bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen enhances the proliferation and migration of ovarian cancer cells by activating transient receptor potential channel C3
Authors: Li Shengnan , Jiang Kuo , Li Jia , Hao Xiaohua , Chu Wenguang , Luo Ceng , Zhu Yuanyuan , Xie Rougang , Chen Biliang 
Published: February 2020

Abstract
Background
Recent studies have suggested that estrogen (E2) plays an important role in epithelial ovarian cancer (EOC). However, the mechanism of E2 in ovarian cancers is unclear. The purpose of this study was to investigate the effect of E2 on ovarian cancers and illuminate the mechanism of E2 in promote ovarian cancers proliferation.

Results
We demonstrated that E2 stimulated the proliferation and invasion of ovarian cancer cells. In this study, ovarian cancer specimens were also analyzed for transient receptor potential channel C3 (TRPC3) expression; TRPC3 expression levels were higher in ovarian cancer samples than in normal ovarian tissue samples. Previous studies have shown that TRPC3 contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between E2 and TRPC3. We found that E2 stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. E2 stimulation enhanced the influx of Ca2+. Moreover, siRNA-mediated silencing of TRPC3 expression inhibited the ability of E2 to stimulate the influx of Ca2+.

Conclusions
In conclusion, TRPC3 plays a significant role in the stimulatory activity of E2 and could be a therapeutic target for the treatment of EOC. Furthermore, this study elucidates the molecular mechanism by which E2 promotes the proliferation and migration of EOC cells.
Neuroprem: the Neuro-developmental outcome of very low birth weight infants in an Italian region
Authors:   Neuroprem Working Group, Lugli Licia , Pugliese Marisa , Plessi Carlotta , Berardi Alberto , Guidotti Isotta , Ancora Gina , Grandi Sara , Gargano Giancarlo , Braibanti Silvia , Sandri Fabrizio , Soffritti Silvia , Ballardini Elisa , Arena Vittoria , Stella Marcello , Perrone Serafina , Moretti Sabrina , Rizzo Vittoria , Ferrari Fabrizio , Picciolini Odoardo , Bellù Roberto , Turoli Daniela , Corvaglia Luigi Tommaso , Garani Gianpaolo , Paoletti Vittoria , Biasucci Giacomo , Biasini Augusto , Benenati Belinda , Stagi Paolo , Magnani Cristina , Dallaglio Sara , DellaCasa Muttini Elisa , Roversi Maria Federica , Bedetti Luca , Lucaccioni Laura , Bertoncelli Natascia , Boncompagni Alessandra 
Published: February 2020

Abstract
Introduction
The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome.

Aims
Neuroprem is an area-based prospective cohort study on the neuro-developmental outcome of very low birth weight (VLBW) infants that aims to define severe functional disability at 2 years of age.

Methods
Surviving VLBW infants from an Italian network of 7 neonatal intensive care units (NICUs) were assessed for 24 months through the Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and neuro-functional evaluation according to the International Classification of Disability and Health (ICF-CY). The primary outcome measure was severe functional disability at 2 years of age, defined as cerebral palsy, a BSDI III cognitive composite score < 2 standard deviation (SD) or a GMDS-R global quotients score < 2 SD, bilateral blindness or deafness.

Results
Among 211 surviving VLBW infants, 153 completed follow-up at 24 months (72.5%). Thirteen patients (8.5%) developed a severe functional disability, of whom 7 presented with cerebral palsy (overall rate of 4.5%). Patients with cerebral palsy were all classified with ICF-CY scores of 3 or 4. BSDI III composite scores and GMDS-R subscales were significantly correlated with ICF-CY scores (p < 0.01).

Conclusion
Neuroprem represents an Italian network of NICUs aiming to work together to ensure preterm neuro-developmental assessment. This study updates information on VLBW outcomes in an Italian region, showing a rate of cerebral palsy and major developmental disabilities in line with or even lower than those of similar international studies. Therefore, Neuroprem provides encouraging data on VLBW neurological outcomes and supports the implementation of a preterm follow-up programme from a national network perspective.
Randomized trial comparing low-pressure versus standard-pressure pneumoperitoneum in laparoscopic colectomy: PAROS trial
Authors: Celarier S. , Monziols S. , Francois M. O. , Assenat V. , Carles P. , Capdepont M. , Fleming C. , Rullier E. , Napolitano G. , Denost Q. 
Published: February 2020

Abstract
Background
Laparoscopy, by its minimally invasive nature, has revolutionized digestive and particularly colorectal surgery by decreasing post-operative pain, morbidity, and length of hospital stay. In this trial, we aim to assess whether low pressure in laparoscopic colonic surgery (7 mm Hg instead of 12 mm Hg) could further reduce pain, analgesic consumption, and morbidity, resulting in a shorter hospital stay.

