bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of airborne N,N-dimethylformamide on liver toxicity measured in industry workers: A systematic review and meta-analysis
Authors: Antoniou Evangelia E , Gelbke Heinz-Peter , Ballach Jochen , Zeegers Maurice P
Published: January 2020

Background:

Modern industry is developing and so is the consumption of N, N-dimethylformamide (DMF) and the occupational population exposed to DMF. However, chronic occupational and experimental exposure to DMF has been especially linked to liver and gastrointestinal disturbances.

Aims:

This study aims to systematically review and evaluate with a meta-analysis the influence of DMF exposure on human liver toxicity.

Methods:

The PubMed/Medline, the ECHA restriction dossier and the Web of Science were searched. Midpoint DMF exposure levels were calculated, and the association between DMF exposure and liver toxicity was investigated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results:

Of 92 screened articles, 19 articles were included in the review and of them, 10 articles were included in the meta-analysis. No association was observed when the midpoint DMF exposure was less than 20 mg/m3 (OR: 1.58, 95% CIs: 0.68–3.65). A positive association between DMF exposure and liver toxicity was observed when the midpoint DMF exposure was between 21 mg/m3 and 25 mg/m3 (OR: 3.26, 95% CIs: 1.38–7.73).

Conclusions:

Higher exposure DMF levels are associated with liver toxicity. However, these results tend to overestimate potential risks because the use of midpoint exposures includes and gives weight to populations at the upper end of the exposure distributions and because liver toxicity was defined as a statistical significant difference in liver enzyme levels compared to control groups, which is not identical to biologically relevant effects and adverse health effects.
Flexural behavior of bamboo–concrete composite beams with perforated steel plate connections
Authors: Wang Zhiyuan , Wei Yang , Li Ning , Zhao Kang , Ding Mingmin
Published: January 2020

A new type of bamboo–concrete composite structure using perforated steel plates as connectors was proposed. To study the composite effect of this new type of composite structure, the slip behavior of bamboo–concrete shear connectors was first studied through push-out tests. Subsequently, four-point bending tests of ten bamboo–concrete composite beams were carried out. The results show that the failure of bamboo–concrete shear connectors occurred between the perforated steel plate and the concrete, and there was no obvious damage between the perforated steel plate and the bamboo. The load carrying capacity of perforated steel plate connectors was relatively stable. The failure mode was moderate failure. Considering the three stages of the load–slip curve, an exponential function is proposed to describe the load–slip curve. The failure modes of composite beams can be summarized as two types. In the first type, the bamboo beam ruptures on the bottom and the concrete dose not suffer significant damage; in the second type, the top surface of the concrete first exhibits longitudinal cracks, and finally, the bamboo beam ruptures. Compared with bamboo beams, the ultimate load of composite beams increased by 1.2–1.5 times, and the sectional stiffness of composite beams increased by 2.9–4.2 times. The equivalent section stiffness was obtained after determining the connection coefficient, and the connection coefficient γb ranged between 0.50 and 0.80 and decreased as the center spacing of the perforated steel plate increased. The equivalent cross-section stiffness obtained by different load stages of the shear slip stiffness was calculated to predict the mid-span displacement. The calculation results show that the effect of slip stiffness on the equivalent stiffness of cross section is not sensitive, and a 35% increase in slip stiffness results in a maximum increase in equivalent section stiffness of only 6%.
Measuring the placebo effect in carpal tunnel syndrome
Authors: Faig-Martí Jordi , Martínez-Catassús Adriana
Published: January 2020

Background

The placebo effect can account for part of the improvement seen in patients undergoing any type of treatment, be it surgical or pharmacological. The objective of this study is to quantify the placebo effect in carpal tunnel syndrome treatment.

Materials and methods

A double-blinded randomized trial was performed with 68 patients suffering from mild to moderate carpal tunnel syndrome, divided into two groups with no statistically significant differences regarding age, weight, or degree of nerve compression. The patients were evaluated clinically and electromyographically before and after 2 months of treatment with either palmitoylethanolamide (PEA) or placebo.

Results

The results, comparing the two groups, showed an improvement in both groups on a visual analogue scale (VAS) and Levine’s questionnaire, which have been reported to show statistical differences in only a few items. In the placebo group, the mean age was 53.32 years (±13.43) and the BMI was 28.85 kg/m2 (±4.84). Before treatment, the average symptom severity score (SSS) on the Levine questionnaire was 2.57 (±0.74) and the functional status score (FSS) was 2.24 (±0.66). After treatment, these decreased to 2.11 (±0.81) and 1.96 (±0.77), being statistically nonsignificant for SSS (p = 0.0865) but significant for FSS (p = 0.0028). VAS showed a statistically nonsignificant decrease from 4.06 to 3.25 (p = 0.3407). After placebo treatment, SSS, FSS, and VAS improved by 0.46, 0.28, and 0.81 points or 17.89%, 12.5%, and 19.95%, respectively.

