bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDX10 promotes human lung carcinoma proliferation by U3 small nucleolar ribonucleoprotein IMP4
Authors: Liu Chunquan , Tang Jizheng , Duan Xinchun , Du Yanlin , Wang Xiaoran , Cui Yong 
Published: May 2021

AbstractBackgroundLung cancer is a common tumor and a leading cause of death worldwide. DEAD/H box RNA helicases (DDX) include several family members which regulate mRNA translation in cancer cells. In this study, we demonstrated that DEAD/H box RNA helicase 10 (DDX10) was significantly upregulated in lung cancer tissues compared with adjacent nontumor tissues.MethodsDDX10 expression was knocked down with shRNA in order to investigate the impact on A549 lung cancer cell growth and related molecular mechanisms in vitro and in vivo. DDX10 expression in lung cancer was assessed using online databases and patient samples.ResultsDDX10 knockdown significantly inhibited the proliferation of lung cancer cells in vitro and in vivo. Furthermore, the bioinformatic tool indicated the putative downstream protein U3 small nucleolar ribonucleoprotein 4 (IMP4). Our data showed a positive correlation between IMP4 and DDX10. We found that IMP4 overexpression could reverse the effect of DDX10 knockdown on the proliferation and apoptosis of A549 cells.ConclusionsThe findings of this study suggest that DDX10/IMP4 might be a novel target for lung cancer diagnosis and treatment.
Projection from the basolateral amygdala to the anterior cingulate cortex facilitates the consolidation of long‐term withdrawal memory
Authors: Shao Da , Cao Zixuan , Fu Yali , Yang Hao , Gao Pengyu , Zheng Ping , Lai Bin 
Published: May 2021

AbstractThe process through which early memories are transferred to the cerebral cortex to form long‐term memories is referred to as memory consolidation, and the basolateral amygdala (BLA) is an important brain region involved in this process. Although functional connections between the BLA and multiple brain regions are critical for the consolidation of withdrawal memory, whether the projection from the BLA to the anterior cingulate cortex (ACC) is involved in the formation or consolidation of withdrawal memory remains unclear. In this paper, we used a chemical genetic method to specifically label the BLA–ACC projection in a combined morphine withdrawal and conditioned place aversion (CPA) animal model. We found that (1) the inhibition of the BLA–ACC projection during conditioning had no effects on the formation of early withdrawal memory; (2) the inhibition of the BLA–ACC projection had no effects on the retrieval of either early or long‐term withdrawal memory; and (3) the persistent inhibition of the BLA–ACC projection after early withdrawal memory formation could inhibit the formation of long‐term withdrawal memory and decrease Arc protein expression in the ACC. These results suggested that the persistent activation of the BLA–ACC projection after the formation of early withdrawal memory facilitates the formation of long‐term withdrawal memory by increasing the plasticity of ACC neurons.
Developmental trajectories of sleep during childhood and adolescence are related to health in young adulthood
Authors: McVeigh Joanne A. , Smith Anne , Howie Erin K. , Stamatakis Emmanuel , Ding Ding , Cistulli Peter A. , Eastwood Peter , Straker Leon 
Published: May 2021

AbstractAimSleep behaviour is correlated and causally related to physical and mental health. Limited longitudinal data exist on the associations of poor sleep behaviour in childhood and adolescence with adult health. Parent‐reported sleep behaviours from 1993 participants of the Raine Study (at ages 5, 8, 10, 14, 17) were used to determine sleep trajectories (using latent class growth analysis).MethodsMeasures of physical and mental health were compared between sleep trajectories using generalised linear models (at age 20).ResultsThree sleep trajectories were identified as follows: 43% of participants belonged to a trajectory with ‘consistently minimal’ sleep problems, 49% showed some ‘declining’ in reporting of sleep problems incidence and 8% had ‘persistent’ sleep problems. Participants in the ‘consistently minimal’ trajectory had better physical and mental health outcomes at age 20 compared to those in the ‘declining’ and ‘persistent’ trajectories. For example, ‘consistently minimal’ participants had significantly lower body fat percentage (mean difference: −3.89% (95% CI: −7.41 to −0.38)) and a higher (better) SF‐12 mental component score (mean difference: 4.78 (95% CI: 2.35–7.21)) compared to participants in the ‘persistent’ trajectory.ConclusionPoor sleep behaviour across childhood and adolescent years is related to poorer physical and mental health in young adulthood.
National Swedish survey showed that child health services and routine immunisation programmes were resilient during the early COVID‐19 pandemic
Authors: Falkenstein Hagander Kathy , Aronsson Bernice , Danielsson Madelene , Lepp Tiia , Kulane Asli , Schollin Ask Lina 
Published: May 2021

