bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of adaptive computer assisted instruction on reading comprehension: Identifying the main idea
Authors: Toonder Scott , Sawyer L. Brook 
Published: June 2021

AbstractResearch has demonstrated that computer assisted instruction (CAI) can have positive impacts on various literacy skills, however its impact on specific comprehension skills is currently unclear. This study employed a small‐scale randomized control trial to examine the impact of a researcher‐developed adaptive computer assisted instructional program, Digital Comprehension, on 47 upper elementary struggling readers' comprehension skills, specifically main idea identification. Students were randomly assigned to treatment and control groups, with students in the treatment group engaging in the Digital Comprehension program and students in the control group receiving only business‐as‐usual classroom instruction. Students completed measures assessing main idea and general reading comprehension skills at pre‐ and post‐intervention. Students in the treatment group demonstrated statistically significant greater growth in main idea skills than students in the control group. No main effect for the intervention was found for general reading comprehension skills, although there was a significant interaction between condition and student's pretest scores. Results indicate that adaptive CAI may be an effective means for remediating struggling readers' main idea skills.
CRKL is a critical target of Hh‐GLI2 pathway in lung adenocarcinoma
Authors: Liu Xiaoming , Hu Yan , Yu Bentong , Peng Kai , Gan Xin 
Published: June 2021

AbstractLung adenocarcinoma (LUAD) is one of the important components of non‐small‐cell lung cancer (NSCLC) and leads to many deaths every year. During the initiation and progression of the LUAD, the Hh‐GLI2 pathway plays critical roles. Several components of this pathway have been shown to be amplified or overexpressed in LUAD, providing this pathway as an attractive target for therapeutics. However, a gap in our understanding of the Hh‐GLI2 pathway is the identity of transcriptional targets of GLI2 that drive LUAD tumorigenesis. Here, we show that the oncogene CRKL is a direct target of GLI2. GLI2 turns on CRKL transcription through binding its second intron. Furthermore, CRKL is an essential mediator for GLI2‐driven proliferation and migration of LUAD cells. Depletion of CRKL blunts Hh‐GLI2 pathway‐mediated cell proliferation and invasion. Lastly, we find that CRKL knockout cells are more sensitive to EGFR‐TKI and chemotherapeutics. Taken together, our work here identifies a specific target for Hh‐related malignancies and provides CRKL as a promising therapeutic target for LUAD.
Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition
Authors: Wei Jingjing , Zhao Qiuyan , Yang Guo , Huang Ruoxuan , Li Chao , Qi Yuanmeng , Hao Changfu , Yao Wu 
Published: June 2021

AbstractSilicosis is a devastating occupational disease caused by long‐term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self‐renewal capacity, multi‐lineage differentiation potential and immunomodulatory properties. The aim of this study was to explore the effect of bone marrow‐derived mesenchymal stem cells (BMSCs) in a silica‐induced rat model of pulmonary fibrosis. The rats were treated with BMSCs on days 14, 28 and 42 after perfusion with silica. Histological examination and hydroxyproline assays showed that BMSCs alleviated silica‐induced pulmonary fibrosis in rats. Results from ELISA and qRT‐PCR indicated that BMSCs inhibited the expression of inflammatory cytokines TNF‐α, IL‐1β and IL‐6 in lung tissues and bronchoalveolar lavage fluid of rats exposed to silica particles. We also performed qRT‐PCR, Western blot and immunohistochemistry to examine epithelial‐mesenchymal transition (EMT)–related indicators and demonstrated that BMSCs up‐regulate E‐cadherin and down‐regulate vimentin and extracellular
matrix (ECM) components such as fibronectin and collagen Ⅰ. Additionally, BMSCs inhibited the silica‐induced increase in TGF‐β1, p‐Smad2 and p‐Smad3 and decrease in Smad7. These results suggested that BMSCs can inhibit inflammation and reverse EMT through the inhibition of the TGF‐β/Smad signalling pathway to exhibit an anti‐fibrotic effect in the rat silicosis model. Our study provides a new and meaningful perspective for silicosis treatment strategies.
METTL16 promotes cell proliferation by up‐regulating cyclin D1 expression in gastric cancer
Authors: Wang Xiao‐Kun , Zhang Ya‐Wei , Wang Chun‐Ming , Li Bo , Zhang Tian‐Zhi , Zhou Wen‐Jie , Cheng Lyu‐jia , Huo Ming‐Yu , Zhang Chang‐Hua , He Yu‐Long 
Published: June 2021

