bluuebunny/crossref_metadata_2025 huggingface dataset:
Scleraxis and fibrosis in the pressure-overloaded heart
Authors: Nagalingam Raghu S , Chattopadhyaya Sikta , Al-Hattab Danah S , Cheung David Y C , Schwartz Leah Y , Jana Sayantan , Aroutiounova Nina , Ledingham D Allison , Moffatt Teri L , Landry Natalie M , Bagchi Rushita A , Dixon Ian M C , Wigle Jeffrey T , Oudit Gavin Y , Kassiri Zamaneh , Jassal Davinder S , Czubryt Michael P
Published: October 2022

Aims

In response to pro-fibrotic signals, scleraxis regulates cardiac fibroblast activation in vitro via transcriptional control of key fibrosis genes such as collagen and fibronectin; however, its role in vivo is unknown. The present study assessed the impact of scleraxis loss on fibroblast activation, cardiac fibrosis, and dysfunction in pressure overload-induced heart failure.

Methods and results

Scleraxis expression was upregulated in the hearts of non-ischemic dilated cardiomyopathy patients, and in mice subjected to pressure overload by transverse aortic constriction (TAC). Tamoxifen-inducible fibroblast-specific scleraxis knockout (Scx-fKO) completely attenuated cardiac fibrosis, and significantly improved cardiac systolic function and ventricular remodelling, following TAC compared to Scx+/+ TAC mice, concomitant with attenuation of fibroblast activation. Scleraxis deletion, after the establishment of cardiac fibrosis, attenuated the further functional decline observed in Scx+/+ mice, with a reduction in cardiac myofibroblasts. Notably, scleraxis knockout reduced pressure overload-induced mortality from 33% to zero, without affecting the degree of cardiac hypertrophy. Scleraxis directly regulated transcription of the myofibroblast marker periostin, and cardiac fibroblasts lacking scleraxis failed to upregulate periostin synthesis and secretion in response to pro-fibrotic transforming growth factor β.

Conclusion

Scleraxis governs fibroblast activation in pressure overload-induced heart failure, and scleraxis knockout attenuated fibrosis and improved cardiac function and survival. These findings identify scleraxis as a viable target for the development of novel anti-fibrotic treatments.
Machine learning in sudden cardiac death risk prediction: a systematic review
Authors: Barker Joseph , Li Xin , Khavandi Sarah , Koeckerling David , Mavilakandy Akash , Pepper Coral , Bountziouka Vasiliki , Chen Long , Kotb Ahmed , Antoun Ibrahim , Mansir John , Smith-Byrne Karl , Schlindwein Fernando S , Dhutia Harshil , Tyukin Ivan , Nicolson William B , Ng G Andre
Published: October 2022

Aims

Most patients who receive implantable cardioverter defibrillators (ICDs) for primary prevention do not receive therapy during the lifespan of the ICD, whilst up to 50% of sudden cardiac death (SCD) occur in individuals who are considered low risk by conventional criteria. Machine learning offers a novel approach to risk stratification for ICD assignment.

Methods and results

Systematic search was performed in MEDLINE, Embase, Emcare, CINAHL, Cochrane Library, OpenGrey, MedrXiv, arXiv, Scopus, and Web of Science. Studies modelling SCD risk prediction within days to years using machine learning were eligible for inclusion. Transparency and quality of reporting (TRIPOD) and risk of bias (PROBAST) were assessed. A total of 4356 studies were screened with 11 meeting the inclusion criteria with heterogeneous populations, methods, and outcome measures preventing meta-analysis. The study size ranged from 122 to 124 097 participants. Input data sources included demographic, clinical, electrocardiogram, electrophysiological, imaging, and genetic data ranging from 4 to 72 variables per model. The most common outcome metric reported was the area under the receiver operator characteristic (n = 7) ranging between 0.71 and 0.96. In six studies comparing machine learning models and regression, machine learning improved performance in five. No studies adhered to a reporting standard. Five of the papers were at high risk of bias.

Conclusion

Machine learning for SCD prediction has been under-applied and incorrectly implemented but is ripe for future investigation. It may have some incremental utility in predicting SCD over traditional models. The development of reporting standards for machine learning is required to improve the quality of evidence reporting in the field.
Evaluation of a pharmacist’s impact on the use of glucagon-like peptide-1 receptor agonists for weight management in a family medicine setting
Authors: Crocetta Nicholas , Guay Kyle , Watson Alexandra
Published: October 2022

Background

Glucagon-like peptide-1 receptor (GLP-1) agonists carry benefits and risks that must be evaluated prior to use and monitored throughout weight management therapy. Pharmacists possess the accessibility and extensive medication knowledge to evaluate and monitor the use of GLP-1 therapy in weight management patients.