AbstractAimRoutine immunisation programmes are at risk of disruption due to the COVID‐19 pandemic. This study aimed to investigate the resilience of the Swedish national immunisation programme for children up to the age of five years during the early stages of the pandemic.MethodsThis was a cross‐sectional, web‐based survey of regional child health offices in Sweden between 10 September and 9 October 2020. It explored the organisation of child health services during the early stages of the pandemic, focusing on routine child immunisation.ResultsAll 21 Swedish regional child health offices responded. They stated that child immunisation had been prioritised, communication with families had been intensified and there was greater flexibility at all organisational levels of child health services. In addition, the vaccine supply was sustained and child health centres remained open. However, there were periodic staff shortages, increased numbers of health visits cancelled by parents and most parent education groups were paused.ConclusionThe Swedish immunisation programme was resilient during the early COVID‐19 pandemic, thanks to sustainable organisation co‐ordinated by Sweden's network of regional child health offices.
Sex‐influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: Systematic review and meta‐analysis
Authors: Costa Viana Catiane , da Silva Praxedes Marcus Fernando , Freitas Nunes de Sousa Waleska Jaclyn , Bartolazzi Frederico , Sousa Vianna Mayara , Padilha da Silva José Luiz , Parreiras Martins Maria Auxiliadora 
Published: May 2021

AimsWe sought to investigate the association between sex and oral anticoagulation control employing coumarin derivatives.MethodsElectronic sources were MEDLINE, Biblioteca Virtual em Saúde (BVS), The Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central and Web of Science. Inclusion criteria were: observational and experimental studies; age ≥18 years; both sexes; treatment with any coumarin derivative for ≥3 months; any indication of long‐term use; quality of oral anticoagulation measured by time in therapeutic range (TTR). The meta‐analysis was developed with odds ratios (OR) for binary variables and mean differences (MD) for continuous variables, using random‐effects models (DerSimonian and Laird) with 95% confidence intervals (CI).ResultsOverall, 22 articles were selected, comprising 16 cohort studies, four cross‐sectional studies and two clinical trials. The number of participants ranged from 110 to 104 505 (183 612; women: 45%). The main indication of oral anticoagulation was atrial fibrillation. Most studies reported the use of warfarin. In the meta‐analysis, 15 studies were analysed using TTR as a binary variable (OR = 0.87; 95% CI = 0.78, 0.96; z = −2.75; P = .006.; I2 = 67%) and seven studies as a continuous variable (MD = −2.97; 95% CI = −4.80, −1.14; z = −3.19; P = .0014; I2 = 75%). The pooled estimates indicated that women were associated with lower TTR than men.ConclusionsOur findings revealed an association between female sex and worse oral anticoagulation control. Further studies are needed with primary design to investigate sex‐related factors influencing oral anticoagulation control with coumarin derivatives. Innovative strategies focused on women's health may be useful to improve patient‐centred care.
Extrapolation and dosing recommendations for raxibacumab in children from birth to age <18 years
Authors: Oosterholt Sean P. , Della Pasqua Oscar 
Published: May 2021

