bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and function prediction of novel microRNAs in adenosine monophosphate activated protein kinase‐activated Sertoli cells of immature boar
Authors: Zhang Jiao Jiao , Wang Yu Sha , Li Ya Qi , Chen Liang , Wang Xian Zhong 
Published: August 2021

AbstractThis study was carried out with the objective to identify function prediction of novel microRNAs (miRNAs) in immature boar Sertoli cells (SCs) treated with 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR), which is an agonist of adenosine monophosphate‐activated protein kinase (AMPK) for regulating cellular energy homeostasis. Two small RNA libraries (control and AICAR treatment) prepared from immature boar SCs were constructed and sequenced by the Illumina small RNA deep sequencing. We identified 77 novel miRNAs and predicted 177 potential target genes for 26 differential novel miRNAs (four miRNAs up‐regulation and 22 miRNAs down‐regulation) in AICAR‐treated SCs. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway suggested that target genes of differential novel miRNAs were implicated in many biological processes and metabolic pathways. Our findings provided useful information for the functional regulation of novel miRNAs and target mRNAs on AMPK‐activated immature boar SCs.
A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer
Authors: Furrer Marc A. , Papa Nathan , Luetolf Sandro , Roth Beat , Cumberbatch Marcus , Dorin Vartolomei Mihai , Thomas Benjamin C. , Thoeny Harriet C. , Seiler Roland , Thalmann George N. , Kiss Bernhard 
Published: August 2021

ObjectivesTo evaluate the usefulness of radiological re‐staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re‐staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC).Patients and MethodsWe conducted a longitudinal, single‐centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle‐invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re‐staging after two cycles of NAC and after completion of NAC before RC.ResultsOf 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25–0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC.ConclusionsRe‐staging of muscle‐invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re‐staging after completion of NAC by CT is a strong predictor of overall survival.
Reactivation of a hyperextended rift system: The Basque–Cantabrian Pyrenees case
Authors: Miró Jordi , Manatschal Gianreto , Cadenas Patricia , Muñoz Josep Anton 
Published: August 2021

AbstractThis contribution investigates the role of a hyperextended rift system in the formation of the Basque–Cantabrian Pyrenees by discussing their present‐day architecture as well as the inherited rift template. Moreover, this work attempts to decipher the onset of reactivation of a hyperextended system and to discuss the related processes during collision. To carry out this study, two regional, crustal‐scale cross‐sections are presented that provide geological and geophysical information and interpretations across the Central and Western Basque–Cantabrian Pyrenees. Moreover, the two sections are restored back to the Cenomanian and Barremian, corresponding to the end of two independent rift stages respectively. The two sections document different structural styles observed along the orogenic belt. The Central section, involving the Iberian and European plates, shows a thin‐skinned structural style, where the Upper Triassic salt acted as a decoupling level between the sedimentary cover and the underlying basement during both extension and reactivation. The Western section, by contrast, crosses only the Iberian plate (i.e., intra‐plate section) and displays a hybrid situation showing both thin‐ and thick‐skinned structural styles that were conditioned by the irregular distribution of Triassic salt. Extensional deformation was localised in the north (i.e., Bay of Biscay) and less important in the south. Despite compressional reactivation, the northern part of the Western section preserves its rift template, which provides key insights to restore the internal part of the Central section. In contrast to the Western section, the Central section shows stacked depocenters, resulting from overprinted Mesozoic rift events that had a first order control on the subsequent reactivation. This study corroborates the importance of rift inheritance during the onset of convergence by reactivating the most distal and weak part of the rift system (i.e., serpentinised mantle) before starting the collision phase. A key learning is that the understanding of the nature and distribution of decoupling levels at a crustal scale is fundamental to reconstruct the structural evolution during the formation and reactivation of a hyperextended rift system.
ELF3‐AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood
Authors: Song Shubin , He Xuezhi , Wang Jing , Wang Rong , Wang Leilei , Zhao Wei , Wang Yimin , Zhang Yongle , Yu Zhiyong , Miao Dengshun , Xue Yingwei 
Published: August 2021

AbstractNumerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3‐AS1 on gastric cancer (GC) cell function and explored the exact mechanism. Quantitative real‐time polymerase chain reaction was used to detect the expression of ELF3‐AS1 in GC tissues and adjacent nontumor tissues. Knockdown and overexpression of ELF3‐AS1 was used to detect the effect of ELF3‐AS1 on cell function. Potential downstream target genes were identified using RNA transcriptome sequencing, while RNA immunoprecipitation, chromatin immunoprecipitation, and Western blotting were performed to explore the tumor promotion mechanisms of ELF3‐AS1. We observed that ELF3‐AS1 was highly expressed in GC tissues, and high ELF3‐AS1 expression predicted poor prognosis. The knockdown of ELF3‐AS1 significantly inhibited cell proliferation, migration, and epithelial‐mesenchymal transition and promoted apoptosis. Mechanistic investigations revealed that ELF3‐AS1 may regulate the downstream target gene, C‐C motif chemokine 20, by binding with the RNA‐binding protein hnRNPK. Additionally, we found that high ELF3‐AS1 expression was associated with thrombocytosis. Interleukin‐6 and thrombopoietin may be involved in ELF3‐AS1–induced paraneoplastic thrombocytosis. Together, our results demonstrate that aberrantly expressed ELF3‐AS1 in GC may play important roles in oncogenesis and progression and is expected to become a new target for the diagnosis and treatment of GC.
Long noncoding RNA plasmacytoma variant translocation 1 promotes progression of colorectal cancer by sponging microRNA‐152‐3p and regulating E2F3/MAPK8 signaling
Authors: Liu Xin , Li Lei , Bai Jing , Li Liang , Fan Jianghe , Fu Zexian , Liu Jianxia 
Published: August 2021

AbstractThe purpose of this study was to investigate the pathogenesis of colorectal cancer (CRC) and the effects of the long noncoding RNA plasmacytoma variant translocation 1 (PVT1) on CRC progression. Bioinformatics analysis verified PVT1 expression in tumor and normal tissues. Quantitative PCR and western blotting were used to measure mRNA and protein levels, respectively. The MTT, Transwell, colony formation, and in vivo assays were used to assess the effects of PVT1 on proliferation, migration, and invasion by CRC cells. Both PVT1 and microRNA (miR)‐152‐3p were shown to be colocalized in CRC cells using FISH assay. The target genes of miR‐152‐3p were predicted and verified by bioinformatics analysis, luciferase assay, and RNA pull‐down assay. The ChIP assay revealed that E2F3 binds with the promoter of MAPK8. We found that PVT1 was overexpressed in CRC specimens, and its expression was higher in CRC cells than normal intestinal cells. Overexpression of PVT1 enhanced the proliferation, migration, and invasion of CRC cells, whereas PVT1 knockdown inhibited these processes. MicroRNA‐152‐3p was a target of PVT1, and E2F3 was a target of miR‐152‐3p. Rescue experiments confirmed the interaction between miR‐152‐3p and PVT1 and between miR‐152‐3p and E2F3. Luciferase and ChIP assay results confirmed that E2F3 modulates the transcriptional activation of MAPK8. Long noncoding RNA PVT1 activated E2F3 signaling by sponging miR‐152‐3p. The PVT1/miR‐152‐3p/E2F3/MAPK8 axis promoted CRC progression.
The effect of spanking on early social‐emotional skills
Authors: Cuartas Jorge 
Published: August 2021

AbstractWhether spanking is detrimental for social‐emotional (SE) development remains controversial, mostly due to disputes around the internal and external validity of existing evidence. This study examined the effect of spanking on the SE development of Bhutanese children, using a national, longitudinal sample (N = 1377; Mage = 50.5 months old; 50% girls). Following best‐practice recommendations for mitigating issues of selection bias in observational developmental research, the study employed conservative methods (i.e., child fixed‐effects and lagged‐dependent variables) and robustness checks to assess the internal validity of estimates. Across approaches, spanking predicted reductions in SE skills of .09–.17 SD, even after controlling for all time‐invariant confounders and baseline levels of SE skills. These findings strengthen the argument that spanking might be harmful to young children's SE development.
Periodontal health predicts self‐rated general health: A time‐lagged cohort study
Authors: Nguyen Vy Thi Nhat , Furuta Michiko , Zaitsu Takashi , Oshiro Akiko , Shimazaki Yoshihiro , Ando Yuichi , Miyazaki Hideo , Kambara Masaki , Fukai Kakuhiro , Aida Jun 
Published: August 2021

