bluuebunny/crossref_metadata_2025 huggingface dataset:
Alexander the Great, reception of
Authors: Spencer Diana
Published: November 2019

What makes Alexander Great? His story has captured the imagination of authors, artists, philosophers, and politicians across more than two millennia. He has provided a point of convergence for religious and spiritual thinkers, he has been co-opted as a champion for gender and sexual openness, he represents a paradigm for would-be charismatic dictators (and their opponents), he gives us scientific imperialism and justification for conquistadorial dreaming, and he exemplifies the risks of cultural appropriation. To understand why Alexander resonates so widely across so many different fields of study, interest groups, and media, is an exercise in reception. This Alexander who has captured the imagination is triumphantly equivocal and it is in the plurality of traditions through which this complexity is expressed that his enduring “greatness” lies. The imaginary quality of Alexander is unsurprising because more profoundly than for any comparable individual from classical antiquity, his history is a product of reception from the start: every encounter with Alexander the Great is part of a conversation that depends substantially on accounts and narrative evidence from long after his death, and at the least at one remove from the historians who first and contemporaneously chronicled his life and achievements.

These ancient traditions of Alexander are rooted in the contradictory and multifarious strands in which his achievements were retold and repurposed, even within his own lifetime. His rapid development as an ideological and cultural icon rather than as a purely historical character accelerated and amplified his significance far beyond that of the short-lived empire that he conquered. To trace all of these traditions and their significance, from antiquity to the 21st century, would be impossible. The aim here is to present a broad overview, focusing on Western reception but with citations and references enabling more detailed study of individual aspects and the Eastern traditions.
The Nature of Productivity (Including Word Formation Versus Creative Coining)
Authors: Spencer Andrew
Published: November 2019

The term productivity most commonly applies to word formation, but in principle it can be applied to any linguistic process. A process is said to be productive if it applies without restriction to give rise to novel expressions, for instance, new words. Ideally, speakers apply productive processes without conscious deliberation and in principle they can be applied by any and all competent native speakers. Creative coining of words, by contrast, is typically a one-off intentional act (nonce word creation), often of one individual, and often with the aim of drawing attention to the coined word for the purposes of advertising, humor, and so on. Creative coining often involves extra-grammatical processes which cannot be described deterministically, unlike bona fide linguistic rules. However, many productive processes are restricted in various ways, and some of the extra-grammatical devices are very frequent, so the distinction between productive, grammatical word formation and (nonce) word creation is blurred.
The Production of Public Goods, Services, and Regulations for Natural Hazards
Authors: Jacob Benoy
Published: November 2019

Hazard management scholars have begun to develop an important line of inquiry based upon the idea of governance. This growing body of work focuses attention on how the hazard functions that were formerly carried out by public entities are now frequently dispersed among diverse sets of actors that include not only governmental institutions but also private-sector and civil society entities. While informative, this body of work is unduly narrow. In particular, it takes an actor-centric approach to the governance of hazards. A more comprehensive view would account for the relationship between the governance system and the underlying good being produced.

Generally speaking, governance systems emerge to manage—or produce—particular goods. Accordingly, these systems will vary depending upon the nature of the underlying good. Thus, while it is important to describe the actors that shape the governance system—as the extant literature does— the failure to recognize or appreciate the relationship between hazards governance and its underlying good is non-trivial. At minimum, without this information scholars and practitioners cannot reasonably assess the efficacy of the system.

To better understand hazards governance, there needs to be a clear picture of what the governance system is producing, as well as the defining characteristics thereof. The good being produced by hazards governance systems is resilience, which is both non-rivalrous and non-excludable. Simply stated, resilience can be conceptualized as a public good. Moreover, governance systems in general are comprised of multiple subsystems. In the case of hazards management, the subsystems are mitigation, preparedness, response, and recovery. Thus, the production technologies—aggregate effort, single best effort, and weakest link—will likely vary across the hazards governance system. Showing how these technologies potentially vary across hazard governance systems opens new and important lines of inquiry.
Natural Hazards Governance in Western Europe
Authors: Roth Florian , Prior Timothy , Käser Marco
Published: November 2019

Western Europe is an area dominated by established democratic governments, backed by strong economies, for the most part. Drawing on refined technical risk analyses, preventive measures, and comprehensive resources for emergency response, countries from Western Europe have managed to mitigate the most prevalent and recurring hazards. Over the centuries, European governments have been successful in reducing the death toll related to natural phenomena. This has been achieved by addressing all three dimensions of the risk triangle—hazards, exposure, and vulnerability. However, cultural and political differences result in subtle, but distinct differences in the context of natural hazard governance. While these differences can be considered a strength in dealing with local hazards under specific contexts, they can complicate effective and coordinated prevention, preparedness, and response measures toward large-scale hazards. This is especially the case with transboundary hazards, the regional response to which has strongly influenced hazard governance in Western Europe. Evolving risk circumstances have resulted in constant adaptations in hazard governance in the region, including local, national, and transboundary arrangements, and a more recent re-localization in the face of new complex threats that has fallen under the umbrella of resilience building.
Health Care Challenges After Disasters in Lesser Developed Countries
Authors: Balikuddembe Joseph Kimuli , Fu Binhua , Reinhardt Jan D.
Published: November 2019

