bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization and serodiagnostic potential of two serpin proteins in Psoroptes ovis var. cuniculi
Authors: Gu Xiaobin , Chen Yuhang , Zhang Chongyang , Xie Yue , Shen Nengxing , Wang Ce , Zhou Xuan , Yang Guangyou , He Ran , Peng Xuerong , Yang Deying , He Zhi , Zhong Zhijun 
Published: December 2020

Abstract
Background
Psoroptes ovis var. cuniculi is a common ectoparasite of wild and domestic rabbits worldwide that causes economically devastating losses in commercial rabbit husbandry and significantly affects the overall health of rabbits. Serine proteinase inhibitor (serpin) is present in almost all organisms that are involved in host–pathogen interactions, inflammatory responses, and reproductive development, among others. However, very little research has been carried out on P. ovis var. cuniculi serpins.

Methods
Two serpin genes of P. ovis var. cuniculi (Pso c 27 and PsoSP2 cDNAs) were cloned and molecularly characterized. The transcriptional profiles and tissue localization of these two serpins in P. ovis var. cuniculi were investigated by quantitative real-time PCR and immunohistochemistry, respectively. The potential function of recombinant Pso c 27 and PsoSP2 (rPso c 27 and rPsoSP2) in the serodiagnosis of P. ovis var. cuniculi infestation in rabbits was evaluated using a newly devleoped indirect enzyme-linked immunosorbent assay.

Results
Both the 523-residue Pso c 27 and the 240-residue PsoSP2 proteins contained typical serpin domains and signatures. Both Pso c 27and PsoSP2 cDNAs were expressed throughout the life-cycle; specifically, the cDNAs showed significantly higher expression in female mites than in larva, nymph, and male mites (Pso c 27: F(3, 8) = 1935.953, P < 0.0001; PsoSP2: F(3, 8) = 660.669, P < 0.0001). The native Pso c 27 and PsoSP2 proteins localized in the ovary and mouthparts of adult female mites, respectively. Compared to rPsoSP2, rPso c 27 showed better diagnostic efficiency, with higher values of sensitivity, specificity, and area under the receiver operating characteristic curve (rPso c 27 vs rPsoSP2: 96.0 vs 90.0%; 90.91 vs 78.18%; 0.988 vs 0.964, respectively). Moreover, rPso c 27 showed seropositivity in 80% of the rabbits as early as the 2 weeks post-infestation, prior to visible clinical signs and microscopy-positive of skin scrapings.

Conclusions
These results suggest that these two serpins may play essential roles in reproductive development, serum-feeding, and pathogenicity of P. ovis var. cuniculi. Compared to PsoSP2, Pso c 27 appears to be a potential antigen for serodiagnosis of P. ovis var. cuniculi infestation in rabbits, especially at the early stage of infestation.

Graphical Abstract
Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis
Authors: Good Misty , Chu Tianjiao , Shaw Patricia , McClain Lora , Chamberlain Austin , Castro Carlos , Rimer Jamie M. , Mihi Belgacem , Gong Qingqing , Nolan Lila S. , Cooksey Krista , Linneman Laura , Agrawal Pranjal , Finegold David N. , Peters David 
Published: December 2020

AbstractBackgroundNecrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.MethodsUsing laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.ResultsWe found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.ConclusionsWe have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.
Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm
Authors: Santos Jr Hudson P. , Bhattacharya Arjun , Joseph Robert M. , Smeester Lisa , Kuban Karl C. K. , Marsit Carmen J. , O’Shea T. Michael , Fry Rebecca C. 
Published: December 2020

AbstractBackgroundChildren born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes.MethodsWe examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS.ResultsGenes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case–control status.LimitationsThe ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited.ConclusionsAggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic.
Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study
Authors: Brkić Diandra , Ng-Cordell Elise , O’Brien Sinéad , Scerif Gaia , Astle Duncan , Baker Kate 
Published: December 2020

Abstract
Background
The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants.

