. However, the performance of these methods is hampered by using limited information, i.e. only the title and abstract of biomedical articles.

Results

We propose FullMeSH, a large-scale MeSH indexing method taking advantage of the recent increase in the availability of full text articles. Compared to DeepMeSH and other state-of-the-art methods, FullMeSH has three novelties: (i) Instead of using a full text as a whole, FullMeSH segments it into several sections with their normalized titles in order to distinguish their contributions to the overall performance. (ii) FullMeSH integrates the evidence from different sections in a ‘learning to rank’ framework by combining the sparse and deep semantic representations. (iii) FullMeSH trains an Attention-based Convolutional Neural Network for each section, which achieves better performance on infrequent MeSH headings. FullMeSH has been developed and empirically trained on the entire set of 1.4 million full-text articles in the PubMed Central Open Access subset. It achieved a Micro F-measure of 66.76% on a test set of 10 000 articles, which was 3.3% and 6.4% higher than DeepMeSH and MeSHLabeler, respectively. Furthermore, FullMeSH demonstrated an average improvement of 4.7% over DeepMeSH for indexing Check Tags, a set of most frequently indexed MeSH headings.

Availability and implementation

The software is available upon request.

Supplementary information

Supplementary data are available at Bioinformatics online.
Fifty per cent and all that: what Haldane actually said
Authors: Cook Laurence M , Turner John R G
Published: October 2019

In 1924, J. B. S. Haldane used the observation of increasing melanic frequencies in peppered moths (Biston betularia L.) to illustrate strong selection in a natural population. Since the phenomenon was first observed, there has been criticism and misinterpretation of work on industrial melanism in moths coming from a number of directions, increasingly on the Internet. Haldane’s calculation, its reception and his other interests in peppered moths are reviewed. An example of Internet comments attributing opinions to him, and their origin and background, are discussed.
New insights into cortico-basal-cerebellar connectome: clinical and physiological considerations
Authors: Quartarone Angelo , Cacciola Alberto , Milardi Demetrio , Ghilardi Maria Felice , Calamuneri Alessandro , Chillemi Gaetana , Anastasi Giuseppe , Rothwell John
Published: October 2019

The current model of the basal ganglia system based on the ‘direct’, ‘indirect’ and ‘hyperdirect’ pathways provides striking predictions about basal ganglia function that have been used to develop deep brain stimulation approaches for Parkinson’s disease and dystonia. The aim of this review is to challenge this scheme in light of new tract tracing information that has recently become available from the human brain using MRI-based tractography, thus providing a novel perspective on the basal ganglia system. We also explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum in the pathophysiology of movement disorders.
High frequency oscillations in MEG: next steps in source imaging for focal epilepsy
Authors: van Klink Nicole , Zijlmans Maeike
Published: October 2019

This scientific commentary refers to ‘Magnetoencephalography imaging of high frequency oscillations strengthens presurgical localization and outcome prediction’, by Velmurugan et al. (doi:10.1093/brain/awz284).
Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy
Authors: Chandrasekaran Krish , Salimian Mohammad , Konduru Sruthi R , Choi Joungil , Kumar Pranith , Long Aaron , Klimova Nina , Ho Cheng-Ying , Kristian Tibor , Russell James W
Published: October 2019

In diabetic neuropathy, there is activation of axonal and sensory neuronal degeneration pathways leading to distal axonopathy. The nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase enzyme, Sirtuin 1 (SIRT1), can prevent activation of these pathways and promote axonal regeneration. In this study, we tested whether increased expression of SIRT1 protein in sensory neurons prevents and reverses experimental diabetic neuropathy induced by a high fat diet (HFD). We generated a transgenic mouse that is inducible and overexpresses SIRT1 protein in neurons (nSIRT1OE Tg). Higher levels of SIRT1 protein were localized to cortical and hippocampal neuronal nuclei in the brain and in nuclei and cytoplasm of small to medium sized neurons in dorsal root ganglia. Wild-type and nSIRT1OE Tg mice were fed with either control diet (6.2% fat) or a HFD (36% fat) for 2 months. HFD-fed wild-type mice developed neuropathy as determined by abnormal motor and sensory nerve conduction velocity, mechanical allodynia, and loss of intraepidermal nerve fibres. In contrast, nSIRT1OE prevented a HFD-induced neuropathy despite the animals remaining hyperglycaemic. To test if nSIRT1OE would reverse HFD-induced neuropathy, nSIRT1OE was activated after mice developed peripheral neuropathy on a HFD. Two months after nSIRT1OE, we observed reversal of neuropathy and an increase in intraepidermal nerve fibre. Cultured adult dorsal root ganglion neurons from nSIRT1OE mice, maintained at high (30 mM) total glucose, showed higher basal and maximal respiratory capacity when compared to adult dorsal root ganglion neurons from wild-type mice. In dorsal root ganglion protein extracts from nSIRT1OE mice, the NAD+-consuming enzyme PARP1 was deactivated and the major deacetylated protein was identified to be an E3 protein ligase, NEDD4-1, a protein required for axonal growth, regeneration and proteostasis in neurodegenerative diseases. Our results indicate that nSIRT1OE prevents and reverses neuropathy. Increased mitochondrial respiratory capacity and NEDD4 activation was associated with increased axonal growth driven by neuronal overexpression of SIRT1. Therapies that regulate NAD+ and thereby target sirtuins may be beneficial in human diabetic sensory polyneuropathy.
miR-203 is an independent molecular predictor of prognosis and treatment outcome in ovarian cancer: a multi-institutional study
Authors: Panoutsopoulou Konstantina , Avgeris Margaritis , Mavridis Konstantinos , Dreyer Tobias , Dorn Julia , Obermayr Eva , Reinthaller Alexander , Michaelidou Kleita , Mahner Sven , Vergote Ignace , Vanderstichele Adriaan , Braicu Ioana , Sehouli Jalid , Zeillinger Robert , Magdolen Viktor , Scorilas Andreas
Published: October 2019

