bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic Kidney Injury: An Observational Descriptive Study
Authors: Khoschnau Sherwan , Jabbour Gaby , Al-Hassani Ammar , El-Menyar Ayman , Abdelrahman Husham , Afifi Ibrahim , Momin Umais Ziad , Peralta Ruben , Al-Thani Hassan
Published: December 2019

Background: Trauma is a major cause of death and disability worldwide. Renal injuries account for 8–10% of abdominal trauma. We aimed to describe the incidence, presentation, and management of traumatic kidney injury in our institution. Methods: This is a retrospective analysis of all patients admitted with traumatic kidney injury at a level 1 trauma center between January 2014 and December 2017. Results: During a period of 3 years, a total of 152 patients with blunt renal trauma were admitted to a level 1 trauma center; 91% of these were males, with a mean age of 32.8 ± 13.7 years. Motor vehicle crashes accounted for 68% of cases, followed by fall from height (23%). Seventy-one percent of patients had associated chest injuries, 38% had pelvis injuries, and 32% had head injury. Associated abdominal injuries included the liver (35%) and spleen (26%). The mean abdominal abbreviated injury scale was 2.8 ± 1.0; and for those with severe renal injury, it was 3.9 ± 0.9. The mean injury severity score was 24.9 ± 13.7 (31.8 ± 14.2 with renal vs. 21.9 ± 12.9 without renal injury, p = 0.004). Most of the patients were treated conservatively (93%), including severe renal injuries (grades IV and V), and 7% had surgical exploration, mainly those with severe injuries (grades IV and V). The mortality rate was 11%. Conclusions: High-grade renal injuries in hemodynamically stable patients can be managed conservatively. A multidisciplinary approach coordinated by trauma, urology, and radiology services facilitates the care of these patients in our trauma center.
Concomitant BRAF Mutation in Hairy Cell Leukemia and Papillary Thyroid Cancer: Case Report
Authors: Mohamed Shehab F. , Helmi Feryal , El-Akiki Susanna , El Omri Halima , Nashwan Abdulqadir , Yassin Mohamed A.
Published: December 2019

Hairy cell leukemia (HCL) is rare type of leukemia. This neoplasm is well-known to present with pancytopenia and splenomegaly. HCL is associated with BRAF mutation in 100% of cases. It is also associated with hematological and oncological malignancies such as melanoma and papillary thyroid cancer. Although the association of both cancers (HCL and papillary thyroid cancer) with BRAF mutation is well established in the literature, as far as we know it has not been reported before in the same patient. Here we report 48-year-old male diagnosed with HCL and papillary thyroid cancer and who is BRAF positive in both diagnostic tissues.
Portfolio Analysis of Research Grants in Data Science Funded by the National Heart, Lung, and Blood Institute
Authors: Li Huiqing , Miller Marissa , Burke Catherine , Danthi Narasimhan , Charette Marc , Gan Weiniu , Qasba Pankaj , Wei Gina S. , Goff David C. , Luo Xiao-zhong James
Published: December 2019

Leveraging emerging opportunities in data science to open new frontiers in heart, lung, blood, and sleep research is one of the major strategic objectives of the National Heart, Lung, and Blood Institute (NHLBI), one of the 27 Institutes/Centers within the National Institutes of Health (NIH). To assess NHLBI’s recent funding of research grants in data science and to identify its relative areas of focus within data science, a portfolio analysis from fiscal year 2008 to fiscal year 2017 was performed. In this portfolio analysis, an efficient and reliable methodology was used to identify data science research grants by utilizing several NIH databases and search technologies (iSearch, Query View Reporting system, and IN-SPIRE [Pacific Northwest National Laboratory, Richland, WA]). Six hundred thirty data science–focused extramural research grants supported by NHLBI were identified using keyword searches based primarily on NIH’s working definitions of bioinformatics and computational biology. Further analysis characterized the distribution of these grants among the heart, lung, blood, and sleep disease areas as well as the subtypes of data science projects funded by NHLBI. Information was also collected for data science research grants funded by other NIH institutes/centers using the same search and analysis methodology. The funding comparison among different NIH institutes/centers highlighted relative data science areas of emphasis and further identified opportunities for potential data science areas in which NHLBI could foster research advances.
Identifying brain network topology changes in task processes and psychiatric disorders
Authors: Rezaeinia Paria , Fairley Kim , Pal Piya , Meyer François G. , Carter R. McKell
Published: December 2019

