bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance comparison of modified ComBat for harmonization of radiomic features for multicenter studies
Authors: Da-ano R. , Masson I. , Lucia F. , Doré M. , Robin P. , Alfieri J. , Rousseau C. , Mervoyer A. , Reinhold C. , Castelli J. , De Crevoisier R. , Rameé J. F. , Pradier O. , Schick U. , Visvikis D. , Hatt M. 
Published: June 2020

AbstractMulticenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the “batch effect” in gene expression microarray data and was used in radiomics studies to deal with the “center-effect”. Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models.
Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals
Authors: Brunner Jesse L. 
Published: June 2020

AbstractThe regional and international trade of live animals facilitates the movement, spillover, and emergence of zoonotic and epizootic pathogens around the world. Detecting pathogens in trade is critical for preventing their continued movement and introduction, but screening a sufficient fraction to ensure rare infections are detected is simply infeasible for many taxa and settings because of the vast numbers of animals involved—hundreds of millions of live animals are imported into the U.S.A. alone every year. Batch processing pools of individual samples or using environmental DNA (eDNA)—the genetic material shed into an organism’s environment—collected from whole consignments of animals may substantially reduce the time and cost associated with pathogen surveillance. Both approaches, however, lack a framework with which to determine sampling requirements and interpret results. Here I present formulae for pooled individual samples (e.g,. swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. While empirical validation is key, these formulae illustrate the potential for eDNA-based detection in particular to reduce sample sizes and help bring clean trade into reach for a greater number of taxa, places, and contexts.
The association between Single Nucleotide Polymorphisms of Klotho Gene and Mortality in Elderly Men: The MrOS Sweden Study
Authors: Wu Ping-Hsun , Westerberg Per-Anton , Kindmark Andreas , Tivesten Åsa , Karlsson Magnus K. , Mellström Dan , Ohlsson Claes , Fellström Bengt , Linde Torbjörn , Ljunggren Östen 
Published: June 2020

AbstractThe Klotho (KL) gene is involved in phosphate homeostasis. Polymorphisms in this gene have been reported to be associated with the risk of cardiovascular disease. Here we used computational tools to predict the damage-associated single nucleotide polymorphisms (SNPs) in the human KL gene. We further investigated the association of SNPs in the KL gene and mortality in the Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort. This study included 2921 men (aged 69–81 years) with mean 4.49 ± 1.03 years follow-up. 18 SNPs in the KL gene were genotyped using Sequenom. These SNPs were identified by in silico tools for the coding and noncoding genome to predict the damaging SNPs. After quality analyses, SNPs were analyzed for mortality risk using two steps approach on logistic regression model screening and then Cox regression model confirmation. Two non-synonymous SNPs rs9536314 and rs9527025 were found to be potentially damaging SNPs that affect KL protein stability and expression. However, these two SNPs were not statistically significantly associated with all-cause mortality (crude Hazard ratio [HR] 1.72, 95% confidence interval [CI] 0.96–3.07 in rs9536314; crude HR 1.82, 95% CI 0.998–3.33 in rs9527025) or cardiovascular mortality (crude HR 1.52, 95% CI 0.56–4.14 in rs9536314; crude HR 1.54, 95% CI 0.55–4.33 in rs9527025) in additive model using Cox regression analysis. In conclusion, these two potentially damaging SNPs (rs9536314 and rs9527025) in the KL gene were not associated with all-cause mortality or cardiovascular mortality in MrOs cohort. Larger scales studies and meta-analysis are needed to confirm the correlation between polymorphisms of the KL gene and mortality.
Lifestyle risk score and mortality in Korean adults: a population-based cohort study
Authors: Lee Dong Hoon , Nam Jin Young , Kwon Sohyeon , Keum NaNa , Lee Jong-Tae , Shin Min-Jeong , Oh Hannah 
Published: June 2020

