bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between common sleep disturbances and cardiovascular risk in patients with obstructive sleep apnea: A large-scale cross-sectional study
Authors: Zhang Xiaoman , Huang Weijun , Xu Huajun , Li Xinyi , Wang Fan , Wu Kejia , Li Chenyang , Liu Yupu , Zou Jianyin , Zhu Huaming , Yi Hongliang , Guan Jian , Qian Di , Yin Shankai
Published: October 2022

Objectives

Studies have shown that obstructive sleep apnea (OSA) is inextricably linked with cardiovascular diseases (CVD). However, the roles of certain common sleep disturbances, such as low slow-wave sleep, excessive daytime sleepiness and short sleep duration, in the pathogenesis and progression of CVD in patients with OSA have not been determined. Therefore, we conducted a large cross-sectional study to explore the effect of low slow-wave sleep, excessive daytime sleepiness and short sleep duration on the risk of CVD in patients with OSA.

Methods

Subjects were consecutively enrolled to participate in the sleep center of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital. All OSA patients were diagnosed by standard polysomnography, while controls were all simple snorers. A total of 4,475 participants were strictly recruited. The Framingham Risk Score were employed to assess the 10-year risk of CVD, and logistic regression was used to measure the association between sleep disturbances and the moderate-to-high CVD risk.

Results

In the whole cohort, OSA, excessive daytime sleepiness, and low slow-wave sleep were all risk factors for the moderate-to-high 10-year CVD risk (odds ratio [OR] = 3.012, 95% confidence interval [CI] 2.418–3.751; OR = 1.407, 95% CI: 1.228–1.613, and OR = 0.973,95% CI: 0.967–0.980), but sleep duration did not contribute significantly to that risk. Whether in patients with OSA and controls, low SWS (<12.8%) could increase the risk of CVD. Subjective excessive daytime sleepiness would significantly increase the risk of CVD only in patients with severe OSA.

Conclusion

It is important to pay more attention to the impact of sleep on cardiovascular health. Patients with sleep disturbances should adopt a healthy lifestyle and undergo regular follow-up of cardiovascular indicators to prevent cardiovascular complications.

Trial registration

[http://www.chictr.org.cn/showproj.aspx?proj=43057], identifier [ChiCTr1900025714].
Interactive contribution of hyperinsulinemia, hyperglycemia, and mammalian target of rapamycin signaling to valvular interstitial cell differentiation and matrix remodeling
Authors: Selig Jessica I. , Krug H. Viviana , Küppers Caroline , Ouwens D. Margriet , Kraft Felix A. , Adler Elena , Bauer Sebastian J. , Lichtenberg Artur , Akhyari Payam , Barth Mareike
Published: October 2022

Diabetes and its major key determinants insulin resistance and hyperglycemia are known risk factors for calcific aortic valve disease (CAVD). The processes leading to molecular and structural alterations of the aortic valve are yet not fully understood. In previous studies, we could show that valvular interstitial cells (VIC) display canonical elements of classical insulin signaling and develop insulin resistance upon hyperinsulinemia and hyperglycemia accompanied by impaired glucose metabolism. Analyses of cultured VIC and aortic valve tissue revealed extracellular matrix remodeling and degenerative processes. Since PI3K signaling through mammalian target of rapamycin (mTOR) is involved in fibrotic processes of the heart, we aim at further functional investigation of this particular Akt-downstream signaling pathway in the context of diabetes-induced CAVD. Primary cultures of VIC were treated with hyperinsulinemia and hyperglycemia. Phosphorylation of mTOR(Ser2448) was determined by Western blot analysis after acute insulin stimulus. Inhibition of mTOR phosphorylation was performed by rapamycin. Phosphorylation of mTOR complex 1 (MTORC1) downstream substrates 4E-BP1(Thr37/46) and P70S6K(Thr389), and MTORC2 downstream substrate Akt(Ser473) as well as the PDK1-dependent phosphorylation of Akt(Thr308) was investigated. Markers for extracellular matrix remodeling, cell differentiation and degenerative changes were analyzed by Western blot analysis, semi-quantitative real-time PCR and colorimetric assays. Hyperinsulinemia and hyperglycemia lead to alterations of VIC activation, differentiation and matrix remodeling as well as to an abrogation of mTOR phosphorylation. Inhibition of mTOR signaling by rapamycin leads to a general downregulation of matrix molecules, but to an upregulation of α-smooth muscle actin expression and alkaline phosphatase activity. Comparison of expression patterns upon diabetic conditions and rapamycin treatment reveal a possible regulation of particular matrix components and key degeneration markers by MTORC1 downstream signaling. The present findings broaden the understanding of mitogenic signaling pathways in VIC triggered by hyperinsulinemia and hyperglycemia, supporting the quest for developing strategies of prevention and tailored treatment of CAVD in diabetic patients.
Prevalence of left ventricular hypertrophy in children and young people with primary hypertension: Meta-analysis and meta-regression
Authors: Sinha Manish D. , Azukaitis Karolis , Sladowska-Kozłowska Joanna , Bårdsen Tonje , Merkevicius Kajus , Karlsen Sletten Ida Sofie , Obrycki Łukasz , Pac Michał , Fernández-Aranda Fernando , Bjelakovic Bojko , Jankauskiene Augustina , Litwin Mieczysław ,   HyperChildNet Working Group
Published: October 2022

Background

Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH).