Objective

Evaluate the clinical and financial impact of a pharmacist-directed weight management service utilizing GLP-1 receptor agonists in a family practice setting.

Methods

A retrospective cohort study including patients at 2 family practices, aged 18 and older, prescribed a weight management GLP-1 between October 1, 2021 and March 1, 2022 was performed. Patients who met inclusion and were prescribed a weight loss GLP-1 but were not managed by the clinical pharmacist were compared with the pharmacist cohort. Descriptive statistics and inferential statistics including an independent t-test were used in the data analysis.

Results

There were 46 and 39 patients identified in the clinical pharmacist and primary care physician cohorts respectively. Patients in the clinical pharmacist cohort achieved a mean body weight reduction of 9.32% compared to 5.11% body weight reduction for patients in the primary care physician cohort (P = 0.01). There were 63 months identified of inappropriate GLP-1 therapy deprescribed in the clinical pharmacist cohort resulting in an estimated cost savings of $101,985.66.

Conclusions

The implementation of a pharmacist-led weight management clinic in 2 family medicine offices resulted in a significant reduction in body weight and reduction in total costs to the healthcare system compared to patients receiving weight management services from their primary care physician alone.
Video Conferencing With Residents and Families for Care Planning During COVID-19: Experiences in Canadian Long-Term Care
Authors: Connelly Denise , Hay Melissa , Garnett Anna , Hung Lillian , Yous Marie-Lee , Furlan-Craievich Cherie , Snelgrove Shannon , Babcock Melissa , Ripley Jacqueline , Snobelen Nancy , Gao Harrison , Zhuang Ruthie , Hamilton Pam , Sturdy-Smith Cathy , O’Connell Maureen
Published: October 2022

Background and Objectives

Government-mandated health and safety restrictions to mitigate the effects of coronavirus disease 2019 (COVID-19) intensified challenges in caring for older adults in long-term care (LTC) without family/care partners. This article describes the experiences of a multidisciplinary research team in implementing an evidence-based intervention for family-centered, team-based, virtual care planning—PIECESTM approach—into clinical practice. We highlight challenges and considerations for implementation science to support care practices for older adults in LTC, their families, and the workforce.

Research Design and Methods

A qualitative descriptive design was used. Data included meetings with LTC directors and Registered Practical Nurses (i.e., licensed nurse who graduated with a 2-year diploma program that allows them to provide basic nursing care); one-on-one interviews with family/care partners, residents, Registered Practical Nurses, and PIECES mentors; and reflections of the academic team. The Consolidated Framework for Implementation Research provided sensitizing constructs for deductive coding, while an inductive approach also allowed themes to emerge.

Results

Findings highlighted how aspects related to planning, engagement, execution, reflection, and evaluation influenced the implementation process from the perspectives of stakeholders. Involving expert partners on the research team to bridge research and practice, developing relationships from a distance, empowering frontline champions, and adapting to challenging circumstances led to shared commitments for intervention success.

Discussion and Implications

Lessons learned include the significance of stakeholder involvement throughout all research activities, the importance of clarity around expectations of all team members, and the consequence of readiness for implementation with respect to circumstances (e.g., COVID-19) and capacity for change.
An analysis of core–mantle boundary related seismic waves using full-waveform modelling and adjoint methods
Authors: Koroni Maria , Borgeaud Anselme , Fichtner Andreas , Deschamps Frédéric
Published: October 2022

