bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Familial Predictors of Proband Outcomes in Neurogenetic Disorders: Initial Application in XYY Syndrome
Authors: Wilson Kathleen E. , Fish Ari M. , Mankiw Catherine , Xenophontos Anastasia , Warling Allysa , Whitman Ethan , Clasen Liv , Torres Erin , Blumenthal Jonathan , Raznahan Armin
Published: November 2020

Background: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome – a sex chromosome aneuploidy that is known to increase risk for psychopathology.Methods: We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits.Results: Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R2 ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring.Conclusions: We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggests that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. Trial registrations: ClinicalTrials.gov NCT00001246, “89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls.” Date of registry: 01/10/1989.
Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact
Authors: Holbrook Anne Marie , Wang Mei , Lee Munil , Chen Zhiyuan , Garcia Michael , Nguyen Laura , Ford Angela , Manji Selina , Law Michael R
Published: November 2020

Background Cost-related nonadherence to medications (CRNA) is common in many countries and thought to be associated with adverse outcomes. The characteristics of CRNA in Canada, with its patchwork coverage of increasingly expensive medications, is unclear. Objectives Our objective in this systematic review was to summarize the literature evaluating CRNA in Canada in three domains: prevalence, predictors, and effect on clinical outcomes.Methods We searched MEDLINE, Embase, Google Scholar, and the Cochrane Library from 1992 to December 2019 using search terms covering medication adherence, costs, and Canada. Eligible studies, without restriction on design, had to have original data on at least one of the three domains specifically for Canadian participants. Articles were identified and reviewed in duplicate. Risk of bias was assessed using design-specific tools.Results: Twenty-six studies of varying quality (n=483,065 Canadians) were eligible for inclusion. Sixteen studies reported on the overall prevalence of CRNA, with population-based estimates ranging from 5.1% to 10.2%. Factors predicting CRNA included high out of pocket spending, low income or financial flexibility, lack of drug insurance, younger age, and poorer health. A single randomized trial of free essential medications with free delivery in Ontario improved adherence but did not find any change in clinical outcomes at one year. Conclusion: CRNA affects many Canadians. The estimated percentage depends on the sampling frame, the main predictors tend to be financial, and its association with clinical outcomes in Canada remains unproven.
Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre
Authors: Bailo Paula Sienes , Lahoz Raquel , Marín Juan Pelegrín Sánchez , Álvarez Silvia Izquierdo
Published: November 2020

Background: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases.Methods: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100 000 inhabitants per year during the period 2007-2019 in Aragon (Spain). Results: 50 (27.9%) incident cases of HD (CAG repeat length ≥36) were identified from a total of 179 persons studied. The remaining 129/179 (73.4%) were HD negative (CAG repeat length <36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 64.8 per 100 000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 10 and the most common CAG length among HD negative individuals was 16.Conclusions: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.
Patterns of white matter degeneration in remote brain areas from the basal ganglion lesion of ischemic stroke patients with motor impairment
Authors: cao xuejin , Wang Zan , Chen Xiaohui , Liu Yanli , Wang Wei , Abdoulaye Idriss Ali , Yang Xi , Zhang Shiyao , Guo Xiaoying , Wu Shanshan , Guo Yijing
Published: November 2020

