bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA‐320c inhibits articular chondrocytes proliferation and induces apoptosis by targeting mitogen‐activated protein kinase 1 (MAPK1)
Authors: Zhao Like , Zhou Rongwei , Wang Qian , Cheng Yongjing , Gao Ming , Huang Cibo 
Published: January 2021

AbstractAimTo clarify the interaction of microRNA‐320c (miR‐320c) and mitogen‐activated protein kinase 1 (MAPK1), and to investigate the effects of miR‐320c on articular chondroctye proliferation and apoptosis.MethodsLentiviral expression vectors were constructed and dual luciferase assays containing MAPK1 3ʹ‐untranslated regions (3'‐UTRs) were performed. Small hairpin RNA (shRNA) was utilized to modulate MAPK1 expression. The messenger RNA and protein expression levels were determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting respectively. Cell Counting Kit‐8 and flow cytometry were conducted to detect the proliferation and apoptosis of Human Chondrocyte‐articular (HC‐a) cells. Besides that, the influences of miR‐320c and MAPK1 on MAPK pathway activation were also evaluated.ResultsOur data identified MAPK1 as a direct target gene of miR‑320c, and miR‐320c can negatively regulate MAPK1 expression by directly binding to MAPK1 3ʹ‐UTR in HC‐a cells. Further functional study displayed that miR‐320c overexpression and MAPK1 shRNA significantly suppressed the proliferation of HC‐a cells and promoted cell apoptosis. Meanwhile, MAPK1 shRNA could attenuate miR‐320c inhibitor promotive effects on HC‐a cell proliferation and reverse its inhibitory effect on cell apoptosis. MAPK1 overexpression could rescue the inhibitory effect of miR‑320c on HC‐a cell proliferation, and weaken the accelerating effect of miR‐320c on cell apoptosis. However, neither miR‐320c or MAPK1 shRNA regulate the expression of c‐JUN, JNK and c‐Fos.ConclusionmiR‐320c inhibits articular chondrocyte proliferation and induces apoptosis by targeting MAPK1, suggesting that miR‐320c perhaps participates in the pathogenesis of osteoarthritis and acts as a potential target for the therapeutic treatment of osteoarthritis.
Fatigue in psoriatic arthritis: Is it related to disease activity?
Authors: Lai Tin Lok , Au Chi Kit , Chung Ho Yin , Leung Man Chi , Ng Woon Leung , Lau Chak Sing 
Published: January 2021

AbstractAimFatigue is commonly associated with psoriatic arthritis (PsA). However, information about its prevalence and associated factors is sparse. The primary objective here was to find the prevalence and magnitude of PsA fatigue. The secondary objective was to explore its associated risk factors, particularly emphasis on the effect of disease activity control.MethodsPsA patients who fulfilled Classification Criteria For Psoriatic Arthritis were consecutively recruited from local rheumatology clinics. Fatigue was assessed by a 13‐item self‐administered questionnaire (Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT‐F]) (0‐52). Data collected and analyzed included: demographic data, disease activity data, comorbidities and medications use.ResultsThere were 231 eligible PsA patients recruited. The mean FACIT‐F score was 37.5 ± 9.1. Severe fatigue, defined as FACIT‐F score < 30, was found in 49 (22.1%) of them. The univariate model identified these associated factors of fatigue: tender and swollen joint count, dactylitis count, Psoriasis Area and Severity Index (PASI) score, pain and general health perception, Disease Activity in Psoriatic Arthritis (DAPSA) score, Health Assessment Questionnaire, the use of cyclosporine, sulphasalazine and biologic agents. The final regression model identified DAPSA and PASI were closely associated with severe fatigue (P = .003 and P = .04 respectively). No associations with fatigue were found between age, gender, disease duration, comorbidities and medication use. However, there were weak correlations between the magnitude of FACIT‐F score, DAPSA and PASI with r = −.3 and r = −.26 respectively.ConclusionSevere fatigue was common in PsA patients, and its magnitude was closely correlated with DAPSA and PASI score, indicating its multifactorial nature. Achieving DAPSA and PASI remission could significantly alleviate the fatigue intensity to a certain extent. However, treatment for PsA‐related fatigue should adopt a multidisciplinary approach in addition to disease activity control.
Propofol suppresses lung cancer tumorigenesis by modulating the circ‐ERBB2/miR‐7‐5p/FOXM1 axis
Authors: Gao Jie , Ding Chengzhi , Zhou Junhui , Wu Gang , Han Zongmao , Li Jianchao , Hei Feilong 
Published: January 2021

