bluuebunny/crossref_metadata_2025 huggingface dataset:
Bending, shear, and compressive properties of three- and five-layer cross-laminated timber fabricated with black spruce
Authors: He Minjuan , Sun Xiaofeng , Li Zheng , Feng Wei
Published: May 2020

Cross-laminated timber (CLT) is an innovative engineering wood product made by gluing layers of solid-sawn lumber at perpendicular angles. The commonly used wood species for CLT manufacturing include spruce-pine-fir (SPF), douglas fir-larch, and southern pine lumber. With the hope of broadening the wood species for CLT manufacturing, the purposes of this study include evaluating the mechanical properties of black spruce CLT and analyzing the influence of CLT thickness on its bending or shear properties. In this paper, bending, shear, and compressive tests were conducted respectively on 3-layer CLT panels with a thickness of 105 mm and on 5-layer CLT panels with a thickness of 155 mm, both of which were fabricated with No. 2-grade Canadian black spruce. Their bending or shear resisting properties as well as the failure modes were analyzed. Furthermore, comparison of mechanical properties was conducted between the black spruce CLT panels and the CLT panels fabricated with some other common wood species. Finally, for both the CLT bending panels and the CLT shear panels, their numerical models were developed and calibrated with the experimental results. For the CLT bending panels, results show that increasing the CLT thickness whilst maintaining identical span-to-thickness ratios can even slightly reduce the characteristic bending strength of the black spruce CLT. For the CLT shear panels, results show that increasing the CLT thickness whilst maintaining identical span-to-thickness ratios has little enhancement on their characteristic shear strength. For the CLT bending panels, their effective bending stiffness based on the Shear Analogy theory can be used as a more accurate prediction on their experiment-based global bending stiffness. The model of the CLT bending specimens is capable of predicting their bending properties; whereas, the model of the CLT shear specimens would underestimate their ultimate shear resisting capacity due to the absence of the rolling shear mechanism in the model, although the elastic stiffness can be predicted accurately. Overall, it is attested that the black spruce CLT can provide ideal bending or shear properties, which can be comparable to those of the CLT fabricated with other commonly used wood species. Besides, further efforts should focus on developing a numerical model that can consider the influence of the rolling shear mechanism.
Persistence of pregabalin treatment in Taiwan: a nation-wide population-based study
Authors: Wang Yen-Feng , Chen Yung-Tai , Tsai Ching-Wen , Yen Yu-Chun , Chen Yi-Chun , Shia Ben-Chang , Wang Shuu-Jiun
Published: May 2020

Background

Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored.

Methods

This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis.

Results

Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7 ± 15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥ 300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14–118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09–1.18), older age (OR 1.01 per year, 95% CI 1.01–1.01), indications other than PHN, especially epilepsy (OR 8.04, 95% CI 7.33–8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI = 1.10–1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35–0.47).

Conclusions

Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was frequently below the recommended ranges. Potential causes included the duration of natural history of PHN, and off-label prescriptions for pain in acute herpes zoster, rather than PHN, as well as intolerance to the side effects.
Uncovering the prognostic gene signatures for the improvement of risk stratification in cancers by using deep learning algorithm coupled with wavelet transform
Authors: Zhao Yiru , Zhou Yifan , Liu Yuan , Hao Yinyi , Li Menglong , Pu Xuemei , Li Chuan , Wen Zhining
Published: May 2020

Background

The aim of gene expression-based clinical modelling in tumorigenesis is not only to accurately predict the clinical endpoints, but also to reveal the genome characteristics for downstream analysis for the purpose of understanding the mechanisms of cancers. Most of the conventional machine learning methods involved a gene filtering step, in which tens of thousands of genes were firstly filtered based on the gene expression levels by a statistical method with an arbitrary cutoff. Although gene filtering procedure helps to reduce the feature dimension and avoid overfitting, there is a risk that some pathogenic genes important to the disease will be ignored.

Results

In this study, we proposed a novel deep learning approach by combining a convolutional neural network with stationary wavelet transform (SWT-CNN) for stratifying cancer patients and predicting their clinical outcomes without gene filtering based on tumor genomic profiles. The proposed SWT-CNN overperformed the state-of-art algorithms, including support vector machine (SVM) and logistic regression (LR), and produced comparable prediction performance to random forest (RF). Furthermore, for all the cancer types, we firstly proposed a method to weight the genes with the scores, which took advantage of the representative features in the hidden layer of convolutional neural network, and then selected the prognostic genes for the Cox proportional-hazards regression. The results showed that risk stratifications can be effectively improved by using the identified prognostic genes as feature, indicating that the representative features generated by SWT-CNN can well correlate the genes with prognostic risk in cancers and be helpful for selecting the prognostic gene signatures.

