bluuebunny/crossref_metadata_2025 huggingface dataset:
NFT — the latest digital copyright object or form of expression
Authors: Tarasenko Leonid
Published: November 2022

Keywords: NFT, copyright, work, token, blockchain, digital environment, judicialexpertise

The article is dedicated to current issues of NFT legal protection. There wereanalysed the legal nature of NFT as an object of copyright, the legal regime of NFT —the work, and some proposals for improving the legal regulation of these relations aresubstantiated. It has been proven that in a separate group of copyright objects it is expedientto allocate new digital objects that appear recently — NFT, multimediaworks, video games (computer games), Internet site, blockchain, and others. The legalnature of new digital copyright objects has been found to be controversial. It is establishedthat in the scientific literature NFT is interpreted as an independent object ofcopyright, as a way to use the object of copyright (for example, conversion of art into adigital token form), as an objective form of expression (digital token form), as securitydigital document, as a way of technical protection of the copyright object from encroachmenton it. It has been proven that converting a work into an NFT form is away to commercialize a copyright object. Furthermore, it is substantiated that NFT isa form of expression (existence) of the object of copyright, and NFT-work (photography,video, painting, drawing, music etc.) in the presence of originality (creative nature)is the object of copyright, which is fixed in specific digital tokenized form.It has been established that tokenization of works provides additional opportunitiesfor copyright protection of such objects due to blockchain — the technology onwhich NFT operates.It has been proven that NFT as a digital certificate certifies the uniqueness of thework, which allows increasing its value and avoid illegal distribution in the digital environmentin the future (which is typical of almost all digital and digitized copyrightobjects). Likewise, it has been proven that most NFT disputes should be resolvedbased on the findings of judicial intellectual property and computer science expertise.It has been established that copyright law is not adapted to regulate the use of worksin the digital environment, so NFT works have an undefined legal regime as objects ofcopyright. It has been proven that the current copyright law, which is imperfect in regulatingrelations in the digital environment in general, should be applied to the relationsrelated to the creation, use, exercise, and protection of NFT works.
Certain aspects of allocation of obligation and burden of proof in criminal proceedings on infringement of intellectual property rights
Authors: Kompanets Yevhenii
Published: November 2022

Keywords: criminal procedure proving, obligation of proof, burden of proof, allocationof proof, reverse burden of proof

Different approaches of national and foreign scientists and judges to themeaning of the concepts of «obligation» and «burden» of proof and allocation thereofbetween parties to criminal proceedings have been analysed. The basic features fordistinguishing the concepts of «obligation» and «burden» (compulsion and material interest)and property (dynamism) have been given. It has been noted that in the legislationof some European countries, despite the existence of the presumption of innocence,in certain categories of criminal proceedings, the obligation of proving innocenceis placed on the defence. The global trends of shifting the obligations of proof,simplifying the criminal procedure in certain categories of cases, and expanding therights of participants in the criminal proceedings have been observed. The provisionsof the Federal Rules of Criminal Procedure of the USA and the Criminal ProcedureCode of Ukraine regarding the mechanism of demanding evidence by the prosecutionfrom the defence have been compared. The norms of Clause 6, Part 2, Art. 242 of theCriminal Procedure Code of Ukraine, which shifted the obligation of proving materialdamage (damages) from the prosecution to the victim, have been analysed. Based onthis norm, it is expected to increase the procedural activity of the victim regarding establishingand proving this circumstance during the pre-trial investigation and thetrial. Based on the decisions of the European Court of Human Rights, it has beenproven that silence can be, although not the only, basis for issuing a guilty verdict. Itis proposed to define and consolidate in the judicial practice of the Supreme Court thepresumptions typical for cases of infringement of intellectual property rights: eventsof criminal offence and guilt.
International transfer of technologies in the conditions of modern challenges
Authors: Bakalinska Olha
Published: November 2022

Keywords: international technology transfer, innovation, European Union, implementation

