bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study
Authors: Motta Benedetta M. , Grander Christoph , Gögele Martin , Foco Luisa , Vukovic Vladimir , Melotti Roberto , Fuchsberger Christian , De Grandi Alessandro , Cantaloni Chiara , Picard Anne , Mascalzoni Deborah , Rossini Alessandra , Pattaro Cristian , Tilg Herbert , Pramstaller Peter P. 
Published: December 2019

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants.

Methods
Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out.

Results
We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17).

Discussion
Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.
PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?
Authors: Pavone Piero , Corsello Giovanni. , Cho Sung Yoon , Pappalardo Xena Giada , Ruggieri Martino , Marino Simona Domenica , Jin Dong Kyu , Marino Silvia , Falsaperla Raffaele 
Published: December 2019

Abstract
Background
Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders.

Case presentation
We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing.

Conclusion
Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.
Assessment of quality of edible vegetable oils accessed in Gondar City, Northwest Ethiopia
Authors: Negash Yonnas Adugna , Amare Dagnachew Eyachew , Bitew Bikes Destaw , Dagne Henok 
Published: December 2019

Abstract
Objective
Edible vegetable oils are prone to quality deterioration through oxidation and microbial degradation resulting in nutritional loss and off-flavors. Quality deterioration may contribute in the formation of oxidation products that are reactive and toxic, which ultimately pose health risks including cancer and inflammation. The objective of this study was to assess quality of both imported and locally made edible vegetable oils accessed in Gondar City, Ethiopia. Cross-sectional study design was used to collect 60 samples randomly; 30 from locally made (Niger seed at market 14, Niger seed at production center 11, sunflower at the market 5) and 30 from imported palm oil brands (Avena 11, Hayat 4, Jersey 5 and Chef 10).

Results
The mean value for: moisture content (%) (0.333 ± 0.08 while 0.089 ± 0.11), specific-gravity (0.823 ± 0.14 and 0.807 ± 0.115), peroxide value (15.09 ± 1.61 and 7.05 ± 0.102 mill-equivalents of oxygen/kg), acid value (2.43 ± 0.9 and 0.98 ± 0.23 mg KOH/g oil) and iodine value (115.63 ± 6.77 and 21.8 ± 3.4 g I2/100 g oil) for local and imported edible oils, respectively. The results highlight that all rancidity quality parameters of the locally made oil samples were not within the joint WHO/FAO standards whilst the imported oils showed a greater fatty acid saturation.
Improving selectivity of DNA–RNA binding zinc finger using directed evolution
Authors: Sulej Agata A. 
Published: December 2019

Abstract
Objective
Type C2H2 zinc fingers bind a variety of substrates, specific sequences in the double-stranded DNA counting among them. Engineering efforts led to the discovery of a set of general rules that enable obtaining zinc fingers modules that bind to almost any given sequence. The objective of this work was to determine an analogical set of rules for the binding of specific sequences in DNA–RNA hybrids using directed evolution of ZfQQR zinc finger. The target regions for evolution included the amino acid residues that directly interact with the substrate and linkers between the zinc finger modules.

Results
The directed evolution was performed using selection based on biopanning of phage-displayed libraries of randomized regions in the ZfQQR zinc finger. The applied strategy of randomization of the middle module of the zinc finger along with input library bias and materials used for biopanning hindered the selection of the modules with altered specificity. However, the directed evolution of the linker sequence between modules enabled selection of variants with improved selectivity towards DNA–RNA hybrids in the presence of double-stranded DNA in comparison to the original ZfQQR. This confirms the necessity of linker optimization between modules in zinc finger domains.
Chest imaging using signs, symbols, and naturalistic images: a practical guide for radiologists and non-radiologists
Authors: Chiarenza Alessandra , Esposto Ultimo Luca , Falsaperla Daniele , Travali Mario , Foti Pietro Valerio , Torrisi Sebastiano Emanuele , Schisano Matteo , Mauro Letizia Antonella , Sambataro Gianluca , Basile Antonio , Vancheri Carlo , Palmucci Stefano 
Published: December 2019