A public health disaster occurs when the adverse health effects of an event such as a natural hazard or threat exceed the coping capacity of the affected human population. The coping capacity of the affected population is hereby dependent on available resources including financial and human resources, health infrastructure, as well as knowledge, planning and organizational capabilities, and social capital. Disasters therefore disproportionally affect lesser resourced regions and countries of the world and pose specific challenges to their health systems as well as to the international humanitarian community in terms of dealing with mortality and injuries, communicable and noncommunicable disease, mental health effects, and long-term disability. Challenges for health care delivery in disaster situations in lesser resourced settings include deficiencies in the construction of resilient health care facilities, the lack of disaster response plans, shortage of specialized medical personnel, shortcomings regarding training in disaster response, and scarcity of resources such as medicines and portable medical devices and supplies. Other challenges include the absence of appropriate algorithms for the distribution of scarce resources; lack of coordination of medical teams and other volunteers; limited awareness of particular health issues such as mental health problems or disability and rehabilitation; and lack of plans for evacuation, sheltering, and continuation of treatment of those with preexisting health conditions. Many challenges lesser resourced settings face with regard to health care delivery after disasters such as the organization of mortality management, triage and treatment of the injured, or the delivery of rehabilitative and mental health care cannot be reduced to the lack of baseline resources in terms of health infrastructure, technology, and personnel but are related to the absence of proper planning for future disaster scenarios including implementation strategies and simulation exercises. This not only encompasses the formal drafting of disaster preparedness and response plans, contingency planning of hospitals, and the provision of disaster-related training to health personnel but also in particular the identification and involvement of the potentially and traditionally affected communities and especially vulnerable groups in all the process of disaster risk reduction.
UPObase: an online database of unspecific peroxygenases
Authors: Faiza Muniba , Lan Dongming , Huang Shengfeng , Wang Yonghua
Published: November 2019

There are many unspecific peroxygenases (UPOs) or UPO-like extracellular enzymes secreted by fungal species. These enzymes are considered special in their ways of catalyzing a wide variety of reactions such as epoxidation, peroxygenation and electron oxidations. This enzyme family exhibits diverse functions with thousands of UPOs and UPO-like sequences. These sequences are difficult to analyze without proper management tool and therefore desperately calls for a unified platform that can aide with annotation, classification, navigation and easy sequence retrieval. This prompted us to create an online database called Unspecific Peroxygenase Database (UPObase) (upobase.bioinformaticsreview.com) which currently includes 1948 peroxygenase-encoding protein sequences mined from more than 800 available fungal genomes. It provides information such as classification and motifs about each sequence and has functions such as homology search against UPObase sequence analyses such as multiple sequence alignments and phylogenetic trees. It also provides a new sequence submission facility. The database has been made user-friendly facilitating systematic search and filters. UPObase allows users to search for the sequences by organism name, cluster ID and accession number. Notably, in our previous study, 113 UPOs were classified into five subfamilies (I, II, III, IV and V) and an undetermined group (Pog) which remain established. In this study, using 1948 UPOs in our database, we were able to further identify six novel sub-superfamilies (Pog-a, Pog-b, Pog-c, Pog-d, Pog-e and Pog-f) with signature motifs and two distinct groups in Subfamily I and III, Ia and Ib, IIIa and IIIb, respectively. With the novel UPO-like sequences and classification, UPObase may serve for researchers working in the area of enzyme engineering and related fields.
Tripal EUtils: a Tripal module to increase exchange and reuse of genome assembly metadata
Authors: Condon B , Almsaeed A , Buehler S , Childers C P , Ficklin S P , Staton M E , Poelchau M F
Published: November 2019

Data and metadata interoperability between data storage systems is a critical component of the FAIR data principles. Programmatic and consistent means of reconciling metadata models between databases promote data exchange and thus increases its access to the scientific community. This process requires (i) metadata mapping between the models and (ii) software to perform the mapping. Here, we describe our efforts to map metadata associated with genome assemblies between the National Center for Biotechnology Information (NCBI) data resources and the Chado biological database schema. We present mappings for multiple NCBI data structures and introduce a Tripal software module, Tripal EUtils, to pull metadata from NCBI into a Tripal/Chado database. We discuss potential mapping challenges and solutions and provide suggestions for future development to further increase interoperability between these platforms.

Database URL: https://github.com/NAL-i5K/tripal_eutils
O10 GIANT ESOPHAGEAL POLYP PROTRUDING THROUGH THE MOUTH: A RARE CASE
Authors: Tsomidis I , Kalopitas G , Dinaki K , Germanidis G , Constantinidis J
Published: November 2019

Aim

Giant esophageal polyps are a relative rare and benign entity, which can lead to major complications. Our knowledge about their pathology and management originates from scattered case reports. Our aim is to report the clinical presentation and management of this rare case in order to enrich the current literature.