The globalization of international economic and technological cooperation increases the importance of international technology transfer. It is thanks to him that technology spreads as the most important resource of socio-economicdevelopment. At the international legal level, the international transfer of technologies is regulated by the norms contained in the provisions of universal, regional and bilateral agreements. Ukraine's acquisition of the status of a candidate for EU membership necessitated the implementation of the norms of European law into the legal system of Ukraine.The article examines the main problems of harmonizing the norms of competition law with the norms of legislation on the protection of intellectual property, in particular in the field of technology transfer. Particular attention is paid to the analysis of mergers and acquisitions and other forms of technology transfer, as well as Ukraine's fulfillment of its obligations under the association agreement between Ukraine and the EU, problems and trends in further improvement of the regulatory regulation of technology transfer issues in the field of public procurement and state aid are identified. It is determined that the technical assistance provided to Ukraine by the partner states requires a review not only of national norms regarding technology transfer, but also the creation of new norms of international technical cooperation in the military, technical and medical spheres. It is noted that access to the latest equipment and technologies can be a significant impetus for the development and restoration of the state, however, this requires working out new mechanisms of cooperation with international partners and support from the state and business, in particular in terms of the creation of new industries and joint scientific research, the results of which can become the basis for the restoration of the state and a long-term strategic partnership.
СТАРИЦА МОСКОВСКОГО ИВАНОВСКОГО МОНАСТЫРЯ ДОСИФЕЯ КАК ДУХОВНАЯ НАСТАВНИЦА БРАТЬЕВ ПУТИЛОВЫХ
Authors: Каширина Варвара Викторовна
Published: November 2022

Старица-затворница Московского Ивановского монастыря (ныне Московский Иоанно-Предтеченский ставропигиальный женский монастырь) монахиня Досифея (1746–1810), по преданию, была дочерью императрицы Елизаветы Петровны от тайного морганатического брака с графом Алексеем Григорьевичем Разумовским. Приняв монашеский постриг по воле императрицы Екатерины II, монахиня Досифея после многих лет строгой иноческой жизни стала опытной старицей, к которой обращались за советами многие богомольцы, среди них Тимофей и Иона Путиловы, впоследствии преподобный схиархимандрит Моисей, около сорока лет возглавлявший Оптину пустынь (1826–1862), и игумен Исаия II, настоятель Саровской пустыни (1842–1858). Для окончательного решения о поступлении в монастырь старица благословила братьев обратиться к близким ей по духу старцам Новоспасского монастыря Александру (Подгорченкову) и Филарету (Пуляшкину). На основе известных публикаций и новых архивных источников выявлена специфика духовного наставничества. Можно сказать, что старица Досифея имела большое влияние не только на духовную жизнь братьев Путиловых, но и на две известные обители, которые они затем возглавили – Оптину пустынь и Саровскую пустынь.

The recluse eldress of the Moscow St. John Monastery (now the Moscow St. John the Forerunner Stauropegia Convent), the nun Dosithea (1746–1810), according to legend, was the daughter of Empress Elizabeth Petrovna from a secret morganatic marriage with Count Alexei Grigoryevich Razumovsky. By the will of Empress Catherine II, the nun Dosithea took monastic vows. After many years of strict monastic life, she became an experienced eldress, to whom many pilgrims began to turn for advice, among them Timothy and Jonah Putilov, later the Monk Archimandrite Moses, who headed the Optina Monastery for about forty years (1826–1862), and Abbot Isaiah II, abbot of the Sarov Desert (1842–1858). For the final decision on admission to the monastery, the eldress blessed the brothers to turn to the elders of the Novospassky monastery, Alexander (Podgorchenkov) and Filaret (Pulyashkin), who were close to her in spirit. On the basis of well–known publications and new archival sources, the specifics of spiritual mentoring are revealed and it is shown that the elder Dosithea had a great influence not only on the spiritual life of the Putilov brothers, but also on two famous monasteries that they then headed – Optina Monastery and Sarov Monastery.
Building thermal resilience framework (BTRF): A novel framework to address the challenge of extreme thermal events, arising from climate change
Authors: Serdar Mohammad Zaher , Macauley Nadine , Al-Ghamdi Sami G.
Published: November 2022

Over the past 2 decades, many parts of the world have experienced unprecedented record-breaking temperatures; these extremes fall on both ends of the temperature spectrum ranging from excessively hot to freezing low. Moreover, recently, the rate and the impacts of these extremes have increased, despite all the mitigation efforts, necessitating a resilience-based approach to address these challenges stemming from the accelerated global warming and the advent of climate change. Examples of such extremes include the 2003 and 2022 heatwaves in Europe, claiming approximately 4,000 and 12,000 lives, respectively as well as the 2021 heatwave in the Pacific Northwest region of North America and the deep freeze in Southeast Texas. In this paper, we reflect on previous studies, identifying both internal and external aspects that contribute to a building’s thermal performance. We then incorporate these factors into a proposed framework, covering the important phases of a building’s life cycle, to reflect its thermal resilience. During each phase, an associated Building Thermal Resilience Profile (BTRP), taken from accumulated data of previous phases, provides the needed assessment of the building, and is regularly adapted to changes in the building and its surroundings. BTRP will be a valuable tool for the resilience evaluation of different design options. Furthermore, during the operation phase, it will contribute to real-time monitoring and assessment, facilitating disaster management and response, at both the buildings and city scale, reducing the causalities of extreme events. Thus, the BTRF has the potential to expand into various fields such as healthcare, green and resilient buildings rating systems, and even to improve the municipal regulations. Nevertheless, the prime aim of this paper is to address the challenge of extreme thermal events, arising from climate change, and pave the way for the adoption of effective thermal resilience in building design and operation practices.
Influence of different additives on the creep property of oil well cement
Authors: Song Meimei , Gao Yang , Zhang Yafei
Published: November 2022