Conclusions

These results show an improvement in the studied parameters by up to 20%, but when compared with those published in literature, these show great variability due to the wide variety of factors involved in the placebo effect. Several factors that affect the placebo effect are discussed, and the present work tries to quantify it in carpal tunnel syndrome.

Level of Evidence

Level 2 of evidence according to “The Oxford 2011 Level of Evidence.”
Cost-Constrained feature selection in binary classification: adaptations for greedy forward selection and genetic algorithms
Authors: Jagdhuber Rudolf , Lang Michel , Stenzl Arnulf , Neuhaus Jochen , Rahnenführer Jörg
Published: January 2020

Background

With modern methods in biotechnology, the search for biomarkers has advanced to a challenging statistical task exploring high dimensional data sets. Feature selection is a widely researched preprocessing step to handle huge numbers of biomarker candidates and has special importance for the analysis of biomedical data. Such data sets often include many input features not related to the diagnostic or therapeutic target variable. A less researched, but also relevant aspect for medical applications are costs of different biomarker candidates. These costs are often financial costs, but can also refer to other aspects, for example the decision between a painful biopsy marker and a simple urine test. In this paper, we propose extensions to two feature selection methods to control the total amount of such costs: greedy forward selection and genetic algorithms. In comprehensive simulation studies of binary classification tasks, we compare the predictive performance, the run-time and the detection rate of relevant features for the new proposed methods and five baseline alternatives to handle budget constraints.

Results

In simulations with a predefined budget constraint, our proposed methods outperform the baseline alternatives, with just minor differences between them. Only in the scenario without an actual budget constraint, our adapted greedy forward selection approach showed a clear drop in performance compared to the other methods. However, introducing a hyperparameter to adapt the benefit-cost trade-off in this method could overcome this weakness.

Conclusions

In feature cost scenarios, where a total budget has to be met, common feature selection algorithms are often not suitable to identify well performing subsets for a modelling task. Adaptations of these algorithms such as the ones proposed in this paper can help to tackle this problem.
FocAn: automated 3D analysis of DNA repair foci in image stacks acquired by confocal fluorescence microscopy
Authors: Memmel Simon , Sisario Dmitri , Zimmermann Heiko , Sauer Markus , Sukhorukov Vladimir L. , Djuzenova Cholpon S. , Flentje Michael
Published: January 2020

Background

Phosphorylated histone H2AX, also known as γH2AX, forms μm-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity and sensitivity, γH2AX immunoassays have become the gold standard for studying DSB induction and repair. One of these assays relies on the immunofluorescent staining of γH2AX followed by microscopic imaging and foci counting. During the last years, semi- and fully automated image analysis, capable of fast detection and quantification of γH2AX foci in large datasets of fluorescence images, are gradually replacing the traditional method of manual foci counting. A major drawback of the non-commercial software for foci counting (available so far) is that they are restricted to 2D-image data. In practice, these algorithms are useful for counting the foci located close to the midsection plane of the nucleus, while the out-of-plane foci are neglected.

Results

To overcome the limitations of 2D foci counting, we present a freely available ImageJ-based plugin (FocAn) for automated 3D analysis of γH2AX foci in z-image stacks acquired by confocal fluorescence microscopy. The image-stack processing algorithm implemented in FocAn is capable of automatic 3D recognition of individual cell nuclei and γH2AX foci, as well as evaluation of the total foci number per cell nucleus. The FocAn algorithm consists of two parts: nucleus identification and foci detection, each employing specific sequences of auto local thresholding in combination with watershed segmentation techniques. We validated the FocAn algorithm using fluorescence-labeled γH2AX in two glioblastoma cell lines, irradiated with 2 Gy and given up to 24 h post-irradiation for repair. We found that the data obtained with FocAn agreed well with those obtained with an already available software (FoCo) and manual counting. Moreover, FocAn was capable of identifying overlapping foci in 3D space, which ensured accurate foci counting even at high DSB density of up to ~ 200 DSB/nucleus.

Conclusions

FocAn is freely available an open-source 3D foci analyzer. The user-friendly algorithm FocAn requires little supervision and can automatically count the amount of DNA-DSBs, i.e. fluorescence-labeled γH2AX foci, in 3D image stacks acquired by laser-scanning microscopes without additional nuclei staining.
Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle
Authors: Hudson Nicholas J. , Reverter Antonio , Griffiths William J. , Yutuc Eylan , Wang Yuqin , Jeanes Angela , McWilliam Sean , Pethick David W. , Greenwood Paul L.
Published: January 2020

Background

This study used a genome-wide screen of gene expression to better understand the metabolic and functional differences between commercially valuable intramuscular fat (IMF) and commercially wasteful subcutaneous (SC) fat depots in Bos taurus beef cattle.