The core–mantle boundary (CMB) is the most abrupt internal discontinuity in the Earth, marking the solid–fluid boundary between mantle and outer core that strongly affects the dynamics of the Earth’s interior. However, good agreement between models of CMB topographic variations is still lacking. This is probably due to difficulties relating to observations on seismograms and to the lack of good models of lowermost mantle velocity structure. Using spectral-element synthetic seismograms and adjoint methods, we perform traveltime analyses of seismic waves interacting with the CMB. We focus on reflected and refracted P and S waves. We select some of the most important and routinely used seismic phases: ScS, SKS, SKKS, PcP, PKP, PKKP and PcS, given their path through mantle and core and their interaction with the CMB. These seismic waves have been widely deployed by seismologists trying to image CMB topography and lowermost mantle structure. To analyse the reliability of measuring their traveltimes to infer CMB topography, we perform experiments in two ways. First, we compute synthetic seismograms with a dominant period of T ≈ 11s, for computational efficiency, using existing models of CMB topography. We compare traveltime perturbations measured by cross-correlation on the synthetics to those predicted using ray theory. We find deviations from a perfect agreement between ray theoretical predictions of time shifts and those measured on synthetics with and without CMB topography. Second, we calculate Fréchet sensitivity kernels of traveltimes with respect to shear and compressional wave speeds. We also explicitly compute boundary sensitivities with respect to the CMB interface. We observe that the overall sensitivity of the traveltimes is mostly due to volumetric velocity structure and that imprints of CMB on traveltimes are less pronounced. Our study explains the observed difficulties relating to inferring CMB topography using traveltimes and provides a suite of finite frequency sensitivity kernels computed with the adjoint method. The kernels allow us to qualitatively explain the behaviour of measured traveltimes and understand the trade-off between velocity and CMB topography. They can also serve as reference of finite frequency effects on traveltimes of observed seismic phases. From our analyses we conclude that: i) traveltime anomalies measured on Swaves are more in accord with ray theoretical predictions, ii) PcP, PKP, ScS and SKS phases have more pronounced sensitivity to the boundary and iii) separating the greater effects of velocity from those due to the boundary structure is difficult, as they intricately affect the traveltime. We propose that jointly inverting for CMB topography and lowermost mantle velocity structure using full-waveform synthetics and adjoint sensitivity kernels can progress our understanding of deep Earth structure and finite frequency effects on observed waveforms.
Criterion validity of 14-item Health Literacy Scale (HLS-14) questionnaire in Brazilian adults and older people
Authors: Puello Sthefanie del Carmen Perez , Silva-Júnior Manoelito Ferreira , de Sousa Maria da Luz Rosário , Batista Marília Jesus
Published: October 2022

The objective of this study was to evaluate the criterion validity of the 14-item Health Literacy Scale (HLS-14) in Brazilian adults and older adults. The cross-sectional study performed in an oral health (OH) prospective cohort was conducted in 2017 in Piracicaba, Brazil. The HLS-14 questionnaire was applied to evaluate Health Literacy (HL) by dimensions: Functional literacy (FunL), Communicative literacy (ComL) and Critical literacy (CriL). An evaluation protocol (EP) was proposed to evaluate the criterion validity of HLS-14 considering HL dimensions (FunL: reading of the drug information leaflets; ComL: reading of the medical prescription and CriL: identification of OH conditions). HL (total) was dichotomized by the median in high (≥35 point) or low (<35 point) HL. Kendall’s rank correlation coefficient (p < 0.05) and chi-squared test (p < 0.05) were applied. There was agreement between EP and HLS-14 for FunL (p < 0.01). There was association between high HL, measured through the HLS-14 questionnaire, assessing the reading of the drug information leaflets (p < 0.01) and the need for help to read them (p < 0.01). EP showed association between high HL and being able to read the drug information leaflet (p < 0.01), not needing help to read (p < 0.01), having found in the prescription all the information to take the medicine (p < 0.01) and knowing two or more health and OH information in the educational material (p < 0.01). The HSL-14 questionnaire showed criterion validity to measure FunL, and for some items of ComL and CriL evaluation. HL evaluation in a practical and multidimensional way could have an effect on the communication between health professional and patient, motivation and health outcomes.
Supt16haploinsufficiency causes neurodevelopment disorder by disrupting MAPK pathway in neural stem cells
Authors: Wang Junwen , Zhu Xintong , Dai Limeng , Wang Ziyi , Guan Xingying , Tan Xiaoyin , Li Jia , Zhang Mao , Bai Yun , Guo Hong
Published: October 2022

