bluuebunny/crossref_metadata_2025 huggingface dataset:
CoDRIVE – Delivering High Accuracy, Ubiquitous Positioning Through Combined Radio Navigation and Inertial Sensing Technologies
Authors: Roberts Simon
Published: September 2020

The CoDRIVE solution builds on R&D in the development of connected and autonomous vehicles (CAVs). The mainstay of the system is a low-cost GNSS receiver integrated with a MEMS grade IMU powered with CoDRIVE algorithms and high precision data processing software. The solution integrates RFID (radio-frequency identification) localisation information derived from tags installed in the roads around the University of Nottingham. This aids the positioning solution by correcting the long-term drift of inertial navigation technology in the absence of GNSS. The solution is informed of obscuration of GNSS through city models of skyview and elevation masks derived from 360-degree photography. The results show that predictive intelligence of the denial of GNSS and RFID aiding realises significant benefits compared to the inertial only solution. According to the validation, inertial only solutions drift over time, with an overall RMS accuracy over a 300 metres section of GNSS outage of 10 to 20 metres. After deploying the RFID tags on the road, experiments show that the RFID aided algorithm is able to constrain the maximum error to within 3.76 metres, and with 93.9% of points constrained to 2 metres accuracy overall.
Comparison of Strength and Dexterity in Professional and Student Violinists: Setting Foundations to Guide Rehabilitation
Authors: Prada Valeria , Mori Laura , Prato Elena , Hamedani Mehrnaz , Susanna Accogli , Marina Grandis , Angelo Schenone
Published: September 2020

AIMS: The musician’s hand represents a complex system, which requires important motor skills. Although several studies have already investigated rehabilitation outcomes and techniques in musicians after hand lesions, none have been addressed specifically to objectively quantifiable
functional parameters. The purpose of our study was to study hand functionality in violinists in order to provide foundations on which to establish and develop more appropriate rehabilitation protocols. STUDY DESIGN: An observational cross-sectional cohort study consisting of 34 subjects,
including 23 students and 11 professional violinists who were either studying or working at a conservatory. Results were compared to a data set of a non-musician control group. METHODS: Nine-hole peg test and hand test system (HTS) were used to perform the study. A hand-held dynamometer was
used to measure hand grip and tripod pinch maximal isometric voluntary contraction of both hands. RESULTS: Hand strength did not significantly differ on either side between professional and student violinists. A significant difference was seen when comparing violinists as a whole versus the
non-musician control group. HTS highlighted significant differences in dexterity. CONCLUSION: Violinists develop better overall motor performances of the left hand, and their performance is better than normal “non-musician” controls. Dexterity and precision of execution positively
correlate to years of practice. We conclude that rehabilitation of a violinist’s hand should be aimed at enhancing motor performance of the left hand and should be focused to maximize dexterity of both hands.
Morphological Response of Bolivina Lowmani to Sediment Composition and Organic Matter: Applying Geometric Morphometrics for Potential Bio-Monitoring
Authors: Bayrón-Arcelay Margarette , Rodríguez-Camacho Kyara , Acosta-Mercado Dimaris
Published: September 2020

It is well established that sediment composition plays an important role in shaping the community of benthic foraminifera (e.g., species richness). To our knowledge, there is little information about morphometric variations in benthic foraminifera in relation to sediment composition and organic matter content. However, given their sensitivity to these environmental variables, variations in size (width and height of the test) and shape (form of the test) of the foraminifera could provide information about potential disturbances, serving as an index of anthropogenic pressure for coastal ecosystems. In this study, we used geometric morphometrics to compare the average size and shape of a common species, Bolivina lowmani, among islets in La Parguera, Puerto Rico. We hypothesized that the average size and shape of B. lowmani will be different among islets. We further hypothesize that there will be a concomitant morphometric gradient of B. lowmani with sediment particle size and organic matter content. After a random sampling approach, we found that size regressed as a function of mud content and shape variations regressed as a function of organic matter content. Therefore, sediment composition could be a factor affecting foraminiferal growth rates highlighting that the morphometrics of benthic foraminifera could be added to the list of potential indexes that could be used to track current environmental degradation in coastal habitats. Furthermore, our data validate the sensitivity of foraminifera and their usefulness as indicators of environmental hazards.
Imprint of Regional Oceanography on Foraminifera of Eastern Pacific Coral Reefs
Authors: Zamora-Duran M. Angelica , Aronson Richard B. , Leichter James J. , Flannery Jennifer A. , Richey Julie N. , Toth Lauren T.
Published: September 2020

