bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up
Authors: De Strooper Lise M.A. , Berkhof Johannes , Steenbergen Renske D.M. , Lissenberg‐Witte Birgit I. , Snijders Peter J.F. , Meijer Chris J.L.M. , Heideman Daniëlle A.M. 
Published: April 2018

DNA methylation analysis of cervical scrapes using FAM19A4 and mir124‐2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV‐positive women. To date, longitudinal data on the cancer risk of methylation test‐negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124‐2 methylation analysis in an HPV‐positive screening cohort with 14 years of follow‐up. Archived HPV‐positive cervical scrapes of 1,040 women (age 29–61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124‐2 methylation. By linkage with the nationwide network and registry of histo‐ and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow‐up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124‐2 methylation, including 24 women with cervical cancer in follow‐up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow‐up. Within screening round capability of FAM19A4/mir124‐2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5–100). Kaplan–Meier estimate of 14‐year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66–3.0) among baseline methylation‐negative and 2.4% (95% CI: 1.4–3.6) among baseline cytology‐negative women (risk difference: 0.71% [95% CI: 0.16–1.4]). In conclusion, a negative FAM19A4/mir124‐2 methylation test provides a low cervical cancer risk in HPV‐positive women of 30 years and older. FAM19A4/mir124‐2 methylation testing merits consideration as an objective triage test in HPV‐based cervical screening programs.
Inside Cover: Noninvasive, high‐speed, near‐infrared imaging of the biomolecular distribution and molecular mechanism of embryonic development in fertilized fish eggs (J. Biophotonics 4/2018)
Authors: Ishigaki Mika , Nishii Takashi , Puangchit Paralee , Yasui Yui , Huck Christian W. , Ozaki Yukihiro 
Published: April 2018

The biomaterial distribution and its molecular mechanism of embryonic development in Japanese medaka fish were visualized without staining using high‐speed near‐infrared imaging. It was a remarkable achievement to visualize the structures of eyes, lipid bilayer membranes, micelles, and water structural variations at the interface of different substances. Furthermore, insights on lipid metabolism and membrane functions were obtained from the biased distribution of lipoproteins and the presence of unsaturated fatty acids in the egg membrane.Further details can be found in the article by Mika Ishigaki (e201700115)
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Back Cover: Autofluorescence and white light imaging‐guided endoscopic Raman and diffuse reflectance spectroscopy for in vivo nasopharyngeal cancer detection (J. Biophotonics 4/2018)
Authors: Lin Duo , Qiu Sufang , Huang Wei , Pan Jianji , Xu Zhihong , Chen Rong , Feng Shangyuan , Chen Guannan , Li Yongzeng , Short Michael , Zhao Jianhua , Fawzy Yasser , Zeng Haishan 
Published: April 2018

An integrated 4‐modality endoscopy system combining white light imaging, autofluorescence imaging, diffuse reflectance spectroscopy and Raman spectroscopy technologies was developed for in vivo endoscopic nasopharyngeal cancer detection. Both high diagnostic sensitivity (98.6%) and high specificity (95.1%) for differentiating cancer from normal tissue sites were achieved using this system combined with multivariate diagnostic algorithm, demonstrating great potential for improving real‐time, in vivo diagnosis of cancer at endoscopy.Further details can be found in the article by Duo Lin et al. (e201700251)
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25-Hydroxyvitamin D Threshold for the Effects of Vitamin D Supplements on Bone Density: Secondary Analysis of a Randomized Controlled Trial
Authors: Macdonald Helen M , Reid Ian R , Gamble Gregory D , Fraser William D , Tang Jonathan C , Wood Adrian D 
Published: April 2018