Background & Methods

Large pedunculated esophageal polyps are a rare entity encountered in clinical practice. The majority of these polyps are located near the upper esophageal sphincter or upper esophagus. They are slowly growing and asymptomatic. Most common clinical symptoms, associated with polyp size, include dysphagia, chest pain, regurgitation and, rarely, acute respiratory distress. Histology reveals benign submucosal tumors with fibrous and vascular components, covered by normal squamous cells, in most cases. Malignant transformation of these polyps has been infrequently described. Surgical approach, either with endoscopic resection or with open surgery, is the treatment of choice and recurrence is extremely uncommon. A review of current literature was conducted, followed by presentation of our rare case.

Results

A 50 year-old woman with clear medical history presented with a 3-month history of dysphagia and endoscopy revealed a large esophageal polyp extending from the upper esophageal sphincter to the lower esophageal sphincter. The initial attempt of endoscopic resection of the polyp led to regurgitation and intraoral prolapse of the polyp, causing respiratory distress. The patient was transferred to the ENT operation room and an orotracheal intubation was performed. The tumor was successfully removed transorally after ligation of its stem. Histopathology showed an inflammatory fibroid polyp (IFP) and postsurgical follow-up revealed no recurrence of the mass.

Conclusion

Giant IFPs are an extremely rare entity among upper esophageal polyps and the pathogenesis of these tumors remains poorly understood. Life threatening regurgitation of the polyp causing respiratory distress is an uncommon complication demanding urgent surgical approach. Once diagnosed, these benign tumors can be removed either with open surgery or endoscopic resection depending on the location and the size of the tumor. The impressive size of these polyps renders them a challenge for surgeons and endoscopists, whose cooperation is often in need.
Decreased Enteric Bacterial Composition and Diversity in South American Crohn’s Disease Vary With the Choice of Treatment Strategy and Time Since Diagnosis
Authors: Cruz-Lebrón Angélica , D’argenio Garcia Leticia , Talla Aarthi , Joussef-Piña Samira , Quiñones-Mateu Miguel E , Sékaly Rafick-Pierre , de Carvalho Karina Inacio Ladislau , Levine Alan D
Published: November 2019

Background and Aims

The symptomology of Crohn’s disease [CD], a chronic inflammatory disease of the digestive tract, correlates poorly with clinical, endoscopic or immunological assessments of disease severity. The prevalence of CD in South America is rising, reflecting changes in socio-economic stability. Many treatment options are available to CD patients, including biological agents and corticosteroids, each of which offers variable efficacy attributed to host genetics and environmental factors associated with alterations in the gut microbiota.

Methods

Based on 16S rRNA gene sequencing and taxonomic differences, we compared the faecal microbial population of Brazilian patients with CD treated with corticosteroid or anti-tumour necrosis factor [anti-TNF] immunotherapy. Faecal calprotectin and plasma sCD14 levels were quantified as markers for local and systemic inflammation, respectively.

Results

Anti-TNF treatment led to an increased relative abundance of Proteobacteria and a decreased level of Bacteroidetes. In contrast, corticoid treatment was associated with an increase in the relative abundance of Actinobacteria, which has been linked to inflammation in CD. Disruption of the faecal microbiota was related to decreased bacterial diversity and composition. Moreover, the choice of clinical regimen and time since diagnosis modulate the character of the resulting dysbiosis.

Conclusions

Enteric microbial populations in CD patients who have been treated are modulated by disease pathogenesis, local inflammatory microenvironment and treatment strategy. The dysbiosis that remains after anti-TNF treatment due to decreased bacterial diversity and composition abates restoration of the microbiota to a healthy state, suggesting that the identification and development of new clinical treatments for CD must include their capacity to normalize the gut microbiota.
How Should We Think about the Winners and Losers from Globalization? Three Narratives and Their Implications for the Redesign of International Economic Agreements
Authors: Lamp Nicolas
Published: November 2019

In the wake of Donald Trump’s election to the US presidency, the ‘losers’ from globalization have received unprecedented attention. While few would contest that manufacturing workers in developed countries have lost out over the past decades, the remedies proposed by President Trump have been met with a mixture of concern and ridicule by the trade establishment. And, yet, it seems clear that, at least in the USA, politicians and trade officials are no longer able to convince voters that international economic agreements will ‘lift all boats’. Instead, those engaged in debates about trade policy will need to be open about the fact that international economic agreements create both winners and losers. This article identifies three narratives about who those winners and losers are. The article argues that the contestation between these three narratives is not one that can be resolved through empirical analysis but, instead, that the narratives contain irreducible normative elements. The article further explores the implications of these narratives for the redesign of international economic agreements.
Resilience or Vulnerability of the Rear-Edge Distributions of Pinus halepensis and Pinus pinaster Plantations Versus that of Natural Populations, under Climate-Change Scenarios
Authors: Silvério E , Duque-Lazo J , Navarro-Cerrillo R M , Pereña F , Palacios-Rodríguez G
Published: November 2019