The marginal marine environments of the eastern tropical Pacific (ETP) serve as an ideal natural laboratory to study how oceanographic and climatic variability influence coral-reef ecosystems. Reefs along the Pacific coast of Panamá span a natural gradient of nutrients, pH, and temperature as a result of stronger seasonal upwelling in the Gulf of Panamá relative to the Gulf of Chiriquí. The ecosystems are not only influenced by spatial and seasonal variations in oceanography but are affected by the climatic variability of the El Niño-Southern Oscillation (ENSO). Foraminifera can be robust indicators of ecosystem condition because the composition of their assemblages and the geochemistry of their tests can change rapidly in response to environmental variability. We studied benthic foraminifera in sediment samples collected from 3 m below mean sea level in the Gulf of Panamá and the Gulf of Chiriquí. Temperature loggers deployed from 2016 to 2019 showed that average temperatures were lower and more variable in the Gulf of Panamá due to seasonal upwelling. All sites in both gulfs were dominated by heterotrophic foraminifera, which was likely the result of nutrient enrichment due to upwelling, combined with ENSO effects. However, the Gulf of Chiriquí was characterized by higher abundances of symbiont-bearing foraminifera than the Gulf of Panamá. The orders Miliolida and Rotaliida dominated the foraminiferal assemblages in both gulfs, with Quinqueloculina and Rosalina being the most abundant genera in the two orders, respectively. Miliolids were less abundant in the Gulf of Panamá than in the Gulf of Chiriquí, whereas rotaliid densities were not significantly different between the two gulfs. Lower pH in the Gulf of Panamá as a result of upwelling may have contributed to the lower abundance of miliolids, which secrete tests of high-magnesium calcite. Geochemical analysis of tests of the symbiont-bearing miliolid Sorites marginalis revealed that foraminiferal Mg/Ca ratios were lower in the Gulf of Panamá than in the Gulf of Chiriquí. The offset in foraminiferal Mg/Ca is consistent with the lower mean annual temperature observed in the Gulf of Panamá due to stronger seasonal upwelling. Because the geochemistry and assemblages of foraminifera reflect differences in environmental conditions, they could potentially be used in tandem with coral proxies to reconstruct past environmental change and project the future of coral-reef systems within the ETP.
Artificial Diagenesis of Carbonates: Temperature-Dependent Inorganic and Organic Modifications in Reservoir Mimetic Fluids
Authors: Rao Ashit , Kumar Saravana , Annink Carla , Le-Anh Duy , Ayirala Subhash C. , Alotaibi Mohammed B. , Siretanu Igor , Duits Michel H. G. , Yousef Ali A. , Mugele Frieder
Published: September 2020

Within reservoirs, spatial variations related to mineralogy and fluid chemistry determine the success of improved oil recovery (IOR) technologies. However, the composition and structure of mineral-adsorbent/fluid interfaces, which fundamentally determine the wettability of reservoir rocks and crude oil (CRO) displacement, are unclear. Replicating the diagenetic alterations of carbonates, this study addresses the temperature dependence of the inorganic and organic modifications of calcite by reservoir pertinent fluids as well as its consequences on mineral wettability and reactivity.

We apply a suite of characterization methods, namely confocal Raman, scanning electron, and atomic force microscopy (AFM) as well as infrared spectroscopy, to investigate the modifications of carbonates on aging in formation water (FW), CRO-equilibrated FW, and FW-equilibrated CRO. The microscopic modifications of carbonates show a strong dependence on the aging temperature and are varied, encompassing topographical alterations, substitution of lattice Ca2+ ions by Mg2+ ions and the deposition of particles enriched with polyaromatic hydrocarbons (PAHs) as organic adlayers. Aging in the FWs leads to substantial reconstruction of calcite surfaces, with the deposition of magnesium calcite layers at elevated temperatures. Subsequent aging in FW-equilibrated CRO produces an organic coating on the mineral surfaces, which is composed of PAH-enriched particles. Deposited most strongly at high temperature, these organic layers render contact angles more “oil-wet.” In addition, these layers present a limited permeability for ionic species and substantially reduce the dissolution rates of calcite. The multilayer deposition of organic particles, which thus turns out as a key factor for wettability alteration, is attributed to the interconnected bulk and surface reactions for interfacially active constituents of CRO and the surface precipitation of organo-calcium complexes.

