bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of symptomatic spinal stenosis in Norwegian adults with achondroplasia: a population-based study
Authors: Fredwall Svein O. , Steen Unni , de Vries Olga , Rustad Cecilie F. , Eggesbø Heidi Beate , Weedon-Fekjær Harald , Lidal Ingeborg B. , Savarirayan Ravi , Månum Grethe 
Published: May 2020

AbstractBackgroundSymptomatic spinal stenosis (SSS) is a well-known medical complication in achondroplasia. The reported prevalence of SSS is 10 to 30%, an estimate based on small studies or selected populations. No population-based studies exist currently. Furthermore, the relationship between SSS and physical functioning has not been investigated in detail. The aims of this study were to describe the prevalence of SSS in Norwegian adults with achondroplasia, and to explore the impact of SSS on physical functioning.MethodsThis was a population-based study on Norwegian community-dwelling adults with genetically confirmed achondroplasia. Prevalence of SSS was defined by clinical symptoms, and confirmed by imaging or surgical reports. Physical functioning was assessed by walking capacity (6-min walk test), hand strength (Grippit), and activities of daily living (the Health Assessment Questionnaire, HAQ). Pain was assessed by pain site locations and intensity (Numeric Rating Scale, NRS).ResultsIn total, 50 participants were included (27 males, 23 females). Median age was 41 years (range 16 to 87 years), 34 (68%) had SSS. The estimated median age at first symptom onset was 33 years (95% confidence interval (CI) 29 to 43 years), range 10 to 67 years. The majority had multiple spinal levels affected. The walking distance was 110 m shorter in the SSS group (95% CI − 172 to − 40 m) as compared with the non-SSS group (p < 0.01). There was no considerable difference in hand strength between the two groups. Mean HAQ scores (0–3) for walking and hygiene were significantly higher in the SSS group, reflecting more activity limitations. Mean differences were 0.9 (95% CI 0.3 to 1.4,p < 0.01) and 0.6 (95% CI 0.2 to 1.0, p < 0.01). Pain intensity (NRS 0–10) was also significantly higher in the SSS group with a mean difference of 3.2 (95% CI 0.6 to 5.6,p = 0.02).ConclusionsSSS was highly prevalent in Norwegian adults with achondroplasia, with symptom onset at young age, and multiple spinal levels affected. The presence of SSS was associated with reduced walking distance, activity limitations, and more pain. The findings underline the importance of thorough assessment and monitoring of SSS in achondroplasia, including a formal assessment of physical functioning.
Accounting for cell type hierarchy in evaluating single cell RNA-seq clustering
Authors: Wu Zhijin , Wu Hao 
Published: May 2020

AbstractCell clustering is one of the most common routines in single cell RNA-seq data analyses, for which a number of specialized methods are available. The evaluation of these methods ignores an important biological characteristic that the structure for a population of cells is hierarchical, which could result in misleading evaluation results. In this work, we develop two new metrics that take into account the hierarchical structure of cell types. We illustrate the application of the new metrics in constructed examples as well as several real single cell datasets and show that they provide more biologically plausible results.
Personalized and graph genomes reveal missing signal in epigenomic data
Authors: Groza Cristian , Kwan Tony , Soranzo Nicole , Pastinen Tomi , Bourque Guillaume 
Published: May 2020

Abstract
Background
Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesize that using a generic reference could lead to incorrectly mapped reads and bias downstream results.

Results
We show that accounting for genetic variation using a modified reference genome or a de novo assembled genome can alter histone H3K4me1 and H3K27ac ChIP-seq peak calls either by creating new personal peaks or by the loss of reference peaks. Using permissive cutoffs, modified reference genomes are found to alter approximately 1% of peak calls while de novo assembled genomes alter up to 5% of peaks. We also show statistically significant differences in the amount of reads observed in regions associated with the new, altered, and unchanged peaks. We report that short insertions and deletions (indels), followed by single nucleotide variants (SNVs), have the highest probability of modifying peak calls. We show that using a graph personalized genome represents a reasonable compromise between modified reference genomes and de novo assembled genomes. We demonstrate that altered peaks have a genomic distribution typical of other peaks.