Conclusions

Our results indicated that gene expression-based SWT-CNN model can be an excellent tool for stratifying the prognostic risk for cancer patients. In addition, the representative features of SWT-CNN were validated to be useful for evaluating the importance of the genes in the risk stratification and can be further used to identify the prognostic gene signatures.
Direct comparison shows that mRNA-based diagnostics incorporate information which cannot be learned directly from genomic mutations
Authors: Ravkin Hersh D. , Givton Ofer , Geffen David B. , Rubin Eitan
Published: May 2020

Background

Compared to the many uses of DNA-level testing in clinical oncology, development of RNA-based diagnostics has been more limited. An exception to this trend is the growing use of mRNA-based methods in early-stage breast cancer. Although DNA and mRNA are used together in breast cancer research, the distinct contribution of mRNA beyond that of DNA in clinical challenges has not yet been directly assessed. We hypothesize that mRNA harbors prognostically useful information independently of genomic variation. To validate this, we use both genomic mutations and gene expression to predict five-year breast cancer recurrence in an integrated test model. This is accomplished first by comparing the feature importance of DNA and mRNA features in a model trained on both, and second, by evaluating the difference in performance of models trained on DNA and mRNA data separately.

Results

We find that models trained on DNA and mRNA data give more weight to mRNA features than to DNA features, and models trained only on mRNA outperform models trained on DNA alone.

Conclusions

The evaluation process presented here may serve as a framework for the interpretation of the relative contribution of individual molecular markers. It also suggests that mRNA has a distinct contribution in a diagnostic setting, beyond and independently of DNA mutation data.
Transposable element persistence via potential genome-level ecosystem engineering
Authors: Kremer Stefan C. , Linquist Stefan , Saylor Brent , Elliott Tyler A. , Gregory T. Ryan , Cottenie Karl
Published: May 2020

Background

The nuclear genomes of eukaryotes vary enormously in size, with much of this variability attributable to differential accumulation of transposable elements (TEs). To date, the precise evolutionary and ecological conditions influencing TE accumulation remain poorly understood. Most previous attempts to identify these conditions have focused on evolutionary processes occurring at the host organism level, whereas we explore a TE ecology explanation.

Results

As an alternative (or additional) hypothesis, we propose that ecological mechanisms occurring within the host cell may contribute to patterns of TE accumulation. To test this idea, we conducted a series of experiments using a simulated asexual TE/host system. Each experiment tracked the accumulation rate for a given type of TE within a particular host genome. TEs in this system had a net deleterious effect on host fitness, which did not change over the course of experiments. As one might expect, in the majority of experiments TEs were either purged from the genome or drove the host population to extinction. However, in an intriguing handful of cases, TEs co-existed with hosts and accumulated to very large numbers. This tended to occur when TEs achieved a stable density relative to non-TE sequences in the genome (as opposed to reaching any particular absolute number). In our model, the only way to maintain a stable density was for TEs to generate new, inactive copies at a rate that balanced with the production of active (replicating) copies.

Conclusions

From a TE ecology perspective, we suggest this could be interpreted as a case of ecosystem engineering within the genome, where TEs persist by creating their own “habitat”.
Uncovering the role of Symbiodiniaceae assemblage composition and abundance in coral bleaching response by minimizing sampling and evolutionary biases
Authors: Swain Timothy D. , Lax Simon , Backman Vadim , Marcelino Luisa A.
Published: May 2020

Background

Biodiversity and productivity of coral-reef ecosystems depend upon reef-building corals and their associations with endosymbiotic Symbiodiniaceae,which offer diverse functional capabilities to their hosts. The number of unique symbiotic partners (richness) and relative abundances (evenness) have been hypothesized to affect host response to climate change induced thermal stress. Symbiodiniaceae assemblages with many unique phylotypes may provide greater physiological flexibility or form less stable symbioses; assemblages with low abundance phylotypes may allow corals to retain thermotolerant symbionts or represent associations with less-suitable symbionts.

Results

Here we demonstrate that true richness of Symbiodiniaceae phylotype assemblages is generally not discoverable from direct enumeration of unique phylotypes in association records and that cross host-species comparisons are biased by sampling and evolutionary patterns among species. These biases can be minimized through rarefaction of richness (rarefied-richness) and evenness (Probability of Interspecific Encounter, PIE), and analyses that account for phylogenetic patterns. These standardized metrics were calculated for individual Symbiodiniaceae assemblages composed of 377 uniqueITS2phylotypes associated with 123 coral species. Rarefied-richness minimized correlations with sampling effort, while maintaining important underlying characteristics across host bathymetry and geography. Phylogenetic comparative methods reveal significant increases in coral bleaching and mortality associated with increasing Symbiodiniaceae assemblage richness and evenness at the level of host species.

Conclusions

These results indicate that the potential flexibility afforded by assemblages characterized by many phylotypes present at similar relative abundances does not result in decreased bleaching risk and point to the need to characterize the overall functional and genetic diversity of Symbiodiniaceae assemblages to quantify their effect on host fitness under climate change.
A novel gene expression system for Ralstonia eutropha based on the T7 promoter
Authors: Hu Muzi , Xiong Bin , Li Zhongkang , Liu Li , Li Siwei , Zhang Chunzhi , Zhang Xueli , Bi Changhao
Published: May 2020

Background

Ralstonia eutropha (syn. Cupriavidus necator) is a model microorganism for studying metabolism of polyhydroxyalkanoates (PHAs) and a potential chassis for protein expression due to various advantages. Although current plasmid systems of R. eutropha provide a basic platform for gene expression, the performance of the expression-inducing systems is still limited. In addition, the sizes of the cloned genes are limited due to the large sizes of the plasmid backbones.