As the exploitation of oil and gas field becomes more difficulty nowadays, severe casing deformation may occur if anti-extrusion strength of casing decreases to a certain degree and this brings large economic loss and severe safety problems. As an annular sheath between casing and formation, creep of oil well cement paste is one of the most important factors in deciding abnormal casing deformation and wellbore integrity. To figure out the mechanism on how to reduce the creep value of oil well cement paste, effect of different additives, e.g., retarder, glass fibre reinforcement and CSA expansive agent on the creep value of oil well cement are investigated in this study. It can be found out that retarder plays a negative role in reducing the creep deformation and creep value of cement with 1, 2, 3% retarder is 2.39%, 7.85%, and 15.02% higher than that without retarder at 12 h. Results from heat flow indicates that retarder may play an important role in prolonging the early induction period of hydration and reducing the hydration rate in the middle and later stages. On the contrary, Glass fibre shows a positive effect in reducing the creep value of oil well cement paste and creep value reaches with 0.2%, 0.4%, 0.6%, and 0.8% is 1.27%, 6.61%, 9.82%, and 12.60% lower than that without fibre addition at 72 h. This is because high porosity between and around fibers based on a microstructure observation may lead to a more continuous and uniform stress field between cement paste, and consequently reduce the creep value of cement paste. It can also be found out that CSA cement is considerably effective in limiting creep deformation of oil well cement paste at early ages. There is also an acceleration effect on the heat flow of oil well cement in both induction and acceleration periods and the corresponding maximum heat flow is 7.3%, 9.0%, and 11.2% higher than the reference cement with no CSA addition. The results obtained in this study are aimed to provide theoretical basis for the wellbore integrity and improvement of oil and gas recovery.
Personality and weight management in adults with type 2 diabetes: A systematic review
Authors: Geerling Ralph , Kothe Emily J. , Anglim Jeromy , Emerson Catherine , Holmes-Truscott Elizabeth , Speight Jane
Published: November 2022

Aims

Managing weight in the context of type 2 diabetes presents unique hormonal, medicinal, behavioural and psychological challenges. The relationship between weight management and personality has previously been reviewed for general and cardiovascular disease populations but is less well understood in diabetes. This systematic review investigated the relationship between personality constructs and weight management outcomes and behaviours among adults with type 2 diabetes.

Methods

Medline, PubMed, Embase, PsycINFO and SPORTDiscus databases were searched to July 2021. Eligibility: empirical quantitative studies; English language; adults with type 2 diabetes; investigation of personality-weight management association. Search terms included variants of: diabetes, physical activity, diet, body mass index (BMI), adiposity, personality constructs and validated scales. A narrative synthesis, with quality assessment, was conducted.

Results

Seventeen studies were identified: nine cross-sectional, six cohort and two randomised controlled trials (N=6,672 participants, range: 30-1,553). Three studies had a low risk of bias. Personality measurement varied. The Big Five and Type D personality constructs were the most common measures. Higher emotional instability (neuroticism, negative affect, anxiety, unmitigated communion and external locus of control) was negatively associated with healthy diet and physical activity, and positively associated with BMI. Conscientiousness had positive associations with healthy diet and physical activity and negative associations with BMI and anthropometric indices.

Conclusions

Among adults with type 2 diabetes, evidence exists of a relationship between weight management and personality, specifically, negative emotionality and conscientiousness. Consideration of personality may be important for optimising weight management and further research is warranted.

Systematic review registration

www.crd.york.ac.uk/prospero/, identifier CRD42019111002.
Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids
Authors: Tian Yu , Tsujisaka Yuta , Li Vanessa Y. , Tani Kanae , Lucena-Cacace Antonio , Yoshida Yoshinori
Published: November 2022