AbstractN6‐methyladenosine (m6A) is a well‐known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT‐qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down‐regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock‐down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16‐mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.
Sexual orientation and adolescent suicide attempt and self‐harm: a co‐twin control study
Authors: O'Reilly Lauren M. , Pettersson Erik , Donahue Kelly , Quinn Patrick D. , Klonsky E. David , Lundström Sebastian , Larsson Henrik , Lichtenstein Paul , D’Onofrio Brian M. 
Published: June 2021

BackgroundResearch has demonstrated that individuals who identify as a sexual minority (e.g., gay/lesbian, bisexual) are at increased risk for suicidality‐related outcomes. However, previous research is primarily limited by the lack of adjustment for unmeasured (i.e., genetic and environmental) confounding factors and previous psychopathology.MethodsUsing the Child and Adolescent Twin Study in Sweden, we employed a co‐twin control design to examine the extent to which the association between sexual orientation and adolescent suicide attempt and self‐harm (SA/SH) was independent of genetic and environmental factors shared by twins, as well as measured symptoms of childhood psychopathology.ResultsAdolescents who identified as a sexual minority (i.e., gay/lesbian, bisexual, or other sexual orientation) were at two‐fold increased odds for SA/SH (OR, 2.01 [95% confidence interval, 1.63–2.49) compared to heterosexual adolescents. When adjusting for all genetic and shared environmental factors that make twins similar and for measured childhood psychopathology, the association remained positive but attenuated to OR, 1.55 (1.11–2.16).ConclusionsIdentifying as a sexual minority was associated with approximately 50% increased odds of SA/SH in adolescence after adjusting for unmeasured genetic and environmental factors shared by twins and for childhood psychopathology. The results support that environmental factors specifically associated with identifying as a sexual minority likely increase risk for SA/SH. Our findings highlight the need to monitor suicidality risk among this group.
Adult skin acute stress responses to short‐term environmental and internal aggression from exposome factors
Authors: Passeron T. , Zouboulis C.C. , Tan J. , Andersen M.L. , Katta R. , Lyu X. , Aguilar L. , Kerob D. , Morita A. , Krutmann J. , Peters E.M.J. 
Published: June 2021

AbstractExposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short‐term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine‐immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell‐mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.
Complete clearance and Psoriasis Area and Severity Index response for brodalumab and ustekinumab by previous treatment history in AMAGINE‐2 and AMAGINE‐3
Authors: Reich K. , Hansen J.B. , Puig L. , Konstantinou M.P. , Warren R.B. 
Published: June 2021

AbstractBackgroundThe pathway for treatment of psoriasis is partly dependent upon disease severity, and patients may experience inadequate response at any point along the treatment pathway. Patients who repeatedly fail therapy represent a population in whom effective and well‐tolerated treatment options are limited.ObjectivesTo investigate and describe patients achieving Psoriasis Area and Severity Index (PASI) 100 and cumulative treatment benefit over time in patients with moderate‐to‐severe psoriasis receiving brodalumab or ustekinumab by prior treatment.MethodsWe conducted a post hoc analysis of data from two phase 3, randomized, controlled, 52‐week AMAGINE trials of brodalumab to describe patients who achieved complete clearance as measured by PASI 100 by prior treatment subgroup (naïve to systemic and biologic treatment, systemic‐treated but biologic‐naïve, biologic‐treated without failure, and biologic‐treated with failure). A competing risk model was used to assess cumulative incidence over a 52‐week period with outcomes of PASI 100 or inadequate response. Cumulative clinical benefit of treatment was determined with an area under the curve analysis.ResultsThe 52‐week cumulative incidence of patients achieving PASI 100 was consistently higher for brodalumab vs. ustekinumab across treatment pathway subgroups (76% vs. 58% in systemic/biologic‐naïve patients, 78% vs. 55% in systemic‐treated/biologic‐naïve patients, 75% vs. 41% in biologic‐treated patients without failure, and 70% vs. 30% in biologic‐treated patients with failure). Rates of inadequate response were lower with brodalumab compared with ustekinumab across all subgroups. Cumulative treatment benefit was also higher for all subgroups treated with brodalumab compared with those treated with ustekinumab.ConclusionTreatment with brodalumab was associated with higher levels of complete clearance and greater cumulative benefit over time compared with ustekinumab, in patients with moderate‐to‐severe psoriasis, regardless of prior treatment experience.
A Bayesian network meta‐analysis of comparison of cancer therapeutic vaccines for melanoma
Authors: Lau P. , Shen M. , Ma F. , Chen Y. , Zhang J. , Su J. , Chen X. , Liu H. 
Published: June 2021