Chromatin regulators constitute a fundamental means of transcription regulation, which have been implicated in neurodevelopment and neurodevelopment disorders (NDDs). Supt16, one of candidate genes for NDDs, encodes the large subunit of facilitates chromatin transcription. However, the underlying mechanisms remain poorly understood. Here, Supt16+/− mice was generated, modeling the neurodevelopment disorder. Abnormal cognitive and social behavior was observed in the Supt16  +/− mice. Simultaneously, the number of neurocytes in the cerebral cortex and hippocampus is decreased, which might be resulted from the impairment of mouse neural stem cells (mNSCs) in the SVZ. Supt16 haploinsufficiency affects the proliferation and apoptosis of mNSCs. As the RNA-seq and chromatic immunoprecipitation sequencing assays showed, Supt16 haploinsufficiency disrupts the stemness of mNSCs by inhibiting MAPK signal pathway. Thus, this study demonstrates a critical role of Supt16 gene in the proliferation and apoptosis of mNSCs and provides a novel insight in the pathogenesis of NDDs.
Should AI-enabled medical devices be explainable?
Authors: Matulionyte Rita , Nolan Paul , Magrabi Farah , Beheshti Amin
Published: October 2022

Despite its exponential growth, artificial intelligence (AI) in healthcare faces various challenges. One of them is a lack of explainability of AI medical devices, which arguably leads to insufficient trust in AI technologies, quality, and accountability and liability issues. The aim of this paper is to examine whether, why and to what extent AI explainability should be demanded with relation to AI-enabled medical devices and their outputs. Relying on a critical analysis of interdisciplinary literature on this topic and an empirical study, we conclude that the role of AI explainability in the medical AI context is a limited one. If narrowly defined, AI explainability principle is capable of addressing only a limited range of challenges associated with AI and is likely to reach fewer goals than sometimes expected. The study shows that, instead of technical explainability of medical AI devices, most stakeholders need more transparency around its development and quality assurance process.
Type III Interferons, Viral Loads, Age, and Disease Severity in Young Children With Respiratory Syncytial Virus Infection
Authors: Taveras Jeanette , Garcia-Maurino Cristina , Moore-Clingenpeel Melissa , Xu Zhaohui , Mertz Sara , Ye Fang , Chen Phyl , Cohen Shira H , Cohen Daniel , Peeples Mark E , Ramilo Octavio , Mejias Asuncion
Published: October 2022

Background

The interplay among respiratory syncytial virus (RSV) loads, mucosal interferons (IFN), and disease severity in RSV-infected children is poorly understood.

Methods

Children <2 years of age with mild (outpatients) or severe (inpatients) RSV infection and healthy controls were enrolled, and nasopharyngeal samples obtained for RSV loads and innate cytokines quantification. Patients were stratified by age (0–6 and >6–24 months) and multivariable analyses performed to identify predictors of disease severity.

Results

In 2015–2019 we enrolled 219 RSV-infected children (78 outpatients; 141 inpatients) and 34 healthy controls. Type I, II, and III IFN concentrations were higher in children aged >6 versus 0–6 months and, like CXCL10, they were higher in outpatients than inpatients and correlated with RSV loads (P < .05). Higher IL6 concentrations increased the odds of hospitalization (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.07–5.36) only in children >6 months, while higher IFN-λ2/3 concentrations had the opposite effect irrespective of age (OR, 0.38; 95% CI, .15–.86). Likewise, higher CXCL10 concentrations decreased the odds of hospitalization (OR, 0.21; 95% CI, .08–.48), oxygen administration (OR, 0.42; 95% CI, .21–.80),PICU admission (OR, 0.39; 95% CI, .20–.73), and prolonged hospitalization (OR, 0.57; 95% CI, .32–.98) irrespective of age.

Conclusions

Children with milder RSV infection and those aged >6 months had higher concentrations of mucosal IFNs, suggesting that maturation of mucosal IFN responses are associated with protection against severe RSV disease.
Evaluation of Biorational Insecticides for Management of Euproctis chrysorrhoea (Lepidoptera: Erebidae)
Authors: Groden Eleanor , Boyd Karla S , Donahue Charlene
Published: October 2022