Methods
Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n = 29) or chromatin regulation (n = 23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components—Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks.

Results
We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety.

Limitations
Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups.

Conclusion
We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful.
Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway
Authors: Xu Chu , Liu Haijie , He Yuanjia , Li Yuanqing , He Xiaoning 
Published: December 2020

Abstract
Background
The role of bone tissue engineering is to regenerate tissue using biomaterials and stem cell-based approaches. Combination of two or more cell types is one of the strategies to promote bone formation. Endothelial progenitor cells (EPCs) may enhance the osteogenic properties of mesenchymal stem cells (MSCs) and promote bone healing; this study aimed to investigate the possible mechanisms of EPCs on promoting osteogenic differentiation of MSCs.

Methods
MSCs and EPCs were isolated and co-cultured in Transwell chambers, the effects of EPCs on the regulation of MSC biological properties were investigated. Real-time PCR array, and western blotting were performed to explore possible signaling pathways involved in osteogenesis. The expression of osteogenesis markers and calcium nodule formation was quantified by qRT-PCR, western blotting, and Alizarin Red staining.

Results
Results showed that MSCs exhibited greater alkaline phosphatase (ALP) activity and increased calcium mineral deposition significantly when co-cultured with EPCs. The mitogen-activated protein kinase (MAPK) signaling pathway was involved in this process. p38 gene expression and p38 protein phosphorylation levels showed significant upregulation in co-cultured MSCs. Silencing expression of p38 in co-cultured MSCs reduced osteogenic gene expression, protein synthesis, ALP activity, and calcium nodule formation.

Conclusions
These data suggest paracrine signaling from EPCs influences the biological function and promotes MSCs osteogenic differentiation. Activation of the p38MAPK pathway may be the key to enhancing MSCs osteogenic differentiation via indirect interactions with EPCs.
Autologous adipose mesenchymal stem cell administration in arteriosclerosis and potential for anti-aging application: a retrospective cohort study
Authors: Ohta Hiroki , Liu Xiaolan , Maeda Miho 
Published: December 2020

Abstract
Objective
Arteriosclerosis is an age-related disease and a leading cause of cardiovascular disease. In animal experiments, mesenchymal stem cells and its culture-conditioned medium have been shown to be promising tools for prevention or treatment of arteriosclerosis. On the basis of these evidences, we aimed to assess whether administration of autologous adipose-derived mesenchymal stem cells (Ad-MSC) is safe and effective for treatment of arteriosclerosis.

Methods
We retrospectively reviewed clinical records of patients with arteriosclerosis who had received autologous Ad-MSC administration at our clinic. Patients’ characteristics were recorded and data on lipid profile, intimal-media thickness (IMT), cardio-ankle vascular index (CAVI), and ankle-brachial index (ABI) before and after Ad-MSC administration were collected and compared.

Results
Treatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels. No adverse effect or toxicity was observed in relation to the treatment. Of the patients with abnormal HDL values before treatment, the vast majority showed improvement in the values. Overall, the measurements after treatment were significantly increased compared with those before treatment (p < 0.01). In addition, decreases in LDL cholesterol and RLP levels were observed after treatment in patients who had abnormal LDL cholesterol or RLP levels before treatment. The majority of patients with pre-treatment abnormal CAVI values had improved values after treatment. In patients with available IMT values, a significant decrease in the IMT values was found after therapy (p < 0.01). All patients with borderline arteriosclerosis disease had improved laboratory findings after treatment. In general, post-treatment values were significantly decreased as compared with pre-treatment values. Of the patients with normal ABI values before treatment at the same time as CAVI, the vast majority remained normal after treatment.