AbstractIndividual lifestyle risk factors have been associated with an increased risk of mortality. However, limited evidence is available on the combined association of lifestyle risk factors with mortality in non-Western populations. The analysis included 37,472 participants (aged ≥19 years) in the Korea National Health and Nutrition Examination Surveys (2007–2014) for whom the data were linked to death certificates/medical records through December 2016. A lifestyle risk score was created using five unhealthy behaviors: current smoking, high-risk alcohol drinking, unhealthy weight, physical inactivity, and insufficient/prolonged sleep. Cox proportional hazards models were used to estimate hazard ratio (HR) and 95% confidence interval (CI). During up to 9 years of follow-up, we documented 1,057 total deaths. Compared to individuals with zero lifestyle risk factor, those with 4–5 lifestyle risk factors had 2.01 times (HR = 2.01, 95% CI = 1.43–2.82) and 2.59 times (HR = 2.59, 95% CI = 1.24–5.40) higher risk of all-cause and cardiovascular mortality, respectively. However, higher lifestyle risk score was not significantly associated with cancer mortality (p-trend >0.05). In stratified analyses, the positive associations tended to be stronger in adults aged <65 years, unemployed, and those with lower levels of education. In conclusion, combined unhealthy lifestyle behaviors were associated with substantially increased risk of total and cardiovascular mortality in Korean adults.
Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes
Authors: Tomizawa Nobuo , Chou Shengpu , Fujino Yusuke , Matsuoka Satoshi , Yamamoto Kodai , Inoh Shinichi , Nojo Takeshi , Kumamaru Kanako K. , Fujimoto Shinichiro , Nakamura Sunao 
Published: June 2020

AbstractThe objective of this study was to investigate the incremental prognostic value for adverse events of myocardial blood flow (MBF) derived from stress computed tomography perfusion (CTP) at remote myocardium over cardiac risk factors and ischemia. We prospectively analyzed 242 patients who underwent dynamic CTP and CT angiography. Adverse events were defined as a composite of all-cause mortality, non-fatal myocardial infarction, unstable angina, heart failure requiring hospitalization, peripheral artery disease, and stroke. MBF value was calculated in each myocardial segment and ischemia was defined as mild decrease in MBF in two consecutive segments or moderate decrease in a single segment accompanied with a coronary stenosis ≥50%. The mean MBF of the non-ischemic segments was defined as remote MBF. We divided the patients into two groups by median MBF value of 1.15 ml/min/g. During a median follow-up of 18 months, 18 patients had adverse events. Annual event rate showed a significant difference between patients with low (≤1.15 ml/min/g) and high (>1.15 ml/min/g) MBF (6.1% vs 1.8%, p = 0.02). Univariate analysis showed that low MBF was a significant predictor of events (hazard ratio (HR): 3.4; 95% confidence interval (CI): 1.2 to 12.0; p = 0.02). This relationship maintained significant after adjusted for the presence of ischemia and cardiac risk factors (HR: 3.0; 95%CI: 1.1 to 11.1; p = 0.04). In conclusion, MBF value ≤1.15 ml/min/g derived from dynamic CTP in remote myocardium is significantly related with poor outcome and this relationship was independent of myocardial ischemia and cardiac risk factors.
Hydrogel-based milliwell arrays for standardized and scalable retinal organoid cultures
Authors: Decembrini S. , Hoehnel S. , Brandenberg N. , Arsenijevic Y. , Lutolf M. P. 
Published: June 2020