The browntail moth (Euproctis chrysorrhoea L.) is an invasive species which over the past five years, has been undergoing outbreaks on a scale not seen in the northeastern U.S. in over 100 years. Browntail moth larvae feed on and defoliate a number of deciduous tree species, but the health issues caused by contact with the toxic urticating hairs of the overwintered larvae have resulted in very low tolerance for this pest amongst homeowners and land managers. Few recent studies have been conducted to assess management options for browntail moth, which is abundant in ecologically sensitive areas along coastal waters, and around people’s homes. We investigated the potential to manage overwintered larvae with currently available biorational insecticides. Laboratory bioassays revealed susceptibility to Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Cordycipitaceae), Bacillus thuringiesis kurstaki (Berliner), azadirachtin, and spinosad products. A field trial was conducted to assess efficacy of B. bassiana, Btk, and azadirachtin. All treatments reduced the abundance of larvae compared with the control, but only two applications of Btk and single application of a tank mix of B. bassiana and Btk reduced pupal nest abundance. A laboratory experiment revealed that temperature did not affect the feeding and survival of larvae exposed to the field trial foliage from the Btk and the Btk/B. bassiana tank mix treatments, whereas slower feeding rates and increased time to death were observed with the control and B. bassiana alone treatment.
Reference optical turbulence and wind profiles for single conjugate and extreme adaptive optics
Authors: Farley O J D
Published: October 2022

We present a simple method of extracting a small number of reference optical turbulence and wind profiles from a large data set for single conjugate and extreme adaptive optics (AO) simulations. These reference profiles can be used in slow end-to-end AO simulations to represent the variability of the atmosphere. The method is based on the assumption that performance for these systems is correlated with integrated atmospheric parameters r0, θ0, and τ0. Profiles are selected from a large data set that conforms concurrently to the distributions of these parameters, and hence represents the variability of the atmosphere as seen by the AO system. We also extend the equivalent layers method of profile compression to include wind profiles. The method is applied to stereo-SCIDAR data from ESO Paranal to extract five turbulence and wind profiles that cover a broad range in atmospheric variability, and we show using analytical AO simulation that this correlates to the equivalent range of AO-corrected Strehl ratios.
Detection of 125.5-day optical periodic modulation of the neutron star M51 ULX-8
Authors: Allak S
Published: October 2022

Studying Ultraluminous X-ray sources (ULXs) in the optical wavelengths provides important clues about the accretion mechanisms and the evolutionary processes of X-ray binary systems. In this study, three (C1, C2, and C3) possible optical counterparts were identified for well-known neutron star (NS) candidate M51 ULX-8 through advanced astrometry based on the Chandra and Hubble Space Telescope (HST) observations, as well as the GAIA optical source catalogue. Optical periodic modulation of 125.5 d with an amplitude of 0.14 mag was determined for C3, which has evidence to represent the optical nature of ULX-8 using one-year (2016–2017) 34 HST Advanced Camera for Surveys (ACS)/Wide Field Camera (WFC) observations. Moreover, surprisingly, the observed optical fluxes of C3 exhibit a bi-modal distribution. This could mean that there is a possible correlation between the optical and the X-ray flux variabilities of the ULX-8. The possible scenarios which are frequently mentioned in the literature proposed for the nature of optical emission and optical super-orbital period. The most probable scenario is that the optical emission could have originated from the accretion disc of the ULX-8.
Imprint of primordial gravitational wave with extremely low frequency on gravitational lens system
Authors: Liu Wenshuai
Published: October 2022

Primordial gravitational waves with extremely low frequency are expected to origin from inflation in the early Universe. The detection of such kind of gravitational waves is of great significance to verify the inflationary theory and determine the energy scale of inflation. The B mode of polarization of cosmic microwave background shows to be a promising probe of extremely low frequency primordial gravitational wave. In order to find a complementary observational feature induced by primordial gravitational wave with extremely low frequency, we propose an alternative way of detection by investigating the effect of primordial gravitational wave with extremely low frequency on a gravitational lens system with a non-aligned source–deflector–observer configuration. The results show that, with a series of chosen parameters, a gravitational lens system with perturbation from extremely low frequency primordial gravitational wave could induce time delay that could deviate from the time delay deduced from the theoretical model as much as 100 per cent, meaning that a gravitational lens system with a non-aligned configuration could serve as a potential long-baseline detector of extremely low frequency primordial gravitational wave.
Weighting by Gene Tree Uncertainty Improves Accuracy of Quartet-based Species Trees
Authors: Zhang Chao , Mirarab Siavash
Published: October 2022