Conclusions
These findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.
Mitochondrial dysfunction and consequences in calpain-3-deficient muscle
Authors: Jahnke Vanessa E. , Peterson Jennifer M. , Van Der Meulen Jack H. , Boehler Jessica , Uaesoontrachoon Kitipong , Johnston Helen K. , Defour Aurelia , Phadke Aditi , Yu Qing , Jaiswal Jyoti K. , Nagaraju Kanneboyina 
Published: December 2020

AbstractBackgroundNonsense or loss-of-function mutations in the non-lysosomal cysteine protease calpain-3 result in limb-girdle muscular dystrophy type 2A (LGMD2A). While calpain-3 is implicated in muscle cell differentiation, sarcomere formation, and muscle cytoskeletal remodeling, the physiological basis for LGMD2A has remained elusive.MethodsCell growth, gene expression profiling, and mitochondrial content and function were analyzed using muscle and muscle cell cultures established from healthy and calpain-3-deficient mice. Calpain-3-deficient mice were also treated with PPAR-delta agonist (GW501516) to assess mitochondrial function and membrane repair. The unpairedttest was used to assess the significance of the differences observed between the two groups or treatments. ANOVAs were used to assess significance over time.ResultsWe find that calpain-3 deficiency causes mitochondrial dysfunction in the muscles and myoblasts. Calpain-3-deficient myoblasts showed increased proliferation, and their gene expression profile showed aberrant mitochondrial biogenesis. Myotube gene expression analysis further revealed altered lipid metabolism in calpain-3-deficient muscle. Mitochondrial defects were validated in vitro and in vivo. We used GW501516 to improve mitochondrial biogenesis in vivo in 7-month-old calpain-3-deficient mice. This treatment improved satellite cell activity as indicated by increased MyoD and Pax7 mRNA expression. It also decreased muscle fatigability and reduced serum creatine kinase levels. The decreased mitochondrial function also impaired sarcolemmal repair in the calpain-3-deficient skeletal muscle. Improving mitochondrial activity by acute pyruvate treatment improved sarcolemmal repair.ConclusionOur results provide evidence that calpain-3 deficiency in the skeletal muscle is associated with poor mitochondrial biogenesis and function resulting in poor sarcolemmal repair. Addressing this deficit by drugs that improve mitochondrial activity offers new therapeutic avenues for LGMD2A.
Measurement site of inferior vena cava diameter affects the accuracy with which fluid responsiveness can be predicted in spontaneously breathing patients: a post hoc analysis of two prospective cohorts
Authors: Caplan Morgan , Durand Arthur , Bortolotti Perrine , Colling Delphine , Goutay Julien , Duburcq Thibault , Drumez Elodie , Rouze Anahita , Nseir Saad , Howsam Michael , Onimus Thierry , Favory Raphael , Preau Sebastien 
Published: December 2020

Abstract
Background
The collapsibility index of the inferior vena cava (cIVC) has potential for predicting fluid responsiveness in spontaneously breathing patients, but a standardized approach for measuring the inferior vena cava diameter has yet to be established.
The aim was to test the accuracy of different measurement sites of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with sepsis-related circulatory failure and examine the influence of a standardized breathing manoeuvre.

Results
Among the 81 patients included in the study, the median Simplified Acute Physiologic Score II was 34 (24; 42). Sepsis was of pulmonary origin in 49 patients (60%). Median volume expansion during the 24 h prior to study inclusion was 1000 mL (0; 2000). Patients were not severely ill: none were intubated, only 20% were on vasopressors, and all were apparently able to perform a standardized breathing exercise. Forty-one (51%) patients were responders to volume expansion (i.e. a ≥ 10% stroke volume index increase). The cIVC was calculated during non-standardized (cIVC-ns) and standardized breathing (cIVC-st) conditions. The accuracy with which both cIVC-ns and cIVC-st predicted fluid responsiveness differed significantly by measurement site (interaction p < 0.001 and < 0.0001, respectively). Measuring inferior vena cava diameters 4 cm caudal to the right atrium predicted fluid responsiveness with the best accuracy. At this site, a standardized breathing manoeuvre also significantly improved predictive power: areas under ROC curves [mean and (95% CI)] for cIVC-ns = 0.85 [0.78–0.94] versus cIVC-st = 0.98 [0.97–1.0], p < 0.001. When cIVC-ns is superior or equal to 33%, fluid responsiveness is predicted with a sensitivity of 66% and a specificity of 92%. When cIVC-st is superior or equal to 44%, fluid responsiveness is predicted with a sensitivity of 93% and a specificity of 98%.