Results of this study are relevant to multiple aspects of reservoir development and maintenance, including laboratory scale wettability and coreflooding experiments, and in-silico modeling. The observed nano- and microscopic surface alterations of carbonates within reservoir mimetic environments improve our understanding of the physicochemical relations between mineralogy and fluid chemistry at the mineral-sorbent/fluid interfaces within reservoirs and thereby provide a starting point for the development of novel advanced IOR strategies.
LncRNA and transcriptomic analysis of fetal membrane reveal potential targets involved in oligohydramnios
Authors: Ou Yu-hua , Liu Yu-kun , Zhu Li-qiong , Chen Man-qi , Yi Xiao-chun , Chen Hui , Zhang Jian-ping
Published: September 2020

Background: The multiple causes of oligohydramnios make it challenging to study. Long noncoding RNAs (lncRNAs) are sets of RNAs that have been proven to function in multiple biological processes. The purpose of this study is to study expression level and possible role of lncRNAs in oligohydramnios.Methods: In this study, total RNA was isolated from fetal membranes resected from oligohydramnios pregnant women (OP) and normal amount of amniotic fluid pregnant women (Normal). LncRNA microarray was used to analyze the differentially expressed lncRNAs and mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the main enrichment pathways of differentially expressed mRNAs. Real-time quantitative PCR (qPCR) was used to validate the lncRNA expression level.Results: LncRNA microarray analysis revealed that a total of 801 lncRNAs and 367 mRNAs were differentially expressed in OP; in these results, 638 lncRNAs and 189 mRNAs were upregulated, and 163 lncRNAs and 178 mRNAs were downregulated. Of the lncRNAs, 566 were intergenic lncRNAs, 351 were intronic antisense lncRNAs, and 300 were natural antisense lncRNAs. The differentially expressed lncRNAs were primarily located in chromosomes 2, 1, and 11. KEGG enrichment pathways revealed that the differentially expressed mRNAs were enriched in focal adhesion as well as in the signaling pathways of Ras, tumor necrosis factor (TNF), estrogen, and chemokine. The qPCR results confirmed that LINC00515 and RP11-388P9.2 were upregulated in OP. Furthermore, the constructed lncRNA–miRNA–mRNA regulatory network revealed tenascin R (TNR), cystic fibrosis transmembrane conductance regulator (CFTR), ATP-binding cassette sub-family A member 12 (ABCA12), and collagen 9A2 (COL9A2) as the candidate targets of LINC00515 and RP11-388P9.2.Conclusions: In summary, we revealed the profiles of lncRNA and mRNA in OP. These results might offer potential targets for biological prevention for pregnant women with oligohydramnios detected before delivery and provided a reliable basis for clinical biological treatment in OP.
p.Arg72Pro polymorphism of P53 and Breast Cancer Risk: A meta-analysis of case-control studies
Authors: Diakite Brehima , Kassogue Yaya , Dolo Guimogo , Wang Jun , Neuschler Erin , Kassogue Oumar , Keita Mamadou L , Traore Cheick Bougari , Kamate Bakarou , Dembele Etienne , Sellama Nadifi , Murphy Robert L , Doumbia Seydou , Hou Lifang , Maiga Mamoudou
Published: September 2020

Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cases age-matched controls including7841disease cases and 8876controls were evaluated in this meta-analysis. Overall, our results suggested that p.Arg72ProP53 was associated with a risk for breast cancer for the dominant model (OR= 1.09, 95% CI = 1.02-1.16; P= 0.01) and the additive model (OR= 1.09, 95% CI = 1.01-1.17; P= 0.03), but not in the recessive model (OR = 1.07, 95% CI = 0.97-1.16; P= 0.19). According to the ethnic group, allele Pro has been associated with breast cancer risk in Europeans for the dominant and additive models. Conclusions : This meta-analysis found a significant association between p.Arg72Pro in the P53 gene and the risk of breast cancer. Individuals carrying at least one Pro allele of the P53 gene are more likely to have breast cancer with dominant and additive models than individualsharboringthe Arg allele.
Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma
Authors: Kim Min-Young , Shin Jung-Young , Kim Jeong-Oh , Son Kyoung-Hwa , Kim Yeon Sil , Jung Chan Kwon , Kang Jin-Hyoung
Published: September 2020

Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.
Financial risk protection of Thailand’s Universal Health Coverage: results from series of national household surveys between 1996 and 2015
Authors: Tangcharoensathien Viroj , Tisayaticom Kanjana , Suphanchaimat Rapeepong , Vongmongkol Vuthiphan , Viriyathorn Shaheda , Limwattananon Supon
Published: September 2020

Background: Thailand, an upper-middle income country, has demonstrated exemplary outcomes of Universal Health Coverage (UHC). The country achieved full population coverage and a high level of financial risk protection since 2002, through implementing three public health insurance schemes. UHC has two explicit goals of improved access to health services and financial protection where use of these services does not create financial hardship. Prior studies in Thailand do not however provide evidence of long-term UHC financial risk protection. This study assessed financial risk protection as measured by the incidence of catastrophic health spending and impoverishment in Thai households prior to and after UHC in 2002.Methods: We used data from a fifteen-year series of annual national household socioeconomic surveys between 1996 and 2015, which were conducted by the National Statistical Office. The survey covered about 52,000 nationally representative households in each round. Descriptive statistics were used to assess the incidence of catastrophic payment as measured by the share of out-of-pocket payments for health by households exceeding 10% and 25% of household total consumption expenditure, and the incidence of impoverishment as determined by the additional number of non-poor households falling below the national and international poverty lines after making health payments. Results: Using the 10% threshold, the incidence of catastrophic spending dropped from 6.0% in 1996 to 2% in 2015. This incidence reduced more significantly when the 25% threshold was applied from 1.8% to 0.4% during the same period. The incidence of impoverishment against the national poverty line reduced considerably from 2.2% in 1996 to approximately 0.3% in 2015. When the international poverty line of US$ 3.1 per capita per day was applied, the incidence of impoverishment was 1.4% and 0.4% in 1996 and 2015 respectively; and when US$ 1.9 per day was applied, the incidence was negligibly low. Conclusion: The significant decline in the incidence of catastrophic health spending and impoverishment was attributed to the deliberate design of Thailand’s UHC, which provides a comprehensive benefits package and zero co-payment at point of services. The well-founded healthcare delivery system and favourable benefit package concertedly support the achievement of UHC goals of access and financial risk protection.
The impact of occupational and personal factors on musculoskeletal pain - A cohort study of female nurses, sonographers and teachers.
Authors: Arvidsson Inger , Simonsen Jenny Gremark , Andersson Agneta Lindegård , Björk Jonas , Nordander Catarina
Published: September 2020

Background: Musculoskeletal pain is common in the general population and constitutes a major public health problem. A large proportion of these conditions may be work related. The aim of this study was to explore the relative importance of physical, psychosocial and personal factors, in number of pain sites and in five specific pain sites, among women in common professions with a broad variety of occupational exposures. Methods: A cohort of 1115 women responded to a questionnaire on ergonomic, psychosocial, personal and life-style factors, and the outcome measure of musculoskeletal pain (based on frequency and intensity of complaints at nine anatomical sites), at baseline and at follow-up. Sum scores of ergonomic and psychosocial factors were created. The importance of exposure at baseline for the number of pain sites at follow-up were estimated using ordinal regression. The importance of exposure at baseline for pain in the neck, shoulders, hands, lower back and feet at follow-up were estimated using multi-exposure Poisson regression models. Results: High sum scores for ergonomic and psychosocial factors were of importance for a high number of pain sites, although the strongest risk factor was a high number of pain sites already at baseline. On the individual level, there was a large fluctuation in number of pain sites between the two time points. Eighteen percent reported persistent (or recurrent) ≥four pain sites, while only eleven percent did not report any pain at baseline or at follow-up. Among the specific pain sites, a high sum score of ergonomic factors was associated with pain in the neck, hands and feet. A high sum score of psychosocial factors was associated with neck and shoulder pain. The strongest risk factor was, however, pain at that specific anatomical site at baseline. Only a few of the personal and life-style factors were associated with pain. Conclusions: An overwhelming majority of the women in common occupations were affected by musculoskeletal pain. Both ergonomic and psychosocial factors were predictive of a high number of pain sites and of specific pain sites. These findings indicate the need for preventive measures on the individual, organizational and societal level.
A phase I study of a dual PI3-Kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia
Authors: Lang Fabian , Wunderle Lydia , Badura Susanne , Schleyer Eberhard , Brüggemann Monika , Serve Hubert , Schnittger Susanne , Gökbuget Nicola , Pfeifer Heike , Wagner Sebastian , Ashelford Kevin , Bug Gesine , Ottmann Oliver
Published: September 2020