AbstractSeveral imaging findings of thoracic diseases have been referred—on chest radiographs or CT scans—to signs, symbols, or naturalistic images. Most of these imaging findings include the air bronchogram sign, the air crescent sign, the arcade-like sign, the atoll sign, the cheerios sign, the crazy paving appearance, the comet-tail sign, the darkus bronchus sign, the doughnut sign, the pattern of eggshell calcifications, the feeding vessel sign, the finger-in-gloove sign, the galaxy sign, the ginkgo leaf sign, the Golden-S sign, the halo sign, the headcheese sign, the honeycombing appearance, the interface sign, the knuckle sign, the monod sign, the mosaic attenuation, the Oreo-cookie sign, the polo-mint sign, the presence of popcorn calcifications, the positive bronchus sign, the railway track appearance, the scimitar sign, the signet ring sign, the snowstorm sign, the sunburst sign, the tree-in-bud distribution, and the tram truck line appearance. These associations are very helpful for radiologists and non-radiologists and increase learning and assimilation of concepts.Therefore, the aim of this pictorial review is to highlight the main thoracic imaging findings that may be associated with signs, symbols, or naturalistic images: an “iconographic” glossary of terms used for thoracic imaging is reproduced—placing side by side radiological features and naturalistic figures, symbols, and schematic drawings.
Adult human cardiac stem cell supplementation effectively increases contractile function and maturation in human engineered cardiac tissues
Authors: Murphy Jack F. , Mayourian Joshua , Stillitano Francesca , Munawar Sadek , Broughton Kathleen M. , Agullo-Pascual Esperanza , Sussman Mark A. , Hajjar Roger J. , Costa Kevin D. , Turnbull Irene C. 
Published: December 2019

Abstract
Background
Delivery of stem cells to the failing heart is a promising therapeutic strategy. However, the improvement in cardiac function in animal studies has not fully translated to humans. To help bridge the gap between species, we investigated the effects of adult human cardiac stem cells (hCSCs) on contractile function of human engineered cardiac tissues (hECTs) as a species-specific model of the human myocardium.

Methods
Human induced pluripotent stem cell-derived cardiomyoctes (hCMs) were mixed with Collagen/Matrigel to fabricate control hECTs, with an experimental group of hCSC-supplemented hECT fabricated using a 9:1 ratio of hCM to hCSC. Functional testing was performed starting on culture day 6, under spontaneous conditions and also during electrical pacing from 0.25 to 1.0 Hz, measurements repeated at days 8 and 10. hECTs were then frozen and processed for gene analysis using a Nanostring assay with a cardiac targeted custom panel.

Results
The hCSC-supplemented hECTs displayed a twofold higher developed force vs. hCM-only controls by day 6, with approximately threefold higher developed stress and maximum rates of contraction and relaxation during pacing at 0.75 Hz. The spontaneous beat rate characteristics were similar between groups, and hCSC supplementation did not adversely impact beat rate variability. The increased contractility persisted through days 8 and 10, albeit with some decrease in the magnitude of the difference of the force by day 10, but with developed stress still significantly higher in hCSC-supplemented hECT; these findings were confirmed with multiple hCSC and hCM cell lines. The force-frequency relationship, while negative for both, control (− 0.687 Hz− 1; p = 0.013 vs. zero) and hCSC-supplemented (− 0.233 Hz− 1;p = 0.067 vs. zero) hECTs, showed a significant rectification in the regression slope in hCSC-supplemented hECT (p = 0.011 vs. control). Targeted gene exploration (59 genes) identified a total of 14 differentially expressed genes, with increases in the ratios of MYH7/MHY6, MYL2/MYL7, and TNNI3/TNNI1 in hCSC-supplemented hECT versus controls.

Conclusions
For the first time, hCSC supplementation was shown to significantly improve human cardiac tissue contractility in vitro, without evidence of proarrhythmic effects, and was associated with increased expression of markers of cardiac maturation. These findings provide new insights about adult cardiac stem cells as contributors to functional improvement of human myocardium.
Stability of functional differential systems applied to the model of testosterone regulation
Authors: Domoshnitsky Alexander , Volinsky Irina , Pinhasov Olga , Bershadsky Marina 
Published: December 2019

