bluuebunny/crossref_metadata_2025 huggingface dataset:
Paeonol attenuates inflammation by confining HMGB1 to the nucleus
Authors: Miao Jifei , Zhong Jun , Lan Jiao , Ye Sen , Ye Peng , Li Siyan , You Aijia , Chen Xianjie , Liu Xiaoyi , Li Hui
Published: February 2021

Inflammation is a biological process that exists in a large number of diseases. If the magnitude or duration of inflammation becomes uncontrolled, inflammation may cause pathological damage to the host. HMGB1 and NF‐κB have been shown to play pivotal roles in inflammation‐related diseases. New drugs aimed at inhibiting HMGB1 expression have become a key research focus. In the present study, we showed that paeonol (Pae), the main active component of Paeonia suffruticosa, decreases the expression of inflammatory cytokines and inhibits the translocation of HMGB1 induced by lipopolysaccharide (LPS). By constructing HMGB1‐overexpressing (HMGB1+) and HMGB1‐mutant (HMGB1m) RAW264.7 cells, we found that the nuclear HMGB1 could induce an LPS‐tolerant state in RAW264.7 cells and that paeonol had no influence on the expression of inflammatory cytokines in HMGB1m RAW264.7 cells. In addition, the anti‐inflammatory property of paeonol was lost in HMGB1 conditional knockout mice, indicating that HMGB1 is a target of paeonol and a mediator through which paeonol exerts its anti‐inflammatory function. Additionally, we also found that HMGB1 and P50 competitively bound with P65, thus inactivating the NF‐κB pathway. Our research confirmed the anti‐inflammation property of paeonol and suggests that inhibiting the translocation of HMGB1 could be a new strategy for treating inflammation.
Brahma‐Related Gene‐1 (BRG1) promotes the malignant phenotype of glioblastoma cells
Authors: Wang Yinan , Yang Chuan He , Schultz Andrew P. , Sims Michelle M. , Miller Duane D. , Pfeffer Lawrence M.
Published: February 2021

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumour that is resistant to existing therapeutics. Identifying signalling pathways deregulated in GBM that can be targeted therapeutically is critical to improve the present dismal prognosis for GBM patients. In this report, we have identified that the BRG1 (Brahma‐Related Gene‐1) catalytic subunit of the SWI/SNF chromatin remodelling complex promotes the malignant phenotype of GBM cells. We found that BRG1 is ubiquitously expressed in tumour tissue from GBM patients, and high BRG1 expression levels are localized to specific brain tumour regions. Knockout (KO) of BRG1 by CRISPR‐Cas9 gene editing had minimal effects on GBM cell proliferation, but significantly inhibited GBM cell migration and invasion. BRG1‐KO also sensitized GBM cells to the anti‐proliferative effects of the anti‐cancer agent temozolomide (TMZ), which is used to treat GBM patients in the clinic, and selectively altered STAT3 tyrosine phosphorylation and gene expression. These results demonstrate that BRG‐1 promotes invasion and migration, and decreases chemotherapy sensitivity, indicating that it functions in an oncogenic manner in GBM cells. Taken together, our findings suggest that targeting BRG1 in GBM may have therapeutic benefit in the treatment of this deadly form of brain cancer.
The Prize of Governance. How the European Union Uses Symbolic Distinctions to Mobilize Society and Foster Competitiveness
Authors: Foret François , Vargovčíková Jana
Published: February 2021

Since its origins, the European Union (EU) has increasingly relied on prizes to highlight the values and principles channelling European integration. In the last two decades, such symbolic tools of governance have shifted away from the kind of distinctions granted by elites to elites and aiming to honour prominent figures offered as role models mainly in the field of identity, memory and cultural policies. In an increasingly market‐oriented Europe, prizes are used as incentives and disciplining instruments to enhance self‐compliance of economic and social actors with an ethos of competitiveness and innovation. They work as a magnifying glass of the evolution of the EU towards a government at distance through policy instruments. The focus is on four areas where prizes have multiplied since the 2000s: research and innovation, economic governance, territorial and environmental policies, and communication policies. The article draws on a qualitative analysis of a corpus of ninety‐one prizes, institutional documentation, parliamentary debates and media controversies related to prizes.
Politicizing Europe in Elections to the European Parliament (1994–2019): The Crucial Role of Mainstream Parties
Authors: Braun Daniela , Grande Edgar
Published: February 2021

Based on original data, this article analyses the politicization of European issues in European elections. Contrary to scholarly expectations, our findings show a higher level of politicization of European issues compared to national elections. However, politicization has been declining in both electoral arenas from the early 2000s until 2014 despite the increasing visibility of radical Eurosceptic parties. This paper suggests that this decline in politicization is a consequence of relatively low levels of emphasis put on the EU issue by mainstream political parties. It argues that Eurosceptic parties have had a paradoxical effect on politicization, since mainstream parties have responded to the former's mobilizing efforts by de‐emphasizing European issues rather than pursuing a confrontational strategy. This finding is corroborated by the 2019 elections, where we observe remarkably high levels of politicization in those countries where mainstream parties have been forced to open the debate around European issues.
Remaking the Regional: Legitimacy and Political Participation in Regional Integration
Authors: Gerard Kelly , Mickler David
Published: February 2021