A central goal in neuroscience is to understand how dynamic networks of neural activity produce effective representations of the world. Advances in the theory of graph measures raise the possibility of elucidating network topologies central to the construction of these representations. We leverage a result from the description of lollipop graphs to identify an iconic network topology in functional magnetic resonance imaging data and characterize changes to those networks during task performance and in populations diagnosed with psychiatric disorders. During task performance, we find that task-relevant subnetworks change topology, becoming more integrated by increasing connectivity throughout cortex. Analysis of resting state connectivity in clinical populations shows a similar pattern of subnetwork topology changes; resting scans becoming less default-like with more integrated sensory paths. The study of brain network topologies and their relationship to cognitive models of information processing raises new opportunities for understanding brain function and its disorders.
Introduction to The Silent Majority: Invertebrates in Human-Animal Studies
Authors: Moore Lisa Jean , Wilkie Rhoda M.
Published: December 2019

This essay introduces the rationale for and the contributions to the special issue The Silent Majority: Invertebrates in Human-Animal Studies.
Grotius and the Marginalization of Cosmopolitan Duties
Authors: Glanville Luke
Published: December 2019

This article expounds the role played by Hugo Grotius in marginalizing positive duties for the protection of vulnerable people beyond the sovereign state. In the sixteenth century, theorists writing within a range of traditions had posited solemn and demanding duties to assist and rescue vulnerable subjects of other rulers from tyranny and persecution. In the early seventeenth century, Grotius explicitly subordinated such duties to the duty to seek the preservation and advantage of one’s own state. He claimed that, while the care of the vulnerable subjects of others was praiseworthy, it was not obligatory. No state was bound to accept trouble or inconvenience for the sake of vulnerable outsiders. Grotius turns out to be less of an exemplar for present day notions of the Responsibility to Protect and other international duties of human protection than he is often said to be.
Migration as a Catalyst of Serbia’s Development
Authors: Rašević Mirjana
Published: December 2019

This article examines the link between Serbia’s demographic and socioeconomic momentum on the one hand, and the migration phenomenon on the other. This is done both to determine the restrictions for development and to identify the potential scope for using migration as a catalyst of Serbia’s development as an emigration country. The revised push and pull model by Fassmann and Musil (2013) and the migration transition model (from emigration to immigration countries), developed by Fassmann and Reeger (2012) have been chosen as the article’s theoretical frame of reference. The emphasis in the article is on qualitative consideration of these topics, but one that is based on various types of records. To that end, the author has used statistics and the findings of various national studies conducted in the recent years.
Exploring Diaspora Contribution to North Macedonia’s Development
Authors: Petreski Marjan
Published: December 2019

The objective of this article is to qualitatively assess the scope of diaspora contribution to the economic development of North Macedonia. The author’s key argument is that diaspora presents an indispensable source of opportunities for helping the development of the country. The author collected qualitative data and used existing quantitative data, and set them in an exploratory framework. Findings suggest that diaspora works positively for the economic and, broadly societal development of North Macedonia. The contribution of the various forms of diaspora engagement has been assessed as positive. The more systematic evidence existing on the role of remittances in development supports their poverty-alleviation role, as well their acting as informal social protection for the receiving households. However, findings suggest that the potential for diaspora engagement in North Macedonia’s development remains significantly underutilized, particularly in terms of diaspora investment. The insufficiently systematic approach in dealing with the issue, government inefficiency and the perception of political uncertainty and the (deficiency in) rule of law are identified key stumbling blocks.
Four new species of Cerambycidae (Coleoptera) from Bolivia and Brazil
Authors: GALILEO MARIA HELENA M. , MARTINS UBIRAJARA R. , SANTOS-SILVA ANTONIO
Published: December 2019

Four new species of Cerambycidae are described: Sphaerion iuasanga (Elaphidiini), Glypthaga arena, Hypsioma albosericea (Onciderini) from Bolivia (Santa Cruz), and Hesycha jataiensis (Onciderini) from Brazil.
Checklist of beetles in the subgenus Copris (Paracopris) Balthasar from Asia with description of a new species, and redescription of Copris (Paracopris) punctulatus Wiedemann (Coleoptera: Scarabaeidae: Scarabaeinae)
Authors: BUI VAN BAC , ZIEGLER THOMAS , BONKOWSKI MICHAEL
Published: December 2019