Results

In this study, an R. eutropha T7 expression system was established by integrating a T7 RNA polymerase gene driven by the PBAD promoter into the genome of R. eutropha, as well as adding a T7 promoter into a pBBR1-derived plasmid for gene expression. In addition, the essential DNA sequence necessary for pBBR1 plasmid replication was identified, and the redundant parts were deleted reducing the expression plasmid size to 3392 bp, which improved the electroporation efficiency about 4 times. As a result, the highest expression level of RFP was enhanced, and the L-arabinose concentration for expression induction was decreased 20 times.

Conclusions

The R. eutropha T7 expression system provides an efficient platform for protein production and synthetic biology applications.
Viral metagenomic analysis of fecal samples reveals an enteric virome signature in irritable bowel syndrome
Authors: Ansari Mina Hojat , Ebrahimi Mehregan , Fattahi Mohammad Reza , Gardner Michael G. , Safarpour Ali Reza , Faghihi Mohammad Ali , Lankarani Kamran Bagheri
Published: May 2020

Background

Changes in the enteric microbiota have been suggested to contribute to gastrointestinal diseases, including irritable bowel syndrome. Most of the published work is on bacterial dysbiosis with meager data on the role of the virome in irritable bowel syndrome and other gastrointestinal diseases. In the current study, we therefore aimed to investigate the viral community composition of the gut and test for potential dysbiosis linked to irritable bowel syndrome.

Results

A metagenomics analysis on fecal samples of 50 individuals — 30 of whom met the Rome IV criteria for IBS and 20 healthy controls— was conducted. There was a noticeable alteration in viral taxa observed in association with irritable bowel syndrome when compared to healthy individuals — where some eukaryotic viral taxa noticeably prevail over others. We observed a significant decrease in the diversity and abundance of enteric virome particularly in eukaryotic viruses of Megavirales in patients with irritable bowel syndrome.

Conclusions

These findings shed light on a new hypothesis that the alteration of the viral taxa contributes to the pathogenesis of irritable bowel syndrome and related symptoms, and therefore, pave the way for developing a new diagnostic biomarker or anti-viral drugs for the treatment of irritable bowel syndrome.
Troponin I as a mortality marker after lung resection surgery – a prospective cohort study
Authors: Uchoa Ricardo B. , Caramelli Bruno
Published: May 2020

Background

Cardiovascular complications associated with thoracic surgery increase morbidity, mortality, and treatment costs. Elevated cardiac troponin level represents a predictor of complications after non-cardiac surgeries, but its role after thoracic surgeries remains undetermined. The objective of this study was to analyze the relationship between troponin I elevation and morbidity and mortality after one year in patients undergoing lung resection surgery.

Methods

This prospective cohort study evaluated 151 consecutive patients subjected to elective lung resection procedures using conventional and video-assisted thoracoscopic techniques at a University Hospital in Brazil, from July 2012 to November 2015. Preoperative risk stratification was performed using the scores obtained by the American College of Physicians (ACP) and the Society of Cardiology of the state of São Paulo (EMAPO) scoring systems. Troponin I levels were measured in the immediate postoperative period (POi) and on the first and second postoperative days.

Results

Most patients had a low risk for complications according to the ACP (96.7%) and EMAPO (82.8%) scores. Approximately 49% of the patients exhibited increased troponin I (≥0.16 ng/ml), at least once, and 22 (14.6%) died in one year. Multivariate analysis showed that the elevation of troponin I, on the first postoperative day, correlated with a 12-fold increase in mortality risk within one year (HR 12.02, 95% CI: 1.82–79.5; p = 0.01).

Conclusions

In patients undergoing lung resection surgery, with a low risk of complications according to the preoperative evaluation scores, an increase in troponin I levels above 0.16 ng/ml in the first postoperative period correlated with an increase in mortality within one year.
Pharmacological management of modifiable cardiovascular risk factors (blood pressure and lipids) following diagnosis of myocardial infarction, stroke and diabetes: comparison between population-based studies in Russia and Norway
Authors: Cook Sarah , Hopstock Laila A. , Eggen Anne Elise , Bates Katie , Iakunchykova Olena , Kontsevaya Anna , McKee Martin , Schirmer Henrik , Voevoda Michael , Kudryavtsev Alexander V. , Malyutina Sofia , Leon David A.
Published: May 2020

Background

Cardiovascular disease (CVD) mortality is substantially higher in Russia than in neighbouring Norway. We aimed to compare blood pressure- and lipid-lowering medication use and proportion meeting treatment targets between general population samples in the two countries in those with CVD and diabetes.

Methods

The study population was adults aged 40–69 years reporting a diagnosis of myocardial infarction (MI), stroke and/or diabetes participating in cross-sectional population-based studies in Russia (Know Your Heart (KYH) 2015–18 N = 626) and Norway (The Tromsø Study 2015–16 (Tromsø 7) N = 1353). Reported medications were coded according to the 2016 WHO Anatomical Therapeutic Chemical Classification system. Treatment targets were defined using the Joint European Societies guidelines for CVD prevention in clinical practice (2016).