Results

We confirmed many findings previously made at the biochemical level and made new discoveries. The fundamental lipogenic machinery, such as ACACA and FASN encoding the rate limiting Acetyl CoA carboxylase and Fatty Acid synthase were expressed at 1.6–1.8 fold lower levels in IMF, consistent with previous findings. The FA elongation pathway including the rate limiting ELOVL6 was also coordinately downregulated in IMF compared to SC as expected. A 2-fold lower expression in IMF of ACSS2 encoding Acetyl Coenzyme A synthetase is consistent with utilisation of less acetate for lipogenesis in IMF compared to SC as previously determined using radioisotope incorporation. Reduced saturation of fat in the SC depot is reflected by 2.4 fold higher expression of the SCD gene encoding the Δ9 desaturase enzyme. Surprisingly, CH25H encoding the cholesterol 25 hydroxylase enzyme was ~ 36 fold upregulated in IMF compared to SC. Moreover, its expression in whole muscle tissue appears representative of the proportional representation of bovine marbling adipocytes. This suite of observations prompted quantification of a set of oxysterols (oxidised forms of cholesterol) in the plasma of 8 cattle exhibiting varying IMF. Using Liquid Chromatography-Mass Spectrometry (LC-MS) we found the levels of several oxysterols were significantly associated with multiple marbling measurements across the musculature, but (with just one exception) no other carcass phenotypes.

Conclusions

These data build on our molecular understanding of ruminant fat depot biology and suggest oxysterols represent a promising circulating biomarker for cattle marbling.
De novo transcriptome assembly for the five major organs of Zanthoxylum armatum and the identification of genes involved in terpenoid compound and fatty acid metabolism
Authors: Hui Wen-Kai , Zhao Fei-Yan , Wang Jing-Yan , Chen Xiao-Yang , Li Jue-Wei , Zhong Yu , Li Hong-Yun , Zheng Jun-Xing , Zhang Liang-Zhen , Que Qing-Min , Wu Ai-Min , Gong Wei
Published: January 2020

Background

Zanthoxylum armatum (Z. armatum) is a highly economically important tree that presents a special numbing taste. However, the underlying regulatory mechanism of the numbing taste remains poorly understood. Thus, the elucidation of the key genes associated with numbing taste biosynthesis pathways is critical for providing genetic information on Z. armatumand the breeding of high-quality germplasms of this species.

Results

Here, de novo transcriptome assembly was performed for the five major organs of Z. armatum, including the roots, stems, leaf buds, mature leaves and fruits. A total of 111,318 unigenes were generated with an average length of 1014 bp. Additionally, a large number of SSRs were obtained to improve our understanding of the phylogeny and genetics of Z. armatum. The organ-specific unigenes of the five major samples were screened and annotated via GO and KEGG enrichment analysis. A total of 53 and 34 unigenes that were exclusively upregulated in fruit samples were identified as candidate unigenes for terpenoid biosynthesis or fatty acid biosynthesis, elongation and degradation pathways, respectively. Moreover, 40 days after fertilization (Fr4 stage) could be an important period for the accumulation of terpenoid compounds during the fruit development and maturation of Z. armatum. The Fr4 stage could be a key point at which the first few steps of the fatty acid biosynthesis process are promoted, and the catalysis of subsequent reactions could be significantly induced at 62 days after fertilization (Fr6 stage).

Conclusions

The present study realized de novo transcriptome assembly for the five major organs of Z. armatum. To the best of our knowledge, this study provides the first comprehensive analysis revealing the genes underlying the special numbing taste of Z. armatum. The assembled transcriptome profiles expand the available genetic information on this species and will contribute to gene functional studies, which will aid in the engineering of high-quality cultivars of Z. armatum.
Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches
Authors: Assefa Teshale , Zhang Jiaoping , Chowda-Reddy R. V. , Moran Lauter Adrienne N. , Singh Arti , O’Rourke Jamie A. , Graham Michelle A. , Singh Asheesh K.
Published: January 2020

Background

Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.

Results

A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.

Conclusions

This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.
Genome-wide identification and expression profiling of SET DOMAIN GROUP family in Dendrobium catenatum
Authors: Chen Dong-Hong , Qiu Han-Lin , Huang Yong , Zhang Lei , Si Jin-Ping
Published: January 2020

Background

Dendrobium catenatum, as a precious Chinese herbal medicine, is an epiphytic orchid plant, which grows on the trunks and cliffs and often faces up to diverse environmental stresses. SET DOMAIN GROUP (SDG) proteins act as histone lysine methyltransferases, which are involved in pleiotropic developmental events and stress responses through modifying chromatin structure and regulating gene transcription, but their roles in D. catenatum are unknown.

Results

In this study, we identified 44 SDG proteins from D. catenatum genome. Subsequently, comprehensive analyses related to gene structure, protein domain organization, and phylogenetic relationship were performed to evaluate these D. catenatum SDG (DcSDG) proteins, along with the well-investigated homologs from the model plants Arabidopsis thaliana and Oryza sativa as well as the newly characterized 42 SDG proteins from a closely related orchid plant Phalaenopsis equestris. We showed DcSDG proteins can be grouped into eight distinct classes (I~VII and M), mostly consistent with the previous description. Based on the catalytic substrates of the reported SDG members mainly in Arabidopsis, Class I (E(z)-Like) is predicted to account for the deposition of H3K27me2/3, Class II (Ash-like) for H3K36me, Class III (Trx/ATX-like) for H3K4me2/3, Class M (ATXR3/7) for H3K4me, Class IV (Su (var)-like) for H3K27me1, Class V (Suv-like) for H3K9me, as well as class VI (S-ET) and class VII (RBCMT) for methylation of both histone and non-histone proteins. RNA-seq derived expression profiling showed that DcSDG proteins usually displayed wide but distinguished expressions in different tissues and organs. Finally, environmental stresses examination showed the expressions of DcASHR3, DcSUVR3, DcATXR4, DcATXR5b, and DcSDG49 are closely associated with drought-recovery treatment, the expression of DcSUVH5a, DcATXR5a and DcSUVR14a are significantly influenced by low temperature, and even 61% DcSDG genes are in response to heat shock.