Background: Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom mapping, recent studies have demonstrated extensive structural and functional alterations of remote areas to local lesions caused by stroke in the brain. Here, we further investigated the structural changes from a global level using DTI data through multivariate pattern analysis (MVPA) and network-based statistic (NBS). Methods: Ten ischemic stroke patients with basal ganglia lesions and motor dysfunctions and eleven demographically matched adults as controls underwent brain Magnetic Resonance Imaging scans. DTI data were processed to obtain fractional anisotropy (FA) maps and MVPA was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber tracking approach according to the Automated Anatomical Labeling (AAL) atlas. NBS was used to explore differences in structural networks between groups. Results: MVPA applied to FA images correctly identified stroke patients with a statistically significant accuracy of 100% (P≤0.001). Compared with the controls, the study patients showed FA reductions in the perilesional basal ganglia and brainstem, with a few showing reductions in bilateral frontal lobes. Using NBS, we found a significant decrease in FA-weighted WM subnetwork in stroke patients. Conclusions: We identified some patterns of WM degeneration affecting brain areas remote to the ischemic lesion, revealing the abnormal organization of WM network in stroke patients, which may be helpful for the understanding of the neural mechanisms of stroke sequela.
Economic evaluation of a web-based menu planning intervention to improve childcare service adherence with dietary guidelines.
Authors: Reeves Penny , Edmunds Kim , Szewczyk Zoe , Grady Alice , Yoong Sze Lin , Wolfenden Luke , Wyse Rebecca , Finch Megan , Stacey Fiona , Wiggers John , Searles Andrew
Published: November 2020

BackgroundDespite the known benefits of healthy eating in childhood, few Australian childcare services provide food that is consistent with dietary guidelines. The effectiveness of a web-based menu planning intervention to increase childcare service provision of healthy foods and decrease provision of discretionary foods in long day-care services in Australia was assessed in a randomised controlled trial. Here we consider the costs, consequences, cost-effectiveness and budget impact of the intervention using data collected within the trial. MethodsThe prospective trial-based economic evaluation involved 54 childcare services across New South Wales (NSW), Australia. Services were randomised to a 12-month intervention or usual care. The intervention involved access to a web-based menu planning and decision support tool, and online resources. Effectiveness measures included: mean number of food groups, overall menu and individual food group compliance with dietary guidelines, and mean servings of food groups at 12 months. Costs (reported in $AUD, 2017/18) were evaluated from both health sector and societal perspectives. The direct cost to support uptake of the intervention was calculated, as were costs to each childcare service. The incremental cost of the intervention was calculated as the net difference in the cost to undertake menu planning and review plus the direct cost of the intervention. Incremental cost–effectiveness ratios (ICERs) including uncertainty intervals, were estimated for differences in costs and effects between intervention and control groups. A relative value index was calculated to determine overall value for money.ResultsOver the 12 months of the trial, we calculated a difference in cost between usual practice and intervention groups of -$482 (95% UI -$859, -$56). While the measured increase in menu and food group compliance within the trial did not reach statistical significance, there were significant improvements in mean servings of fruit and discretionary food, represented in the cost-consequence analysis. The calculated relative value index of 1.1 suggests that the intervention returns acceptable value for money for the outcomes generated.ConclusionCompared to usual practice, web-based programs may offer an efficient and sustainable alternative for childcare services to improve the provision of healthy foods to children in their care. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12616000974404
Forest land use discontinuity and northern red oak Quercus rubra introduction change biomass allocation and life strategy of lingonberry Vaccinium vitis-idaea
Authors: Woziwoda Beata , Dyderski Marcin K. , Jagodziński Andrzej M.
Published: November 2020