We present the first checklist of Asian beetles of the subgenus Copris (Paracopris) Balthasar, 1939 including new data on the distribution. In addition, Copris (Paracopris) javanensis Bui, Ziegler & Bonkowski, new species from Java (Indonesia) is described and Copris (Paracopris) punctulatus Wiedemann, 1823 is redescribed based on specimens deposited in the Muséum National d’Histoire Naturelle (Paris, France), including detailed illustrations of both sexes and male genitalia. At the same time, a neotype is designated for C. (P.) punctulatus as the type specimen was lost.
Two new species of Lobellini from Central-South China (Collembola: Neanuridae)
Authors: HU YA-HUI , JIANG CHENG , JIANG JI-GANG , JIANG JI-GANG
Published: December 2019

Four species of the tribe Lobellini (Collembola: Neanuridae: Neanurinae) are recorded from Langshan National Geopark, Hunan Province, Central-South China. Two of them, Crossodonthina langshanensis sp. nov. and Lobellina gladius sp. nov., are new to science and described in this paper. Crossodonthina langshanensis sp. nov. is characterized by 2+2 black eyes on head; labral chaetotaxy as 2/4, 2; cephalic chaeta O present; mandible with 2 teeth and 2 fringed rami; maxilla outer lamella with filaments on inner edge. Lobellina gladius sp. nov. can be recognized by mandible with six teeth, cephalic chaeta O present and included in tubercle Fr, non-cross type chaetotaxy on cephalic posterior area, cephalic lateral tubercle Dl, L and So independent, Ant. I with 9 chaetae, Th. I with 4+4 tubercles, VT with 6–8 (usually 7) chaetae. New localities of Crossodonthina choui Jiang & Zhang, 2012 and Lobellina yinae Jiang, Huang & Luan, 2018 are also provided.
Region of interest–based segmented tiled adaptive streaming using head-mounted display tracking sensing data
Authors: Kim Hyun-Wook , Yang Sung-Hyun
Published: December 2019

To support 360 virtual reality video streaming services, high resolutions of over 8K and network streaming technology that guarantees consistent quality of service are required. To this end, we propose 360 virtual reality video player technology and a streaming protocol based on MPEG Dynamic Adaptive Streaming over HTTP Spatial Representation Description to support the player. The player renders the downsized video as the base layer, which has a quarter of the resolution of the original video, and high-quality video tiles consisting of tiles obtained from the tiled-encoded high-quality video (over 16K resolution) as the enhanced layer. Furthermore, we implemented the system and conducted experiments to measure the network bandwidth for 16K video streaming and switching latency arising from changes in the viewport. From the results, we confirmed that the player has a switching latency of less than 1000 ms and a maximum network download bandwidth requirement of 100 Mbps.
Costs and benefits of agricultural ammonia emission abatement options for compliance with European air quality regulations
Authors: Giannakis Elias , Kushta Jonilda , Bruggeman Adriana , Lelieveld Jos
Published: December 2019

Background

In Europe, ammonia (NH3) emissions strongly contribute to fine particulate matter (PM2.5) pollution and associated premature human mortality. The National Emission Ceilings Directive 2016/2284/EU has set an obligation for all European Union countries to reduce the NH3 emissions by 6%, relative to 2005, by 2020. This study aims to assess the costs and benefits of four NH3 emission abatement options for the compliance of the agricultural sector with the commitments of the European air quality regulatory framework. A regional atmospheric model (WRF/Chem) was used to assess the effects of regulating NH3 emissions reductions on PM2.5 concentrations over Europe. Non-market valuation techniques (value of statistical life) were used to monetize the associated health outcomes.

Results

We calculated that 16 out of the 28 EU member states exceeded their 2020 NH3 emission ceilings in 2016. The highest exceedances from the 2020 emission commitment level occurred in Latvia (15%), Germany (12%) and the UK (12%). Simulation of the required NH3 emission reduction by WRF/Chem showed that relatively large reductions in PM2.5 concentrations occur over central-western Europe and the UK. The largest health benefits (> 5% reduction in premature mortality) were found for Scandinavia. The economic benefit from avoided premature deaths over Europe amounts to 14,837 M€/year. The costs of four NH3 emission abatement options, where each would fully achieve the required emission reduction, range from 80 M€/year for low nitrogen feed to 3738 M€/year for low-emission animal housing, with covered manure storage (236 M€/year) and urea fertilizer application (253 M€/year), in between.