Background: Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single center open label study was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia.Methods: Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300-400 mg BID (cohort -1/1)) to assess safety, tolerability, preliminary efficacy and pharmacokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3+3 rule (“Rolling Six”), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase.Results: Twenty-four patients with ALL (n=11) or AML (n=12) or CML-BP (n=1) were enrolled. All patients had failed one (n=5) or more lines of therapy (n=5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability.Conclusions: Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML.Trial registration: ClinicalTrials.gov, identifier NCT01756118. retrospectively registered 19th December 2012, https://clinicaltrials.gov/ct2/show/NCT01756118.
RNA-seq analysis of galaninergic neurons from ventrolateral preoptic nucleus identifies expression changes between sleep and wake
Authors: Guo Xiaofeng , Gao Xiaoling , Keenan Brendan T. , Zhu Jingxu , Sarantopoulou Dimitra , Lian Jie , Galante Raymond J. , Grant Gregory R. , Pack Allan I.
Published: September 2020

Background: Previous studies show that galanin neurons in ventrolateral preoptic nucleus (VLPO-Gal) are essential for sleep regulation. Here, we explored the transcriptional regulation of the VLPO-Gal neurons in sleep by comparing their transcriptional responses between sleeping mice and those kept awake, sacrificed at the same diurnal time. Results: RNA-sequencing (RNA-seq) analysis was performed on eGFP(+) galanin neurons isolated using laser captured microdissection (LCM) from VLPO. Expression of Gal was assessed in our LCM eGFP(+) neurons via real time qPCR and showed marked enrichment when compared to LCM eGFP(-) cells and to bulk VLPO samples. Gene set enrichment analysis utilizing data from a recent single-cell RNA-seq study of the preoptic area demonstrated that our VLPO-Gal samples were highly enriched with galanin-expressing inhibitory neurons, but not galanin-expressing excitatory neurons. A total of 263 genes were differentially expressed between sleep and wake in VLPO-Gal neurons. When comparing differentially expressed genes in VLPO-Gal neurons to differentially expressed genes in a wake-active neuronal region (the medial prefrontal cortex), evidence indicates that both systemic and cell-specific mechanisms contribute to the transcriptional regulation in VLPO-Gal neurons. In both wake-active and sleep-active neurons, ER stress pathways are activated by wake and cold-inducible RNA-binding proteins are activated by sleep. In contrast, expression of DNA repair genes is increased in VLPO-Gal during wakefulness, but increased in wake-active cells during sleep. Conclusion: Our study identified transcriptomic responses of the galanin neurons in the ventrolateral preoptic nucleus during sleep and sleep deprivation. Data indicate that VLPO contains mainly sleep-active inhibitory galaninergic neurons. The VLPO galanin neurons show responses to sleep and wake similar to wake-active regions, indicating these responses, such as ER stress and cold-inducible RNA-binding proteins, are systemic affecting all neuronal populations. Region-specific differences in sleep/wake responses were also identified, in particular DNA repair. Our study expands knowledge about the transcriptional response of a distinct group of neurons essential for sleep.
An immunochemistry-based screen for chemical inhibitors of DNA-protein interactions and its application to human CGGBP1
Authors: Patel Manthan , Patel Divyesh , Datta Subhamoy , Singh Umashankar
Published: September 2020