Conclusions

This study systematically identifies and classifies SDG genes in orchid plant D. catenatum, indicates their functional divergence during the evolution, and discovers their broad roles in the developmental programs and stress responses. These results provide constructive clues for further functional investigation and epigenetic mechanism dissection of SET-containing proteins in orchids.
Flow-controlled ventilation (FCV) improves regional ventilation in obese patients – a randomized controlled crossover trial
Authors: Weber Jonas , Straka Leonie , Borgmann Silke , Schmidt Johannes , Wirth Steffen , Schumann Stefan
Published: January 2020

Background

In obese patients, high closing capacity and low functional residual capacity increase the risk for expiratory alveolar collapse. Constant expiratory flow, as provided by the new flow-controlled ventilation (FCV) mode, was shown to improve lung recruitment. We hypothesized that lung aeration and respiratory mechanics improve in obese patients during FCV.

Methods

We compared FCV and volume-controlled (VCV) ventilation in 23 obese patients in a randomized crossover setting. Starting with baseline measurements, ventilation settings were kept identical except for the ventilation mode related differences (VCV: inspiration to expiration ratio 1:2 with passive expiration, FCV: inspiration to expiration ratio 1:1 with active, linearized expiration). Primary endpoint of the study was the change of end-expiratory lung volume compared to baseline ventilation. Secondary endpoints were the change of mean lung volume, respiratory mechanics and hemodynamic variables.

Results

The loss of end-expiratory lung volume and mean lung volume compared to baseline was lower during FCV compared to VCV (end-expiratory lung volume: FCV, − 126 ± 207 ml; VCV, − 316 ± 254 ml;p < 0.001, mean lung volume: FCV, − 108.2 ± 198.6 ml; VCV, − 315.8 ± 252.1 ml;p < 0.001) and at comparable plateau pressure (baseline, 19.6 ± 3.7; VCV, 20.2 ± 3.4; FCV, 20.2 ± 3.8 cmH2O;p = 0.441), mean tracheal pressure was higher (baseline, 13.1 ± 1.1; VCV, 12.9 ± 1.2; FCV, 14.8 ± 2.2 cmH2O;p < 0.001). All other respiratory and hemodynamic variables were comparable between the ventilation modes.

Conclusions

This study demonstrates that, compared to VCV, FCV improves regional ventilation distribution of the lung at comparable PEEP, tidal volume, PPlatand ventilation frequency. The increase in end-expiratory lung volume during FCV was probably caused by the increased mean tracheal pressure which can be attributed to the linearized expiratory pressure decline.

Trial registration

German Clinical Trials Register:DRKS00014925. Registered 12 July 2018.
Prevalence and multivariable factors associated with inadvertent intraoperative hypothermia in video-assisted thoracoscopic surgery: a single-center retrospective study
Authors: Li Yinan , Liang Hansheng , Feng Yi
Published: January 2020

Background

Inadvertent intraoperative hypothermia increases the risk of adverse events, but its related risk factors have not been defined in video-assisted thoracoscopic surgery (VATS). This study aimed at analyzing the prevalence and factors related to inadvertent intraoperative hypothermia in adults undergoing elective VATS under general anesthesia.

Methods

This was a retrospective study using data from the Peking University People’s Hospital from January through December, 2018. Data were collected on age, sex, height, weight, American Society of Anesthesiologists physical status, the duration of preparation and surgery, timing of surgery, surgery types, anesthesia types, intraoperative core temperature and the length of stay (LOS) in the hospital from the electronic database in our center. Patients were covered with a cotton blanket preoperatively and the surgical draping during the operation. A circulation-water warming mattress set to 38 °C were placed under the body of the patients. Inadvertent intraoperative hypothermia was identified as a core temperature monitored in nasopharynx < 36 °C. Multivariate logistic regression analysis was used to identify independent risk factors of hypothermia.