Ovarian cancer (OC) accounts for the most gynecological cancer-related deaths in developed countries. Unfortunately, the lack of both evident early symptoms and effective asymptomatic population screening results in late diagnosis and inevitably poor prognosis. Hence, it is urgent to identify novel molecular markers to support personalized prognosis. In the present study, we have analyzed the clinical significance of miR-203 in OC using two institutionally independent cohorts. miR-203 levels were quantified in a screening (n = 125) and a validation cohort (n = 100, OVCAD multicenter study). Survival analysis was performed using progression and death as clinical endpoint events. Internal validation was conducted by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit. Increased miR-203 levels in OC patients were correlated with unfavorable prognosis and higher risk for disease progression, independently of FIGO stage, tumor grade, residual tumor after surgery, chemotherapy response and age. The analysis of the institutionally independent validation cohort (OVCAD study) clearly confirmed the shorter survival outcome of the patients overexpressing miR-203. Additionally, integration of miR-203 levels with the established disease prognostic markers led to a superior stratification of OC patients that can ameliorate prognosis and benefit patient clinical management. In this regard, miR-203 expression constitutes a novel independent molecular marker to improve patients’ prognosis in OC.
α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer
Authors: Jung Jaeyeon , Kim Suhyun , An Hyoung-Tae , Ko Jesang
Published: October 2019

Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.
Multielectrode Transcranial Electrical Stimulation of the Left and Right Prefrontal Cortices Differentially Impacts Verbal Working Memory Neural Circuitry
Authors: Koshy Sam M , Wiesman Alex I , Spooner Rachel K , Embury Christine , Rezich Michael T , Heinrichs-Graham Elizabeth , Wilson Tony W
Published: October 2019

Recent studies have examined the effects of conventional transcranial direct current stimulation (tDCS) on working memory (WM) performance, but this method has relatively low spatial precision and generally involves a reference electrode that complicates interpretation. Herein, we report a repeated-measures crossover study of 25 healthy adults who underwent multielectrode tDCS of the left dorsolateral prefrontal cortex (DLPFC), right DLPFC, or sham in 3 separate visits. Shortly after each stimulation session, participants performed a verbal WM (VWM) task during magnetoencephalography, and the resulting data were examined in the time–frequency domain and imaged using a beamformer. We found that after left DLPFC stimulation, participants exhibited stronger responses across a network of left-lateralized cortical areas, including the supramarginal gyrus, prefrontal cortex, inferior frontal gyrus, and cuneus, as well as the right hemispheric homologues of these regions. Importantly, these effects were specific to the alpha-band, which has been previously implicated in VWM processing. Although stimulation condition did not significantly affect performance, stepwise regression revealed a relationship between reaction time and response amplitude in the left precuneus and supramarginal gyrus. These findings suggest that multielectrode tDCS targeting the left DLPFC affects the neural dynamics underlying offline VWM processing, including utilization of a more extensive bilateral cortical network.
MIRKB: a myocardial infarction risk knowledge base
Authors: Zhan Chaoying , Shi Manhong , Wu Rongrong , He Hongxin , Liu Xingyun , Shen Bairong
Published: October 2019

Myocardial infarction (MI) is a common cardiovascular disease and a leading cause of death worldwide. The etiology of MI is complicated and not completely understood. Many risk factors are reported important for the development of MI, including lifestyle factors, environmental factors, psychosocial factors, genetic factors, etc. Identifying individuals with an increased risk of MI is urgent and a major challenge for improving prevention. The MI risk knowledge base (MIRKB) is developed for facilitating MI research and prevention. The goal of MIRKB is to collect risk factors and models related to MI to increase the efficiency of systems biological level understanding of the disease. MIRKB contains 8436 entries collected from 4366 articles in PubMed before 5 July 2019 with 7902 entries for 1847 single factors, 195 entries for 157 combined factors and 339 entries for 174 risk models. The single factors are classified into the following five categories based on their characteristics: molecular factor (2356 entries, 649 factors), imaging (821 entries, 252 factors), physiological factor (1566 entries, 219 factors), clinical factor (2523 entries, 561 factors), environmental factor (46 entries, 26 factors), lifestyle factor (306 entries, 65 factors) and psychosocial factor (284 entries, 75 factors). MIRKB will be helpful to the future systems level unraveling of the complex mechanism of MI genesis and progression.
Prognostic factors related to postoperative survival in the newly classified clinical T4 lung cancer
Authors: Yamanashi Keiji , Menju Toshi , Hamaji Masatsugu , Tanaka Satona , Yutaka Yojiro , Yamada Yoshito , Nakajima Daisuke , Ohsumi Akihiro , Aoyama Akihiro , Sato Toshihiko , Chen-Yoshikawa Toyofumi Fengshi , Sonobe Makoto , Date Hiroshi
Published: October 2019