Background: Multi-purpose use of forests in a sustainable way forces a recognition of how introduction of alien woody species in forests with different land use histories affect native plants other than trees. Lingonberry Vaccinium vitis-idaea is an important understory component of temperate and boreal forests and provider of valuable non-wood forest products. Here we studied effects of land use changes and introduction of Northern red oak Quercus rubra on lingonberry in mesic Scots pine forests (in central Poland). We measured lingonberry cover, height of shoots, biomass of stems and leaves, and fruit productivity. Shoots were collected within 200 research plots located in recent and ancient Scots pine forests, with and without Q. rubra.Results: We found that V. vitis-idaea reached lower cover, aboveground biomass and fruit production in recent than ancient forests and in forests with than without Q. rubra. The fruit production in recent pine forest was only 2% of that reported in ancient pine forest, and V. vitis-idaea did not reproduce generatively in forests with Q. rubra. Biomass and carbon sequestration of V. vitis-idaea in forests with alien (invasive) trees decreased by 75% compared to ancient pine forest. Effects were also clear at the individual shoot level – in less suitable conditions we found taller heights and higher biomass allocation into stems than foliage. Biomass allocation in fruiting and non-fruiting shoots in pine forests was also different – less of the dry biomass of fruiting shoots was allocated to leaves than to stems.Conclusions: In the age of high interest in ecosystem services and discussions about usage of alien tree species as alternatives in forest management, our results clearly indicate disruption of ecosystem services provided by V. vitis-idaea in the presence of Q. rubra. Lingonberry benefited from the continuity of forest land use, however, regardless of land-use legacy, alien tree introduction led to decline in abundance of species crucial for ecosystem functioning. Therefore, to maintain valuable native species and for conservation of ecosystem services delivery, we suggest limiting the introduction of Q. rubra in areas with abundant V. vitis-idaea, especially in forests with continuous forest land-use history.
Peer mentoring experience on becoming a good doctor: Student perspectives.
Authors: Shafiaai Mohd Syameer Firdaus Mohd , Kadirvelu Amudha , Pamidi Narendra
Published: November 2020

Background: PASS is a peer-led structured academic mentoring program designed to provide academic assistance for new students in their transition from college to university studies and also for students struggling in certain units. This study aims to establish acquired skills by peer leaders associated with peer-led mentoring via the PASS program, and to explore the role played by these acquired skills in their journey to become a successful doctor.Methods: Study participants were forty selected second-year undergraduate medical students at Monash University Malaysia with commendable examination results. Validated pre-test and post-test questionnaires were administered to explore changes in the level of communication, leadership, professional, and pedagogical skills before and after participation in peer mentoring program. Qualitative analysis of focused group interviews was performed by an independent investigator to identify how the skills developed as a peer mentor may help with becoming a good doctor. Major themes were identified with the thematic-analysis approach.Results: Thirty-eight students completed the pre-test and post-test questionnaires. Peer leaders reported improvement in oral and written skills for teaching; increased confidence to give constructive feedback; better stress management; efficient time management; improved interpersonal skills; and enhanced problem-solving and critical thinking capabilities. Eight major themes were identified from the interview and peer leaders reported positive experience of working in diverse environments and shouldering of responsibilities.Conclusions: Peer-led mentoring provides a good opportunity for medical students to shoulder responsibilities as a leader and offers an experience of managing a team of their peers and juniors which in turn may enhance their communication, interpersonal, and leadership skills.
Communication of Pharmacogenomic Test Results and Treatment Plans in Pediatric Oncology: Deliberative Stakeholder Consultations with Parents
Authors: Longo Cristina , Rahimzadeh Vasiliki , Bartlett Gillian
Published: November 2020

Background: Effective communication in support of clinical decision-making is central to the pediatric cancer care experience for families. A new laboratory derived pharmacogenetic test (LDT) that can diagnose difficult-to-treat brain cancers has been developed to stratify children based on their ability to respond to available treatment; however, the potential implementation of the LDT may make effective communication challenging since it can potentially remove the option for curative treatment in those children identified as non-responders, i.e. those with a catastrophic diagnosis. Objective: We solicited the perspectives of parents of children with difficult-to-treat brain cancer on communication preferences surrounding the potential implementation of the LDT in standard care using deliberative stakeholder consultations.Methods: Eight bereaved parents of children who succumbed to difficult-to-treat brain cancer, and four parents of children currently undergoing treatment for similar cancers attended separate small-group deliberative consultations – a stakeholder engagement method that enables the co-creation of recommendations following the consideration of competing arguments and diverse opinions of parents with different experiences. In the small-group consultations (Phase I), parents discussed four questions about potential communication issues that may arise with the LDT in practice. In Phase II, a total of five parents from both stakeholder groups (4 bereaved and 1 in current treatment) attended a consultation, known as the ‘mixed’ consultation, with the purpose of co-developing concrete recommendations for implementation of the LDT.Results: Explaining the risks, benefits, and accuracy of the LDT were considered essential to parents. Once an LDT-based diagnosis/prognosis can be made, parents valued honesty, empathy, and clarity in communication. Parents also requested that all results and treatment options be presented to them in measured doses, and in an unbiased manner over the course of several meetings. This communication strategy allowed sufficient time to understand and accept the diagnosis/prognosis, particularly if it was catastrophic. Continuous access to the appropriate psychological and social support or counselling at and post-diagnosis was also strongly recommended.Conclusions: Deliberants co-created family-centered recommendations surrounding communication issues of the LDT, providing guidance to pediatric oncologists that could implement the test in practice.
Cognitive and Motor Deficits Contribute to Longer Braking Time in Stroke 
Authors: Lodha Neha , Patel Prakruti , Shad Joanna M , Casamento-Moran Agostina , Christou Evangelos A
Published: November 2020