AbstractObjectivesThere is limited evidence of a temporal relationship between periodontal diseases and self‐perceived general health. To plug this knowledge gap, we aimed to assess how periodontal health affects future self‐rated health (SRH).MethodsWe collected data from five waves of an annual nationwide Japanese survey of dental patients from 2015 to 2019. The analysis of repeated measurements included 9306 observations from 4242 patients aged 20 years or older. The clinical periodontitis measurements were bleeding on probing, deepest periodontal pocket depth and most severe clinical attachment loss (CAL). We used a self‐administered questionnaire to collect data on sociodemographic characteristics, diabetes history, health behaviour, SRH and self‐reported periodontitis. We applied 2‐level ordered logistic regression models for repeated measurements to examine the relationships between SRH (time t) and 1‐year‐lagged periodontal health (time t‐1) after adjusting for covariates.ResultsThe percentage of SRH responses recorded at time t as ‘good’, ‘moderate’ and ‘poor’ were 36.9%, 52.4% and 10.7%, respectively. Multivariate analyses showed that the risk of poorer SRH at time t increased in patients with CAL ≥7 mm (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.02–1.30), those who reported bleeding gums (OR = 1.33, 95% CI = 1.21–1.46) and those who perceived swollen gums (OR = 1.40, 95% CI = 1.26–1.56) at time t‐1. Sensitivity analyses using the 4‐year follow‐up model and 3‐year‐lagged cohort model also showed consistent results.ConclusionPeriodontitis shows a gradual contribution to future SRH in dental patients, even after adjusting for sociodemographic characteristics, general health and health‐related behaviours.
Myeloid differentiation protein‐2 has a protective role in house dust mite‐mediated asthmatic characteristics with the proinflammatory regulation of airway epithelial cells and dendritic cells
Authors: Ishii Takashi , Murakami Yusuke , Narita Tomoya , Nunokawa Hiroki , Miyake Kensuke , Nagase Takahide , Yamashita Naomi 
Published: August 2021

AbstractBackgroundMyeloid differentiation protein‐2 (MD‐2) is a lipopolysaccharide‐binding protein involved in lipopolysaccharide signalling via Toll‐like receptor 4 (TLR4). TLR4 plays an essential role in HDM‐mediated allergic airway inflammation. Moreover, MD‐2 is structurally similar to Der f 2, a major allergen from house dust mite (HDM).ObjectivesWe aimed to clarify the role of MD‐2 in the pathogenesis of HDM‐mediated allergic airway inflammation.MethodsWild‐type (WT), TLR4 knockout and MD‐2 knockout mice were subjected to intranasal instillation of HDM extract, and asthmatic features were evaluated. We also evaluated gene sets regulated by MD‐2 in HDM‐treated airway epithelial cells and examined the function of dendritic cells from lymph nodes and from lungs.ResultsAggravated allergic airway inflammation with increased airway hyperresponsiveness was observed in MD‐2 knockout mice compared with WT and TLR4 knockout mice. Global gene expression analysis revealed an MD‐2 regulated proinflammatory response and reconstituted TLR4 signalling in airway epithelial cells. The ability of dendritic cells to evoke an allergic immune response was enhanced in MD‐2 knockout mice.Conclusions & clinical relevanceMD‐2 plays a protective role in HDM‐induced airway allergy with the proinflammatory regulation of airway epithelial cells and dendritic cells. MD‐2 may serve as a therapeutic target in the treatment of asthma.
T cell activator-carrying extracellular vesicles induce antigen-specific regulatory T cells
Authors: Mo Li-Hua , Han Hai-Yang , Jin Qiao-Ruo , Song Yan-Nan , Wu Gao-Hui , Zhang Youming , Yang Li-Teng , Liu Tao , Liu Zhi-Gang , Feng Yan , Yang Ping-Chang 
Published: August 2021