Conclusion

Our analysis indicates that the costs of compliance by the agricultural sector with the commitments of the European air quality regulations are much lower than the economic benefit. Thus, much more ambitious reduction commitments for NH3 emissions could be applied by the EU-28. The monetization of the health benefits of NH3 emission abatement policies and the assessment of the implementation costs can help policy-makers devise effective air pollution control programmes.
Distinguishing successive ancient polyploidy levels based on genome-internal syntenic alignment
Authors: Zhang Yue , Zheng Chunfang , Sankoff David
Published: December 2019

Background

A basic tool for studying the polyploidization history of a genome, especially in plants, is the distribution of duplicate gene similarities in syntenically aligned regions of a genome. This distribution can usually be decomposed into two or more components identifiable by peaks, or local maxima, each representing a different polyploidization event. The distributions may be generated by means of a discrete time branching process, followed by a sequence divergence model. The branching process, as well as the inference of fractionation rates based on it, requires knowledge of the ploidy level of each event, which cannot be directly inferred from the pair similarity distribution.

Results

For a sequence of two events of unknown ploidy, either tetraploid, giving rise to whole genome doubling (WGD), or hexaploid, giving rise to whole genome tripling (WGT), we base our analysis on triples of similar genes. We calculate the probability of the four triplet types with origins in one or the other event, or both, and impose a mutational model so that the distribution resembles the original data. Using a ML transition point in the similarities between the two events as a discriminator for the hypothesized origin of each similarity, we calculate the predicted number of triplets of each type for each model combining WGT and/or WGD. This yields a predicted profile of triplet types for each model. We compare the observed and predicted triplet profiles for each model to confirm the polyploidization history of durian, poplar and cabbage.

Conclusions

We have developed a way of inferring the ploidy of up to three successive WGD and/or WGT events by estimating the time of origin of each of the similarities in triples of genes. This may be generalized to a larger number of events and to higher ploidies.
Generating normal networks via leaf insertion and nearest neighbor interchange
Authors: Zhang Louxin
Published: December 2019

Background

Galled trees are studied as a recombination model in theoretical population genetics. This class of phylogenetic networks has been generalized to tree-child networks and other network classes by relaxing a structural condition imposed on galled trees. Although these networks are simple, their topological structures have yet to be fully understood.

Results

It is well-known that all phylogenetic trees on n taxa can be generated by the insertion of the n-th taxa to each edge of all the phylogenetic trees on n−1 taxa. We prove that all tree-child (resp. normal) networks with k reticulate nodes on n taxa can be uniquely generated via three operations from all the tree-child (resp. normal) networks with k−1 or k reticulate nodes on n−1 taxa. Applying this result to counting rooted phylogenetic networks, we show that there are exactly $\frac {(2n)!}{2^{n} (n-1)!}-2^{n-1} n!$(2n)!2n(n−1)!−2n−1n! binary phylogenetic networks with one reticulate node on n taxa.

Conclusions

The work makes two contributions to understand normal networks. One is a generalization of an enumeration procedure for phylogenetic trees into one for normal networks. Another is simple formulas for counting normal networks and phylogenetic networks that have only one reticulate node.
Modeling aspects of the language of life through transfer-learning protein sequences
Authors: Heinzinger Michael , Elnaggar Ahmed , Wang Yu , Dallago Christian , Nechaev Dmitrii , Matthes Florian , Rost Burkhard
Published: December 2019

Background

Predicting protein function and structure from sequence is one important challenge for computational biology. For 26 years, most state-of-the-art approaches combined machine learning and evolutionary information. However, for some applications retrieving related proteins is becoming too time-consuming. Additionally, evolutionary information is less powerful for small families, e.g. for proteins from theDark Proteome. Both these problems are addressed by the new methodology introduced here.

Results

We introduced a novel way to represent protein sequences as continuous vectors (embeddings) by using the language model ELMo taken from natural language processing. By modeling protein sequences, ELMo effectively captured the biophysical properties of the language of life from unlabeled big data (UniRef50). We refer to these new embeddings asSeqVec(Sequence-to-Vector) and demonstrate their effectiveness by training simple neural networks for two different tasks. At the per-residue level, secondary structure (Q3 = 79% ± 1, Q8 = 68% ± 1) and regions with intrinsic disorder (MCC = 0.59 ± 0.03) were predicted significantly better than through one-hot encoding or through Word2vec-like approaches. At the per-protein level, subcellular localization was predicted in ten classes (Q10 = 68% ± 1) and membrane-bound were distinguished from water-soluble proteins (Q2 = 87% ± 1). AlthoughSeqVecembeddings generated the best predictions from single sequences, no solution improved over the best existing method using evolutionary information. Nevertheless, our approach improved over some popular methods using evolutionary information and for some proteins even did beat the best. Thus, they prove to condense the underlying principles of protein sequences. Overall, the important novelty is speed: where the lightning-fastHHblitsneeded on average about two minutes to generate the evolutionary information for a target protein,SeqVeccreated embeddings on average in 0.03 s. As this speed-up is independent of the size of growing sequence databases,SeqVecprovides a highly scalable approach for the analysis of big data in proteomics, i.e. microbiome or metaproteome analysis.