BACKGROUND: Braking is a critical determinant of safe driving that depends on the integrity of cognitive and motor processes. Following stroke, both cognitive and motor capabilities are impaired to varying degrees. The current study examines the combined impact of cognitive and motor impairments on braking time in chronic stroke. METHODS: Twenty stroke survivors and 20 aged-matched healthy controls performed cognitive, motor, and simulator driving assessments. Cognitive abilities were assessed with processing speed, divided attention, and selective attention. Motor abilities were assessed with maximum voluntary contraction (MVC) and motor accuracy of the paretic ankle. Driving performance was examined with the braking time in a driving simulator and self-reported driving behavior. RESULTS: Braking time was 16% longer in stroke group compared with the control group. The self-reported driving behavior in stroke group was correlated with braking time (r = -0.53, p = 0.02). The stroke group required significantly longer time for divided and selective attention task and showed significant decrease in motor accuracy. Together, selective attention time and motor accuracy contributed to braking time (R2 = 0.40, p = 0.01) in stroke survivors. CONCLUSIONS: This study provides novel evidence that decline in selective attention and motor accuracy together contribute to slowed braking in stroke survivors. Driving rehabilitation after stroke may benefit from the assessment and training of attentional and motor skills to improve braking during driving.
The association of priori and posteriori dietary patterns with the risk of incident hypertension: Tehran Lipid and Glucose Study
Authors: Ramezankhani Azra , Hosseini-Esfahani Firoozeh , Mirmiran Parvin , Azizi Fereidoun , Hadaegh Farzad
Published: November 2020

Background: The aim of this study was to investigate the association of dietary patterns with incident hypertension.Materials/methods: This prospective study was conducted on 4793 individuals of Tehran lipid and glucose study participants, aged ≥18 years who were followed for a median of 6.3 years from 2008-11 to 2016-18. A valid and reliable semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Anthropometrics and blood pressure were assessed at baseline and during follow up examinations. Dietary patterns were derived using principal component analysis (PCA). Healthy eating index (HEI) and dietary approach to stop hypertension (DASH) score were measured based on dietary recommendations. Time-dependent Cox models adjusting for confounders were used to examine the association between dietary patterns and the risk of hypertension.Results: During follow-up, a total of 727 incident cases of hypertension were identified. The mean±SD age at baseline was 40.3±13.5 and 37.9±12.1 years in men and women, respectively. Two dietary patterns (the healthy and unhealthy) were extracted by PCA. Compared with participants in the first quartile, a 23% (HR: 1.23; 95%CI: 1.00-1.53; P trend: 0.056) increased risk of hypertension was found in the fourth quartile of HEI score. This association was disappeared after further adjustment for confounders. Increasing DASH score, the healthy and unhealthy dietary pattern were not associated with risk of hypertension.Conclusion: Based on our findings, higher adherence to the posteriori- and priori-dietary patterns was not associated with risk of hypertension.
Application of the PET ligand [11C]ORM-13070 to examine receptor occupancy by the α2C-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain
Authors: Shahid Mohammed , Rinne Juha O. , Scheinin Mika , Virta Jere , Marjamäki Päivi , Solin Olof , Arponen Eveliina , Sallinen Jukka , Kuokkanen Katja , Rouru Juha
Published: November 2020