AbstractBackgroundPropofol is a commonly used anesthetic for cancer surgery. Previous studies have shown that propofol has an anticancer role in various cancers, including lung cancer. This study aimed to investigate the role of propofol in lung cancer and its underlying mechanism.MethodsCell proliferation was determined by cell counting kit‐8 (CCK‐8) and colony formation assays. Flow cytometry and transwell assays were used to detect cell apoptosis and invasion, respectively. Glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratios. The levels of circular RNA erb‐b2 receptor tyrosine kinase 2 (circ‐ERBB2), microRNA‐7‐5p (miR‐7‐5p) and forkhead box M1 (FOXM1) were tested by quantitative real‐time PCR and Western blot. The binding relationship between miR‐7‐5p and circ‐ERBB2/FOXM1 was verified by dual‐luciferase reporter assay. Moreover, in vivo experiments were performed by establishing a mouse xenograft model.ResultsPropofol suppressed cell proliferation, invasion and glycolysis and expedited apoptosis in lung cancer cells. Circ‐ERBB2 and FOXM1 were upregulated, while miR‐7‐5p was decreased in lung cancer tissues and cells. Propofol suppressed lung cancer cell progression by regulating circ‐ERBB2. Additionally, miR‐7‐5p directly interacted with circ‐ERBB2 and FOXM1. Also, propofol played an antitumor role in lung cancer via modulating miR‐7‐5p or FOXM1. Moreover, circ‐ERBB2 knockdown enhanced the suppressive effect of propofol on tumor growth in vivo.ConclusionsPropofol inhibited lung cancer progression via mediating circ‐ERBB2/miR‐7‐5p/FOXM1 axis, which might provide an effective therapeutic target for lung cancer therapy.
Insights into the status and distribution of cheetah (Acinonyx jubatus) in an understudied potential stronghold in southern Tanzania
Authors: Strampelli Paolo , Searle Charlotte E. , Smit Josephine , Grau Ana , Henschel Philipp , Lobora Alex L. , Mitchell Nicholas , Macdonald David W. , Dickman Amy J. 
Published: January 2021

AbstractResearch on the African cheetah (Acinonyx jubatus) exhibits strong geographical biases, with most studies taking place within a few, well‐studied populations. Here, we provide the first insights into the status and distribution of a globally important cheetah population in the 50,000 km2 Ruaha‐Rungwa landscape in southern Tanzania. We employed data from four methods (systematic camera trap surveys, sign surveys, community camera trapping, and observations by photo‐tourism guides) to improve knowledge of this understudied population. Our findings indicate that cheetah are widespread across the landscape, although they appear to exist at relatively low population densities, likely primarily due to biotic factors. Our surveys revealed an extension of confirmed geographical range of the species and provide some of the first evidence that miombo woodlands may be an important habitat for cheetah across its eastern African range. We employ these findings to identify research priorities for the species elsewhere in the region. Community camera trapping revealed that cheetah are using unprotected areas, although rarely. Finally, we show that collaborations with tourism operators can be employed to monitor cheetah populations, but also identify limitations of this method. Our results have implications for conservation of the species both in southern Tanzania and across its African range.
Neuroblastoma: the association of anatomical tumour site, molecular biology and patient outcomes
Authors: Salim Adeline , Raitio Arimatias , Pizer Barry , Mullassery Dhanya , Losty Paul D. 
Published: January 2021