The EU's profound crisis has drawn into sharp relief the challenges of reconfiguring national democratic processes around regional political communities. Over the same period for which the EU has fractured, however, other regional organizations have intensified integration. These divergent trends raise urgent questions regarding how regional organizations seek to legitimate integration and associated measures to regionalize decision‐making, and how these legitimation processes can be compared across regional organizations. This article focuses not on specifying how regional organizations should legitimate their activities, but instead on explaining how and why legitimation processes have been crafted in particular ways. Drawing on recent contributions in state theory and political geography, as well as political participation and de‐politicisation, the article advances an innovative approach to understanding how regional integration is (de)legitimated by, first, analysing state‐making and regionalism as ongoing and mutually constituted processes, and second, examining the design and function of participatory innovations.
Effects of low‐dose rhBMP‐2 on peri‐implant ridge augmentation in a canine model
Authors: Chao Yueh‐Ling , Wang Tong‐Mei , Chang Hao‐Hueng , Lin Li‐Deh
Published: February 2021

Aims

The aim of this study was to investigate the potential of low‐dose rhBMP‐2 combined with Hydroxyapatite (HAp)/β‐tricalcium phosphate (TCP)/ Collagen (Col) composite in repairing the peri‐implant critical size defect and to determine the optimal rhBMP‐2 concentration.

Materials and Methods

Fifty saddle‐type alveolar defects (10 mm mesiodistally and 4 mm apicocoronally) were surgically prepared on edentulous ridges in ten beagle dogs. Following implant placement, the defects with vertically exposed implant fixtures either received (a) no graft, (b) HAp/TCP/Col composite, (c) HAp/TCP/Col +0.02 mg/ml rhBMP‐2, (d) HAp/TCP/Col +0.08 mg/ml rhBMP‐2 or (e) HAp/TCP/Col +0.2 mg/ml rhBMP‐2. After healing for 4 or 8 weeks, bone regeneration and mineralization were assessed through radiography, micro‐CT, fluorescence labelling and histologic analyses. Implant stability was measured through resonance frequency analysis.

Results

It was evident HAp/TCP/Col with 0.2 mg/ml rhBMP‐2 manifested strong osteogenic potential in this large animal model, as significantly more and faster new bone formation with better implant stability was identified compared to the HAp/TCP/Col‐alone control group (adjusted p < .05).

Conclusions

Our results highlight the constructs of HAp/TCP/Col +0.2 mg/ml rhBMP‐2 without barrier membranes as a promising tool for peri‐implant ridge augmentation.
Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID‐19: A continuous glucose monitoring‐based observational study
Authors: Wu Xiumei , Luo Sihui , Zheng Xueying , Ding Yu , Wang Siqi , Ling Ping , Yue Tong , Xu Wen , Yan Jinhua , Weng Jianping
Published: February 2021

Aims/Introduction

The coronavirus disease 2019 (COVID‐19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people’s lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long‐term effect. We aimed to investigate the impact of COVID‐19 lockdown on glycemic control in children and adolescents with type 1 diabetes.

Materials and Methods

This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud‐based platform before, during and after lockdown. Demographics and lifestyle change‐related information were collected from the database or questionnaires. We compared these data before, during and after lockdown.

Results

A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9–10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25–9.53%) before lockdown to 2.91% (IQR 1.43–5.95%) during lockdown, but reversed to 4.95% (IQR 2.11–9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14–2.21%), 0.38% (IQR 0.05–1.35%) and 0.82% (IQR 0.22–1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently.

Conclusion

Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID‐19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long‐term effect.
Position statement for a pragmatic approach to immunotherapeutics in patients with inflammatory skin diseases during the coronavirus disease 2019 pandemic and beyond
Authors: Beecker J. , Papp K.A. , Dutz J. , Vender R.B. , Gniadecki R. , Cooper C. , Gisondi P. , Gooderham M. , Hong C.H. , Kirchhof M.G. , Lynde C.W. , Maari C. , Poulin Y. , Puig L.
Published: February 2021

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS‐CoV‐2 is reflected by its rapid global spread. The SARS‐CoV‐2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS‐CoV‐2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS‐CoV‐2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms.
Three‐dimensional histology vs. serial section histology in the treatment of primary basal cell carcinoma: a randomized, prospective, blinded study of 569 tumours
Authors: Kofler L. , Breuninger H. , Schreiber R.H. , Eichner M. , Häfner H.‐M. , Schnabl S.M.
Published: February 2021

Background

For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three‐dimensional histology (3D‐histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections.

Objectives

To investigate the rate of local recurrence (LR) as well as the number of required re‐excisions for basal cell carcinomas with serial section histology vs. 3D‐histology.

Methods

We compared serial sections histology with 3D‐histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections.

Results

Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re‐excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D‐histology group, re‐excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow‐up was 4.5 years.

