bluuebunny/crossref_metadata_2025_split huggingface dataset:
phyloregion: R package for biogeographical regionalization and macroecology
Authors: Daru Barnabas H. , Karunarathne Piyal , Schliep Klaus 
Published: August 2020

Abstract

Biogeographical regionalization is the classification of regions in terms of their biota and is key to our understanding of the ecological and historical drivers affecting species distribution in macroecological or large‐scale conservation studies. However, despite the mass production of species distributions and phylogenetic data, statistical and computational infrastructure to successfully incorporate, manipulate and analyse such massive amounts of data had not been fully developed.

Here, we present phyloregion, a statistical package for the analysis of biogeographical regionalization and macroecology in the R computing environment, tailored for mega phylogenies and macroecological datasets of ever‐increasing size and complexity.

Compared to available packages, phyloregion is several times faster and allocates less memory than other packages for analysis of alpha diversity (including phylogenetic diversity, phylogenetic endemism and evolutionary distinctiveness and global endangerment) and beta diversity (including cluster analysis, determining optimal number of clusters and evolutionary distinctiveness of regions).

We demonstrate the scalability of the package to large datasets with comprehensive phylogenies and global distribution maps of squamate reptiles (amphisbaenians, lizards and snakes), and show that different phyloregions differ strongly in evolutionary distinctiveness across scales. Visualization tools allow graphical exploration of the generated patterns of biogeographical regionalization and macroecology in geographical space.

Ultimately, phyloregion will facilitate rapid biogeographical analyses that will accommodate the ongoing mass production of species occurrence records and phylogenetic datasets at any scale and for any taxonomic group into completely reproducible R workflows.
Tensor decomposition for infectious disease incidence data
Authors: Korevaar Hannah , Metcalf C. Jessica , Grenfell Bryan T. 
Published: August 2020

Abstract

Many demographic and ecological processes generate seasonal and other periodicities. Seasonality in infectious disease transmission can result from climatic forces such as temperature and humidity; variation in contact rates as a result of migration or school calendar; or temporary surges in birth rates. Seasonal drivers of acute immunizing infections can also drive longer‐term fluctuations.

Tensor decomposition has been used in many disciplines to uncover dominant trends in multi‐dimensional data. We introduce tensors as a novel method for decomposing oscillatory infectious disease time series.

We illustrate the reliability of the method by applying it to simulated data. We then present decompositions of measles data from England and Wales. This paper leverages simulations as well as much‐studied data to illustrate the power of tensor decomposition to uncover dominant epidemic signals as well as variation in space and time. We then use tensor decomposition to uncover new findings and demonstrate the potential power of the method for disease incidence data. In particular, we are able to distinguish between annual and biennial signals across locations and shifts in these signals over time.

Tensor decomposition is able to isolate variation in disease seasonality as a result of variation in demographic rates. The method allows us to discern variation in the strength of such signals by space and population size. Tensors provide an opportunity for a concise approach to uncovering heterogeneity in disease transmission across space and time in large datasets.
Similar burden of pathogenic coding variants in exceptionally long‐lived individuals and individuals without exceptional longevity
Authors: Gutman Danielle , Lidzbarsky Gabriel , Milman Sofiya , Gao Tina , Sin-Chan Patrick , Gonzaga‐Jauregui Claudia ,   Regeneron Genetics Center, Deelen Joris , Shuldiner Alan R. , Barzilai Nir , Atzmon Gil 
Published: August 2020