Cardiac reactive fibrosis is a fibroblast-derived maladaptive process to tissue injury that exacerbates an uncontrolled deposition of large amounts of extracellular matrix (ECM) around cardiomyocytes and vascular cells, being recognized as a pathological entity of morbidity and mortality. Cardiac fibrosis is partially controlled through the sustained activation of TGF-β1 through IL-11 in fibroblasts. Yet, preclinical studies on fibrosis treatment require human physiological approaches due to the multicellular crosstalk between cells and tissues in the heart. Here, we leveraged an iPSC-derived multi-lineage human heart organoid (hHO) platform composed of different cardiac cell types to set the basis of a preclinical model for evaluating drug cardiotoxicity and assessing cardiac fibrosis phenotypes. We found that the inhibition of the p38-MAPK pathway significantly reduces COL1A1 depositions. Yet, concomitant treatment with organ-rejection immunosuppressant drugs Tacrolimus or Sirolimus reverts this effect, opening new questions on the clinical considerations of combined therapies in reducing fibrosis after organ transplantation.
Epidemiology of hand, foot, and mouth disease and the genetic characteristics of Coxsackievirus A16 in Taiyuan, Shanxi, China from 2010 to 2021
Authors: Guo Jiane , Cao Zijun , Liu Hongyan , Xu Jihong , Zhao Lifeng , Gao Li , Zuo Zhihong , Song Yang , Han Zhenzhi , Zhang Yong , Wang Jitao
Published: November 2022

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by human enteroviruses (EV). This study aimed to describe the epidemiological features of HFMD and the genetic characteristics of Coxsackievirus A16 (CVA16) in Taiyuan, Shanxi, China, from 2010 to 2021. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD and the genetic characteristics of CVA16. Except being affected by the COVID-19 epidemic in 2020, HFMD epidemics were sporadic from January to March each year, and began to increase in April, with a major epidemic peak from May to August, which declined in September, followed by a secondary peak from October to December. The prevalence of EV infection was the highest in children aged one to five years (84.42%), whereas its incidence was very low in children under one year of age (5.48%). Enterovirus nucleic acid was detected by real-time reverse transcription polymerase chain reaction in 6641 clinical specimens collected from patients with HFMD from 2010 to 2021, and 4236 EV-positive specimens were detected, including 988 enterovirus A71 (EV-A71), 1488 CVA16, and 1760 other enteroviruses. CVA16 remains prevalent and has co-circulated with other EVs in Taiyuan from 2010 to 2021. A phylogenetic tree constructed based on theVP1region showed that all CVA16 strains belonged to two different clades of the B1 genotype, B1a and B1b. They showed a nucleotide similarity of 86.5–100%, and an amino acid similarity of 96.9–100%. Overall, these findings add to the global genetic resources of CVA16, demonstrate the epidemiological characteristics of HFMD as well as the genetic features of CVA16 in Taiyuan City during 2010–2021, and provide supporting evidence for the prevention and control of HFMD.
Baihu renshen decoction ameliorates type 2 diabetes mellitus in rats through affecting gut microbiota enhancing gut permeability and inhibiting TLR4/NF-κB-mediated inflammatory response
Authors: Yao Bin , Pan Baochao , Tian Tian , Su Xiuhai , Zhang Shufang , Li Hanzhou , Li Wendong , Wang Yuansong , Lv Shuquan , Zhang Zhaiyi
Published: November 2022

Baihu Rensheng decoction (BHRS) can effectively improve insulin resistance (IR) and decrease blood glucose in diabetic patients. However, its specific mechanism of action remains unclear. In this study, a type 2 diabetes mellitus (T2DM) rat model was established using a high-fat diet combined with streptozotocin (STZ) injection and treated with BHRS. Firstly, the therapeutic and anti-inflammatory effects of BHRS on T2DM were evaluated. Secondly, the effects of BHRS on gut permeability were evaluated and western blot was used to detect the changes of TLR4/NF-κB pathway-related protein expressions in liver. Finally, 16S rRNA sequencing was used to detect alteration of gut microbiota diversity and abundance in rats after BHRS treatment. Our results showed that BHRS could alleviate the hyperglycemia, hyperlipidemia, IR, and pathological changes of liver, pancreas, and kidney in T2DM rats. BHRS could also decrease the levels of pro-inflammatory cytokines and inhibit the oxidative stress. Immunohistochemistry showed BHRS could increase the expression tight junction-related proteins (ZO-1 and occludin) in colon. Besides, the level of LPS in serum was decreased after BHRS treatment. Western blot results showed that the protein expression of TLR4, MyD88 and the phosphorylation IκB, and NF-κBp65 were lowered after BHRS treatment. 16S rRNA sequencing showed that BHRS treatment altered the diversity of gut microbiotra and decreases the Firmicutes/Bacteroidetes (F to B) ratio at the phylum level. At the genus level, BHRS could increase the relative abundances of Lactobacillus, Blautia, and Anaerostipes and decrease the relative abundances of Allobaculum, Candidatus Saccharimonas, and Ruminococcus. In conclusion, our study revealed the various ameliorative effects of BHRS on T2DM, including improving the liver and kidney functions and alleviating the hyperglycemia, hyperlipidemia, pathological changes, oxidative stress and inflammatory response. The mechanisms of BHRS on T2DM are likely linked to the repair of gut barrier and the inhibition of TLR4/NF-κB-mediated inflammatory response and the improvement in the dysbiosis of gut microbiota.
MitraClip for the treatment of heart failure with mitral regurgitation: A cost-effectiveness analysis in a Chinese setting
Authors: Xia Wengang , Han Kangning , Lou Yake
Published: November 2022

