bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the organization and interactivity of metabolic pathfinding with precomputed pathways
Authors: Kim Sarah M. , Peña Matthew I. , Moll Mark , Bennett George N. , Kavraki Lydia E.
Published: January 2020

Background

The rapid growth of available knowledge on metabolic processes across thousands of species continues to expand the possibilities of producing chemicals by combining pathways found in different species. Several computational search algorithms have been developed for automating the identification of possible heterologous pathways; however, these searches may return thousands of pathway results. Although the large number of results are in part due to the large number of possible compounds and reactions, a subset of core reaction modules is repeatedly observed in pathway results across multiple searches, suggesting that some subpaths between common compounds were more consistently explored than others.To reduce the resources spent on searching the same metabolic space, a new meta-algorithm for metabolic pathfinding, Hub Pathway search with Atom Tracking (HPAT), was developed to take advantage of a precomputed network of subpath modules. To investigate the efficacy of this method, we created a table describing a network of common hub metabolites and how they are biochemically connected and only offloaded searches to and from this hub network onto an interactive webserver capable of visualizing the resulting pathways.

Results

A test set of nineteen known pathways taken from literature and metabolic databases were used to evaluate if HPAT was capable of identifying known pathways. HPAT found the exact pathway for eleven of the nineteen test cases using a diverse set of precomputed subpaths, whereas a comparable pathfinding search algorithm that does not use precomputed subpaths found only seven of the nineteen test cases. The capability of HPAT to find novel pathways was demonstrated by its ability to identify novel 3-hydroxypropanoate (3-HP) synthesis pathways. As for pathway visualization, the new interactive pathway filters enable a reduction of the number of displayed pathways from hundreds down to less than ten pathways in several test cases, illustrating their utility in reducing the amount of presented information while retaining pathways of interest.

Conclusions

This work presents the first step in incorporating a precomputed subpath network into metabolic pathfinding and demonstrates how this leads to a concise, interactive visualization of pathway results. The modular nature of metabolic pathways is exploited to facilitate efficient discovery of alternate pathways.
LDpop: an interactive online tool to calculate and visualize geographic LD patterns
Authors: Alexander T. A. , Machiela M. J.
Published: January 2020

Background

Linkage disequilibrium (LD)—the non-random association of alleles at different loci—defines population-specific haplotypes which vary by genomic ancestry. Assessment of allelic frequencies and LD patterns from a variety of ancestral populations enables researchers to better understand population histories as well as improve genetic understanding of diseases in which risk varies by ethnicity.

Results

We created an interactive web module which allows for quick geographic visualization of linkage disequilibrium (LD) patterns between two user-specified germline variants across geographic populations included in the 1000 Genomes Project. Interactive maps and a downloadable, sortable summary table allow researchers to easily compute and compare allele frequencies and LD statistics of dbSNP catalogued variants. The geographic mapping of each SNP’s allele frequencies by population as well as visualization of LD statistics allows the user to easily trace geographic allelic correlation patterns and examine population-specific differences.

Conclusions

LDpop is a free and publicly available cross-platform web tool which can be accessed online athttps://ldlink.nci.nih.gov/?tab=ldpop
Custom selected reference genes outperform pre-defined reference genes in transcriptomic analysis
Authors: dos Santos Karen Cristine Gonçalves , Desgagné-Penix Isabel , Germain Hugo
Published: January 2020

Background

RNA sequencing allows the measuring of gene expression at a resolution unmet by expression arrays or RT-qPCR. It is however necessary to normalize sequencing data by library size, transcript size and composition, among other factors, before comparing expression levels. The use of internal control genes or spike-ins is advocated in the literature for scaling read counts, but the methods for choosing reference genes are mostly targeted at RT-qPCR studies and require a set of pre-selected candidate controls or pre-selected target genes.

Results

Here, we report an R-based pipeline to select internal control genes based solely on read counts and gene sizes. This novel method first normalizes the read counts to Transcripts per Million (TPM) and then excludes weakly expressed genes using the DAFS script to calculate the cut-off. It then selects as references the genes with lowest TPM coefficient of variation. We used this method to pick custom reference genes for the differential expression analysis of three transcriptome sets from transgenic Arabidopsis plants expressing heterologous fungal effector proteins tagged with GFP (using GFP alone as the control). The custom reference genes showed lower coefficient of variation and fold change as well as a broader range of expression levels than commonly used reference genes. When analyzed with NormFinder, both typical and custom reference genes were considered suitable internal controls, but the custom selected genes were more stably expressed. geNorm produced a similar result in which most custom selected genes ranked higher (i.e. were more stably expressed) than commonly used reference genes.

