bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review
Authors: Kalia Namarta , Singh Jatinder , Kaur Manpreet 
Published: January 2020

AbstractRecurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and differentTrichomonas vaginalisstrains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale forLactobacillidominance and changes that occur in healthy VMB throughout a women’s life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. “VMB dominated withLactobacilliis healthier than a diverse VMB”. These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women’s response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.
Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
Authors: He Jiehua , Huang Zuoyu , He Mingliang , Liao Jianyou , Zhang Qianqian , Wang Shengwen , Xie Lin , Ouyang Leping , Koeffler H. Phillip , Yin Dong , Liu Anmin 
Published: January 2020

AbstractBackgroundRecent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS.MethodsA bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitroand vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p.ResultsIn this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P < 0.05). Next, we verified that circ-MAPK4 promoted the survival and inhibited the apoptosis of glioma cells in vitroandin vivo. Furthermore, we proved that circ-MAPK4 was involved in regulating p38/MAPK pathway, which affected glioma proliferation and apoptosis. Finally, miR-125a-3p, a miRNA exhibited tumor-suppressive function through impairing p38/MAPK pathway, which was increased by inhibiting circ-MAPK4 and could be pulled down by circ-MAPK4. Inhibition of miR-125a-3p could partly rescue the increased phosphorylation levels of p38/MAPK and the elevated amount of apoptosis inducing by knockdown of circ-MAPK4.ConclusionsOur findings suggest that circ-MAPK4 is a critical player in glioma cell survival and apoptosis via p38/MAPK signaling pathway through modulation of miR-125a-3p, which can serve as a new therapeutic target for treatment of gliomas.
Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance
Authors: Dadfar Seyed Mohammadali , Camozzi Denise , Darguzyte Milita , Roemhild Karolin , Varvarà Paola , Metselaar Josbert , Banala Srinivas , Straub Marcel , Güvener Nihan , Engelmann Ulrich , Slabu Ioana , Buhl Miriam , van Leusen Jan , Kögerler Paul , Hermanns-Sachweh Benita , Schulz Volkmar , Kiessling Fabian , Lammers Twan 
Published: January 2020

AbstractSuperparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.
Carbon nanoparticles enhance potassium uptake via upregulating potassium channel expression and imitating biological ion channels in BY-2 cells
Authors: Chen Lijuan , Yang Jinchu , Li Xiang , Liang Taibo , Nie Cong , Xie Fuwei , Liu Kejian , Peng Xiaojun , Xie Jianping 
Published: January 2020

Abstract
Background
Carbon nanoparticles (CNPs) have been reported to boost plant growth, while the mechanism that CNPs enhanced potassium uptake for plant growth has not been reported so far.

Results
In this study, the function that CNPs promoted potassium uptake in BY-2 cells was established and the potassium accumulated in cells had a significant correlation with the fresh biomass of BY-2 cells. The K+ accumulation in cells increased with the increasing concentration of CNPs. The K+ influx reached high level after treatment with CNPs and was significantly higher than that of the control group and the negative group treated with K+ channels blocker, tetraethylammonium chloride (TEA+). The K+ accumulation was not reduced in the presence of CNPs inhibitors. In the presence of potassium channel blocker TEA+ or CNPs inhibitors, the NKT1 gene expression was changed compared with the control group. The CNPs were found to preferentially transport K+ than other cations determined by rectification of ion current assay (RIC) in a conical nanocapillary.

Conclusions
These results indicated that CNPs upregulated potassium gene expression to enhance K+ accumulation in BY-2 cells. Moreover, it was speculated that the CNPs simulated protein of ion channels via bulk of carboxyl for K+ permeating. These findings will provide support for improving plant growth by carbon nanoparticles.
Unravelling Functional Neurology: an overview of all published documents by FR Carrick, including a critical review of research articles on its effect or benefit
Authors: Demortier Marine , Leboeuf-Yde Charlotte 
Published: January 2020

Abstract
Background
Functional Neurology (FN), founded by FR Carrick, is an approach used by some chiropractors to treat a multitude of conditions via the nervous system including the brain. However, it seems to lack easily obtainable scientific evidence for its clinical validity.