Abstract
The mechanism of antigen-specific regulatory T cell (Treg) induction is not yet fully understood. Curcumin has an immune regulatory function. This study aims to induce antigen-specific Tregs by employing extracellular vesicles (EVs) that carry two types of T cell activators. Two types of T cell activators, ovalbumin (OVA)/major histocompatibility complex-II (MHC-II) and tetramethylcurcumin (FLLL31) (a curcumin analog) were carried by dendritic cell-derived extracellular vesicles, designated OFexo. A murine model of allergic rhinitis (AR) was developed with OVA as the specific antigen. AR mice were treated with a nasal instillation containing OFexo. We observed that OFexo recognized antigen-specific T cell receptors (TCR) on CD4+ T cells and enhanced Il10 gene transcription in CD4+ T cells. Administration of the OFexo-containing nasal instillation induced antigen-specific type 1 Tregs (Tr1 cells) in the mouse airway tissues. OFexo-induced Tr1 cells showed immune suppressive functions on CD4+ T cell proliferation. Administration of OFexo efficiently alleviated experimental AR in mice. In conclusion, OFexo can induce antigen-specific Tr1 cells that can efficiently alleviate experimental AR. The results suggest that OFexo has the translational potential to be employed for the treatment of AR or other allergic disorders.
Visual effects of concussion: A review
Authors: Fraser Clare L. , Mobbs Rowena 
Published: August 2021

AbstractA concussion occurs when a direct or indirect force is transmitted to the brain, causing a change in brain function. Given that approximately half the brain circuits are involved in vision and the control of eye movements, a concussion frequently results in visual symptoms. Ophthalmic abnormalities are helpful in the assessment of acute concussion, identified by rapid automized naming tasks and eye movement assessments. In particular, convergence, eye‐tracking and the vestibular‐ocular motor screening tool may be used. For patients suffering from post‐concussion syndrome more than 3 months from the original injury, abnormalities may be found in convergence, accommodation and smooth pursuit. Orthoptic exercises are useful rehabilitation tools to allow patients to return to school, work and recreation. This article provides a brief overview of concussion as it relates to vision and ophthalmic practice.
Towards coexistence: Can people's attitudes explain their willingness to live with Sumatran elephants in Indonesia?
Authors: Ardiantiono  , Sugiyo  , Johnson Paul J. , Lubis Muhammad Irfansyah , Amama Fahrul , Sukatmoko  , Marthy William , Zimmermann Alexandra 
Published: August 2021

AbstractUnderstanding coexistence between humans and threatened wildlife is a central focus in conservation. Way Kambas National Park in Sumatra Island, Indonesia, harbors one of the largest populations of the critically endangered Sumatran elephant (Elephas maximus sumatranus). The people who live alongside this population are affected by intensive crop foraging. Our study investigated the factors which influenced attitudes toward elephants. We then evaluated the implications of reported attitudes for future willingness to live with elephants. We surveyed 660 respondents in 22 villages around the park. People generally reported positive attitudes toward elephants (smartness 95%, usefulness 62%, importance 57%, and pleasantness 53%), apart from where human safety was concerned (safety 11%). Each dimension of attitude was explained by different factors including age, gender, knowledge of elephants, and distance to crop foraging locations. Most respondents (62%) expressed no willingness to coexist with elephants. Such willingness was lower when elephants were perceived to be more dangerous, but higher if beliefs in the benefits of elephants were greater. Efforts to improve crop foraging mitigation practice and to increase people's awareness of elephant benefits may promote support for their conservation. Through this study, we advocate the integration of social science to promote human–wildlife coexistence strategies, an approach that is currently limited in Indonesia.
Normative coherence for development: What relevance for responsive regionalism?
Authors: Koff Harlan , Häbel Sandra 
Published: August 2021