Background: Inhibition of DNA-binding of proteins by small-molecule chemicals holds immense potential in manipulating the activities of DNA-binding proteins. Such a chemical inhibition of DNA-binding of proteins can be used to modulate processes such as replication, transcription, DNA repair and maintenance of epigenetic states. This prospect is currently challenged with the absence of robust and generic protocols to identify DNA-protein interactions. Additionally, much of the current approaches to designing inhibitors requires structural information of the target proteins.Methods: We have developed a simple dot blot and immunodetection-based assay to screen chemical libraries for inhibitors of DNA-protein interactions. The assay has been applied to a library of 1685 FDA-approved chemicals to discover inhibitors of CGGBP1, a multifunctional DNA-binding protein with no known structure. Additional in vitro and in cellulo assays have been performed to verify and supplement the findings of the screen.Results: Our primary screen has identified multiple inhibitors of direct or indirect interactions between CGGBP1 and genomic DNA. Of these, one inhibitor, Givinostat, was found to inhibit direct DNA-binding of CGGBP1 in the secondary screen using purified recombinant protein as the target. DNA and chromatin immunoprecipitation assays reinforced the findings of the screen that Givinostat inhibits CGGBP1-DNA binding.Conclusions: The assay we have described successfully identifies verifiable inhibitors of DNA-binding of protein; in this example, the human CGGBP1. This assay is customizable for a wide range of targets for which primary antibodies are available. It works with different sources of the target protein, cell lysates or purified recombinant preparations and does not require special equipment, DNA modifications or protein structural data. This assay is scalable and highly adaptable with the potential to discover inhibitors of transcription factors with implications in cancer biology.
A hybrid cost-sensitive ensemble for heart disease prediction
Authors: Qi Zhenya , Zhang Zuoru
Published: September 2020

Background: Heart disease is the primary cause of morbidity and mortality in the world. It includes numerous problems and symptoms. The diagnosis of heart disease is difficult because there are too many factors to analyze. What’s more, the misclassification cost could be very high.

Methods: A cost-sensitive ensemble model was proposed to improve the efficiency of diagnosis and reduce the misclassification cost. The proposed model contains five heterogeneous classifiers: random forest, logistic regression, support vector machine, extreme learning machine and k-nearest neighbor. T-test was used to investigate if the performance of the ensemble model was better than individual classifiers and the contribution of Relief algorithm.

Results: The best performance was achieved by the proposed model according to ten-fold cross validation. The statistical tests demonstrated that the performance of the proposed model was significantly superior to individual classifiers, and the efficiency of classification was distinctively improved by Relief algorithm.

Conclusions: The proposed ensemble model gained significantly better results compared with individual classifiers and previous studies, which implies that it can be used as a promising alternative tool in medical decision making for heart disease diagnosis.
Three-dimensional versus two-dimensional derived strain echocardiography for assessing right ventricular myocardial deformation in patients with chronic left ventricular heart failure: A proof-of-concept study
Authors: Gao Fei , Liu Chong , Guo Qiang , Jiang Shuang-quan , Wang Zhen-zhen , Liu Li , Li Hai-Ru , Du Guo-Qing , Tian Jia-wei
Published: September 2020

Background: A novel three-dimensional echocardiography (3DE)-derived strain analysis software specialized for right ventricular (RV) monitoring is emerging that could definitely evaluate RV free wall and interventricular septum longitudinal strain. The aim of this study was to compare the diagnostic performance in evaluating RV function between 3DE and two-dimensional echocardiography (2DE)-derived longitudinal strain.Methods: Echocardiographic examinations were performed in 82 patients with RV dysfunction associated with chronic left-sided heart failure and 40 control subjects. RV dysfunction was defined as a 3DE-derived RV ejection fraction (EF) <45%. Both 2DE and 3DE-derived strain analyses were performed in all the patients to measure the longitudinal strain of RV.Results: 3DE-derived peak systolic longitudinal strain of RV free wall (RV-fwLS) was significantly lower in patients with RV dysfunction compared to control subjects (-14.0±4.1 vs. -26.7±4.7%; p<0.001), and it correlated well with cardiac magnetic resonance-derived RVEF (r=0.74, p<0.001). On receiver operator characteristic analysis, a 3DE-derived RV-fwLS cutoff value of >-21.1% was most useful in identifying patients at higher risk of RV dysfunction (sensitivity: 90% and specificity: 85%), also higher than 2DE-derived strain parameters. Additionally, RV dysfunctional patients with pulmonary hypertension (PH) had significantly reduced 3DE-derived RV-fwLS value than the subgroup without PH (-13.1±3.8 vs. -15.0±4.2; p<0.05).Conclusion：Assessment of impaired RV systolic function by 3DE-derived longitudinal strain is better than 2DE in chronic left-sided heart failure patients with left ventricular EF <45%. 3DE-derived strain analysis specialized for RV should be considered as a complementary tool for assessing RV function.
Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admitted to intensive care units
Authors: Fujiwara Toshifumi , Tokuda Kentaro , Momii Kenta , Shiomoto Kyohei , Tsushima Hidetoshi , Akasaki Yukio , Ikemura Satoshi , Fukushi Jun-ichi , Maki Jun , Kaku Noriyuki , Akahoshi Tomohiko , Taguchi Tomoaki , Nakashima Yasuharu
Published: September 2020