AbstractThe development of improved methods to culture retinal organoids is relevant for the investigation of mechanisms of retinal development under pathophysiological conditions, for screening of neuroprotective compounds, and for providing a cellular source for clinical transplantation. We report a tissue-engineering approach to accelerate and standardize the production of retinal organoids by culturing mouse embryonic stem cells (mESC) in optimal physico-chemical microenvironments. Arrayed round-bottom milliwells composed of biomimetic hydrogels, combined with an optimized medium formulation, promoted the rapid generation of retina-like tissue from mESC aggregates in a highly efficient and stereotypical manner: ∼93% of the aggregates contained retinal organoid structures. 26 day-old retinal organoids were composed of ∼80% of photoreceptors, of which ∼22% are GNAT2-positive cones, an important and rare sensory cell type that is difficult to study in rodent models. The compartmentalization of retinal organoids into predefined locations on a two-dimensional array not only allowed us to derive almost all aggregates into retinal organoids, but also to reliably capture the dynamics of individual organoids, an advantageous requirement for high-throughput experimentation. Our improved retinal organoid culture system should be useful for applications that require scalability and single-organoid traceability.
Lysosomal perturbations in human dopaminergic neurons derived from induced pluripotent stem cells with PARK2 mutation
Authors: Okarmus Justyna , Bogetofte Helle , Schmidt Sissel Ida , Ryding Matias , García-López Silvia , Ryan Brent James , Martínez-Serrano Alberto , Hyttel Poul , Meyer Morten 
Published: June 2020

AbstractMutations in the PARK2 gene encoding parkin, an E3 ubiquitin ligase, are associated with autosomal recessive early-onset Parkinson’s disease (PD). While parkin has been implicated in the regulation of mitophagy and proteasomal degradation, the precise mechanism leading to neurodegeneration in both sporadic and familial PD upon parkin loss-of-function remains unknown. Cultures of isogenic induced pluripotent stem cell (iPSC) lines with and without PARK2 knockout (KO) enable mechanistic studies of the effect of parkin deficiency in human dopaminergic neurons. We used such cells to investigate the impact of PARK2 KO on the lysosomal compartment and found a clear link between parkin deficiency and lysosomal alterations. PARK2 KO neurons exhibited a perturbed lysosomal morphology with enlarged electron-lucent lysosomes and an increased lysosomal content, which was exacerbated by mitochondrial stress and could be ameliorated by antioxidant treatment. We also found decreased lysosomal enzyme activity and autophagic perturbations, suggesting an impairment of the autophagy-lysosomal pathway in parkin-deficient cells. Interestingly, activity of the GBA-encoded enzyme, β-glucocerebrosidase, was increased, suggesting the existence of a compensatory mechanism. In conclusion, our data provide a unique characterization of the morphology, content, and function of lysosomes in PARK2 KO neurons and reveal an important new connection between mitochondrial dysfunction and lysosomal dysregulation in PD pathogenesis.
Nanosilver as a novel biocide for control of senescence in garden cosmos
Authors: Skutnik Ewa , Jędrzejuk Agata , Rabiza-Świder Julita , Rochala-Wojciechowska Julia , Latkowska Monika , Łukaszewska Aleksandra 
Published: June 2020

AbstractTo prolong their vase life, cut flowers are commonly kept in holding solutions. These must include a biocide to retard bacterial growth. In this study, the effect of nanosilver (NS) on certain aspects of senescence in cut garden cosmos (Cosmos bipinnatus) flowers was compared to that of the commonly used 8-hydroxyquinoline citrate (8-HQC). In combination with sucrose, both biocides prolonged cosmos vase life but did not prevent the occurrence of stem blockages. NS was more effective in limiting a reduction in endogenous soluble carbohydrates. The malondialdehyde (MDA) contents increased in senescing ray florets, both in intact and control cut flowers held in water. Both biocides were comparably effective in limiting this effect. The hydrogen peroxide content tripled in intact flowers but dropped in flowers held in water or the 8-HQC solutions; in flowers kept in NS solutions its increase was moderate. Also, the catalase activity increased in intact flowers but dropped in all cut flowers. Both biocides had similar effects on the enzyme activity, in both pure solutions and with sucrose. Most of these parameters were not significantly correlated with vase life. Overall, the effect of nanosilver on senescence in cut cosmos flowers was similar to that of 8-HQC.
Metabolomic and Lipidomic Profiling of Bone Marrow Plasma Differentiates Patients with Monoclonal Gammopathy of Undetermined Significance from Multiple Myeloma
Authors: Gonsalves Wilson I. , Broniowska Katarzyna , Jessen Erik , Petterson Xuan-Mai , Bush Alexander Graham , Gransee Jaimee , Lacy Martha Q. , Hitosugi Taro , Kumar Shaji K. 
Published: June 2020