Conclusions

The proposed method is innovative, rapid and simple. Since it does not depend on genome annotation, it can be used with any organism, and does not require pre-selected reference candidates or target genes that are not always available.
Correction to: Detection of Candidatus Neoehrlichia mikurensis in Norway up to the northern limit of Ixodes ricinus distribution using a novel real time PCR test targeting the groEL gene
Authors: Jenkins Andrew , Raasok Cecilie , Pedersen Benedikte N. , Jensen Kristine , Andreassen Åshild , Soleng Arnulf , Edgar Kristin Skarsfjord , Lindstedt Heidi Heggen , Kjelland Vivian , Stuen Snorre , Hvidsten Dag , Kristiansen Bjørn-Erik
Published: January 2020

After publication of our article [1] it came to our notice that the source of the sequence for the control plasmid, pNeo (Materials and methods: Controls) was incorrectly stated as AB094461. The correct accession number is AB074461. The authors apologize for any confusion this may have caused.
The Prognostic Significance of Different Bleeding Classifications in off-pump coronary artery bypass grafting
Authors: Xi Ziwei , Gao Yanan , Yan Zhenxian , Zhou Yu-Jie , Liu Wei
Published: January 2020

Background

Perioperative bleeding during cardiac surgery are known to make patients susceptible to adverse outcomes and several bleeding classifications have been developed to stratify the severity of bleeding events. Further validation of different classifications was needed. The aim of present study was to validate and explore the prognostic value of different bleeding classifications in patients undergoing off-pump coronary artery bypass grafting (OPCAB).

Methods

Data on baseline and operative characteristics of 3988 patients who underwent OPCAB in Beijing Anzhen Hospital from February 2008 to December 2014 were available. The primary endpoint was a composite of in-hospital death and nonfatal postoperative myocardial infarction (MI). The secondary endpoint was postoperative acute kidney injury (AKI). We explored the association of major bleeding defined by the European registry of Coronary Artery Bypass Grafting (E-CABG), Universal Definition of Perioperative Bleeding (UDPB), Bleeding Academic Research Consortium (BARC) classification and Study of Platelet Inhibition and Patient Outcomes (PLATO) with primary endpoints by multivariable logistic regression analysis and investigated their significance of adverse event prediction using goodness-of-fit tests of − 2 log likelihood.

Results

In-hospital mortality was 1.23% (n = 49) and postoperative MI was observed in 4.76% (n = 190) of patients, AKI in 24.69% (n = 985). The incidence of the primary outcome was 5.99% (n = 239). Multivariable logistic regression analysis showed that BARC type 4 (OR = 2.64, 95% CI: 1.66–4.19, P < 0.001), UDPB class 4 (OR = 3.52, 95% CI: 2.05–6.02, P < 0.001) and E-CABG class 2–3 (class 2: OR = 2.24, 95% CI: 1.36–3.70, P = 0.001; class 3: OR = 12.65, 95% CI: 2.74–18.43, P = 0.002) bleeding but not PLATO bleeding were associated with an increased risk of in-hospital death and postoperative MI. Major bleeding defined by all the four classifications mentioned above was an independent risk factor of AKI after surgery. Inclusion of major bleeding defined by these four classifications improved the predictive performance of the multivariable model with baseline characteristics.

Conclusions

Bleeding assessed by BARC, E-CABG and UDPB classifications were significantly associated with poorer immediate outcomes. These classifications seemed to be valuable tool in the assessment of prognostic effect of perioperative bleeding.
Reliability and validity of a sedentary behavior questionnaire for South American pediatric population: SAYCARE study
Authors: De Moraes Augusto César Ferreira , Nascimento-Ferreira Marcus Vinícius , Forjaz Claudia Lucia de Moraes , Aristizabal Juan Carlos , Azzaretti Leticia , Nascimento Junior Walter Viana , Miguel-Berges Maria L. , Skapino Estela , Delgado Carlos , Moreno Luis A. , Carvalho Heráclito Barbosa
Published: January 2020

Background

Multicenter studies from Europe and the United States have developed specifically standardized questionnaires for assessing and comparing sedentary behavior, but they cannot be directly applied for South American countries. The aim of this study was to assess the reliability and validity of the South American Youth Cardiovascular and Environmental (SAYCARE) sedentary behavior questionnaire.