ABSTRACT

Most trials of vitamin D supplementation have shown no benefits on bone mineral density (BMD), although severe vitamin D deficiency causes osteomalacia, which is associated with profound BMD deficits. Recently, the ViDA-BMD study from New Zealand demonstrated a threshold of baseline 25-hydroxyvitamin D (25OHD; 30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now reexamined data from a similar trial in Aberdeen to determine whether a baseline 25OHD threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/d, or vitamin D 1000 IU/d over 1 year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/d only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25OHD was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25OHD ≤30 nmol/L, but no significant effects were apparent in those with baseline 25OHD above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25OHD ≤30 nmol/L. This moves us further toward a trial-based definition of vitamin D deficiency in adults with adequate calcium intakes and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25OHD concentrations in this range. © 2018 American Society for Bone and Mineral Research.
MiR‐135a represses oxidative stress and vascular inflammatory events via targeting toll‐like receptor 4 in atherogenesis
Authors: Du Xian‐Jin , Lu Jing‐Min 
Published: April 2018

AbstractPlenty of microRNAs have been identified as critical mediators in atherosclerosis progression, which is still a great threat to human health. Oxidative stress and inflammation have been implicated to contribute a lot to atherosclerosis development. MiR‐135a is abnormally expressed in various cancer types, however its function in atherosclerosis is largely unexplored. Ox‐LDL is commonly recognized as a crucial atherosclerosis regulator. In our current study, we observed ox‐LDL was able to induce RAW264.7 cell apoptosis and meanwhile miR‐135a was restrained by ox‐LDL both dose‐dependently and time‐ dependently. CD36 has been reported to participate in atherosclerosis process and miR‐135a mimics can inhibit its expression while miR‐135a inhibitors exhibited a reverse phenomenon. Meanwhile, miR‐135a overexpression can suppress foam cell formation, TC, TG levels, and cell apoptosis induced by 20 µg/mL ox‐LDL. Subsequently, it was found that miR‐135a overexpression can inhibit oxidative stress by decreasing ROS, MDA levels, and increasing SOD levels. Reversely, miR‐135a inhibition demonstrated an inhibitory effect in vitro. Apart from these, miR‐135a can also modulate inflammation molecules including IL‐6, IL‐1β, and TNF‐α. TLR4 was predicted as a target of miR‐135a and the negative correlation between them was confirmed by dual‐luciferase reporter assay in our study. This work improves our understanding of atherosclerosis events mediated by miR‐135a/TLR4 and helps to develop new approaches for atherosclerosis.
Matrix metalloproteinases‐2 (MMP‐2) and matrix metalloproteinases ‐9 (MMP‐9) are differentially expressed in different regions of normal and preeclampsia placentae
Authors: Sahay Akriti S. , Jadhav Anjali T. , Sundrani Deepali P. , Wagh Girija N. , Mehendale Savita S. , Joshi Sadhana R. 
Published: April 2018

AbstractMatrix metalloproteinases (MMPs) are involved in the extracellular matrix (ECM) remodeling during human placentation and parturition and have been shown to be associated with oxidative stress. Placental regional changes in oxygen availability and oxidative stress indices may influence regional differences in expression of MMPs. This study examines the protein and mRNA levels of MMP‐2 and MMP‐9 in different regions of the placenta in normotensive control (NC) women and women with preeclampsia (PE). Fifty‐two NC women and 43 women with PE (18 delivered at term [T‐PE] and 25 delivered preterm [PT‐PE]) were recruited. Placental samples were taken from four regions: central basal (CM), central chorionic (CF), peripheral basal (PM), and peripheral chorionic (PF). MMP protein and mRNA levels were measured by ELISA and quantitative real time PCR, respectively. MMP‐2 protein levels were higher in all the placental regions (P < 0.05) from PT‐PE group as compared to the respective regions from the NC and T‐PE groups. MMP‐9 mRNA levels were higher in CM region as compared to CF and PM regions (P < 0.05) in the NC group and compared to CF and PF regions (P < 0.05) in the T‐PE group. The MMP‐9 mRNA levels were lower in the CF region in the PT‐PE and T‐PE groups (P < 0.05) as compared to the NC group. Elevated levels of MMP‐2 protein levels were observed in all regions of PT‐PE placenta possibly influencing the degradation of placental ECM. Lower mRNA expression of MMP‐9 both in PT‐PE and T‐PE may contribute to a disturbed placental vascularization.
Identification of variants in the mitochondrial lysine‐tRNA (MT‐TK) gene in myoclonic epilepsy—pathogenicity evaluation and structural characterization by in silico approach
Authors: Nadeem Muhammad S. , Ahmad Habib , Mohammed Kaleemuddin , Muhammad Khushi , Ullah Inam , Baothman Othman A. S. , Ali Nasir , Anwar Firoz , Zamzami Mazin A. , Shakoori Abdul Rauf 
Published: April 2018