Background

Heart failure (HF) with mitral regurgitation is associated with decreased survival. Guideline-directed medical therapy and transcatheter edge-to-edge repair (TEER) are the main options for HF patients with severe mitral regurgitation who are considered high-risk or prohibitive. To date, there have been no studies investigating the cost-effectiveness of MitraClip vs. optimal medical therapy (OMT) in a Chinese setting.

Methods

A combined decision tree and Markov model were developed to compare the cost-effectiveness MitraClip vs. OMT with a lifetime simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represented incremental costs per quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was set three times of per capita gross domestic product (GDP) in China in 2021, which was 242,928 CNY. MitraClip would be considered cost-effective if the ICER obtained was lower than the WTP threshold. Otherwise, it would be not considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses were performed to validate the robustness of the results.

Results

After a simulation of the lifetime, the overall cost for a patient in the MitraClip cohort was 423,817 CNY, and the lifetime cost in the OMT was 28,369 CNY. The corresponding effectiveness in both cohorts was 2.32 QALY and 1.80 QALY per person, respectively. The incremental cost and increment effectiveness were 395,448 CNY and 0.52 QALY, respectively, and the ICER was 754,410 CNY/QALY. The ICER obtained was higher than the WTP threshold. Sensitivity analysis validated our finding.

Conclusion

MitraClip provided effectiveness but with more costs compared with OMT, and the incremental cost-effectiveness ratio obtained was higher than the WTP threshold. MitraClip was considered not cost-effective in Chinese HF patients with secondary mitral regurgitation.
Prenatal polycyclic aromatic hydrocarbon (PAH) exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE pregnancy cohort
Authors: Barrett Emily S. , Workman Tomomi , Hazlehurst Marnie F. , Kauderer Sophie , Loftus Christine , Kannan Kurunthachalam , Robinson Morgan , Smith Alicia K. , Smith Roger , Zhao Qi , LeWinn Kaja Z. , Sathyanarayana Sheela , Bush Nicole R.
Published: November 2022

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism is through disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. As an extension of recent research identifying pCRH as a potential target of endocrine disruption, we examined maternal PAH exposure in relation to pCRH in a large, diverse sample. Participants, drawn from the CANDLE cohort, part of the ECHO-PATHWAYS Consortium, completed study visits at 16-29 weeks (V1) and 22-39 weeks (V2) gestation (n=812). Seven urinary mono-hydroxylated PAH metabolites (OH-PAHs) were measured at V1 and serum pCRH at V1 and V2. Associations between individual log-transformed OH-PAHs (as well as two summed PAH measures) and log(pCRH) concentrations across visits were estimated using mixed effects models. Minimally-adjusted models included gestational age and urinary specific gravity, while fully-adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by pregnancy complications, fetal sex, and maternal childhood trauma history. We observed associations between 2-OH-Phenanthrene (2-OH-PHEN) and rate of pCRH change that persisted in fully adjusted models (β=0.0009, 0.00006, 0.0017), however, positive associations with other metabolites (most notably 3-OH-Phenanthrene and 1-Hydroxypyrene) were attenuated after adjustment for sociodemographic characteristics. Associations tended to be stronger at V1 compared to V2 and we observed no evidence of effect modification by pregnancy complications, fetal sex, or maternal childhood trauma history. In conclusion, we observed modest evidence of association between OH-PAHs, most notably 2-OH-PHEN, and pCRH in this sample. Additional research using serial measures of PAH exposure is warranted, as is investigation of alternative mechanisms that may link PAHs and timing of birth, such as inflammatory, epigenetic, or oxidative stress pathways.
Endocrine and paracrine characteristics of neuroendocrine prostate cancer
Authors: Arman Tarana , Nelson Peter S.
Published: November 2022

Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
Gut microbial DNA and immune checkpoint gene Vsig4/CRIg are key antagonistic players in healthy aging and age-associated development of hypertension and diabetes
Authors: Liu Matthew A. , Shahabi Shandy , Jati Suborno , Tang Kechun , Gao Hong , Jin Zhongmou , Miller Wyatt , Meunier Frédéric A. , Ying Wei , Bogaart Geert van den , Ghosh Gourisankar , Mahata Sushil K.
Published: November 2022

Aims

Aging is associated with the development of insulin resistance and hypertension which may stem from inflammation induced by accumulation of toxic bacterial DNA crossing the gut barrier. The aim of this study was to identify factors counter-regulating these processes. Taking advantage of the Chromogranin A (CgA) knockout (CgA-KO) mouse as a model for healthy aging, we have identified Vsig4 (V-set and immunoglobulin domain containing 4) as the critical checkpoint gene in offsetting age-associated hypertension and diabetes.