Conclusions

3D‐histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re‐excisions. 3D‐histology was associated with a significantly lower LR rate than serial section histology.
Entrepreneurial experience and firm exit over the business cycle
Authors: McGuire Erin
Published: February 2021

In this paper, I explore business cycle‐related dynamics in differences in exit decisions between serial and novice entrepreneurs. Using time series geographic variation in economic conditions, I examine how businesses founded by serial and novice entrepreneurs differentially respond to changes on average state personal income, alternative employment options, and home values. Weibull survival model estimates indicate that serial entrepreneurs are more likely to endure declines in aggregate income and credit availability, but are relatively more likely to go out of business as slack increases in the labor market (increases in unemployment rate). In the second part of the paper, I provide evidence that these dynamics are driven by differences in business strategies and the use of financial resources.
Identification, expression and enzyme activity of the group III sPLA2s in Cyprinus carpio L
Authors: Xu Yuxin , Li Hongxia , Xu Dihui , Li Jianlin , Yu Fan , Wang Meiyao , Wang Qin , Wu Yunsheng , Zhang Qiyuan , Tang Yongkai , Yu Juhua
Published: February 2021

Five group III secreted phospholipase (pla2g3s) homologous genes located on different linkage groups were identified from common carp (Cyprinus carpio), which we named Ccpla2g3a1, Ccpla2g3a2, Ccpla2g3b, Ccpla2g3c1 and Ccpla2g3c2. The five genes encode 530, 525, 461, 752 and 753 amino acids, respectively. Sequence analysis showed that the Ccpla2g3as contain seven exons and the others contain four exons. Synteny analysis of fish pla2g3s indicated that pla2g3a and pla2g3b were from the same ancestor gene, and Ccpla2g3a1, Ccpla2g3a2, Ccpla2g3c1 and Ccpla2g3c2 were from the specific genome duplication of common carp. Due to the significant variation of the pla2g3bs from common carp and zebrafish (Danio rerio), they formed a separate group in the phylogenetic tree. The tissue distributions of Ccpla2g3s coincided with their expression profiles during the embryo stages. The expression levels of Ccpla2g3as and Ccpla2g3cs were low at the embryo stages, and they were abundant in the liver and brain, respectively, whereas the expression of Ccpla2g3b was high at 0.5 h after fertilization and in the ovary. We obtained three soluble recombinant proteins of the bee venom‐like PLA2 (BVLP) from Ccpla2g3 and evaluated their PLA2 enzyme properties. The optimum pHs of MBP‐a1‐BVLP, MBP‐b‐BVLP and MBP‐c1‐BVLP were 7.5, 7.0 and 8.0, respectively, and specific activities were 7.68 ± 0.66, 4.155 ± 0.158 and 1.93 ± 0.05 U μmol–1, respectively. The Kd for Ca2+ of MBP‐b‐BVLP was the lowest (2.6 μM), whereas the values for both MBP‐a1‐BVLP and MBP‐c1‐BVLP were about 15 μM. The Km values of three proteins ranged from 31.9 to 41.91 μM.
Bedside risk‐scoring model for predicting 6‐week mortality in cirrhotic patients undergoing endoscopic band ligation for acute variceal bleeding
Authors: Kim Jung Hee , Park Se Woo , Jung Jang Han , Park Da Hae , Bang Chang Seok , Park Chan Hyuk , Park Ji Won , Park Jae Gun
Published: February 2021

Background and Aim

Acute variceal bleeding (AVB) is a fatal adverse event of cirrhosis, and endoscopic band ligation (EBL) is the standard treatment for AVB. We developed a novel bedside risk‐scoring model to predict the 6‐week mortality in cirrhotic patients undergoing EBL for AVB.

Methods

Cox regression analysis was used to assess the relationship of clinical, biological, and endoscopic variables with the 6‐week mortality risk after EBL in a derivation cohort (n = 1373). The primary outcome was the predictive accuracy of the new model for the 6‐week mortality in the validation cohort. Moreover, we tested the adequacy of the mortality risk‐based stratification and the discriminative performance of our new model in comparison with the Child–Turcotte–Pugh (CTP) and the model for end‐stage liver disease scores in the validation cohort (n = 200).

Results

On multivariate Cox regression analysis, five objective variables (use of beta‐blockers, hepatocellular carcinoma, CTP class C, hypovolemic shock at initial presentation, and history of hepatic encephalopathy) were scored to generate a 12‐point risk‐prediction model. The model stratified the 6‐week mortality risk in patients as low (3.5%), intermediate (21.1%), and high (53.4%) (P < 0.001). Time‐dependent area under the receiver operating characteristic curve for 6‐week mortality showed that this model was a better prognostic indicator than the CTP class alone in the derivation (P < 0.001) and validation (P < 0.001) cohorts.