OBJECTIVES

T4 lung cancer has become a more heterogeneous group since the 8th edition of tumour, node, metastasis classification. The aim of this study was to identify predictive factors related to post-surgical survival in patients with clinical T4 non-small-cell lung cancer (NSCLC), based on the 8th edition of the classification.

METHODS

We retrospectively reviewed consecutive patients with clinical T4 NSCLC who underwent resection between January 2006 and December 2016, to identify factors associated with overall survival.

RESULTS

Ninety-three patients were identified. The criteria for clinical T4 disease included tumours larger than 7 cm (n = 54), great vessels or left atrial invasion (n = 22), mediastinal invasion (n = 11), vertebral invasion (n = 3), tracheal or carina invasion (n = 3), diaphragm invasion (n = 1) and ipsilateral different lobe pulmonary metastasis (n = 2). The postoperative nodal status was 0, 1, 2 and 3 in 59, 18, 15 and 1 patient, respectively. R0 resection was achieved in 80 patients, and the 30-day mortality was 0%. The median follow-up time was 37.6 months, and the 5-year overall survival rate was 56.3%. The multivariable analysis revealed that nodal status and R-status were significant prognostic factors for postoperative survival [hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.20–5.72, P = 0.016 and HR 3.29, 95% CI 1.45–7.44, P = 0.004].

CONCLUSIONS

Surgery provided encouraging survival outcomes for clinical T4 NSCLC based on the 8th edition of classification. The nodal status and R-status were significant prognostic factors for postoperative survival.
The Many Faces of Emerging and Reemerging Infectious Disease
Authors: Lessler Justin , Orenstein Walter A
Published: October 2019

The emergence of disease threats can take many forms, from the adaptation of a traditionally zoonotic pathogen for efficient spread in humans, to the development of antibiotic resistance in well-known pathogens, to the creation of new niches for established disease through social and societal changes. In this commentary, the authors explore these various facets of disease emergence through the lens of the papers included in this issue of Epidemiologic Reviews. The authors explore multiple aspects of emergence and the ways in which emergent pathogens can be controlled with the limited tools available. In doing so, they put the papers in this issue in the context of the broader research agenda around understanding and combatting emergent pathogens.
European Union initiatives in child immunization— the need for child centricity, e-health and holistic delivery
Authors: Rigby Michael J , Chronaki Catherine E , Deshpande Shalmali S , Altorjai Peter , Brenner Maria , Blair Mitch E
Published: October 2019

Background

Low childhood immunization rates in Europe are causing concern and have triggered several EU initiatives. However, these are counter-factual as they make immunization a stand-alone issue and cut across best practice in integrated child health services. They also focus unduly on ‘anti-vax’ pressures, generalize ‘vaccine hesitancy’ and overlook practical difficulties and uncertainties encountered by parents in real world situations about presenting children for immunization. Meanwhile European expertize in child health electronic record systems and relevant standards are ignored despite their being a potentially sound foundation ripe for enhancement.

Methods

Situation and literature reviews, and cohesion of two European research projects, led to shared investigation. As a result, two cross-sectoral expert workshops were held to consider digital health standards for harmonizing integrated preventive child health including immunization, and the work of other stakeholders such as the World Health Organisation and the European Centre for Disease Control.

Results

Progress in child health information models and digital health standards was assessed, areas needing further standards development identified and desirable steps towards innovation in service delivery and record keeping agreed.

Conclusion

The European Commission, member states and child health stakeholders should take an integrated approach to child health with immunization as a component. Service delivery should be sensitive to parental concerns and challenges, and the way child- and family-centric data are recorded and used should be enhanced. Services should be enabled by the International Patient Summary and related electronic health record standards and linkages, and evaluated to assess most effective systems and practice.
Reflection waveform inversion based on full-band seismic data reconstruction for salt structure inversion
Authors: Chen Guoxin , Chen Shengchang , Yang Wencai
Published: October 2019