Methods

A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity.

Results

The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2–33.9), while heterogeneity was high (I2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08–0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%).

Conclusion

Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.
The effectiveness of video animations as information tools for patients and the general public: A systematic review
Authors: Moe-Byrne Thirimon , Evans Ella , Benhebil Nadia , Knapp Peter
Published: October 2022

Background and objectives

Video animations are used increasingly as patient information tools; however, we do not know their value compared to other formats of delivery, such as printed materials, verbal consultations or static images.

Methods

This review compares the effectiveness of video animations as information tools vs. other formats of delivery on patient knowledge, attitudes and cognitions, and behaviours. Included studies had the following features: controlled design with random or quasi-random allocation; patients being informed about any health condition or members of the public being informed about a public health topic; comparing video animation with another delivery format. Multiple digital databases were searched from 1996-June 2021. We also undertook citation searching. We used dual, independent decision-making for inclusion assessment, data extraction and quality appraisal. Included studies were appraised using the Cochrane ROB2 tool. Findings were reported using narrative synthesis.

Results

We included 38 trials, focussed on: explaining medical or surgical procedures (n = 17); management of long-term conditions (n = 11); public health, health-promotion or illness-prevention (n = 10). Studies evaluated cartoon animations (n = 29), 3D animations (n = 6), or 2D animations, “white-board” animations or avatars (n = 1 each). Knowledge was assessed in 30 studies, showing greater knowledge from animations in 19 studies, compared to a range of comparators. Attitudes and cognitions were assessed in 21 studies, and animations resulted in positive outcomes in six studies, null effects in 14 studies, and less positive outcomes than standard care in one study. Patient behaviours were assessed in nine studies, with animations resulting in positive outcomes in four and null effects in the remainder. Overall risk of bias was “high” (n = 18), “some concerns” (n = 16) or “low” (n = 4). Common reasons for increased risk of bias were randomisation processes, small sample size or lack of sample size calculation, missing outcome data, and lack of protocol publication.

Discussion

The overall evidence base is highly variable, with mostly small trials. Video animations show promise as patient information tools, particularly for effects on knowledge, but further evaluation is needed in higher quality studies.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42021236296.
Post-COVID-19 strategies for higher education institutions in dealing with unknown and uncertainties
Authors: Rasli Amran , Tee Mcxin , Lai Yin Ling , Tiu Zian Cheak , Soon Eu Hui
Published: October 2022

The COVID-19 global pandemic outbreak has presented higher education institutions with the impediment of transforming to a new curriculum, pedagogy, and educational management. Inevitable transformation in higher education triggered by COVID-19 is still ongoing, albeit most countries are now at the endemic stage. However, transformation should not just be about simply changing instructional delivery. The COVID-19 pandemic is a unique opportunity for educators and policymakers to rethink education systems and reimagine what is important, necessary, and desirable for future generations. Hence, this study focuses on identifying strategies for higher education institutions to deal with unknown uncertainties during and after the pandemic. Expert Opinion Method was conducted involving five professors who are senior management in their respective universities and have been directly involved in formulating strategies and policies during the pandemic. Four major dimensions were developed from the findings: (1) Resilience and Change Management, (2) Digital Transformation and Online Learning, (3) Curriculum Change, and (4) Sustainability. Flexibility is also the most common issue discussed by experts. Based on thematic analysis, post COVID-19 strategic framework for higher education institution sustainability is proposed. In addition, this study can be a roadmap for educators, policymakers, and all relevant stakeholders to prepare for future disruptions in the education sector.
Northern dimming and southern brightening in eastern China during the first decade of the 21st century
Authors: Li Jingxin , Ma Wenzhe , Yang Su , Liu Ge , Chen Siyu , Ding Minghu
Published: October 2022