AbstractVariations in mitochondrial genes have an established link with myoclonic epilepsy. In the present study we evaluated the nucleotide sequence of MT‐TK gene of 52 individuals from 12 unrelated families and reported three variations in 2 of the 13 epileptic patients. The DNA sequences coding for MT‐TK gene were sequenced and mutations were detected in all participants. The mutations were further analyzed by the in silico analysis and their structural and pathogenic effects were determined. All the investigated patients had symptoms of myoclonus, 61.5% were positive for ataxia, 23.07% were suffering from hearing loss, 15.38% were having mild to severe dementia, 69.23% were males, and 61.53% had cousin marriage in their family history. DNA extracted from saliva was used for the PCR amplification of a 440 bp DNA fragment encompassing complete MT‐TK gene. The nucleotide sequence analysis revealed three mutations, m.8306T>C, m.8313G>C, and m.8362T>G that are divergent from available reports. The identified mutations designate the heteroplasmic condition. Furthermore, pathogenicity of the identified variants was predicted by in silico tools viz., PON‐mt‐tRNA and MitoTIP. Secondary structure of altered MT‐TK was predicted by RNAStructure web server. Studies by MitoTIP and PON‐mt‐tRNA tools have provided strong evidences of pathogenic effects of these mutations. Single nucleotide variations resulted in disruptive secondary structure of mutant MT‐TK models, as predicted by RNAStructure. In vivo confirmation of structural and pathogenic effects of identified mutations in the animal models can be prolonged on the basis of these findings.
Mouse serum exosomal proteomic signature in response to asbestos exposure
Authors: Munson Phillip , Lam Ying‐Wai , MacPherson Maximilian , Beuschel Stacie , Shukla Arti 
Published: April 2018

AbstractAsbestos‐induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty‐six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.
Development of a barbershop based violence intervention for young Black emerging adult men
Authors: Baker Jillian Lucas , Stevenson Howard C. , Talley Lloyd Matthew , Jemmott Loretta Sweet , Jemmott John B. 
Published: April 2018

AbstractA crucial gap in the education literature are the health interventions situated for the unique experiences of Black emerging adult men (BEAM), one of the most vulnerable populations in the United States The article describes the systematic development of a theory‐based, culturally tailored, barbershop‐based violence intervention for BEAM, aged 18–24 years. The process included developing a community advisory board, selecting a theoretical framework, incorporating community‐based participatory research principles, and conducting formative research with BEAM and barbershop owners. The result was Shape Up: Barbers Building Better Brothers, a 2‐day retaliation violence risk reduction intervention focused on increasing retaliation restraint self‐efficacy beliefs and skills and reducing the number of violent incidents. Intervention sessions were facilitated by barbers who used iPads to deliver the content. As a high‐risk population, this intervention has great public health significance for the health of BEAM.
The influence of school sense of community on students’ well‐being: A multilevel analysis
Authors: Prati Gabriele , Cicognani Elvira , Albanesi Cinzia 
Published: April 2018