Objectives
1) To define the topics of FR Carrick’s publications, 2) to define the proportion of articles that are research studies, case studies, abstracts and conference papers, 3) to define how many of these are clinical research studies that purported or appeared to deal with the effect or benefit of FN, 4) in these studies, to establish whether the design and overall study method were suitable for research into the effect or benefit of FN, and 5) to describe the evidence available in relation to the clinical effect or benefit of FN, taking into account seven minimal methodological criteria.

Method
A literature search was done on Pubmed from its inception till October 2018, supplemented by a search on Scopus and ResearchGate to find all published documents by FR Carrick. We identified their types and topics, retaining for a critical review full text scientific articles appearing to test effect/benefit of FN procedures, subjecting them to a basic quality assessment (scoring 0–7). Results from studies of methodologically acceptable standard would be taken into account.

Results
We found 121 published texts, 39 of which were full scientific research articles. Of these, 23 dealt with topics relating to FN. Fourteen articles reported on clinical validity but only seven included a control group. The methodological quality of these seven articles was low, ranging between 1.5–4 out of 7. We therefore did not further report the outcomes of these studies.

Conclusion
We found no acceptable evidence in favour of effect/benefit of the FN approach. We therefore do not recommend its promotion as an evidence-based method. Further research on this topic should be conducted in collaboration with independent scientific institutions using commonly accepted research methods.

Trial registration
PROSPERO This review was registered in PROSPERO (application date 23.02.2019; no CRD42019126345).
Bleeding complications after cardiac surgery, before anticoagulation start and then with argatroban or heparin in the early postoperative setting
Authors: Klingele Matthias , Enkel Julia , Speer Timo , Bomberg Hagen , Baerens Lea , Schäfers Hans-Joachim 
Published: January 2020

Abstract
Objectives
After elective cardiac surgery a postoperative anticoagulation is obligatory. With critically ill patients the conventional anticoagulation standard heparin is sometimes impossible, e.g. based on HIT II. Then, argatroban is currently a possible alternative, however, due to its impaired metabolism in critically ill patients, anticoagulation effect is harder to anticipate, thus resulting in higher bleeding risk. Furthermore, to date no antidote is available. Hence, severe postoperative bleeding incidents under anticoagulation are commonly mono-causal attributed to the anticoagulation itself. This study concentrates on the number of well-defined postoperative bleeding incidents before any anticoagulation started, then actually under argatroban as well as compared to those under heparin (or switched from heparin to argatroban).

Material and methods
Retrospective study including 215 patients undergoing elective cardiac surgery with a postoperative stay in ICU ≥48 h. Postoperative bleeding complications before and after start of anticoagulation were evaluated. Definition of bleeding complications were: decrease of hemoglobin by more than 2 g/dl without dilution (mean value of volume balance plus one standard deviation) and/or increased need of red blood cell transfusion/day (average transfusion rate + 2 standard deviations).

Results
Within the study group of 215 patients, 143 were treated with heparin, 43 with argatroban, 29 switched from heparin to argatroban. Overall, 26.5% (57/215) postoperative bleeding complications occurred. In 54.4% (31/57) bleeding complications occurred before start of anticoagulation; in 43.6% (26/57) after. Of these, 14 bleeding incidents occurred under heparin 9.8% (14/143), 6 under argatroban 14% (6/43) and 6 switched 20.7% (6/29). Higher bleeding complications before start of anticoagulation was related to concomitant factors influencing the overall bleeding risk; e.g. score of severity of illness. These observations further correlate with postoperative, but not anticoagulation induced mortality rate of 2.8% of then given heparin, 20.9% then argatroban, 20.7% then switched.

Conclusions
Postoperative bleeding complications cannot simply be attributed to anticoagulation since occurring often before anticoagulation was started. The risk for bleeding complications after start of anticoagulation was quite comparable for argatroban and heparin. Accordingly, the influence of argatroban on bleeding complications in the postoperative period may be less significant than previously thought.
Depressive symptoms in Fabry disease: the importance of coping, subjective health perception and pain
Authors: Körver Simon , Geurtsen Gert J. , Hollak Carla E. M. , van Schaik Ivo N. , Longo Maria G. F. , Lima Marjana R. , Vedolin Leonardo , Dijkgraaf Marcel G. W. , Langeveld Mirjam 
Published: January 2020

Abstract
Background
Despite the high prevalence of depressive symptoms in Fabry disease (FD), it is unclear which patient characteristics are important in relation to these symptoms. Additionally, the impact of coping styles in relation to depressive symptoms in FD has been unexplored. Determining the impact of different factors relating to depressive symptoms in FD can guide both prevention and treatment of these symptoms.

