bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study
Authors: Buse Dawn C. , Reed Michael L. , Fanning Kristina M. , Bostic Ryan , Dodick David W. , Schwedt Todd J. , Munjal Sagar , Singh Preeti , Lipton Richard B.
Published: March 2020

Background

Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.

Methods

The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities “confirmed by a healthcare professional diagnosis” were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination.

Results

Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever.

Conclusions

In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.
Trade-offs in traffic: does being mainly a car driver or a cyclist affect adaptive behaviour while driving and cycling?
Authors: Nygårdhs Sara , Kircher Katja , Johansson Björn J. E.
Published: March 2020

Aim

Road users, such as cyclists and car drivers, are constantly adapting to each other and to the road infrastructure. This study aimed to investigate what trade-offs can be observed when drivers and cyclists adapt to other road users and to the infrastructure.

Methods

A semi-controlled study was carried out in an urban traffic environment, where all participants travelled the same route twice, once as a cyclist and once as a car driver. The extended control model was used as an analytical framework to examine how people adapt depending on their main and current road-user role, experiencing different infrastructure and complexity.

Results

The results revealed possible trade-offs made while adapting, mainly in relation to rule-following. No differences in adaptive behaviour between people who mostly drive and people who mostly cycle were found. The current situational demands influence both the need to adapt and the adaptation carried out. A more complex traffic environment led to increased information intake, measured by glance behaviour.
LK-DFBA: a linear programming-based modeling strategy for capturing dynamics and metabolite-dependent regulation in metabolism
Authors: Dromms Robert A. , Lee Justin Y. , Styczynski Mark P.
Published: March 2020

Background

The systems-scale analysis of cellular metabolites, “metabolomics,” provides data ideal for applications in metabolic engineering. However, many of the computational tools for strain design are built around Flux Balance Analysis (FBA), which makes assumptions that preclude direct integration of metabolomics data into the underlying models. Finding a way to retain the advantages of FBA’s linear structure while relaxing some of its assumptions could allow us to account for metabolite levels and metabolite-dependent regulation in strain design tools built from FBA, improving the accuracy of predictions made by these tools. We designed, implemented, and characterized a modeling strategy based on Dynamic FBA (DFBA), called Linear Kinetics-Dynamic Flux Balance Analysis (LK-DFBA), to satisfy these specifications. Our strategy adds constraints describing the dynamics and regulation of metabolism that are strictly linear. We evaluated LK-DFBA against alternative modeling frameworks using simulated noisy data from a small in silico model and a larger model of central carbon metabolism inE. coli, and compared each framework’s ability to recapitulate the original system.

Results

In the smaller model, we found that we could use regression from a dynamic flux estimation (DFE) with an optional non-linear parameter optimization to reproduce metabolite concentration dynamic trends more effectively than an ordinary differential equation model with generalized mass action rate laws when tested under realistic data sampling frequency and noise levels. We observed detrimental effects across all tested modeling approaches when metabolite time course data were missing, but found these effects to be smaller for LK-DFBA in most cases. With theE. colimodel, we produced qualitatively reasonable results with similar properties to the smaller model and explored two different parameterization structures that yield trade-offs in computation time and accuracy.

Conclusions

LK-DFBA allows for calculation of metabolite concentrations and considers metabolite-dependent regulation while still retaining many computational advantages of FBA. This provides the proof-of-principle for a new metabolic modeling framework with the potential to create genome-scale dynamic models and the potential to be applied in strain engineering tools that currently use FBA.
Genome-wide discovery, and computational and transcriptional characterization of an AIG gene family in the freshwater snail Biomphalaria glabrata, a vector for Schistosoma mansoni
Authors: Lu Lijun , Loker Eric S. , Zhang Si-Ming , Buddenborg Sarah K. , Bu Lijing
Published: March 2020

Background

The AIG (avrRpt2-induced gene) family of GTPases, characterized by the presence of a distinctive AIG1 domain, is mysterious in having a peculiar phylogenetic distribution, a predilection for undergoing expansion and loss, and an uncertain functional role, especially in invertebrates. AIGs are frequently represented as GIMAPs (GTPase of the immunity associated protein family), characterized by presence of the AIG1 domain along with coiled-coil domains. Here we provide an overview of the remarkably expanded AIG repertoire of the freshwater gastropod Biomphalaria glabrata, compare it with AIGs in other organisms, and detail patterns of expression in B. glabrata susceptible or resistant to infection with Schistosoma mansoni, responsible for the neglected tropical disease of intestinal schistosomiasis.