Results

We found that 72.7% (95% CI 70.5 to 75.0%) of 1467 adult patients who underwent VATS suffered hypothermia during surgery. The factors associated with inadvertent intraoperative hypothermia included age (OR = 1.23, 95% CI 1.11 to 1.36, p < 0.001), BMI (OR = 1.83, 95% CI 1.43 to 2.35, p < 0.001), the duration of preparation (OR = 1.01, 95% CI 1.00 to 1.02, p = 0.014), the duration of surgery (OR = 2.10, 95% CI 1.63 to 2.70, p < 0.001), timing of surgery (OR = 1.64, 95% CI 1.28 to 2.12, p < 0.001), ambient temperature in the operating room (OR = 0.67, 95% CI 0.53 to 0.85, p = 0.001) and general anesthesia combined with paravertebral block after induction of anesthesia (OR = 2.30, 95% CI 1.31 to 4.03, p = 0.004). The average LOS in the hospital in the hypothermia group and the normothemic group was 9 days and 8 days, respectively (p < 0.001).

Conclusions

We highlight the high prevalence of inadvertent intraoperative hypothermia during elective VATS and identify key risk factors including age, duration of surgery more than 2 h, surgery in the morning and general anesthesia combined with paravertebral block (PVB) after intubation. We also find that hypothermia did prolong the LOS in the hospital.
Health mediators as members of multidisciplinary group practice: lessons learned from a primary health care model programme in Hungary
Authors: Kósa Karolina , Katona Cintia , Papp Magor , Fürjes Gergely , Sándor János , Bíró Klára , Ádány Róza
Published: January 2020

Background

A Model Programme of primary care group practices was implemented in Hungary between 2013 and 2017 – where virtually all GPs had worked in single practices – aiming to increase preventive service uptake and reduce inequalities based on a bilateral agreement between the Swiss and Hungarian governments. Group practices employed a wide variety of health professionals as well as support workers called health mediators. Employment of the latter was based on two decades of European experience of health mediators who specifically facilitate access to and use of health services in Roma minority groups. Health mediators had been recruited from local communities, received training on the job, and were tasked to increase uptake of new preventive services provided by the group practices by personal contacts in the local minority populace. The paper describes the contribution of the work of health mediators to the uptake of two new services provided by group practices.

Methods

Quantitative analysis of depersonalized administrative data mandatorily reported to the Management of the Programme during 43 months of operation was carried out on the employment of health mediators and their contribution to the uptake of two new preventive services (health status assessment and community health promoting programmes).

Results

80% of all clients registered with the GPs participated at health status assessment by invitation that was 1.3–1.7 times higher than participation at the most successful national screening programmes in the past 15 years. Both the number of mediator work minutes per client and participation rate at health status assessment, as well as total work time of mediators and participants at community health events showed high correlation. Twice as many Roma minority patients were motivated for service use by health mediators compared to all patients. The very high participation rate reflects the wide impact of health mediators who probably reached not only Roma minority, but vulnerable population groups in general.

Conclusion

The future of general practices lays in multidisciplinary teams in which health mediators recruited from the serviced communities can be valuable members, especially in deprived areas.
Poor oral health and mortality in geriatric patients admitted to an acute hospital: an observational study
Authors: Maeda Keisuke , Mori Naoharu
Published: January 2020

Background

Poor oral health at hospital admission is a potential higher mortality risk predictor. We aimed to determine in-hospital mortality by assessing poor oral health using a validated tool.

Methods

A retrospective observational study was conducted in an acute care hospital, and 624 consecutive geriatric patients were included. Patients were divided into three groups according to oral health, stratified by the Oral Health Assessment Tool (OHAT) scores. Nutritional status, daily living activities, cognitive impairment, and comorbidities were collected as covariates. Univariate and multivariate analyses were performed to identify the relationship between oral health and survival.

Results

The mean age was 83.8 ± 7.9 years, and 41% were males. Groups with an OHAT score equivalent to 0, 1–2, and ≥ 3 comprised 213, 206, and 205 patients, and 11 (5.2%), 13 (6.3%), and 37 (18.0%) of those patients died in the hospital, respectively. Patients in the OHAT score ≥ 3 group had higher mortality than those in the other groups (log-rank test: p = 0.012 for the OHAT = 0 group; p = 0.010 for the OHAT = 1–2 group after Bonferroni corrections). Patients in the OHAT score ≥ 3 group continued to have poor survival even after adjusting for confounders in the Cox’s regression analysis (hazard ratio: 2.514, 95% confidence interval: 1.220–5.183, p = 0.012).

Conclusion

In geriatric patients, poor oral health at hospital admission was an independent in-hospital mortality predictor. Future studies on oral care intervention stratified by oral health conditions are warranted.
Schistosoma and Strongyloides screening in migrants initiating HIV Care in Canada: a cross sectional study
Authors: McLellan Jessica , Gill M. John , Vaughan Stephen , Meatherall Bonnie
Published: January 2020

Background

Following migration fromSchistosomaandStrongyloidesendemic to non-endemic regions, people remain at high risk for adverse sequelae from these chronic infections. HIV co-infected persons are particularly vulnerable to the serious and potentially fatal consequences of untreated helminth infection. While general screening guidelines exist for parasitic infection screening in immigrant populations, they remain silent on HIV positive populations. This study assessed the seroprevalence, epidemiology and laboratory characteristics of these two parasitic infections in a non-endemic setting in an immigrant/refugee HIV positive community.