AbstractCentenarians (exceptionally long‐lived individuals—ELLI) are a unique segment of the population, exhibiting long human lifespan and healthspan, despite generally practicing similar lifestyle habits as their peers. We tested disease‐associated mutation burden in ELLI genomes by determining the burden of pathogenic variants reported in the ClinVar and HGMD databases using data from whole exome sequencing (WES) conducted in a cohort of ELLI, their offspring, and control individuals without antecedents of familial longevity (n = 1879), all descendent from the founder population of Ashkenazi Jews. The burden of pathogenic variants did not differ between the three groups. Additional analyses of variants subtypes and variant effect predictor (VEP) biotype frequencies did not reveal a decrease of pathogenic or loss‐of‐function (LoF) variants in ELLI and offspring compared to the control group. Case–control pathogenic variants enrichment analyses conducted in ELLI and controls also did not identify significant differences in any of the variants between the groups and polygenic risk scores failed to provide a predictive model. Interestingly, cancer and Alzheimer's disease‐associated variants were significantly depleted in ELLI compared to controls, suggesting slower accumulation of mutation. That said, polygenic risk score analysis failed to find any predictive variants among the functional variants tested. The high similarity in the burden of pathogenic variation between ELLI and individuals without familial longevity supports the notion that extension of lifespan and healthspan in ELLI is not a consequence of pathogenic variant depletion but rather a result of other genomic, epigenomic, or potentially nongenomic properties.
Cocaine treatment demands in 10 western European countries: observed trends between 2011 and 2018
Authors: Antoine Jérôme , Berndt Nadine , Astudillo Mariana , Cairns Donal , Jahr Stefan , Jones Andrew , Kuijpers Wil , Llorens Noelia , Lyons Suzi , Maffli Etienne , Magliocchetti Natalia , Molina Olivas Marta , Palle Christophe , Schwarzkopf Larissa , Wisselink Jeroen , Montanari Linda 
Published: August 2020

AbstractAimsTo describe cocaine treatment demand in 10 western European countries and to examine the size, direction and temporality of recent trends in the proportion of cocaine users among all clients entering treatment.DesignAggregated data collected through the European Union standardized treatment demand monitoring system (TDI) between 2011 and 2018 were used.SettingBelgium, England, France, Germany, Ireland, Italy, Luxembourg, Spain, Switzerland and the Netherlands.ParticipantsIn total, more than 700 000 cocaine treatment records were analysed. Clients in treatment for cocaine as primary drug were predominantly male (85%), with an average age of 35 years.MeasurementsNumber of treatment episodes for substance use and for cocaine as primary or secondary drug were collected year‐ and country‐wise. When available, powder cocaine and crack and patients with and without previous treatment were differentiated.FindingsAmong the participating countries the share of cocaine as primary drug in treatment demand ranged between 4.7% [95% confidence interval (CI) = 4.6–4.9%] in Germany and 43.1% in Spain (95% CI = 42.6–43.5%). The general trend analysis showed a decreasing proportion of cocaine‐related treatment entrants between 2011 and 2014 among all subgroups followed by a strong increase in 2015. The increase appeared stronger than for powder cocaine. Seven of 10 countries observed a recent significant increase in the proportion of treatment entrants reporting cocaine as the primary substance: Belgium [annual percentage change (APC) = 9.6%, P < 0.01], England (APC = 14.9%, P < 0.05), France (APC = 21.8%, P < 0.01), Ireland (APC = 28.2%, P < 0.01), Italy (APC = 7.8%, P < 0.01), Spain (APC = 7.0%, P < 0.05) and Switzerland (APC = 12.0%, P < 0.05). Trends were similar when looking at cocaine reported as primary or adjunctive substance.ConclusionsDespite substantial country‐specific variation regarding cocaine prevalence and treatment demand, there has been an overall significant increase since 2015 in the share of cocaine‐related treatment demand in western Europe.
The landscape configuration and lethality of snare poaching of sympatric guilds of large carnivores and ungulates
Authors: Mudumba Tutilo , Jingo Sophia , Heit David , Montgomery Robert A. 
Published: August 2020