Methods and analysis
The PAROS trial is a phase III, double-blind, randomized controlled trial. We aim to recruit 138 patients undergoing laparoscopic colectomy. Participants will be randomly assigned to either a low-pressure group (7 mm Hg) or a standard-pressure group (12 mm Hg). The primary outcome will be a comparison of length of hospital stay between the two groups. Secondary outcomes will compare post-operative pain, consumption of analgesics, morbidity within 30 days, technical and oncological quality of the surgical procedure, time to passage of flatus and stool, and ambulation. All adverse events will be recorded. Analysis will be performed on an intention-to-treat basis.

Trial registration
This research received the approval from the Committee for the Protection of Persons and was the subject of information to the ANSM. This search is saved in the ID-RCB database under registration number 2018-A03028–47. This research is retrospectively registered January 23, 2019, at http://clinicaltrials.gov/ed under the name “LaPAroscopic Low pRessure cOlorectal Surgery (PAROS)”. This trial is ongoing.
GERiatric Screening in the treatment of elderly patients with Ovarian Carcinoma (GERSOC): study protocol for a pragmatic, cluster randomised controlled trial
Authors: van Soolingen Neeltje J. , Smorenburg Carolina H. , Hamaker Marije E. , Groen Wim G. , Retèl Valesca P. , Lok Christianne A. R. , van de Poll-Franse Lonneke V. , Trum Johannes W. 
Published: February 2020

AbstractBackgroundApproximately 40% of the newly diagnosed patients with advanced ovarian cancer are aged 70 years or older. Standard treatment for advanced disease consists of cytoreductive surgery and combination chemotherapy. In older patients, standard treatment is often withheld or prematurely stopped due to suspected frailty. It remains challenging to distinguish fit elderly patients who can endure standard therapy from frail patients who may benefit from an adapted treatment strategy. As a comprehensive geriatric assessment (CGA) can contribute to the identification of frail patients and improve tailored therapy in this population, screening tests were developed to select those who may benefit from a CGA. However, the use of these geriatric screening tests has rarely been compared with usual clinical care. The GERSOC-trial will evaluate whether geriatric screening in elderly patients with advanced-stage ovarian cancer improves treatment completion and quality of life.MethodsThis pragmatic, cluster randomised controlled trial will be conducted at a minimum of 20 hospitals in the Netherlands. Hospitals are randomly assigned to geriatric screening care (in which a geriatric screening comprised of the G8 questionnaire and the Timed Up and Go test is performed), or care as usual (in which current usual care is continued). A total of 320 patients aged ≥ 70 years with primary, advanced-stage ovarian carcinoma will be included. Patients considered fit on geriatric screening will receive standard treatment; patients who are considered unfit will be referred to a geriatrician for analysis and treatment advice. The primary outcome is the percentage difference in completed standard and adapted therapies between the two study arms. Secondary outcomes include quality of life, cost-effectiveness and survival.DiscussionThis trial aims to gather evidence for the use of geriatric screening in treatment decision-making in elderly patients with advanced ovarian cancer. If proven feasible, beneficial and cost-effective, geriatric screening may be implemented in routine clinical practice.Trial registrationNetherlands Trial Registry, ID:NL6745. Registered on 2 August 2017.
Rodents as intermediate hosts of cestode parasites of mammalian carnivores and birds of prey in Poland, with the first data on the life-cycle of Mesocestoides melesi
Authors: Bajer Anna , Alsarraf Mohammed , Dwużnik Dorota , Mierzejewska Ewa J. , Kołodziej-Sobocińska Marta , Behnke-Borowczyk Jolanta , Banasiak Łukasz , Grzybek Maciej , Tołkacz Katarzyna , Kartawik Natalia , Stańczak Łukasz , Opalińska Patrycja , Krokowska-Paluszak Małgorzata , Górecki Grzegorz , Alsarraf Mustafa , Behnke Jerzy M. 
Published: February 2020

Abstract
Background
Rodents constitute an important part of the diet of many carnivore species. This predator-prey food chain is exploited by helminth parasites, such as cestodes, whose larval stages develop in rodents and then mature to the adult stage in predators. The main aim of our study was to use molecular techniques for identification of cestode species recovered from both intermediate and definitive hosts, with a particular focus on the genus Mesocestoides.