SummaryMotivationThe Sustainable Development Goals (SDGs) call for transformative development rooted in international norms, such as human rights, rule of law, and gender equality. Often, however, nation‐states do not implement these norms to the extent to which they are envisaged. Against this backdrop, regions have the potential to fill this implementation vacuum.PurposeWithout a normative dimension, transformative development risks reproducing traditional economic development. In this special issue we focus on norm implementation in different world regions through the lens of normative coherence for development.Methods and approachThe articles in this special issue all use qualitative methods, such as text analysis and in‐depth interviews. Given the different regional contexts, each article has its own approach to normative coherence for development depending on the regional normative framework.FindingsThis special issue indicates that regions are an important interlocutor between the global, national, and sub‐national level and, as such, are crucial for implementing the sustainable development agenda. The articles show, however, that to date normative coherence for development has not been achieved due to overriding priorities and technical approaches to policy coherence for development.Policy implicationsWith this special issue we aim to draw more attention to the topic of normative coherence for development and show that policies need to be adjusted in order to reflect the normative dimension of sustainable development.
Three‐year U.S. pharmacovigilance report of brodalumab
Authors: Lebwohl Mark , Leonardi Craig , Armstrong April , Rawnsley Nicole , Alexander Binu , Goehring Earl , Kerdel Francisco , Jacobson Abby 
Published: August 2021

AbstractBrodalumab, an interleukin‐17 receptor A antagonist, is approved for treatment of moderate‐to‐severe plaque psoriasis in adults without response or with loss of response to other systemic therapies. In the United States, there is a boxed warning for brodalumab regarding suicidal ideation and behavior; however, no causal relationship between brodalumab and suicidality was established during pivotal trials. In the 2‐year pharmacovigilance data, no completed suicides or suicide attempts were reported. The most frequent adverse event (AE) was arthralgia. The safety profile of brodalumab is now being updated after 3 years of pharmacovigilance data. Here, we outline pharmacovigilance data reported to Ortho Dermatologics by patients and healthcare professionals in the United States from August 15, 2017, to August 14, 2020. Brodalumab exposure estimates were obtained by calculating the time between first and last prescription‐dispensing authorization dates. Data from 1854 patients were collected, and brodalumab exposure was estimated to be 2736 patient‐years. The most frequent AE was arthralgia (111 events; 0.04 events per patient‐year). One episode of suicide attempt was reported in a patient with a history of depression. No completed suicides were reported. There were 81 serious infections reported, none of which were fungal. Over the 3‐year period, 30 malignancies occurred in 25 patients, none of which were determined to be related to brodalumab. Three‐year pharmacovigilance data are consistent with the safety profile of brodalumab previously reported in long‐term analyses of clinical trials and the 2‐year pharmacovigilance data.
Effectiveness of brodalumab after previous treatment failure of interleukin‐17A inhibitors in patients with psoriasis
Authors: Loft Nikolai , Bregnhøj Anne , Fage Simon , Nielsen Claus Henrik , Enevold Christian , Zachariae Claus , Iversen Lars , Skov Lone 
Published: August 2021

AbstractStudies on switch between interleukin (IL)‐17 inhibitors are scarce. We assessed the effectiveness of brodalumab in patients with previous treatment failure of IL‐17A inhibitor(s). Patients with psoriasis and previous treatment failure of an IL‐17A inhibitor were treated with brodalumab at standard dose. Effectiveness was assessed after 12, 26, and 52 weeks of treatment. The primary outcome was the proportion of patients that had achieved an absolute psoriasis area and severity index (PASI) ≤2 and/or a relative reduction of PASI of 75% (PASI75) at week 12. Plasma cytokine levels were measured at baseline and after 12 weeks of treatment. In total, 20 patients were included, seven (35%) were female, the median age was 50 years, and the median baseline PASI was 13.5. Analyzing the data using nonresponder imputation, 14 (70%) patients had achieved either PASI75 and/or PASI ≤2, 8 (40%) had achieved PASI90, and three (15%) had achieved PASI100 at week 12. In total, nine patients (45%) completed the 52‐weeks trial and seven patients (35%) still had PASI75 throughout 52 weeks. Seventeen out of 20 patients experienced any adverse events (AEs) during 52 weeks with no serious AEs or deaths. Patients responding to treatment had lower levels of tumor necrosis factor (TNF)‐α and IL‐6 at baseline compared with those who did not respond to treatment (TNF‐α, p = 0.041, IL‐6, p = 0.0054). In conclusion, treatment with brodalumab despite previous treatment failure with an IL‐17A inhibitor can be effective and well‐tolerated.