AbstractPoaching of wildlife presents one of the biggest conservation challenges in the 21st century. Snaring is one of the primary means of capturing target animals. To prioritise interventions intending to reduce snaring, we describe an approach for quantifying the configuration and lethality of snares. We conducted transect surveys in Murchison Falls National Park. All the snares that we recovered were made of wire with the majority (81.0%, n = 546 of 674) deriving from vehicle tire wire. The density of snares ranged from 0.08 to 4.58 snares/km2, which is the highest known density in sub‐Saharan Africa. The majority (63%) of the animals caught in wire snares were unrecovered and wasted. We found that noose width, vertical drop, wire circumference, anchor height, proportion of un‐thicketed area, grass height, distance to river and village had a significant positive relationships to lethality, while snare thickness, charms, tree DBH, thicket diameter, distance to nearest road negatively affected lethality. We recommend adopting wholistic anti‐snare countermeasures such as the human heritage‐centred conservation to empower local people. Our method illustrates the opportunity to standardise temporal and spatial measurements of snare density and configuration necessary to stop illegal wildlife poaching.
Recurrent miscarriage is not associated with a higher prevalence of inherited and acquired thrombophilia
Authors: Vomstein Kilian , Herzog Anna , Voss Pauline , Feil Katharina , Goeggl Tamara , Strowitzki Thomas , Toth Bettina , Kuon Ruben‐Jeremias 
Published: August 2020

AbstractProblemAlthough not being recommended in guidelines, many physicians perform routine screening for thrombophilia in RM patients suspecting a higher prevalence in these patients. The aim of this study was to analyze the prevalence of inherited and acquired thrombophilia in a large cohort of RM patients.Method of studyWithin a multicenter case‐control study, n = 820 RM patients and n = 141 controls were included. The prevalence of inherited and acquired thrombophilia including deficiency of protein C/S and antithrombin, elevation of factor VIII activity, APC resistance including mutation in the factor V Leiden gene, mutation in the prothrombin gene and antiphospholipid antibodies were assessed. Further, we performed a meta‐analysis of the prevalence of thrombophilia in RM patients including studies between 01/2000 and 01/2020.ResultsAn antiphospholipid syndrome (APLS) was only present in RM patients. Increased factor VIII concentration was significantly more prevalent in controls (RM vs controls: 5.8% vs 11.0%). None of the other thrombophilia did differ significantly between RM patients and controls. The meta‐analysis revealed no significant difference in the occurrence of these thrombophilia between RM patients and controls.ConclusionThe prevalence of inherited thrombophilia does not differ between RM patients and controls. When analyzing rare events like thrombophilia, a high number of patients are needed to obtain reliable results, which might explain contradictory findings in previous studies analyzing small cohorts of RM patients. Despite being less prevalent than previously described, we still recommend screening for APLS as it is associated with severe pregnancy complications.
From Partisan Universal to Concrete Universal? The Pashtun Tahaffuz Movement in Pakistan
Authors: Mallick Ayyaz 
Published: August 2020

AbstractThis paper explores the question of universal‐particular through the anti‐war Pashtun Tahaffuz (Protection) Movement in Pakistan. With its demands couched in the language of pain, rights to life and “dignity”, the PTM mobilises popular Pashtun sentiments as a “partisan universal”: a political formulation which achieves the common good even as it attends to particular interests. However, within the re‐formulated urban question in post‐9/11 Pakistan, PTM also attempts to make common cause with other ethnic‐spatial communities through shared—but situated and differentiated—experiences of dispossession. Thus, the PTM’s “dialectic of experience” is a partisan universal in search of a “concrete universal”: a non‐totalising but encompassing and open universality, a universal politics which works through the particularity of specific groups’ experiences. It is in this terrain of political practice, and its attendant theoretical articulations, that we will find the—contingent and processual—resolution of the transition from particularity to universality.
Evaluation of analytical accuracy of HER2 status in patients with breast cancer
Authors: Jensen Steffen Grann , Thomas Peter Engel , Christensen Ib Jarle , Balslev Eva , Hansen Alastair , Høgdall Estrid 
Published: August 2020