AbstractBackgroundNumerous factors have been identified as carrying prognostic value in neuroblastoma (NB) and therefore incorporated in risk stratification of disease. Here, we investigate the association of anatomical site of NB with molecular biology and clinical outcomes.MethodsA total of 117 patients with NB were studied over a 30‐year period. Tumour location was confirmed with computed tomography/magnetic resonance imaging. Data on molecular biology were obtained as testing became available. Chi‐squared, Fisher's exact test and Kaplan–Meier log‐rank tests were used for statistical analysis.ResultsTumour originated in the thoracic region (thoracic NB, TNB) in 15 patients (13%), adrenal gland (adrenal NB, ANB) in 88 patients (75%) and abdominal/paravertebral chain (paravertebral NB, PVNB) in 14 patients (12%). Overall survival (OS) for ANB was significantly lower (38%; P = 0.015). ANB cases were more frequently diagnosed at stage IV (69%; P = 0.001). MYCN amplification was noted in 33% of ANB cases and associated with lower OS (17% versus 62% MYCN non‐amplified ANB; P = 0.01). The vast majority of TNB and PVNB were non‐MYCN amplified (100% and 86%, respectively) and carried better prognosis (OS 86% and 83%, respectively). Forty‐two percent of ANB cases were diploid and had lower OS (20% versus 71% hyperdiploid ANB; P = 0.079). TNB and PVNB were found to be mostly hyperdiploid (86% and 100%, respectively) with better OS (83% and 33%, respectively). Segmental chromosomal alterations had prognostic significance in those with PVNB (P = 0.03).ConclusionTNB tumours have better outcomes than adrenal tumours. This may be due to varied factors reported here including non‐metastatic disease at presentation, non‐amplification of the MYCN oncogene and overall favourable molecular biology characteristics.
Disclosure of disability or misconduct in veterinary graduate registration: balancing confidentiality, equity and stakeholder interests
Authors: Raidal S L , Neutze D , Strous J 
Published: January 2021

AbstractBackgroundVeterinary registration processes, including disclosure of disability or misconduct, vary across jurisdictions in Australasia, and there is currently no clear mechanism for the communication of registration requirements to prospective or current students. Procedures for registration of graduating students are evolving but are not necessarily responsive to conflicting imperatives for confidentiality, protection of stakeholder interests and graduate support.ObjectiveTo obtain opinions from members of the veterinary profession in Australasia on issues relating to graduate registration, including communication between veterinary schools and registration bodies.MethodThis was an online survey.ResultsResponses were received from 245 members of the profession, including employers, educators, current students, recent graduates and board members. Respondents agreed on the importance of the survey topic to all stakeholder groups, and responses reflected the complex, contestable and nuanced nature of inherent concepts. Responses were strongly polarised between individuals with an appetite for reform, improved discourse around disability and remediation of unprofessional conduct and those with concerns and experiences suggesting boards and educators could not responsibly manage processes that included increased disclosure of disability or prior conduct.ConclusionIssues related to disability and misconduct should be addressed separately in any change to registration processes. A harmonisation of registration processes across jurisdictions is desirable, but the legal implications of any potential changes require careful consideration. There is a need for improved support of disability, remediation of misconduct and a desire to promote diversity within the profession. The survey evoked strong emotions, and future discussion requires sensitivity, empathy and insight.
Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF‐1α regulator
Authors: Isomura Hisanori , Taguchi Ayumu , Kajino Taisuke , Asai Naoya , Nakatochi Masahiro , Kato Seiichi , Suzuki Keiko , Yanagisawa Kiyoshi , Suzuki Motoshi , Fujishita Teruaki , Yamaguchi Tomoya , Takahashi Masahide , Takahashi Takashi 
Published: January 2021