Salt structures are high potential targets for oil and gas exploration. However, large-scale salt domes with irregular surfaces pose significant challenges for velocity model building. For full waveform inversion, in the absence of a high-fidelity initial model, the success of the inversion depends on low-frequency seismic data, which are scarce in the exploration data sets. This paper presents a new idea to solve the problem of salt structure velocity modelling. First, we propose an envelope-based full-band seismic data reconstruction algorithm. The smoothness of envelope is used to segment the events in seismic data, and the phase independence of envelope is used for the identification of the seismic event's arrival-time to obtain the apparent reflection sequences of the subsurface. Full-band seismic data are obtained by convolving the apparent reflection sequence with full-band source. Window averaging function and threshold strategy are used to ensure the accuracy of seismic event segmentation and the stability of the algorithm when dealing with noisy data. Then the multiscale reflection waveform inversion based on reconstructed data is proposed for salt structure velocity building. The numerical experiment results of the Sigbee2A model demonstrate the performance of the inversion algorithm in the case where the seismic data lack low-frequency components and contain noise. The limitations of the algorithm have also been analysed and studied.
Coal-mine fire-related fine particulate matter and medical-service utilization in Australia: a time-series analysis from the Hazelwood Health Study
Authors: Johnson Amanda L , Gao Caroline X , Dennekamp Martine , Williamson Grant J , Carroll Matthew T C , Dimitriadis Christina , Dipnall Joanna F , Ikin Jillian F , Johnston Fay H , McFarlane Alexander C , Sim Malcolm R , Stub Dion A , Abramson Michael J , Guo Yuming
Published: October 2019

Background

This study assessed the association between coal-mine-fire-related fine particulate matter (PM2.5) and medical-service utilization, following a 6-week coal-mine fire in Australia, in 2014. Areas in the immediate vicinity of the mine experienced hourly mine-fire-related PM2.5 concentrations of up to 3700 μg/m3.

Methods

Data on medical-service utilization were collected from the Medicare Benefits Schedule—a national database of payment for medical services. PM2.5 concentrations were modelled using atmospheric chemical transport modelling. Quasi-Poisson interrupted distributed lag time-series analysis examined the association between daily mine-fire-related PM2.5 concentrations and medical-service utilization, including General Practitioner (GP) consultations and respiratory, cardiovascular and mental health services. Confounders included seasonality, long-term trend, day of the week, maximum daily temperature and public holidays. Gender and age stratification were conducted.

Results

A 10-μg/m3 increase in PM2.5 was associated with an increased relative risk of service usage for all long and short GP consultations [11% (95% confidence interval: 7 to 15%)] and respiratory services [22% (4 to 43%)] in both men and women. Sex stratification found an increased relative risk in mental health consultations in men [32% (2 to 72%)] but not women. No associations were found for cardiovascular services in men or women.

Conclusions

Coal-mine-fire-related PM2.5 exposure was associated with increased use of medical services for GP consultations and respiratory services in men and women and mental health consultations in men. These findings can inform the development of future public-health-policy responses in the event of major air-pollution episodes.
Informed and uninformed empirical therapy policies
Authors: Houy Nicolas , Flaig Julien
Published: October 2019

We argue that a proper distinction must be made between informed and uninformed decision making when setting empirical therapy policies, as this allows one to estimate the value of gathering more information about the pathogens and their transmission and thus to set research priorities. We rely on the stochastic version of a compartmental model to describe the spread of an infecting organism in a health care facility and the emergence and spread of resistance to two drugs. We focus on information and uncertainty regarding the parameters of this model. We consider a family of adaptive empirical therapy policies. In the uninformed setting, the best adaptive policy allowsone to reduce the average cumulative infected patient days over 2 years by 39.3% (95% confidence interval (CI), 30.3–48.1%) compared to the combination therapy. Choosing empirical therapy policies while knowing the exact parameter values allows one to further decrease the cumulative infected patient days by 3.9% (95% CI, 2.1–5.8%) on average. In our setting, the benefit of perfect information might be offset by increased drug consumption.
A Sharp Rearrangement Principle in Fourier Space and Symmetry Results for PDEs with Arbitrary Order
Authors: Lenzmann Enno , Sok Jérémy
Published: October 2019

We prove sharp inequalities for the symmetric-decreasing rearrangement in Fourier space of functions in $\mathbb{R}^d$. Our main result can be applied to a general class of (pseudo-)differential operators in $\mathbb{R}^d$ of arbitrary order with radial Fourier multipliers. For example, we can take any positive power of the Laplacian $(-\Delta )^s$ with $s> 0$ and, in particular, any polyharmonic operator $(-\Delta )^m$ with integer $m \geqslant 1$. As applications, we prove radial symmetry and real-valuedness (up to trivial symmetries) of optimizers for (1) Gagliardo–Nirenberg inequalities with derivatives of arbitrary order, (2) ground states for bi- and polyharmonic nonlinear Schrödinger equations (NLS), and (3) Adams–Moser–Trudinger type inequalities for $H^{d/2}(\mathbb{R}^d)$ in any dimension $d \geqslant 1$. As a technical key result, we solve a phase retrieval problem for the Fourier transform in $\mathbb{R}^d$. To achieve this, we classify the case of equality in the corresponding Hardy–Littlewood majorant problem for the Fourier transform in $\mathbb{R}^d$.
A Cross-Reactive Humanized Monoclonal Antibody Targeting Fusion Glycoprotein Function Protects Ferrets Against Lethal Nipah Virus and Hendra Virus Infection
Authors: Mire Chad E , Chan Yee-Peng , Borisevich Viktoriya , Cross Robert W , Yan Lianying , Agans Krystle N , Dang Ha V , Veesler David , Fenton Karla A , Geisbert Thomas W , Broder Christopher C
Published: October 2019

