bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
Authors: Gupta Sonal , Khan Juveria , Kumari Priti , Narayana Chintam , Ayana R. , Chakrabarti Malabika , Sagar Ram , Singh Shailja 
Published: October 2019

AbstractBackgroundMalaria is one of the deadliest infectious diseases caused by protozoan parasite ofPlasmodiumspp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates.MethodsTwo series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened againstPlasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay onP. falciparum3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid12by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid12treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid12on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay.Results2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid12exhibited maximum growth inhibitory potential againstPlasmodiumwith IC50value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid12arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid12binds to α,β-heterodimer of tubulin and affects microtubule dynamics.ConclusionThese findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions againstP. falciparum.
Reduced expression of PD-L1 in autoimmune thyroiditis attenuate trophoblast invasion through ERK/MMP pathway
Authors: Chen Mengya , Gilbert Nduwimana , Liu Haixia 
Published: October 2019

Abstract

Background
Autoimmune thyroiditis (AIT) with euthyroid is associated with miscarriage. But the exact mechanism remains unclear. Studies have shown that the programmed cell death-1 (PD-1)/programmed cell death -ligand 1 (PD-L1) pathway is essential for normal pregnancy. However, the expression of PD-L1 in gestational trophoblasts in mice with autoimmune thyroiditis and the mechanisms leading to miscarriage have not been fully investigated.

Methods
Immunofluorescence and Western blot were used to detect the expression of PD-L1, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells of pregnant mice with AIT. The expression of PD-L1 in HTR-8/SVneo cells were silenced, and the expression of PD-L1, MMP-2, MMP-9, ERK and p-ERK1/2 was detected by Western blot analyses and immunofluorescence assays. Invasive assays were performed in PD-L1 silenced HTR-8/SVneo cells using a Transwell chamber.

Results
Compared with normal pregnancy, the expression of PD-L1, ERK, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells was significantly lower in pregnant mice with AIT. Compared with the negative control (NC) group (cells transfected with negative control siRNA), phosphorylation of MMP-2, MMP-9 and P-ERK1/2 proteins was significantly reduced in HTR-8/SVneo cells transfected with PD-L1 siRNA, and the number of cells penetrating the membrane was reduced.

Conclusion
AIT inhibits ERK/MMP-2 and MMP-9 pathways through PD-L1 reduction, attenuates embryonic trophoblast invasion and ultimalely induces miscarriage ultimately.
A systematic review and meta-analysis of the overall effects of school-based obesity prevention interventions and effect differences by intervention components
Authors: Liu Zheng , Xu Han-Meng , Wen Li-Ming , Peng Yuan-Zhou , Lin Li-Zi , Zhou Shuang , Li Wen-Hao , Wang Hai-Jun 
Published: October 2019

Abstract

Background
Childhood obesity is a serious public health concern. School-based interventions hold great promise to combat the rising trend of childhood obesity. This systematic review aimed to assess the overall effects of school-based obesity prevention interventions, and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity.

Methods
We systematically searched MEDLINE, CENTRAL and Embase databases to identify randomized- or cluster randomized- controlled trials of school-based obesity interventions published between 1990 and 2019. We conducted meta-analyses and subgroup analyses to determine the overall effects of obesity prevention programs and effect differences by various characteristics of intervention components on body mass index (BMI) or BMI Z-score of children.

Results
This systematic review included a total of 50 trials (reported by 56 publications). Significant differences were found between groups on BMI (− 0.14 kg/m2 (95% confidence interval: − 0.21, − 0.06)) and BMI Z-score (− 0.05 (− 0.10, − 0.01)) for single-component interventions; significant differences were also found between groups on BMI (− 0.32 (− 0.54, − 0.09) kg/m2) and BMI Z-score (− 0.07 (− 0.14, − 0.001)) for multi-component interventions. Subgroup analyses consistently demonstrated that effects of single-component (physical activity) interventions including curricular sessions (− 0.30 (− 0.51, − 0.10) kg/m2 in BMI) were stronger than those without curricular sessions (− 0.04 (− 0.17, 0.09) kg/m2 in BMI); effects of single-component (physical activity) interventions were also strengthened if physical activity sessions emphasized participants’ enjoyment (− 0.19 (− 0.33, − 0.05) kg/m2 in BMI for those emphasizing participants’ enjoyment; − 0.004 (− 0.10, 0.09) kg/m2 in BMI for those not emphasizing participants’ enjoyment). The current body of evidence did not find specific characteristics of intervention components that were consistently associated with improved efficacy for multi-component interventions (P > 0.05).

Conclusions
School-based interventions are generally effective in reducing excessive weight gain of children. Our findings contribute to increased understandings of potentially effective intervention characteristics for single-component (physical activity) interventions. The impact of combined components on effectiveness of multi-component interventions should be the topic of further research. More high-quality studies are also needed to confirm findings of this review.
Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management
Authors: Rawat Chitra , Kukal Samiksha , Dahiya Ujjwal Ranjan , Kukreti Ritushree 
Published: October 2019

AbstractEpilepsy, a common multifactorial neurological disease, affects about 69 million people worldwide constituting nearly 1% of the world population. Despite decades of extensive research on understanding its underlying mechanism and developing the pharmacological treatment, very little is known about the biological alterations leading to epileptogenesis. Due to this gap, the currently available antiepileptic drug therapy is symptomatic in nature and is ineffective in 30% of the cases. Mounting evidences revealed the pathophysiological role of neuroinflammation in epilepsy which has shifted the focus of epilepsy researchers towards the development of neuroinflammation-targeted therapeutics for epilepsy management. Markedly increased expression of key inflammatory mediators in the brain and blood-brain barrier may affect neuronal function and excitability and thus may increase seizure susceptibility in preclinical and clinical settings. Cyclooxygenase-2 (COX-2), an enzyme synthesizing the proinflammatory mediators, prostaglandins, has widely been reported to be induced during seizures and is considered to be a potential neurotherapeutic target for epilepsy management. However, the efficacy of such therapy involving COX-2 inhibition depends on various factors viz., therapeutic dose, time of administration, treatment duration, and selectivity of COX-2 inhibitors. This article reviews the preclinical and clinical evidences supporting the role of COX-2 in seizure-associated neuroinflammation in epilepsy and the potential clinical use of COX-2 inhibitors as a future strategy for epilepsy treatment.
Factors influencing decision-making power regarding reproductive health and rights among married women in Mettu rural district, south-west, Ethiopia
Authors: Tadele Afework , Tesfay Amanuel , Kebede Alemi 
Published: October 2019

Abstract

Background
Women’s decision-making power regarding reproductive health and rights (RHR) was the central component to achieve reproductive well-being. Literatures agree that a women having higher domestic decision-making power regarding their health care were more likely to utilize health services. More than 80% of women in Ethiopia reside in rural areas where they considered as the subordinates of their husbands. This would restrict women to fully exercise their RHR. Thus, this study aims to determine the factors influencing the women’s decision-making power regarding RHR in Mettu rural district, South West Ethiopia.

Methods
A community based cross-sectional study was done among 415 by using randomly selected married women of reproductive age from March to April 2017. Data was entered by using Epi-data manger 1.4 and analyzed by SPSS version 21. Descriptive and multivariate logistic regression analysis was carried out.

Result
One hundred sixty-eight (41.5%) of the women had greater decision-making power regarding RHR. Woman’s primary education AOR 2.62[95% C. I 1.15, 5.97], secondary (9+) education AOR 3.18[95% C. I 1.16, 8.73] and husband’s primary education AOR 4.0[95% C. I 1.53, 10.42], secondary (9+) education AOR 3.95 [95% C. I 1.38, 11.26], being knowledgeable about RHR AOR 3.57 [95% C. I 1.58, 8.09], marriage duration of more than 10 years AOR 2.95 [95% C. I 1.19, 7.26], access to micro-credit enterprises AOR 4.26[95% C. I 2.06, 8.80], having gender equitable attitude AOR 6.38 [95% C. I 2.52, 12.45] and good qualities of spousal relation AOR 2.95 [95% C. I 1.30, 6.64] were positively influencing women’s decision-making power regarding RHR.

Conclusion
More than four in ten rural women had greater decision-making power regarding RHR. External pressures (qualities of spousal relation, gender equitable attitude) and knowledge about RHR were found to influence women’s decision-making power. Public health interventions targeting women’s RHR should take into account strengthening rural micro-credit enterprises, qualities of spousal relations and priority should be given to women with no formal education of husband or herself and marriage duration of < 5 years.
Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity
Authors: Rubio Laura , Pyrgiotakis Georgios , Beltran-Huarac Juan , Zhang Yipei , Gaurav Joshi , Deloid Glen , Spyrogianni Anastasia , Sarosiek Kristopher A. , Bello Dhimiter , Demokritou Philip 
Published: October 2019

Abstract

Background
Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles.

Results
Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content.

Conclusion
Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.
Hearing loss after radiosurgery-blame it on Cochlear dose or the radiation tool!
Authors: Deora Harsh , Tripathi Manjul 
Published: October 2019

Abstract
While sudden hearing loss after stereotactic radiosurgery has been demonstrated in some cases a recent article by Linge et al. and have demonstrated the need for further discussion on this topic. We attempt to delineate the fact that the type of dosing regimen or technology used will not affect the hearing or radio-graphical control outcomes and thus should not be a consideration while administering treatment. Also we discuss the role of location of the lesion and vascularity and potential new therapies for this unexpected outcome after radiosurgery.
Connecting the dots between different networks: miRNAs associated with bladder cancer risk and progression
Authors: Braicu Cornelia , Buiga Rares , Cojocneanu Roxana , Buse Mihail , Raduly Lajos , Pop Laura Ancuta , Chira Sergiu , Budisan Liviuta , Jurj Ancuta , Ciocan Cristina , Magdo Lorand , Irimie Alexandru , Dobrota Florentin , Petrut Bogdan , Berindan-Neagoe Ioana 
Published: October 2019

Abstract

Background
Bladder cancer (BC) is a common urothelial malignancy, characterized by a high recurrence rate. The biology of bladder cancer is complex and needs to be deciphered. The latest evidence reveals the critical role of the non-coding RNAs, particularly microRNAs (miRNAs), as vital regulatory elements in cancer.

Method
We performed a miRNAs microarray using paired tissues (tumor and adjacent normal bladder tissue), followed by the validation with qRT-PCR of five selected transcripts. Additional next-generation sequencing investigation established the interconnection among the altered miRNAs and mutated genes. Based on the overlapping between TCGA data and data obtained in the study, we focused on the systematic identification of altered miRNAs and genes mutated involved in bladder cancer tumorigenesis and progression.

Results
By overlapping the miRNAs expression data, the two patient cohorts, we identified 18 miRNAs downregulated and, 187 miRNAs upregulated. qRT-PCR validation was completed using a selected panel of two downregulated (miR-139-5p and miR-143-5p) and three up-regulated miRNAs (miR-141b, miR-200 s or miR-205). Altered miRNAs patterns are interrelated to bladder tumorigenesis, allowing them to be used for the development of novel diagnostic and prognostic biomarkers. Three EMT-related upregulated miRNAs have an essential role in the molecular mechanisms, specifically key processes underlying tumorigenesis, invasion and metastasis. Using the Ampliseq Cancer Panel kit and Ion Torrent PGM Next-Generation Sequencing an increased mutation rate for TP53, FGFR3, KDR, PIK3CA and ATM were observed, but the mutational status for only TP53 was correlated to the survival rate. The miRNAs pattern, along with the gene mutation pattern attained, can assist for better patient diagnosis.

Conclusion
This study thereby incorporates miRNAs as critical players in bladder cancer prognosis, where their altered gene expression profiles have a critical biological function in relationship with tumor molecular phenotype. The miRNA-mRNA regulatory networks identified in BC are ripe for exploitation as biomarkers or targeted therapeutic strategies.
European survey on national training activities in clinical research
Authors: Magnin A. , Iversen V. Cabral , Calvo G. , Čečetková B. , Dale O. , Demlova R. , Blasko Gy. , Keane F. , Kovacs G. L. , Levy-Marchal C. , Monteiro E. C. , Palmisano L. , Pella D. , Portolés Pérez A. , Rascol O. , Schmid C. , Tay F. , von der Leyen H. , Ohmann C. 
Published: October 2019

Abstract

Background
Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists.

Methods
To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action.

Results
The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries.

Conclusions
There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.
Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel
Authors: Isaksson Eva , Wester Per , Laska Ann Charlotte , Näsman Per , Lundström Erik 
Published: October 2019

Abstract

Background
Many randomised controlled trials (RCT) fail to meet their recruitment goals. Study personnel play a key role in recruitment. The aim of this study was to identify successful strategies that study personnel consider to be important in patient recruitment to RCT.

Methods
We constructed a questionnaire based on the literature, discussions with colleagues and our own experience as trialists. The survey was named “What is Important for Making a Study Successful questionnaire” (WIMSS-q). Our target group was the study personnel in the ongoing EFFECTS study. The questionnaire was sent out electronically to all physicians and nurses (n = 148). Success factors and barriers were divided according to patient, centre and study level, respectively.

Results
Responses were received from 94% of the study personnel (139/148). The five most important factors at centre level for enhancing recruitment were that the research question was important (97%), a simple procedure for providing information and gaining consent (92%), a highly engaged local principal investigator and research nurse (both 87%), and that study-related follow-ups are practically feasible and possible to coordinate with the clinical follow-up (87%). The most significant barrier at the local centre was lack of time and resources devoted to research (72%). Important patient-related barriers were fear of side effects (35%) and language problems (30%).

Conclusions
For recruitment in an RCT to be successful, the research question must be relevant, and the protocol must be simple and easy to implement in the daily routine.

Trial registration
The protocol for this study was registered at the Northern Ireland Hub for trials methodology research (SWAT ID 64). The EFFECTS study has EudraCT number 2011–006130-16 and was registered 17 February 2016 at ClinicalTrials.gov number NCT02683213.
Two new species of Acanthocotyle Monticelli, 1888 (Monogenea: Acanthocotylidae), parasites of two deep-sea skates (Elasmobranchii: Rajiformes) in the South-East Pacific
Authors: Ñacari Luis A. , Sepúlveda Fabiola A. , Escribano Ruben , Oliva Marcelo E. 
Published: October 2019

Abstract

Background
Parasites of deep-sea fishes from the South-East Pacific (SPO) are poorly known. Of c.1030 species of fish found in this area, 100–150 inhabit the deep-sea (deeper than 200 m). Only six articles concerning metazoan parasites of fish from deep-waters of SOP are known, and nine monogenean species have been reported. Currently, ten species are known in Acanthocotyle Monticelli, 1888 (Monogenea) and when stated, all of them are found in shallow waters (10–100 m). Acanthocotyle gurgesiella Ñacari, Sepulveda, Escribano & Oliva, 2018 is the only known species parasitizing deep-sea skates (350–450 m) in the SPO. The aim of this study was the description of two new species of Acanthocotyle from two Rajiformes.

Methods
In September 2017, we examined specimens of two species of deep-sea skates (Rajiformes), Amblyraja frerichsi (Krefft) and Bathyraja peruana McEachran & Myyake, caught at c.1500 m depth off Tocopilla, northern Chile, as a by-catch of the Patagonian tooth fish Dissostichus eleginoides Smitt fishery. Specimens of Acanthocotyle were collected from the skin of the skates. Morphometric (including multivariate analysis of proportional measurements, standardized by total length), morphological and molecular analyses (LSU rRNA and cox1 genes) were performed in order to identify the collected specimens.

Results
The three approaches used in this study strongly suggest the presence of two new species in the genus Acanthocotyle: Acanthocotyle imo n. sp. and Acanthocotyle atacamensis n. sp. parasitizing the skin of the thickbody skate Amblyraja frerichsi and the Peruvian skate Bathyraja peruana, respectively. The main morphological differences from the closely related species Acanthocotyle verrilli Goto, 1899 include the number of radial rows of sclerites, the non-discrete vitelline follicles and the number of testes.

Conclusions
The two species of monogeneans described here are the only recorded parasites from their respective host species in the SPO. Assessing host specificity for members of Acanthocotyle requires clarifying the systematics of Rajiformes.