Conclusion

Transfer-learning succeeded to extract information from unlabeled sequence databases relevant for various protein prediction tasks. SeqVec modeled the language of life, namely the principles underlying protein sequences better than any features suggested by textbooks and prediction methods. The exception is evolutionary information, however, that information is not available on the level of a single sequence.
Comparative transcriptomic analysis of surf clams (Paphia undulate) infected with two strains of Vibrio spp. reveals the identity of key immune genes involved in host defense
Authors: Yu Mingjia , Zheng Lin , Wang Xiaobo , Wu Minfu , Qi Ming , Fu Wandong , Zhang Yang
Published: December 2019

Background

Vibrio spp. is the major infection-producing marine bacteria in commercially important bivalve Paphia undulata. The host resistance is the major determining factor for the development of pathogenesis. To explore defense mechanisms, researchers have focused primarily on the study of differential expression of individual or specific groups of host immune genes during pathogen-challenge.

Results

We compared the expression profile in the surf clams infected with avirulent V. alginolyticus and virulent V. parahaemolyticus to mark the possible molecular mechanisms of pathogenesis. Comparison of the differentially expressed genes between the two groups of Vibrio-infected clams revealed that the number of down-regulate genes in V. parahaemolyticus injected clams (1433) were significantly higher than the other group (169). Based on Gene Ontology classification, a large proportion of these down-regulate genes were found to be associated with cellular and molecular mechanisms for pathogen recognition, and immunity development thereby explaining the low survival rate for the V. parahaemolyticus-treated clams and suggesting a higher virulence of this bacterium towards the surf clams. Quantitative real-time PCR of 24 candidate genes related to immunity involving the JAK-STAT signaling pathway, complementary cascade, cytokine signaling pathway, oxidative stress, phagocytosis and apoptosis down regulated under V. parahaemolyticus infection, indicating compromised host defense. Furthermore, we could demonstrate a central role of JAK-STAT pathway in bacterial clearance. dsRNA mediated depletion of a clam STAT homolog gene results in dramatic increase in the infection by V. alginolyticus, a mildly pathogenic strain under control conditions.

Conclusions

The difference in gene expression profiles in surf clams treated with two Vibrio species with a differential pathogenicity to P. undulate and downstream molecular analysis could enlighten on the probable molecular mechanisms of the Vibrio pathogenesis and the virulence of V. parahaemolyticus in surf clams, which also benefits to develop new strategies for disease control in surf calm aquaculture.
Protein expression profiles in Meishan and Duroc sows during mid-gestation reveal differences affecting uterine capacity, endometrial receptivity, and the maternal–fetal Interface
Authors: Wang Kejun , Yang Kaijie , Xu Qiao , Liu Yufang , Li Wenting , Bai Ying , Wang Jve , Ding Cui , Liu Ximing , Tang Qiguo , Luo Yabiao , Zheng Jie , Wu Keliang , Fang Meiying
Published: December 2019

Background

Embryonic mortality is a major concern in the commercial swine industry and primarily occurs early in gestation, but also during mid-gestation (~ days 50–70). Previous reports demonstrated that the embryonic loss rate was significant lower in Meishan than in commercial breeds (including Duroc). Most studies have focused on embryonic mortality in early gestation, but little is known about embryonic loss during mid-gestation.

Results

In this study, protein expression patterns in endometrial tissue from Meishan and Duroc sows were examined during mid-gestation. A total of 2170 proteins were identified in both breeds. After statistical analysis, 70 and 114 differentially expressed proteins (DEPs) were identified in Meishan and Duroc sows, respectively. Between Meishan and Duroc sows, 114 DEPs were detected at day 49, and 98 DEPs were detected at day 72. Functional enrichment analysis revealed differences in protein expression patterns in the two breeds. Around half of DEPs were more highly expressed in Duroc at day 49 (DUD49), relative to DUD72 and Meishan at day 49 (MSD49). Many DEPs appear to be involved in metabolic process such as arginine metabolism. Our results suggest that the differences in expression affect uterine capacity, endometrial matrix remodeling, and maternal-embryo cross-talk, and may be major factors influencing the differences in embryonic loss between Meishan and Duroc sows during mid-gestation.