Methods and Results

The CgA-KO mice display two opposite aging phenotypes: hypertension but heightened insulin sensitivity at young age, whereas the blood pressure normalizes at older age and insulin sensitivity further improves. In comparison, aging WT mice gradually lost glucose tolerance and insulin sensitivity and developed hypertension. The gut barrier, compromised in aging WT mice, was preserved in CgA KO mice leading to major 35-fold protection against bacterial DNA-induced inflammation. Similarly, RNA sequencing showed increased expression of the Vsig4 gene (which removes bacterial DNA) in the liver of 2-yr-old CgA-KO mice, which may account for the very low accumulation of microbial DNA in the heart. The reversal of hypertension in aging CgA-KO mice likely stems from (i) low accumulation of microbial DNA, (ii) decreased spillover of norepinephrine in the heart and kidneys, and (iii) reduced inflammation.

Conclusion

We conclude that healthy aging relies on protection from bacterial DNA and the consequent low inflammation afforded by CgA-KO. Vsig4 also plays a crucial role in “healthy aging” by counteracting age-associated insulin resistance and hypertension.
Circulating microRNA responses to acute whole-body vibration and resistance exercise in postmenopausal women
Authors: Buchanan Samuel R. , Miller Ryan M. , Nguyen Michelle , Black Christopher D. , Kellawan J. Mikhail , Bemben Michael G. , Bemben Debra A.
Published: November 2022

Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) (3 sets 10 reps 70% 1 repetition maximum (1RM), 5 exercises) and a bout of whole-body vibration (WBV) (5 sets 1 min bouts 20Hz 3.38mm peak to peak displacement, Vibraflex vibration platform). DXA was used to measure body composition and areal bone mineral density (aBMD) of the total body, AP lumbar spine, and dual proximal femur. pQCT was used to measure tibia bone characteristics (4%, 38%, 66% sites). Blood samples were collected before exercise (Pre), immediately-post (IP), 60 minutes post (60P), 24 hours (24H), and 48 hours (48H) after exercise to measure serum miR-21-5p, -23a-3p, -133a-3p, -148a-3p (qPCR) and TRAP5b (ELISA). There was a significant modality × time interaction for c-miR-21-5p expression (p=0.019), which decreased from 60P to 24H after WBV only. TRAP5b serum concentrations significantly increased IP then decreased below Pre at 24H for both WBV and RE (p<0.01). Absolute changes in TRAP5b were negatively correlated with c-miR-21-5p fold changes (r= -0.642 to -0.724, p<0.05) for both exercise modalities. There were significant negative correlations between baseline c-miRNAs and bone status variables (r= -0.639 to -0.877, p<0.05). Our findings suggest that whole-body vibration is a sufficient mechanical stimulus for altering c-miR-21-5p expression, whereas a high intensity resistance exercise protocol did not elicit any c-miRNA responses in postmenopausal women. Increases in the bone resorption marker, TRAP5b, were associated with greater downregulation of c-miR-21-5p expression.
First Trimester Plasma MicroRNA Levels Predict Risk of Developing Gestational Diabetes Mellitus
Authors: Légaré Cécilia , Desgagné Véronique , Thibeault Kathrine , White Frédérique , Clément Andrée-Anne , Poirier Cédrik , Luo Zhong Cheng , Scott Michelle S. , Jacques Pierre-Étienne , Perron Patrice , Guérin Renée , Hivert Marie-France , Bouchard Luigi
Published: November 2022

Aims

Our objective is to identify first-trimester plasmatic miRNAs associated with and predictive of GDM.

Methods

We quantified miRNA using next-generation sequencing in discovery (Gen3G: n = 443/GDM = 56) and replication (3D: n = 139/GDM = 76) cohorts. We have diagnosed GDM using a 75-g oral glucose tolerance test and the IADPSG criteria. We applied stepwise logistic regression analysis among replicated miRNAs to build prediction models.

Results

We identified 17 miRNAs associated with GDM development in both cohorts. The prediction performance of hsa-miR-517a-3p|hsa-miR-517b-3p, hsa-miR-218-5p, and hsa-let7a-3p was slightly better than GDM classic risk factors (age, BMI, familial history of type 2 diabetes, history of GDM or macrosomia, and HbA1c) (AUC 0.78 vs. 0.75). MiRNAs and GDM classic risk factors together further improved the prediction values [AUC 0.84 (95% CI 0.73–0.94)]. These results were replicated in 3D, although weaker predictive values were obtained. We suggest very low and higher risk GDM thresholds, which could be used to identify women who could do without a diagnostic test for GDM and women most likely to benefit from an early GDM prevention program.