Conclusions

A simplified scoring model with high potential for generalization refines the prediction of 6‐week mortality in high‐risk cirrhotic patients, thereby aiding the targeting and individualization of treatment strategies for decreasing the mortality rate.
Colon volvulus in rhesus macaques (Macaca mulatta) at the Oregon National Primate Research Center—Retrospective analysis
Authors: Johnson Amanda L. , Bronson Steven , Prongay Kamm , Norris Reed A. , Lewis Anne D.
Published: February 2021

Colonic volvulus is an uncommon, often life‐threatening condition, in non‐human primates. Twenty‐six cases of colonic volvulus in rhesus macaques (Macaca mulatta) were identified in necropsy records spanning 38 years at the Oregon National Primate Research Center (ONPRC). This report represents the largest collection of colonic volvuli in rhesus macaques.
Chemogenetic approaches to identify metabolically important GPCR signaling pathways: Therapeutic implications
Authors: Meister Jaroslawna , Wang Lei , Pydi Sai P. , Wess Jürgen
Published: February 2021

DREADDs (Designer Receptors Exclusively Activated by a Designer Drug) are designer G protein‐coupled receptors (GPCRs) that are widely used in the neuroscience field to modulate neuronal activity. In this review, we will focus on DREADD studies carried out with genetically engineered mice aimed at elucidating signaling pathways important for maintaining proper glucose and energy homeostasis. The availability of muscarinic receptor‐based DREADDs endowed with selectivity for one of the four major classes of heterotrimeric G proteins (Gs, Gi, Gq, and G12) has been instrumental in dissecting the physiological and pathophysiological roles of distinct G protein signaling pathways in metabolically important cell types. The novel insights gained from this work should inform the development of novel classes of drugs useful for the treatment of several metabolic disorders including type 2 diabetes and obesity.

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Mass spectrometry analysis of tau and amyloid‐beta in iPSC‐derived models of Alzheimer’s disease and dementia
Authors: Arber Charles , Alatza Argyro , Leckey Claire A. , Paterson Ross W. , Zetterberg Henrik , Wray Selina
Published: February 2021

Induced pluripotent stem cell (iPSC) technology enables the generation of human neurons in vitro, which contain the precise genome of the cell donor, therefore permitting the generation of disease models from individuals with a disease‐associated genotype of interest. This approach has been extensively used to model inherited forms of Alzheimer's disease and frontotemporal dementia. The combination of iPSC‐derived neuronal models with targeted mass spectrometry analysis has provided unprecedented insights into the regulation of specific proteins in human neuronal physiology and pathology. For example enabling investigations into tau and APP/Aβ, specifically: protein isoform expression, relative levels of cleavage fragments, aggregated species and functionally critical post‐translational modifications. The use of mass spectrometry has enabled a determination of how closely iPSC‐derived models recapitulate disease profiles observed in the human brain. This review will highlight the progress to date in studies using iPSCs and mass spectrometry to model Alzheimer's disease and dementia. We go on to convey our optimism, as studies in the near future will make use of this precedent, together with novel techniques such as genome editing and stable isotope labelling, to provide real progress towards an in depth understanding of early neurodegenerative processes and development of novel therapeutic agents.

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Clinical brightening efficacy and safety of Melasolv™ (3,4,5‐trimethoxy cinnamate thymol ester, TCTE) in Southeast Asian women
Authors: Kim Seung Hun , Paik Byung Ryol , Lee Sung Hoon , Lee So Mi , Kim Mi Jin , Kim Eun Joo , Leow Chin Yong , Cho Changhui , Park Won‐Seok , Suh Byung‐Fhy
Published: February 2021

Background

Skin darkening because of increased and irregular synthesis of melanin causes melasma, solar lentigo, and freckles. Melasolv™, produced in the early 2000s, shows potent depigmenting effect and has low cytotoxicity. It has been used as a brightening agent in cosmetics for decades.

Aims

This study was conducted to investigate whether Melasolv™ is effective for the skin of ASEAN (Southeast Asia) women.

Methods

We recruited ASEAN women in Singapore and divided them into two groups (active group vs. placebo group). Melasolv™ and placebo formulations were applied twice a day for 12 weeks. The changes in the pigmented spots were visually evaluated by an expert and assessed using a spectrophotometer and Mexameter at 0, 4, 8, and 12 weeks.

Results

The visual evaluation revealed significant improvements, in both size and color intensity, in the active group compared with those in the placebo group at 12 weeks. In the spectrophotometric evaluation, the L* value of the pigmented spots in the active group was significantly higher than that in the placebo group at 12 weeks. Similar results were obtained in the evaluation using the Mexameter. After 12 weeks, the melanin index of the pigmented spots significantly decreased, and it was significantly higher than that in the placebo group. There was no significant change in the erythema index. In the image analysis, there were no significant differences in skin color brightness and evenness in the active group compared with those in the placebo group.

Conclusion

Melasolv™ can be effective used for skin brightening.
Quantifiable clinical efficacy of injectable porcine collagen for the treatment of structural dark circles
Authors: Zhao Rui , Qiu He , Liu Shuo , Cao Lideng , Yu Donglei , Wang Hang
Published: February 2021

Background

Dark circles are one of the most perplexing cosmetic problems for modern people. Nowadays, a new porcine collagen filler has been popular in China and many countries and has high safety.

Aims

The purpose of this study is to explore and quantify the efficacy of this collagen filler in treating structured dark circles objectively and systematically.

Methods

This is a prospective study. Twenty patients were included and took standard facial photographs at preoperative (Tp), immediately postoperative (T0), 1 week (T1), 2 weeks (T2), 4 weeks (T4), 8 weeks (T8), and 12 weeks (T12). The efficacy was quantified by measuring the depression of the tear trough and infraorbital melanin content. Three dermatologists blinded to the treatment were responsible for completing the subjective evaluations.