AbstractOncogenic drivers of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) such as c-MYC have downstream effects on intracellular metabolic pathways of clonal plasma cells (PCs). Thus, extracellular environments such as the bone marrow (BM) plasma likely have unique metabolite profiles that differ from patients with MGUS compared to MM. This study utilized an untargeted metabolite and targeted complex lipid profiling of BM plasma to identify significant differences in the relative metabolite levels between patients with MGUS and MM from an exploratory cohort. This was followed by verification of some of the metabolite differences of interest by targeted quantification of the metabolites using isotopic internal standards in the exploratory cohort as well as an independent validation cohort. Significant differences were noted in the amino acid profiles such as decreased branch chain amino acids (BCAAs) and increased catabolism of tryptophan to the active kynurenine metabolite 3-hydroxy-kynurenine between patients with MGUS and MM. A decrease in the total levels of complex lipids such as phosphatidylethanolamines (PE), lactosylceramides (LCER) and phosphatidylinositols (PI) were also detected in the BM plasma samples from MM compared to MGUS patients. Thus, metabolite and complex lipid profiling of the BM plasma identifies differences in levels of metabolites and lipids between patients with MGUS and MM. This may provide insight into the possible differences of the intracellular metabolic pathways of their clonal PCs.
Combinatory actions of CP29 phosphorylation by STN7 and stability regulate leaf age-dependent disassembly of photosynthetic complexes
Authors: Poudyal Roshan Sharma , Rodionova Margarita V. , Kim Hyunmin , Lee Seongsin , Do Eunjeong , Allakhverdiev Suleyman I. , Nam Hong Gil , Hwang Daehee , Kim Yumi 
Published: June 2020

AbstractA predominant physiological change that occurs during leaf senescence is a decrease in photosynthetic efficiency. An optimal organization of photosynthesis complexes in plant leaves is critical for efficient photosynthesis. However, molecular mechanisms for regulating photosynthesis complexes during leaf senescence remain largely unknown. Here we tracked photosynthesis complexes alterations during leaf senescence in Arabidopsis thaliana. Grana stack is significantly thickened and photosynthesis complexes were disassembled in senescing leaves. Defects in STN7 and CP29 led to an altered chloroplast ultrastructure and a malformation of photosynthesis complex organization in stroma lamella. Both CP29 phosphorylation by STN7 and CP29 fragmentation are highly associated with the photosynthesis complex disassembly. In turn, CP29 functions as a molecular glue to facilitate protein complex formation leading phosphorylation cascade and to maintain photosynthetic efficiency during leaf senescence. These data suggest a novel molecular mechanism to modulate leaf senescence via CP29 phosphorylation and fragmentation, serving as an efficient strategy to control photosynthesis complexes.
Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3
Authors: Yoshitomi Ren , Nakayama Kai , Yamashita Shuya , Kumazoe Motofumi , Lin Ting-An , Mei Chen-Yi , Marugame Yuki , Fujimura Yoshinori , Maeda-Yamamoto Mari , Kuriyama Shinichi , Tachibana Hirofumi 
Published: June 2020