Methods

Children and adolescents from seven South American cities were involved in the test-retest reliability (children: n = 55; adolescents: n = 106) and concurrent validity (children: n = 93; adolescents: n = 94) studies. The SAYCARE sedentary behavior questionnaire was administered twice with two-week interval and the behaviors were parent-reported for children and self-reported for adolescents. Questions included time spent watching television, using a computer, playing console games, passive playing (only in children) and studying (only in adolescents) over the past week. Accelerometer was used for at least 3 days, including at least one weekend day. We compared values of sedentary time, using accelerometers, by quartiles of reported sedentary behavior time and their sum.

Results

The reliability of sedentary behavior time was moderate for children (rho ≥0.45 and k ≥ 0.40) and adolescents (rho ≥0.30). Comparisons between the questionnaire and accelerometer showed a low overall agreement, with the questionnaire systematically underreporting sedentary time in children (at least, − 332.6 ± 138.5 min/day) and adolescents (at least, − 399.7 ± 105.0 min/day).

Conclusion

The SAYCARE sedentary behavior questionnaire has acceptable reliability in children and adolescents. However, the findings of current study indicate that SAYCARE questionnaire is not surrogate of total sedentary time.
Assessing and reducing PET radiotracer infiltration rates: a single center experience in injection quality monitoring methods and quality improvement
Authors: Osborne Dustin R. , Acuff Shelley N. , Fang Michael , Weaver Melissa D. , Fu Yitong
Published: January 2020

Background

Successful injection of radiolabeled compounds is critical for positron emission tomography (PET) imaging. A poor quality injection limits the tracer availability in the body and can impact diagnostic results. In this study, we attempt to quantify our infiltration rates, develop an actionable quality improvement plan to reduce potentially compromised injections, and compare injection scoring to PET/CT imaging results.

Methods

A commercially available system that uses external radiation detectors was used to monitor and score injection quality. This system compares the time activity curves of the bolus relative to a control reading in order to provide a score related to the quality of the injection. These injection scores were used to assess infiltration rates at our facility in order to develop and implement a quality improvement plan for our PET imaging center. Injection scores and PET imaging results were reviewed to determine correlations between image-based assessments of infiltration, such as liver SUVs, and injection scoring, as well as to gather infiltration reporting statistics by physicians.

Results

A total of 1033 injections were monitored at our center. The phase 1 infiltration rate was 2.1%. In decision tree analysis, patients < 132.5lbs were associated with infiltrations. Additional analyses suggested patients > 127.5 lbs. with non-antecubital injections were associated with lower quality injections. Our phase 2 infiltration rate was 1.9%. Comparison of injection score to SUV showed no significant correlation and indicated that only 63% of suspected infiltrations were visible on PET/CT imaging.

Conclusions

Developing a quality improvement plan and monitoring PET injections can lead to reduced infiltration rates. No significant correlation between reference SUVs and injection score provides evidence that determination of infiltration based on PET images alone may be limited. Results also indicate that the number of infiltrated PET injections is under-reported.
Uveitis–glaucoma–hyphema syndrome with sclera-fixed posterior-chamber two-haptic intraocular lens in a highly myopic eye: a case report
Authors: Du Yu , Zhu Xiangjia , Yang Jin , Zhang Yinglei , Cai Lei , Lu Yi
Published: January 2020

Background

We report a case of uveitis–glaucoma–hyphema (UGH) syndrome in a highly myopic pseudophakic eye with seemingly normal positioning of a two-haptic intraocular lens (IOL).

Case presentation

The patient was a 61-year-old woman suffering recurrent episodes of blurred vision, floaters, redness, elevated intraocular pressure (IOP), and pain in the right eye following implantation of a sclera-fixed IOL. The symptoms were alleviated by the systemic and topical administration of IOP-lowering and anti-inflammatory medications. A slit-lamp examination revealed depigmentation and atrophy of the iris, and a quiet anterior chamber in the right eye. Endophthalmitis caused by hypovirulent bacteria and UGH syndrome were both considered. Ultrasound biomicroscopy (UBM) and gonioscopy provided direct evidence of malpositioned IOL haptics, which pushed the root of the iris forward, resulting in persistent mechanical chaffing, the probable cause of UGH syndrome. IOL explantation resolved her symptoms. Negative bacterial culture results for the IOL excluded the possibility of endophthalmitis.