Results

The depression volume, depression‐affected area, and depression maximum depth of the tear trough decreased significantly immediately postoperation, and then all values increased slowly with time (P <.05). After 3‐month observation, we found that the residual effect of the treatment is 45.08% ± 15.53% (T8) and 17.37% ± 16.79% (T12). The melanin contents at the medial point (A), the middle point (B), and the lateral point (C) all decreased instantly after injection (A: 8.23% ± 5.07%, B: 6.29% ± 5.05%, C: 5.11% ± 5.44% ), which suggested that collagen filler had an instant covering effect for structural dark circles. Patients showed only slight redness and swelling after the treatment.

Conclusion

Collagen filler is a very effective treatment method for structural dark circles. Besides, it may also have a certain therapeutic effect on the other three dark circles types.
LncRNA DCST1‐AS1 inhibits PDLCs’ proliferation in periodontitis and may bind with miR‐21 precursor to upregulate PLAP‐1
Authors: Wang Xiaoying , Wang Yanhua
Published: February 2021

Objective

This study aimed to investigate the potential interactions among long noncoding RNA domain containing 1‐antisense (lncRNA DCST1‐AS1), miR‐21, and periodontal ligament–associated protein‐1 (PLAP‐1) in periodontitis.

Background data discussing the present state of the field

It has been verified that miR‐21 can target PLAP‐1 to regulate the osteogenic differentiation of periodontal ligament cells (PDLCs).

Methods

Differential expression of DCST1‐AS1 and miR‐21 in PDLCs derived from periodontitis patients and healthy controls was determined by qPCR and unpaired t test. QPCR and Western blots were conducted to evaluate the effects of overexpression of DCST1‐AS1 and miR‐21 on the expression of PLAP‐1. CCK‐8 assay was applied to evaluate the effect of DCST1‐ASI, miR‐21, or PLAP‐1 on PDLCs’ proliferation. Western blotting was conducted to detect the expression levels of CKD family (CDK4, CDK6, and CCND1).

Results

DCST1‐AS1 was downregulated in PDLCs derived from periodontitis patients, and its expression was inversely correlated with the expression of miR‐2 but positively correlated with PLAP‐1. Bioinformatics analysis showed that DCST1‐AS1 might bind with miR‐21 precursor but not mature miR‐21. Transfection experiments showed that overexpression of DCST1‐AS1 led to decreased expression levels of miR‐21 and significantly increased the expression levels of PLAP‐1 at both mRNA and protein levels, while overexpression of miR‐21 resulted in a dramatic lower level of PLAP‐1. CCK‐8 assay indicated that overexpression of DCST1‐AS1 or PLAP‐1 prohibited PDLCs’ proliferation. However, elevation of miR‐21 had a contrary effect on the proliferation of PDLCs. And increased expression levels of DCST1‐AS1 could significantly inhibit the expression of CDK4, CDK6, and CCND‐1, while overexpression of miR‐21 inversed the effects of DCST1‐AS1.

Conclusion

Therefore, the expression levels of DCST1‐AS1 are much lower in periodontitis patients compared to that in healthy controls, and overexpression of DCST1‐AS1 can significantly elevate the expression of PLAP‐1 by inhibiting miR‐21 in PDLCs.
Optimizing citric acid protocol to control implant‐related infections: Anin vitroandin situstudy
Authors: Cordeiro Jairo M. , Pires Júlia M. , Souza João G. S. , Lima Carolina V. , Bertolini Martinna M. , Rangel Elidiane C. , Barão Valentim A. R.
Published: February 2021

Objective

The present study aimed to establish an optimized protocol for biofilm removal from titanium (Ti) surfaces using citric acid (CA) solutions.

Background

Biofilm accumulation is the main factor to trigger peri‐implant infections and to increase the risk of treatment failures. Although CA has been suggested as the anti‐infective agent with highest potential for biofilm removal on Ti, there is no consensus that CA could improve the anti‐infective treatment and its effect.

Methods

Physical and chemical alterations, electrochemical behavior, cytotoxicity, and antimicrobial effect of CA on Ti discs were evaluated using four concentrations (1, 10, 20, and 40%) and two application methods (immersion and rubbing). Negative control using 0.9% NaCl was used in all experiments. To evaluate whether different application times can have similar response, polymicrobial biofilm (microcosm model) was formed on Ti and treated with CA for 1, 2, 4, and 8 min. Anin situstudy was conducted to verify whether the established protocol is equally effective in biofilms formed on machined and sandblasted, large‐grit, and acid‐etched (SLA) Ti surfaces.

Results

CA 40% induced significantly higher surface alterations observed by confocal images and profilometry. In general, rubbing protocol decreased the surface roughness and increased the wettability (p < 0.05), exhibiting better surface cleaning by biofilm removal. CA 10% presented no indirect cytotoxicity and, when applied by rubbing for 8 min, presented properin vitroantibacterial action and potential corrosion inhibition. When CA 10% was rubbed on Ti surfaces for 4 min, it displayed optimum cleaning ability as 8 min, working equally to removein situbiofilm on machined and SLA surfaces.