Methods

Between February 2015 and 2018 individuals born outside of Canada receiving care at the centralized HIV clinic serving southern Alberta, Canada were screened by serology and direct stool analysis for schistosomiasis and strongyloidiasis. Canadian born persons with travel-based exposure risk factors were also screened. Epidemiologic and laboratory values were analyzed using bivariate logistic regression. We assessed the screening utility of serology, direct stool analysis, eosinophilia and hematuria.

Results

253 HIV positive participants were screened. The prevalence of positive serology forSchistosomaandStrongyloideswas 19.9 and 4.4%, respectively. Age between 40 and 50 years (OR 2.50, 95% CI 1.13–5.50), refugee status (3.55, 1.72–7.33), country of origin within Africa (6.15, 2.44–18.60), eosinophilia (3.56, 1.25–10.16) and CD4 count < 200 cells/mm3(2.46, 1.02–5.92) were associated with positiveSchistosomaserology. Eosinophilia (11.31, 2.03–58.94) was associated with positiveStrongyloidesserology. NoSchistosomaorStrongyloidesparasites were identified by direct stool microscopy. Eosinophilia had poor sensitivity for identification of positive serology. Hematuria was not associated with positiveSchistosomaserology.

Conclusion

PositiveSchistosomaandStrongyloidesserology was common in this migrant HIV positive population receiving HIV care in Southern Alberta. This supports the value of routine parasitic screening as part of standard HIV care in non-endemic areas. Given the high morbidity and mortality in this relatively immunosuppressed population, especially forStrongyloidesinfection, screening should include both serologic and direct parasitological tests. Eosinophilia and hematuria should not be used forSchistosomaandStrongyloidesserologic screening in HIV positive migrants in non-endemic settings.
A novel association of CCDC80 with gestational diabetes mellitus in pregnant women: a propensity score analysis from a case-control study
Authors: Liu Lei , Hu Jiajin , Wang Ningning , Liu Yang , Wei Xiaotong , Gao Ming , Ma Yanan , Wen Deliang
Published: January 2020

Background

Gestational diabetes mellitus (GDM) is a growing global epidemic. Our study aims to confirm the association between circulatory coiled-coil domain-containing 80 (CCDC80) in pregnant women with GDM, to investigate the discriminatory power of CCDC80 on GDM, and to explore the relationships between this molecular level and clinical cardiometabolic parameters.

Methods

A 1:2 matched case-control study with 61 GDM patients and 122 controls was conducted using a propensity score matching protocol. All participants were screened from a multicenter prospective pre-birth cohort: Born in Shenyang Cohort Study (BISCS). During 24 and 28 weeks of gestation, follow-up individuals underwent an oral glucose tolerance test (OGTT) and blood sampling for cardiometabolic characterization.

Results

Following propensity score matching adjustment for clinical variables, including maternal age, gestational age, body mass index, SBP and DBP, plasma CCDC80 levels were significantly decreased in patients with GDM when compared with controls (0.25 ± 0.10 vs. 0.31 ± 0.12 ng/ml, P = 0.003). Conditional multi-logistic regression analyses after adjustments for potential confounding factors revealed that CCDC80 was a strong and independent protective factor for GDM (ORs < 1). In addition, the results of the ROC analysis indicated the CCDC80 exhibited the capability to identify pregnant women with GDM (AUC = 0.633). Finally, multivariate regression analyses showed that CCDC80 levels were positively associated with AST, monoamine oxidase, complement C1q, LDL-C, apolipoprotein A1and B, and negatively associated with blood glucose levels at 1 h post- OGTT.

Conclusions

Biomarker CCDC80 could be of great value for the development of prediction, diagnosis and therapeutic strategies against GDM in pregnant women.
NFкB is a critical transcriptional regulator of atypical cadherin FAT1 in glioma
Authors: Srivastava Chitrangda , Irshad Khushboo , Gupta Yakhlesh , Sarkar Chitra , Suri Ashish , Chattopadhyay Parthaprasad , Sinha Subrata , Chosdol Kunzang
Published: January 2020

Background

Overexpression of FAT1 gene and its oncogenic effects have been reported in several cancers. Previously, we have documented upregulation of FAT1 gene in glioblastoma (GBM) tumors which was found to increase the expression of proinflammatory markers, HIF-1α, stemness genes and EMT markers in glioma cells. Here, we reveal NFкB (RelA)/RelA/p65 as the transcriptional regulator of FAT1 gene in GBM cells.

Methods

In-silico analysis of FAT1 gene promoter was performed using online bioinformatics tool Promo alggen (Transfac 8.3) to identify putative transcription factor(s) binding motifs. A 4.0 kb FAT1 promoter (− 3220 bp to + 848 bp w.r.t. TSS + 1) was cloned into promoter less pGL3Basic reporter vector. Characterization of FAT1 promoter for transcriptional regulation was performed by in-vitro functional assays using promoter deletion constructs, site directed mutagenesis and ChIP in GBM cells.

