bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for the delayed viral clearance in COVID‐19 patients
Authors: Chen Xiaoping , Hu MT Wenjia , Yang Miao , Ling Jiaxin , Zhang Yongxi , Deng Liping , Li Jinlin , Lundkvist Åke , Lindahl Johanna F , Xiong Yong 
Published: June 2021

AbstractComorbidities are important for the disease outcome of COVID‐19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID‐19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID‐19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID‐19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan‐Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS‐CoV‐2 virus clearance, however, the use of Angiotensin‐Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID‐19 patients.
Ajuba transactivates N‐cadherin expression in colorectal cancer cells through interaction with Twist
Authors: Wu Zhaoxia , Zou Xiuqun , Xu Ying , Zhou Fengli , Kuai Rong , Li Ji , Yang Daming , Chu Yimin , Peng Haixia 
Published: June 2021

AbstractAjuba is a multiple LIM domain‐containing protein and functions as a transcriptional coregulator to modulate many gene expressions in various cellular processes. Here, we describe that the LIM domain of Ajuba interacts with Twist, and the Twist box is a pivotal motif for the interaction. Biologically, Ajuba enhances transcription of target gene N‐cadherin as an obligate coactivator of Twist. The enhancement is achieved by binding to the E‐box element within N‐cadherin promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays. Mechanistic investigation demonstrates that Ajuba recruits CBP and Twist to form a ternary complex at the Twist target promoter region and concomitantly enhances histone acetylation at these sites. These findings identify that Twist is a new interacting protein of Ajuba and Ajuba/Twist/CBP ternary complex may be a potential treatment strategy for Twist‐related tumour metastasis.
CircPLCE1 facilitates the malignant progression of colorectal cancer by repressing the SRSF2‐dependent PLCE1 pre‐RNA splicing
Authors: Chen Zhilei , Chen Hongyu , Yang Lei , Li Xiangnan , Wang Zhenjun 
Published: June 2021

AbstractStudies have demonstrated that circular RNAs (circRNAs) play important roles in various types of cancer; however, the mechanisms of circRNAs located in the nucleus have rarely been explored. Here, we report a novel circular RNA circPLCE1 (hsa_circ_0019230) that facilitates the malignant progression of colorectal cancer (CRC) by repressing serine/arginine‐rich splicing factor 2 (SRSF2)‐dependent phospholipase C epsilon 1 (PLCE1) pre‐RNA splicing. Quantitative real‐time polymerase chain reaction was used to determine the expression of circPLCE1 in CRC tissues and cells. Cell Counting Kit‐8, Transwell and flow cytometric assays were used to assess the role of circPLE1 in CRC cell proliferation, migration and apoptosis, respectively. An animal study was conducted to test the role of circPLCE1 in vivo. Furthermore, catRAPID and RPISeq were used to predict the possible binding proteins of circPLCE1. RNA fractionation and RNA immunoprecipitation assays were used to confirm the RNA‐protein interaction. In this study, we found that circPLCE1 was more significantly down‐regulated in CRC tissues compared with that in adjacent normal tissues. However, circPLCE1 knockdown suppressed CRC cell proliferation, migration and invasion and increased apoptosis. Nude mouse experiments showed that ectopic expression of circPLCE1 dramatically increased tumour growth in vivo. Mechanistically, circPLCE1 directly bound to the SRSF2 protein, repressing SRSF2‐dependent PLCE1 pre‐RNA splicing, resulting in the progression of CRC. Individually mutating the binding sites of circPLCE1 abolished the inhibition of PLCE1 mRNA production. Our study revealed a novel molecular mechanism in the regulation of PLCE1 and suggested a new function of circular RNA.
Behavioral and biological divergence in monozygotic twin pairs discordant for autism phenotypes: A systematic review
Authors: Myers Lynnea , Pan Pei‐Yin , Remnélius Karl Lundin , Neufeld Janina , Marschik Peter B. , Jonsson Ulf , Bölte Sven 
Published: June 2021

AbstractBackgroundNon‐shared environment (NSE) effects account for around one‐third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce.MethodsA systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co‐twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle–Ottawa Scale.ResultsTwenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health‐related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible.ConclusionsOur results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co‐occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.
Telephone follow‐up to reduce unplanned hospital returns for older emergency department patients: A randomized trial
Authors: van Loon‐van Gaalen Merel , van der Linden M. Christien , Gussekloo Jacobijn , van der Mast Roos C. 
Published: June 2021