AbstractIn this paper we propose a method for stability studies of functional differential systems. The idea of our method is to reduce the analysis of ann-dimensional system to one for an$(n+m)$(n+m)-dimensional system, wheremis a natural number, to obtain stability and then to come back and make conclusions on the stability of the givenn-dimensional system. As an example, a model describing testosterone by distributed inputs feedback control is considered. The aim of the regulation is to hold testosterone concentration above an appropriate level. The feedback control with integral term is proposed. We have to increase the testosterone level to the normal one. The control we proposed could destroy the stability of the model. That is why we have to choose the parameters of our distributed control, namely a dosage or intensity of assimilation of a medicine in a human body in such a form that the stability of our system is preserved. Thus the problem of regulation of testosterone level leads us to the stability analysis of the functional differential system describing a connection between the concentrations of hormones (GnRH), (LH), and testosterone (Te). Constructing the system, we discard the connections which seem nonessential. To estimate the effect of these connections is an important problem. We construct the Cauchy matrix of integro-differential system to estimate this influence.
FOXC2-AS1 regulates phenotypic transition, proliferation and migration of human great saphenous vein smooth muscle cells
Authors: Zhang Chuang , Li Huixiang , Guo Xueli 
Published: December 2019

Abstract
Objectives
In varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2–Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process.

Methods
The effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition.

Results
The human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2.

Conclusion
FOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.
Bacillus thuringiensis kurstaki strains produce vegetative insecticidal proteins (Vip 3) with high potential
Authors: Güney Ebru , Adıgüzel Aysun , Demirbağ Zihni , Sezen Kazım 
Published: December 2019

AbstractBacillus thuringiensis(Bt) produces vegetative insecticidal proteins (Vip) during its vegetative growth stage. Vip3 proteins have a significant role in insecticidal activity of this bacterium. Each new bacterial isolate may encode Vip with different significance. The Vip protein coding by vip genes of twoBtstrains (BnBt and MnD) with high insecticidal activity was characterized in this study. Polymerase chain reaction (PCR)-based screening for Vip genes of theseBtisolates expressed the detected Vip gene and tested the protein for insecticidal activity against the cotton leafworm,Spodoptera littoralislarvae. As a result of the screening tests, Vip3 genes were determined in MnD and BnBt isolates. Vip3 genes of both isolates were expressed and confirmed by 90 kDa proteins. Partially purified and trypsin-activated protein samples of BnBt and MnD isolates were tested against the second instar larvae ofS. littoralis.The results showed that the highest insecticidal activity of the Vip3 proteins of BnBt and MnD was 86.66% and 83.33% mortality in 10 days, respectively. The median lethal concentrations (LC50) of BnBt and MnD were determined as 41.860 and 55.154 ng/μl, respectively. The results suggest that Vip3 protein is effective for preventing resistance in various insect-pest species. The expressed proteins may be utilized as a biopesticide against nocuous insects.
In vitro evaluation of some isolated bacteria against the plant parasite nematode Meloidogyne incognita
Authors: Soliman Gaziea Mohamed , Ameen Hoda Hussein , Abdel-Aziz Shadia Mohamed , El-Sayed Ghada M. 
Published: December 2019

AbstractBackgroundMicrobial cultures are extensively used as environment friendly ways for biological control of parasitic pests, including the root-knot nematodes, alternative to the use of chemical nematicides. The present study was conducted to isolate some lytic rhizobacteria and examine their nematicidal activity againstMeloidogyne incognitaJ2mortality and egg hatching in in vitro test.ResultsLytic Rhizobacteria were isolated from soil samples adhering to tomato plant roots from different localities at Giza governorate, Egypt. Six bacterial isolates, exhibited high efficacy against root-knot nematodes, were identified based on the analysis of the 16S rRNA gene sequence asPseudomonas aeruginosa,Paenibacillus polymyxa,Lysinibacillus sphaericus,Bacillus cereus,Bacillus subtilis, andAchromobacter xylosoxidans. These strains showed high production of chitinase, chitosanase, and protease using colloidal chitin and soluble chitosan as carbon sources. Two strains,Paenibacillus polymyxaandBacillus subtilis, produced the highest levels of chitinase in the media. Except forPseudomonas aeruginosa, all the bacterial strains produced high levels of chitosanase.ConclusionThe results revealed that high amounts of protease were, however, secreted byPseudomonas aeruginosaas compared to the other strains. In in vitro tests, all the bacterial culture filtrates potentially displayed nematicidal effect inM. incognitaegg hatching and an obvious increase in J2mortality as compared to control.Paenibacillus polymyxacaused 100% juvenile mortality followed byBacillus subtilis97.25%,Bacillus cereus94%,Achromobacter xylosoxidans93%,Lysinibacillus sphaericus92%, andPseudomonas aeruginosa84.29% after 48 h of exposure, as compared to control.
Optimization of energy storage and system flexibility in the context of the energy transition: Germany’s power grid as a case study
Authors: K. Maia Leonardo K. , Zondervan Edwin 
Published: December 2019

AbstractIn this work we explore the ramifications of incoming changes brought by the energy transition, most notably the increased penetration of variable renewable energy (VRE) and phase-out of nuclear and other conventional electricity sources. The power grid will require additional flexibility capabilities to accommodate such changes, as the mismatch between generation and demand is bound to increase. Through mathematical modeling and optimization, we simulate the German power grid and investigate the requirements of on-grid large-scale storage. Different scenarios are evaluated up to 2050, when 80% of the gross electricity consumption is planned to be provided by renewable energy. Dispatchable power plants will play a key role in the transition to an energy mix with high shares of VRE. Around 120 GW of additional large-scale storage are required until 2050. Between the electrochemical technologies evaluated, lithium-ion was the best candidate. A strong reliance on dispatchables was observed, in case the commissioning of VRE plants goes slower than planned. Energy curtailment increases with VRE shares, with up to 14 TWh curtailed in high VRE scenarios in 2050.
Prevalence and Predictors of Frailty in Childhood Cancer Survivors and Siblings: A Report From the Childhood Cancer Survivor Study
Authors: Hayek Samah , Gibson Todd M. , Leisenring Wendy M. , Guida Jennifer L. , Gramatges Maria Monica , Lupo Philip J. , Howell Rebecca M. , Oeffinger Kevin C. , Bhatia Smita , Edelstein Kim , Hudson Melissa M. , Robison Leslie L. , Nathan Paul C. , Yasui Yutaka , Krull Kevin R. , Armstrong Gregory T. , Ness Kirsten K. 
Published: December 2019

PURPOSE To estimate the prevalence of frailty among childhood cancer survivors and to determine the direct and indirect effects of treatment exposures, lifestyle factors, and severe, disabling, and life-threatening chronic condition on frailty. METHODS Childhood cancer survivors (≥ 5 years since diagnosis), treated between 1970 and 1999 when < 21 years old (n = 10,899; mean age, 37.6 ± 9.4 years; 48% male, 86% white) and siblings were included (n = 2,097; mean age, 42.9 ± 9.4 years). Frailty was defined as ≥ 3 of the following: low lean mass, exhaustion, low energy expenditure, walking limitations, and weakness. Generalized linear models were used to evaluate direct and indirect associations between frailty and treatment exposures, sociodemographic characteristics, lifestyle factors, and chronic condition. RESULTS The overall prevalence of frailty among survivors was 3 times higher compared with siblings (6.4%; 95% CI, 4.1% to 8.7%; v 2.2%; 95% CI, 1.2% to 3.2%). Survivors of CNS tumors (9.5%; 95% CI, 5.2% to 13.8%) and bone tumors (8.1%; 95% CI, 5.1% to 11.1%) had the highest prevalence of frailty. Survivors exposed to cranial radiation, pelvic radiation ≥ 34 Gy, abdominal radiation > 40 Gy, cisplatin ≥ 600 mg/m2, amputation, or lung surgery had increased risk for frailty. These associations were partially but not completely attenuated when sociodemographic characteristics, lifestyle factors, and chronic conditions were added to multivariable models. Cranial radiation (prevalence ratio [PR], 1.47; 95% CI, 1.20 to 1.76), pelvic radiation ≥ 34 Gy (PR, 1.46; 95% CI, 1.01 to 2.11), and lung surgery (PR, 1.75; 95% CI, 1.28 to 2.38) remained significant after sociodemographic, lifestyle, and chronic conditions were accounted for. CONCLUSION Childhood cancer survivors reported a higher prevalence of frailty compared with siblings. Radiation and lung surgery exposures were associated with increased risk for frailty. Interventions to prevent, delay onset, or remediate chronic disease and/or promote healthy lifestyle are needed to decrease the prevalence of frailty and preserve function in this at-risk population.