It is predicted that changes in climate will lead to episodes of large forest decline and mortality. Therefore, the distributions of forest plantations and natural stands might already be facing such impacts. We selected the most arid zone of south-eastern Europe (eastern Andalusia) to assess how the distributions of Pinus halepensis Miller. and Pinus pinaster Aiton forest plantations and natural stands cope with climate change and to determine whether natural or planted distributions would be more stable under future climate-change scenarios. We used presence-point locations from natural distributions, obtained from the third Spanish National Forest Inventory, to develop ensemble species distribution models. The forecast predicted a slight increase in the potential distribution of both species by 2040, with a subsequent drastic decrease until 2099. Pinus halepensis had larger current and future potential distributions than P. pinaster but a slightly greater decrease with time in the potential distribution than that of P. pinaster. On the other hand, the natural and planted distributions of P. halepensis were more vulnerable to future climate change scenarios than those of P. pinaster. Natural populations will likely be more resilient to climate change than planted populations.
The Frequency of Sleep Medication Use and the Risk of Subjective Cognitive Decline (SCD) or SCD With Functional Difficulties in Elderly Individuals Without Dementia
Authors: Lee Joo Eun , Ju Yeong Jun , Chun Ki Hong , Lee Soon Young
Published: November 2019

Background

The present study investigated whether the frequency of sleep medication use affects subjective cognitive decline (SCD) or SCD with functional difficulties in elderly individuals.

Methods

The 2018 Korea Community Health Survey data, which consists of national representative and community-based data, was used in this study. A total of 57,050 individuals aged 65 years or older were included in this study. SCD was measured using the Behavioral Risk Factor Surveillance System. A logistic regression analysis was used to analyze the data.

Results

In total, 16,966 (29.7%) participants had SCD and 3,487 (6.1%) had SCD with functional difficulties. The elderly individuals who took sleep medication more than once a week had higher risks of both SCD and SCD with functional difficulties than those who did not take any sleep medication in a month (SCD: odds ratio [OR] = 1.329, 95% confidence interval [CI] = 1.194–1.480; SCD with functional difficulties: OR = 1.752, 95% CI = 1.491–2.058).

Conclusions

Frequent sleep medication use was associated with both SCD and SCD with functional difficulties. This study suggests that early detection of cognitive impairment and efforts to reduce the frequent use of sleeping pills in patients with insomnia might be helpful to reduce the burden of SCD and SCD with functional difficulties in the elderly population.
Algebraic Reduced Genus One Gromov–Witten Invariants for Complete Intersections in Projective Spaces
Authors: Lee Sanghyeon , Oh Jeongseok
Published: November 2019

In [ 17, 18], Zinger defined reduced Gromov–Witten (GW) invariants and proved a comparison theorem of standard and reduced genus one GW invariants for every symplectic manifold (with all dimension). In [ 3], Chang and Li provided a proof of the comparison theorem for quintic Calabi–Yau three-folds in algebraic geometry by taking a definition of reduced invariants as an Euler number of certain vector bundle. In [ 5], Coates and Manolache have defined reduced GW invariants in algebraic geometry following the idea by Vakil and Zinger in [ 14] and proved the comparison theorem for every Calabi–Yau threefold. In this paper, we prove the comparison theorem for every (not necessarily Calabi–Yau) complete intersection of Dimension 2 or 3 in projective spaces by taking a definition of reduced GW invariants in [ 5].
Seismic impedance inversion using second-order overlapping group sparsity with A-ADMM
Authors: Wu Hao , Li Shu , Chen Yingpin , Peng Zhenming
Published: November 2019

The anisotropic total variation with overlapping group sparsity (ATV_OGS) regularisation term is an improvement on the anisotropic total variation (ATV) regularisation term. It has been employed successfully in seismic impedance inversion as it can enhance the boundary information and relieve the staircase effect by exploring the structured sparsity of seismic impedance. However, because ATV_OGS constrains only the structured sparsity of the impedance's first-order difference and ignores the structured sparsity of the second-order difference, the staircase effect still occurs in an inversion result based on ATV_OGS. To further fit the structured sparsity of the impedance's second-order gradients, we introduce the overlapping group sparsity into the second-order difference of the impedance and propose a novel second-order ATV with overlapping group sparsity (SATV_OGS) seismic impedance inversion method. The proposed method reduces the interference of the large amplitude noise and further mitigates the staircase effect of the ATV_OGS. Furthermore, the accelerated alternating direction method of multipliers (A-ADMM) framework applied to this novel method. It can increase the efficiency of inversion. The experiments are carried out on a general model data and field data. Based on the experimental results, the proposed method can obtain higher resolution impedance than some impedance inversion methods based on total variation.
Formation resistivity measurement based on a transient electromagnetic field excited by an acoustic probe in an open-hole
Authors: Sheng Xiaofei , Shen Jianguo , Shen Yongjin
Published: November 2019