AbstractBackground/ObjectivesTelephone follow‐up calls could optimize the transition from the emergency department (ED) to home for older patients. However, the effects on hospital return rates are not clear. We investigated whether telephone follow‐up reduces unplanned hospitalizations and/or unplanned ED return visits within 30 days of ED discharge.DesignPragmatic randomized controlled trial with allocation by month; odd months intervention group, even months control group.SettingTwo ED locations of a non‐academic teaching hospital in The Netherlands.ParticipantsCommunity‐dwelling adults aged ≥70 years, discharged home from the ED were randomized to the intervention group (N = 4732) or control group (N = 5104).InterventionIntervention group patients: semi‐scripted telephone call from an ED nurse within 24 h after discharge to identify post‐discharge problems and review discharge instructions. Control group patients: scripted satisfaction survey telephone call.MeasurementsPrimary outcome: total number of unplanned hospitalizations and/or ED return visits within 30 days of ED discharge. Secondary outcomes: separate numbers of unplanned hospitalizations and ED return visits. Subgroup analysis by age, sex, living condition, and degree of crowding in the ED at discharge.ResultsOverall, 42% were males, and median age was 78 years. In the intervention group, 1516 of 4732 patients (32%) consented, and in the control group 1659 of 5104 (33%) patients. Unplanned 30‐day hospitalization and/or ED return visit was found in 16% of intervention group patients and 14% of control group patients (odds ratio 1.16; 95% confidence interval: 0.96–1.42). Also, no statistically significant differences were found in secondary outcome measures. Within the subgroups, the intervention did not have beneficial effects for the intervention group.ConclusionTelephone follow‐up after ED discharge in older patients did not result in reduction of unplanned hospital admissions and/or ED return visits within 30 days. These results raise the question of whether other outcomes could be improved by post‐discharge ED telephone follow‐up.
Nesfatin‐1 is an inhibitor of the growth hormone‐insulin‐like growth factor axis in goldfish (Carassius auratus)
Authors: Blanco Ayelén M. , Pemberton Joshua G. , Gonzalez Ronald , Hatef Azadeh , Pham Vi , Chang John P. , Unniappan Suraj 
Published: June 2021

AbstractNesfatin‐1, an 82 amino acid peptide cleaved from the N‐terminal of its precursor nucleobindin‐2 (NUCB2), is emerging as a multifunctional peptide in fish. The present study aimed to determine whether nesfatin‐1 plays a role in fish somatic growth by modulating the growth hormone (GH)/insulin‐like growth factor (IGF) axis, using a representative teleost model, the goldfish (Carassius auratus). The results demonstrated that a single i.p. injection of synthetic goldfish nesfatin‐1 significantly decreased the expression of hypothalamic pacap (approximately 90%) and pituitary Gh (approximately 90%) mRNAs at 15 minutes post‐injection. Serum GH levels were also reduced as a result of nesfatin‐1 administration, by approximately 45% and 55% at 15 and 30 minutes post‐injection, respectively. Likewise, in vitro treatment of goldfish dispersed pituitary cells with nesfatin‐1 reduced Gh secretion, suggesting that nesfatin‐1 acts directly on pituitary somatotrophs to inhibit Gh release. Exposure of cultured liver fragments to nesfatin‐1 (0.1, 1 and 10 nmol L‐1) led to a significant reduction in igf‐1 mRNA at 120 minutes and of igf‐II mRNA at 30 and 60 minutes post‐incubation. Collectively, these results indicate a suppressive role for nesfatin‐1 on the goldfish GH/IGF axis. Immunohistochemical studies demonstrated that NUCB2/nesfatin‐1‐like immunoreactivity, although present in the goldfish pituitary, is not colocalised with GH in goldfish somatotrophs. Thus, nesfatin‐1 does not appear to act in an autocrine manner to regulate GH secretion. Taken together, this research found that the pituitary gland is an important source of endogenous NUCB2/nesfatin‐1 and also that nesfatin‐1 directly suppresses the Gh/IGF axis in goldfish.
Fractional carbon dioxide laser versus carbon‐assisted Q‐switched Nd: YAG laser in the treatment of dilated facial pores
Authors: Eldeeb Fatma , Wahid Reham M. , Alakad Rania 
Published: June 2021