Background

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses that cause severe disease in both animals and humans. There are no approved vaccines or treatments for use in humans; however, therapeutic treatment of both NiV and HeV infection in ferrets and non-human primates with a cross-reactive, neutralizing human monoclonal antibody (mAb), m102.4, targeting the G glycoprotein has been demonstrated. In a previous study, we isolated, characterized, and humanized a cross-reactive, neutralizing anti-F mAb (h5B3.1). The mAb h5B3.1 blocks the required F conformational change needed to facilitate membrane fusion and virus infection, and the epitope recognized by h5B3.1 has been structurally defined; however, the efficacy of h5B3.1 in vivo is unknown.

Methods

The post-infection antiviral activity of h5B3.1 was evaluated in vivo by administration in ferrets after NiV and HeV virus challenge.

Results

All subjects that received h5B3.1 from 1 to several days after infection with a high-dose, oral-nasal virus challenge were protected from disease, whereas all controls died.

Conclusions

This is the first successful post-exposure antibody therapy for NiV and HeV using a humanized cross-reactive mAb targeting the F glycoprotein, and the findings suggest that a combination therapy targeting both F and G should be evaluated as a therapy for NiV/HeV infection.
Moving Global IR Forward—A Road Map
Authors: Gelardi Maiken
Published: October 2019

Many disciplinary analyses have exposed international realtions (IR) as a Western-centric discipline, unaware of or unconcerned with its own ethnocentric outlook. A growing consensus in the global IR framework argues that it is time to move beyond disciplinary critique, but scholars disagree on how to proceed. Three key issues are still being debated: who can speak, how to go local, and how to make the local global. This article confronts these questions by offering three interlinked contributions. First, it develops a typology of scholarly profiles by combining the typically isolated debates on scholarly origin, embeddedness within local context, and location. Second, the article identifies three main strategies for discovering and developing theories outside the core. Third, it offers four different avenues for applying local theories to the larger global canvas, underlining that Global South theories should not necessarily be limited to their “own” regions. Together these three contributions constitute a comprehensive roadmap for how to advance global IR's research agenda. The article provides examples focused on Latin America, highlighting the benefits of the roadmap while also giving agency to regional theoretical debates that are often overlooked in the Global IR debate.
User-focused data sharing agreements: a foundation for the genomic future
Authors: Petersen Carolyn
Published: October 2019

Data sharing agreements that clearly describe what individuals are agreeing to and what responsibilities data stewards will undertake are crucial for the establishment, maintenance, and flourishing of genomic datasets. To optimize genomic data resources, researchers, care professionals, and informaticians must regard system design, user objectives, and environmental considerations through users’ eyes, identifying fundamental values on which to build and potential barriers to success that must be avoided. Design of agreements that promote desired data sharing and protect valuable data resources as necessary begins with a review of user interests and concerns. Nontraditional approaches for informed consent (eg, abbreviated informed consent, electronic informed consent, and dynamic consent) can facilitate achievement of data donors’ privacy-related goals while making data available to researchers. Transparency in individual-researcher interactions, recognition and accommodation of cultural differences, and identification of shared needs and goals create a foundation for data sharing agreements that work over short and long terms.
MiRNA-96-5p contributed to the proliferation of gastric cancer cells by targeting FOXO3
Authors: He Xionghui , Zou Kejian
Published: October 2019

Various microRNAs (miRNAs, miRs) and the forkhead box O (FOXO) family proteins have been shown to influence gastric cancer progression and development. Here, we aimed to identify the gastric cancer related miRNAs and their relationship with the FOXO family. MiRNA profiles were generated by miRNA microarray screening from pre-operative plasma samples. Quantitative reverse transcription PCR and western bolt were used to determine the expression levels of miR-96 and FOXO family. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay and colony formation assay were used to test the cell viability. The miR-96-5p and FOXO3 interaction were confirmed by luciferase reporter assay. Our results demonstrated the excessive expression of miR-96-5p in gastric cancer cell lines and plasma samples from gastric cancer patients. In addition, the protein levels of FOXO3 were decreased in tissue samples from gastric cancer patients. Moreover, miR-96-5p accelerated the gastric cancer cell proliferation by directly targeting FOXO3. Therefore, we conclude that iR-96-5p might promote the progression of gastric cancer by directly targeting FOXO3 mRNA and downregulating the expression of FOXO3 protein, which provides new insights for the molecular mechanism of gastric cancer.
The Autophagy-Related Protein GABARAP Is Induced during Overwintering in the Bean Bug (Hemiptera: Alydidae)
Authors: Tachibana Shin-Ichiro , Matsuzaki Shinji , Tanaka Masako , Shiota Masayuki , Motooka Daisuke , Nakamura Shota , Goto Shin G
Published: October 2019