The monopole probe commonly used in acoustic logging can generate vibrations in its natural frequency under the excitation of the pulse signal, and excite transient electromagnetic (TEM) signals of the same frequency. The acoustic probe receives both acoustic and TEM field signals. The TEM field propagates and attenuates in conductive well fluid and formations, carrying formation resistivity information that could be used for formation evaluation. Based on the axisymmetry of the TEM field in an open-hole, theoretical calculation of the TEM field components in an open-hole model was performed. The results revealed that TEM response signals decay rapidly with time, and electric field intensity along the well axis Ez is approximately linear with formation resistivity. On this basis, we proposed a new method for measuring formation resistivity in an open-hole, which could supplement conventional logging methods. Also, it does not affect signal processing of acoustic logging and only applies the TEM signal to determine formation resistivity. The new method could accomplish a more comprehensive petroleum formation evaluation, which is of great significance to the integrated design of the well logging instrument.
Effect of an intensive lifestyle intervention on the prevalence of metabolic syndrome and its components among overweight and obese adults
Authors: Guzmán M , Zbella E , Alvarez S Shah , Nguyen J L , Imperial E , Troncale F J , Holub C , Mallhi A K , VanWyk S
Published: November 2019

Background

Despite the fact that up to a third of the global population has metabolic syndrome (MetS), it has been overlooked in clinical settings. This study assesses the impact of a physician-supervised nonsurgical weight management program on the prevalence of MetS and its key indicators.

Methods

Four-hundred seventy-nine overweight and obese participants aged 19 years or older were included in a prospective longitudinal study. Changes in MetS and its key indicators were assessed using the binomial exact, chi-square and Wilcoxon signed-rank tests in an intent-to-treat study population. Differences in age strata were assessed using a generalized linear model.

Results

Fifty-two percent of participants (n = 249) had MetS at baseline. Prevalence of MetS decreased steadily with significant changes from baseline observed at weeks 13 (31.8%, P < 0.0001), 26 (28.7%, P < 0.0012) and 39 (21.6%, P < 0.0002); changes from baseline were observed at week 52 as statistically significant (16.7%, P < 0.0012). Improvements in anthropometrics and levels of key indicators of MetS were observed throughout the study.

Conclusion

These findings confirm that weight loss is inversely associated with prevalence of MetS and its key indicators among overweight and obese individuals. Future studies may benefit from a larger sample size and better retention (ClinicalTrials.gov ID: NCT03588117).
Beta Risk in the Cross-Section of Equities
Authors: Boloorforoosh Ali , Christoffersen Peter , Fournier Mathieu , Gouriéroux Christian
Published: November 2019

We develop a conditional capital asset pricing model in continuous time that allows for stochastic beta exposure. When beta comoves with market variance and the stochastic discount factor (SDF), beta risk is priced, and the expected return on a stock deviates from the security market line. The model predicts that low-beta stocks earn high returns, because their beta positively comoves with market variance and the SDF. The opposite is true for high-beta stocks. Estimating the model on equity and option data, we find that beta risk explains expected returns on low- and high-beta stocks, resolving the “betting against beta” anomaly.

Authors have furnished code and an Internet Appendix, which are available on the Oxford University Press Web site next to the link to the final published paper online.
Population Structure and Aggressiveness of Sclerotinia sclerotiorum From Rapeseed (Brassica napus) in Chongqing City
Authors: Yu Yang , Cai Junsong , Ma Linhao , Huang Zhiqiang , Wang Yabo , Fang Anfei , Yang Yuheng , Qing Ling , Bi Chaowei
Published: November 2019

Sclerotinia sclerotiorum is one of the most devastating fungal plant pathogens of oilseed Brassica and is distributed worldwide. In particular, Sclerotinia stem rot has always been a serious threat to rapeseed production in Chongqing City, China. In this study, simple sequence repeat (SSR) markers and mycelial compatibility groups (MCGs) were used to characterize the population structure of 90 geographic isolates of S. sclerotiorum collected from rapeseed in nine counties of Chongqing. A total of 52 microsatellite haplotypes were identified, and a few haplotypes were found with high frequency. Gene diversity ranged from 0.1570 to 0.4700 in nine populations. A constructed unweighted pair group with arithmetic mean dendrogram based on Nei genetic distance and a STRUCTURE analysis revealed that the genetic composition of the isolates collected in the five counties located in western Chongqing are different from those collected in the two eastern counties, suggesting that breed lines should be cultivated in both the western and eastern regions to effectively evaluate resistance levels. A total of 47 MCGs were identified, and 72% of the MCGs was represented by single isolates. Seven of 13 MCGs that included at least two isolates contained isolates from only one county. SSR haplotypes were not correlated with MCGs. A subset of 34 isolates were inoculated on rapeseed stems, and the aggressiveness showed variation. This research revealed the population genetic structure and aggressiveness of this pathogen in Chongqing, and the results will help to develop disease management and resistance screening strategies.
Autophagy mediates hepatic GRK2 degradation to facilitate glucagon‐induced metabolic adaptation to fasting
Authors: Cruces‐Sande Marta , Arcones Alba C. , Vila‐Bedmar Rocío , Val‐Blasco Almudena , Sharabi Kfir , Díaz‐Rodríguez Daniel , Puigserver Pere , Mayor Federico , Murga Cristina
Published: November 2019