AbstractFolic acid and folate receptors (FOLRs) play an important role in the downregulation of homocysteine (Hcy), a risk factor of Alzheimer’s disease, thrombosis, neuropsychiatric illness and fractures. While several studies have reported that FOLR1 and FOLR2 import folic acid into cells, the role of FOLR3 remains unknown. In this study, we evaluated the impact of FOLR3 on the metabolism of Hcy alongside its protective effect against homocysteine-induced neurotoxicity. To reveal the role of FOLR3, we constructed FOLR3-overexpressed HEK293 cells (FOLR3+ cells) and evaluated cell growth, folic acid intake and Hcy-induced neurotoxicity. Subjects with a high expression of FOLR3 exhibited low levels of plasma homocysteine. The ectopic expression of FOLR3 enhanced cell growth, and the enhanced effect was neutralised by folic acid-deficient media. The Western blot analysis revealed that FOLR3 is secreted into cell supernatant. The folic acid intake of FOLR3+ cells was higher than that of wild-type cells. Supernatant from FOLR3+ cells showed a protective effect on Hcy-induced cytotoxicity. FOLR3 expression in plasma is negatively correlated with plasma homocysteine. Our study emphasizes the role of FOLR3 in the intake of folic acid into cells on the one hand and its protective role in Hcy-induced cytotoxicity on the other.
Rolling circle amplification of synthetic DNA accelerates biocatalytic determination of enzyme activity relative to conventional methods
Authors: Hadi Timin , Nozzi Nicole , Melby Joel O. , Gao Wei , Fuerst Douglas E. , Kvam Erik 
Published: June 2020

AbstractThe ability to quickly and easily assess the activity of large collections of enzymes for a desired substrate holds great promise in the field of biocatalysis. Cell-free synthesis, although not practically amenable for large-scale enzyme production, provides a way to accelerate the timeline for screening enzyme candidates using small-scale reactions. However, because cell-free enzyme synthesis requires a considerable amount of template DNA, the preparation of high-quality DNA “parts” in large quantities represents a costly and rate-limiting prerequisite for high throughput screening. Based on time-cost analysis and comparative activity data, a cell-free workflow using synthetic DNA minicircles and rolling circle amplification enables comparable biocatalytic activity to cell-based workflows in almost half the time. We demonstrate this capability using a panel of sequences from the carbon-nitrogen hydrolase superfamily that represent possible green catalysts for synthesizing small molecules with less waste compared to traditional industrial chemistry. This method provides a new alternative to more cumbersome plasmid- or PCR-based protein expression workflows and should be amenable to automation for accelerating enzyme screening in industrial applications.
Hypertension is associated with oral, laryngeal, and esophageal cancer: a nationwide population-based study
Authors: Seo Jae-Hyun , Kim Young-Du , Park Chan-Seok , Han Kyung-do , Joo Young-Hoon 
Published: June 2020

AbstractSeveral studies have reported an association between hypertension and upper aerodigestive tract cancer, but no large-scale, population-based studies have been conducted to confirm this.The aim of this study was to explore the association between hypertension and risk of upper aerodigestive tract cancer in Koreans. Participants who underwent a national health screening examination from January 1 to December 31, 2009 (n = 9,746,606) were enrolled. We assessed the development of oral, laryngeal, or esophageal cancer until 2016 using records from the Korean Health Insurance claims database during the study period. During the seven-year follow-up period, 6,062, 2,658, and 4,752 subjects were newly diagnosed with oral, laryngeal, and esophageal cancer, respectively. Participants with metabolic syndrome had the highest risk of developing oral cancer (hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.03–1.16), laryngeal cancer (HR 1.27, 95% CI 1.17–1.38), and esophageal cancer (HR 1.11, 95% CI 1.04–1.19). Hypertension was a remarkable risk factor for each cancer (HR 1.11, 95% CI 1.04–1.17 for oral cancer; HR 1.23, 95% CI 1.13–1.33 for laryngeal cancer; HR 1.25, 95% CI 1.18–1.33 for esophageal cancer) after adjusting for age and other variables including gender, smoking status, alcohol intake, exercise, body mass index, and diabetes. Patients with untreated hypertension were at highest risk of developing oral cancer (HR 1.15; 95% CI 1.05–1.26), laryngeal cancer (HR 1.25; 95% CI 1.09–1.44), and esophageal cancer (HR 1.47; 95% CI 1.33–1.63) after adjusting for confounders. Hypertension was associated with the risk of oral, laryngeal, and esophageal cancer, despite of the lack of detailed biochemical information including the cancer cell types (squamous cell carcinoma or adenocarcinoma), cancer stage, physical findings and other medical history. Further studies are warranted to determine the reasons for this association and to establish effective interventions in this vulnerable population.