In most insects dependent on food resources that deplete seasonally, mechanisms exist to protect against starvation. Insects overcome periods of food depletion using diapause-associated physiological mechanisms, such as increased energy resources in fat bodies and suppression of metabolism. Because autophagy supplies energy resources through the degradation of intracellular components, we hypothesized that it might be an additional strategy to combat starvation during overwintering. In this study, we measured the abundance of the proteins involved in the signaling pathway of autophagy during overwintering in adults of the bean bug Riptortus pedestris (Fabricius) (Hemiptera: Alydidae), which must withstand the periodic depletion of its host plants from late fall to early spring. Although the levels of gamma-aminobutyric acid receptor-associated protein (GABARAP) markedly increased after the cessation of food supply, AMP-activated protein kinase (AMPK) and target of rapamycin (TOR) were not found to be associated with food depletion. Thus, food depletion appears to induce autophagy independent of AMPK and TOR. The GABARAP levels significantly increased universally when the food supply ceased, irrespective of the diapause status of adults and low-temperature conditions. In overwintering diapause adults under seminatural conditions, the GABARAP levels significantly increased during early spring. Thus, autophagy appears to assist the survival of the bean bugs under natural conditions of food deficiency.
Toward a Geoeconomic Order in International Trade and Investment
Authors: Roberts Anthea , Choer Moraes Henrique , Ferguson Victor
Published: October 2019

Recent developments suggest that the international economic order is transitioning away from the Neoliberal Order that has flourished for much of the post-Cold War period toward a new Geoeconomic Order. The shift to this new order, which is characterized by a growing ‘securitisation of economic policy and economisation of strategic policy’, will likely see the rules, norms, and institutions of international trade and investment law undergoing significant change. We expose the differences in the underlying logic of these orders, explore how this shift is being driven by the emerging USA–China tech/trade war, and consider the consequences of this transition for global economic governance.
Scientific Practice in Modeling Diseases: Stances from Cancer Research and Neuropsychiatry
Authors: Bertolaso Marta , Campaner Raffaella
Published: October 2019

In the last few decades, philosophy of science has increasingly focused on multilevel models and causal mechanistic explanations to account for complex biological phenomena. On the one hand, biological and biomedical works make extensive use of mechanistic concepts; on the other hand, philosophers have analyzed an increasing range of examples taken from different domains in the life sciences to test—support or criticize—the adequacy of mechanistic accounts. The article highlights some challenges in the elaboration of mechanistic explanations with a focus on cancer research and neuropsychiatry. It jointly considers fields, which are usually dealt with separately, and keeps a close eye on scientific practice. The article has a twofold aim. First, it shows that identification of the explananda is a key issue when looking at dynamic processes and their implications in medical research and clinical practice. Second, it discusses the relevance of organizational accounts of mechanisms, and questions whether thorough self-sustaining mechanistic explanations can actually be provided when addressing cancer and psychiatric diseases. While acknowledging the merits of the wide ongoing debate on mechanistic models, the article challenges the mechanistic approach to explanation by discussing, in particular, explanatory and conceptual terms in the light of stances from medical cases.
Metastatic melanoma of the gallbladder presenting as polyp in acute cholecystitis
Authors: Saraswat Nirvana B , DeVoe William B
Published: October 2019

Malignant melanoma is an aggressive neural crest cell-derived neoplasm with a propensity for metastasis to almost any organ. Gastrointestinal metastasis may manifest as gallbladder polyps. We report a case of metastatic malignant melanoma diagnosed in an 81-year-old male after cholecystectomy performed for acute cholecystitis. Cholecystectomy remains the standard of care for treatment of isolated gallbladder metastasis, especially in the setting of symptomatic disease. Mutation-directed chemotherapeutic and immunotherapeutic modalities serve as efficacious adjunctive therapy in addition to primary surgical resection for this rare condition.
Endophytes alleviate the elevated CO2-dependent decrease in photosynthesis in rice, particularly under nitrogen limitation
Authors: Rho Hyungmin , Doty Sharon Lafferty , Kim Soo-Hyung
Published: October 2019

The positive effects of high atmospheric CO2 concentrations [CO2] decrease over time in most C3 plants because of down-regulation of photosynthesis. A notable exception to this trend is plants hosting N-fixing bacteria. The decrease in photosynthetic capacity associated with an extended exposure to high [CO2] was therefore studied in non-nodulating rice that can establish endophytic interactions. Rice plants were inoculated with diazotrophic endophytes isolated from the Salicaceae and CO2 response curves of photosynthesis were determined in the absence or presence of endophytes at the panicle initiation stage. Non-inoculated plants grown under elevated [CO2] showed a down-regulation of photosynthesis compared to those grown under ambient [CO2]. In contrast, the endophyte-inoculated plants did not show a decrease in photosynthesis associated with high [CO2], and they exhibited higher photosynthetic electron transport and mesophyll conductance rates than non-inoculated plants under high [CO2]. The endophyte-dependent alleviation of decreases in photosynthesis under high [CO2] led to an increase in water-use efficiency. These effects were most pronounced when the N supply was limited. The results suggest that inoculation with N-fixing endophytes could be an effective means of improving plant growth under high [CO2] by alleviating N limitations.
Isavuconazole for the treatment of patients with invasive fungal diseases involving the central nervous system
Authors: Schwartz Stefan , Cornely Oliver A , Hamed Kamal , Marty Francisco M , Maertens Johan , Rahav Galia , Herbrecht Raoul , Heinz Werner J
Published: October 2019