Background: Availability of the α2C -adrenoceptor (α2C-AR) positron emission tomography (PET) tracer, [11C]ORM-13070, and the α2C-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [11C]ORM-13070 autoradiography and PET to determine α2C-AR occupancy by ORM-12741 in rat and human brain, respectively. Results: ORM-12741 has high affinity (Ki: 0.08 nM) and potent antagonist activity (Kb: 0.04 nM) as well as selectivity (Ki estimates for the human α2A-AR and α2B-AR were 8.3 nM and 0.8 nM, respectively) for the human α2C-AR subtype. [11C]ORM-13070 had highest uptake in the basal ganglia of rat and human brain. Pretreatment with ORM-12741 inhibited [11C]ORM-13070 binding in rat striatum in a time- and dose-dependent manner at 10 and 50 µg/kg (s.c.) with an EC50 estimate of 1.42 ng/mL in rat plasma, corresponding to protein-free drug concentration of 0.23 nM. In the living human brain, time- and dose-related α2C-AR occupancy was detected with EC50 estimates of 24 ng/mL and 31 ng/mL for the caudate nucleus and putamen, respectively, corresponding to protein-free concentrations in plasma of 0.07 nM and 0.1 nM. Modelling-based maximum α2C-AR occupancy estimates were 63 % and 52 % in the caudate nucleus and the putamen, respectively.Conclusions: ORM-12741 is a selective α2C-AR antagonist which penetrates the rat and human brain to occupy α2C-ARs in a manner consistent with its receptor pharmacology.Trial registration number and date of registration: ClinicalTrial.cov NCT00829907. Registered 11 December 2008. https://clinicaltrials.gov/.
Transcriptome analysis identifies genes involved in the somatic embryogenesis of Eucalyptus
Authors: Xiao Yufei , Li Junji , Zhang Ye , Zhang Xiaoning , Liu Hailong , Qin Zihai , Chen Bowen
Published: November 2020

Background: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE.Results: We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus species – E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). Initially, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9,229 and 8,989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively, and 2,687 up-regulated and 2,581 down-regulated genes shared. Next, we identified 2,003 up-regulated and 1,958 down-regulated genes only in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone, 122 cell wall related and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in the dedifferentiation process of E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4,723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla. Conclusions: This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. It will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.
Integrated analysis of Transcriptomic Data Reveal AP-1 as a Potential Regulation Hub in Inflammation Induced Hyperalgesia Rat
Authors: Zhu Xiang , Li Feng , Wang Miqun , Su Huibin , Wu Xuedong , Qiu Haiyan , Zhou Wang , Shan Chunli , Wang Cancan , Wei Lei
Published: November 2020

Inflammation associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanism of inflammation associated chronic pain remains unclear. Complete Freund's adjuvant (CFA) induced cutaneous inflammation rat has been widely used as an inflammation-induced pain hypersensitivity model. Herein, we presented a transcriptomic profile of CFA-induced rat dorsal root ganglion via an approach targeting gene expression, DNA methylation and post-transcriptional regulation. We identified 418 differentially expressed mRNAs, 120 differentially expressed microRNAs and 2670 differentially methylated regions, which are all highly associated with multiple inflammation related pathways, including NF-κB signaling pathways and IFN signaling pathways. Integrated analysis further demonstrated that AP-1 network, which may work as a regulator of inflammation response, is sophisticatedly regulated at both transcriptomic and epigenetic level. We believe our data will not only provide drug screening targets for treating chronic pain and inflammation, but also shed a light on the molecular network inflammation induced hyperalgesia.
Clinical impact of digital and conventional PET control databases for semi-quantitative analysis of brain 18F-FDG digital PET scans 
Authors: Mairal Elise , Doyen Matthieu , Rivasseau-Jonveaux Thérèse , Malaplate Catherine , Guedj Eric , Verger Antoine
Published: November 2020