Methods
Larval cestodes were obtained during our long-term studies on rodent helminth communities in the Mazury Lake District in the north-east Poland in 2000–2018. Cestode larvae/cysts were collected from body cavities or internal organs (e.g. liver) during autopsies. Adult tapeworms were derived from nine red foxes, three Eurasian badgers and one Eurasian lynx. PCR amplification, sequencing and phylogenetic analyses were conducted employing three genetic markers: 18S rDNA, mitochondrial (mt) 12S rDNA and the mt cytochrome c oxydase subunit 1 (cox1) gene fragment.

Results
Altogether 19 Mesocestoides samples were analyzed, including 13 adult tapeworms from definitive hosts and six larval samples from 4 bank voles and 2 yellow-necked mice. Phylogenetic analyses revealed three well-supported trees of similar topology. In each case the Mesocestoides samples formed two separate clades. All isolates from foxes, the lynx isolate and two isolates from rodents grouped with Mesocestoides litteratus. Four isolates from rodents and all three isolates from Eurasian badgers were resolved in a separate clade, most similar to North American M. vogae (syn. M. corti). Examination of fixed, stained adult specimens from Eurasian badgers revealed consistency with the morphology of Mesocestoides melesi. Therefore, this clade is likely to represent M. melesi, a species first described in 1985 from the Eurasian badger Meles meles. Molecular analysis allowed also the identification of Taenia crassiceps, Hydatigera kamiyai and Cladotaenia globifera among larvae derived from rodents.

Conclusions
Molecular and phylogenetic analyses support the recognition of M. melesi as a valid species. Our data represent the first record of the larvae of this species in rodents. This is the first report on the occurrence of H. kamiyai in rodents from Poland.
Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection
Authors: Hendrickx Sarah , Van Bockstal Lieselotte , Bulté Dimitri , Mondelaers Annelies , Aslan Hamide , Rivas Luis , Maes Louis , Caljon Guy 
Published: February 2020

Abstract
Background
Since the introduction of miltefosine (MIL) as first-line therapy in the kala-azar elimination programme in the Indian subcontinent, treatment failure rates have been increasing. Since parasite infectivity and virulence may become altered upon treatment relapse, this laboratory study assessed the phenotypic effects of repeated in vitro and in vivo MIL exposure.

Methods
Syngeneic Leishmania donovani lines either or not exposed to MIL were compared for drug susceptibility, rate of promastigote multiplication and metacyclogenesis, macrophage infectivity and behaviour in the sand fly vector, Lutzomyia longipalpis.

Results
Promastigotes of both in vitro and in vivo MIL-selected strains displayed a slightly reduced drug susceptibility that was associated with a reduced MIL-accumulation linked to a lower copy number (disomic state) of chromosome 13 harboring the miltefosine transporter (LdMT) gene. In vitro selected promastigotes showed a lower rate of metacyclogenesis whereas the in vivo derived promastigotes displayed a moderately increased growth rate. Repeated MIL exposure did neither influence the parasite load nor metacyclogenesis in the sand fly vector.

Conclusions
Recurrent in vitro and in vivo MIL exposure evokes a number of very subtle phenotypic and genotypic changes which could make promastigotes less susceptible to MIL without attaining full resistance. These changes did not significantly impact on infection in the sand fly vector.
Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer
Authors: Zhou Qing , Perakis Samantha O. , Ulz Peter , Mohan Sumitra , Riedl Jakob M. , Talakic Emina , Lax Sigurd , Tötsch Martin , Hoefler Gerald , Bauernhofer Thomas , Pichler Martin , Gerger Armin , Geigl Jochen B. , Heitzer Ellen , Speicher Michael R. 
Published: February 2020

Abstract
Background
Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are largely unknown. Here, we employed whole-genome sequencing of plasma DNA to evaluate the tumor genome of patients undergoing treatment with bevacizumab to determine novel aberrations associated with resistance.

Methods
Using longitudinal plasma analyses, we studied the evolution of tumor genomes in a mCRC cohort (n = 150) and conducted analyses of CRC cases from The Cancer Genome Atlas (TCGA) database (n = 619) to identify associations between genomic aberrations and clinical features. We employed whole-genome sequencing to identify the most frequently occurring focal somatic copy number alterations (SCNAs). Using the TCGA data as a comparative and supporting dataset, we defined the minimally amplified overlapping region and studied the mechanistic consequences of copy number gain of the involved genes in this segment. In addition, we established an in vitro cell model and conducted downstream gene expression and cell viability assays to confirm our findings from the patient dataset.