Results

Age- and sex-standardized prevalence of use of lipid-lowering medications was higher in Tromsø 7 for all three conditions with a disproportionately large difference in those reporting MI (+ 48% (95% CI 39, 57%)). Proportion meeting treatment targets for LDL cholesterol was poor in both studies (age- and sex-standardized prevalence of control KYH vs Tromsø 7: MI 5.1% vs 10.1%; stroke 11.6% vs 5.8%; diabetes 24.9% vs 23.3%). Use of antihypertensive medication was higher in KYH for stroke (+ 40% (95% CI 30, 50%)) and diabetes (+ 27% (95% CI 19, 34%)) groups but approximately equal for the MI group (− 1% (95% CI -1, 1%)). Proportion meeting blood pressure targets was lower in KYH vs Tromsø 7 (MI 51.8% vs 76.3%; stroke 49.5% vs 69.6%; diabetes 51.9% vs 63.9%).

Conclusions

We identified different patterns of medication use in people with CVD and diabetes. However despite higher use of lipid-lowering medication in the Norwegian study treatment to target for total cholesterol was poor in both Russian and Norwegian studies. In contrast we found higher levels of use of antihypertensive medications in the Russian study but also that less participants met treatment targets for blood pressure. Further work should investigate what factors are responsible for this seeming paradox and how management of modifiable risk factors for secondary prevention could be improved.
Burden and correlates of atrial fibrillation among hypertensive patients attending a tertiary hospital in Tanzania
Authors: Bhalia Smita , Pallangyo Pedro , Dalidali Abuu , Salum Saada , Kawajika Richard , Kajuna Edna , Kusiima Happiness , Kifai Engerasiya , Kisenge Peter , Waane Tatizo , Janabi Mohamed
Published: May 2020

Background

Atrial fibrillation (AF) is the most common supra ventricular cardiac arrhythmia, which presents with variety of clinical symptoms. Hypertension increases risk of developing Atrial fibrillation by 1.5 fold. Together Atrial fibrillation and hypertension doubles the risk of morbidity and mortality. We aimed to determine the prevalence of AF and describe associated factors among hypertensive patients attending tertiary hospital in Tanzania.

Methods

A cross-sectional hospital-based study, involving 391 hypertensive patients visiting the Jakaya Kikwete Cardiac Institute was conducted between October to December 2017. Categorical variables were analyzed using chi square while student t- test was used to analyze continuous variables. Multivariate logistic regression analysis was performed to determine factors associated with AF. All analysis was two sided and p- value of < 0.05 was used to be not significant.

Results

AF was detected in 40 (10.2%) patients. Atrial fibrillation was associated with BMI ≥ 25 (OR 4.4, 95% CI 1.1–7.7,p-value 0.02), ejection fraction < 50% (OR 3.0, 95%CI 1.1–8.2, p-value 0.03), Left Atrial diameter > 40 mm (OR 9.4,95%CI 2.1–43.2, p-value < 0.01) and eGFR< 60 (OR 2.9, 95%CI 1.1–7.8, p-value 0.04).

Conclusion

Atrial fibrillation is considerably prevalent among the hypertensive sub-population. Prompt diagnosis and timely management is vital to prevent complications and premature mortality.
Potential impacts of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline on Chinese adults and how to address them
Authors: Jiao Yundi , Sun Zhaoqing , Xie Yanxia , Zheng Jia , Li Zhao , Guo Xiaofan , Dai Yue , Zheng Liqiang , Sun Yingxian
Published: May 2020

Background

The current analysis was performed to estimate the percentage and number of Chinese adults with hypertension and the percentage and number of Chinese adults recommended to receive pharmacological antihypertensive treatment according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline compared with the same parameters according to the 2010 Chinese guideline.

Methods

We used 2011 data from the China Health and Nutrition Survey (CHNS). A total of 12,499 Chinese adults aged ≥18 years with complete blood pressure (BP) values were selected for the present analysis.

Results

The crude prevalence rates (95% CI) of hypertension according to the definitions from the 2017 ACC/AHA guideline and the 2010 Chinese guideline were 58.0% (57.2 to 58.9%) and 25.4% (24.7 to 26.2%), respectively. Moreover, the percentage of the participants recommended to take antihypertensive medications were 31.5 and 28.8%, respectively. Among adults who took antihypertensive medications, 88.8% had above-goal BP levels compared to 53.3%. Overall, 613.3 million Chinese adults (aged ≥18 years) met the criteria for hypertension according to the 2017 ACC/AHA guideline, and 267.7 million met the criteria according to 2010 Chinese guideline. An additional 28.4 million (2.7%) Chinese adults were recommended to take antihypertensive medication.

Conclusions

The present analysis revealed that the 2017 ACC/AHA hypertension guideline will result in a substantial increase in the percentage and number of Chinese adults defined as having hypertension and a small increase in the percentage of adults who are recommended to take antihypertensive medications compared to the same parameters based on the 2010 Chinese guideline. More intensive management and antihypertensive medications use are suggested to improve the control rate of hypertension among Chinese adults.
Prevalence of self-reported coronary heart disease and its associated risk factors in Tabari cohort population
Authors: Ghaemian Ali , Nabati Maryam , Saeedi Majid , Kheradmand Motahareh , Moosazadeh Mahmood
Published: May 2020

Background

Prevalence of coronary heart disease (CHD) risk factors are increasing in developing countries. The present study aimed to assess the prevalence of self-reported CHD and evaluate the role of various risk factors on its prevalence in the Tabari cohort study (TCS) population.