Conclusions
Analyzing epigenomic datasets with personalized and graph genomes allows the recovery of new peaks enriched for indels and SNVs. These altered peaks are more likely to differ between individuals and, as such, could be relevant in the study of various human phenotypes.
Radiotherapy-related skin toxicity (RAREST-02): A randomized trial testing the effect of a mobile application reminding head-and-neck cancer patients to perform skin care (reminder app) on radiation dermatitis
Authors: Rades Dirk , Narvaez Carlos Andres , Doemer Claudia , Janssen Stefan , Olbrich Denise , Tvilsted Soeren , Conde-Moreno Antonio J. , Cacicedo Jon 
Published: May 2020

Abstract
Background
Radiotherapy of head-and-neck cancer can be associated with significant toxicities including dermatitis and oral mucositis. Severe toxicities may require interruptions of the radiation treatment associated with impairment of the patients’ prognoses. This study will investigate whether the addition of a reminder app to standard care can reduce dermatitis and oral mucositis rates during radiotherapy in these patients.

Methods
This randomized trial compares standard care supported by a reminder app (Arm A) to standard care alone (Arm B) with respect to grade ≥ 2 radiation dermatitis and oral mucositis at 60 Gy of radiotherapy, the minimum planned dose for patients receiving definitive or adjuvant radiotherapy for locally advanced head- and-neck cancer. Moreover, radiation-induced dermatitis and oral mucositis grade ≥ 3 at 60 Gy and both grade ≥ 2 and grade ≥ 3 at the end of radiation treatment (EOT) will be evaluated, as well as quality of life and pain. According to sample size calculations, 80 patients are required per arm within the full analysis set. Taking into account that 5% of patients will not qualify for full analysis set, 168 patients should be randomized. The impact of the reminder app will be considered clinically relevant, if the rates of grade ≥ 2 radiation dermatitis (primary endpoint) and oral mucositis (secondary endpoint) can be reduced by 20%.

Discussion
If the addition of a reminder app to standard care will lead to a significant reduction of radiation dermatitis and oral mucositis, it could become a helpful tool for patients with head-and-neck cancer during radiotherapy.

Trial registration
clinicaltrials.gov (NCT04110977). Registered on September 27, 2019. First patient is planned to be included in December 2019.
Analysis of responder-based endpoints: improving power through utilising continuous components
Authors: Wason James , McMenamin Martina , Dodd Susanna 
Published: May 2020

AbstractBackgroundClinical trials and other studies commonly assess the effectiveness of an intervention through the use of responder-based endpoints. These classify patients based on whether they meet a number of criteria which often involve continuous variables categorised as being above or below a threshold. The proportion of patients who are responders is estimated and, where relevant, compared between groups. An alternative method called the augmented binary method keeps the definition of the endpoint the same but utilises information contained within the continuous component to increase the power considerably (equivalent to increasing the sample size by > 30%). In this article we summarise the method and investigate the variety of clinical conditions that use endpoints to which it could be applied.MethodsWe reviewed a database of core outcome sets (COSs) that covered physiological and mortality trial endpoints recommended for collection in clinical trials of different disorders. We identified responder-based endpoints where the augmented binary method would be useful for increasing power.ResultsOut of the 287 COSs reviewed, we identified 67 new clinical areas where endpoints were used that would be more efficiently analysed using the augmented binary method. Clinical areas that had particularly high numbers were rheumatology (11 clinical disorders identified), non-solid tumour oncology (10 identified), neurology (9 identified) and cardiovascular (8 identified).ConclusionsThe augmented binary method can potentially provide large benefits in a vast array of clinical areas. Further methodological development is needed to account for some types of endpoints.
High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes
Authors: Oliveira Dennis , Stegmayr Carina , Heinzel Alexander , Ermert Johannes , Neumaier Bernd , Shah N. Jon , Mottaghy Felix M. , Langen Karl-Josef , Willuweit Antje 
Published: May 2020

Abstract
Background
Recent studies reported on high uptake of the PSMA ligands [68Ga]HBED-CC (68Ga-PSMA) and 18F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of 68Ga-PSMA and 18F-DCFPyL in three different rat glioma models.