AbstractPrevious studies have demonstrated the role of students’ school sense of community (i.e., emotional connection and bonds with other students at school and sense of belonging to the school as a community) in predicting well‐being (presence of positive feelings and positive functioning in life). Specifically, these studies have found that individual sense of community in the school is associated with well‐being. However, individual sense of community in the school does not constitute a school‐level characteristic, and the influence of sense of community at the school level on students’ well‐being was not investigated. To address this gap in the literature, we conducted a study investigating the influence of sense of community at the school level on students’ well‐being, using multilevel analysis. Our sample comprised 1,800 students (age ranged from 11 to 20 years) from public lower and upper secondary schools in Italy. Results showed that higher sense of community scores at the school level were associated with higher well‐being scores, while controlling for individual sense of community, gender, and age. These results provide support for a school‐level theory of school sense of community (i.e., moving school sense of community theory from the individual to the school level).
Predicting Pharmacokinetics/Pharmacodynamics in the Individual Patient: Separating Reality From Hype
Authors: Benet Leslie Z. 
Published: April 2018

AbstractIndividualization of patient drug dosing to maximize efficacy and minimize toxicity is the goal of clinical pharmacology. Here we review the history of drug dosing individualization from early predictions for renally eliminated drugs based on kidney function through the introduction of clearance concepts for metabolic processes, the differentiation of volume of distribution between pharmacokinetics and chemistry, the role of transporters, the unique pharmacokinetic aspects of oral dosing, and the relevance of protein binding to the emergence of pharmacogenomics. The Food and Drug Administration listing of pharmacogenomic markers in approved drug labeling is analyzed with respect to the promise of genomics in terms of picking the right drug for the patient based on genetic information vs selecting or adjusting the dosage regimen based on genetic information: the former resulting in a great advance, whereas the latter has shown less convincing evidence of clinical relevance. Finally, new information on individualized predictive methodologies based on marker drugs for enzymes and transporters is reviewed. We conclude that although individualization of drug dosing will work for most drugs primarily excreted unchanged in the urine, individualization of dosing regimens is not critical for wide‐therapeutic‐index drugs, whereas for narrow‐therapeutic‐index drugs predictions are most often more hype than reality, with therapeutic drug monitoring required. However, continuing advances in discovering and validating biomarkers will lead to predictions of pharmacokinetics/pharmacodynamics in the individualized patient that should result in shifting the hype to reality with time.
Development of continuous cultivation process for oil production through bioconversion of minimally treated waste streams from second‐generation bioethanol production
Authors: Singh Dilip , Mehta Preeti , Saxena Rohit , Barrow Colin J , Puri Munish , Tuli Deepak K , Mathur Anshu S 
Published: April 2018

AbstractBACKGROUNDEfficient conversion of inhibitor containing pentose rich stream into bioethanol or biogas is still challenging due to several technological challenges; however, this stream can be efficiently assimilated into lipids by oleaginous yeasts such as Rhodotorula. In this work, a continuous and nonsterile process was developed for bioconversion of waste streams into lipids for biodiesel using growth‐inhibitor‐tolerant oleaginous yeast.RESULTSAn inhibitor‐tolerating property of the strain was used to develop a cyclic and continuous near axenic cultivation process in a 2 L nonsterile bioreactor to enhance valorization of waste streams and to reduce energy requirements for media and vessel sterilization. After media optimization, continuous cultivation resulted in significant increase in biomass (14.90 g L−1 day−1) and lipid productivity (6.15 g L−1 day−1) as compared to flask (biomass ∼3 g L−1 day−1 and lipid productivity ∼0.6 g L−1 day−1) results. Palmitic acid (C16:0) and oleic acid (C18:1) were the major fatty acids, accounting for almost 80% of total lipids, thus making lipid produced in the process suitable for biodiesel production.CONCLUSIONInhibitors present in waste streams successfully maintained near axenic conditions during the cultivation. Maximum dilution rate of 1 was achieved after media optimization, which resulted in complete valorization of nutrients into biomass and lipids with high productivity. © 2018 Society of Chemical Industry
Understanding the in vivo fate of radioimmunoconjugates for nuclear imaging
Authors: Vivier Delphine , Sharma Sai Kiran , Zeglis Brian M. 
Published: April 2018