Purpose: Digital PET cameras markedly improve sensitivity and spatial resolution of brain 18F-FDG PET images compared to conventional cameras. Our study aimed to assess whether specific control databases are required to improve the diagnostic performance of these recent advances.Methods: We retrospectively selected two groups of subjects, twenty-seven Alzheimer's Disease (AD) patients and twenty-two healthy control (HC) subjects. All subjects underwent a brain 18F-FDG PET on a digital camera (Vereos, Philips®). These two group (AD and HC) are compared, using a Semi-Quantitative Analysis (SQA), to two age and sex matched controls acquired with a digital PET/CT (Vereos, Philips®) or a conventional PET/CT (Biograph 6, Siemens®) camera, at group and individual levels. Moreover, individual visual interpretation of SPM T-maps was provided for the positive diagnosis of AD by 3 experienced raters.Results: At group level, SQA using digital controls detected more marked hypometabolic areas in AD (+ 116 cm3 at p<0.001 uncorrected for the voxel, corrected for the cluster) than SQA using conventional controls. At the individual level, the accuracy of SQA for discriminating AD using digital controls was higher than SQA using conventional controls (86 % vs. 80 %, p<0.01, at p<0.005 uncorrected for the voxel, corrected for the cluster), with higher sensitivity (89 % vs. 78 %) and similar specificity (82 % vs. 82 %). These results were confirmed by visual analysis (accuracies of 84 % and 82 % for digital and conventional controls respectively, p=0.01).Conclusion: There is an urgent need to establish specific digital PET control databases for SQA of brain 18F-FDG PET images as such databases improve the accuracy of AD diagnosis.
Spatial-Temporal Calculation Simulation of Ecological Footprint of Resource and Environmental Pollution in Green Communication
Authors: Chen Roulin , Zhang Duanmin , li bo
Published: November 2020

As a quantitative evaluation method, the ecological footprint analysis method (EFA) is a frontier topic in the field of sustainable development. Human production activities will inevitably produce certain consumption, including the occupation of natural resources, resource consumption and waste production, which will have a certain impact on the ecological environment. This paper proposes to use the ecological footprint to inversely analyze the ecological environment and resource consumption, quantitatively convert the material consumption produced by human activities into the area of biological production land, and compare it with the supply area of the study area. The ecological footprint analysis method is used to reflect the changes in the indicators of regional sustainable development, and the regional sustainable development indicator system and analysis framework based on the ecosystem are constructed. The experimental result shows that the proposed model can effectively divide the resource space, and at the same time can measure the degree of resource transfer, which has important guidance for revealing the internal relationship between regional ecological footprint characteristics and regional development and evolution. significance.
Two novel anticancer compounds with minimum cardiotoxic property
Authors: Afsharirad Tayebeh , Tahmasvand Raheleh , Amini Mohsen , Daraei Bahram , Salimi Mona
Published: November 2020