Methods
F98, 9 L, or U87 rat gliomas were implanted into the brains of 38 rats. After 13 days of tumor growth, 68Ga-PSMA (n = 21) or 18F-DCFPyL (n = 17) was injected intravenously, and animals were sacrificed 40 min later. Five animals for each tracer and tumor model were additionally investigated by micro-PET at 20–40 min post injection. Cryosections of the tumor bearing brains were analyzed by ex vivo autoradiography and immunofluorescence staining for blood vessels, microglia, astrocytes, and presence of PSMA. Blood-brain barrier (BBB) permeability was tested by coinjection of Evans blue dye (EBD). 68Ga-PSMA uptake after restoration of BBB integrity by treatment with dexamethasone (Dex) was evaluated in four animals with U87 gliomas. Competition experiments using the PSMA-receptor inhibitor 2-(phosphonomethyl)pentane-1,5-dioic acid (PMPA) were performed for both tracers in two animals each.

Results
Autoradiography demonstrated a strong 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral area and moderate binding in the center of the tumors. PMPA administration led to complete inhibition of 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral region. Restoration of BBB by Dex treatment reduced EBD extravasation but 68Ga-PSMA binding remained unchanged. Expression of activated microglia (CD11b) was low in the intra- and peritumoral area but GFAP staining revealed strong activation of astrocytes in congruency to the tracer binding in the peritumoral area. All tumors were visualized in micro PET, showing a lower tumor/brain contrast with 68Ga-PSMA than with 18F-DCFPyL.

Conclusions
High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of all glioma models is presumably caused by activated astrocytes. This may represent a limitation for the clinical application of PSMA ligands in gliomas.
Trends in burden of chronic obstructive pulmonary disease in Iran, 1995–2015: findings from the global burden of disease study
Authors: Hashemi Seyed Yaser , Momenabadi Victoria , Faramarzi Ahmad , Kiani Amin 
Published: May 2020

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder that progresses over time, and currently it is the fourth leading cause of death across the globe. The World Health Organization (WHO) predicts that the disease will become the third leading cause of death by 2030. The present study aimed to assess the burden trends of COPD in Iran by estimating the disability-adjusted life years (DALYs) from 1995 to 2015.

Methods
Data were retrospectively collected as the Global Burden of Disease (GBD) from 1995 to 2015 and published by the Institute for Health Metrics and Evaluation. We applied DALYs, incidence and prevalence rate to report the burden of COPD in Iran. To assess the statistical significance according to trend, the Cochran-Armitage test was applied. Additionally, the t-test was used to analyze the DALYs number by gender and Onaway ANOVA by age groups at a significance level set atP < 0.05.

Results
From 1995 to 2015, there were approximately 1.1 million DALYs attributable to COPD in Iran. In both genders and at all ages, the number of DALYs increased significantly from 176,224 in 1995 to 253,618 in 2015. The incidence and prevalence rate were 76.65 and 1491.37 per 100,000 population, respectively in both genders in 2015 in Iran. It is noticeable that the number of deaths during the study years, 1995 to 2015, was 39,064. This study showed that the COPD burden was significantly different by age groups and gender.

Conclusions
COPD is still a public health problem in Iran and has an increasing trend. The majority of DALYs were due to the years of life lost as a result of premature death (YLLs), indicating that prevention and early detection, especially in the age groups of 15 to 70 years, should be considered.
Trends in response rates and respondent characteristics in five National Maternity Surveys in England during 1995–2018
Authors: Harrison Siân , Alderdice Fiona , Henderson Jane , Redshaw Maggie , Quigley Maria A. 
Published: May 2020