Over the past 25 years, antibodies have emerged as extraordinarily promising vectors for the delivery of radionuclides to tumors for nuclear imaging. While radioimmunoconjugates often produce very high activity concentrations in target tissues, they also are frequently characterized by elevated activity concentrations in healthy organs as well. The root of this background uptake lies in the complex network of biological interactions between the radioimmunoconjugate and the subject. In this review, we seek to provide an overview of these interactions and thus paint a general picture of the in vivo fate of radioimmunoconjugates. To cover the entire story, we have divided our discussion into 2 parts. First, we will address the path of the entire radioimmunoconjugate as it travels through the body. And second, we will cover the fate of the radionuclide itself, as its course can diverge from the antibody under certain circumstances. Ultimately, our goal is to provide the nuclear imaging field with a resource covering these important—yet often underestimated—pathways.
Effect of heart rate and pacing mode on QRS fragmentation
Authors: Zagkli Fani , Despotopoulos Stefanos , Spiliotopoulos Christos , Chiladakis John 
Published: April 2018

AbstractBackgroundThe study was designed to investigate the effect of heart rate and pacing mode on QRS fragmentation (f‐QRS). Moreover, the usefulness of f‐QRS in distinguishing patients with impaired left ventricular ejection function (EF) and ventricular tachycardia (VT) from patients with normal EF was assessed.MethodsThree hundred and six recipients, with dual‐chamber device, with intrinsic narrow or wide QRS complex and preserved atrioventricular conduction were grouped into normal‐EF or impaired‐EF VT. We analyzed intrinsic narrow f‐QRS and wide f‐QRS as well as ventricular‐paced f‐QRS following different heart rates (baseline, 100 bpm) and pacing modes.ResultsIn the baseline state, overall, patients with impaired‐EF VT (35 ± 9%), compared to those with normal‐EF, had more f‐QRS (56% vs 27%, P < .001) and ventricular‐paced f‐QRS (62% vs 16%, P < .0001). Ventricular pacing conferred both at baseline and at higher heart rate more ventricular‐paced f‐QRS in patients with impaired‐EF VT than in normal‐EF (P < .001). Detection of ventricular‐paced f‐QRS markedly improved overall specificity (84%) and positive predictive value (91%) in identifying patients with impaired‐EF VT.ConclusionsIncreased heart rate or/and ventricular pacing uncover QRS fragmentations. Detection of ventricular‐paced f‐QRS adds value toward noninvasive identification of patients with impaired‐EF VT.
Holocene temperature trends in the extratropical Northern Hemisphere based on inter‐model comparisons
Authors: Zhang Yurui , Renssen Hans , Seppä Heikki , Valdes Paul J. 
Published: April 2018

ABSTRACTLarge uncertainties exist in Holocene climate estimates, especially for the early Holocene when large‐scale reorganization occurred in the climate system. To improve our understanding of these uncertainties, we compare four Holocene simulations performed with the LOVECLIM, CCSM3, HadCM3 and FAMOUS climate models. The simulations are generally consistent for the large‐scale Northern Hemisphere extratropics, while the multi‐simulation consistencies are heterogeneous on the sub‐continental scale. Consistently simulated temperature trends are found in Greenland, northern Canada, north‐eastern and north‐western Europe, and central‐west Siberia. These Holocene temperatures show a pattern of an early Holocene warming, mid‐Holocene warmth and gradual decrease towards the pre‐industrial in winter, and the extent of early Holocene warming varies spatially, with 9 °C warming in northern Canada compared with 3 °C warming in central‐west Siberia. In contrast, mismatched temperatures are detected: in Alaska, the warm early Holocene winter in LOVECLIM primarily results from strongly enhanced southerly winds induced by the ice sheets; in eastern Siberia, the intense early‐Holocene summer warmth anomaly in CCSM3 is caused by large negative albedo anomalies due to overestimated snow cover at 0 ka; in the Arctic, cool winter conditons in FAMOUS can be attributed to extensive sea ice coverage probably due to simplified sea ice representations. Thus, the Holocene temperature trends in these regions remain inconclusive.