bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoQ10 ameliorates monosodium glutamate-induced alteration in detrusor activity and responsiveness in rats via anti-inflammatory, anti-oxidant and channel inhibiting mechanisms
Authors: El Agamy Dalia F. , Naguib Yahya M. 
Published: October 2019

Abstract

Background
Competent detrusor muscles with coordinated contraction and relaxation are crucial for normal urinary bladder storage and emptying functions. Hence, detrusor instability, and subsequently bladder overactivity, may lead to undesirable outcomes including incontinence. Multiple mechanisms may underlie the pathogenesis of detrusor overactivity including inflammation and oxidative stress. Herein, we tested the possibility that CoQ10 may have a potential therapeutic role in detrusor overactivity.

Methods
Forty adult male Wistar albino rats weighing 100-150 g were used in the present study. Rats were divided (10/group) into control (receiving vehicles), monosodium glutamate (MSG)-treated (receiving 5 mg/kg MSG daily for 15 consecutive days), MSG + OO-treated (receiving concomitantly 5 mg/kg MSG and olive oil for 15 consecutive days), MSG + CoQ10-treated (receiving concomitantly 5 mg/kg MSG and 100 mg/kg CoQ10 daily for 15 consecutive days) groups.

Results
MSG resulted in significant increase in bladder weight and sensitised the bladder smooth muscles to acetylcholine. MSG has also resulted in significant increase in bladder TNF-α, IL-6, malondialdehyde, nerve growth factor and connexion 43, with significant decrease in the antioxidant enzymes superoxide dismutase and catalase. Olive oil had no effect on MSG induced alterations of different parameters. Treatment with CoQ10 has resulted in a significant restoration of all the altered parameters.

Conclusion
Taken together, our results suggest that CoQ10 antagonizes the deleterious effects of MSG on detrusor activity. We propose that CoQ10 could be a therapeutic strategy targeting urinary bladder dysfunction.
Hypoparathyroidism, Sensorineural deafness and renal disease (Barakat syndrome) caused by a reduced gene dosage in GATA3: a case report and review of literature
Authors: Joseph Anne D. D. , Sirisena Nirmala D. , Kumanan Thirunavukarasu , Sujanitha Vathualan , Strelow Veronika , Yamamoto Raina , Wieczorek Stefan , Dissanayake Vajira H. W. 
Published: October 2019

Abstract

Background
Barakat syndrome is an autosomal dominant rare genetic disease caused by haploinsufficiency of the GATA binding protein 3 (GATA3) gene. It is also known as HDR syndrome, and is characterized by varying degrees of hypoparathyroidism, sensorineural deafness and renal disease. This is the first report of a heterozygous GATA3 whole gene deletion causing HDR syndrome in a Sri Lankan family.

Case presentation
A 13-year-old boy with an acute febrile illness, hypocalcaemia and bilateral carpopedal spasm was referred for evaluation. A past medical history of treatment for persistent hypocalcaemic symptoms since the age of 7 months was obtained. Biochemical investigations showed persistent low serum corrected calcium levels with hyperphosphataemia, hypomagnesaemia, low parathyroid hormone levels, hypercalciuria, and low total 25-hydroxy vitamin D levels. His renal functions and renal sonography were normal. Audiometry showed bilateral moderate to severe sensorineural hearing loss. On screening, his mother was also found to have asymptomatic hypocalcaemia, hypomagnesaemia, hyperphosphataemia, hypercalciuria and low total 25-hydroxy vitamin D levels. She had impaired renal functions and chronic parenchymal changes in the renal scan. Audiometry showed bilateral profound sensorineural hearing loss. Genetic analysis using multiplex-ligation dependent probe amplification showed a reduced gene dosage for GATA3 that is consistent with a heterozygous whole gene deletion in both the child and mother.

Conclusions
This report demonstrates the wide intra-familial phenotypic variability observed in HDR syndrome and adds further to the existing scientific literature on the genotype-phenotype correlation of this syndrome. It highlights the need for HDR syndrome to be considered in the differential diagnosis of persistent hypocalcaemia with sensorineural deafness and/or renal involvement, and for appropriate genetic evaluation to be done to confirm the diagnosis.
Phytochemical composition of wormwood (Artemisia gmelinii) extracts in respect of their antimicrobial activity
Authors: Mamatova Aliya S. , Korona-Glowniak Izabela , Skalicka-Woźniak Krystyna , Józefczyk Aleksandra , Wojtanowski Krzysztof K. , Baj Tomasz , Sakipova Zuriyadda B. , Malm Anna 
Published: October 2019

Abstract

Background
Extracts from medicinal plants with phytochemicals with known antimicrobial properties can be an effective adjunct in the complex treatment of infectious diseases. This study aimed to evaluate the antimicrobial activity of wormwood extracts collected in Kazakhstan (Artemisia gmelinii Weber ex Stechm.), along with their phytochemical analysis.

Methods
The ethanolic and chloroform extracts were subjected to HPLC combined with quadrupole time-of-flight mass spectrometry method. For quantitative assessment of antimicrobial activity, minimal inhibitory concentration (MIC) of the tested extracts was determined by micro-dilution broth method for the panel of the reference microorganisms. Minimal bactericidal concentration (MBC) or minimal fungicidal concentration (MFC) were also determined.

Results
LC/MS analysis showed the presence of 13 compounds in the tested extracts, including flavonoids: apigenin, luteolin, rutin, two O-methylated flavonols (isorhamnetin, rhamnazine), coumarin compounds (umbelliferone, scopoletin and scopolin (scopoletin 7-glucoside), 3-hydroxycoumarin and 4-hydroxycoumarin), chlorogenic acid and two dicaffeoylquinic acid isomers. Quantitative HPLC analysis showed that umbelliferone was dominant in the chloroform extract while chlorogenic acid was identified as a main compound in the ethanolic extract. The antibacterial and antifungal activity of chloroform and ethanolic extracts was comparable. The most sensitive were the Gram-positive bacteria represented by staphylococci, Micrococcus luteus and Bacillus spp. (MIC = 1.25–5 mg/ml) and yeasts represented by Candida spp. (MIC = 2.5–5 mg/ml), irrespective of the assayed extract.

Conclusions
Extracts of wormwood Artemisia gmelinii have shown a wide spectrum of antibacterial and antifungal activity. Luteolin, rutin, isorhamnetin and scopolin were identified in A. gmelinii species for the first time. The determining of the most potential compounds of Artemisia gmelinii can be used to develop effective antibacterial and antifungal agents.
Association between medical student debt and choice of specialty: a 6-year retrospective study
Authors: Fritz Erik M. , van den Hoogenhof Suzanne , Braman Jonathan P. 
Published: October 2019

Abstract

Background
The effect of rapidly increasing student debt on medical students’ ultimate career plans is of particular interest to residency programs desiring to enhance recruitment, including primary care specialties. Previous survey studies of medical students indicate that amount of student debt influences choice of medical specialty. Research on this topic to date remains unclear, and few studies have included the average income of different specialties in analyses. The purpose of this study is to observe whether empirical data demonstrates an association between debt of graduating medical students and specialties into which students match.

Methods
This was a retrospective cross-sectional study of a public institution including data from graduation years 2010–2015. For each included student, total educational debt at graduation and matched specialty were obtained. Average income of each specialty was also obtained. Statistical hypothesis testing was performed to analyze any differences in average debt among specialties; subanalysis was performed assessing debt for primary care (PC) versus non-primary care (NPC) specialties. Correlation between student debt and average specialty income was also evaluated.

Results
One thousand three hundred ten students met the inclusion criteria and 178 were excluded for a final study population of 1132 (86%). The average debt was $182,590. Average debt was not significantly different among the different specialties (P = 0.576). There was no significant difference in average debt between PC and NPC specialties (PC $182,345 ± $64,457, NPC $182,868 ± $70,420, P = 0.342). There was no correlation between average specialty income and graduation debt (Spearman’s rho = 0.021, P = 0.482).

Conclusions
At our institution, student indebtedness did not appear to affect matched medical specialty, and no correlation between debt and average specialty income was observed. Different subspecialties and residency programs interested in recruiting more students or increasing diversity may consider addressing alternative factors which may have a stronger influence on student choices.
Using concept mapping to inform the development of a transitional reintegration intervention program for formerly incarcerated people with HIV
Authors: Antoniou Tony , Mishra Sharmistha , Matheson Flora , Smith-Merrill Diane , Challacombe Laurel , Rowe Janet , DiCenso Anne Marie , Kouyoumdjian Fiona G. , Wobeser Wendy , Kendall Claire , Loutfy Mona , Tsang Jenkin , Kanee Lauren , Strike Carol 
Published: October 2019

AbstractBackgroundAccessing HIV-related care is challenging for formerly incarcerated people with HIV. Interventions informed by the perspectives of these individuals could facilitate engagement with care and address competing priorities that may act as barriers to this process.MethodsWe used concept mapping to identify and prioritize the main obstacles to engaging with HIV-related care following prison release. In brainstorming sessions, formerly incarcerated people with HIV generated responses to a focused prompt regarding the main barriers to reengaging with care. These were consolidated in 35 statements. Next, participants sorted the consolidated list of responses into groups and rated each from lowest to highest in terms of its importance and feasibility of being addressed. We used cluster analysis to generate concept maps that were interpreted with participants.ResultsOverall, 39 participants participated in brainstorming sessions, among whom 18 returned for rating and sorting. Following analysis, a seven-cluster map was generated, with participants rating the ‘Practical Considerations’ (e.g. lack of transportation from prison) and ‘Survival Needs’ (e.g. securing housing and food) clusters as most important. Although ratings were generally similar between women and men, women assigned greater importance to barriers related to reconnecting with children.ConclusionsUsing concept mapping, we worked with formerly incarcerated people with HIV to identify and prioritize key challenges related to accessing health and social services following prison release. Transitional intervention programs should include programs and processes that address meeting basic subsistence needs and overcoming logistical barriers related to community re-entry.
PIK3CA-CDKN2A clonal evolution in metastatic breast cancer and multiple points cell-free DNA analysis
Authors: Palmieri Maria , Baldassarri Margherita , Fava Francesca , Fabbiani Alessandra , Campennì Giuseppe Maria , Mencarelli Maria Antonietta , Tita Rossella , Marsili Stefania , Renieri Alessandra , Frullanti Elisa 
Published: October 2019

Abstract

Background
Daily experience tells us that breast cancer can be controlled using standard protocols up to the advent of a relapse. Now new frontiers in precision medicine like liquid biopsy of cell free DNA (cfDNA) give us the possibility to understand cancer evolution and pick up the key mutation on specific cancer driver gene. However, tight schedule of standardized protocol may impair the use of personalized experimental drugs in a timely therapeutic window.

Main body
Here, using a combination of deep next generation sequencing and cfDNA liquid biopsy, we demonstrated that it is possible to monitor cancer relapse over time. We showed for the first time the exact correspondence from the increasing clonal expansion and clinical worsening of metastatic breast cancer.

Conclusion
Thanks to liquid biopsy may be possible to introduce new experimental drugs in the correct therapeutic window which would lead in the near future to an effective treatment which otherwise remains challenging.
Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin
Authors: Shen Yanwei , Li Shuting , Wang Xin , Wang Mengying , Tian Qi , Yang Jiao , Wang Jichang , Wang Biyuan , Liu Peijun , Yang Jin 
Published: October 2019

Abstract

Background
A promising strategy to overcome the chemoresistance is the tumor blood vessel normalization, which restores the physiological perfusion and oxygenation of tumor vasculature. Thalidomide (Thal) has been shown to increase the anti-tumor effect of chemotherapy agents in solid tumors. However, it is not yet known whether the synergistic effect of Thal combined with other cytotoxic drugs is attributable to tumor vascular normalization.

Methods
We used two homograft mice models (4 T1 breast tumor model and CT26 colorectal tumor model) to investigate the effect of Thal on tumor growth, microvessel density, vascular physiology, vascular maturity and function, drug delivery and chemosensitivity. Immunofluorescence, immunohistochemistry and scanning electron microscopy were performed to determine the vessel changes. Protein array assay, qPCR and western blotting were used to detect the molecular mechanism by which Thal regulates tumor vascular.

Results
Here we report that Thal potently suppressed tumor growth, angiogenesis, hypoxia, and vascular permeability in animal models. Thal also induced a regular monolayer of endothelial cells in tumor vessels, inhibiting vascular instability, and normalized tumor vessels by increasing vascular maturity, pericyte coverage and endothelial junctions. The tumor vessel stabilization effect of Thal resulted in a decrease in tumor vessel tortuosity and leakage, and increased vessel thickness and tumor perfusion. Eventually, the delivery of cisplatin was highly enhanced through the normalized tumor vasculature, thus resulting in profound anti-tumor and anti-metastatic effects. Mechanistically, the effects of Thal on tumor vessels were caused in part by its capability to correct the imbalance between pro-angiogenic factors and anti-angiogenic factors.

Conclusions
Our findings provide direct evidence that Thal remodels the abnormal tumor vessel system into a normalized vasculature. Our results may lay solid foundation for the development of Thal as a novel candidate agent to maximize the therapeutic efficacy of chemotherapeutic drugs for solid tumors.
Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop
Authors: Shi Wanyue , Tang Tingting , Li Xinping , Deng Siwei , Li Ruiyi , Wang Yingshan , Wang Yifei , Xia Tiansong , Zhang Yanfeng , Zen Ke , Jin Liang , Pan Yi 
Published: October 2019

Abstract

Background
miR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure.

Methods
qRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells.

Results
We confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter.

Conclusion
Taken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.
Variation in accessibility of the population to an Emergency Medical Communication Centre: a multicentre observational study
Authors: Penverne Yann , Leclere Brice , Lecarpentier Eric , Marx Jean-Sébastien , Gicquel Benjamin , Goix Laurent , Reuter Paul-Georges 
Published: October 2019

Abstract

Background
Access to an Emergency Medical Communication Centre is essential for the population in emergency situations. Handling inbound calls without delay requires managing activity, process and outcome measures of the Emergency Medical Communication Centre to improve the workforce management and the level of service. France is facing political decisions on the evolution of the organisation of Emergency Medical Communication Centres to improve accessibility for the population. First, we aim to describe the variation in activity between Emergency Medical Communication Centres, and second, to explore the correlation between process measures and outcome measures.

Methods
Using telephone activity data extraction, we conducted an observational multicentre study of six French Emergency Medical Communication Centres from 1 July 2016 to 30 June 2017. We described the activity (number of incoming calls, call rate per 1000 inhabitants), process measure (agent occupation rate), and outcome measure (number of calls answered within 20 s) by hourly range and estimated the correlation between them according to the structural equation methods.

Results
A total of 52,542 h of activity were analysed, during which 2,544,254 calls were received. The annual Emergency Medical Communication Centre call rate was 285.5 [95% CI: 285.2–285.8] per 1000 inhabitants. The average hourly number of calls ranged from 29 to 61 and the call-handled rate from 75 to 98%. There are variations in activity between Emergency Medical Communication Centres. The mean agent occupation rate was correlated with the quality of service at 20 s (coefficient at − 0.54). The number of incoming calls per agent was correlated with the mean occupation rate (coefficient at 0.67). Correlation coefficients varied according to the centres and existed between different process measures.

Conclusions
The activity dynamics of the six Emergency Medical Communication Centres are not identical. This variability, illustrating the particularity of each centre, must be accurately assessed and should be taken into account in managerial considerations. The call taker occupation rate is the leverage in the workforce management to improve the population accessibility.
RaGOO: fast and accurate reference-guided scaffolding of draft genomes
Authors: Alonge Michael , Soyk Sebastian , Ramakrishnan Srividya , Wang Xingang , Goodwin Sara , Sedlazeck Fritz J. , Lippman Zachary B. , Schatz Michael C. 
Published: October 2019

Abstract
We present RaGOO, a reference-guided contig ordering and orienting tool that leverages the speed and sensitivity of Minimap2 to accurately achieve chromosome-scale assemblies in minutes. After the pseudomolecules are constructed, RaGOO identifies structural variants, including those spanning sequencing gaps. We show that RaGOO accurately orders and orients 3 de novo tomato genome assemblies, including the widely used M82 reference cultivar. We then demonstrate the scalability and utility of RaGOO with a pan-genome analysis of 103 Arabidopsis thaliana accessions by examining the structural variants detected in the newly assembled pseudomolecules. RaGOO is available open source at https://github.com/malonge/RaGOO.
Prevention of postpartum suicidality in Israel
Authors: Klomek Anat Brunstein 
Published: October 2019

Abstract
Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic—not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.