Methods
Depressive symptoms (Center for Epidemiologic Studies Depression scale (CESD)) and coping styles (Utrecht Coping List) were assessed in a Dutch FD cohort. Other potentially important variables were identified from FD literature and assessed in this cohort. Relations were evaluated using multiple linear models.

Results
Potentially important variables in FD literature were: pain, unemployment, health perception, being single, comorbidities and stroke. Employed coping styles were “avoidance and brooding”, “positivity and problem solving” and “seeking social support”. Thirty-one of the 81 FD patients (38%) had depressive symptoms. CESD-scores were lower in patients with better health perception and more “positivity and problem solving” and higher in patients with more pain and “avoidance and brooding”. The best model explained 70% (95%CI: 54–76%) of observed variance of the CESD.

Conclusions
Depressive symptoms in FD are related to pain, negative health perception and use of specific coping styles. Psychological interventions could be employed to alter coping behavior and alleviate depressive symptoms.
Merkel cell polyomavirus detected in head and neck carcinomas from Chile
Authors: Muñoz Juan P. , Blanco Rancés , Osorio Julio C. , Oliva Carolina , Diaz María José , Carrillo-Beltrán Diego , Aguayo Rebeca , Castillo Andrés , Tapia Julio C. , Calaf Gloria M. , Gaggero Aldo , Aguayo Francisco 
Published: January 2020

Abstract
Background
The role of human polyomaviruses (HPyVs) in epithelial tumors such as head and neck carcinomas (HNSCCs) including oral and oropharyngeal carcinomas has not been established. In this study, we evaluated for the first time the presence of Merkel cell polyomavirus (MCPyV), BK human polyomavirus (BKPyV), and JC human polyomavirus (JCPyV) in HNSCCs from Chilean subjects.

Methods
One hundred and twenty HNSCCs were analyzed for the presence of MCPyV, BKPyV and JCPyV using real-time polymerase chain reaction procedures. In addition, 54 oral brushes from age- and sex-paired subjects were analyzed.

Results
Of the total of 120 HNSCCs, 15 were positive for MCPyV (12.5%). Only one case was positive for BKPyV (0.8%) and none for JCPyV (0%). In subjects without cancer, only one case (1.8%) resulted positive for MCPyV and none for JCPyV and BKPyV. MCPyV was associated with HNSCCs (p = 0.0239; OR = 7.571; 95% CI: 1.192–81.46). No association was found between age (p = 0.1996), gender (p = 0.7111) or differentiation status (p > 0.9999) and MCPyV presence in HNSCCs.

Conclusions
MCPyVs were detected in HNSCCs from Chilean patients and were not detected in oral brushes from patients without cancer. More studies are warranted for defining an etiological role and clinical/molecular consequences of these viruses in HNSCCs.
Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury
Authors: Yu Jiangtao , Zhang Yuxian , Ma Haoli , Zeng Rong , Liu Ruining , Wang Pengcheng , Jin Xiaoqing , Zhao Yan 
Published: January 2020

Abstract
Background
N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated.

Results
In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23–2.

Conclusion
This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.
Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia
Authors: Elgamal Ola A. , Mehmood Abeera , Jeon Jae Yoon , Carmichael Bridget , Lehman Amy , Orwick Shelley J. , Truxall Jean , Goettl Virginia M. , Wasmuth Ronni , Tran Minh , Mitchell Shaneice , Lapalombella Rosa , Eathiraj Sudharshan , Schwartz Brian , Stegmaier Kimberly , Baker Sharyn D. , Hertlein Erin , Byrd John C. 
Published: January 2020

Abstract
Background
Acute myeloid leukemia (AML) is the most common type of adult leukemia. Several studies have demonstrated that oncogenesis in AML is enhanced by kinase signaling pathways such as Src family kinases (SFK) including Src and Lyn, spleen tyrosine kinase (SYK), and bruton’s tyrosine kinase (BTK). Recently, the multi-kinase inhibitor ArQule 531 (ARQ 531) has demonstrated potent inhibition of SFK and BTK that translated to improved pre-clinical in vivo activity as compared with the irreversible BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) models. Given the superior activity of ARQ 531 in CLL, and recognition that this molecule has a broad kinase inhibition profile, we pursued its application in pre-clinical models of AML.