Global solar radiation (GSR) reaching the Earth’s surface can directly alter the energy balance of the climate system. The potential influence of inhomogeneity issues on Chinese GSR records on dimming and brightening in China has been argued for years. In this study, we explored the temporal evolution and spatial distribution of the long-term trend of GSR in eastern China (EC) during 1961–2018 using a homogenized GSR dataset, which removed the artificial signals. Results demonstrate that EC experienced a significant dimming period from 1961 to 1999, a brightening period from 2010 until 2018 and a leveling-off period between them (2000–2010), which resulted from opposite trends of GSR in the northern (dimming) and southern (brightening) regions of EC. The reduction of cloud coverage after the dimming period (2000) induced an early coming brightening in the southern region of China between 2000 and 2010, while the increase in aerosols and the rapidly extending cloud fraction resulted in the continuing dimming in northern China.
Land subsidence and its affecting factors in Cangzhou, North China Plain
Authors: Guo Haipeng , Hao Aibing , Li Wenpeng , Zang Xisheng , Wang Yunlong , Zhu Juyan , Wang Liya , Chen Ye
Published: October 2022

Land subsidence is a typical geo-hazard in Cangzhou, North China Plain, having caused severe damages to transportation networks, public utilities, and other civil infrastructures. The mechanism of land subsidence and its affecting factors were revealed by theoretical model analysis, and doing geotechnical tests and monitoring of soil deformation as well as groundwater level. Theoretical analysis shows that groundwater withdrawal from both unconfined and confined aquifers can lead to land subsidence. Land subsidence of the Cangzhou Plain is mainly caused by the exploitation of deep confined groundwater. Geotechnical tests show a general trend that the compressive modulus increases with the increase of soil depth. The strata of the Upper Pleistocene and Holocene are mostly normally consolidated and partially under-consolidated, which are prone to produce large compression after pumping. Land subsidence in the Cangzhou Plain has a strong hysteresis because of seepage consolidation and creep. The deformation characteristics of strata change at different depth. The shallow aquifers are mainly elastic deformation. The area of severe land subsidence in the Cangzhou Plain is closely related to rainfall, mainly because the large amount of water are used for agricultural irrigation. InSAR results show a sudden change in regional subsidence across the Cangdong fault, which is caused by the difference in the thickness of Quaternary sediments and the difference in the deep confined groundwater level.
Achieving cleaner water for UN sustainable development goal 6 with natural processes: Challenges and the future
Authors: Crockford Lucy
Published: October 2022

UN Sustainable Development Goal 6 aims to achieve clean water for all. Access to clean water is a basic human right but can be costly and challenging. Using natural processes to provide cleaner water for treatment is a cost effective, and often beneficial to other ecosystem services, method. Unfortunately, there are a number of barriers to the implementation of natural processes for cleaner water such as the difficulty of funding these nature-based solutions which is linked to the requirement of accurate valuation. Once funded, partnership with land practitioners is important to ensure that detrimental impacts are not experienced elsewhere and to ensure that these natural processes such as ponds and constructed wetlands are maintained and managed appropriately. The future in the United Kingdom and Europe, in general, is optimistic despite the large funding gap for nature-based solutions overall. Green finance, essentially a loan or investment to support environmentally-friendly activities, has been developed to funnel money towards sustainable investments with an environmental focus, and the percentage of world wealth spent on such investments has increased.
The effect of urban environments on the diversity of plants in unmanaged grasslands in Los Angeles, United States
Authors: English John , Barry Kathryn E. , Wood Eric M. , Wright Alexandra J.
Published: October 2022

Urbanization is a strong driver of plant diversity and may have complex effects on developed ecosystems. Nevertheless, it remains unclear whether urban environments increase or decrease plant biodiversity compared with rural environments. Further, it is also unclear how non-native plant species contribute to spatial diversity patterns and ecosystem services. Better understanding these diversity drivers across gradients of urbanization has the potential to enhance native species conservation (e.g., targeted restoration activities), leading to positive feedbacks for broader promotion of biodiversity and societal benefits (e.g., links with native biodiversity and human health). In this study, we hypothesized that for plant species in unmanaged grasslands, urbanization would lead to declines in diversity at both small and medium scales. We established a network of remnant grassland sites across an urban to rural gradient in Los Angeles, CA, USA. Across this gradient we assessed patterns of alpha and beta diversity during the 2019 growing season. We found that local plant alpha diversity in remnant grasslands declined in urban landscapes (measured by surrounding percent development) due mostly to loss of native species. However, at intermediate scales across unmanaged parks and greenspaces, we saw increases in beta diversity at more urban locations. This was possibly due to the patchy dominance of different exotic species at urban locations; whereas, in rural locations non-native and native species were common across plots. Conservation is often informed by examinations of large scale, city-wide assessment of diversity, however, our results show that urban plant diversity, particularly native species, is affected at all spatial scales and beta-diversity can add important insights into how to manage urban ecosystems. Conservation that accounts for alpha and beta diversity may promote “virtuous cycle” frameworks where the promotion and protection of biodiversity simultaneously reduces the negative effects of invasion.
Forest structure characteristics on soil carbon and nitrogen storage of Pinus massoniana plantations in southern subtropic region
Authors: Zhang Kexin , Gao Dongli , Guo Hong , Zeng Ji , Liu Xianzhao
Published: October 2022