The incidence of invasive fungal diseases (IFDs) with central nervous system (CNS) involvement is increasing due to the rising numbers of immunocompromised individuals, such as patients receiving chemotherapy, transplantation procedures, or immune-modulating therapies. CNS IFDs cause significant morbidity and mortality, and treatments are complicated by difficulties in identifying fungal pathogens and delivering antifungal agents to the CNS. Isavuconazole is a novel triazole with broad-spectrum activity that has shown good blood–brain barrier penetration in animal models. We present a retrospective analysis of isavuconazole in the treatment of patients with CNS IFDs and who either participated in the phase III VITAL or SECURE clinical trials, or were included in a named-patient program. A total of 36 patients were identified, including 27 patients from the clinical trials. Of these patients, 47.2% had hematologic malignancies, while 13.9% had no identifiable underlying conditions. Mucorales, Aspergillus species, and Cryptococcus species accounted for 30.6%, 22.2%, and 13.9% of infections, respectively. The overall survival rate was 80.6% at day 42 and 69.4% at day 84, and at the end of treatment, a complete or partial clinical response was achieved in 58.3% of patients. Isavuconazole exhibited clinical activity in a variety of CNS IFDs.
A resistive extension for ideal magnetohydrodynamics
Authors: Wright Alex James , Hawke Ian
Published: October 2019

We present an extension to the special relativistic, ideal magnetohydrodynamic (MHD) equations, designed to capture effects due to resistivity. The extension takes the simple form of an additional source term that, when implemented numerically, is shown to emulate the behaviour produced by a fully resistive MHD description for a range of initial data. The extension is developed from first principles arguments, and thus requires no fine-tuning of parameters, meaning it can be applied to a wide range of dynamical systems. Furthermore, our extension does not suffer from the same stiffness issues arising in resistive MHD, and thus can be evolved quickly using explicit methods, with performance benefits of roughly an order of magnitude compared to current methods.
Dark matter heating of gas accreting onto Sgr A*
Authors: Bennewitz Elizabeth R , Gaidau Cristian , Baumgarte Thomas W , Shapiro Stuart L
Published: October 2019

We study effects of heating by dark matter (DM) annihilation on black hole gas accretion. We observe that, for reasonable assumptions about DM densities in spikes around supermassive black holes, as well as DM masses and annihilation cross-sections within the standard WIMP model, heating by DM annihilation may have an appreciable effect on the accretion on to Sgr A* in the Galactic Centre. Motivated by this observation we study the effects of such heating on Bondi accretion, i.e. spherically symmetric, steady-state Newtonian accretion on to a black hole. We consider different adiabatic indices for the gas, and different power-law exponents for the DM density profile. We find that typical transonic solutions with heating have a significantly reduced accretion rate. However, for many plausible parameters, transonic solutions do not exist, suggesting a breakdown of the underlying assumptions of steady-state Bondi accretion. Our findings indicate that heating by DM annihilation may play an important role in the accretion onto supermassive black holes at the centre of galaxies, and may help explain the low accretion rate observed for Sgr A*.
The inner view of NGC 1052 using multiple X-ray observations
Authors: Osorio-Clavijo N , González-Martín O , Papadakis I E , Masegosa J , Hernández-García L
Published: October 2019

In this paper, we present a multi-epoch analysis of NGC 1052, a prototypical low-luminisity active galactic nucleus, using XMM–Newton, Suzaku and NuSTAR observations taken from 2001 to 2017. This is the first time that results from NuSTAR observations have been reported for NGC 1052. Regarding technical aspects, we found a wavelength-dependent calibration issue between simultaneous XMM–Newton and NuSTAR spectra, characterized by a change in the photon index of $\rm { \Gamma _{NuSTAR}- \Gamma _{XMM-Newton}=0.17\pm 0.04}$. We use ancillary Chandra data to decontaminate the nuclear spectrum from circumnuclear contributors. We find that two baseline models can fit the broad (0.5–50 keV) X-ray spectrum of the source. One consists of a power-law-like continuum that is absorbed by a uniform absorber, and is reflected by neutral material, and a separate power-law component in the soft band. The second model consists of a clumpy absorber. The reflection component is still present, but not the soft-band power law. Instead, absorption by a warm absorber is necessary to fit the spectra. This is the first time that a reflection component has been established in this object, thanks to high-energy data from NuSTAR. This component is constant in flux and shape, supporting the idea that it is produced away from the central source (probably in the torus). We find flux, spectral slope and absorption variations on time-scales of months to years. We also find that a patchy absorber can explain the behaviour of this source better, as it is ∼200 times more likely than the uniform absorber and yields smaller intrinsic variations.
Void Formation: Does the Void-in-Cloud Process Matter?
Authors: Chan Hei Yin Jowett , Chiba Masashi , Ishiyama Tomoaki
Published: October 2019