Conclusions

Heightened awareness of underlying UGH syndrome and prompt UBM are important when doctors encounter a patient with a sclera-fixed IOL suffering from recurrent anterior segment inflammation and elevated IOP.
Adult low-risk drinkers and abstainers are not the same
Authors: Mugavin Janette , MacLean Sarah , Room Robin , Callinan Sarah
Published: January 2020

Background

Alcohol consumption, even at low-levels, can not be guaranteed as safe or risk free. Specifically, the 2009 Australian National Health and Medical Research Council drinking guidelines recommend that adults should not drink more than two standard drinks on any day on average, and no more than four drinks on a single occasion. Nearly 40% of Australians aged 12 years and older drink alcohol but don’t exceed these recommended limits, yet adult low-risk drinkers have been largely overlooked in Australian alcohol survey research, where they are usually grouped with abstainers. This paper examines the socio-demographic profile of low-risk drinking adults (18+ years old), compared to those who abstain.

Methods

Data from the 2013 National Drug Strategy Household Survey were used. In the past 12 months, 4796 Australians had not consumed alcohol and 8734 had consumed alcohol at low-risk levels, accounting for both average volume and episodic drinking (hereafter low-risk).

Results

Multivariate logistic regression results indicated that low-risk drinkers were more likely to be older, married, Australian-born, and reside in a less disadvantaged neighbourhood compared with abstainers. There was no significant difference by sex between low-risk drinkers and abstainers.

Conclusions

The socio-demographic profile of low-risk drinkers differed from that of abstainers. Combining low-risk drinkers and abstainers into a single group, which is often the practice in survey research, may mask important differences. The study may support improved targeting of health promotion initiatives that encourage low-risk drinkers not to increase consumption or, in view of increasing evidence that low-risk drinking is not risk free, to move towards abstinence.
Knowledge of heart attack and stroke symptoms among US Native American Adults: a cross-sectional population-based study analyzing a multi-year BRFSS database
Authors: Van Hooser Jared C. , Rouse Krista L. , Meyer Mandy L. , Siegler Amanda M. , Fruehauf Beth M. , Ballance Elliot H. , Solberg Sarah M. , Dibble Michael J. , Lutfiyya M. Nawal
Published: January 2020

Background

Heart disease and stroke are among the leading causes of death in Native Americans. Knowledge of heart attack and stroke symptomology are essential for prompt identification of symptoms and for appropriate action in seeking care. Knowledge of heart attack and stroke symptoms among US Native American adults was this study’s focus.

Methods

Multivariate techniques were used to analyze national surveillance data. Native American adults comprised the study population. Low heart attack and stroke knowledge score was the dependent variable.

Results

Logistic regression analysis yielded that Native American adults with low heart attack and stroke composite knowledge scores were more likely to be: older, less educated, poorer, uninsured, a rural resident, male, without a primary health care provider, and lacking a recent medical checkup.

Conclusions

The identified characteristics of Native American adults with heart attack and stroke knowledge deficits or disparities should guide educational initiatives by health care providers focusing on improving such knowledge.
SALaMA study protocol: a mixed methods study to explore mental health and psychosocial support for conflict-affected youth in Detroit, Michigan
Authors: Stark Lindsay , Robinson Mackenzie V. , Seff Ilana , Hassan Wafa , Allaf Carine
Published: January 2020

Background

Families resettling to the U.S. from conflict-affected countries in the Middle East and North Africa (MENA) face countless challenges. These families must cope with experiences of armed conflict and forced migration while also assimilating to a new society. According to the ‘immigrant paradox,’ time spent in a new country can compound the effects of migration and assimilation challenges and lead to deteriorated mental health. This study aims to assess the psychosocial wellbeing of MENA-born or first-generation adolescents attending school in the Detroit metropolitan area (DMA) to understand how schools, families, and communities play a role in supporting these adolescents’ wellbeing.

Methods

The quantitative component of this mixed methods study will involve a self-administered survey with a sample of students whose responses will be linked to academic records and behavioral assessments. The survey will utilize validated instruments to measure depressive and anxiety symptoms (Hopkins Symptom Checklist-37A), hope (Children’s Hope Scale), resilience (Child and Youth Resilience Measure-12), externalizing and prosocial behavior (Hopkins Symptom Checklist-37A, Strengths and Difficulties Questionnaire), school belonging (Psychological Sense of School Membership), and peer relationships (Multidimensional Scale of Perceived Social Support). Differences in outcomes will be analyzed across two strata: students born in the MENA region and first-generation students whose parents immigrated to the US from the MENA region. The qualitative component will involve semi-structured key informant interviews with parents, school administrators, educators, and mental health providers, and focus group discussions (FGDs) with a purposive sample of adolescents born – or whose parents were born - in the MENA region. The FGDs will include a participatory ranking activity where participants will be asked to free-list and rank ideas about how schools can better support students like them. Thematic content analysis will be conducted to identify common themes.

Discussion

This study will contribute evidence about the wellbeing of adolescents who come from – or whose parents come from - conflict-affected countries currently living in the U.S. Findings can be used to inform program and policy development to enable schools and their community partners to serve this population more effectively.
Age-specific incidence of allergic and non-allergic asthma
Authors: Pakkasela Johanna , Ilmarinen Pinja , Honkamäki Jasmin , Tuomisto Leena E. , Andersén Heidi , Piirilä Päivi , Hisinger-Mölkänen Hanna , Sovijärvi Anssi , Backman Helena , Lundbäck Bo , Rönmark Eva , Kankaanranta Hannu , Lehtimäki Lauri
Published: January 2020

Background

Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma.

Methods

Questionnaires were sent to 8000 randomly selected recipients aged 20–69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported.

Results

The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0–9, 10–19, 20–29, 30–39, 40–49, 50–59 and 60–69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50–59 years old).

Conclusions

The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.
Madurella mycetomatis infection of the foot: a case report of a neglected tropical disease in a non-endemic region
Authors: Karrakchou Basma , Boubnane Ibtissam , Senouci Karima , Hassam Badreddine
Published: January 2020

Background

Mycetoma is an uncommon chronic granulomatous infection of cutaneous and subcutaneous tissues that can be caused by filamentous bacteria (actinomycetoma) or fungi (eumycetoma). It is the prerogative of young men between the third and fourth decade and is transmitted through any trauma causing an inoculating point. The classic clinical triad associates a painless hard and swelling subcutaneous mass, multiple fistulas, and the pathognomonic discharge of grains. Although endemic in many tropical and subtropical countries, mycetoma can also be found in non-endemic areas as in Morocco, and causes then diagnosis problems leading to long lasting complications. Therefore, we should raise awareness of this neglected disease for an earlier management. Under medical treatment however, mycetoma has a slow healing and surgery is often needed, and relapses are possible.

Case presentation

Herein we report a case of a 64 years old patient, with a history of eumycetoma occurring ten years ago treated with oral terbinafine coupled with surgery. A complete remission was seen after 2 years. He presented a relapse on the previous scar 6 months ago. There wasn’t any bone involvement in the magnetic resonance imaging (MRI). The patient was put under oral terbinafine with a slow but positive outcome.

Conclusion

Through this case report, we perform a literature review and highlight the importance of increase awareness of mycetoma in clinical practice especially in non-endemic regions.
Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
Authors: Bafadhel Mona , Singh Dave , Jenkins Christine , Peterson Stefan , Bengtsson Thomas , Wessman Peter , Fagerås Malin
Published: January 2020

Background

Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD.

Methods

This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models.

Results

The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69–84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count.

Conclusions

Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.
Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression
Authors: Wang Hongbin , Ren Yanlv , Qian Cheng , Liu Jiaxin , Li Ge , Li Zhigao
Published: January 2020

Background

microRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells. However, the underlying mechanism of its involvement in breast cancer remains largely unknown. With our research, our endeavor is to explore the role of the CDX2/let-7b/COL11A1 axis in breast cancer cell activities.

Methods

Tumor tissues and adjacent normal tissues were collected from 86 patients with breast cancer. Human breast cancer epithelial cell line MCF-7 was treated with over-expressed CDX2, let-7b mimic, shRNA against COL11A1 and their negative controls. The expression of CDX2, let-7b, and COL11A1 in the tissues and cells was determined by RT-qPCR. Interactions among CDX2, let-7b, and COL11A1 were detected by ChIP and dual-luciferase reporter assay, respectively. After different transfections, cell invasion, migration, and proliferation abilities were determined by Transwell and EdU assays. Lastly, tumor xenografts in nude mice were established and hematoxylin and eosin staining was performed to assess the tumor growth and lymph node metastasis.