The liver plays a key role during fasting to maintain energy homeostasis and euglycemia via metabolic processes mainly orchestrated by the insulin/glucagon ratio. We report here that fasting or calorie restriction protocols in C57BL6 mice promote a marked decrease in the hepatic protein levels of G protein‐coupled receptor kinase 2 (GRK2), an important negative modulator of both G protein‐coupled receptors (GPCRs) and insulin signaling. Such downregulation of GRK2 levels is liver‐specific and can be rapidly reversed by refeeding. We find that autophagy, and not the proteasome, represents the main mechanism implicated in fasting‐induced GRK2 degradation in the liver in vivo. Reducing GRK2 levels in murine primary hepatocytes facilitates glucagon‐induced glucose production and enhances the expression of the key gluconeogenic enzyme Pck1. Conversely, preventing full downregulation of hepatic GRK2 during fasting using adenovirus‐driven overexpression of this kinase in the liver leads to glycogen accumulation, decreased glycemia, and hampered glucagon‐induced gluconeogenesis, thus preventing a proper and complete adaptation to nutrient deprivation. Overall, our data indicate that physiological fasting‐induced downregulation of GRK2 in the liver is key for allowing complete glucagon‐mediated responses and efficient metabolic adaptation to fasting in vivo.
MiR‐9‐5p protects from kidney fibrosis by metabolic reprogramming
Authors: Fierro‐Fernández Marta , Miguel Verónica , Márquez‐Expósito Laura , Nuevo‐Tapioles Cristina , Herrero J. Ignacio , Blanco‐Ruiz Eva , Tituaña Jessica , Castillo Carolina , Cannata Pablo , Monsalve María , Ruiz‐Ortega Marta , Ramos Ricardo , Lamas Santiago
Published: November 2019

MicroRNAs (miRNAs) regulate gene expression posttranscriptionally and control biological processes (BPs), including fibrogenesis. Kidney fibrosis remains a clinical challenge and miRNAs may represent a valid therapeutic avenue. We show that miR‐9‐5p protected from renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). This was reflected in reduced expression of pro‐fibrotic markers, decreased number of infiltrating monocytes/macrophages, and diminished tubular epithelial cell injury and transforming growth factor‐beta 1 (TGF‐β1)‐dependent de‐differentiation in human kidney proximal tubular (HKC‐8) cells. RNA‐sequencing (RNA‐Seq) studies in the UUO model revealed that treatment with miR‐9‐5p prevented the downregulation of genes related to key metabolic pathways, including mitochondrial function, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and glycolysis. Studies in human tubular epithelial cells demonstrated that miR‐9‐5p impeded TGF‐β1‐induced bioenergetics derangement. The expression of the FAO‐related axis peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC‐1α)‐peroxisome proliferator‐activated receptor alpha (PPARα) was reduced by UUO, although preserved by the administration of miR‐9‐5p. We found that in mice null for the mitochondrial master regulator PGC‐1α, miR‐9‐5p was unable to promote a protective effect in the UUO model. We propose that miR‐9‐5p elicits a protective response to chronic kidney injury and renal fibrosis by inducing reprogramming of the metabolic derangement and mitochondrial dysfunction affecting tubular epithelial cells.
Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy for Lung Cancer: protocol for a multicenter, double-blind and randomized controlled trial
Authors: Zhou Jian-Guo , Li Pei-Jie , Jin Su-Han , Liu Da-Hai , Huang Lang , Cao Ming-Ze , Zou Yu , Ma Hu
Published: November 2019

Background

Chemotherapy-induced nausea and vomiting (CINV) is frequently observed after the administration of chemotherapy and significantly influences the quality of life (QoL) of patients. Olanzapine has a high control rate of CINV in patients with cancer when combined with the NK-1 receptor antagonist dexamethasone and 5-hydroxytryptamine (5-HT3) receptor antagonists. The efficacy of a regimen without an NK-1 receptor antagonist remains unknown. Therefore, we designed this randomized trial to provide evidence for the management of CINV.

Methods and ananlysis

This is a double-blind, multicenter and randomized controlled trial. Patients with histologically confirmed lung cancer will be assessed by physicians based on the inclusion and exclusion criteria, and 156 participants will be enrolled and randomized to a placebo group or experiment group to receive treatment for CINV. The primary endpoint is the incidence of delayed CINV. The secondary endpoints are complete response (CR) of acute CINV, CR of delayed CINV, effective control rate (ECR) of CINV and QoL. During the six days after administration, these endpoints will be evaluated and recorded by physicians.

Ethic and dissemination

This study has received approval from the institutional ethical review board of the Affiliated Hospital of Zunyi Medical University (ref approval No. 58). Written informed consent will be signed by all participants prior to enrolling. Participants will be randomly assigned to the experimental group or comparator group by blocked randomization.