AbstractWe previously reported that ROR1 is a crucial downstream gene for the TTF‐1/NKX2‐1 lineage‐survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP‐C promoter–driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia‐induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF‐1α expression under normoxia and clearly hampered HIF‐1α induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif‐1α. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted.
Inferior Auditory Time Perception in Children With Motor Difficulties
Authors: Chang Andrew , Li Yao‐Chuen , Chan Jennifer F. , Dotov Dobromir G. , Cairney John , Trainor Laurel J. 
Published: January 2021

Accurate time perception is crucial for hearing (speech, music) and action (walking, catching). Motor brain regions are recruited during auditory time perception. Therefore, the hypothesis was tested that children (age 6–7) at risk for developmental coordination disorder (rDCD), a neurodevelopmental disorder involving motor difficulties, would show nonmotor auditory time perception deficits. Psychophysical tasks confirmed that children with rDCD have poorer duration and rhythm perception than typically developing children (N = 47,d = 0.95–1.01). Electroencephalography showed delayed mismatch negativity or P3a event‐related potential latency in response to duration or rhythm deviants, reflecting inefficient brain processing (N = 54,d = 0.71–0.95). These findings are among the first to characterize perceptual timing deficits in DCD, suggesting important theoretical and clinical implications.
Fish Oil Supplementation in Pregnancy and Neurodevelopment in Childhood—A Randomized Clinical Trial
Authors: Sass Laerke , Bjarnadóttir Elín , Stokholm Jakob , Chawes Bo , Vinding Rebecca K. , Mora‐Jensen Anna‐Rosa C. , Thorsen Jonathan , Noergaard Sarah , Ebdrup Bjørn H. , Jepsen Jens R.M. , Fagerlund Birgitte , Bønnelykke Klaus , Lauritzen Lotte , Bisgaard Hans 
Published: January 2021

A double‐blind randomized controlled trial of n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother‐child cohort consisting of 736 women and their children. The objective was to determine if maternal n‐3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n‐3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n‐3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.
Gastric enterochromaffin‐like cell changes in multiple endocrine neoplasia type 1
Authors: Manoharan Jerena , Anlauf Martin , Albers Max B. , Denzer Ulrike W. , Mintziras Ioannis , Wächter Sabine , Di Fazio Pietro , Bollmann Carmen , Bartsch Detlef K. 
Published: January 2021

AbstractBackgroundGastric enterochromaffin‐like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES.MethodsMultiple endocrine neoplasia type 1 patients being part of a regular screening program (2014–2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin‐ and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed.ResultsThirty‐eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p < .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464).ConclusionEnterochromaffin‐like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.
A new case of Smith‐Kingsmore syndrome with somatic MTOR pathogenic variant expands the phenotypic spectrum to lateralized overgrowth
Authors: Carli Diana , Ferrero Giovanni Battista , Fusillo Anna , Coppo Paola , La Selva Roberta , Zinali Federica , Cardaropoli Simona , Ranieri Carlotta , Iacoviello Matteo , Resta Nicoletta , Mussa Alessandro 
Published: January 2021

AbstractSmith‐Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by heterozygous germline activating pathogenic variants in mammalian target of rapamycin (MTOR) on chromosome 1p36. A few patients with disseminated mosaicism have been described so far and they seem to display a different phenotype when compared to germline cases. Here we report the sixth case with a disseminated mosaic MTOR pathogenic variant, a 7‐year‐old boy with hemimegalencephaly, epilepsy, developmental delay, hypomelanosis of Ito, and lateralized overgrowth. Genetic testing revealed a pathogenic variant (c.4448G > A, p.Cys1483Tyr) in MTOR with a frequency of 32% in the DNA extracted from a skin sample, 3% in saliva and 0.46% in blood. The clinical features observed in our patient further corroborate the existence of differences in phenotypic presentation of germline and mosaic SKS cases. Moreover, lateralized overgrowth, a finding never described so far in SKS, further expands the phenotypic spectrum of SKS and allows the inclusion of MTOR pathogenic variants among the several causes of asymmetric body overgrowth.
Should businesses keep consistent performance between channels? Empirical evidence from the impact of rating discrepancy on demand
Authors: Yan Nina , Xu Xun , Tong Tingting 
Published: January 2021