Results

We define the 7 conserved motifs that comprise the AIG1 domain in B. glabrata and detail its association with at least 7 other domains, indicative of functional versatility of B. glabrata AIGs. AIG genes were usually found in tandem arrays in the B. glabrata genome, suggestive of an origin by segmental gene duplication. We found 91 genes with complete AIG1 domains, including 64 GIMAPs and 27 AIG genes without coiled-coils, more than known for any other organism except Danio (with > 100). We defined expression patterns of AIG genes in 12 different B. glabrata organs and characterized whole-body AIG responses to microbial PAMPs, and of schistosome-resistant or -susceptible strains of B. glabrata to S. mansoni exposure. Biomphalaria glabrata AIG genes clustered with expansions of AIG genes from other heterobranch gastropods yet showed unique lineage-specific subclusters. Other gastropods and bivalves had separate but also diverse expansions of AIG genes, whereas cephalopods seem to lack AIG genes.

Conclusions

The AIG genes of B. glabrata exhibit expansion in both numbers and potential functions, differ markedly in expression between strains varying in susceptibility to schistosomes, and are responsive to immune challenge. These features provide strong impetus to further explore the functional role of AIG genes in the defense responses of B. glabrata, including to suppress or support the development of medically relevant S. mansoni parasites.
The structure, functional evolution, and evolutionary trajectories of the H+-PPase gene family in plants
Authors: Zhang Yiming , Feng Xue , Wang Lihui , Su Yanping , Chu Zhuodong , Sun Yanxiang
Published: March 2020

Background

The H+-PPase (pyrophosphatase) gene family is an important class of proton transporters that play key roles in plant development and stress resistance. Although the physiological and biochemical functions of H+-PPases are well characterized, the structural evolution and functional differentiation of this gene family remain unclear.

Results

We identified 124 H+-PPase members from 27 plant species using complete genomic data obtained from algae to angiosperms. We found that all analyzed plants carried H+-PPase genes, and members were not limited to the two main types (type I and II). Differentiation of this gene family occurred early in evolutionary history, probably prior to the emergence of algae. The type I and II H+-PPase genes were retained during the subsequent evolution of higher plants, and their copy numbers increased rapidly in some angiosperms following whole-genome duplication (WGD) events, with obvious expression pattern differentiation among the new copies. We found significant functional divergence between type I and II H+-PPase genes, with both showing evidence for positive selection pressure. We classified angiosperm type I H+-PPases into subtypes Ia and non-Ia, which probably differentiated at an early stage of angiosperm evolution. Compared with non-Ia subtype, the Ia subtype appears to confer some advantage in angiosperms, as it is highly conserved and abundantly expressed, but shows no evidence for positive selection.

Conclusions

We hypothesized that there were many types of H+-PPase genes in the plant ancestral genome, and that different plant groups retained different types of these genes. In the early stages of angiosperm evolution, the type I H+-PPase genes differentiated into various subtypes. In addition, the expression pattern varied not only among genes of different types or subtypes, but also among copies of the same subtype. Based on the expression patterns and copy numbers of H+-PPase genes in higher plants, we propose two possible evolutionary trajectories for this gene family.
Barley ROP-Interactive Partner-a organizes into RAC1- and MICROTUBULE-ASSOCIATED ROP-GTPASE ACTIVATING PROTEIN 1-dependent membrane domains
Authors: Hoefle Caroline , McCollum Christopher , Hückelhoven Ralph
Published: March 2020

Background

Small ROP (also called RAC) GTPases are key factors in polar cell development and in interaction with the environment. ROP-Interactive Partner (RIP) proteins are predicted scaffold or ROP-effector proteins, which function downstream of activated GTP-loaded ROP proteins in establishing membrane heterogeneity and cellular organization. Grass ROP proteins function in cell polarity, resistance and susceptibility to fungal pathogens but grass RIP proteins are little understood.

