bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide identification of A-to-I RNA editing events provides the functional implications in PDAC
Authors: Mei Yue , Liang Dong , Ai Bin , Wang Tengjiao , Guo Shiwei , Jin Gang , Yu Dong 
Published: February 2023

IntroductionRNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.MethodWe characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.ResultA large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.ConclusionRNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.
Elicitation of domain knowledge for a machine learning model for paediatric critical illness in South Africa
Authors: Pienaar Michael A. , Sempa Joseph B. , Luwes Nicolaas , George Elizabeth C. , Brown Stephen C. 
Published: February 2023

ObjectivesDelays in identification, resuscitation and referral have been identified as a preventable cause of avoidable severity of illness and mortality in South African children. To address this problem, a machine learning model to predict a compound outcome of death prior to discharge from hospital and/or admission to the PICU was developed. A key aspect of developing machine learning models is the integration of human knowledge in their development. The objective of this study is to describe how this domain knowledge was elicited, including the use of a documented literature search and Delphi procedure.DesignA prospective mixed methodology development study was conducted that included qualitative aspects in the elicitation of domain knowledge, together with descriptive and analytical quantitative and machine learning methodologies.SettingA single centre tertiary hospital providing acute paediatric services.ParticipantsThree paediatric intensivists, six specialist paediatricians and three specialist anaesthesiologists.InterventionsNone.Measurements and main resultsThe literature search identified 154 full-text articles reporting risk factors for mortality in hospitalised children. These factors were most commonly features of specific organ dysfunction. 89 of these publications studied children in lower- and middle-income countries. The Delphi procedure included 12 expert participants and was conducted over 3 rounds. Respondents identified a need to achieve a compromise between model performance, comprehensiveness and veracity and practicality of use. Participants achieved consensus on a range of clinical features associated with severe illness in children. No special investigations were considered for inclusion in the model except point-of-care capillary blood glucose testing. The results were integrated by the researcher and a final list of features was compiled.ConclusionThe elicitation of domain knowledge is important in effective machine learning applications. The documentation of this process enhances rigour in such models and should be reported in publications. A documented literature search, Delphi procedure and the integration of the domain knowledge of the researchers contributed to problem specification and selection of features prior to feature engineering, pre-processing and model development.
Trend analysis of mortality rates and causes of death in children under 5 years of age in Xuzhou, China from 2016 to 2020
Authors: Xu Zhiyuan , Liu Haonan , Zhou Shuaishuai , Chen Tiancheng , Meng Chao , Li Shengli , Yan Xianliang , Liu Xiao 
Published: February 2023

ObjectivesTo analyze the trends in mortality and causes of death among children under 5 years of age in Xuzhou, China between 2016 and 2020, in order to protect children's health and provide a basis for formulating child survival, development, and protection strategies.MethodsA population-based epidemiological study was conducted. Data were obtained from the Xuzhou Center for Disease Control Prevention. We input the data into the excel database and analyzed with SPSS20.0.ResultsThere were 1,949 children under 5 years of age died in Xuzhou, The number of deaths from 2016 to 2020 were 573 (29.40%), 577 (29.60%), 371 (19.04%), 334 (17.14%), and 94 (4.82%) respectively, mortality in children showed a downward trend. The number of deaths was relatively high in January (195 cases, 10.01%), February (190 cases, 9.75%), and May (180 cases, 9.24%), while was relatively small in July (147 cases, 7.54%), August (139 cases, 7.13%), and September (118 cases, 6.05%). The leading causes of death (COD) in children under 5 years of age were neonatal suffocation and hypoxia (323 cases, 16.57%). Pizhou (528 cases, 27.09%) showed the highest number of deaths in children under 5 years of age in China, and the Kaifa (25 cases, 1.28%) zone showed the lowest death toll.ConclusionsOur research suggested that the current strategies for reducing child mortality should prioritize the actions on neonatal deaths and conduct targeted interventions for the main cause.
Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review
Authors: Balalian Arin A. , Graeve Richard , Richter Matthias , Fink Astrid , Kielstein Heike , Martins Silvia S. , Philbin Morgan M. , Factor-Litvak Pam 
Published: February 2023

AimThis systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies.MethodsWe searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using “Covidence” systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment.ResultsData were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis.ConclusionWe explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.
3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma
Authors: Lian Zheng , Sang Chenglin , Li Nianhu , Zhai Honglin , Bai Wenzhe 
Published: February 2023

Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds.Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models.Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4).Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q2 (0.63) and R2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability.Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma.
A molecular perspective on the invasibility of the southern ocean benthos: The impact of hypoxia and temperature on gene expression in South American and Antarctic Aequiyoldia bivalves
Authors: Martínez Mariano , González-Aravena Marcelo , Held Christoph , Abele Doris 
Published: February 2023