AimsThe US Food and Drug Administration's Animal Rule allows for the approval of drugs when human efficacy studies are not ethical. While the therapeutic doses of raxibacumab, a monoclonal antibody for the prophylaxis and treatment of inhalational anthrax, have been based on pharmacokinetic data from adult subjects, its disposition in children has not been investigated in clinical trials. Here we evaluate the effect of demographic covariates and maturation processes on the pharmacokinetics of raxibacumab and explore opportunities for the optimisation of paediatric doses.MethodsA population pharmacokinetic model was used as basis for the extrapolation of raxibacumab disposition from adults to children. Different extrapolation scenarios, including weight‐banded dosing regimens, were considered to assess the effect of growth and maturation on the pharmacokinetic parameters of interest. Area under the concentration–time curve, maximum plasma concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28 days in any monkey challenged with Bacillus anthracis that died were derived and compared with the currently approved US doses.ResultsBased on practical considerations, a weight‐banded dosing regimen consisting of 4 dose levels (75 mg/kg for individuals ≤1.5 kg, 55 mg/kg for individuals <10 kg, 45 mg/kg for individuals <50 kg, 40 mg/kg for all individuals >50 kg) was required to optimise target exposure across the paediatric population.ConclusionsAge‐related maturation processes may affect raxibacumab clearance in very young patients. The proposed dosing regimens take into account effects of body weight and maturation processes on the elimination of raxibacumab.
A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab‐refractory iNHL (COMPLEMENT A + B study)
Authors: Rummel Mathias J. , Janssens Ann , MacDonald David , Keating Mary‐Margaret , Zaucha Jan M. , Davis Jaclyn , Lasher Janet , Babanrao Pisal Chaitali , Izquierdo Miguel , Friedberg Jonathan W. 
Published: May 2021

SummaryThe standard of care for indolent non‐Hodgkin lymphoma (iNHL) is rituximab, an anti‐CD20 antibody, with/without chemotherapy. However, multiple relapses are common in these patients. This phase 3, randomized study compared outcomes of a combination of ofatumumab (a second‐generation anti‐CD20 antibody) and bendamustine, with bendamustine alone in patients unresponsive to prior rituximab‐based treatment. Overall, 346 patients were randomized to receive either the combination or bendamustine alone. Bendamustine was given for ≤8 cycles and ofatumumab for ≤12 cycles. The primary end‐point was progression‐free survival (PFS) after 215 protocol‐defined events assessed by independent review committee (IRC). Median IRC‐assessed PFS was 16·7 and 13·8 months in the combination and monotherapy arms respectively [hazard ratio (HR) = 0·82; P = 0·1390]. Median overall survival (OS) was 58·2 and 51·8 months in the combination and monotherapy arms respectively (HR = 0·89, P = 0·4968). The safety profile was consistent with previous reports. Overall, 73% and 80% of patients in the combination and monotherapy arms, respectively, experienced a ≥grade 3 adverse event. The study did not meet its primary end‐point. No significant improvement in PFS and OS was seen with the combination of ofatumumab and bendamustine as compared with bendamustine alone in rituximab‐refractory iNHL (NCT01077518).
Clinical and molecular characteristics and treatment patterns of adolescent and young adult patients with chronic lymphocytic leukaemia
Authors: Cherng Hua‐Jay J. , Jammal Nadya , Paul Shilpa , Wang Xuemei , Sasaki Koji , Thompson Philip , Burger Jan , Ferrajoli Alessandra , Estrov Zeev , O’Brien Susan , Keating Michael , Wierda William G. , Jain Nitin 
Published: May 2021

SummaryChronic lymphocytic leukaemia (CLL) rarely presents in adolescent and young adult (AYA) patients (patients aged 15–39 years). Disease characteristics and outcomes of AYA patients with CLL are not well understood, particularly in the era of novel oral targeted therapies. We analysed outcomes of 227 AYA patients with CLL diagnosed in the last two decades and evaluated at our institution. Median time to first treatment (TTFT) was 2·2 years, and five‐ and 10‐year overall survival (OS) were 90% and 78%, respectively. Pre‐treatment elevated beta 2‐microglobulin, advanced Rai stage, del(11q) or del(17p) by FISH, unmutated IGHV and CD38 positivity were associated with both shorter TTFT and OS. Within the subgroup of patients who received oral targeted therapy at any time, del(11q) or del(17p) and complex karyotype were associated with shorter OS. First‐line treatment choice was significantly associated with time to second treatment (P < 0·001). Patients harbouring del(11q) or del(17p) experienced shorter time to Richter transformation and were more likely to undergo an allogeneic stem cell transplant. There was a significant association between age and both OS and time to Richter transformation. Our study is the first analysis of AYA patients with CLL with a large number of patients treated with oral targeted therapies.
Primary Gleason grade and Gleason grade group at positive surgical margins: a systematic review and meta‐analysis
Authors: John Athul , John Hritik , Catterwell Rick , Selth Luke A , Callaghan Michael O 
Published: May 2021