Methods
The potency of ARQ 531 was examined in vitro using FLT3 wild type and mutated (ITD) AML cell lines and primary samples. The modulation of pro-survival kinases following ARQ 531 treatment was determined using AML cell lines. The effect of SYK expression on ARQ 531 potency was evaluated using a SYK overexpressing cell line (Ba/F3 murine cells) constitutively expressing FLT3-ITD. Finally, the in vivo activity of ARQ 531 was evaluated using MOLM-13 disseminated xenograft model.

Results
Our data demonstrate that ARQ 531 treatment has anti-proliferative activity in vitro and impairs colony formation in AML cell lines and primary AML cells independent of the presence of a FLT3 ITD mutation. We demonstrate decreased phosphorylation of oncogenic kinases targeted by ARQ 531, including SFK (Tyr416), BTK, and fms-related tyrosine kinase 3 (FLT3), ultimately leading to changes in down-stream targets including SYK, STAT5a, and ERK1/2. Based upon in vitro drug synergy data, we examined ARQ 531 in the MOLM-13 AML xenograft model alone and in combination with venetoclax. Despite ARQ 531 having a less favorable pharmacokinetics profile in rodents, we demonstrate modest single agent in vivo activity and synergy with venetoclax.

Conclusions
Our data support consideration of the application of ARQ 531 in combination trials for AML targeting higher drug concentrations in vivo.
Increased ethylene production by overexpressing phosphoenolpyruvate carboxylase in the cyanobacterium Synechocystis PCC 6803
Authors: Durall Claudia , Lindberg Pia , Yu Jianping , Lindblad Peter 
Published: January 2020

AbstractBackgroundCyanobacteria can be metabolically engineered to convert CO2 to fuels and chemicals such as ethylene. A major challenge in such efforts is to optimize carbon fixation and partition towards target molecules.ResultsTheefegene encoding an ethylene-forming enzyme was introduced into a strain of the cyanobacteriumSynechocystisPCC 6803 with increased phosphoenolpyruvate carboxylase (PEPc) levels. The resulting engineered strain (CD-P) showed significantly increased ethylene production (10.5 ± 3.1 µg mL−1 OD−1 day−1) compared to the control strain (6.4 ± 1.4 µg mL−1 OD−1 day−1). Interestingly, extra copies of the nativepepcor the heterologous expression of PEPc from the cyanobacteriumSynechococcusPCC 7002 (Synechococcus) in the CD-P, increased ethylene production (19.2 ± 1.3 and 18.3 ± 3.3 µg mL−1 OD−1 day−1, respectively) when the cells were treated with the acetyl-CoA carboxylase inhibitor, cycloxydim. A heterologous expression of phosphoenolpyruvate synthase (PPSA) fromSynechococcusin the CD-P also increased ethylene production (16.77 ± 4.48 µg mL−1 OD−1 day−1) showing differences in the regulation of the native and the PPSA fromSynechococcusinSynechocystis.ConclusionsThis work demonstrates that genetic rewiring of cyanobacterial central carbon metabolism can enhance carbon supply to the TCA cycle and thereby further increase ethylene production.
Investigating relationship between religious commitment and moral sensitivity in nurses working in ICU
Authors: Khalighi Ebrahim , Solaimanizadeh Laleh , Borji Milad , Tarjoman Asma , Soltany Behrouz , Zareie Farzad 
Published: January 2020

Abstract
Objectives
This study aimed at determining the relationship between religious commitment and moral sensitivity among nurses working in the ICU sections in the west of Iran. The present study was a cross-sectional descriptive-analytic study carried out on nurses working in ICU wards of two western cities in Iran. The instrument used includes a demographic questionnaire, religious commitment questionnaire and moral sensitivity questionnaire in nurses. First, the researchers referred to the ICU wards of the hospitals in the cities after receiving permission from the relevant authorities by referring to three shifts in the morning, evening and night shifts and holidays. The researchers, while explaining the research goals for the nurses participating in the study, obtained their informed consent to participate in this study.

Results
According to the findings, mean (SD) of the overall score of religious commitment was equal to 36.38 (4.58) and mean (SD) of MS score of nurses was 59.21 (12.65). Also, 91 nurses (82.7%) had average MS, 7 (6.4%) had low MS and 12 (10.9%) had high MS.