Results

We found that the barley (Hordeum vulgare L.) RIPa protein can interact with barley ROPs in yeast. Fluorescent-tagged RIPa, when co-expressed with the constitutively activated ROP protein CA RAC1, accumulates at the cell periphery or plasma membrane. Additionally, RIPa, locates into membrane domains, which are laterally restricted by microtubules when co-expressed with RAC1 and MICROTUBULE-ASSOCIATED ROP-GTPASE ACTIVATING PROTEIN 1. Both structural integrity of MICROTUBULE-ASSOCIATED ROP-GTPASE ACTIVATING PROTEIN 1 and microtubule stability are key to maintenance of RIPa-labeled membrane domains. In this context, RIPa also accumulates at the interface of barley and invading hyphae of the powdery mildew fungus Blumeria graminis f.sp. hordei.

Conclusions

Data suggest that barley RIPa interacts with barley ROPs and specifies RAC1 activity-associated membrane domains with potential signaling capacity. Lateral diffusion of this RAC1 signaling capacity is spatially restricted and the resulting membrane heterogeneity requires intact microtubules and MICROTUBULE-ASSOCIATED ROP-GTPASE ACTIVATING PROTEIN 1. Focal accumulation of RIPa at sites of fungal attack may indicate locally restricted ROP activity at sites of fungal invasion.
Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study
Authors:   International Consortium to Predict PTSD, van der Mei Willem F. , Barbano Anna C. , Ratanatharathorn Andrew , Bryant Richard A. , Delahanty Douglas L. , deRoon-Cassini Terri A. , Lai Betty S. , Lowe Sarah R. , Matsuoka Yutaka J. , Olff Miranda , Qi Wei , Schnyder Ulrich , Seedat Soraya , Kessler Ronald C. , Koenen Karestan C. , Shalev Arieh Y.
Published: March 2020

Background

Previous work has indicated that post-traumatic stress disorder (PTSD) symptoms, measured by the Clinician-Administered PTSD Scale (CAPS) within 60 days of trauma exposure, can reliably produce likelihood estimates of chronic PTSD among trauma survivors admitted to acute care centers. Administering the CAPS is burdensome, requires skilled professionals, and relies on symptoms that are not fully expressed upon acute care admission. Predicting chronic PTSD from peritraumatic responses, which are obtainable upon acute care admission, has yielded conflicting results, hence the rationale for a stepwise screening-and-prediction practice. This work explores the ability of peritraumatic responses to produce risk likelihood estimates of early CAPS-based PTSD symptoms indicative of chronic PTSD risk. It specifically evaluates the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) as a risk-likelihood estimator.

Methods

We used individual participant data (IPD) from five acute care studies that used both the PDEQ and the CAPS (n = 647). Logistic regression calculated the probability of having CAPS scores ≥ 40 between 30 and 60 days after trauma exposure across the range of initial PDEQ scores, and evaluated the added contribution of age, sex, trauma type, and prior trauma exposure. Brier scores, area under the receiver-operating characteristic curve (AUC), and the mean slope of the calibration line evaluated the accuracy and precision of the predicted probabilities.

Results

Twenty percent of the sample had CAPS ≥ 40. PDEQ severity significantly predicted having CAPS ≥ 40 symptoms (p < 0.001). Incremental PDEQ scores produced a reliable estimator of CAPS ≥ 40 likelihood. An individual risk estimation tool incorporating PDEQ and other significant risk indicators is provided.

Conclusion

Peritraumatic reactions, measured here by the PDEQ, can reliably quantify the likelihood of acute PTSD symptoms predictive of chronic PTSD and requiring clinical attention. Using them as a screener in a stepwise chronic PTSD prediction strategy may reduce the burden of later CAPS-based assessments. Other peritraumatic metrics may perform similarly and their use requires similar validation.

Trial registration

Jerusalem Trauma Outreach and Prevention Study (J-TOPS): NCT00146900.
Effects of simultaneous cognitive and aerobic exercise training on dual-task walking performance in healthy older adults: results from a pilot randomized controlled trial
Authors: Raichlen David A. , Bharadwaj Pradyumna K. , Nguyen Lauren A. , Franchetti Mary Kathryn , Zigman Erika K. , Solorio Abigail R. , Alexander Gene E.
Published: March 2020

Background

The ability to walk and perform cognitive tasks simultaneously is a key aspect of daily life. Performance declines in these dual-tasks may be associated with early signs of neurodegenerative disease and increased risk of falls. Thus, interventions to improve dual-task walking performance are of great interest for promoting healthy aging. Here, we present results of a pilot randomized controlled trial (RCT) to evaluate the effects of a simultaneous aerobic exercise and cognitive training intervention on dual-task walking performance in healthy older adults.

Methods

Community-dwelling, healthy older adults were recruited to participate in a 12-week RCT. Participants were randomized into one of four groups (n = 74): 1) cognitive training (COG), 2) aerobic exercise (EX), 3) combined aerobic exercise and cognitive training (EXCOG), and 4) video-watching control (CON). The COG and EXCOG groups both used a tablet-based cognitive training program that challenged aspects of executive cognitive function, memory, and processing speed. Performance on a dual-task walking test (DTWT; serial subtraction during two-minute walk) was assessed by researchers blinded to groupings before the intervention, and at 6 and 12 weeks. We included all participants randomized with baseline measurements in an intention to treat analysis using linear mixed effects models.

Results

We found a significant group by time interaction for cognitive performance on the DTWT (p = 0.039). Specifically, participants in the EXCOG, EX, and COG groups significantly improved on the cognitive aspect of the DTWT following the full 12-week intervention (p = 3.5e-7,p = 0.048,p = 0.048, respectively). The improvements in EXCOG were twice as large as in the other groups, and were significant at 6 weeks (p = 0.019). The CON group did not show a significant change in cognitive performance on the DTWT, and no group significantly altered dual-task gait measures following the intervention.

Conclusions

A simultaneous aerobic exercise and cognitive training intervention significantly improved cognitive performance during a DTWT in healthy older adults. Despite no change in DTWT gait measures, significant improvements in cognitive performance indicate that further investigation in a larger RCT is warranted.

Trial registration

Clinicaltrials.gov,NCT04120792, Retrospectively Registered 08 October 2019.
Correction to: Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis
Authors: Antel Katherine , Oosthuizen Jenna , Malherbe Francois , Louw Vernon J. , Nicol Mark P. , Maartens Gary , Verburgh Estelle
Published: March 2020

After publication of the original article [1], we were notified that there is a mistake in the article note.
Identification of differentially expressed miRNAs and mRNAs in synovial of osteoarthritis via RNA-sequencing
Authors: Zhou Yu , Wang Zhicong , Chen Xi , Zhang Jianjun , Yang Ling , Liu Shuping , Liu Yuehong
Published: March 2020

Background

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. This study attempted to investigate the key mRNAs and miRNAs related to OA.

Patients and methods

From April 17th, 2018 to May 17th, 2018, five patients with OA and three normal controls were enrolled in this present study. To identify the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) between patients with OA and normal controls, RNA-sequencing was performed. Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. To validate the RNA-sequencing results, quantitative real time-PCR (RT-PCR) and western blot analysis were performed as well.

Results

A total of 1068 DEmRNAs, 21 DEmiRNAs and 395 DEmiRNA-DEmRNA pairs were identified in synovial tissues of patients with OA. The functional annotation of DEmiRNA-target DEmRNAs revealed that Pathways in cancer and PI3K-Akt signaling pathway were significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. QRT-PCR and western blot results revealed that except for TLR7, the expression level of the others was consistent with the RNA-sequencing results, generally.

Conclusion

The findings of this present study may provide new clues for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of OA.
How addicted are newly admitted undergraduate medical students to smartphones?: a cross-sectional study from Chitwan medical college, Nepal
Authors: Karki Sirisa , Singh Jaya Prasad , Paudel Gita , Khatiwada Sushma , Timilsina Sameer
Published: March 2020

Background

Increasing smartphone use among adolescents in todays’ world has made this handy device an indispensable electronic tool, however, it comes at a price of problematic overuse or addiction. We aim to investigate the prevalence of smartphone addiction among undergraduate medical students and explore its association with various demographic and personal factors.

Methods

A pool of 250 undergraduate students completed a survey composed of socio-demographics information, smartphone-use related variables and 10-point Smartphone Addiction Scale-Short Version in February 2019.

Results

Smartphone addiction among medical students was estimated at around 36.8% with higher percentage of male smartphone addicts. Phubbing was reported by 37.6% participants with more than 60% reporting overuse. Statistically significant association was observed between smartphone addiction and gender and overuse. Self-acknowledgement of addiction was found to be the biggest predictor of smartphone addiction.