AbstractConsumers often search for and compare the online and offline performance of businesses, indicated by consumer ratings, before they make purchases. In this study, using empirical evidence from the restaurant industry, we examine the impact of consumer rating discrepancy between online and offline channels on online demand. We find that channel rating discrepancy for overall performance, products, and services negatively affects online demand. In addition, higher prices amplify the negative effect of channel rating discrepancy on consumer online purchase behavior. The negative discrepancy effect has heterogeneity that depends on the business's properties (i.e., chain vs. independent). Our findings suggest that companies should take an integrated approach to make cross‐channel performance consistent. With consistent performance, companies can have a better overall performance that will attract consumer demand.
Incidence and risk factors of cerebral sinovenous thrombosis in infants
Authors: Sorg Anna‐Lisa , Von Kries Rüdiger , Klemme Mathias , Gerstl Lucia , Beyerlein Andreas , Lack Nicholas , Felderhoff‐Müser Ursula , Dzietko Mark 
Published: January 2021

AimTo describe the incidence of term and preterm neonatal cerebral sinovenous thrombosis (CSVT) and identify perinatal risk factors.MethodThis was a national capture‐recapture calculation‐corrected surveillance and nested case–control study. Infants born preterm and at term with magnetic resonance imaging‐confirmed neonatal CSVT were identified by surveillance in all paediatric hospitals in Germany (2015–2017). Incidence was corrected for underreporting using a capture‐recapture method in one federal state and then extrapolated nationwide. We reviewed PubMed for comparisons with previously reported incidence estimators. We used a population‐based perinatal database for quality assurance to select four controls per case and applied univariate and multivariable regression for risk factor analysis.ResultsFifty‐one newborn infants (34 males, 17 females; 14 born preterm) with neonatal CSVT were reported in the 3‐year period. The incidence of term and preterm neonatal CSVT was 6.6 (95% confidence interval [CI] 4.4–8.7) per 100 000 live births. Median age at time of confirmation of the diagnosis was 9.95 days (range 0–39d). In the univariate analysis, male sex, preterm birth, hypoxia and related indicators (umbilical artery pH <7.1; 5‐minute Apgar score <7; intubation/mask ventilation; perinatal asphyxia), operative vaginal delivery, emergency Caesarean section, and pathological fetal Doppler sonography were associated (p<0.05) with neonatal CSVT. Multivariable regression yielded hypoxia (odds ratio=20.3; 95% CI 8.1–50.8) as the independent risk factor.InterpretationIncidence of neonatal CSVT was within the range of other population‐based studies. The results suggest that hypoxia is an important perinatal risk factor for the aetiology of neonatal CSVT.
How disturbance history alters invasion success: biotic legacies and regime change
Authors: Miller Adam D. , Inamine Hidetoshi , Buckling Angus , Roxburgh Stephen H. , Shea Katriona 
Published: January 2021

AbstractDisturbance is a key factor shaping ecological communities, but little is understood about how the effects of disturbance processes accumulate over time. When disturbance regimes change, historical processes may influence future community structure, for example, by altering invasibility compared to communities with stable regimes. Here, we use an annual plant model to investigate how the history of disturbance alters invasion success. In particular, we show how two communities can have different outcomes from species introduction, solely due to past differences in disturbance regimes that generated different biotic legacies. We demonstrate that historical differences can enhance or suppress the persistence of introduced species, and that biotic legacies generated by stable disturbance history decay over time, though legacies can persist for unexpectedly long durations. This establishes a formal theoretical foundation for disturbance legacies having profound effects on communities, and highlights the value of further research on the biotic legacies of disturbance.