Forest carbon and nitrogen storage significantly affect forest ecosystems and global carbon and nitrogen cycles. Forest management can achieve sustainable development by regulating stand structure. Therefore, the relationship between stand structure and soil carbon (SOCD) and nitrogen storage (SOND) needs in depth study. In this study, experiments were carried out in mixed and pure Pinus massoniana forests to analyze the effects of stand density, stand age, and their interaction on the change trends in SOCD and SOND in different soil layers. The results showed that, in upper (0–20 cm), middle (20–40 cm), and lower (40–60 cm) soil layers, with increased stand density, the SOCD of pure P. massoniana stands first increased and then decreased, while SOND increased monotonically; in mixed P. massoniana stands, SOCD and SOND both increased monotonically. In different development stages (young, middle-aged, and near-mature), the average SOCD of pure P. massoniana stands were 91.31, 88.56, and 85.98 t/ha, respectively, while the average SOCD of mixed P. massoniana stands were 55.92, 48.61, and 55.05 t/ha. The SOCD of pure P. massoniana stands was significantly higher than mixed P. massoniana stands at all growth and development stages. In pure P. massoniana stands, with increasing stand density, the SOCD of young, middle-aged, and near-mature stands first increased and then decreased, while the SOND increased monotonically. In the mixed P. massoniana stands, with increasing stand density, the SOCD of young, middle-aged, and near-mature stands increased monotonically, while the SOND of young stands increased initially and then decreased, while those of middle-aged and near-mature stands increased monotonically. These results emphasized that the artificial regulation of stand density at the appropriate development stage can maximize the carbon and nitrogen fixation potential of forest soil.
Metformin: Activation of 5′ AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action
Authors: Goel Sanjay , Singh Ravinder , Singh Varinder , Singh Harmanjit , Kumari Pratima , Chopra Hitesh , Sharma Rohit , Nepovimova Eugenie , Valis Martin , Kuca Kamil , Emran Talha Bin
Published: October 2022

Metformin is a plant-based drug belonging to the class of biguanides and is known to treat type-2 diabetes mellitus (T2DM). The drug, combined with controlling blood glucose levels, improves the body’s response to insulin. In addition, trials have identified the cardioprotective potential of metformin in the diabetic population receiving the drug. Activation of 5′ AMP-activated protein kinase (AMPK) is the major pathway for these potential beneficial effects of metformin. Historically, much emphasis has been placed on the potential indications of metformin beyond its anti-diabetic use. This review aims to appraise other potential uses of metformin primarily mediated by the activation of AMPK. We also discuss various mechanisms, other than AMPK activation, by which metformin could produce beneficial effects for different conditions. Databases including PubMed/MEDLINE and Embase were searched for literature relevant to the review’s objective. Reports from both research and review articles were considered. We found that metformin has diverse effects on the human body systems. It has been shown to exert anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects and has now even been identified as effective against SARS-CoV-2. Above all, the AMPK pathway has been recognized as responsible for metformin’s efficiency and effectiveness. Owing to its extensive potential, it has the capability to become a part of treatment regimens for diseases apart from T2DM.
The reference genome and organelle genomes of wasabi (Eutrema japoniacum)
Authors: Liu Hexia , Qiao Qinghua , Ye Xiaoxia , Guo Yipeng , Ye Baojian , Xu Qiuyuan , Zhou Xingwen , Li Bo
Published: October 2022

Wasabi (Eutrema japonicum) is one of the most famous vegetable crops in the family Brassicaceae. However, a limited genomic resource is available, which hinders genomic breeding and understanding of the genetic basis of vital traits. Here, we generated the genome assembly of wasabi using the hybrid genome assembly strategy, which combined the Nanopore long reads and Illumina reads. The genome assembly contains 687M bp and 39,534 high-quality annotated gene models. Besides, we annotated 68.85% of the genomic sequences as repetitive elements, including 43.72% of retrotransposons and 18.99% of DNA transposons. Using the customized pipeline, we also generated the complete organelle genomes of wasabi. This reference genome could provide essential genomic resources for evolution, breeding, and exploring the unique biological traits of wasabi.
De-novo genome assembly and annotation of sobaity seabream Sparidentex hasta
Authors: Karam Qusaie , Kumar Vinod , Shajan Anisha B. , Al-Nuaimi Sabeeka , Sattari Zainab , El-Dakour Saleem
Published: October 2022

Sparidentexhasta (Valenciennes, 1830) of the Sparidae family, is an economically important fish species. However, the genomic studies on S. hasta are limited due to the absence of its complete genome. The goal of the current study was to sequence, assemble, and annotate the genome of S. hasta that will fuel further research related to this seabream. The assembled draft genome of S. hasta was 686 Mb with an N50 of 80 Kb. The draft genome contained approximately 22% repeats, and 41,201 genes coding for 44,555 transcripts. Furthermore, the assessment of the assembly completeness was estimated based on the detection of ∼93% BUSCOs at the protein level and alignment of >99% of the filtered reads to the assembled genome. Around 68% of the predicted proteins (n = 30,545) had significant BLAST matches, and 30,473 and 13,244 sequences were mapped to Gene Ontology annotations and different enzyme classes, respectively. The comparative genomics analysis indicated S. hasta to be closely related to Acanthopagrus latus. The current assembly provides a solid foundation for future population and conservation studies of S. hasta as well as for investigations of environmental adaptation in Sparidae family of fishes. Value of the Data: This draft genome of S. hasta would be very applicable for molecular characterization, gene expression studies, and to address various problems associated with pathogen-associated immune response, climate adaptability, and comparative genomics. The accessibility of the draft genome sequence would be useful in understanding the pathways and functions at the molecular level, which may further help in improving the economic value and their conservation.
Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Authors: Kümmel Lara S. , Krumbein Hanna , Fragkou Paraskevi C. , Hünerbein Ben L. , Reiter Rieke , Papathanasiou Konstantinos A. , Thölken Clemens , Weiss Scott T. , Renz Harald , Skevaki Chrysanthi
Published: October 2022

Vitamin D supplementation and its impact on immunoregulation are widely investigated. We aimed to assess the prevention and treatment efficiency of vitamin D supplementation in the context of coronavirus disease 2019 (COVID-19) and any disease-related complications. For this systematic review and meta-analysis, we searched databases (PubMed, Embase, Scopus, Web of Science, The Cochrane Library, medRxiv, Cochrane COVID-19 Study Register, and ClinicalTrial.gov) for studies published between 1 November 2019 and 17 September 2021. We considered randomized trials (RCTs) as potentially eligible when patients were tested for SARS-CoV-2 infection and received vitamin D supplementation versus a placebo or standard-of-care control. A random-effects model was implemented to obtain pooled odds ratios for the effect of vitamin D supplementation on the main outcome of mortality as well as clinical outcomes. We identified a total of 5,733 articles, of which eight RCTs (657 patients) met the eligibility criteria. Although no statistically significant effects were reached, the use of vitamin D supplementation showed a trend for reduced mortality [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.32–1.71, p = 0.48] compared with the control group, with even stronger effects, when vitamin D was administered repeatedly (OR 0.33, 95% CI 0.1–1.14). The mean difference for the length of hospitalization was −0.28 (95% CI −0.60 to 0.04), and the ORs were 0.41 (95% CI 0.15–1.12) and 0.52 (95% CI 0.27–1.02) for ICU admission and mechanical ventilation, respectively. In conclusion, vitamin D supplementation did not improve the clinical outcomes in COVID-19 patients, but trends of beneficial effects were observed. Further investigations are required, especially studies focusing on the daily administration of vitamin D.
Understanding the role of Toll-like receptors in lung cancer immunity and immunotherapy
Authors: Hoden Bettina , DeRubeis David , Martinez-Moczygemba Margarita , Ramos Kenneth S. , Zhang Dekai
Published: October 2022

Lung cancer is currently the leading cause of cancer-related deaths worldwide. Significant improvements in lung cancer therapeutics have relied on a better understanding of lung cancer immunity and the development of novel immunotherapies, as best exemplified by the introduction of PD-1/PD-L1-based therapies. However, this improvement is limited to lung cancer patients who respond to anti-PD-1 immunotherapy. Further improvements in immunotherapy may benefit from a better understanding of innate immune response mechanisms in the lung. Toll-like receptors (TLRs) are a key component of the innate immune response and mediate the early recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLR signaling modulates the tumor microenvironment from “cold” to “hot” leading to immune sensitization of tumor cells to treatments and improved patient prognosis. In addition, TLR signaling activates the adaptive immune response to improve the response to cancer immunotherapy through the regulation of anti-tumor T cell activity. This review will highlight recent progress in our understanding of the role of TLRs in lung cancer immunity and immunotherapy.
Humoral and cellular immunogenicity of COVID-19 booster dose vaccination in inflammatory arthritis patients
Authors: Wroński Jakub , Jaszczyk Bożena , Roszkowski Leszek , Felis-Giemza Anna , Bonek Krzysztof , Kornatka Anna , Plebańczyk Magdalena , Burakowski Tomasz , Lisowska Barbara , Kwiatkowska Brygida , Maśliński Włodzimierz , Wisłowska Małgorzata , Massalska Magdalena , Ciechomska Marzena , Kuca-Warnawin Ewa
Published: October 2022

Introduction

Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA).

Patients and methods

49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine.

Results

After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine.

Conclusion

Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.
Differential regulation of Type 1 and Type 2 mouse eosinophil activation by apoptotic cells
Authors: Dolitzky Avishay , Hazut Inbal , Avlas Shmulik , Grisaru-Tal Sharon , Itan Michal , Zaffran Ilan , Levi-Schaffer Francesca , Gerlic Motti , Munitz Ariel
Published: October 2022

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis, host defense and cancer. Although eosinophils have been studied mostly in the context of Type 2 inflammatory responses, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Notably, both Type 1- and Type 2 inflammatory environments are characterized by tissue damage and cell death. Collectively, this raises the possibility that eosinophils can interact with apoptotic cells, which can alter eosinophil activation in the inflammatory milieu. Herein, we demonstrate that eosinophils can bind and engulf apoptotic cells. We further show that exposure of eosinophils to apoptotic cells induces marked transcriptional changes in eosinophils, which polarize eosinophils towards an anti-inflammatory phenotype that is associated with wound healing and cell migration. Using an unbiased RNA sequencing approach, we demonstrate that apoptotic cells suppress the inflammatory responses of eosinophils that were activated with IFN-γ + E. coli (e.g., Type 1 eosinophils) and augment IL-4-induced eosinophil activation (e.g., Type 2 eosinophils). These data contribute to the growing understanding regarding the heterogeneity of eosinophil activation patterns and highlight apoptotic cells as potential regulators of eosinophil polarization.
Potent anti-inflammatory activity of the lectin-like domain of TNF in joints
Authors: Pinto Ana Carolina Matias Dinelly , Nunes Rodolfo de Melo , Nogueira Igor Albuquerque , Fischer Bernhard , Lucas Rudolf , Girão-Carmona Virgínia Claudia Carneiro , de Oliveira Vivian Louise Soares , Amaral Flavio Almeida , Schett Georg , Rocha Francisco Airton Castro
Published: October 2022

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N′N′-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.
Paradoxical attenuation of neuroinflammatory response upon LPS challenge in miR-146b deficient mice
Authors: Chithanathan Keerthana , Jürgenson Monika , Guha Mithu , Yan Ling , Žarkovskaja Tamara , Pook Martin , Magilnick Nathaniel , Boldin Mark P. , Rebane Ana , Tian Li , Zharkovsky Alexander
Published: October 2022

The miR-146 family consists of two microRNAs (miRNAs), miR-146a and miR-146b (miR-146a/b), both of which are known to suppress immune responses in a variety of conditions. Here, we studied how constitutive deficiency of miR-146b (Mir146b-/-) affects lipopolysaccharide (LPS)-induced neuroinflammation in mice. Our experiments demonstrated that miR-146b deficiency results in the attenuation of LPS-induced neuroinflammation, as it was evidenced by the reduction of sickness behavior, a decrease in the inflammatory status of microglia, and the loss of morphological signs of microglial activation in the hippocampus. Gene expression analysis revealed that LPS-induced upregulation of hippocampal pro-inflammatory cytokines is attenuated in Mir146b-/- mice, compared to wild-type (WT) mice. In addition, reduced expression of the NF-κB nuclear protein p65, reduced miR-146 family target TLR4 expression and relatively stronger upregulation of miR-146a was found in Mir146b-/- mice as compared to WT mice upon LPS challenge. Compensatory upregulation of miR-146a can explain the attenuation of the LPS-induced neuroinflammation. This was supported by experiments conducted with miR-146a/b deficient mice (Mir146a/b-/-), which demonstrated that additional deletion of the miR-146a led to the restoration of LPS-induced sickness behavior and proinflammatory cytokines. Our experiments also showed that the observed upregulation of miR-146a in Mir146b-/- mice is due to the overexpression of a miR-146a transcription inducer, interferon regulatory factor 7 (Irf7). Altogether, our results show the existence of crosstalk between miR-146a and mir-146b in the regulation of LPS-induced neuroinflammation.
Characteristics of shoreline changes around the South China Sea from 1980 to 2020
Authors: Cui Yikun , Yan Fengqin , He Bin , Ju Chengyuan , Su Fenzhen
Published: October 2022

As one of the most sensitive factors in the sea–land interaction zone, the shoreline is significantly influenced by natural processes and anthropogenic activities. Monitoring long-term shoreline changes offers a basis for the integrated management and protection of coastal zones. The spatiotemporal distribution and the utilization types of shorelines had changed a lot, along with the advancement of the socioeconomics of the countries around the South China Sea (SCS) since 1980. However, the changes in shoreline characteristics for a long time around the whole SCS under anthropogenic influence remain uncertain. Using Landsat and high-resolution satellite images, this study monitored the changes in the spatial location and type of shorelines around the SCS from 1980 to 2020. Additionally, the possible reasons for the shoreline changes around the SCS were analyzed. The results showed the following: 1) the length of shorelines around the SCS maintained growth, especially in the 1990s, which increased by 734.8 km, from 28,243.8 km (1990) to 28,978.6 km (2000). 2) The proportion of natural shorelines around the SCS decreased from 92.4% to 73.3% during the past 40 years. Bedrock and mangrove shorelines disappeared most sharply by 34.2% and 21.6%, respectively. The increase of artificial shorelines was mostly driven by the expansion of constructed and aquaculture dikes. 3) The spatial location changes of most artificial shorelines can be attributed to seaward advancement, with an average advancing speed of 7.98 m/year. Of the natural shorelines, 58.4% changed in terms of their location (30.4% advancement and 28.0% retreat). Most natural shorelines around the SCS were threatened by erosion, but the extent of which was largely determined by the shorelines’ own stability, with less influence from the surrounding environment. Artificialization was the most prominent feature of shorelines around the SCS over the past 40 years, which was closely related to the original types of shorelines and the socioeconomic conditions of the area where they are located, and often accompanied by dramatic changes in shoreline morphology and spatial location. In addition, human interventions were not only the dominant factor in shoreline artificialization but also a major driver of natural shoreline protection.
MBE growth and optimization of the InGaAs/InAlAs materials system for quantum cascade laser
Authors: Tian Wang , Zhang Dong-liang , Zheng Xian-tong , Yang Ruo-ke , Liu Yuan , Lu Li-dan , Zhu Lian-qing
Published: October 2022

High material quality is the foundation for the excellent performance of quantum cascade lasers. This paper investigates the growth conditions for InGaAs/InAlAs/InP superlattices combined solid-source molecular beam epitaxy with metal-organic chemical vapor deposition. Based on the optimization of growth conditions of InGaAs buffer epilayers, the effects of the growth temperature, interruption time, and V/III flux ratio on the quality of InGaAs/InAlAs/InP superlattices were systematically investigated. High-resolution x-ray diffraction and atomic force microscopy prove that this optimized InP-based superlattice has excellent periodicity and sharp interfaces.
Mandatory requirements for pediatric drug development in the EU and the US for novel drugs—A comparative study
Authors: Christiansen Helle , De Bruin Marie L. , Hallgreen Christine E.
Published: October 2022

Mandatory pediatric legislation has been implemented in the European Union (EU) and the United States (US) to increase research and the availability of drugs for the pediatric population. Differences in the legislative framework can cause different pediatric requirements for similar indications granted for similar drugs across jurisdictions. This cross-sectional study compares the pediatric requirements for therapeutic indications granted at the time of initial approval for novel drugs approved in the two regions from 2010 to 2018. We collected the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) decisions to grant a waiver and/or to agree on a pediatric development plan and deferrals hereof at marketing authorization (MA) from publicly available documents. An agreed pediatric development plan was required for 66% (N = 188/285) and 63% (N = 134/212) of the indications granted in the EU and the US at the time of approval, respectively. Almost all (EU; 98%, US; 89%) were deferred until after MA. Based on the broad scope of the EU Pediatric Regulation, an additional 36 PIPs originated from the indications granted at MA. In the subset of indications granted for drugs approved in both the EU and the US (N = 232), significantly more indications resulted in an agreed pediatric development plan for one or more subsets of the pediatric population in the EU (N = 185) as compared to the US (N = 82). This was based on the exemption of orphan designated drugs in the US and the broader scope of the EU Pediatric Regulation. However, indications subject to the mandatory pediatric legislation in both regions (N = 131) most often had similar regulatory requirements for the inclusion of the pediatric population from the EMA and the US FDA (83%, N = 109). In conclusion, when comparing mandatory pediatric requirements, more pediatric development plans were agreed upon in the EU than in the US, in line with the broader mandates of the EU Pediatric Regulation. However, authorities most often had similar regulatory requirements when an indication was subject to pediatric legislation in both regions.
Impact of frailty, mild cognitive impairment and cognitive frailty on adverse health outcomes among community-dwelling older adults: A systematic review and meta-analysis
Authors: Chen Baoyu , Wang Mingting , He Qin , Wang Yong , Lai Xiaoxing , Chen Hongguang , Li Mengqian
Published: October 2022

Aims

This study analyzes the impact of frailty, mild cognitive impairment, and cognitive frailty on adverse outcomes in community-dwelling older adults.