Conclusions

The application of CA 10% by rubbing for at least 4 min demonstrated to be a promising protocol to eliminate biofilms formed in smooth and rougher surfaces, which could improve implant‐related infection therapies.
Value of thoracic and abdominal screening in dogs with neurological signs
Authors: Destri A. , Shea A. , Sparkes A. H. , Dennis R.
Published: February 2021

Objectives

To detect the incidence of clinically important thoracic and abdominal imaging abnormalities in patients with neurological signs but with no clinical signs or laboratory findings consistent with thoracic or abdominal disease.

Materials and Methods

Review of imaging findings in dogs with neurological signs but no thoracic or abdominal signs that underwent thoracic, or thoracic and abdominal screening during the same hospitalisation as the neurological investigation.

Results

Two hundred and six dogs were included in the thoracic study. Of those, only eight (3.9%) had clinically important findings and in only five cases (2.4%) were the findings related to pathology identified on MRI. One hundred and forty‐seven dogs were included in the abdominal study. Abnormalities were found in 23 dogs (15.6%), but in only eight (5.4%) were they considered to be of current clinical importance and in only three (2%) were they related to the pathology identified on MRI. Ultrasonography provided valuable additional information in 22 cases (15%) but this was only considered important in four (2.7%) and related to the neurological condition in one (0.7%). As expected, abdominal ultrasonography often provided more information than radiography alone in the abdominal screening but this was rarely clinically relevant or related to the reason for referral.

Clinical Significance

Thoracic and abdominal screening of neurological patients with no clinically evident thoracic or abdominal clinical signs only infrequently identified occult but clinically important pathology which changed the current management plan, regardless of neurolocalisation or age.
Daily associations between sleep and pain in patients with chronic musculoskeletal pain
Authors: Abeler Karin , Bergvik Svein , Sand Trond , Friborg Oddgeir
Published: February 2021

Patients with chronic pain commonly report sleep problems, and the evidence for a relationship between sleep disturbance and pain seems robust. The day‐to‐day associations between these constructs are less well studied, particularly with objective sleep measures such as actigraphy. Moreover, the concurrent presence of negative affective symptoms, as well as seasonality effects at extreme latitudes may complicate it further. Here, we studied 56 patients with chronic primary musculoskeletal pain conditions, contributing data in two separate 7‐day data‐collection periods during the summer and winter, respectively. The effect of self‐reported sleep quality, and actigraphy measured sleep duration, efficiency and timing on next‐day pain, as well as the effect of pain on the same sleep indices were estimated by generalised linear mixed regression models. The models were additionally adjusted for age, sex, education, data collection period, weekend, season and mental distress, with the latter two also specified as moderators. We observed a significant effect of pain as a predictor of next‐night sleep quality (p = .003) and marginally of next‐night sleep duration (p = .079). Conversely, sleep quality tentatively predicted next‐day pain (p = .063). No other day‐to‐day associations were present. Mental distress was the strongest predictor of pain, but it did not modify the sleep–pain associations, nor did season. In conclusion pain, sleep quality and mental distress are closely related, underscoring the importance of encompassing this complexity in assessment and treatment of patients with chronic pain.
Prevalence of gastrointestinal lesions in dogs chronically treated with nonsteroidal anti‐inflammatory drugs
Authors: Mabry Kasey , Hill Tracy , Tolbert Mary Katherine
Published: February 2021

Background

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most common pharmaceutical associated with gastroduodenal ulceration and perforation. The prevalence of gastrointestinal (GI) injury associated with chronic use of NSAIDs in dogs is unknown.

Objective/Hypothesis

To determine the prevalence of GI mucosal erosions in dogs receiving chronic treatment with NSAIDs. We hypothesized that dogs receiving NSAIDs would have more GI mucosal erosions and longer GI transit time than a control population.

Animals

Fourteen client‐owned medium‐ and large‐breed dogs receiving an NSAID for at least 30 days and 11 client‐owned control dogs undergoing video capsule endoscopy (VCE) for evaluation of chronic GI disease.

Methods

Dogs were prospectively recruited after determining no clinically relevant comorbidities were present and VCE was performed. The GI transit time and the presence of mucosal lesions were recorded.

Results

Twelve dogs receiving NSAIDs and 11 retrospectively evaluated control dogs were included. The NSAIDs administered included carprofen (9 dogs), meloxicam (2 dogs), and firocoxib (1 dog) for a median of 6 months. Ten (83.3%; 95% confidence interval; 51.6%‐97.9%) NSAID‐treated dogs had GI erosions. Erosions were seen with all 3 NSAIDs in at least 1 dog. Three of 11 control dogs had gastric erosions. Dogs receiving NSAIDs had more erosions detected (P= .004).