Conclusions

Our data showed differential protein expression pattern in endometrium between Meishan and Duroc sows and provides insight into the development process of endometrium. These findings could help us further uncover the molecular mechanism involved in prolificacy.
Effectiveness of immunosuppressive therapy for nephrotic syndrome in a patient with late-onset Fabry disease: a case report and literature review
Authors: Fujisawa Hironobu , Nakayama Yosuke , Nakao Shoichiro , Yamamoto Ryo , Kurokawa Yuka , Nakamura Nao , Nagata Akiko , Tsukimura Takahiro , Togawa Tadayasu , Sakuraba Hitoshi , Fukami Kei
Published: December 2019

Background

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of theGLAgene, followed by deficiency in α-galactosidase A (α-gal) activity. Nephrotic syndrome, as the renal phenotype of FD, is unusual. Here, we report the rare case of a patient with FD with nephrotic syndrome whose proteinuria disappeared by immunotherapy.

Case presentation

A 67-year-old Japanese man was admitted to our hospital because of emesis, abdominal pain, and facial edema due to nephrotic syndrome. The patient was diagnosed with focal segmental glomerulosclerosis (FSGS) by renal biopsy before being diagnosed with FD, and immunotherapy was initiated. After treatment, the kidney biopsy results showed typical glycosphingolipid accumulation in the podocytes of this patient. The white blood cell α-gal activity was very low, and genetic analysis revealed aGLAgene variant (M296I), which is known as a late-onset genetic mutation of FD. Immunotherapy (steroids and cyclosporine A) dramatically improved the massive proteinuria. Currently, he has been undergoing enzyme replacement therapy, and his proteinuria has further decreased. There is the possibility that other nephrotic syndromes, such as minimal change nephrotic syndrome or FSGS, may co-exist in this patient.

Conclusions

We experienced the rare case of a FD patient whose nephrotic syndrome disappeared by immunotherapy. These findings suggest that immunosuppressive treatment may be considered if nephrotic syndrome develops, even in patients with FD.
The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease
Authors: Sun Hong-Xiao , Li Guo-Ju , Du Zhan-Hui , Bing Zhen , Ji Zhi-Xian , Luo Gang , Pan Si-Lin
Published: December 2019

Background

Pulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD.

Methods

In this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /μL of peripheral blood was calculated using the following formula: EPCs /μL = WBC /L × lymphocytes % × EPCs % × 10− 6.

Results

The median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/μL, 1.30 /μL and 0.98/μL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16–0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05).

Conclusion

The findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.
A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation
Authors: Demond Hannah , Anvar Zahra , Jahromi Bahia Namavar , Sparago Angela , Verma Ankit , Davari Maryam , Calzari Luciano , Russo Silvia , Jahromi Mojgan Akbarzadeh , Monk David , Andrews Simon , Riccio Andrea , Kelsey Gavin
Published: December 2019

Background

Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses: in the devastating gestational abnormality biparental complete hydatidiform mole (BiCHM) or in multi-locus imprinting disease (MLID). However, the developmental timing, genomic extent and mechanistic basis of these imprinting defects are unknown. The rarity of these disorders and the possibility that methylation defects originate in oocytes have made these questions very challenging to address.

Methods

Single-cell bisulphite sequencing (scBS-seq) was used to assess methylation in oocytes from a patient with BiCHM identified to be homozygous for an inactivating mutation in the human SCMC component KHDC3L. Genome-wide methylation analysis of a preimplantation embryo and molar tissue from the same patient was also performed.

Results

High-coverage scBS-seq libraries were obtained from five KHDC3Lc.1A>G oocytes, which revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. Importantly, germline differentially methylated regions (gDMRs) of imprinted genes were affected similarly to other sequence features that normally become methylated in oocytes, indicating no selectivity towards imprinted genes. A range of methylation losses was observed across genomic features, including gDMRs, indicating variable sensitivity to defects in the SCMC. Genome-wide analysis of a pre-implantation embryo and molar tissue from the same patient showed that following fertilisation methylation defects at imprinted genes persist, while most non-imprinted regions of the genome recover near-normal methylation post-implantation.

Conclusions

We show for the first time that the integrity of the SCMC is essential for de novo methylation in the female germline. These findings have important implications for understanding the role of the SCMC in DNA methylation and for the origin of imprinting defects, for counselling affected families, and will help inform future therapeutic approaches.
Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases
Authors: Salfati Elias L. , Spencer Emily G. , Topol Sarah E. , Muse Evan D. , Rueda Manuel , Lucas Jonathan R. , Wagner Glenn N. , Campman Steven , Topol Eric J. , Torkamani Ali
Published: December 2019

Background

Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis.