Results
We observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of CRC cases from the TCGA database suggested that this amplicon is associated with more advanced stages. We confirmed that this 13q12.2 amplicon frequently emerges later during the clinical course of disease. After defining the minimally amplified region, we observed that the amplification and expression of one gene, POLR1D, impacted cell proliferation and resulted in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab treatment. In fact, in several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with therapy resistance.

Conclusions
Non-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients.
Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
Authors: Li Hui , Ding Xiang , Terkeltaub Robert , Lin Hang , Zhang Yuqing , Zhou Bin , He Ke , Li Kun , Liu Zhichen , Wei Jie , Yang Yuanheng , Xie Hui , Zeng Chao , Lei Guanghua 
Published: February 2020

Abstract
Background
Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model.

Methods
Eighty 10-week-old male C57BL/6 mice were randomized to 6 groups: non-operation, sham-operation, destabilization of the medial meniscus (DMM)-operation with intragastric saline/metformin, and DMM-operation with intraarticular saline/metformin. Articular cartilage degeneration was examined by scanning electron microscopy (SEM) and graded using the scoring system recommended by Osteoarthritis Research Society International (OARSI). Mechanical withdrawal threshold and hind paw weight distribution were measured to assess the pain-related behavior. Cell Counting Kit-8 assay, quantificational real-time polymerase chain reaction, and western blot analysis were conducted to examine the anabolic and anti-catabolic effect of metformin and the role of AMPK in mediating its effects on interleukin-1β stimulated primary mice chondrocytes.

Results
Compared with mice receiving intragastric and intraarticular saline, mice in both intragastric and intraarticular metformin displayed attenuated articular cartilage degeneration, indicated by less cartilage damage under SEM and significantly lower OARSI scores. A higher paw withdrawal threshold and a decreased weight-bearing asymmetry were observed in the intragastric and intraarticular metformin mice compared with their corresponding saline groups in DMM model of osteoarthritis. In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway.

Conclusions
Metformin attenuates osteoarthritis structural worsening and modulates pain, suggesting its potential for osteoarthritis prevention or treatment.
Integrated Mobile Element Scanning (ME-Scan) method for identifying multiple types of polymorphic mobile element insertions
Authors: Loh Jui Wan , Ha Hongseok , Lin Timothy , Sun Nawei , Burns Kathleen H. , Xing Jinchuan 
Published: February 2020

Abstract
Background
Mobile elements are ubiquitous components of mammalian genomes and constitute more than half of the human genome. Polymorphic mobile element insertions (pMEIs) are a major source of human genomic variation and are gaining research interest because of their involvement in gene expression regulation, genome integrity, and disease.

Results
Building on our previous Mobile Element Scanning (ME-Scan) protocols, we developed an integrated ME-Scan protocol to identify three major active families of human mobile elements, AluYb, L1HS, and SVA. This approach selectively amplifies insertion sites of currently active retrotransposons for Illumina sequencing. By pooling the libraries together, we can identify pMEIs from all three mobile element families in one sequencing run. To demonstrate the utility of the new ME-Scan protocol, we sequenced 12 human parent-offspring trios. Our results showed high sensitivity (> 90%) and accuracy (> 95%) of the protocol for identifying pMEIs in the human genome. In addition, we also tested the feasibility of identifying somatic insertions using the protocol.

Conclusions
The integrated ME-Scan protocol is a cost-effective way to identify novel pMEIs in the human genome. In addition, by developing the protocol to detect three mobile element families, we demonstrate the flexibility of the ME-Scan protocol. We present instructions for the library design, a sequencing protocol, and a computational pipeline for downstream analyses as a complete framework that will allow researchers to easily adapt the ME-Scan protocol to their own projects in other genomes.
Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project
Authors:   the EU-AIMS LEAP group, Moessnang Carolin , Baumeister Sarah , Tillmann Julian , Goyard David , Charman Tony , Ambrosino Sara , Baron-Cohen Simon , Beckmann Christian , Bölte Sven , Bours Carsten , Crawley Daisy , Dell’Acqua Flavio , Durston Sarah , Ecker Christine , Frouin Vincent , Hayward Hannah , Holt Rosemary , Johnson Mark , Jones Emily , Lai Meng-Chuan , Lombardo Michael V. , Mason Luke , Oldenhinkel Marianne , Persico Antonio , Cáceres Antonia San José , Spooren Will , Loth Eva , Murphy Declan G. M. , Buitelaar Jan K. , Banaschewski Tobias , Brandeis Daniel , Tost Heike , Meyer-Lindenberg Andreas 
Published: February 2020

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the “social brain,” a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD.MethodsAs part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N= 205) and typically developing (TD) individuals (N= 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits.ResultsWe observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders.ConclusionsContrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition.