bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavivirus Infection Induce a Golgi Stress Response in Vertebrate and Mosquito Cells
Authors: Viettri Mercedes , Zambrano José L. , Rosales-Ramirez Romel , Gutierrez-Escolano Ana Lorena , Ludert Juan E 
Published: June 2021

Abstract
The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. Few examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on Golgi complex imposed by virion and NS1 processing and secretion.
The Attitude of Patients with Progressive Ataxias Towards Clinical Trials
Authors: Thomas-Black Gilbert , Dumitrascu Andrada , Garcia-Moreno Hector , Vallortigara Julie , Greenfield Julie , Hunt Barry , Walther Susan , Wells Mackenzie , Lynch David , Montgomery Hugh , Giunti Paola 
Published: June 2021

Abstract
Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.Results: Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.Conclusions: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
Heterogeneous clinical features in Cockayne syndrome-A patients with the same mutation and in siblings
Authors: CHIKHAOUI Asma , Kraoua Ichraf , Calmels Nadège , Bouchoucha Sami , Obringer Cathy , Zayoud Khouloud , Montagne Benjamin , M'rad Ridha , Abdelhak Sonia , Laugel Vincent , Ricchetti Miria , Turki Ilhem , Yacoub-Youssef Houda 
Published: June 2021

Abstract
Background

Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and little data is available for affected siblings. CS is largely undiagnosed in North Africa.
Methods

We report here the clinical description as well as genetic and functional characterization of eight North African CS patients, including siblings. These patients, who belonged to six unrelated families, underwent complete clinical examination and biochemical analyses. Sanger sequencing was performed for the recurrent mutation in five families, and targeted gene sequencing for one patient of the other family. We also performed RRS (Recovery RNA Synthesis) to confirm the functional impairment of DNA repair in the identified mutations.
Results

Six out of eight patients carried a homozygous indel mutation (c.598_600delinsAA) in exon 7 of ERCC8, and displayed a variable clinical spectrum, including between siblings, despite sharing the same mutation. The other two patients were Tunisian siblings who carried a homozygous splice-site variant in ERCC8 (c.843 + 1 G > C). They presented more severe clinical manifestations, which are in general rarely associated with CSA mutations, leading to gastrostomy and hepatic damage. Impaired TC-NER was confirmed by RRS in six tested patients.
Conclusions

This study provides the first deep characterization of case series of rare CS-A patients in North Africa. They carry mutations described to date only in this region and the Middle-East. We also provide the largest characterization of unrelated patients, as well as siblings, with the same mutation, providing a framework for dissecting elusive genotype-phenotype correlations in CS.
Evolution of the Earth Microbial Co-occurrence Network
Authors: Lv Xiaofei , Stirling Erinne , Zhao Kankan , Wang Yiling , Ma Bin , Xu Jianming 
Published: June 2021

Abstract
Background: Co-occurrence pattern provides vital insight into complex microbial interactions of microbiomes. Although network analysis offers useful tools for describing microbial co-occurrence pattern, evolution of co-occurrence networks remains largely uncharacterized. Here, we simulated the evolution of the Earth microbial co-occurrence network and estimated topological fitness of its nodes based on the degree growth exponent.Results: We showed that the Earth microbial co-occurrence network evolved following Bianconi-Barabasi model. The Earth microbial co-occurrence network had reached to a stable status with around 500 nodes. Degree growth exponent was the major determinant of accumulated degree of taxa. The positive correlation between topological fitness and gene numbers in corresponding genomes suggests the intrinsic feature of topological fitness. The gamma distribution of topological fitness suggests the extinction of taxa with low topological fitness. We then examined the impact of node extinction and decay, finding that the link acquisition of hub nodes was not affected.Conclusions: This study glimpses the evolution feature of Earth microbial co-occurrence network and provides a framework for predicting potential hubs in the evolving network in future.
Lysosome Lipid Signaling from the Periphery to Neurons Regulates Longevity
Authors: Savini Marzia , Duffy Jonathon , Folick Andrew , Lee Yi-Tang , Hu Pei-Wen , Neve Isaiah , Jin Feng , Zhang Qinghao , Tillman Matthew , Ye Youqiong , Mair William , Wang Jin , Han Leng , Ortlund Eric , Wang Meng 
Published: June 2021

Abstract
Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in Caenorhabditis elegans. We discovered that lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation requires the secretion from the fat storage tissue of a lipid chaperone protein LBP-3 and polyunsaturated fatty acids (PUFAs). LBP-3 binds to specific PUFAs, and acts through a nuclear hormone receptor NHR-49 and neuropeptide NLP-11 in neurons to extend lifespan. Together, these results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and lysosomal signaling mediated inter-tissue communication in promoting longevity.
Modelling the Impact of Delaying Vaccination Against SARS-CoV-2 Assuming Unlimited Vaccines Supply
Authors: Massad Eduardo , Amaku Marcos , Covas Dimas Tadeu , Coutinho Francisco Antonio Bezerra , Azevedo Raymundo Soares 
Published: June 2021

Abstract
BackgroundAt the moment we have more than 109 million cases and 2.4 million deaths around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far.MethodsWe propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus induces disease (COVID-19) on the number of cases and deaths by the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations.ResultsThe model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths until the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, that for each month of delay the number of deaths increases monotonically in a logarithm fashion, for both the State of Sao Paulo and Brazil as a whole.ConclusionsOur model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.
Telocytes Promote Hepatocellular Carcinoma by Activating The ERK Signaling Pathway and miR-942-3p/MMP9 Axis
Authors: Xu Ying , Tian Hu , Luan Chao Guang , Sun Kai , Bao Peng Jin , Zhang Hua Yu , Zhang Nan 
Published: June 2021

Abstract
Background

In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but theirs functions in HCC are still unknown.
Methods

TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using 3 types of liver cancer cell lines in vivo.
Results

TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; however, this had no significant effect on TC proliferation and apoptosis. miR-942-3p suppressed MMP9 expression in TCs.
Conclusion

Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.
A molecular signature for the Metabolic Syndrome by urine metabolomics
Authors: Bruzzone Chiara , Gil-Redondo Rubén , Seco Marisa , Barragán Rocío , Cruz Laura de la , Cannet Claire , Schäfer Hartmut , Fang Fang , Diercks Tammo , Bizkarguenaga Maider , González-Valle Beatriz , Laín Ana , Sanz-Parra Arantza , Coltell Oscar , de Letona Ander López , Spraul Manfred , Lu Shelly C , Buguianesi Elisabetta , Embade Nieves , Anstee Quentin M , Corella Dolores , Mato José M , Millet Oscar 
Published: June 2021

Abstract
BACKGROUND. Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine.METHODS. We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18–75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4–5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS.RESULTS. MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (19 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.86 and 0.92). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome.CONCLUSIONS. Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.
Efficacy and Safety of Endoscopic Sleeve Gastroplasty versus Laparoscopic Sleeve Gastrectomy in Obese Subjects with non-alcoholic steatohepatitis (NASH): Study protocol for a randomised controlled trial (TESLA-NASH study)
Authors: LAVIN-ALCONERO LUCIA , FERNANDEZ-LANAS TATIANA , COZ PAULA IRUZUBIETA , ARIAS-LOSTE MARIA TERESA , DUQUE JUAN CARLOS RODRIGUEZ , RIVAS CORAL , CAGIGAL MARIA LUISA , MONTALBAN CORAL , USEROS ANTONIO LOPEZ , CANCELO ANA ALVAREZ , GARCIA-SAIZ MARIA DEL MAR , GARCIA JAVIER CRESPO 
Published: June 2021

Abstract
Background : Non-alcoholic steatohepatitis (NASH) is a growing public health problem that affects more than 5% of the population. The standard treatment is weight loss with diet and exercise, which has been shown a histological and analytical improvement in patients capable to achieve a 5-10% reduction in their body weight. However, less than 25% of subjects achieve this goal. Bariatric surgery (BS) is the treatment of choice for its efficacy in obese patients. This intervention has resolved NASH in 85% of cases. However, bariatric endoscopy (BE) is presented as a therapeutic alternative with good results in terms of efficacy, long-term weight loss, and safety, decrease of adverse events. Methods : The TESLA-NASH study is a randomized, controlled, open-label, unicentric clinical trial with a medical device. The aim of this study is to evaluate and compare the efficacy and safety of endoscopic sleeve gastroplasty (ESG) versus laparoscopic sleeve gastrectomy (LSG) in liver histology improvement of patients with obesity +/- metabolic syndrome and NASH. A total of 30 patients will be randomized 1:1 to the experimental or control group. Discussion : Gastric bypass surgery and restrictive surgical treatments have been successful improving metabolic syndrome, insulin resistance and liver histology of obese patients. Currently, endoscopic techniques which are less invasive, are being developed, showing fewer complications and lower sanitary cost, and gastric restrictions with similar characteristics to the traditional surgical method. The tubulization or vertical gastroplasty with the OverStitch system (Apollo Endosurgery, Austin, TX, USA) is one of the most promising one. However, currently, any method is accepted as a standard treatment for NASH. Trial registration : Clinical trial.gov: NCT04060368. Registred on 19 August 2019, https://clinicaltrials.gov/ct2/show/NCT04060368 Protocol version: v 2.0, dated 15 nov 2019.
Silibinin Promotes Bone Regeneration Through HIF-1α/VEGF and Notch Signaling Pathway in Ovariectomized Rats
Authors: Tao Zhoushan , Li Tian-Lin , Yang Min , Xu Hong-Guang 
Published: June 2021