Results

CDX2 and let-7b were poorly expressed in breast cancer cells and tissues. CDX2 bound to let-7b and promoted the expression of let-7b, which contrarily inhibited the expression of COL11A1. Cancer cell proliferation, invasion, migration, and metastasis were stimulated when CDX2 and let-7b were depleted or COL11A1 was over-expressed. Xenograft tumors growth and metastasis were in accordance with the results of cellular experiments.

Conclusion

In agreement with these observations, we could reach a conclusion that CDX2 could promote let-7b expression, which may exert an inhibitory effect on the proliferation, migration, and metastasis of breast cancer cells via repressing the expression of COL11A1, providing a novel therapeutic strategy for the treatment of metastatic breast cancer.
LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis
Authors: Wu Liangcai , Zhu Lifei , Li Yanchang , Zheng Zhixin , Lin Xi , Yang Chaoying
Published: January 2020

Background

Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied.

Methods

RT-PCR was used to examine the expressions of lncRNA MEG3 and E-cadherin in melanoma patients and cell lines. Then, the biological functions of lncRNA MEG3 and E-cadherin were demonstrated by transfecting lncRNA MEG3-siRNA, lncRNA MEG3-overexpression, E-cadherin-siRNA and E-cadherin-overexpression plasmids in melanoma cell lines. Moreover, CCK8 assay and colony formation assay were utilized to assess the cell proliferation; Transwell assay was performed to evaluate the cell invasive ability; and tumor xenografts in nude mice were applied to test the tumor generation. Additionally, the target interactions among lncRNA MEG3, miR-21 and E-cadherin were determined by dual luciferase reporter assay. Finally, RT-PCR and WB were further conducted to verify the regulatory roles among lncRNA MEG3, miR-21 and E-cadherin.

Results

The clinical data showed that lncRNA MEG3 and E-cadherin expressions were both declined in carcinoma tissues as compared with their para-carcinoma tissues. Moreover, lncRNA MEG3 and E-cadherin expressions in B16 cells were also higher than those in A375 and A2058 cells. Subsequently, based on the differently expressed lncRNA MEG3 and E-cadherin in these human melanoma cell lines, we chose B16, A375 and A2058 cells for the following experiments. The results demonstrated that lncRNA MEG3 could suppress the tumor growth, tumor metastasis and formation; and meanwhile E-cadherin had the same effects on tumor growth, tumor metastasis and formation. Furthermore, the analysis of Kaplan–Meier curves also confirmed that there was a positive correlation between lncRNA MEG3 and E-cadherin. Ultimately, dual luciferase assays were further used to verify that lncRNA MEG3 could directly target miR-21 which could directly target E-cadherin in turn. Additionally, the data of RT-PCR and WB revealed that knockdown of lncRNA MEG3 in B16 cells inhibited miR-21 expression and promoted E-cadherin expression, but overexpression of lncRNA MEG3 in A375 and A2058 cells presented completely opposite results.

Conclusion

Our findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis.
Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis
Authors: Zhao Jiawen , Huang Weijia , Wu Yongxian , Luo Yihuan , Wu Bo , Cheng Jiwen , Chen Junqiang , Liu Deyun , Li Chengyang
Published: January 2020

Background

To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors.

Methods

Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included.

Results

A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer.

Conclusions

Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.
Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy
Authors: Potemin Sergey , Kübler Jens , Uvarov Ivan , Wenz Frederik , Giordano Frank
Published: January 2020

Background

Neoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT.

Methods

We retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS).

Results

A total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4–17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40–50.4 Gy]) and IORT (median dose: 15 Gy [15–17 Gy]). The median age was 65 years [33–82]. The median follow-up was 23 months [0–63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively).

Conclusions

IORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.
Influence of inflammatory arthritis on leukocyte esterase strip results in the diagnosis of periprosthetic joint infection
Authors: Zhang Jinling , Gui Binjie , Cheng Fangyue , Rong Genxiang , Tang Zhi , Shen Cailiang
Published: January 2020

Background

The leukocyte esterase (LE) strip is considered as a helpful method to detect infection, which might be influenced by other inflammatory diseases. This study aims to explore whether the centrifugation of synovial fluid could influence the positive result of LE strip caused by inflammatory arthritis during the diagnosis of periprosthetic joint infection (PJI).