We investigate the basic properties of voids from high resolution, cosmological N-body simulations of Λ–dominated cold dark matter (ΛCDM) models, in order to compare with the analytical model of Sheth and van de Weygaert (SvdW) for void statistics. For the subsample of five dark matter simulations in the ΛCDM cosmology with box sizes ranging from 1000h−1Mpc to 8 h−1Mpc, we find that the standard void–in–cloud effect is too simplified to explain several properties of identified small voids in simulations. (i) The number density of voids is found to be larger than the prediction of the analytical model up to 2 orders of magnitude below 1h−1Mpc scales. The Press-Schechter model with the linear critical threshold of void δv = −2.71, or a naive power law, is found to provide an excellent agreement with the void size function, suggesting that the void-in-cloud effect does not suppress as much voids as predicted by the SvdW model. (ii) We then measured the density and velocity profiles of small voids, and find that they are mostly partially collapsing underdensities, instead of being completely crushed in the standard void–in–cloud scenario. (iii) Finally, we measure the void distributions in four different tidal environments, and find that the void–in-void effect alone can explain the correlation between distribution and environments, whereas the void–in–cloud effect is only weakly influencing the abundance of voids, even in filaments and clusters.
Investigating the multiwavelength behaviour of the flat spectrum radio quasar CTA 102 during 2013–2017
Authors: D’Ammando F , Raiteri C M , Villata M , Acosta-Pulido J A , Agudo I , Arkharov A A , Bachev R , Baida G V , Benítez E , Borman G A , Boschin W , Bozhilov V , Butuzova M S , Calcidese P , Carnerero M I , Carosati D , Casadio C , Castro-Segura N , Chen W-P , Damljanovic G , Di Paola A , Echevarría J , Efimova N V , Ehgamberdiev Sh A , Espinosa C , Fuentes A , Giunta A , Gómez J L , Grishina T S , Gurwell M A , Hiriart D , Jermak H , Jordan B , Jorstad S G , Joshi M , Kimeridze G N , Kopatskaya E N , Kuratov K , Kurtanidze O M , Kurtanidze S O , Lähteenmäki A , Larionov V M , Larionova E G , Larionova L V , Lázaro C , Lin C S , Malmrose M P , Marscher A P , Matsumoto K , McBreen B , Michel R , Mihov B , Minev M , Mirzaqulov D O , Molina S N , Moody J W , Morozova D A , Nazarov S V , Nikiforova A A , Nikolashvili M G , Ohlert J M , Okhmat N , Ovcharov E , Pinna F , Polakis T A , Protasio C , Pursimo T , Redondo-Lorenzo F J , Rizzi N , Rodriguez-Coira G , Sadakane K , Sadun A C , Samal M R , Savchenko S S , Semkov E , Sigua L , Skiff B A , Slavcheva-Mihova L , Smith P S , Steele I A , Strigachev A , Tammi J , Thum C , Tornikoski M , Troitskaya Yu V , Troitsky I S , Vasilyev A A , Vince O ,   (the WEBT Collaboration), Hovatta T , Kiehlmann S , Max-Moerbeck W , Readhead A C S , Reeves R , Pearson T J ,   (the OVRO Team), Mufakharov T , Sotnikova Yu V , Mingaliev M G
Published: October 2019

We present a multiwavelength study of the flat-spectrum radio quasar CTA 102 during 2013–2017. We use radio-to-optical data obtained by the Whole Earth Blazar Telescope, 15 GHz data from the Owens Valley Radio Observatory, 91 and 103 GHz data from the Atacama Large Millimeter Array, near-infrared data from the Rapid Eye Monitor telescope, as well as data from the Swift (optical-UV and X-rays) and Fermi (γ-rays) satellites to study flux and spectral variability and the correlation between flux changes at different wavelengths. Unprecedented γ-ray flaring activity was observed during 2016 November–2017 February, with four major outbursts. A peak flux of (2158 ± 63) × 10−8 ph cm−2 s−1, corresponding to a luminosity of (2.2 ± 0.1) × 1050 erg s−1, was reached on 2016 December 28. These four γ-ray outbursts have corresponding events in the near-infrared, optical, and UV bands, with the peaks observed at the same time. A general agreement between X-ray and γ-ray activity is found. The γ-ray flux variations show a general, strong correlation with the optical ones with no time lag between the two bands and a comparable variability amplitude. This γ-ray/optical relationship is in agreement with the geometrical model that has successfully explained the low-energy flux and spectral behaviour, suggesting that the long-term flux variations are mainly due to changes in the Doppler factor produced by variations of the viewing angle of the emitting regions. The difference in behaviour between radio and higher energy emission would be ascribed to different viewing angles of the jet regions producing their emission.