Human epidermal growth factor receptor 2 (HER2) gene status and overexpression, occurring in ~ 13.6% of primary breast cancers, is essential for identifying patients likely to benefit from biological treatment. In this method of evaluation study, we tested and compared the HER2 gene–protein assay (GPA) with routine HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The GPA was evaluated using 67 formalin‐fixed paraffin‐embedded (FFPE) HER2 equivoval IHC (2+) breast cancer tissue samples. Overall, agreement between GPA silver in situ hybridization (SISH) and FISH was 91.9% (57/62). Regression analysis revealed slightly higher, but non‐significant difference in HER2/chromosome enumeration probe 17 (CEP17) ratio for GPA as compared to FISH (p = 0.074). Intraclass correlation coefficients (ICCs) of 0.94 and Spearman´s rank correlation coefficients of 0.93 (p < 0.0001) for FISH and GPA SISH suggested strong inter‐observer association for methods with one observer counting on average 0.23 significant higher for GPA SISH (p = 0.014). Intra‐observer IHC method reproducibility was 52.6% (κ = 0.3122, p = 0.004) and 79.7% (κ = 0.6428, p = 0.9197), suggesting fair significant and substantial non‐significant difference between tests for reviewers. Inter‐observer reproducibility for IHC methods was 53%. While inter‐observer reproducibility for experienced IHC interpretation suggested significant differences (κ = 0.3636, p = 0.0332), unexperienced interpretation of IHC GPA suggested fair non‐significant difference between reviewers (κ = 0.3101, p = 0.0747). Using FISH as reference, the diagnostic indices for GPA SISH were as follows: sensitivity 100%, specificity 95% and accuracy 92%. Inaccuracy between tests was in 80% of cases due to ISH categorization as equivocal by one of the methods. IHC results highlight that it may be beneficial with a method for simultaneously visualization of HER2 gene and protein status.
Developing an instrument to assess cancer patient preparedness for transition to survivorship care in Korea
Authors: Lim Jung‐won 
Published: August 2020

AbstractPurposeThe current study specified the initial qualitative stage to develop an instrument that assesses whether patients with cancer in Korea are ready for the transition from hospital‐based to community‐based survivorship care, focusing on psychosocial and behavioral aspects.MethodsIndividual interviews with cancer survivors, family members, and healthcare professionals in South Korea were conducted. Subsequently, analyses of qualitative data for creating items and pilot testing were performed to develop an instrument for Korean cancer survivors.ResultsAn item pool for an initial version of a new instrument called the “Preparedness for Transition to Survivorship Care Instrument (PTSCI)” was developed by creating 20 themes and 41 subthemes around each of the 401 codes. After assessing face validity, a set of 46 items was chosen. The 46 items were organized into 6 components: (1) physical, (2) cognitive, (3) psychological, (4) social, (5) health management, and (6) information. The Cronbach's alpha of the instrument in the pilot testing was 0.872.DiscussionThe PTSCI offers an opportunity to identify the psychosocial and behavioral status of patients with cancer in the survivorship phase. This new instrument can be used to test psychosocial and behavioral interventions for individuals who are not ready for the survivorship care phase.
Antipsychotics inhibit the mitochondrial bioenergetics of pancreatic beta cells isolated from CD1 mice
Authors: Elmorsy Ekramy , Alelwani Walla , Kattan Shahad , Babteen Nouf , Alnajeebi Afnan , Ghulam Jihan , Mosad Soad 
Published: August 2020