Conclusions

In summary, three miRNAs combined with classic GDM risk factors provide excellent prediction values, potentially strong enough to improve early detection and prevention of GDM.
The effect of the carbon emission trading scheme on a firm’s total factor productivity: An analysis of corporate green innovation and resource allocation efficiency
Authors: Wang Bo , Yang Maojia , Zhang Xiang
Published: November 2022

This study investigates the effect of the carbon emission trading scheme on a firm’s total factor productivity in China. With a sample from 2008 to 2019, applying the time-varying DID method, our empirical results reveal that the carbon emission trading scheme significantly improves a firm’s total factor productivity, which provides evidence for Porter’s hypothesis. Moreover, there are two channels through which the total factor productivity is impacted: the corporate green innovation channel and the resource allocation efficiency channel. Furthermore, the impact of the carbon emission trading scheme is more pronounced for private firms, and firms in the provinces with higher institutional development, lower environmental quality, and greater law enforcement of environmental protection tend to have larger total factor productivity. Our models survive numerous robustness checks.
Candidate loci for leaf angle in maize revealed by a combination of genome-wide association study and meta-analysis
Authors: Duan Haiyang , Li Jianxin , Sun Yan , Xiong Xuehang , Sun Li , Li Wenlong , Gao Jionghao , Li Na , Zhang Junli , Cui Jiangkuan , Fu Zhiyuan , Zhang Xuehai , Tang Jihua
Published: November 2022

Leaf angle (LA) is a key component of maize plant architecture that can simultaneously govern planting density and improve final yield. However, the genetic mechanisms underlying LA have not been fully addressed. To broaden our understanding of its genetic basis, we scored three LA-related traits on upper, middle, and low leaves of 492 maize inbred lines in five environments. Phenotypic data revealed that the three LA-related traits were normally distributed, and significant variation was observed among environments and genotypes. A genome-wide association study (GWAS) was then performed to dissect the genetic factors that control natural variation in maize LA. In total, 85 significant SNPs (involving 32 non-redundant QTLs) were detected (p ≤ 2.04 × 10–6), and individual QTL explained 4.80%–24.09% of the phenotypic variation. Five co-located QTL were detected in at least two environments, and two QTLs were co-located with multiple LA-related traits. Forty-seven meta-QTLs were identified based on meta-analysis combing 294 LA-related QTLs extracted from 18 previously published studies, 816 genes were identified within these meta-QTLs, and seven co-located QTLs were jointly identified by both GWAS and meta-analysis. ZmULA1 was located in one of the co-located QTLs, qLA7, and its haplotypes, hap1 and hap2, differed significantly in LA-related traits. Interestingly, the temperate materials with hap2 had smallest LA. Finally, we also performed haplotype analysis using the reported genes that regulate LA, and identified a lot of maize germplasms that aggregated favorable haplotypes. These results will be helpful for elucidating the genetic basis of LA and breeding new maize varieties with ideal plant architecture.
Comparative analysis and phylogeny of mitochondrial genomes of Pentatomidae (Hemiptera: Pentatomoidea)
Authors: Lian Dan , Wei Jiufeng , Chen Chao , Niu Minmin , Zhang Hufang , Zhao Qing
Published: November 2022

The Phyllocephalini is a group of herbivorous insects in Pentatomidae, which lack distinctive morphological characteristics and systematic studies. Up to now, there are only two complete mitochondrial genomes of Phyllocephalini have been reported. In this study, we sequenced and analyzed the complete mitochondrial genomes of three Phyllocephalini species, Gonopsis coccinea, Gonopsimorpha nigrosignata, and Chalcopis glandulosus, which were 16,534, 16,531, and 16,534 bp in length, respectively. The mitochondrial genomes contained 37 genes, including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a control region. The gene arrangement was consistent with that of the putative ancestral insect, with no rearrangement. The cox1 gene of Pentatomidae showed the lowest evolutionary rate among the protein-coding genes, the mean genetic distance of species, genera, and subfamilies of Pentatomidae increased hierarchically based on cox1 gene. The 16S rRNA of Pentatomidae was more conserved than 12S rRNA in sequence and secondary structure. All tRNAs could be folded into a typical cloverleaf structure except trnS1. The stem region was more conserved than the loop region in the secondary structure of tRNAs within Pentatomidae. Gonopsis coccinea and Gonopsimorpha nigrosignata had one type of tandem repetition unit in the control region, while C. glandulosus had two types. The heterogeneity analysis of Pentatomidae showed that Phyllocephalinae was the most heterogeneous. Phylogenetic trees based on the newly obtain mitochondrial genomes along with other 50 mitochondrial genomes of Pentatomidae using Bayesian Inference and Maximum Likelihood strongly supported the following three relationships: (((Anaxilaus + (Plautia + Glaucias)) + (Nezara + Palomena)) + (Eysarcorini + Carpocorini)), (Hoplistoderini + (Menidini + Asopinae)), and ((Sephelini + Halyini) + (Caystrini + (Cappaeini + (Placosternum + Phyllocephalini)))). The relationships within Phyllocephalini were (Chalcopis + (Dalsira + (Gonopsimorpha + Gonopsis))). Our results provide valuable molecular data for further phylogenetic analyses of Pentatomidae.
A novel immune signature predicts immunotherapy responsiveness and reveals the landscape of the tumor immune microenvironment in head and neck squamous cell carcinoma
Authors: Wang Qiwei , Zhao Yinan , Wang Fang , Tan Guolin
Published: November 2022