AbstractBackgroundThe treatment of dilated facial pores is difficult, and the ideal modality is not established yet. Different ablative and nonablative lasers have been used in the treatment of dilated pores with variable outcomes.AimTo evaluate and compare the efficacy of fractional CO2 laser versus carbon‐assisted Q‐switched Nd: YAG laser in dilated facial pores.MethodsThe study included 80 patients with dilated pores divided into two groups each containing 40 patients. Group (A) had fractional CO2 laser treatment, and group (B) received Q‐switched Nd: YAG laser treatment after the application of a carbon solution on the face. The treatment was repeated monthly for a total of 3 sessions. Objective and subjective assessments of the clinical outcome were performed.ResultsBoth modalities significantly improved the dilated pores; however, the clinical response was statistically higher and the improvement was maintained for a longer duration of time in the factional laser group compared with the carbon‐assisted Q‐switched Nd: YAG laser group (p = 0.01). The downtime was significantly lower in the Q‐switched Nd: YAG laser group, and the patients’ satisfaction rates were comparable in both groups.ConclusionThe two laser systems appear to be effective, safe, and well‐tolerated in the treatment of dilated pores. The fractional CO2 laser was associated with a significantly higher and more prolonged clinical response.
Beyond clinical trials: Extending the role of the clinical research nurse into social care and homeless research
Authors: Biswell R Elizabeth , Clark Michael , Tinelli Michela , Manthorpe Gillian , Neale Joanne , Whiteford Martin , Cornes Michelle 
Published: June 2021

AbstractAimClinical research nurses work at the fulcrum of clinical trials with clearly defined roles and responsibilities. In England, the National Institute for Health Research (the main funder of health research) has broadened its scope to encompass social care research. The expectation is that clinical research nurses will expand their skill set to support these new studies, many of which will employ qualitative and mixed methods. This discussion paper explores the challenges of facilitating this clinical academic workforce development through a case study of a homeless health and social care research project. This was one of the first studies to engage clinical research nurses in this new and expanded role.BackgroundMuch of what is known about the research nurse workforce has been generated through studies of clinical trials in oncology. The ‘caring‐recruiting’ dichotomy has been used as a heuristic device for identifying workforce issues that can impact on study delivery such as how intense pressure to recruit study participants leads to low job satisfaction.DesignThis case study reflects on the authors' experiences of employing a clinical research nurse in a social care research project concerned with the discharge of homeless people from hospital. The ‘caring‐recruiting’ dichotomy is used to generate new information about the relationship between workforce development and the successful delivery of social care research.ConclusionThe case study illuminates how social care research can generate different pressures and ethical challenges for research nurses. The time and skill it took to recruit study participants identified as ‘hard to reach’ was suggestive of the need to move beyond performance measures that prioritise recruitment metrics. The need for different types of staff supervision and training was also warranted as supporting study participants who were homeless was often distressing, leading to professional boundary issues.Relevance to workforce developmentThis study highlights that performance management, training and supervisory arrangements must be tailored to the characteristics of each new study coming onto the portfolio to ensure research nurses are fully supported in this new and expanded role.
Decellularized matrix could affect the proliferation and differentiation of periodontal ligament stem cells in vitro
Authors: Huang Jia‐Ping , Wu Yan‐Min , Liu Jia‐Mei , Zhang Lan , Li Bo‐Xiu , Chen Li‐Li , Ding Pei‐Hui , Tan Jing‐Yi 
Published: June 2021

AbstractObjective and BackgroundRecently, decellularized matrix (DCM) is considered as a new biomaterial for tissue regeneration. To explore the possible application of DCM in periodontal regeneration, the effect of DCM from three different cells on the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs) was investigated.MethodsDCM derived from human periodontal ligament cells (PDLCs), dental pulp cells (DPCs), and gingival fibroblasts (GFs) were fabricated using Triton X‐100/NH4OH combined with DNase I. Allogeneic PDLSCs were cultured on PDLC‐DCM, DPC‐DCM, and GF‐DCM, respectively. The proliferative capacity of PDLSCs was evaluated by PicoGreen assay kit. The expression of alkaline phosphatase (ALP), runt‐related transcription factor‐2 (RUNX2), osteocalcin (OCN), collagen I (COL1), periostin (POSTN), and cementum protein 1 (CEMP1) were detected by qRT‐PCR and western blotting.ResultsPDLC‐DCM, DPC‐DCM, and GF‐DCM had similar and integrated networks of extracellular matrix, as well as significantly decreased DNA content. Compared with control group in which PDLSCs were directly seeded in culture plates, PDLC‐DCM, DPC‐DCM, and GF‐DCM promoted the proliferation of re‐seeded PDLSCs. Additionally, PDLSCs on DCM exhibited higher mRNA and protein expression levels of ALP, RUNX2, OCN, and COL1. The expression of POSTN in PDLC‐DCM group was significantly higher than control group at both mRNA and protein levels.ConclusionsPDLC‐DCM, DPC‐DCM, and GF‐DCM could enhance the proliferation of PDLSCs. PDLC‐DCM facilitated osteogenic differentiation and periodontal ligament differentiation of PDLSCs, while DPC‐DCM and GF‐DCM promoted osteogenic differentiation.
Multidose pharmacokinetics and safety of a modified, compounded theophylline product in dogs
Authors: Reinhart Jennifer M. , Perkowski Claudia , Lester Courtney , Campos Valeria , Kadotani Saki , Li Zhong , McKiernan Brendan C. , Fries Ryan 
Published: June 2021

AbstractTheophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species‐validated commercial products are available. This study reports the single‐dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well‐established, USP‐compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 μg/ml for 91 +/− 15% of the dosing interval. There was no significant difference in half‐life between single‐dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.
Support for the adaptive decoupling hypothesis from whole‐transcriptome profiles of a hypermetamorphic and sexually dimorphic insect, Neodiprion lecontei
Authors: Herrig Danielle K. , Vertacnik Kim L. , Kohrs Anna R. , Linnen Catherine R. 
Published: June 2021

AbstractThough seemingly bizarre, the dramatic morphological and ecological transformation that occurs when immature life stages metamorphose into reproductive adults is one of the most successful developmental strategies on the planet. The adaptive decoupling hypothesis (ADH) proposes that metamorphosis is an adaptation for breaking developmental links between traits expressed in different life stages, thereby facilitating their independent evolution when exposed to opposing selection pressures. Here, we draw inspiration from the ADH to develop a conceptual framework for understanding changes in gene expression across ontogeny. We hypothesized that patterns of stage‐biased and sex‐biased gene expression are the product of both decoupling mechanisms and selection history. To test this hypothesis, we characterized transcriptome‐wide patterns of gene‐expression traits for three ecologically distinct larval stages (all male) and adult males and females of a hypermetamorphic insect (Neodiprion lecontei). We found that stage‐biased gene expression was most pronounced between larval and adult males, which is consistent with the ADH. However, even in the absence of a metamorphic transition, considerable stage‐biased expression was observed among morphologically and behaviourally distinct larval stages. Stage‐biased expression was also observed across ecologically relevant Gene Ontology categories and genes, highlighting the role of ecology in shaping patterns of gene expression. We also found that the magnitude and prevalence of stage‐biased expression far exceeded adult sex‐biased expression. Overall, our results highlight how the ADH can shed light on transcriptome‐wide patterns of gene expression in organisms with complex life cycles. For maximal insight, detailed knowledge of organismal ecology is also essential.
Abstraction and analogy‐making in artificial intelligence
Authors: Mitchell Melanie 
Published: June 2021

AbstractConceptual abstraction and analogy‐making are key abilities underlying humans' abilities to learn, reason, and robustly adapt their knowledge to new domains. Despite a long history of research on constructing artificial intelligence (AI) systems with these abilities, no current AI system is anywhere close to a capability of forming humanlike abstractions or analogies. This paper reviews the advantages and limitations of several approaches toward this goal, including symbolic methods, deep learning, and probabilistic program induction. The paper concludes with several proposals for designing challenge tasks and evaluation measures in order to make quantifiable and generalizable progress in this area.
Role of experimental periodontitis in inducing pulmonary inflammation in mice
Authors: Tian Huan , Zhang Zheng , Wang Xueyuan , Liu Wenyan , Wang Zuomin 
Published: June 2021

AbstractObjectiveThe aim of the study was to explore the potential role of experimental periodontitis in pulmonary inflammation in mice.Materials and methodsMice were divided into control, ligature‐induced periodontitis (L) and ligature plus Porphyromonas gingivalis (P. gingivalis)‐induced periodontitis (LPG) groups. Alveolar bone resorption, pulmonary function, lung tissue histology and cytokine expression were examined at 2, 4 and 8 weeks. Then cytokines and neutrophils in the peripheral blood and lung tissue were further assessed at 8 weeks to determine the role of cytokines induced by LPG periodontitis, and the effect of P. gingivalis was evaluated using P. gingivalis‐IgG and P. gingivalis gingipain.ResultsAlveolar bone resorption was more severe in the L and LPG groups. However, pulmonary inflammation was observed only in the LPG group at 8 weeks when cytokines and neutrophils in the peripheral blood and lung tissue were the most significant elevation, along with higher levels of P. gingivalis‐IgG and P. gingivalis gingipain. Cytokine levels were also increased in the gingival tissue, peripheral blood and lung tissue in the L group, accompanied by elevated peripheral blood neutrophils, but not as significantly as that in the LPG group.ConclusionsLPG periodontitis can trigger pulmonary inflammation over the long term, in which cytokines and P. gingivalis play an important role.