Background: Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs). Methods: This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU.Results: Upon admission, the median age was 70 (range, 33–96) years, and RA duration was 10 (range, 0–61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22%, 27%, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission.Conclusion: Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.
5-Hydroxytryptamine-3 Receptor Antagonist and Dexamethasone as Prophylaxis for Chemotherapy Induced Nausea and Vomiting during Moderately Emetic Chemotherapy for Solid Tumors: A Multicenter, Prospective, Observational Study
Authors: Matsui Reiko , Suzuki Kenichi , Takiguchi Tomomi , Nishio Makoto , Koike Takeshi , Hayashi Toshinobu , Seto Takashi , Kogure Yuki , Nogami Naoyuki , Fujiwara Kimiko , Kaneda Hiroyasu , Harada Tomohiko , Shimizu Satoru , Kimura Masashi , Kenmotsu Hirotsugu , Shimokawa Mototsugu , Goto Koichi
Published: September 2020

Background: Of patients receiving moderate emetic risk chemotherapy (MEC), 30%–90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial. Methods: In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Results: Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26–84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51% and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC. Conclusion: Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5)+ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.
Risk of stroke after unilateral or bilateral TKA (simultaneous and staged without discharge) in 327,438 matched patients using data from the National Health Insurance Claims for South Korea
Authors: Han Seung-Beom , Yoon Jung-Ro , Cheong Ji-Young , Lee Sang-Soo , Shin Young-Soo
Published: September 2020

Background: Limited data is available regarding the incidence rate and risk factors for stroke associated with unilateral total knee arthroplasty (TKA) and bilateral TKA. This study aims to investigate the incidence rate and risk factors of stroke in patients treated with bilateral TKA compared with patients with unilateral TKA.Methods: In this retrospective nationwide cohort study, we compared patients undergoing unilateral TKA or bilateral TKA using data from the Korean National Health Insurance claims database between January 1, 2009 and August 31, 2017 and included patients older than 40 years of age who underwent primary TKA by the index date as documented primary diagnosis and first additional diagnosis without a history of stroke during the preceding 1 year. We used matched Cox regression models to compare the incidence rate and risk factors of newly acquired stroke among patients treated with unilateral TKA or bilateral TKA after propensity score (PS) matching.Results: In the present study, 163,719 patients who received unilateral TKA were matched to163,719 patients with bilateral TKA (simultaneous and staged without discharge) based on PS. The risk of stroke during the study period was lower in patients treated with bilateral TKA than in patients with unilateral TKA (adjusted hazard ratio [HR] 0.79; P<0.001). Patients who received bilateral TKA were at decreased risk of stroke when the following variables were present: advanced age (70-79 years, HR 0.76; P<0.001), female sex (HR 0.75; P<0.001), rural area (HR 0.77; P<0.001), small- or medium-sized hospital (HR 0.75; P<0.001), health insurance (HR 0.77; P<0.001), history of hypertension drug use (HR 0.75; P<0.001), congestive heart failure (HR 0.70; P=0.032), connective tissue disease (HR 0.71; P=0.01), diabetes (HR 0.77; P<0.001), and diabetes with complication (HR 0.76; P=0.034).Conclusions: The risk of stroke was lower in patients treated with bilateral TKA (simultaneous and staged without discharge) than in patients with unilateral TKA. Patients treated with bilateral TKA were at decreased risk of stroke when the following variables were present: age (70-79 years), female sex, health insurance, history of hypertension drug use, and comorbidities, such as congestive heart failure, connective tissue disease, and diabetes. More importantly, we do state that those with simultaneous bilateral TKA and staged bilateral TKA without discharge could have been healthier. This is precisely what the guidelines implemented by South Korea for patient selection aim to do and our data show that the risk of stroke is not increased in selected patients undergoing SiBTKA and StBTKA without discharge. Therefore, those who underwent 2 unilateral TKAs could have been at more risk of stroke, especially in the 2nd unilateral TKA.
The effect of midwifery led counseling based on Gamble's approach on childbirth fear and self-efficacy in nulligravida women
Authors: Firouzan Laya , Kharaghani Roghieh , Zenoozian Saeedeh , Moloodi Reza , Jafari Elham
Published: September 2020