AbstractSeveral approaches to active immunotherapy for melanoma, including peptide‐based vaccines (PVs), autologous tumour cell vaccines (TCVs), allogeneic TCVs and autologous dendritic cell vaccines (DCVs), have been investigated in clinical trials. However, comprehensive evidence comparing these interventions remains unavailable. The objective of this study was to expand previous work to compare and rank the immunotherapeutic strategies for melanoma in terms of overall survival and toxic effects with a Bayesian network meta‐analysis. Methodologically, we performed a network meta‐analysis of head‐to‐head randomized controlled trials comparing and ranking cancer vaccine approaches for patients with melanoma. PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov were searched up to 31 July 2020. We estimated summary hazard ratios for death and risk ratios for toxicity. The effects of the underlying prognostic variable on survival benefits were examined by meta‐regression. We performed subgroup analysis for the outcomes based on metastatic categories. Overall, we identified 4776 citations, of which 15 head‐to‐head randomized controlled trials (3162 participants) were included in the analysis. In terms of efficacy, allogeneic tumour cell vaccines plus immunotherapy adjuvants, peptide‐based vaccines plus immunotherapy adjuvants and standard therapy were more effective than peptide vaccines. The proportion of women was inversely associated with mortality risk. For safety, all treatments were inferior to allogeneic tumour cell vaccines except for allogeneic tumour cell vaccines plus chemotherapy. Peptide vaccines plus immunotherapy adjuvants led to an increased risk of adverse events compared to allogeneic tumour cell vaccines plus immunotherapy adjuvants. These results suggest that allogeneic TCV and autologous DCV are better than standard therapy. PV plus immune modulators are the most effective strategy among all comparable strategies but is associated with increased toxicity. Any combination regimens for cancer therapeutic vaccines need to be balanced between risk and benefit profiles.
Dermoscopy of porokeratosis: results from a multicentre study of the International Dermoscopy Society
Authors: Zaar O. , Polesie S. , Navarrete‐Dechent C. , Errichetti E. , Akay B.N. , Jaimes J. , Cabo H. , Cohen Sabban E. , Paoli J. 
Published: June 2021

AbstractBackgroundThe diagnosis of porokeratosis can be challenging, and knowledge about its dermoscopic features is limited.ObjectivesTo describe the dermoscopic features of porokeratosis of Mibelli and disseminated superficial actinic porokeratosis (DSAP) and the frequency of these features in a larger case series. The interobserver concordance was also assessed.MethodsIn this retrospective cohort study, members of the International Dermoscopy Society contributed macroscopic and dermoscopic images of histopathologically verified cases of porokeratosis of Mibelli or DSAP. Three observers independently reviewed the collected images to identify the presence of predefined dermoscopic features. Following this, a consensus meeting was held to agree upon which dermoscopic features were present in each lesion.ResultsIn total, 78 clinical and dermoscopic images of porokeratoses were collected. The most common dermoscopic feature was keratin rim, which was present in 74 lesions (92.3%). The most common vascular structures were dotted or glomerular vessels which were present in almost half of the cases (48.7%). Other relatively frequent dermoscopic findings were as follows: non‐peripheral scales (44.9%), grey‐brown dots or pigmentation along the keratin rim (38.5%), and light‐brown pigmentation within the keratin rim (33.3%). Shiny white structures and blood spots or erosions along the keratin rim were findings never before described in porokeratosis and were detected in 16.7% and 17.9% of the lesions, respectively. Dermoscopic findings in porokeratosis of Mibelli and DSAP were similar except for fewer blood spots or erosions along the keratin rim and more light‐brown pigmentation within the keratin rim in DSAP. The interobserver concordance ranged from 0.44 (moderate) to 0.84 (almost perfect).ConclusionsThe dermoscopic hallmark of porokeratosis is the keratin rim, a finding also allowing for almost perfect interobserver agreement. Pigmentation or erosions along the keratin rim, vascular structures, as well as scales, pigmentation or shiny white structures within the keratin rim are additional dermoscopic clues.
A role for sex‐determination genes in life history evolution? Doublesex mediates sexual size dimorphism in the gazelle dung beetle
Authors: Rohner Patrick T. 
Published: June 2021