Conclusion

This study provides preliminary insights into smartphone use, smartphone addiction and various factors predicting smartphone addiction among early undergraduate medical students from Nepal, which should be extended in future studies. Education policymakers and educators need to develop some strategies encouraging student’s smartphone utilization to enhance academic performance.
Trans-hiatal repair for Oesophageal and Junctional perforation: a case series
Authors: Lee Adele H. H. , Kweh Barry T. S. , Gillespie Carla , Johnson Mary Ann
Published: March 2020

Background

Oesophageal perforation is a life-threatening condition that requires urgent intervention. Surgical repair is recommended within 24 h of onset to minimise mortality risk, traditionally via an open thoracotomy or a laparotomy. Primary oesophageal repair via a laparoscopic trans-hiatal approach has been seldomly reported due to concerns of inadequate eradication of soilage in the mediastinum and pleural space, as well as poor access and an increased operative time in an unwell population.

Case presentation

We report a case series of 3 oesophageal and junctional perforations with varying presentations, demonstrating how the laparoscopic trans-hiatal approach can be used successfully to manage oesophageal perforations.

Conclusions

Laparoscopic trans-hiatal repair is an attractive option for oesophageal and junctional perforations, in haemodynamically stable surgical candidates, in the absence of gross contamination of the thoracic cavity.
A systematic review of patient access to medical records in the acute setting: practicalities, perspectives and ethical consequences
Authors: D’Costa Stephanie N. , Kuhn Isla L. , Fritz Zoë
Published: March 2020

Background

Internationally, patient access to notes is increasing. This has been driven by respect for patient autonomy, often recognised as a primary tenet of medical ethics: patients should be able to access their records to be fully engaged with their care. While research has been conducted on the impact of patient access to outpatient and primary care records and to patient portals, there is no such review looking at access to hospital medical records in real time, nor an ethical analysis of the issues involved in such a change in process.

Methods

This study employed a systematic review framework in two stems, to integrate literature identified from two searches: Medline, CINAHL and Scopus databases were conducted, (for (1) hospitalised patients, patient access to records and its effects on communication and trust within the doctor-patient relationship; and (2) patient access to medical records and the ethical implications identified). The qualitative and quantitative results of both searches were integrated and critically analysed.

Results

3954 empirical and 4929 ethical studies were identified; 18 papers representing 16 studies were identified for review (12 empirical and 6 ethical). The review reveals a consensus that our current approach to giving information to patients – almost exclusively verbally – is insufficient; that patient access to notes is a welcome next step for patient-centred care, but that simply allowing full access, without explanation or summary, is also insufficient. Several ethical implications need to be considered: increased information could improve patient trust and knowledge but might transfer an (unwelcome) sense of responsibility to patients; doctors and patients have conflicting views on how much information should be shared and when; sharing written information might increase the already significant disparity in access to health care, and have unforeseen opportunity costs. The impact on medical practice of sharing notes in real time will also need to be evaluated.

Conclusions

The review presents encouraging data to support patient access to medical notes. However, sharing information is a critical part of clinical practice; changing how it is done could have significant empirical and ethical impacts; any changes should be carefully evaluated.
Costs and economic evaluations of Quality Improvement Collaboratives in healthcare: a systematic review
Authors: de la Perrelle Lenore , Radisic Gorjana , Cations Monica , Kaambwa Billingsley , Barbery Gaery , Laver Kate
Published: March 2020

Background

In increasingly constrained healthcare budgets worldwide, efforts to improve quality and reduce costs are vital. Quality Improvement Collaboratives (QICs) are often used in healthcare settings to implement proven clinical interventions within local and national programs. The cost of this method of implementation, however, is cited as a barrier to use. This systematic review aims to identify and describe studies reporting on costs and cost-effectiveness of QICs when used to implement clinical guidelines in healthcare.

Methods

Multiple databases (CINAHL, MEDLINE, PsycINFO, EMBASE, EconLit and ProQuest) were searched for economic evaluations or cost studies of QICs in healthcare. Studies were included if they reported on economic evaluations or costs of QICs. Two authors independently reviewed citations and full text papers. Key characteristics of eligible studies were extracted, and their quality assessed against the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Evers CHEC-List was used for full economic evaluations. Cost-effectiveness findings were interpreted through the Johanna Briggs Institute ‘three by three dominance matrix tool’ to guide conclusions. Currencies were converted to United States dollars for 2018 using OECD and World Bank databases.

Results

Few studies reported on costs or economic evaluations of QICs despite their use in healthcare. Eight studies across multiple healthcare settings in acute and long-term care, community addiction treatment and chronic disease management were included. Five were considered good quality and favoured the establishment of QICs as cost-effective implementation methods. The cost savings to the healthcare setting identified in these studies outweighed the cost of the collaborative itself.