Methods

This systematic review and meta-analysis were conducted using the PRISMA guidelines and MOOSE statement. We developed a specific search strategy for each electronic database and searched PubMed, Web of Science, MEDLINE, and Embase from initial records to July 2021. The studies on adverse outcomes of frailty, pre-frailty, mild cognitive impairment, and mild cognitive impairment with pre-frailty and cognitive frailty were included. Two researchers independently extracted data based on a spreadsheet and assessed the risk of bias. The primary outcomes were mortality, dementia, disability, and hospitalization. The second outcome included quality of life and falls. All analysis was conducted by using Review Manager (RevMan) 5.3 software.

Results

A total of 22 cohort studies (71,544 older adults with mean age ranging from 65.1 to 93.6 years) were included with a low risk of bias and high methodological quality with a NOS score ≥7. Compared to robust elders, individuals identified as frailty were associated with a higher risk of mortality (RR = 2.11, 95% CI: 1.57–2.83) and disability (RR = 5.91, 95% CI: 2.37–14.74). Mild cognitive impairment with pre-frailty was associated with mortality (RR = 1.74, 95% CI: 1.48–2.05) and dementia (RR = 4.15, 95% CI: 1.87–9.20). Pre-frailty was associated with a higher risk of mortality (RR = 1.29, 95% CI: 1.11–1.50). Cognitive frailty was associated with higher risk of incident mortality (RR = 2.41, 95% CI: 1.97–2.94), dementia (RR = 3.67, 95% CI: 2.81–4.78), disability (RR = 11.32, 95% CI: 4.14–30.97), and hospitalization (RR = 2.30, 95% CI: 1.60–3.32), as well as poor quality of life.

Conclusion

Cognitive frailty could be a comprehensive psychosomatic predictor for adverse outcomes among older people. Interactions between frailty, mild cognitive impairment, and cognitive frailty on adverse outcomes must be further explored.

Systematic review registration

[https://inplasy.com/inplasy-2022-5-0064/], identifier [INPLASY202250064].
A scoping review on the significance of programmed death-ligand 1-inhibiting microRNAs in non-small cell lung treatment: A single-cell RNA sequencing-based study
Authors: Shadbad Mahdi Abdoli , Ghorbaninezhad Farid , Hassanian Hamidreza , Ahangar Noora Karim , Hosseinkhani Negar , Derakhshani Afshin , Shekari Najibeh , Brunetti Oronzo , Silvestris Nicola , Baradaran Behzad
Published: October 2022

Background

The programmed death-ligand 1 (PD-L1)/PD-1 axis is one of the well-established inhibitory axes in regulating immune responses. Besides the significance of tumor-intrinsic PD-L1 expression in immune evasion, its oncogenic role has been implicated in various malignancies, like non-small cell lung cancer (NSCLC). As small non-coding RNAs, microRNAs (miRs) have pivotal roles in cancer biology. The current study aimed to systematically review the current knowledge about the significance of PD-L1-inhibiting miRs in NSCLC inhibition and their underlying mechanisms.

Materials and methods

We conducted the current scoping review based on the PRISMA-ScR statement. We systematically searched Embase, Scopus, Web of Science, PubMed, Ovid, EBSCO, ProQuest, Cochrane Library, African Index Medicus, and Pascal-Francis up to 4 April 2021. We also performed in silico tumor bulk RNA sequencing and single-cell RNA sequencing to further the current knowledge of the non-coding RNA-mediated tumor-intrinsic PD-L1 regulation and the PD-L1/PD-1 axis in NSCLC.

Results

The ectopic expression of hsa-miR-194-5p, hsa-miR-326, hsa-miR-526b-3p, hsa-miR-34a-5p, hsa-miR-34c-5p, hsa-miR-138-5p, hsa-miR-377-3p, hsa-let-7c-5p, hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, and hsa-miR-197-3p, as PD-L1-inhibiting miR, inhibits NSCLC development. These PD-L1-inhibiting miRs can substantially regulate the cell cycle, migration, clonogenicity, invasion, apoptosis, tumor chemosensitivity, and host anti-tumoral immune responses. Based on single-cell RNA sequencing results, PD-L1 inhibition might liberate the tumor-infiltrated CD8+ T-cells and dendritic cells (DCs)-mediated anti-tumoral immune responses via disrupting the PD-L1/PD-1 axis.

Conclusion

Given the promising preclinical results of these PD-L1-inhibiting miRs in inhibiting NSCLC development, their ectopic expression might improve NSCLC patients’ prognosis; however, further studies are needed to translate this approach into clinical practice.