When an organism makes a long-distance transition to a new habitat, the associated environmental change is often marked and requires physiological plasticity of larvae, juveniles, or other migrant stages. Exposing shallow-water marine bivalves (Aequiyoldia cf. eightsii) from southern South America (SSA) and the West Antarctic Peninsula (WAP) to changes in temperature and oxygen availability, we investigated changes in gene expression in a simulated colonization experiment of the shores of a new continent after crossing of the Drake Passage, and in a warming scenario in the WAP. Bivalves from SSA were cooled from 7°C (in situ) to 4°C and 2°C (future warmed WAP conditions), WAP bivalves were warmed from 1.5°C (current summer in situ) to 4°C (warmed WAP), gene expression patterns in response to thermal stress by itself and in combination with hypoxia were measured after 10 days. Our results confirm that molecular plasticity may play a vital role for local adaptation. Hypoxia had a greater effect on the transcriptome than temperature alone. The effect was further amplified when hypoxia and temperature acted as combined stressors. The WAP bivalves showed a remarkable ability to cope with short-term exposure to hypoxia by switching to a metabolic rate depression strategy and activating the alternative oxidation pathway, whilst the SSA population showed no comparable response. In SSA, the high prevalence of apoptosis-related differentially expressed genes especially under combined higher temperatures and hypoxia indicated that the SSA Aequiyoldia are operating near their physiological limits already. While the effect of temperature per se may not represent the single most effective barrier to Antarctic colonization by South American bivalves, the current distribution patterns as well as their resilience to future conditions can be better understood by looking at the synergistic effects of temperature in conjunction with short-term exposure to hypoxia.
Transcriptome and proteome depth analysis indicate ABA, MAPK cascade and Ca2+ signaling co-regulate cold tolerance in Rhododendron chrysanthum Pall.
Authors: Zhang Qingyi , Li Yue , Cao Kun , Xu Hongwei , Zhou Xiaofu 
Published: February 2023

IntroductionCold stress is a global common problem that significantly limits plant development and geographical distribution. Plants respond to low temperature stress by evolving interrelated regulatory pathways to respond and adapt to their environment in a timely manner. Rhodoendron chrysanthum Pall. (R. chrysanthum) is a perennial evergreen dwarf shrub used for adornment and medicine that thrives in the Changbai Mountains at high elevations and subfreezing conditions.MethodsIn this study, a comprehensive investigation of cold tolerance (4°C, 12h) in R. chrysanthum leaves under cold using physiological combined with transcriptomic and proteomic approaches.ResultsThere were 12,261 differentially expressed genes (DEGs) and 360 differentially expressed proteins (DEPs) in the low temperature (LT) and normal treatment (Control). Integrated transcriptomic and proteomic analyses showed that MAPK cascade, ABA biosynthesis and signaling, plant-pathogen interaction, linoleic acid metabolism and glycerophospholipid metabolism were significantly enriched in response to cold stress of R. chrysanthum leaves.DiscussionWe analyzed the involvement of ABA biosynthesis and signaling, MAPK cascade, and Ca2+ signaling, that may jointly respond to stomatal closure, chlorophyll degradation, and ROS homeostasis under low temperature stress. These results propose an integrated regulatory network of ABA, MAPK cascade and Ca2+ signaling comodulating the cold stress in R. chrysanthum, which will provide some insights to elucidate the molecular mechanisms of cold tolerance in plants.
Energy saving behavior in university organizations: The value of norm constructions in a “rational choice” action model
Authors: Heib Sascha , Hildebrand Jan , Kortsch Timo 
Published: February 2023

IntroductionIn times of rising energy prices and increasing importance of climate change, saving energy becomes even more important. Universities are large public institutions with significant energy-saving potential. This study investigated the energy-saving behavior of students and employees at a German university. In contrast to previous studies, which often focused on individual buildings, this study took a comprehensive approach and addressed all university members (employees and students). A extended model of the Theory of Planned Behavior (TPB) served as the theoretical basis. Considering the specific organizational context, the main question of the study was to explore the interlinkages between the intention to save energy, corresponding consumption behavior, and the effects of injunctive and descriptive social norms within the social system of the organization. Furthermore, the impact of “not energy related” factors like the identification with the organization was tested.MethodsAs methodological approach a university-wide quantitative online survey was conducted. For the survey, a standardized questionnaire containing several scales on energy consumption behavior and TBP-constructs was used. All in all, data from a total of 1,714 members of the university participating in the study was analyzed.ResultsStructural equation modeling showed that the extended TPB model yields a satisfactory amount of explained variance (approximately 40%) for intention and a moderate amount (approximately 20%) for behavior. The strongest predictors are personal norm and behavioral control. The organizational influence factor identification was also significant for intention, but only to a small extent.DiscussionThe results extend the understanding of the TPB in the context of energy conservation in universities and emphasize that the sense of behavioral control and the personal norm must always be considered when intervening in this context to promote energy conservation and thus provide valuable hints for practical measures.
Toddler home math environment: Triangulating multi-method assessments in a U.S. Sample
Authors: Miller Portia , Elliott Leanne E. , Podvysotska Tamara , Ptak Chelsea , Duong Shirley , Fox Danielle , Coulanges Linsah , Libertus Melissa , Bachman Heather J. , Votruba-Drzal Elizabeth 
Published: February 2023

IntroductionCurrent research has documented the home math environment (HME) of preschoolers and kindergarteners. Very few studies, however, have explored the number and spatial activities in which parents engage with children during their toddler years.MethodsThis study examined the HME of 157 toddlers using several methodologies, including surveys, time diaries, and observations of math talk. Further, it examined correlations within and across data sources to identify areas of convergence and triangulation, and correlated HME measures with measures of toddlers’ number and spatial skills.ResultsFindings showed that, in general, uses of different types of math activities, including both number and spatial, were intercorrelated within method. Across methods, there was high intercorrelation between the frequency of math activities reported on parent surveys and the diversity of types of math activities endorsed in time diary interviews. Parent math talk gleaned from semi-structured interviews functioned as a separate aspect of the HME; different types of math talk shared few intercorrelations with engagement in math activities as reported in either surveys or time diaries. Finally, several HME measures positively correlated with toddlers’ math skills.DiscussionGiven extant research demonstrating that both math activities and math talk predict children’s math skills, our results stress the need for multimethod studies that differentiate among these HME opportunities.
Psychological capital, quality of life, and well-being in mother caregivers of individuals with down syndrome
Authors: Chiracu Alina , Cosma Germina-Alina , Stepan Amalia Raluca , Cosma Marian Alexandru , Corlaci Ionuț , Călugăru Eleonora Daniela Ciupeanu , Voinea Florin , Zăvăleanu Mihaela , Burileanu Horia Alin , Avramescu Taina 
Published: February 2023

IntroductionCaused by an error in cell division that produces an additional chromosome 21, Down syndrome (DS) is one of the most common developmental disorders in the world. This study aims to analyze the relationship between psychological capital, quality of life and well-being of caregivers of individuals with Down syndrome (DS).MethodsThe participants were 98 caregivers (mothers, M = 52.13, SD = 11.39) of individuals with Down syndrome. The instruments used were the Psychological Capital Questionnaire (measuring self-efficacy, resilience, optimism, and hope), Quality of Life Questionnaire (including social support, general satisfaction, physical/psychological health, absence of excessive workload/free time), and Psychological Wellbeing Scale, investigating the following dimensions: self-acceptance, positive relationships with others, autonomy, environmental mastery, purpose in life, and personal growth.ResultsThe mediation analysis showed that self-efficacy, hope, and resilience are positively associated to quality of life, and optimism is positively associated to well-being. The total effects of psychological capital on well-being are positive and significant and quality of life mediates the relationship between psychological capital and well-being.DiscussionThese results show that psychological capital is an important inner resource for caregivers of DS individuals and must be improved through support services, so that caregivers have a higher perception of the quality of life and implicitly of well-being.
Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia
Authors: Bergamini Giorgio , Massinet Helene , Hart Aaron , Durkin Sean , Pierlot Gabin , Steiner Michel Alexander 
Published: February 2023

IntroductionPeople with dementia (PwD) often present with neuropsychiatric symptoms (NPS). NPS are of substantial burden to the patients, and current treatment options are unsatisfactory. Investigators searching for novel medications need animal models that present disease-relevant phenotypes and can be used for drug screening. The Senescence Accelerated Mouse-Prone 8 (SAMP8) strain shows an accelerated aging phenotype associated with neurodegeneration and cognitive decline. Its behavioural phenotype in relation to NPS has not yet been thoroughly investigated. Physical and verbal aggression in reaction to the external environment (e.g., interaction with the caregiver) is one of the most prevalent and debilitating NPS occurring in PwD. Reactive aggression can be studied in male mice using the Resident-Intruder (R-I) test. SAMP8 mice are known to be more aggressive than the Senescence Accelerated Mouse-Resistant 1 (SAMR1) control strain at specific ages, but the development of the aggressive phenotype over time, is still unknown.MethodsIn our study, we performed a longitudinal, within-subject, assessment of aggressive behaviour of male SAMP8 and SAMR1 mice at 4, 5, 6 and 7 months of age. Aggressive behaviour from video recordings of the R-I sessions was analysed using an in-house developed behaviour recognition software.ResultsSAMP8 mice were more aggressive relative to SAMR1 mice starting at 5 months of age, and the phenotype was still present at 7 months of age. Treatment with risperidone (an antipsychotic frequently used to treat agitation in clinical practice) reduced aggression in both strains. In a three-chamber social interaction test, SAMP8 mice also interacted more fervently with male mice than SAMR1, possibly because of their aggression-seeking phenotype. They did not show any social withdrawal.DiscussionOur data support the notion that SAMP8 mice might be a useful preclinical tool to identify novel treatment options for CNS disorders associated with raised levels of reactive aggression such as dementia.