Conclusions

Potential cost savings to the health care system in both acute and chronic conditions may be possible by applying QICs at scale. However, variations in effectiveness, costs and elements of the method within studies, indicated that caution is needed. Consistent identification of costs and description of the elements applied in QICs would better inform decisions for their use and may reduce perceived barriers. Lack of studies with negative findings may have been due to publication bias. Future research should include economic evaluations with societal perspectives of costs and savings and the cost-effectiveness of elements of QICs.

Trial registration

PROSPERO registration number:CRD42018107417.
Patient satisfaction and survey response in 717 hospital surveys in Switzerland: a cross-sectional study
Authors: Perneger Thomas V. , Peytremann-Bridevaux Isabelle , Combescure Christophe
Published: March 2020

Background

The association between patient satisfaction and survey response is only partly understood. In this study, we describe the association between average satisfaction and survey response rate across hospital surveys, and model the association between satisfaction and propensity to respond for individual patients.

Methods

Secondary analysis of patient responses (166′014 respondents) and of average satisfaction scores and response rates obtained in 717 annual patient satisfaction surveys conducted between 2011 and 2015 at 164 Swiss hospitals. The satisfaction score was the average of 5 items scored between 0 and 10. The association between satisfaction and response propensity in individuals was modeled as the function that predicted best the observed response rates across surveys.

Results

Among the 717 surveys, response rates ranged from 16.1 to 80.0% (pooled average 49.8%), and average satisfaction scores ranged from 8.36 to 9.79 (pooled mean 9.15). At the survey level, the mean satisfaction score and response rate were correlated (r = 0.61). This correlation held for all subgroups of surveys, except for the 5 large university hospitals. The estimated individual response propensity function was “J-shaped”: the probability of responding was lowest (around 20%) for satisfaction scores between 3 and 7, increased sharply to about 70% for those maximally satisfied, and increased slightly for the least satisfied. Average satisfaction scores projected for 100% participation were lower than observed average scores.

Conclusions

The most satisfied patients were the most likely to participate in a post-hospitalization satisfaction survey. This tendency produces an upward bias in observed satisfaction scores, and a positive correlation between average satisfaction and response rate across surveys.
Contaminant DNA in bacterial sequencing experiments is a major source of false genetic variability
Authors: Goig Galo A. , Blanco Silvia , Garcia-Basteiro Alberto L. , Comas Iñaki
Published: March 2020

Background

Contaminant DNA is a well-known confounding factor in molecular biology and in genomic repositories. Strikingly, analysis workflows for whole-genome sequencing (WGS) data commonly do not account for errors potentially introduced by contamination, which could lead to the wrong assessment of allele frequency both in basic and clinical research.

Results

We used a taxonomic filter to remove contaminant reads from more than 4000 bacterial samples from 20 different studies and performed a comprehensive evaluation of the extent and impact of contaminant DNA in WGS. We found that contamination is pervasive and can introduce large biases in variant analysis. We showed that these biases can result in hundreds of false positive and negative SNPs, even for samples with slight contamination. Studies investigating complex biological traits from sequencing data can be completely biased if contamination is neglected during the bioinformatic analysis, and we demonstrate that removing contaminant reads with a taxonomic classifier permits more accurate variant calling. We used both real and simulated data to evaluate and implement reliable, contamination-aware analysis pipelines.

Conclusion

As sequencing technologies consolidate as precision tools that are increasingly adopted in the research and clinical context, our results urge for the implementation of contamination-aware analysis pipelines. Taxonomic classifiers are a powerful tool to implement such pipelines.
Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling
Authors: Lin Yueh-Te , Wu Kou-Juey
Published: March 2020