Methods

Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem “molecular autopsy” cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest.

Results

Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively.

Conclusions

The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.
Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice
Authors: Scarneo Scott A. , Eibschutz Liesl S. , Bendele Phillip J. , Yang Kelly W. , Totzke Juliane , Hughes Philip , Fox David A. , Haystead Timothy A. J.
Published: December 2019

Objectives

To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells.

Methods

Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF).

Results

Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling.

Conclusion

Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.
Etiologic workup in cases of cryptogenic stroke: protocol for a systematic review and comparison of international clinical practice guidelines
Authors: Bray Emma P. , McMahon Naoimh E. , Bangee Munirah , Al-Khalidi A. Hakam , Benedetto Valerio , Chauhan Umesh , Clegg Andrew J. , Georgiou Rachel F. , Gibson Josephine , Lane Deirdre A. , Lip Gregory Y. H. , Lightbody Elizabeth , Sekhar Alakendu , Chatterjee Kausik , Watkins Caroline L.
Published: December 2019

Background

Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases, the exact aetiology cannot be determined using existing investigative protocols. Such strokes are classed as ‘cryptogenic’ or as a stroke of unknown origin. However, there exists substantial variation in clinical practice when investigating cases of seemingly cryptogenic stroke, often reflecting local service availability and the preferences of treating clinicians. This variation in practice is compounded by the lack of international consensus as to the optimum level and timing of investigations required following a stroke. To address this gap, we aim to systematically review and compare recommendations in evidence-based clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke, and any subsequent diagnosis of cryptogenic stroke.

Method

We will search for CPGs using electronic databases (MEDLINE, Health Management Information Consortium (HMIC), EMBASE, and CINAHL), relevant websites and search engines (e.g. guideline specific websites, governmental, charitable, and professional practice organisations) and hand-searching of bibliographies and reference lists. Two reviewers will independently screen titles, abstracts and CPGs using a pre-defined relevance criteria form. From each included CPG, we will extract definitions and terms for cryptogenic stroke; recommendations related to assessment and investigation of the aetiology of stroke, including the grade of recommendations and underpinning evidence. The quality of the included CPGs will be assessed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Recommendations across the CPGs will be summarised descriptively highlighting areas of convergence and divergence between CPGs.

Discussion

To our knowledge, this will be the first review to systematically compare recommendations of international CPGs on investigating the aetiology of ischaemic stroke. The findings will allow for a better understanding of international perspectives on the optimum level of investigations required following a stroke and thus contribute to achieving greater international consensus on best practice in this important and complex area.

Systematic review registration

PROSPERO CRD42019127822.
Observation-based estimates of land availability for wind power: a case study for Czechia
Authors: Nitsch Felix , Turkovska Olga , Schmidt Johannes
Published: December 2019

Background

The availability of land for the installation of wind power turbines is restricted by numerous factors. Besides climatic conditions, the deployment of wind energy is limited by technical, social, economic, and environmental factors. Typically, assessments of land availability for wind power use legal and technical criteria to estimate the potential for wind power expansion. In contrast, we use observed characteristics of wind power generation sites existing in Austria and Denmark to estimate its potential expansion in Czechia. We combined data on wind turbine locations with data on land use, wind speeds, human impact on land, and nature conservation areas.

Results

Our analysis shows that the density of wind power in Austria is variable, but higher on average (4.79 MW km−2) than in Denmark (1.76 MW km−2). Austrian wind turbines have been installed in areas where the human impact on land is mostly higher than the Austrian average, while in Denmark, no difference is observed. Regarding the land use composite, the share of agricultural land on sites with wind turbines is on average much higher (86%), while the share of forest is much lower (7%) in both countries. We identified a maximum potential area in Czechia of 543 km2 with Austrian and 421 km2 with Danish characteristics. When conservatively assuming observed historical power densities, this area translates to 2295 MW and 741 MW of installed wind power capacity, respectively. These results are a magnitude of order lower than the potentials found in existing studies. In a sensitivity analysis, we have examined that the availability of potential sites depends mainly on the population density, the human impact on land, prevailing wind speeds, and the height above sea level.