Methods

The enrollment phase of TCS was performed between June 2015 and November 2017. In the current study, data were derived from information collecting from the enrollment phase of TCS. In the enrollment phase, 10,255 individuals aged 35–70 living in urban and mountainous areas of Sari (northern part of Iran) were entered into the study. Educational level, socioeconomic and marital status, history of smoking, opium and alcohol abuse/addiction, level of daily physical activity, indices of obesity, and traditional risk factors of the participants were determined.

Results

The prevalence of CHD was measured at 9.2%. Older individuals (P<0.001), people with a body mass index≥30kg/m2 (P<0.001), diabetics (P<0.001), and hypertensive (P<0.001) have been shown to have an increased risk for CHD compared with participants of without CHD. Furthermore, the CHD was more prevalent in individuals with higher waist circumference (P<0.001), higher low-density lipoprotein cholesterol (P<0.001), lower high-density lipoprotein cholesterol (P<0.001), and a higher waist to hip ratio (P<0.001). In addition, individuals with low socioeconomic status, illiterate people, and opium users had a higher prevalence of CHD (P<0.001). The results of the multivariable logistic regression analysis showed that the probability of CHD among individuals who had 8-10 risk factors was estimated at 8.41 (95% confidence interval: 5.75-12.31) times higher than those with less than 3 risk factors.

Conclusion

According to the results of the present study, it seems that the prevalence of CHD in the Iranian population is relatively high.
Frequently repeated measurements -our experience of collecting data with SMS
Authors: Axén I. , Jensen I. , Butler Forslund E. , Grahn B. , Jørgensen V. , Opava C. H. , Bodin L.
Published: May 2020

Background

As technology is advancing, so are the possibilities for new data collection methods in research, potentially improving data quality and validity of the results. In Sweden, a system using frequent repeated data collection using text messages, SMS Track, has been used in clinical research for more than a decade. In this paper, compliance with repeated text message questions was examined across five different studies, i.e. if compliance was

1: associated with study-specific factors (age or gender of the subjects, the condition, its’ severity or course, i.e. improvement, relapse or steady state) and/or.

2: associated with the methodology itself (the question being asked, the frequency and number of questions, duration of data collection, initial compliance or the management of the system).

Methods

Descriptive comparisons were done across five studies. Three studies were collecting weekly responses over at least 52 weeks (“Weekly studies”) and were used to investigate the effect of age, sex and pain severity on compliance, the effect of early compliance for late compliance, and finally the early occurrence of two successive weeks with non-compliance.

Result

Compliance was excellent across all five studies, and only influenced somewhat by age, sex and pain-level. The factor “study” remained significant in the final model thus the observed differences may be a result of the conditions studied but does not seem to be attributable to severity or development of these conditions. Number and frequency of questions did not influence compliance, nor did study duration.

Conclusions

Compliance was excellent in the included studies and was not affected by population factors. However, differences in compliance were observed that cannot be easily explained and warrant further investigation. In particular, the nature of the variables or the management of the study are potential areas for further investigations.
A randomized trial of mail and email recruitment strategies for a physician survey on clinical trial accrual
Authors: Murphy Caitlin C. , Craddock Lee Simon J. , Geiger Ann M. , Cox John V. , Ahn Chul , Nair Rasmi , Gerber David E. , Halm Ethan A. , McCallister Katharine , Skinner Celette Sugg
Published: May 2020

Background

Patient participation in cancer clinical trials is suboptimal. A challenge to capturing physicians’ insights about trials has been low response to surveys. We conducted a study using varying combinations of mail and email to recruit a nationally representative sample of medical, surgical, and radiation oncologists to complete a survey on trial accrual.

Methods

We randomly assigned eligible physicians identified from the American Medical Association MasterFile (n = 13,251) to mail- or email-based recruitment strategies. Mail-based recruitment included a survey packet with: (1) cover letter describing the survey and inviting participation; (2) paper copy of the survey and postage-paid return envelope; and (3) a web link for completing the survey online. Email-based recruitment included an e-mail describing the survey and inviting participation, along with the web link to the survey, and a reminder postcard 2 weeks later.

Results

Response was higher for mail-based (11.8, 95% CI 11.0–12.6%) vs. email-based (4.5, 95% CI 4.0–5.0%) recruitment. In email-based recruitment, only one-quarter of recipients opened the email, and even fewer clicked on the link to complete the survey. Most physicians in mail-based recruitment responded after the first invitation (362 of 770 responders, 47.0%). A higher proportion of responders vs. non-responders were young (ages 25–44 years), men, and radiation or surgical (vs. medical) oncologists.