Phylogenomic analyses routinely estimate species trees using methods that account for gene tree discordance. However, the most scalable species tree inference methods, which summarize independently inferred gene trees to obtain a species tree, are sensitive to hard-to-avoid errors introduced in the gene tree estimation step. This dilemma has created much debate on the merits of concatenation versus summary methods and practical obstacles to using summary methods more widely and to the exclusion of concatenation. The most successful attempt at making summary methods resilient to noisy gene trees has been contracting low support branches from the gene trees. Unfortunately, this approach requires arbitrary thresholds and poses new challenges. Here, we introduce threshold-free weighting schemes for the quartet-based species tree inference, the metric used in the popular method ASTRAL. By reducing the impact of quartets with low support or long terminal branches (or both), weighting provides stronger theoretical guarantees and better empirical performance than the unweighted ASTRAL. Our simulations show that weighting improves accuracy across many conditions and reduces the gap with concatenation in conditions with low gene tree discordance and high noise. On empirical data, weighting improves congruence with concatenation and increases support. Together, our results show that weighting, enabled by a new optimization algorithm we introduce, improves the utility of summary methods and can reduce the incongruence often observed across analytical pipelines.
Metal binding and oligomerization properties of FurC (PerR) from Anabaena sp. PCC7120: an additional layer of regulation?
Authors: Sarasa-Buisan Cristina , Emonot Etienne , Martínez-Júlvez Marta , Sevilla Emma , Velázquez-Campoy Adrián , Crouzy Serge , Bes M Teresa , Michaud-Soret Isabelle , Fillat María F
Published: October 2022

Metal and redox homeostasis in cyanobacteria is tightly controlled to preserve the photosynthetic machinery from mismetallation and minimize cell damage. This control is mainly taken by FUR (ferric uptake regulation) proteins. FurC works as the PerR (peroxide response) paralog in Anabaena sp. PCC7120. Despite its importance, this regulator remained poorly characterized. Although FurC lacks the typical CXXC motifs present in FUR proteins, it contains a tightly bound zinc per subunit. FurC: Zn stoichiometrically binds zinc and manganese in a second site, manganese being more efficient in the binding of FurC: Zn to its DNA target PprxA. Oligomerization analyses of FurC: Zn evidence the occurrence of different aggregates ranging from dimers to octamers. Notably, intermolecular disulfide bonds are not involved in FurC: Zn dimerization, dimer being the most reduced form of the protein. Oligomerization of dimers occurs upon oxidation of thiols by H2O2 or diamide and can be reversed by 1,4-Dithiothreitol (DTT). Irreversible inactivation of the regulator occurs by metal catalyzed oxidation promoted by ferrous iron. However, inactivation upon oxidation with H2O2 in the absence of iron was reverted by addition of DTT. Comparison of models for FurC: Zn dimers and tetramers obtained using AlphaFold Colab and SWISS-MODEL allowed to infer the residues forming both metal-binding sites and to propose the involvement of Cys86 in reversible tetramer formation. Our results decipher the existence of two levels of inactivation of FurC: Zn of Anabaena sp. PCC7120, a reversible one through disulfide-formed FurC: Zn tetramers and the irreversible metal catalyzed oxidation. This additional reversible regulation may be specific of cyanobacteria.
AgeAnno: a knowledgebase of single-cell annotation of aging in human
Authors: Huang Kexin , Gong Hoaran , Guan Jingjing , Zhang Lingxiao , Hu Changbao , Zhao Weiling , Huang Liyu , Zhang Wei , Kim Pora , Zhou Xiaobo
Published: October 2022

Aging is a complex process that accompanied by molecular and cellular alterations. The identification of tissue-/cell type-specific biomarkers of aging and elucidation of the detailed biological mechanisms of aging-related genes at the single-cell level can help to understand the heterogeneous aging process and design targeted anti-aging therapeutics. Here, we built AgeAnno (https://relab.xidian.edu.cn/AgeAnno/#/), a knowledgebase of single cell annotation of aging in human, aiming to provide comprehensive characterizations for aging-related genes across diverse tissue-cell types in human by using single-cell RNA and ATAC sequencing data (scRNA and scATAC). The current version of AgeAnno houses 1 678 610 cells from 28 healthy tissue samples with ages ranging from 0 to 110 years. We collected 5580 aging-related genes from previous resources and performed dynamic functional annotations of the cellular context. For the scRNA data, we performed analyses include differential gene expression, gene variation coefficient, cell communication network, transcription factor (TF) regulatory network, and immune cell proportionc. AgeAnno also provides differential chromatin accessibility analysis, motif/TF enrichment and footprint analysis, and co-accessibility peak analysis for scATAC data. AgeAnno will be a unique resource to systematically characterize aging-related genes across diverse tissue-cell types in human, and it could facilitate antiaging and aging-related disease research.
Long noncoding RNAlncMREFpromotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex
Authors: Lv Wei , Jiang Wei , Luo Hongmei , Tong Qian , Niu Xiaoyu , Liu Xiao , Miao Yang , Wang Jingnan , Guo Yiwen , Li Jianan , Zhan Xizhen , Hou Yunqing , Peng Yaxin , Wang Jian , Zhao Shuhong , Xu Zaiyan , Zuo Bo
Published: October 2022

Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.
Ethnicity, Politics of Power Sharing, and Nation-Building in Africa
Authors: Otinche Inyokwe Sunday
Published: October 2022

Evidence suggests that ethnic identity and ethnic diversity in Africa have empirical relationships with her historical past and colonial experiences. This chapter examines these summative experiences to underscore the role the colonialist played in ethnic-identity formation, classification, and discrimination and the elevation of ethnicity as a political and economic resource for nation-building. The colonialists constructed ethnic identities where none existed and promoted them to a level of political consciousness, leaving behind legacy of political control and domination, as is evident in Rwanda, Kenya, Nigeria, and South Sudan, among African nations. Lessons are drawn from Arendt Lijphart’sthesis on the consociational model of sharing power to explain the relationships between ethnicity and the corresponding power relations that induce ethnic conflicts in Africa. A call is made to African leaders to promote social harmony, equity, fairness, and social justice in governance and national unity.
Maize PPR-E proteins mediate RNA C-to-U editing in mitochondria by recruiting the trans deaminase PCW1
Authors: Wang Yong , Li Hao , Huang Zi-Qin , Ma Bing , Yang Yan-Zhuo , Xiu Zhi-Hui , Wang Le , Tan Bao-Cai
Published: October 2022

RNA C-to-U editing in organelles is essential for plant growth and development; however, the underlying mechanism is not fully understood. Here, we report that pentatricopeptide repeat (PPR)-E subclass proteins carry out RNA C-to-U editing by recruiting the trans deaminase PPR motifs, coiled-coil, and DYW domain-containing protein 1 (PCW1) in maize (Zea mays) mitochondria. Loss-of-function of bZIP and coiled-coil domain-containing PPR 1 (bCCP1) or PCW1 arrests seed development in maize. bCCP1 encodes a bZIP and coiled-coil domain-containing PPR protein, and PCW1 encodes an atypical PPR–DYW protein. bCCP1 is required for editing at 66 sites in mitochondria and PCW1 is required for editing at 102 sites, including the 66 sites that require bCCP1. The PCW1-mediated editing sites are exclusively associated with PPR-E proteins. bCCP1 interacts with PCW1 and the PPR-E protein Empty pericarp7 (EMP7). Two multiple organellar RNA editing factor (MORF) proteins, ZmMORF1 and ZmMORF8, interact with PCW1, EMP7, and bCCP1. ZmMORF8 enhanced the EMP7–PCW1 interaction in a yeast three-hybrid assay. C-to-U editing at the ccmFN-1553 site in maize required EMP7, bCCP1, and PCW1. These results suggest that PPR-E proteins function in RNA editing by recruiting the trans deaminase PCW1 and bCCP1, and MORF1/8 assist this recruitment through protein–protein interactions.
High-Impact Chronic Pain Transition in Lumbar Surgery Recipients
Authors: Cook Chad E , George Steven Z , Lentz Trevor , Park Christine , Shaffrey Christopher I , Goodwin C Rory , Than Khoi D , Gottfried Oren N
Published: October 2022

Objective

High-impact chronic pain (HICP) is a term that characterizes the presence of a severe and troubling pain-related condition. To date, the prevalence of HICP in lumbar spine surgery recipients and their HICP transitions from before to after surgery are unexplored. The purpose was to define HICP prevalence, transition types, and outcomes in lumbar spine surgery recipients and to identify predictors of HICP outcomes.

Methods

In total, 43,536 lumbar surgery recipients were evaluated for HICP transition. Lumbar spine surgery recipients were categorized as having HICP preoperatively and at 3 months after surgery if they exhibited chronic and severe pain and at least one major activity limitation. Four HICP transition groups (Stable Low Pain, Transition from HICP, Transition to HICP, and Stable High Pain) were categorized and evaluated for outcomes. Multivariate multinomial modeling was used to predict HICP transition categorization.