Conclusions and Clinical Relevance

Subclinical GI erosions are more common in dogs receiving chronic treatment with NSAIDs than in control dogs with chronic GI disease, suggesting that NSAIDs be used with caution, particularly in dogs with comorbidities predisposing them to GI ulceration.
Contrasting effects of the El Niño 2015–16 event on coral reefs from the central pacific coast of Mexico
Authors: Nava Héctor , López Norma , Ramírez‐García Pedro , Garibay‐Valladolid Elizabeth
Published: February 2021

Coral reefs are highly diverse and productive ecosystems, and certain oceanographic processes, such as El Niño, have resulted in severe coral bleaching and mortality of reef‐building corals and to the global decline of the area covered by coral reefs. Here, we report the response of corals and both green and red filamentous and coralline algae from the central Mexican Pacific coast to the 2015–16 El Niño event. Sea surface temperature (SST) was recorded in the area between june 2012 and December 2018. Additionally, SST, DHW and the Oceanic El Niño Index (ONI) provided by NOAA for the El Niño 3 region during the same period were considered. Relative cover (%) of healthy, pale, bleached and dead corals, coral rubble, filamentous algae, rocks, and sand were recorded at five reefs during 2010, 2015, and 2018. Between April 2015 and April 2016, the SST was warmer than average, and the ONI showed temperature anomalies near 3, indicating a strong El Niño event. The response of corals varied among reefs and years. No relevant changes in substrata cover were recorded at two reefs through the years, but extensive coral bleaching occurred at the other reefs in June 2015, with dramatic coral mortality as a consequence. An inability to recover and the resulting dominance of filamentous algae over dead corals was evident at two reefs in January 2018. Multivariate analysis based on the cover of substrata and the comparison with previous studies suggested that the response of the coral reefs was not related to the previous state of conservation or the level of anthropogenic impact at each reef. The causes of such thermal resistance are uncertain; nonetheless, it has a high potential to cope with future El Niño impacts.
The hidden landscape: Evidence that sea‐level change shaped the present population genomic patterns of marginal marine species
Authors: Dolby Greer A.
Published: February 2021

Oftentimes, to understand the genetic relatedness and diversity of today's populations requires considering the ancient landscape on which those populations evolved. Nowhere is this clearer than along Earth's coastline, which has been in its present‐day configuration for only about 6.5% of the past 800,000 years (Dolby et al., 2020; Miller et al., 2005). During ice ages when glaciers expanded in the Northern Hemisphere, they stored enough of the planet's water to drop global sea level by ~120 m below present levels (“lowstand”, Figure 1a), and there have been at least eight of these 100,000‐year cycles preceding today. When glaciers melted, ocean water reflooded shorelines, shifting and re‐forming marginal marine habitats globally and shaping the relatedness of populations (Dolby et al., 2016). In a From the Cover article in this issue of Molecular Ecology, Stiller et al. (2020) integrate population genomic analysis of leafy seadragons in southern Australia with estimates of available seabed area to reveal that the expansion of habitat that accompanied this reflooding led to strong demographic expansions. With statistical models, they also show that western populations were eliminated and then recolonized because the continental shelf there is narrow, leaving little available habitat when sea level was low (Figure 1b). Their results document the dynamic and interrelated nature of a hidden, changing landscape and the evolution of species inhabiting it.
Root presence modifies the long‐term decomposition dynamics of fungal necromass and the associated microbial communities in a boreal forest
Authors: Maillard François , Kennedy Peter G. , Adamczyk Bartosz , Heinonsalo Jussi , Buée Marc
Published: February 2021

Recent studies have highlighted that dead fungal mycelium represents an important fraction of soil carbon (C) and nitrogen (N) inputs and stocks. Consequently, identifying the microbial communities and the ecological factors that govern the decomposition of fungal necromass will provide critical insight into how fungal organic matter (OM) affects forest soil C and nutrient cycles. Here, we examined the microbial communities colonising fungal necromass during a multiyear decomposition experiment in a boreal forest, which included incubation bags with different mesh sizes to manipulate both plant root and microbial decomposer group access. Necromass‐associated bacterial and fungal communities were taxonomically and functionally rich throughout the 30 months of incubation, with increasing abundances of oligotrophic bacteria and root‐associated fungi (i.e., ectomycorrhizal, ericoid mycorrhizal and endophytic fungi) in the late stages of decomposition in the mesh bags to which they had access. Necromass‐associated β‐glucosidase activity was highest at 6 months, while leucine aminopeptidase peptidase was highest at 18 months. Based on an asymptotic decomposition model, root presence was associated with an initial faster rate of fungal necromass decomposition, but resulted in higher amounts of fungal necromass retained at later sampling times. Collectively, these results indicate that microbial community composition and enzyme activities on decomposing fungal necromass remain dynamic years after initial input, and that roots and their associated fungal symbionts result in the slowing of microbial necromass turnover with time.
Febrile temperature causes transcriptional downregulation ofPlasmodium falciparumSirtuins through Hsp90‐dependent epigenetic modification
Authors: Tabassum Wahida , Bhattacharyya Sunanda , Varunan Shalu M. , Bhattacharyya Mrinal Kanti
Published: February 2021

