bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundFabry 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 presentationA 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.ConclusionsWe 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractMedical 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

AbstractObjectivesThe 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.DesignRetrospective Chart Review.MethodsWith 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.ResultsOne 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).ConclusionsThe 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.