Background: Studies show that childbirth fear is a common problem among Iranian women. Therefore, most Iranian women prefer caesarean section for giving birth. This study investigated the effectiveness of a psychoeducational intervention by midwives (birth emotions - looking to improve expectant fear (BELIEF)) on decreasing childbirth fear and self-efficacy among first-time pregnant women who were afraid of giving birth.Methods: A number of 80 pregnant women participated in the study. They had received a score of ≥ 66 on the Wijma delivery expectancy/experience questionnaire. They were randomly assigned into two groups: intervention (n = 40) and control groups (n = 40). The intervention group received two face-to-face counseling sessions based on the BELEF protocol in the 24th and 34th weeks of pregnancy. Between these two sessions, it also received eight telephone-counseling sessions once a week. The control group only received the prenatal routine care. The outcome measures were childbirth fear, childbirth self-efficacy, and childbirth preference. Results: The intervention group showed significantly more reduction in childbirth fear and more increase in childbirth self-efficacy compared to the control group. In addition, more women in the intervention group reported that they preferred to give normal vaginal birth than women in the control group.Conclusion: The BELIEF protocol could be an effective approach in reducing childbirth fear and increasing childbirth self-efficacy among first-time pregnant women who are afraid of giving birth. Trial registration number: IRCT20101219005417N3, Date of Registration: 19-12-2018.
Pre- and Post-operative Differences Between Genders in Idiopathic Macular Holes
Authors: Wang Jing , Yu Yanping , Liang Xida , Wang Zengyi , Qi Biying , Liu Wu
Published: September 2020

Background: To compare idiopathic macular holes (IMHs) between male and female before and after surgery.Methods: Patients with IMHs of stage 3 and stage 4 who underwent 23-gauge vitrectomy were retrospectively enrolled. Pre-operative clinical features like age of onset, and best-corrected visual acuity (BCVA) were reviewed. Optical coherence tomography parameters including minimum linear diameter (MLD), central macular thickness and some other indexes were measured and calculated. Main surgical outcomes included the primary closure rate, the highest BCVA during follow-up, and the recovery duration. All the metrics mentioned above were compared between genders with appropriate statistical methods. Results: A total of 298 eyes from 280 patients (male: 51; female: 229) were enrolled. Compared with men, women demonstrated a significantly higher ratio of stage3/stage4 (P=0.045), larger horizontal MLD (P=0.009), but similar surgical outcomes except for a relatively longer recovery duration (P=0.024). For stage 3 IMHs, women exhibited significantly younger age of onset (P=0.023), larger MLD (P=0.003), and smaller height of the hole (P=0.029). However, for stage 4 IMHs, all the pre- and post-operative metrics showed no differences between genders.Conclusions: Female IMHs seem to demonstrate an earlier age of onset and larger size of hole, especially in IMHs of stage 3. However, these differences, which may owe to normal gender-related variations, have limited influence on the surgical outcomes.
Children, media and food. Food advertising aimed at children audience in Spanish TV
Authors: Jimenez-Marin gloria_jimenez , Garcia Jesus Delgado , Medina Irene Garcia
Published: September 2020

Healthy living habits are the basis for optimal development in children and advertising can affect, positively or negatively, the maintenance of some of these habits. The analysis of food and drink advertising aimed at children during the enhanced protection zone is evidence of the growing problem of obesity in the child population generated through the food industry. The aim of this study is to assess the levels of compliance with the Code of Food and Drink Advertising to Children (Code PAOS). The methodology used was discourse and content analysis. For this purpose, a sample obtained through the recording, during 7 consecutive days, of the content of the advertising cuts in the television broadcast in Spain of three specialized and two generalist channels: Disney Channel, Neox and Boing, on the one hand, and Telecinco and Antena3, on the other. The reason for their choice is that they are the channels, within this segment, with the highest audience ratings. Specifically, the sample was obtained during week from the 12th to the 18th of December 2018.The results reveal a systematic breach of this code that persuades the vulnerable conscience of children through a business network that far from promoting healthy living habits, they cause malnutrition in society. The immediate conclusion is that 9 out of 10 parts of the Food and Beverage Advertising (FBA) did not comply with any of the PAOS Code standards and that self-regulation by advertising companies seems insignificant.