Article summary

Strengths and limitations

This study will provide evidence for physicians to find an affordable and effective treatment regimen for CINV through this study.

Because of the variety of pharmaceutical companies, medical care and other factors, problem of cost will be further explored in the following studies.

Although the study is designed as a double-blind randomized controlled trial, QoL will be measured by a questionnaire that is filled out by patients themselves. This may influence the conclusions.
Porous upconversion nanostructures as bimodal biomedical imaging contrast agents
Authors: Du Ziqing , Gupta Abhishek , Clarke Christian , Cappadana Matt , Clases David , Liu Deming , Yang Zhuoqing , Doble Philip , Price Bill , Xu Xiaoxue
Published: November 2019

Lanthanide ions doped upconversion nanoparticles (UCNPs) hold great promise as the imaging contrast agent for multimodal medical imaging techniques for diagnosis, including fluorescent bioimaging, magnetic resonance imaging, and computed tomography. However, the maximized signal values of fluorescence and MRI cannot be achieved simultaneously from the same upconversion nanoparticles structures because high specific surface areas can benefit the signal gaining of MRI while big size can induce brighter fluorescent imaging. In this work, we designed and fabricated novel core-porous shell structures for UCNPs with much-enhanced signal values for both fluorescent imaging and MRI. The core-porous shell UCNPs were synthesized via a post-treatment process after an inert shell was coated onto the core UCNPs. The formation mechanism was carefully investigated. The fluorescent and magnetic resonance properties have been detailed characterized and compared from core, core-shell and core-porous UCNPs. Large and bright UCNPs in fluorescence and MRI have been achieved and great potential as the dual-modal contrast agent.
A resource of targeted mutant mouse lines for 5,061 genes
Authors: Birling Marie-Christine , Yoshiki Atsushi , Adams David J , Ayabe Shinya , Beaudet Arthur L , Bottomley Joanna , Bradley Allan , Brown Steve DM , Bürger Antje , Bushell Wendy , Chiani Francesco , Chin Hsian-Jean Genie , Christou Skevoulla , Codner Gemma F , DeMayo Francesco J , Dickinson Mary E , Doe Brendan , Donahue Leah Rae , Fray Martin D , Gambadoro Alessia , Gao Xiang , Gertsenstein Marina , Gomez-Segura Alba , Goodwin Leslie O , Heaney Jason D , Hérault Yann , de Angelis Martin Hrabe , Jiang Si-Tse , Justice Monica J , Kasparek Petr , King Ruairidh E , Kühn Ralf , Lee Ho , Lee Young Jae , Liu Zhiwei , Kent Lloyd K C , Lorenzo Isabel , Mallon Ann-Marie , McKerlie Colin , Meehan Terrence F , Newman Stuart , Nutter Lauryl MJ , Oh Goo Taeg , Pavlovic Guillaume , Ramirez-Solis Ramiro , Rosen Barry , Ryder Edward J , Santos Luis A , Schick Joel , Seavitt John R , Sedlacek Radislav , Seisenberger Claudia , Seong Je Kyung , Skarnes William C , Sorg Tania , Steel Karen P , Tamura Masaru , Tocchini-Valentini Glauco P , Leo Wang Chi-Kuang , Wardle-Jones Hannah , Wattenhofer-Donzé Marie , Wells Sara , Willis Brandon J , Wood Joshua A , Wurst Wolfgang , Xu Ying ,   IMPC Consortium, Teboul Lydia , Murray Stephen A
Published: November 2019

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes from targeted embryonic stem cells on the C57BL/6N genetic background. This includes 2,850 null alleles for which no equivalent mutant mouse line exists, 2,987 novel conditional-ready alleles, and 4,433 novel reporter alleles. This nearly triples the number of genes with reporter alleles and almost doubles the number of conditional alleles available to the scientific community. When combined with more than 30 years of community effort, the total mutant allele mouse resource covers more than half of the genome. The extensively validated collection is archived and distributed through public repositories, facilitating availability to the worldwide biomedical research community, and expanding our understanding of gene function and human disease.
Unsupervised content-preserving transformation for optical microscopy
Authors: Li Xinyang , Zhang Guoxun , Qiao Hui , Bao Feng , Deng Yue , Wu Jiamin , He Yangfan , Yun Jingping , Lin Xing , Xie Hao , Wang Haoqian , Dai Qionghai
Published: November 2019

The development of deep learning and the open access to a substantial collection of imaging data provide a potential solution to computational image transformation, which is gradually changing the landscape of optical imaging and biomedical research. However, current implementations of deep learning usually operate in a supervised manner and the reliance on a laborious and error-prone data annotation procedure remains a barrier towards more general applicability. Here, we propose an unsupervised image transformation to facilitate the utilization of deep learning for optical microscopy, even in some cases where supervised models cannot apply. By introducing a saliency constraint, the unsupervised model, dubbed as Unsupervised content-preserving Transformation for Optical Microscopy (UTOM), can learn the mapping between two image domains without requiring paired training data and avoid the distortion of the image content. UTOM shows promising performances in a wide range of biomedical image transformation tasks, including in silico histological staining, fluorescence image restoration, and virtual fluorescence labeling. Quantitative evaluations elucidate that UTOM achieves stable and high-fidelity image transformations across different imaging conditions and modalities. We anticipate that our framework will encourage a paradigm shift in training neural networks and enable more applications of artificial intelligence in biomedical imaging.
A Systems Change Framework for Evaluating Academic Equity and Inclusion in an Ecology & Evolution Graduate Program
Authors: Wallace Kelly J , York Julia M
Published: November 2019