Conclusion
The accuracy with which cIVC measurements predict fluid responsiveness in spontaneously breathing patients depends on both the measurement site of inferior vena cava diameters and the breathing regime. Measuring inferior vena cava diameters during a standardized inhalation manoeuvre at 4 cm caudal to the right atrium seems to be the method by which to obtain cIVC measurements best-able to predict patients’ response to volume expansion.
Lie symmetry reductions and conservation laws for fractional order coupled KdV system
Authors: Jafari Hossein , Sun Hong Guang , Azadi Marzieh 
Published: December 2020

AbstractLie symmetry analysis is achieved on a new system of coupled KdV equations with fractional order, which arise in the analysis of several problems in theoretical physics and numerous scientific phenomena. We determine the reduced fractional ODE system corresponding to the governing factional PDE system.In addition, we develop the conservation laws for the system of fractional order coupled KdV equations.
The role of phagocytic leukocytes following flexible ureterenoscopy, for the treatment of kidney stones: an observational, clinical pilots-study
Authors: Hughes Stephen Fôn , Moyes Alyson Jayne , Lamb Rebecca May , Ella-tongwiis Peter , Snyper Nana Yaa Frempomaa , Shergill Iqbal 
Published: December 2020

AbstractBackgroundThe number of patients undergoing flexible ureterenoscopy (FURS) for the treatment of kidney stones (renal calculi) is increasing annually, and as such the development of post-operative complications, such as acute kidney injury (AKI), haematuria and infection is likely to increase. Phagocytic leukocytes are white blood cells that help fight foreign material such as bacteria and viruses, and they are intrinsically involved in the inflammatory reaction. Investigating the role of phagocytic leukocytes following FURS has not been widely researched. The main aim of the study was to evaluate the role phagocytic leukocytes (neutrophils and monocytes) function, in patients undergoing FURS for the treatment of kidney stones (renal calculi).MethodsFourteen consecutive patients aged between 27 and 70 years (median 49.5 years) undergoing FURS for the treatment of kidney stones were recruited (seven males, seven females). Blood samples were collected from each patient at four time points: baseline (pre-operatively) followed by 30, 120 and 240 min post-operatively. Mononuclear (MN) and polymorphonuclear (PMN) leukocyte sub-populations were isolated by density gradient centrifugation techniques. Neutrophil and monocyte cell function was investigated by measuring the cell surface expression of CD62L (L-selectin), CD11b (Mac-1), CD99 and the intracellular production of hydrogen peroxide (H2O2), via flow cytometry.ResultsSignificant increases was observed in monocyte CD62L expression post FURS for the treatment of kidney stones (p ≤ 0.05); while significant decreases were observed in neutrophil CD62L. The levels of the other activation markers CD11b, CD99 and H2O2corresponded to the increases and decreases seen in CD62L for monocytes and neutrophils respectively, though the changes were not statistically significant (p > 0.05). Limiting factors for this study were the relatively small sample size, and restriction on the recruitment time points.ConclusionsThis study demonstrates that following FURS for the treatment of kidney stones, monocytes are rapidly activated and produce potent reactive oxygen intermediates. Interestingly, the pattern of expression in neutrophils suggests that these cells are deactivated in response to the treatment. The leukocyte biomarkers assessed during this investigation may have a role in monitoring the ‘normal’ post-operative response, as no complications occurred in any of the patients; or may help predict potential infectious complications (e.g. urosepsis) that can occur during the post-operative period. This data, however, will need to be validated and reproduced in larger multi-centre studies.