Epithelial-mesenchymal transition (EMT) is an important process triggered during cancer metastasis. Regulation of EMT is mostly initiated by outside signalling, including TGF-β, growth factors, Notch ligand, Wnt, and hypoxia. Many signalling pathways have been delineated to explain the molecular mechanisms of EMT. In this review, we will focus on the epigenetic regulation of two critical EMT signalling pathways: hypoxia and TGF-β. For hypoxia, hypoxia-induced EMT is mediated by the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5 coupled with the presence of histone 3 lysine 4 acetylation (H3K4Ac) mark that labels the promoter regions of various traditional EMT marker genes (e.g. CDH1, VIM). Recently identified new hypoxia-induced EMT markers belong to transcription factors (e.g. SMO, GLI1) that mediate EMT themselves. For TGF-β-induced ΕΜΤ, global chromatin changes, removal of a histone variant (H2A.Z), and new chromatin modifiers (e.g. UTX, Rad21, PRMT5, RbBP5, etc) are identified to be crucial for the regulation of both EMT transcription factors (EMT-TFs) and EMT markers (EMT-Ms). The epigenetic mechanisms utilized in these two pathways may serve as good model systems for other signalling pathways and also provide new potential therapeutic targets.
Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide
Authors: Li Tengfei , Yang Wanchun , Li Mao , Zhang Shuxin , Zhou Xingwang , Zuo Mingrong , Yuan Qiuyun , Chen Mina , Liu Yanhui
Published: March 2020

Background

Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that Engrailed-2 (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear.

Methods

Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion.

Results

We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells.

Conclusions

Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.
Clinical outcomes of chondroblastoma treated using synthetic bone substitute: risk factors for developing radiographic joint degeneration
Authors: Outani Hidetatsu , Kakunaga Shigeki , Hamada Kenichiro , Takenaka Satoshi , Nakai Sho , Yasuda Naohiro , Imura Yoshinori , Naka Norifumi , Araki Nobuhito , Ueda Takafumi , Yoshikawa Hideki
Published: March 2020

Background

Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB.

Methods

We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. Clinical data, radiographic images, treatments, and local recurrence were analyzed.

Results

We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8–35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13–239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004).

Conclusions

Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.
Tissue microRNAs in non-small cell lung cancer detected with a new kind of liquid bead array detection system
Authors: Zheng Yuan-Yuan , Fei Yun , Wang Zheng , Chen Yue , Qiu Cheng , Li Fu-Rong
Published: March 2020

Background

Commonly used miRNA detection methods cannot be applied for high-throughput analyses. However, this study was aimed to performed a liquid bead array detection system (LBAS) to detect tissue 6 miRNAs in non-small cell lung cancer (NSCLC).

Methods

In this study, evaluation of LBAS was performed to observe the precision, specificity, limitation and stability. Then, a total of 52 primary NSCLC patients who received resection operation without preoperative radiotherapy and chemotherapy between June 2013 and March 2014 were selected, and then the total RNA of the tissues were extracted. We prepared six NSCLC-related miRNAs for LBAS. After optimization and evaluation, LBAS was verified by detecting the relative expression levels of 6 microRNAs in the pathological tissues and corresponding normal tissues of 52 NSCLC patients.

Results

The results of evaluation of LBAS showed that the Mean Fluorescence Intensity (MFI) of the reaction only added with chimeric probes and beads showed no significant change after 180 days (P > 0.05). And the intra-assay Coefficient of Variation (CV) was between 1.57 and 3.5%, while the inter-assay CV was between 4.24 and 11.27%, indicating this system was ideal for diagnostic reagents. In addition, only the beads corresponding to the additional miRNAs showed high MFIs from 8426 to 18,769, whereas the fluorescence values of the other beads were under background levels (MFIs = 20 to 55) in each reaction, indicating no cross reactivity among the miRNAs. The limit of detection of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 were 5.27, 1.39, 1.85, 2.01, 1.34, and 2.73 amol/μL, respectively, showing that the lowest detection limit of miRNA by this system was under pM level. Then, the relative expression levels of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 by using this system were significantly correlated with NSCLC (P < 0.05). And the results of AUC method indicated that specific of the LBAS system was 94.2%.

Conclusions

Our findings suggest that LBAS was simple, high-throughput, and freely combined with absolute quantification. Thus, this system could be applied for tumor miRNAs detection.
Design, synthesis, and biological evaluation of a multifunctional neuropeptide-Y conjugate for selective nuclear delivery of radiolanthanides
Authors: Chastel Adrien , Worm Dennis J. , Alves Isabel D. , Vimont Delphine , Petrel Melina , Fernandez Samantha , Garrigue Philippe , Fernandez Philippe , Hindié Elif , Beck-Sickinger Annette G. , Morgat Clément
Published: March 2020

Background

Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (161Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like 161Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y1 receptor (hY1R).

By using solid-phase peptide synthesis, the hY1R-preferring [F7,P34]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (natTb), as surrogate for 161Tb, or with indium-111 (111In).