While academia is moving forward in terms of diversifying recruitment of undergraduate and graduate students, diverse representation is still not found across the academic hierarchy. At the graduate level, new discussions are emerging around efforts to improve the experiences of women and underrepresented minorities through inclusive graduate programming. Inclusive graduate programs are that which actively center and prioritize support for diverse experiences, identities, career goals, and perspectives, from recruitment through graduation. Establishing regular and rigorous evaluation of equity and inclusion efforts and needs is a critical component of this work. This is recognized by funding agencies that increasingly require reporting on inclusion efforts; here we suggest use of a systems change framework for these evaluations.

A systems change approach emphasizes three levels: explicit change (e.g. policies), semi-explicit change (e.g. power dynamics), and implicit change (e.g. biases). We use the Ecology, Evolution, and Behavior (EEB) PhD Program at the University of Texas at Austin in an exercise to (1) identify areas of concern regarding inclusive programming voiced by graduate students, (2) categorize efforts to address these concerns, and (3) integrating and evaluating which areas of the systems change framework show the greatest progress or potential for progress. We argue this framework is particularly useful for academic systems as they are complex, composed of variable individuals, and must address diverse stakeholder needs.
Gene-flow from steppe individuals into Cucuteni-Trypillia associated populations indicates long-standing contacts and gradual admixture
Authors: Immel Alexander , Țerna Stanislav , Simalcsik Angela , Susat Julian , Šarov Oleg , Sîrbu Ghenadie , Hofmann Robert , Müller Johannes , Nebel Almut , Krause-Kyora Ben
Published: November 2019

The Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100 – 2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about of the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500 – 3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component had arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.
Stromal cell-contact dependent PI3K and APRIL induced NF-κB signaling complement each other to prevent mitochondrial- and endoplasmic reticulum stress induced cell death of bone marrow plasma cells
Authors: Cornelis Rebecca , Hahne Stefanie , Taddeo Adriano , Petkau Georg , Malko Darya , Durek Pawel , Thiem Manja , Heiberger Lukas , Mohr Elodie , Klaeden Cora , Tokoyoda Koji , Siracusa Francesco , Hoyer Bimba Franziska , Hiepe Falk , Mashreghi Mir-Farzin , Melchers Fritz , Chang Hyun-Dong , Radbruch Andreas
Published: November 2019

Persistence of long-lived, memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, provided in niches organized by stromal cells. Here we describe thatex vivowe can prevent apoptosis of bone marrow plasma cells by supplying direct cell contact with stromal cells and the soluble cytokine APRIL. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the PI3K signaling pathway, leading to critical inactivation of FoxO1/3 and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Likely, inhibition of PI3K signalingin vivoablates bone marrow plasma cells. APRIL signaling, via the NF-κB pathway, blocks activation of the endoplasmic reticulum stress-associated initiator caspase 12. Thus, stromal cell-contact induced PI3K and APRIL-induced NF-κB signaling provide necessary and complementary signals to maintain bone marrow memory plasma cells.
Biomarker2vec: Attribute- and Behavior-driven Representation for Multi-type Relationship Prediction between Various Biomarkers
Authors: Guo Zhen-Hao , You Zhu-Hong , Wang Yan-Bin , Yi Hai-Cheng
Published: November 2019

The explosive growth of genomic, chemical and pathological data provides new opportunities and challenges to re-recognize life activities within human cells. However, there exist few computational models that aggregate various biomarkers to comprehensively reveal the physical and functional landscape of the biology system. Here, we construct a graph called Molecular Association Network (MAN) and a representation method called Biomarker2vec. Specifically, MAN is a heterogeneous attribute network consists of 18 kinds of edges (relationships) among 8 kinds of nodes (biomarkers). Biomarker2vec is an algorithm that represents the nodes as vectors by integrating biomarker attribute and behavior. After the biomarkers are described as vectors, random forest classifier is applied to carry out the prediction task. Our approach achieved promising performance on 18 relationships, with AUC of 0.9608 and AUPR of 0.9572. We also empirically explored the contribution of attribute and behavior feature of biomarkers to the results. In addition, a drug-disease association prediction case study was performed to validate our method’s ability on a specific object. These results strongly prove that MAN is a network with rich topological and biological information and Biomarker2vec can indeed adequately characterize biomarkers. Generally, our method can achieve simultaneous prediction of both single-type and multi-type relationships, which bring beneficial inspiration to relevant scholars and expand the medical research paradigm.