AbstractAn organism's fitness depends strongly on its age and size at maturation. Although the evolutionary forces acting on these critical life history traits have been heavily scrutinized, the developmental mechanisms underpinning intraspecific variation in adult size and development time remain much less well‐understood. Using RNA interference, I here show that the highly conserved sex‐determination gene doublesex (dsx) mediates sexual size dimorphism (SSD) in the gazelle dung beetle Digitonthophagus gazella. Because doublesex undergoes sex‐specific splicing and sex‐limited isoforms regulate different target genes, this suggests that dsx contributes to the resolution of intralocus sexual conflict in body size. However, these results contrast with previous studies demonstrating that dsx does not affect body size or SSD in Drosophila. This indicates that intraspecific body size variation is underlain by contrasting developmental mechanisms in different insect lineages. Furthermore, although male D. gazella have a longer development time than females, sexual bimaturism was not affected by dsx expression knockdown. In addition, and in contrast to secondary sexual morphology, dsx did not significantly affect nutritional plasticity in life history. Taken together, these findings indicate that dsx signalling contributes to intraspecific life history variation but that dsx's function in mediating sexual dimorphism in life history differs among traits and species. More generally, these findings suggest that genes ancestrally tasked with sex determination have been co‐opted into the developmental regulation of life history traits and may represent an underappreciated mechanism of life history evolution.
Phosphorylation‐dependent control of Activity‐regulated cytoskeleton‐associated protein (Arc) protein by TNIK
Authors: Walczyk‐Mooradally Alicyia , Holborn Jennifer , Singh Karamjeet , Tyler Marshall , Patnaik Debasis , Wesseling Hendrik , Brandon Nicholas J. , Steen Judith , Graether Steffen P. , Haggarty Stephen J. , Lalonde Jasmin 
Published: June 2021

AbstractActivity‐regulated cytoskeleton‐associated protein (Arc) is an immediate early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self‐assemble into virus‐like capsids that can package mRNAs and transfer those transcripts to other cells. Although a lot has been uncovered about the contributions of Arc to neuron biology and behavior, very little is known about how different functions of Arc are coordinately regulated both temporally and spatially in neurons. The answer to this question we hypothesized must involve the occurrence of different protein post‐translational modifications acting to confer specificity. In this study, we used mass spectrometry and sequence prediction strategies to map novel Arc phosphorylation sites. Our approach led us to recognize serine 67 (S67) and threonine 278 (T278) as residues that can be modified by TNIK, which is a kinase abundantly expressed in neurons that shares many functional overlaps with Arc and has, along with its interacting proteins such as the NMDA receptor, and been implicated as a risk factor for psychiatric disorders. Furthermore, characterization of each residue using site‐directed mutagenesis to create S67 and T278 mutant variants revealed that TNIK action at those amino acids can strongly influence Arc's subcellular distribution and self‐assembly as capsids. Together, our findings reveal an unsuspected connection between Arc and TNIK. Better understanding of the interplay between these two proteins in neuronal cells could lead to new insights about apparition and progression of psychiatric disorders.
image
Cover Image for this issue: https://doi.org/10.1111/jnc.15077
Weekend work and work–family conflict: Evidence from Australian panel data
Authors: Laß Inga , Wooden Mark 
Published: June 2021

AbstractObjectiveThis article investigates whether weekend work is associated with higher levels of work–family conflict (WFC) among parents, and whether resources like schedule control or presence of a partner mitigate this effect.BackgroundThe 24/7 economy requires many workers to work on weekends. Nevertheless, research on the impact of weekend work on families, and on WFC in particular, is underdeveloped, with previous studies relying on cross‐sectional data and small samples.MethodAssociations between regular weekend work and a measure of WFC are examined using data from 14 waves of The Household, Income and Labour Dynamics in Australia (HILDA) Survey. The sample is restricted to workers aged 18–64 years with parenting responsibilities for children aged 17 or less (7747 individuals, 40,192 observations). Both pooled ordinary least squares and fixed‐effects regression models are estimated.ResultsAmong both genders, weekend workers have significantly higher levels of WFC than those who only work weekdays. WFC is particularly high for those who work weekends and simultaneously have little control over their schedule. Furthermore, weekend work affects WFC similarly for couple and single parents and, within dual‐earner families, independently of the partner's working schedule.ConclusionWeekend work generally has a detrimental effect on workers' ability to combine employment with parenting commitments. However, work–domain resources like schedule control can buffer the impact of weekend work.