Conclusions

We estimated available land area for potential wind turbine installations in Czechia using our newly developed methodology based on observed site characteristics of today’s wind power infrastructure in Austria and Denmark. Available land area indicated possible overestimation of wind power capacities proposed in the recent studies on the renewable energy transition. Hence, more rigorous consideration of land availability is required for assessments of potential wind power expansion.
Deep convolutional neural network based medical image classification for disease diagnosis
Authors: Yadav Samir S. , Jadhav Shivajirao M.
Published: December 2019

Medical image classification plays an essential role in clinical treatment and teaching tasks. However, the traditional method has reached its ceiling on performance. Moreover, by using them, much time and effort need to be spent on extracting and selecting classification features. The deep neural network is an emerging machine learning method that has proven its potential for different classification tasks. Notably, the convolutional neural network dominates with the best results on varying image classification tasks. However, medical image datasets are hard to collect because it needs a lot of professional expertise to label them. Therefore, this paper researches how to apply the convolutional neural network (CNN) based algorithm on a chest X-ray dataset to classify pneumonia. Three techniques are evaluated through experiments. These are linear support vector machine classifier with local rotation and orientation free features, transfer learning on two convolutional neural network models: Visual Geometry Group i.e., VGG16 and InceptionV3, and a capsule network training from scratch. Data augmentation is a data preprocessing method applied to all three methods. The results of the experiments show that data augmentation generally is an effective way for all three algorithms to improve performance. Also, Transfer learning is a more useful classification method on a small dataset compared to a support vector machine with oriented fast and rotated binary (ORB) robust independent elementary features and capsule network. In transfer learning, retraining specific features on a new target dataset is essential to improve performance. And, the second important factor is a proper network complexity that matches the scale of the dataset.
Injuries among Amish children: opportunities for prevention
Authors: Strotmeyer Stephen , Koff Abigail , Honeyman Joshua N. , Gaines Barbara A.
Published: December 2019

Objectives

The purpose of this study was to examine the injury risk patterns among Amish children, many of whom may be exposed to uncommon injuries and limited access to care due to their agrarian lifestyle and remote communities.

Design

Retrospective Chart Review.

Methods

With IRB approval, we performed a retrospective review of Amish patients age ≤ 12 years presenting to a level I pediatric trauma center between January 1, 2005, and December 31, 2015. Data abstracted from the institutional trauma registry and electronic medical record were analyzed using descriptive statistics and univariate/multivariate analysis.

Results

One hundred eighty-three Amish children were admitted, and 2 died from injuries. Patients were 72.1% male; the median age was 5 (IQR 3–8); median injury severity score (ISS) was 9 (IQR 4–14), Most injuries were the result of blunt force trauma (91.8%). The most frequent mechanisms were falls (42.6%), followed by animal-related (15.3%), and buggy (12.5%). Most injuries occurred at home (44.4%) or on a farm (33.9%). Hay hole falls were a unique source of injury with a high ISS (12; IQR 6–17). The overall median length of stay (LOS) was 2 days (IQR 1–3), with animal-related injuries associated with the longest LOS (3 days; IQR 1–4.75).

Conclusions

The majority of injuries among Amish children are due to falls. Hay hole falls and animal-related injuries result in the highest ISS and longest LOS. These findings identify the farm as a potential target for culturally appropriate interventions for risk modification.
Correction to: Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in Aspergillus niger submerged culture
Authors: Cairns Timothy C. , Feurstein Claudia , Zheng Xiaomei , Zhang Li Hui , Zheng Ping , Sun Jibin , Meyer Vera
Published: December 2019

Following publication of the original article [1], the authors provided revised images for Figs. 4, 6 and 7 which were not processed by the typesetter during proof-correction stage. The corrected figures are given with this erratum.
First report of Entamoeba moshkovskii in human stool samples from symptomatic and asymptomatic participants in Kenya
Authors: Kyany’a Cecilia , Eyase Fredrick , Odundo Elizabeth , Kipkirui Erick , Kipkemoi Nancy , Kirera Ronald , Philip Cliff , Ndonye Janet , Kirui Mary , Ombogo Abigael , Koech Margaret , Bulimo Wallace , Hulseberg Christine E.
Published: December 2019

Entamoeba moshkovskii is a member of the Entamoeba complex and a colonizer of the human gut. We used nested polymerase chain reaction (PCR) to differentiate Entamoeba species in stool samples that had previously been screened by microscopy. Forty-six samples were tested, 23 of which had previously been identified as Entamoeba complex positive by microscopy. Of the 46 specimens tested, we identified nine (19.5%) as E. moshkovskii-positive. In seven of these nine E. moshkovskii-positive samples, either E. dispar or E. histolytica (or both) were also identified, suggesting that co-infections may be common. E. moshkovskii was also detected in both symptomatic and asymptomatic participants. To the best of our knowledge, this is the first report of E. moshkovskii in Kenya.