Background: Immune-checkpoint blockade (ICB) has been routinely implemented to treat head and neck squamous cell carcinoma (HNSCC) patients. However, only a few patients benefit from immune checkpoint inhibitor (ICI) therapies.

Methods: In this study, we used a combined cohort (including the GSE41613, GSE65858, TCGA, and CELL cohorts) to identify hub genes significantly associated with ICB and activated CD8+ T-cell gene signatures. We performed single‐sample gene set enrichment analysis (ssGSEA) to quantify the expression of hub genes; we then constructed a novel immune signature named “the IMS” that can predict immunotherapy responsiveness, prognosis, immune infiltration, and clinical characteristics. Data from the GSE102349 external cohort and the pembrolizumab cohort obtained from a clinical trial were used to validate the efficiency of the IMS. In addition, we revealed potential mechanisms of the antitumor response by analyzing the HNSCC single-cell database. Finally, we used the LASSO algorithm to build an IMS-related risk model.

Results: The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB. Moreover, a tumor microenvironment with a higher IMS underwent remarkable metabolic reprogramming characterized by enrichment in the glycolysis/gluconeogenesis, oxidative phosphorylation, and citrate cycle (TCA cycle) pathways. We also revealed key information on cellular crosstalk between the IMS and other immune lineages, which may mechanistically explain immune escape. In addition, we constructed and validated a risk prediction model (CD2, TBC1D10C, and CD3E) that could stratify HNSCC patients based on survival and response to ICB treatment.

Conclusion: IMS is a signature closely correlated with the tumor immune microenvironment. The findings of this study contribute to the understanding of the immune landscape in HNSCC patients. IMS may aid in the clinical management of HNSCC patients through the identification of effective immunotherapies for specific patients.
Extending the CARE Principles from tribal research policies to benefit sharing in genomic research
Authors: Carroll Stephanie Russo , Plevel Rebecca , Jennings Lydia L. , Garba Ibrahim , Sterling Rogena , Cordova-Marks Felina M. , Hiratsuka Vanessa , Hudson Maui , Garrison Nanibaa’ A.
Published: November 2022

Indigenous Peoples have historically been targets of extractive research that has led to little to no benefit. In genomics, such research not only exposes communities to harms and risks of misuse, but also deprives such communities of potential benefits. Tribes in the US have been exercising their sovereignty to limit this extractive practice by adopting laws and policies to govern research on their territories and with their citizens. Federally and state recognized tribes are in the strongest position to assert research oversight. Other tribes lack the same authority, given that federal and state governments do not recognize their rights to regulate research, resulting in varying levels of oversight by tribes. These governance measures establish collective protections absent from the US federal government’s research oversight infrastructure, while setting expectations regarding benefits to tribes as political collectives. Using a legal epidemiology approach, the paper discusses findings from a review of Tribal research legislation, policy, and administrative materials from 26 tribes in the US. The discussion specifies issues viewed by tribes as facilitators and barriers to securing benefits from research for their nations and members/citizens, and describes preemptive and mitigating strategies pursued by tribes in response. These strategies are set within the framing of the CARE Principles for Indigenous Data Governance (Collective Benefit, Authority to Control, Responsibility, Ethics), a set of standards developed to ensure that decisions made about data pertaining to Indigenous communities at the individual and tribal levels are responsive to their values and collective interests. Our findings illustrate gaps to address for benefit sharing and a need to strengthen Responsibility and Ethics in tribal research governance.
Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration
Authors: Li Qiaochu , Chen Zhiyu , Yang Chaohua , Wang Linbang , Ma Jingjin , He Tao , Li Huanhuan , Quan Zhengxue
Published: November 2022

Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.