Results

[natTb]Tb-pb12 showed a preserved high binding affinity to endogenous hY1R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY1R-preferring [F7,P34]-NPY. Specific internalization of the 111In-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of 111In was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [111In]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point.

Conclusion

The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide.
Modelling movement and stage-specific habitat preferences of a polyphagous insect pest
Authors: Garcia Adriano G. , Godoy Wesley A. C. , Cônsoli Fernando L. , Ferreira Claudia P.
Published: March 2020

Background

The feeding preferences of Diabrotica speciosa (Coleoptera: Chrysomelidae) cause a parent-offspring conflict, as providing the best host for the offspring development is detrimental to adult survival and fecundity. Understanding the implications of this conflict could help entomologists to implement pest-management programs. With this in mind, the foraging behaviour of D. speciosa was investigated using an individual-based model in two distinct scenarios.

Methods

In an intercropping scenario, parent-offspring conflict was simulated when adult insects exploit two crops (corn and soybean) that provide different nutritional advantages for each insect stage. First, we compared three hypothetical types of adult dispersal, considering a continuous oviposition over time: diffusion, attracted to a fixed host and alternating the preference between hosts with frequency $\frac {1}{\tau }$1τ, where τ is the time in days spent foraging for each host. We also simulated two principles: “mother knows best” (adult females foraging for corn during the oviposition period) and “optimal bad motherhood” (adult females remain foraging for soybean to maximise their own fitness during the oviposition period), but considering the existence of a pre-oviposition period. In a landscape scenario, we investigated the population dynamics in an area composed by 4 crop plots that change over time.

Results

Among dispersal types considering continuous oviposition, the crop-alternating movement a-3 performed best, when close to an optimal τ. Additionally, τ was predicted to be influenced mainly by the width of crop rows. We also verified that the “mother knows best” strategy is better for the population growth than the “optimal bad motherhood”. In the landscape scenario, we observed that including fallow periods in the crop calendar and adopting a more-heterogeneous arrangement of crop plots reduced the density of this insect.

Conclusion

Both the continuous and sequential oviposition simulations indicate that foraging involving switching of target crop benefits population fitness. In the landscape scenario, arranging crop plots more heterogeneously and avoiding vast areas of soybean can help farmers to control this insect pest. Additionally, fallow periods can also reduce significantly D. speciosa populations.
Effect of crocin on antioxidant gene expression, fibrinolytic parameters, redox status and blood biochemistry in nicotinamide-streptozotocin-induced diabetic rats
Authors: Margaritis Ioannis , Angelopoulou Katerina , Lavrentiadou Sophia , Mavrovouniotis Ilias C. , Tsantarliotou Maria , Taitzoglou Ioannis , Theodoridis Alexandros , Veskoukis Aristidis , Kerasioti Efthalia , Kouretas Dimitrios , Zervos Ioannis
Published: March 2020

Background

Diabetes is regarded as an epidemiological threat for the twenty-first century. Phytochemicals with known pharmaceutical properties have gained interest in the field of alleviating secondary complications of diseases. Such a substance is crocin, a basic constituent of saffron (Crocus sativus). The present study aimed at examining the beneficial effects of per os crocin administration on the antioxidant status, blood biochemical profile, hepatic gene expression and plasminogen activator inhibitor-1 activity (PAI-1) in the liver, kidney and plasma (an important marker of pre-diabetic status and major factor of thrombosis in diabetes) of healthy rats, as well as of rats with nicotinamide-streptozotocin-induced diabetes.

Results

Diabetes disrupted the oxidation-antioxidation balance, while crocin improved the antioxidant state in the liver by significantly affecting SOD1 gene expression and/or by restoring SOD and total antioxidant capacity (TAC) levels. In the kidney, crocin improved hydrogen peroxide decomposing activity and TAC. In blood, hepatic transaminases ALT and AST decreased significantly, while there was a trend of decrease regarding blood urea nitrogen (BUN) levels. The expression of PAI-1 gene was affected in the liver by the dose of 50 mg kg−1.

Conclusions

Crocin treatment contributed in restoring some parameters after diabetes induction, primarily by affecting significantly hepatic transaminases ALT and AST, SOD1 and PAI-1 gene expression and nephric H2O2 decomposing activity. In conclusion, crocin did contribute to the alleviation of some complications of diabetes.