AbstractBackgroundThe National Perinatal Epidemiology Unit in England has conducted five National Maternity Surveys (NMS) at varying intervals since 1995. This paper aims to describe the changes in NMS response rates over time and to compare the demographic characteristics of respondents to each NMS.MethodsThis paper is based on secondary data analysis of the NMS (cross-sectional postal surveys) from 1995 to 2018. All women aged 16 years and over who gave birth in England (and Wales in 1995) during specified time periods from 1995 to 2018 were eligible to be selected. For each survey, between 3570 and 16,000 women who were 3–6 months postpartum were selected at random by the Office for National Statistics, using birth registrations. Women could participate on paper, by telephone (from 2006) or online (from 2010).ResultsThe response rate to the NMS decreased from 67% in 1995 to 29% in 2018. The decline was evident across demographic groups. In all NMS, response rates were higher in women who were older (crude prevalence ratios (PR) for 16–24 years versus 30–34 years = 0.51–0.73 (across surveys)), married (crude PR for sole versus married registrants = 0.41–0.62), born in the UK (crude PR for non UK-born versus UK-born = 0.70–0.84), and living in less deprived areas (crude PR for least versus most deprived = 0.42–0.63). However, the association between each demographic characteristic and response varied across surveys, with the youngest women, women who registered the birth of the baby in their sole name, and women living in the most deprived areas becoming relatively less likely to respond over time. In multivariable analysis in 2014 and 2018, the effects of age, marital status, country of birth and level of area deprivation on response were attenuated but all four demographic characteristics remained statistically significantly associated with response.ConclusionsResponse rates to the NMS have declined significantly during the last 23 years. The demographic characteristics associated with response were consistent across surveys, but the size of the effect varied significantly, with underrepresented groups becoming relatively less likely to participate over time. It is important to find strategies to increase response rates, particularly amongst underrepresented groups, and to validate the data collected.
Health risk factors associated with pesticide use by watermelon farmers in Central region, Ghana
Authors: Miyittah Michael K. , Kwadzo Moses , Gyamfua Abigail Peprah , Dodor Daniel E. 
Published: May 2020

Abstract
Background
The export drive for watermelon production is huge and so is pesticide usage. However, the health and safety of the farmers, as well as threat to the environment lie in the shadow. The purpose of the study is to evaluate watermelon farmers’ knowledge and application of pesticides in the Central region of Ghana, to ascertain factors associated with the pesticides application.

Methods
A field survey of 300 farmers were conducted in six communities through questionnaire. Logistic regression model was used to describe and explain burning sensation as the response variable and the factors that likely affect appropriate pesticide usage.

Results
The results show that farmers were aware of the environmental and health impacts of pesticides use. However, their knowledge of the risks associated with pesticides is not translated into actual practice to avoid the exposure of pesticides. The farmers experienced various levels of health risks symptoms. Health risks symptoms of headache, burning sensation, fever, watering eyes, chest pains, etc., were reported. The most common symptom is burning sensation. A model capturing biosocial factors influencing predisposition to burning sensation was developed. The model revealed that knowledge to identify pests, knowledge to identify diseases and wearing coverall were the most significant factors farmers experienced to influence burning sensation.

Conclusion
Significant number of watermelon farmers’ experienced health risks symptoms. In order to minimize the health risk symptoms and environmental consequences, educational training programs must involve the farmers and retailers through strong policy intervention.
Factors affecting severe weather threat index in urban areas of Turkey and Iran
Authors: Rabbani Ghazaleh , Kardani-Yazd Neda , Mansouri Daneshvar Mohammad Reza 
Published: May 2020

Abstract
Background
Distinguishing dynamic variations of the climate from the physical urban indicators is a challenge to assess the factors affecting weather severity. Hence, the time-series of the severe weather threat index (SWEAT) were considered in the four urban areas of Turkey and Iran to identify its affecting factors among the climatic variables and urban indicators in 2018. The SWEAT data were obtained from the upper-air sounding database of the University of Wyoming. The climatic variables were extracted from the Asia Pacific data research center (APDRC). The spatial statistics for urban expansion were collected from global human built-up and settlement extent (HBASE) data sets. A quantitative measuring of the Pearson correlation test was used to expose the relationships between dependent index (SWEAT) and independent variables (climatic and anthropogenic).

Results
Results revealed that the high and extreme severity classes of the weather condition in the Ankara, Istanbul, Mashhad, and Tehran are estimated as 7.7% (28 days), 15.3% (56 days), 1.1% (4 days), and 4.4% (16 days), respectively. The strongest values of the annual SWEAT index, exposing the unstable and severe weather conditions, were observed for Istanbul and Ankara urban regions. This result may be corresponding to the highest values of mean annual precipitation and relative humidity in addition to the largest values of urban expansion and sprawl index. The statistical correlation tests in annual scale confirmed the effective role of climatic elements of precipitation, relative humidity, and cloudiness (R from 0.94 to 0.99) and the urban expansion indicators (R from 0.86 to 0.91) in increasing annual severe weather index of SWEAT at above 85–95% of confidence level.