Background: Although two novel synthesized compounds with tri-aryl structures; 3-(4-chlorophenyl)-5-(4-fluorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (A) and 3,5-bis-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (B) have been previously demonstrated to possess remarkable anti-breast cancer activity, their cardiotoxicity remains a major concern due to their mechanism of action. To address this concern, we assessed the ability of these compounds to cause toxicity towards H9c2 cardiomyocytes as an in vitro model of cardiotoxicity. Methods: Cytotoxic activity of both compounds was explored in vitro on H9c2 cells using MTT assay. Annexin V/PI method, intracellular ROS determination and mitochondrial membrane potential assay were applied to elucidate the mechanism of action of the cell death. Results: MTT assay revealed a concentration- and time-dependent cardiotoxicity. Findings of apoptosis by double staining with annexin V and propidium iodide divulged no cell death including apoptosis and necrosis at the concentration that were effective to inhibit cancer cells proliferation (10 µM) at 24 and 48 hours. Furthermore, flow cytometric measurement of membrane potential and ROS determination using DCFH-DA verified the safe concentration of the compounds against H9c2 cells with no cardiotoxic effect. However, the higher concentration of the compounds could induce cell death through ROS-mediated mitochondrial dysfunction. Conclusions: Altogether, the results represented two novel chemical molecules possessing anti-breast cancer activity with minimum cardiac side effect.
Routine blood parameters are helpful for early identification of influenza infection in children
Authors: Zhu Ronghe , Chen Cuie , Wang Qiu , Zhang Xixi , Lu Chaosheng , Sun Yuanyuan
Published: November 2020

Background Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), lymphocytes multiplied by platelets (LYM*PLT) and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection. Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.
Can statistical adjustment guided by causal inference improve the accuracy of effect estimation? A simulation and empirical research based on meta-analyses of case-control studies
Authors: Yan Ruohua , Liu Tianyi , Peng Yaguang , Peng Xiaoxia
Published: November 2020

Background: Statistical adjustment is often considered to control confounding bias in observational studies, especially case-control studies. However, different adjustment strategies may affect the estimation of odds ratios (ORs), and in turn affect the results of their pooled analyses. Our study is aimed to investigate how to deal with the statistical adjustment in case-control studies to improve the validity of meta-analyses.Methods: Three types of adjustment strategies were evaluated including insufficient adjustment (not all preset confounders were adjusted), full adjustment (all confounders were adjusted under the guidance of causal inference), and improper adjustment (covariates other than confounders were adjusted). We carried out a series of Monte Carlo simulation experiments based on predesigned scenarios, and assessed the accuracy of effect estimations from meta-analyses of case-control studies by combining ORs calculated according to different adjustment strategies. Then we used the data from an empirical review to illustrate the replicability of the simulation results.Results: For all scenarios with different strength of causal relations, combining ORs adjusted for confounders as far as possible would get the most precise effect estimation, regardless of the sampling approaches of case-control studies and the scale of meta-analysis. By contrast, combining ORs that were not sufficiently adjusted for confounders or improperly adjusted for mediators or colliders would easily introduce bias in causal interpretation, especially when the true effect of exposure on outcome was weak or none. The findings of the simulation experiments were further verified by the empirical research.Conclusions: Statistical adjustment guided by causal inference are recommended for effect estimation. Therefore, when conducting meta-analyses of case-control studies, the causal relationship formulated by exposure, outcome, and covariates should be firstly understood through a directed acyclic graph, and then reasonable original ORs could be extracted and combined by suitable methods.
Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling
Authors: Domenichini Alice , Casari Ilaria , Simpson Peter V , Desai Nima Maheshkumar , Chen Lingfeng , Dustin Christopher , Edmands Jeanne S , Vliet Albert van der , Mohammadi Moosa , Massi Massimiliano , Falasca Marco
Published: November 2020

Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.
Genome-wide identification and expression analysis of tomato ADK gene family during development and stress
Authors: Yang Lu , Cao Haohao , Zhang Xiaoping , Gui Liangxian , Chen Qiang , Qian Gui , Xiao Jiaxin , Li Zhengguo
Published: November 2020