Results

Expression levels of NFкB (RelA) and FAT1 were found to be increased and positively correlated in GBM tumors (n = 16), REMBRANDT GBM-database (n = 214) and TCGA GBM-database (n = 153). In addition to glioma, positive correlation between NFкB (RelA) and FAT1 expression was also observed in other tumors like pancreatic, hepatocellular, lung and stomach cancers (data extracted from TCGA tumor data). A 4.0 kb FAT1-promoter-construct [− 3220 bp/+ 848 bp, transcription start site (TSS) + 1, having 17 NFкB (RelA) motifs] showed high FAT1 promoter luciferase-activity in GBM cells (U87MG/A172/U373MG). FAT1 promoter deletion-construct pGL3F1 [− 200 bp/+ 848 bp, with 3-NFкB (RelA)-motifs] showed the highest promoter activity. Exposure of GBM cells to known NFкB (RelA)-activators [severe-hypoxia/TNF-α/ectopic-NFкB (RelA) + IKBK vectors] led to increased pGL3F1-promoter activity and increased endogenous-FAT1 expression. Conversely, siRNA-mediated NFкB (RelA) knockdown led to decreased pGL3F1-promoter activity and decreased endogenous-FAT1 expression. Deletion of NFкB (RelA)-motif at − 90 bp/− 80 bp [pGL3F1δ1-construct] showed significant decrease in promoter activity. Site directed mutagenesis at -90 bp/− 80 bp and ChIP assay for endogenous-NFкB (RelA) confirmed the importance of this motif in FAT1 expression regulation. Significant reduction in the migration, invasion as well as colony forming capacity of the U87MG glioma cells was observed on siRNA-mediated knockdown of NFкB (RelA).

Conclusion

Since FAT1 and NFкB (RelA) are independently known to promote pro-tumorigenic inflammation and upregulate the expression of HIF-1α/EMT/stemness in tumors, targeting the NFкB (RelA)-FAT1 axis may attenuate an important tumor-promoting pathway in GBM. This may also be applicable to other tumors.
CT features and quantitative analysis of subsolid nodule lung adenocarcinoma for pathological classification prediction
Authors: Li Xiaohu , Zhang Wei , Yu Yongqiang , Zhang Guihong , Zhou Lifen , Wu Zongshan , Liu Bin
Published: January 2020

Background

The value of the CT features and quantitative analysis of lung subsolid nodules (SSNs) in the prediction of the pathological grading of lung adenocarcinoma is discussed.

Methods

Clinical data and CT images of 207 cases (216 lesions) with CT manifestations of an SSNs lung adenocarcinoma confirmed by surgery pathology were retrospectively analysed. The pathological results were divided into three groups, including atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). Then, the quantitative and qualitative data of these nodules were compared and analysed.

Results

The mean size, maximum diameter, mean CT value and maximum CT value of the nodules were significantly different among the three groups of AAH/AIS, MIA and IAC and were different between the paired groups (AAH/AIS and MIA or MIA and IAC) (P < 0.05). The critical values of the above indicators between AAH/AIS and MIA were 10.05 mm, 11.16 mm, − 548.00 HU and − 419.74 HU. The critical values of the above indicators between MIA and IAC were 14.42 mm, 16.48 mm, − 364.59 HU and − 16.98 HU. The binary logistic regression analysis of the features with the statistical significance showed that the regression model between AAH/AIS and MIA is logit(p) = − 0.93 + 0.216X1 + 0.004X4. The regression model between MIA and IAC is logit(p) = − 1.242–1.428X5(1) − 1.458X6(1) + 1.146X7(1) + 0.272X2 + 0.005X3. The areas under the curve (AUC) obtained by plotting the receiver operating characteristic curve (ROC) using the regression probabilities of regression models I and II were 0.815 and 0.931.

Conclusions

Preoperative prediction of pathological classification of CT image features has important guiding value for clinical management. Correct diagnosis results can effectively improve the patient survival rate. Through comprehensive analysis of the CT features and qualitative data of SSNs, the diagnostic accuracy of SSNs can be effectively improved. The logistic regression model established in this study can better predict the pathological classification of SSNs lung adenocarcinoma on CT, and the predictive value is significantly higher than the independent use of each quantitative factor.
Efficacy and safety of self-expanding metallic stent placement followed by neoadjuvant chemotherapy and scheduled surgery for treatment of obstructing left-sided colonic cancer
Authors: Han Jia Gang , Wang Zhen Jun , Zeng Wei Gen , Wang Yan Bin , Wei Guang Hui , Zhai Zhi Wei , Zhao Bao Cheng , Yi Bing Qiang
Published: January 2020

Background

This study aimed to evaluate the safety and feasibility of self-expanding metallic stent (SEMS) followed by neoadjuvant chemotherapy prior to elective surgery for obstructing left-sided colon cancer.

Methods

Eleven consecutive patients with obstructing left-sided colon cancer between May 2014 and November 2015 were included retrospectively. All patients received SEMS followed by neoadjuvant chemotherapy. The primary outcome measure was stoma and laparoscopic surgery.