ObjectivesTo systematically review and perform a meta‐analysis of studies investigating the role of primary Gleason grade (PGG), Gleason score (GS) or Gleason grade group (GGG) at positive surgical margins (PSMs) after radical prostatectomy (RP) in predicting biochemical recurrence (BCR) and oncological outcomes.MethodsA systematic search was conducted using the MEDLINE, Scopus, Embase and Cochrane databases according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines. Studies published between 2005 and 2019 were included. The quality of the studies selected was assessed, and a protocol was registered and published in advance (PROSPERO: CRD42019131800). The primary outcome measure was BCR. Secondary outcome measures included cancer‐specific survival, metastasis‐free survival and overall mortality during the follow‐up period.ResultsOur systematic search yielded 3116 unique results. Ten studies were selected for meta‐analysis. The sample sizes of PSM cohorts varied from 200 to 956, while the median follow‐up ranged from 1.5 to 13 years. Most studies used BCR as a surrogate marker for disease progression; only two studies reported other oncological outcomes. Meta‐analysis was performed in selected groups (PGG, GS and GGG). PGG 4 or 5 at the PSM was found to be predictive of BCR (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.37–2.02; P < 0.01). GGG > 1 at margin was also predictive of BCR compared to GGG 1 (GGG 1 vs 2: HR 2.35, 95% CI 1.6 −3.46; P < 0.001; GGG 1 vs 3: HR 3.95, 95% CI 1.82–8.57; P = 0.005; GGG 1 vs 4: HR 7.17, 95% CI 1.76–29.17; P = 0.006; and GGG 1 vs 5: HR 12.37, 95% CI 1.80–84.82; P = 0.01).ConclusionGleason score, PGG and GGG at the PSM are associated with a significantly increased risk of BCR. Longer‐term studies are needed to investigate the utility of PGG, GS or GGG at the PSM in their ability to predict not only BCR but other outcomes such as cancer‐specific survival, metastasis‐free survival and overall survival.
The role of music within the home‐lives of young people with profound and multiple learning disabilities: Parental perspectives
Authors: Rushton Rosie , Kossyvaki Lila 
Published: May 2021

Accessible summaryMusic is often part of our lives.We asked parents what music is like for children and young people with profound learning disabilities at home.People listened to music more than they made music at home.Music is used for different reasons.Music can help families feel more connected.​AbstractBackgroundMusic is weaved within our cultures; it is ever‐present within daily‐life and can considerably influence our mood, well‐being and relationships. This study explores parental perceptions of the role of music in the home‐lives of children and young people with profound and multiple learning disabilities in the UK. It considers parental views of how listening to and making music can shape the mood and behaviours of their child and their relationship.MethodsUsing a mixed‐method explanatory sequential design and cross‐sectional survey methodology, the study collected data from parents and carers of children and young people with profound and multiple learning disabilities. Data were collected from an online questionnaire (n= 48) followed by online one‐to‐one interviews (n= 10).FindingsParents reported that children and young people with profound and multiple learning disabilities more frequently listen to music than make music within the home. They also stated that music is used for enjoyment, to support mood‐regulation and to add structure to the lives of young people with profound and multiple learning disabilities. Parents finally reported that listening to music together helps families feel more connected and strengthened their relationships.ConclusionThis paper outlines the positive role music may have in the home lives of people with profound and multiple learning disabilities and their families.
Preclinical rodent models of cardiac fibrosis
Authors: Wang Yan , Wang Miao , Samuel Chrishan S. , Widdop Robert E. 
Published: May 2021

Cardiac fibrosis (scarring), characterised by an increased deposition of extracellular matrix (ECM) proteins, is a hallmark of most types of cardiovascular disease and plays an essential role in heart failure progression. Inhibition of cardiac fibrosis could improve outcomes in patients with cardiovascular diseases and particularly heart failure. However, pharmacological treatment of the ECM build‐up is still lacking. In this context, preclinical models of heart disease are important tools for understanding the complex pathogenesis involved in the development of cardiac fibrosis which in turn could identify new therapeutic targets and the facilitation of antifibrotic drug discovery. Many preclinical models have been used to study cardiac fibrosis and each model provides mechanistic insights into the many factors that contribute to cardiac fibrosis. This review discusses the most frequently used rodent models of cardiac fibrosis and also provides context for the use of particular models of heart failure.LINKED ARTICLESThis article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc
Hyaluronate carboxymethylcellulose sheets for the prevention of adhesive complications: a model‐based cost–utility analysis
Authors: Sue‐Chue‐Lam Colin , Zhang David D. Q. , Baxter Nancy N. , Zywiel Michael G. , de Mestral Charles 
Published: May 2021