Background: Adenylate kinase (ADK) is widely distributed in organisms and plays an important role in cellular energy homeostasis. In plants, ADK has important functions in plant growth and development regulation as well as adaptation to the environment. However, little information is available about the ADK genes in tomato (Solanum lycopersicum), an important economic crop.Results: To investigate the characteristics and functions of ADK genes in tomato, a total of 11 ADK genes were identified and named according to their chromosomal locations. The ADK family in Arabidopsis tomato, potato and rice was divided into six groups and motif analysis revealed that each SlADK protein contained five to eight conserved motifs. Sequence analysis revealed 4-19 exons in all SlADKs and most members possessed four. Cis-element analysis inferred that several stress response elements were found on the promoters of SlADKs. The 11 SlADKs were randomly distributed on nine of the 12 tomato chromosomes. Three duplication events were observed between tomato chromosome, and a high degree of conservation of synteny was found between tomato and potato. The online TomExpress platform prediction revealed that SlADKs were expressed in various tissues and organs, basically consistent with the data obtained from real-time quantitative PCR (qPCR). The qPCR verification was also used to determine the expression level of SlADKs and demonstrated that the genes responded to multiple abiotic stresses, such as drought, salt and cold. Besides, the qPCR results showed that SlADK transcription was responsive to most of the applied hormone treatment: methyl jasmonate, ethylene, salicylic acid, indole 3-acetic acid and abscisic acid. Notably, SlADK2 and 4 exhibited significant changes under multiple stress treatments. Furthermore, correlation networks analysis revealed co-expressed genes between SlADKs and other tomato functional genes.Conclusions: These results provide valuable information for clarifying the evolutionary relationship of the tomato ADK family and in aiding functional characterization of SlADKs in further research.
Accumulation of the delivered dose based on cone-beam CT and deformable image registration for non-small cell lung cancer treated with hypofractionated radiotherapy
Authors: Wang Bin , Wang DaQuan , Lin MaoSheng , Lu ShiPei , Zhang Jun , Chen Li , Li QiWen , Cheng ZhangKai , Liu FangJie , Guo JinYu , Liu Hui , Qiu Bo
Published: November 2020

Background: This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART).Methods: Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test.Results: Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1% , range -2.9%-44.0%). The V51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p=0.452). Only 11.1% of patients had above 5% relative decrease in V51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase <5%) was observed in doses of total lung (mean dose, V20 and V30), esophagus (mean dose, maximum dose) and heart (mean dose, V30 and V40) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV.Conclusions: LANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.
Low-dosage Ozonation in Gas-phase Biofilter Promotes Community Diversity and Robustness.
Authors: Yeung Marvin , Saingam Prakit , Xu Yang , Xi Jinying
Published: November 2020

BackgroundThe ozonation of biofilters is known to alleviate clogging and pressure drop issues while maintaining removal performances in biofiltration systems treating gaseous volatile organic compounds (VOCs). The effects of ozone on the biofilter microbiome in terms of biodiversity, community structure, metabolic abilities, and dominant taxa correlated with performance remain largely unknown.MethodsThis study investigated two biofilters treating high-concentration toluene operating in parallel, with one acting as control and the other exposed to low-dosage (200 mg/m3) ozonation. The microbial community diversity, metabolic rates of different carbon sources, functional predictions, and microbial co-occurrence networks of both communities were examined.ResultsConsistently higher biodiversity of over 30% was observed in the microbiome after ozonation, with increased overall metabolic abilities for amino acids and carboxylic acids. The relative abundance of species with reported stress-tolerant and biofilm-forming abilities significantly increased, with a consortium of changes in predicted biological pathways, including shifts in degradation pathways of intermediate compounds, while the correlation of top ASVs and genus with performance indicators showed diversifications in microbiota responsible for toluene degradation. A co-occurrence network of the community showed a decrease in average path distance and average betweenness with ozonation.ConclusionMajor degrading species highly correlated with performance shifted after ozonation. Increases in microbial biodiversity, coupled with improvements in metabolizing performances of multiple carbon sources including organic acids could explain the consistent performance commonly seen in the ozonation of biofilters despite the decrease in biomass, while avoiding acid buildup in long term operation. The increased presence of stress-tolerant microbes in the microbiome coupled with the decentralization of the co-occurrence network suggested that ozonation could not only ameliorate clogging issues but also provide a microbiome more robust to loading shock seen in full-scale biofilters.