Methods

From March 2016 to December 2018, 64 patients who were diagnosed as PJI or aseptic arthritis and another 20 patients with inflammatory arthritis were enrolled in our study. After synovial fluid samples were obtained, the LE strip test was performed with and without centrifugation. Then clinicians read the color changes 3 min after the samples were dropped and classify the results based on the instruction of strip. The differences between septic and aseptic arthritis patients and septic and inflammatory arthritis patients were analyzed.

Results

Among the included 21 PJI samples, 19 of them showed positive results (++) of LE strip before centrifugation. After centrifugation, two samples changed from two-positive (++) to one-positive (+), which is also considered as positive. Before centrifugation, 29 of the LE strip tests in the aseptic arthritis group (43 samples included) were ++ or +. After centrifugation, 16 of the samples yielded negative results. Among 20 samples with inflammatory arthritis, LE strip of 18 samples were positive (++ or +) before centrifugation, among which only 3 samples remained as positive after centrifugation.

Conclusion

LE strip test results could be influenced by inflammatory arthritis during the diagnosis of PJI. Centrifugation should be performed for LE strip tests to determine whether the result is a true positive or a false positive influenced by inflammatory arthritis.
Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study
Authors: Wohlfart Sigrun , Meiller Ralph , Hammersen Johanna , Park Jung , Menzel-Severing Johannes , Melichar Volker O. , Huttner Kenneth , Johnson Ramsey , Porte Florence , Schneider Holm
Published: January 2020

Background

X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments.

Methods

25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys.

Results

All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1–12 deciduous teeth erupted and 0–8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development.

Conclusions

This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.
Targeting hypoxia in tumor: a new promising therapeutic strategy
Authors: Bosco Maria Carla , D’Orazi Gabriella , Del Bufalo Donatella
Published: January 2020

Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy, selecting a more malignant and invasive phenotype and playing a negative role in patient prognosis. This commentary wishes to recognize the 2019 Nobel Prize in Medicine awarded to three physicians-scientists, Prof. William G. Kaelin Jr., Prof. Sir Peter J. Ratcliffe, and Prof. Gregg L. Semenza, for their discovery of the mechanisms mediating cell ability to sense and adapt to changes in oxygen availability. Their studies established the basis for our understanding of the role of hypoxia in a variety of diseases, including anemia, renal failure, cardiovascular disease, metabolic diseases, and cancer, paving the way for new promising therapeutic strategies through the development of drugs that can either activate or block the oxygen-sensing machinery.
Study protocol of a randomised controlled feasibility study of food-related computerised attention training versus mindfulness training and waiting-list control for adults with overweight or obesity
Authors: Mercado Daniela , Werthmann Jessica , Campbell Iain C. , Schmidt Ulrike
Published: January 2020

Background

Obesity is a highly prevalent condition with multiple adverse health consequences. Widely available first-line treatments for obesity, such as dietary and other lifestyle interventions, typically have only short-term effects. Thus, new treatment approaches are needed. Novel interventions such as Attention Bias Modification Training (ABMT) and mindfulness-based interventions focus on modifying different maladaptive cognitive patterns typically present in people with obesity (e.g. attention bias to food cues); however, their mechanisms of action remain largely unknown. We describe the theoretical basis and the rationale for a study protocol of a feasibility randomised controlled trial (RCT) comparing two attention trainings (ABMT vs Mindfulness Training [MT]) in people with overweight or obesity. The aim of this study is to inform the development of a large-scale RCT in relation to acceptability and attendance rates and to identify preliminary evidence for the interventions’ clinical efficacy and potential underlying mechanisms.

Design

Forty-five adults who are either overweight or obese (minimum body mass index of 25 kg/m2) will be randomly allocated to receive eight sessions over eight weeks of either computerised ABMT or MT or be on a waiting list. Clinical and cognitive outcomes will be assessed at baseline, post-treatment (8 weeks) and follow-up (12 weeks post-randomisation). These include mood, body composition and attention biases. Credibility and acceptability of the trainings will be assessed using questionnaires, and recruitment and retention rates will be recorded.