Sirtuins (PfSIR2AandPfSIR2B) are implicated to play pivotal roles in the silencing of sub‐telomeric genes and the maintenance of telomere length inP. falciparum3D7 strain. Here, we identify the key factors that regulate the cellular abundance and activity of these two histone deacetylases. Our results demonstrate thatPfSIR2AandPfSIR2Bare transcriptionally downregulated at the mid‐ring stage in response to febrile temperature. We found that the molecular chaperone PfHsp90 acts as a repressor ofPfSIR2A&Btranscription. By virtue of its presence in thePfSIR2A&Bpromoter proximal regions PfHsp90 helps recruiting H3K9me3, conferring heterochromatic state, and thereby leading to the downregulation ofPfSIR2A&Btranscription. Such transcriptional downregulation can be reversed by the addition of 17‐(allylamino)‐17‐demethoxygeldanamycin or Radicicol, two potent inhibitors of PfHsp90. The reduced occupancy of PfSir2 at sub‐telomericvarpromoters leads to the de‐repression ofvargenes. Thus, here we uncover how exposure to febrile temperature, a hallmark of malaria, enables the parasites to manipulate the expression of the two prominent epigenetic modifiers PfSir2A and PfSir2B.
Gastric accumulation of enteral nutrition reduces pressure changes induced by phasic contractility in an isovolumetric intragastric balloon
Authors: Goelen Nick , Doperé Glynnis , Byloos Kris , Ghysels Stefan , Putzeys Guido , Vandecaveye Vincent , Morales John , Van Huffel Sabine , Tack Jan , Janssen Pieter
Published: February 2021

Background

An isovolumetric intragastric balloon to continuously measure gastric phasic contractility was recently developed by us. We aimed to investigate the readout of this technique in relation to gastric content and gastric emptying.

Methods

In this crossover investigation, the VIPUNTM Gastric Monitoring System, which comprises a double lumen nasogastric feeding tube with integrated intragastric balloon, was used to assess phasic gastric contractility by interpretation of the pressure in an isovolumetric balloon in 10 healthy subjects. Balloon pressure was recorded in fasted state, during a 2‐hour intragastric nutrient infusion (1 kcal/ml at 25, 75, or 250 ml/h) and 4 hours post‐infusion, and quantified as Gastric Balloon Motility Index (GBMI), ranging from 0 (no contractility) to 1 (maximal contractility). Gastric accumulation was quantified with magnetic resonance imaging and gastric emptying with a13C‐breath test. Results are expressed as mean(SD).

Key Results

GBMI was significantly lower during infusion at 250 ml/h compared to baseline (0.13(0.05) versus 0.46(0.12)) and compared to infusion at 25 (0.54(0.21)) and 75 ml/h (0.43(0.20)), all P < 0.005. Gastric content volume was larger after infusion at 250 versus 75 ml/h (P < 0.001). Half‐emptying time and accumulation were both negatively correlated with postprandial contractility. Postprandial GBMI was significantly lower when GCV>0 ml compared to when the stomach was empty.

Conclusions and Inferences

Enteral nutrition dose‐dependently decreased the contractility readout. This decrease was linked to gastric accumulation of enteral nutrition.
Making space for the normativity of coherence
Authors: Worsnip Alex
Published: February 2021

This paper offers a new account of how structural rationality, or coherence, is normative. The central challenge to the normativity of coherence – which I term the problem of “making space” for the normativity of coherence – is this: if considerations of coherence matter normatively, it is not clear how we ought to take account of them in our deliberation. Coherence considerations don't seem to show up in reasoning about what to believe, intend, desire, hope, fear, and so on; moreover, they seem awkward to take account of alongside more “substantive” considerations about the merits of such attitudes. I aim here to solve this problem, and in so doing to offer the aforementioned new account of how coherence is normative. On the view I defend, which I call the Reasons‐to‐Structure‐Deliberation model, considerations of coherence constitute reasons for structuring deliberation in certain ways: more particularly, to treat incoherent combinations of attitudes as off‐limits, and so to focus one's deliberation on choosing between the coherent combinations.
The eco‐evolutionary significance of rainfall constancy for facultative CAM photosynthesis
Authors: Schweiger Andreas H. , Nürk Nicolai M. , Beckett Heath , Liede‐Schumann Sigrid , Midgley Guy F. , Higgins Steven I.
Published: February 2021

A flexible use of the crassulacean acid metabolism (CAM) has been hypothesised to represent an intermediate stage along a C3 to full CAM evolutionary continuum, when relative contributions of C3 vs CAM metabolism are co‐determined by evolutionary history and prevailing environmental constraints. However, evidence for such eco‐evolutionary interdependencies is lacking.

We studied these interdependencies for the leaf‐succulent genus Drosanthemum (Aizoaceae, Southern African Succulent Karoo) by testing for relationships between leaf δ13C diagnostic for CAM dependence (i.e. contribution of C3 and CAM to net carbon gain), and climatic variables related to temperature and precipitation and their temporal variation. We further quantified the effects of shared phylogenetic ancestry on CAM dependence and its relation to climate.

CAM dependence is predicted by rainfall and its temporal variation, with high predictive power of rainfall constancy (temporal entropy). The predictive power of rainfall seasonality and temperature‐related variables was negligible. Evolutionary history of the tested clades significantly affected the relationship between rainfall constancy and CAM dependence.

We argue that higher CAM dependence might provide an adaptive advantage in increasingly unpredictable rainfall environments when the anatomic exaptation (succulence) is already present. These observations might shed light on the evolution of full CAM.