Conclusions

Most physicians assigned to mail-based recruitment actually completed the survey online via the link provided in the cover letter, and those in email-based recruitment did not respond until they received a reminder postcard by mail. Providing the option to return a paper survey or complete it online may have further increased participation in the mail-based group, and future studies should examine how combinations of delivery mode and return options affect physicians’ response to surveys.
Caregiver strain on informal caregivers when providing care for older patients undergoing major abdominal surgery: a longitudinal prospective cohort study
Authors: Janssen T. L. , Lodder P. , de Vries J. , van Hoof – de Lepper C. C. H. A. , Gobardhan P. D. , Ho G. H. , van der Laan L.
Published: May 2020

Background

Health-care systems nowadays rely on complementary patient care by informal caregivers. The need for, and burden on, informal caregivers will likely increase in the upcoming years. This study aimed to examine the burden on caregivers when providing care for elderly patients undergoing major abdominal surgery.

Methods

A single-centre longitudinal cohort study was conducted between November 2015 and June 2018 in the Amphia hospital in Breda, the Netherlands. Patients aged 70+ undergoing elective surgery for colorectal carcinoma (CRC) or an abdominal aortic aneurysm (AAA) were included in this study. Informal caregiver burden was assessed and compared over time using the Caregiver Strain Index (CSI) at the outpatient clinic visit, at discharge, 2 weeks post-discharge and after 6 and 12 months. The effects of patient- and caregiver-related factors on the experienced caregiver strain were examined.

Results

CSI scores of 248 caregivers were significantly increased at discharge (3.5 vs 2.6;p < 0.001) and 2 weeks post-discharge (3.3 vs 2.6; p < 0.001). After 12 months, scores dropped below baseline scores (1.8 vs 2.6;p = 0.012). The highest strain was observed 2 weeks post-discharge for AAA patients and at discharge for CRC patients. Older age, physical or cognitive impairment and burden of comorbidity were associated with an increased caregiver strain at baseline. Type of surgery was independently associated with the change in mean CSI scores over time; a bigger change in caregiver burden is observed after open surgery.

Conclusion

In the early postoperative period, perceived caregiver strain was significantly increased. Psychological support for caregivers may be advisable, with timing of this support depending on diagnosis and patient-related factors.

Trial registration

This manuscript was retrospectively registered on 05-04-2016 in the Netherlands Trial Register (NTR5932).http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5932
Pathogen analysis of pertussis-like syndrome in children
Authors: Gu Wenjing , Wang Kun , Zhang Xinxing , Hao Chuangli , Lu Yanhong , Wu Min , Chen Sainan , He Yanyu , Xu Jun , Shao Xuejun , Wang Yuqing
Published: May 2020

Background

The aim of the study was to identify the pathogens, in addition to bordetella pertussis (B. pertussis), which cause pertussis-like syndrome in children and to compare clinical presentation between those with B. pertussis and pertussis-like syndrome.

Methods

A cross-sectional analysis was conducted from March 2016 to September 2018. In total, 281 children with suspected pertussis infections were enrolled in this study. Multi-pathogen detection was performed.

Results

In total, 281 children were enrolled including 139 males and 142 females. Among them, 149 (53.0%) were B. pertussis positive, and 72 (15.6%) children tested positive for other pathogens. Mycoplasma pneumoniae (MP, 27 cases) was the most common causative pathogen in pertussis-like syndrome, followed by human rhinovirus (HRV, 23 cases), Streptococcus pneumoniae (SP, 13 cases), Haemophilus influenzae (HI, 12 cases) and parainfluenza virus 3 (Pinf-3, 9 cases). Children in the B. pertussis group had a higher rate of vaccination and longer hospital stay (P < 0.05). B. pertussis was more likely to be detected in winter than other pathogens, but this difference was not significant (P = 0.074). The number of white blood cells, neutrophils and blood platelets was significantly higher in children in the B. pertussis than in the pertussis-like group (P < 0.05). In addition, the percentage of CD3-CD19+ cells was significantly higher in the B. pertussis group (P = 0.018).

Conclusion

About half of the children with pertussis-like syndrome were B. pertussis positive. MP was the second most common causative pathogen followed by HRV, SP, HI and Pinf-3. Children infected with B. pertussis had longer hospital stay and higher numbers of white blood cells, neutrophil and blood platelets compared with other pathogens.
Spontaneous community-acquired PVL-producing Staphylococcus aureus mediastinitis in an immunocompetent adult – a case report
Authors: Brisset Josselin , Daix Thomas , Tricard Jérémy , Evrard Bruno , Vignon Philippe , Barraud Olivier , François Bruno
Published: May 2020

Background

Mediastinitis caused by hematogenous spread of an infection is rare. We report the first known case of community-acquired mediastinitis from hematogenous origin in an immunocompetent adult. This rare invasive infection was due to Panton-Valentine Leucocidin-producing (PVL+) methicillin-susceptible Staphylococcus aureus (MSSA).

Case presentation

A 22-year-old obese man without other medical history was hospitalized for febrile precordial chest pain. He reported a cutaneous back abscess 3 weeks before. CT-scan was consistent with mediastinitis and blood cultures grew for a PVL+ MSSA. Intravenous clindamycin (600 mg t.i.d) and cloxacillin (2 g q.i.d.), secondary changed for fosfomycin (4 g q.i.d.) because of a related toxidermia, was administered. Surgical drainage was performed and confirmed the presence of a mediastinal abscess associated with a fistula between the mediastinum and right pleural space. All local bacteriological samples also grew for PVL+ MSSA. In addition to clindamycin, intravenous fosfomycin was switched to trimethoprim-sulfamethoxazole after 4 weeks for a total of 10 weeks of antibiotics.