Discussion

Findings will inform the feasibility of developing a large-scale RCT that takes into consideration effect sizes for primary outcome measures and the acceptability of the design. The study will also provide preliminary evidence on the clinical efficacy of two different attention trainings for people with obesity and associated underlying mechanisms.

Trial registration

ISRCTN Registry,ISRCTN15745838. Registered on 22 May 2018.
The Invested in Diabetes Study Protocol: a cluster randomized pragmatic trial comparing standardized and patient-driven diabetes shared medical appointments
Authors: Kwan Bethany M. , Dickinson L. Miriam , Glasgow Russell E. , Sajatovic Martha , Gritz Mark , Holtrop Jodi Summers , Nease Don E. , Ritchie Natalie , Nederveld Andrea , Gurfinkel Dennis , Waxmonsky Jeanette A.
Published: January 2020

Background

Shared medical appointments (SMAs) have been shown to be an efficient and effective strategy for providing diabetes self-management education and self-management support. SMA features vary and it is not known which features are most effective for different patients and practice settings. The Invested in Diabetes study tests the comparative effectiveness of SMAs with and without multidisciplinary care teams and patient topic choice for improving patient-centered and clinical outcomes related to diabetes.

Methods

This study compares the effectiveness of two SMA approaches using the Targeted Training for Illness Management (TTIM) curriculum. Standardized SMAs are led by a health educator with a set order of TTIM topics. Patient-driven SMAs are delivered collaboratively by a multidisciplinary care team (health educator, medical provider, behavioral health provider, and a peer mentor); patients select the order and emphasis on TTIM topics. Invested in Diabetes is a cluster randomized pragmatic trial involving approximately 1440 adult patients with type 2 diabetes. Twenty primary care practices will be randomly assigned to either standardized or patient-driven SMAs. A mixed-methods evaluation will include quantitative (practice- and patient-level data) and qualitative (practice and patient interviews, observation) components. The primary patient-centered outcome is diabetes distress. Secondary outcomes include autonomy support, self-management behaviors, clinical outcomes, patient reach, and practice-level value and sustainability.

Discussion

Practice and patient stakeholder input guided protocol development for this pragmatic trial comparing SMA approaches. Implementation strategies from the enhanced Replicating Effective Programs framework will help ensure practices maintain fidelity to intervention protocols while tailoring workflows to their settings. Invested in Diabetes will contribute to the literature on chronic illness management and implementation science using the RE-AIM model.

Trial registration

ClinicalTrials.gov,NCT03590041. Registered on 5 July 2018.
Acupuncture of fascia points to relieve hand spasm after stroke: a study protocol for a multicenter randomized controlled trial
Authors: Zhang Zeng-Qiao , Li Kun-Peng , He Jing , Jiang Li-Ming , Wang Wu , Hu Xiao-Shen , Feng Wei
Published: January 2020

Background

The loss of functional ability of patients after stroke is mostly caused by dysfunction of the upper limbs, especially the hands. Hand functional exercise is the premise of alleviating hand dysfunction, and the relief of hand spasm is the basis of timely and effective hand functional exercise. Previous clinical observation have shown that fascial-point needling can effectively alleviate hand spasm immediately after stroke, but further evidence from large-sample studies is needed. The overall objective of this trial is to further evaluate the clinical efficacy of fascial-point acupuncture on hand spasm after stroke.

Methods/design

This multicenter randomized controlled trial will compare the efficacy of fascial-point acupuncture versus sham acupuncture and routine rehabilitation therapy in stroke patients with hand spasm. Patients will be randomized to undergo either the fascial-point acupuncture, the sham acupuncture or the control (routine rehabilitation therapy). We will recruit 210 stroke inpatients who meet the trial criteria and observe the remission of hand spasm and improvement of limb function after 4 weeks of intervention. The first evaluation indices are the remission of hand spasm and the duration of spasm remission. The second evaluation indices are the hand function of the affected limbs and the activities of daily living. When the accumulative total number of cases included reaches 120, a mid-term analysis will be conducted to determine any evidence that experimental intervention does have an advantage.

Discussion

Our aim is to evaluate the efficacy of fascial-point acupuncture in relieving hand spasm after stroke. The results should provide more evidence for the clinical application of this therapy in the future.

Trial registration

Chinese Clinical Trial Registry (ChiCTR), ID:ChiCTR1900022379. Registered on 9 April 2019