AbstractAntipsychotics (APs) are widely used medications with reported diabetogenic side effects. This study investigated the effect of commonly used APs, namely chlorpromazine (CPZ), haloperidol (HAL) and clozapine, on the bioenergetics of male CD1 mice isolated pancreatic beta cells as an underlying mechanism of their diabetogenic effects. The effect of APs on Alamar blue reduction, adenosine triphosphate (ATP) production and glucose‐stimulated insulin secretion (GSIS) of isolated beta cells was evaluated. Then, the effects of APs on the activities of mitochondrial complexes and their common coding genes expression, oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and lactate production were investigated. The effects of APs on the mitochondrial membrane fluidity (MMF) and mitochondrial membrane fatty acid composition were also examined. Results showed that the tested APs significantly decreased cellular ATP production and GSIS of the beta cells. The APs significantly inhibited the activities of mitochondrial complexes and their coding gene expression, MMP and OCR of the treated cells, with a parallel increase in lactate production to different extents with the different APs. CPZ and HAL showed increased MMF and mitochondrial membrane polyunsaturated fatty acid content. In conclusion, the tested APs‐induced mitochondrial disruption can play a role in their diabetogenic side effect.
The role of eosinophil morphology in distinguishing between reactive eosinophilia and eosinophilia as a feature of a myeloid neoplasm
Authors: Goasguen Jean E. , Bennett John M. , Bain Barbara J. , Brunning Richard , Zini Gina , Vallespi Maria‐Teresa , Tomonaga Masao , Locher Clara ,   The International Working Group on Morphology of MDS
Published: August 2020

SummaryMorphological features of eosinophils in patients with reactive eosinophilia (28 patients) and clonal eosinophilia (26 patients) have been compared with each other and with the eosinophil characteristics of healthy volunteers (three subjects) and of patients with the idiopathic hypereosinophilic syndrome (three patients). Morphological features, assessed in isolation from other haematological abnormalities, were found to have poor specificity for a myeloid neoplasm. The most useful feature was the presence of basophilic granules in mature eosinophils, which was associated particularly with acute myeloid leukaemia with inv(16). Marked reduction in granules occurred more often in some subsets of the myeloid neoplasm group but nevertheless was lacking in specificity since it was not infrequently seen in reactive eosinophilia. Although experienced morphologists more often considered that a myeloid neoplasm was likely in patients in whom this was the diagnosis (69%), myeloid neoplasia was also considered likely in a considerable proportion (39%) of patients with reactive eosinophilia. Morphological abnormalities of eosinophils therefore cannot be assessed in isolation in seeking to make a diagnosis of a myeloid neoplasm. Morphology is, however, needed and should be integrated with the results of other investigations.
Hydrogen sulfide signalling in the CNS ‐ Comparison with NO
Authors: Kimura Hideo 
Published: August 2020

Hydrogen sulfide (H2S) together with polysulfides (H2Sn, n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H2S and H2Sn diffuse to the target proteins for S‐sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3‐mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3‐mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S‐nitrosylation. S‐sulfuration and S‐nitrosylation by enzymes proceed only inside the cell, while reactions induced by H2S, H2Sn and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S‐sulfuration and S‐nitrosylation causes many nervous system diseases. This review focuses on the signalling by H2S and H2Sn with S‐sulfuration comparing to that of NO with S‐nitrosylation and discusses on their roles in physiology and pathophysiology.
Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
Authors: van Wijk Rob C. , Hu Wanbin , Dijkema Sharka M. , van den Berg Dirk‐Jan , Liu Jeremy , Bahi Rida , Verbeek Fons J. , Simonsson Ulrika S.H. , Spaink Herman P. , van der Graaf Piet H. , Krekels Elke H.J. 
Published: August 2020

Background and PurposeThere is a clear need for innovation in anti‐tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.Experimental ApproachIn zebrafish studies, drugs are usually dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nanoscale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as the test compound. We used pharmacokinetic–pharmacodynamic modelling to quantify the exposure–response relationship responsible for the antibiotic response. To translate isoniazid response to humans, quantitative exposure–response relationships in zebrafish were linked to simulated concentration–time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.Key ResultsBlood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially, and an isoniazid dose corresponding to 15 mg·L−1 internal concentration (minimum inhibitory concentration) leads to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration–effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.Conclusions and ImplicationsThis proof of concept study confirmed the potential of zebrafish larvae as tuberculosis disease models in translational pharmacology and contributes to innovative anti‐tuberculosis drug development, which is very clearly needed.