Conclusions

We present the first community-acquired mediastinitis of hematogenous origin with PVL+ MSSA. Clinical evolution was favorable after surgical drainage and 10 weeks of antibiotics. The specific virulence of MSSA PVL+ strains played presumably a key role in this rare invasive clinical presentation.
The epidemiology of multiple sclerosis in the entre Douro e Vouga region of northern Portugal: a multisource population-based study
Authors: Branco Mariana , Alves Ivânia , Martins da Silva Ana , Pinheiro Joaquim , Sá Maria José , Correia Inês , Sousa Lívia , Brandão Eva , Veira Carlos , Gomes Bernardo , Ruano Luis
Published: May 2020

Background

The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the north–south gradient of prevalence may be disappearing in the Northern hemisphere. The few previous prevalence studies performed in Portugal have reported a lower prevalence than the average for Western Europe. The aim of this study is to estimate the prevalence of MS in the Entre Douro e Vouga region, in Northern Portugal.

Methods

Multiple overlapping sources were used to ascertain all cases from the reference population: records from hospitals in the region and neighbouring regions; diagnostic databases of primary care physicians; and applications for disability benefits. The prevalence date was set at 1 January 2014. The reference population was 274,859 inhabitants. Patients’ neurologists were contacted to retrieve clinical information and confirm the diagnosis based.

Results

A total of 177 patients were identified after eliminating duplicates from different sources. The female to male ratio was 1.9 and the mean age at disease onset was 33.5 (standard deviation: 10.3). Clinically isolated syndrome accounted for 9.0% of patients, relapsing remitting for 58.8%, secondary progressive for 20.3% and primary progressive for 11.8%. The prevalence was estimated in 64.4 patients per 100,000 (95% confidence interval: 54.9;73.9).

Conclusions

In this study we report a higher point prevalence of MS than had been previously described in Portugal, but still far from the higher values recently reported in other Southern European countries.
Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy
Authors: Leung Doris G. , Bocchieri Alex E. , Ahlawat Shivani , Jacobs Michael A. , Parekh Vishwa S. , Braverman Vladimir , Summerton Katherine , Mansour Jennifer , Bibat Genila , Morris Carl , Marraffino Shannon , Wagner Kathryn R.
Published: May 2020

Background

Pathogenic variants in the FKRP gene cause impaired glycosylation of α-dystroglycan in muscle, producing a limb-girdle muscular dystrophy with cardiomyopathy. Despite advances in understanding the pathophysiology of FKRP-associated myopathies, clinical research in the limb-girdle muscular dystrophies has been limited by the lack of normative biomarker data to gauge disease progression.

Methods

Participants in a phase 2 clinical trial were evaluated over a 4-month, untreated lead-in period to evaluate repeatability and to obtain normative data for timed function tests, strength tests, pulmonary function, and body composition using DEXA and whole-body MRI. Novel deep learning algorithms were used to analyze MRI scans and quantify muscle, fat, and intramuscular fat infiltration in the thighs. T-tests and signed rank tests were used to assess changes in these outcome measures.

Results

Nineteen participants were observed during the lead-in period for this trial. No significant changes were noted in the strength, pulmonary function, or body composition outcome measures over the 4-month observation period. One timed function measure, the 4-stair climb, showed a statistically significant difference over the observation period. Quantitative estimates of muscle, fat, and intramuscular fat infiltration from whole-body MRI corresponded significantly with DEXA estimates of body composition, strength, and timed function measures.

Conclusions

We describe normative data and repeatability performance for multiple physical function measures in an adult FKRP muscular dystrophy population. Our analysis indicates that deep learning algorithms can be used to quantify healthy and dystrophic muscle seen on whole-body imaging.

Trial registration

This study was retrospectively registered inclinicaltrials.gov(NCT02841267) on July 22, 2016 and data supporting this study has been submitted to this registry.
Ischemic stroke with a preceding Trans ischemic attack (TIA) less than 24 hours and thrombolytic therapy
Authors: Poupore Nicolas , Strat Dan , Mackey Tristan , Snell Ashley , Nathaniel Thomas
Published: May 2020

Background

Acute ischemic stroke attack with and without a recent TIA may differ in clinical risk factors, and this may affect treatment outcomes following thrombolytic therapy. We examined whether the odds of exclusion or inclusion for thrombolytic therapy are greater in ischemic stroke with TIA less than 24 h preceding ischemic stroke (recent-TIA) as compared to those without recent TIA or non-TIA > 24 h and less than 1 month (past-TIA).

Methods

A retrospective hospital-based analysis was conducted on 6315 ischemic stroke patients, of whom 846 had proven brain diffusion-weighted magnetic resonance imaging (DW-MRI) of an antecedent TIA within 24 h prior to ischemic stroke. The logistic regression model was developed to generate odds ratios (OR) to determine clinical factors that may increase the likelihood of exclusion or inclusion for thrombolytic therapy. The validity of the model was tested using a Hosmer-Lemeshow test, while the Receiver Operating Curve (ROC) was used to test the sensitivity of our model.