Abstract
Objective

The purpose was to observe whether systemic administration with silibinin(SIL) have an positive effect on bone defect regeneration through HIF-1α/VEGF and Notch signaling pathway in an ovariectomized(OVX) rat model.
Methods

The MC3T3-E1 cells were co-cultured with lower SIL and higher SIL and induced to osteogenesis, and the cell viability, osteogenic activity were observed by Cell Count Kit-8(CCK-8), Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining and Western blotting(WB). After the drilling defect model was established, the OVX rats were treated with SIL for 12 weeks. Micro-CT, histology and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism.
Results

CCK-8, ALP and ARS staining results show that the cell mineralization and osteogenic activity of LSIL and HSIL group is significantly higher than the Con group. Protein expressions show that related regulatory proteins such as ALP, OPN, RUNX-2, OC, VEGFA, HIF-1α, Notch 1, JAG 1, HEY 1 and HES 1 of LSIL and HSIL group are significantly higher than Con group. Micro-CT and Histological analysis evaluation show that group SIL + OVX presented the stronger effect on bone regeneration, bone mineralization, higher expression of VEGFA and HIF-1α, when compared with OVX group. RT-qPCR analysis shows that SIL + OVX group showed increased Notch 1, HES1, HEY1 and JAG1 than the OVX group(p < 0.05).
Conclusions

Our current study demonstrated that systemic administration with SIL is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by activating HIF-1α/VEGF and Notch signaling pathway.
Contribution to the molecular taxonomy of cultivated populations of mastic trees on Chios Island
Authors: Kyriakidi Panagiota , Kostas Stefanos , Zeka-Paschou Constantina , Piliou Kleoniki , Mylona Antigoni , Vasileiadis Anastasios , Magklaras Panagiotis , Vasilakis Tilemaxos , Smyrnioudis Ilias , Hatzilazarou Stefanos , Afendra Amalia-Sofia , Economou Athanasios , Hatziloukas Efstathios 
Published: June 2021

Abstract
Background: The mastic tree (formal name: Pistacia lentiscus var. Chia) is extensively cultivated on the southern part of the Greek island of Chios. Its extensive cultivation is due to the production of a special resin, known as mastic gum, or mastiha, which is widely used in several dietary, pharmaceutical and other products since ancient times. Mastic tree is an evergreen, dioecious (consisting of male and female individuals), woody plant. Furthermore, a number of morphological characteristics suggest the existence of several different plant groups, called here “morpho-varieties”, but it is probable that there exist an unknown number of different, deviating genotypes on the island. Nevertheless, five major morphologically determined morpho-varieties of mastic tree are mainly cultivated, namely “Votomos”, “Maroulitis”, “Mavroschinos”, “Stenophyllos” and “Fardyphyllos”. The morpho-varieties exhibit mostly, but not always, distinct morphology, on which their taxonomy was initially based. Since it is observed that different plant populations differ in the quantity and quality of the produced resin, it is important to explore whether these differences have a genetic basis, or are due to other factors, such as agricultural practices, or soil composition. To this end, the genetic diversity among these five morpho-varieties and within each one of them was investigated in the present study, using in a first approximation their Random Amplified Polymorphic DNA profiles and subsequently the sequence divergence of their Internal Transcribed Spacer regions 1 and 2. Results: The results confirm the existence of a considerable genotypic diversity among the five morpho-varieties studied and, furthermore, reveal the existence of genotypic diversity within each one of them, as well as the existence of a number of further deviating genotypes. The possibility, this diversity to be partly a result of reticulate evolution events is also discussed.Conclusions: This study provides evidence that the population of cultivated mastic trees on the island of Chios consists mainly of two species, i.e. Pistacia lentiscus and Pistacia x saportae, although it is clear that there also exist genetically deviating mastic trees, as well as individual plants, probably produced through hybridization between the two afore mentioned species.