Results

Chemotherapy was with two cycles of CAPOX (54.5%) or three cycles mFOLFOX6 (45.5%). Median serum albumin and hemoglobin levels before surgery were significantly higher than before neoadjuvant chemotherapy (p = 0.01 and p = 0.008 respectively) and before SEMS (p = 0.01 and p = 0.003 respectively). Median bowel wall thickness proximal to the upper edge of tumor was significantly more before neoadjuvant chemotherapy than before stent (p = 0.003), and significantly less before surgery than before neoadjuvant chemotherapy (p = 0.003). No patient underwent stoma creation. Laparoscopic surgery was performed in nine (81.8%) patients. No local recurrence or metastases developed over median cancer-specific follow-up of 44 months (range, 37–55 months).

Conclusion

SEMS followed by neoadjuvant chemotherapy prior to elective surgery appears to be safe and well tolerated in patients with obstructing left-sided colon cancer.
Pars plana vitrectomy under melphalan irrigation for recurrent retinal detachment in eyes treated for retinoblastoma: a case report
Authors: Stathopoulos Christina , Sergenti Jessica , Gaillard Marie-Claire , Munier Francis L. , Daruich Alejandra
Published: January 2020

Background

Tractional retinal detachment with or without secondary tear is a rare complication reported in less than 0.5% of in eyes treated for retinoblastoma. Pars plana vitrectomy (PPV) in eyes with history of retinoblastoma has been associated with a significant risk for recurrence, extraocular spread, and systemic metastases. We report here the successful management by PPV under melphalan irrigation of 2 children presenting with tractional retinal detachment after retinoblastoma therapy and scleral buckle surgery.

Case presentation

A 7-year-old girl with a history of bilateral retinoblastoma (group D) presented with light perception best-corrected visual acuity (BCVA) and tractional retinal detachment (RD) in her left eye, 3 years after the last intra-arterial chemotherapy (IAC) injection. Moreover, she had history of left eye rhegmatogenous RD treated by scleral buckle 1 month after the last IAC and cataract surgery 12 months later. PPV associated with retinectomy, laser photocoagulation and silicone oil tamponade was performed. Silicone oil was removed 4 months later. Fifteen months after PPV, BCVA had increased to 20/32 without recurrence of RD and no evidence of tumor activity. A 7-year-old boy with a history of unilateral retinoblastoma (group D) in his left eye presented with rhegmatogenous RD 21 months after the last treatment for retinoblastoma. Scleral buckle surgery was performed, but 3 weeks later the patient presented with tractional RD associated with proliferative vitreo-retinopathy. BCVA was counting fingers. PPV associated with membrane peel, laser photocoagulation and silicone oil tamponade was performed. Silicone oil was removed after 5 months followed by cataract surgery 5 months later. Twenty months after PPV, BCVA was 20/20 and there was no sign of tumor recurrence.

Conclusions

PPV under melphalan irrigation, with retinectomy, if necessary, and silicone oil tamponade, allows anatomical and functional improvement in eyes with history of retinoblastoma and scleral buckling developing tractional RD.
Investigating and managing neonatal seizures in the UK: an explanatory sequential mixed methods approach
Authors: Gossling Lucy , Alix James J. P. , Stavroulakis Theocharis , Hart Anthony R.
Published: January 2020

Background

Neonatal seizures are difficult to diagnose and, when they are, tradition dictates first line treatment is phenobarbital. There is little data on how consultants diagnose neonatal seizures, choose when to treat or how they choose aetiological investigations or drug treatments. The purpose of this study was to assess the variation across the UK in the management of neonatal seizures and explore paediatricians’ views on their diagnosis and treatment.

Methods

An explanatory sequential mixed methods approach was used (QUAN→QUAL) with equal waiting between stages. We collected quantitative data from neonatology staff and paediatric neurologists using a questionnaire sent to neonatal units and via emails from the British Paediatric Neurology Association. We asked for copies of neonatal unit guidelines on the management of seizures. The data from questionnaires was used to identify16 consultants using semi-structured interviews. Thematic analysis was used to interpret qualitative data, which was triangulated with quantitative questionnaire data.

Results

One hundred questionnaires were returned: 47.7% thought levetiracetam was as, or equally, effective as phenobarbital; 9.2% thought it was less effective. 79.6% of clinicians had seen no side effects in neonates with levetiracetam. 97.8% of unit guidelines recommended phenobarbital first line, with wide variation in subsequent drug choice, aetiological investigations, and advice on when to start treatment. Thematic analysis revealed three themes:‘Managing uncertainty with neonatal seizures’,‘Moving practice forward’and‘Multidisciplinary team working’. Consultants noted collecting evidence on anti-convulsant drugs in neonates is problematic, and recommended a number of solutions, including collaboration to reach consensus guidelines, to reduce diagnostic and management uncertainty.

Conclusions

There is wide variation in the management of neonatal seizures and clinicians face many uncertainties. Our data has helped reveal some of the reasons for current practice and decision making. Suggestions to improve certainty include: educational initiatives to improve the ability of neonatal staff to describe suspicious events, greater use of video, closer working between neonatologists and neurologists, further research, and a national discussion to reach a consensus on a standardised approach to managing neonatal epileptic seizures.