Results

In the recent-TIA ischemic stroke population, patients with a history of alcohol abuse (OR = 5.525, 95% CI, 1.003–30.434, p = 0.05), migraine (OR = 4.277, 95% CI, 1.095–16.703, p = 0.037), and increasing NIHSS score (OR = 1.156, 95% CI, 1.058–1.263, p = 0.001) were associated with the increasing odds of receiving rtPA, while older patients (OR = 0.965, 95% CI, 0.934–0.997, P = 0.033) were associated with the increasing odds of not receiving rtPA.

Conclusion

In recent-TIA ischemic stroke patients, older patients with higher INR values are associated with increasing odds of exclusion from thrombolytic therapy. Our findings demonstrate clinical risks factors that can be targeted to improve the use and eligibility for rtPA in in recent-TIA ischemic stroke patients.
CD73 blockade enhances the local and abscopal effects of radiotherapy in a murine rectal cancer model
Authors: Tsukui Hidenori , Horie Hisanaga , Koinuma Koji , Ohzawa Hideyuki , Sakuma Yasunaru , Hosoya Yoshinori , Yamaguchi Hironori , Yoshimura Kotaro , Lefor Alan Kawarai , Sata Naohiro , Kitayama Joji
Published: May 2020

Background

Anti-tumor effects of radiation therapy (RT) largely depend on host immune function. Adenosine with its strong immunosuppressive properties is an important immune checkpoint molecule.

Method

We examined how intra-tumoral adenosine levels modify anti-tumor effects of RT in a murine model using an anti-CD73 antibody which blocks the rate-limiting enzyme to produce extracellular adenosine. We also evaluated CD73 expression in irradiated human rectal cancer tissue.

Results

LuM-1, a highly metastatic murine colon cancer, expresses CD73 with significantly enhanced expression after RT. Subcutaneous (sc) transfer of LuM-1 in Balb/c mice developed macroscopic sc tumors and microscopic pulmonary metastases within 2 weeks. Adenosine levels in the sc tumor were increased after RT. Selective RT (4Gyx3) suppressed the growth of the irradiated sc tumor, but did not affect the growth of lung metastases which were shielded from RT. Intraperitoneal administration of anti-CD73 antibody (200 μg × 6) alone did not produce antitumor effects. However, when combined with RT in the same protocol, anti-CD73 antibody further delayed the growth of sc tumors and suppressed the development of lung metastases presumably through abscopal effects. Splenocytes derived from RT+ CD73 antibody treated mice showed enhanced IFN-γ production and cytotoxicity against LuM-1 compared to controls. Immunohistochemical studies of irradiated human rectal cancer showed that high expression of CD73 in remnant tumor cells and/or stroma is significantly associated with worse outcome.

Conclusion

These results suggest that adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.
Prognostic and diagnostic value of circRNA expression in colorectal carcinoma: a meta-analysis
Authors: Yuan Jinpeng , Guo Dongming , Li Xinxin , Chen Juntian
Published: May 2020

Background

Circular RNAs (circRNAs) are research hotspots in the network of noncoding RNAs in numerous tumours. The purpose of our study was to evaluate the clinicopathological, prognostic and diagnostic value of circRNAs in colorectal cancer.

Methods

The PubMed, Cochrane Library, and Web of Science online databases were searched for relevant studies before May 15, 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, and overall survival (OS) and clinical parameters. Pooled sensitivity, specificity, and the area under the curve (AUC) were employed to assess the diagnostic value of circRNAs.

Results

A total of 19 studies were enrolled in this meta-analysis, with 11 on clinicopathological parameters, 8 on prognosis and 7 on diagnosis. For clinicopathological and prognostic value, elevated expression of oncogenic circRNAs was correlated with poor clinical parameters (tumor size: OR = 1.769, 95% CI: 1.097–2.852; differentiation grade: OR = 1.743, 95% CI: 1.032–2.946; TNM stage: OR = 3.320, 95% CI: 1.529–7.207; T classification: OR = 3.410, 95% CI: 2.088–5.567; lymph node metastasis: OR = 3.357, 95% CI: 2.160–5.215; distal metastasis: OR = 4.338, 95% CI: 2.503–7.520) and worse prognosis (HR = 2.29, 95% CI: 1.50–3.52). However, elevated expression of tumor-suppressor circRNAs was correlated with better clinical parameters (differentiation grade: OR = 0.453, 95% CI: 0.261–0.787; T classification: OR = 0.553, 95% CI: 0.328–0.934; distal metastasis: OR = 0.196, 95% CI: 0.077–0.498) and favorable prognosis (HR = 0.37, 95% CI: 0.22–0.64). For diagnostic value, the pooled sensitivity, specificity, and AUC were 0.82 (95% CI, 0.75–0.88), 0.72 (95% CI, 0.66–0.78), and 0.82 (95% CI, 0.78–0.85), respectively.

Conclusions

These results indicate that circRNAs may be potential biomarkers for the diagnosis and prognosis of colorectal cancer.