AbstractAimClinical trials suggest that hyaluronate carboxymethylcellulose (HA/CMC) prevents adhesion‐related complications after intra‐abdominal surgery, but at a high upfront cost. This study evaluated the cost‐effectiveness of HA/CMC for patients undergoing curative‐intent open colorectal cancer surgery.MethodsUsing a Markov Monte Carlo microsimulation model, we conducted a cost–utility analysis comparing the cost‐effectiveness of HA/CMC at curative‐intent open colorectal cancer surgery versus standard management. We considered a scenario where HA/CMC was used at the index operation only, as well as where it was used at the index operation and any subsequent operations. The perspective was that of the third‐party payer. Costs and utilities were discounted 1.5% annually, with a 1‐month cycle length and 5‐year time horizon. Model input data were obtained from a literature review. Outcomes included cost, quality‐adjusted life‐years (QALYs), small bowel obstructions (SBOs) and operations for SBO.ResultsUsing HA/CMC at the index operation results in an incremental cost increase of CA$316 and provides 0.001 additional QALYs, for an incremental cost‐effectiveness ratio of CA$310,000 per QALY compared to standard management. In our simulated cohort of 10,000 patients, HA/CMC prevented 460 SBOs and 293 surgeries for SBO. Probabilistic sensitivity analysis found that HA/CMC was cost‐effective in 18.5% of iterations, at a cost‐effectiveness threshold of CA$50,000 per QALY. Results of the scenario analysis where HA/CMC was used at the index operation and any subsequent operations were similar.ConclusionsHyaluronate carboxymethylcellulose prevents adhesive bowel obstruction after open colorectal cancer surgery but is unlikely to be cost‐effective given minimal long‐term impact on healthcare costs and QALYs.
miR‐4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol‐induced bone loss in mice
Authors: Yu Hongping , Wang Kaiyang , Liu Pei , Luo Pengbo , Zhu Daoyu , Yin Junhui , Yang Qianhao , Huang Yigang , Gao Junjie , Ai Zisheng , Chen Yixuan , Gao Youshui 
Published: May 2021

AbstractObjectivesAlcohol consumption is one of the leading factors contributing to premature osteopenia. MicroRNA (miRNA) coordinates a cascade of anabolic and catabolic processes in bone homeostasis and dynamic vascularization. The aim was to investigate the protective role of miR‐4286 in alcohol‐induced bone loss and its mechanism.Materials and MethodsThe effect of miR‐4286 and alcohol on bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored via multiple in vitro assays, including cell proliferation, QPCR, Western blot, osteogenesis, angiogenesis etc miR‐4286 directly regulated HDAC3 was investigated by luciferase reporter assay, and the function of HDAC3 was also explored in vitro. Moreover, alcohol‐induced bone loss in mice was established to reveal the preventive effect of miR‐4286 by radiographical and histopathological assays.ResultsIn vitro, ethanol dramatically inhibited the proliferation and osteogenesis of BMSCs, and substantially impaired the proliferation and vasculogenesis of HUVECs. However, a forced overexpression of miR‐4286 within BMSCs and HUVECs could largely abolish inhibitory effects by alcohol. Furthermore, alcohol‐induced inhibition on osteogenic and vasculogenic functions was mediated by histone deacetylase 3 (HDAC3), and dual‐luciferase reporter assay showed that HDAC3 was the direct binding target of miR‐4286. In vivo, micro‐CT scanning and histology assessment revealed that miR‐4286 could prevent alcohol‐induced bone loss.ConclusionsWe firstly demonstrated that miR‐4286 might function via intimate osteogenesis‐angiogenesis pathway to alleviate alcohol‐induced osteopenia via targeting HDAC3.