Conclusions
The correlations between the urban expansion indicators and outcome SWEAT index can be strengthened by some climatic elements (e.g., precipitation, humidity, and cloudiness), revealing the mediator and magnifier task. However, the mentioned correlations can be weakened by another climatic variable (i.e., air temperature), revealing a moderator and modifier task. Ultimately, investigation of the weather severity indices (e.g., SWEAT index) could be applied to identify the local and regional evidence of climate change in the urban areas.
Genome-wide association studies of lactation yields of milk, fat, protein and somatic cell score in New Zealand dairy goats
Authors: Scholtens Megan , Jiang Andrew , Smith Ashley , Littlejohn Mathew , Lehnert Klaus , Snell Russell , Lopez-Villalobos Nicolas , Garrick Dorian , Blair Hugh 
Published: May 2020

Abstract
Background
Identifying associations between genetic markers and traits of economic importance will provide practical benefits for the dairy goat industry, enabling genomic prediction of the breeding value of individuals, and facilitating discovery of the underlying genes and mutations. Genome-wide association studies were implemented to detect genetic regions that are significantly associated with effects on lactation yields of milk (MY), fat (FY), protein (PY) and somatic cell score (SCS) in New Zealand dairy goats.

Methods
A total of 4,840 goats were genotyped with the Caprine 50 K SNP chip (Illumina Inc., San Diego, CA). After quality filtering, 3,732 animals and 41,989 SNPs were analysed assuming an additive linear model. Four GWAS models were performed, a single-SNP additive linear model and three multi-SNP BayesC models. For the single-SNP GWAS, SNPs were fitted individually as fixed covariates, while the BayesC models fit all SNPs simultaneously as random effects. A cluster of significant SNPs were used to define a haplotype block whose alleles were fitted as covariates in a Bayesian model. The corresponding diplotypes of the haplotype block were then fit as class variables in another Bayesian model.

Results
Across all four traits, a total of 43 genome-wide significant SNPs were detected from the SNP GWAS. At a genome-wide significance level, the single-SNP analysis identified a cluster of variants on chromosome 19 associated with MY, FY, PY, and another cluster on chromosome 29 associated with SCS. Significant SNPs mapped in introns of candidate genes (45%), in intergenic regions (36%), were 0–5 kb upstream or downstream of the closest gene (14%) or were synonymous substitutions (5%). The most significant genomic window was located on chromosome 19 explaining up to 9.6% of the phenotypic variation for MY, 8.1% for FY, 9.1% for PY and 1% for SCS.

Conclusions
The quantitative trait loci for yield traits on chromosome 19 confirms reported findings in other dairy goat populations. There is benefit to be gained from using these results for genomic selection to improve milk production in New Zealand dairy goats.
The effects of B cell depletion on immune related adverse events associated with immune checkpoint inhibition
Authors: Risbjerg Rasmus Strøm , Hansen Mie Vennize , Sørensen Anne Sofie , Kragstrup Tue Wenzel 
Published: May 2020

AbstractThis letter describes the potential effect of B cell depletion on immune related adverse events associated with immune checkpoint inhibition. B cell depleting agents such as rituximab reduce B cell to plasma cell differentiation and antibody production. This treatment strategy is used in several immune mediated inflammatory diseases such as rheumatoid arthritis and small vessel vasculitis. The immune related adverse events associated with immune checkpoint inhibition resemble immune mediated inflammatory diseases. Here, we report a lower incidence of hypothyroidism in a trial of combined B cell depletion and immune checkpoint inhibitor treatment compared with studies of immune checkpoint inhibitor monotherapy. This letter aims to increase awareness of the immune related adverse events associated with immune checkpoint inhibition in future clinical trials of immune checkpoint inhibition together with B cell depletion (primarily trials of B cell lymphomas). Hopefully, observations from these clinical trials can guide future treatment strategies to treat or prevent immune related adverse events associated with immune checkpoint inhibition.