Results

In this sample, 15.1% of individuals exhibited HICP preoperatively; this value declined to 5.1% at 3 months after surgery. Those with HICP at baseline and 3 months had more comorbidities and worse overall outcomes. Biological, psychological, and social factors predicted HICP transition or Stable High Pain; some of the strongest involved social factors of 2 or more to transition to HICP (OR = 1.43; 95% CI = 1.21–1.68), and baseline report of pain/disability (OR = 3.84; 95% CI = 3.20–4.61) and psychological comorbidity (OR = 1.78; 95% CI = 1.48–2.12) to Stable Stable High Pain.

Conclusion

The percentage of individuals with HICP preoperatively (15.1%) was low, which further diminished over a 3-month period (5.1%). Postoperative HICP groups had higher levels of comorbidities and worse baseline outcomes scores. Transition to and maintenance of HICP status was predicted by biological, psychological, and social factors.
Macroscopic properties of buyer–seller networks in online marketplaces
Authors: Bracci Alberto , Boehnke Jörn , ElBahrawy Abeer , Perra Nicola , Teytelboym Alexander , Baronchelli Andrea
Published: October 2022

Online marketplaces are the main engines of legal and illegal e-commerce, yet their empirical properties are poorly understood due to the absence of large-scale data. We analyze two comprehensive datasets containing 245M transactions (16B USD) that took place on online marketplaces between 2010 and 2021, covering 28 dark web marketplaces, i.e. unregulated markets whose main currency is Bitcoin, and 144 product markets of one popular regulated e-commerce platform. We show that transactions in online marketplaces exhibit strikingly similar patterns despite significant differences in language, lifetimes, products, regulation, and technology. Specifically, we find remarkable regularities in the distributions of transaction amounts, number of transactions, interevent times, and time between first and last transactions. We show that buyer behavior is affected by the memory of past interactions and use this insight to propose a model of network formation reproducing our main empirical observations. Our findings have implications for understanding market power on online marketplaces as well as intermarketplace competition, and provide empirical foundation for theoretical economic models of online marketplaces.
Participation Among Community-Dwelling Older Adults During the COVID-19 Pandemic: A Cross-Sectional Analysis
Authors: Nguyen Khang , Macedo Luciana G , Vrkljan Brenda , Kirkwood Renata , Ma Jinhui , Vesnaver Elisabeth , Keller Heather , Astephen-Wilson Janie , Beauchamp Marla K
Published: October 2022

Objective

Participation in life situations is a critical aspect of health recognized by the World Health Organization. Guidelines to prevent spreading of COVID-19 place older adults at risk of worsening participation. The purpose of this study was to identify the factors associated with participation during the COVID-19 pandemic among community-dwelling older adults living in Hamilton, Ontario, Canada.

Methods

Participants were recruited from identified census dissemination areas in Hamilton. Participants completed surveys either by phone or online during the months of May to August 2020. Measures were organized into factors related to body functions and structures, activities, participation, as well as personal and environmental contextual factors using the International Classification of Functioning, Disability, and Health (ICF) framework. Multivariable regression analysis was conducted to identify factors associated with participation as measured by the Late-Life Disability Instrument’s (LLDI) frequency and limitations scales.

Results

A total of 272 older adults completed the survey (78 [7.3] years; 70% female). Use of a walking aid, driving status, perceived mental health status, nutrition risk, and physical function explained 48.2% of the variance observed in the LLDI-frequency scale scores. Use of a walking aid, driving status, perceived mental health status, receiving health assistance, and physical function explained 38.5% of the variance observed in the LLDI-limitation scale scores.

Conclusion

Results highlighted factors across multiple ICF domains that are associated with participation restriction among a sample of community-dwelling older adults during the pandemic. Participation during the pandemic was greatest in those that were able to walk without needing to use a walking aid, being a licensed and current driver, perceiving good to excellent mental health, and having greater physical function.

Impact

Our findings contribute to the literature on older adult participation during lockdowns, restrictions, pandemics, and/or other similar circumstances.
Apelin as a new therapeutic target for COVID-19 treatment
Authors: Park J , Park M -Y , Kim Y , Jun Y , Lee U , Oh C -M
Published: October 2022

Background

Apelin is an endogenous neuropeptide that binds to the G-protein-coupled receptor (APJ) and participates in a variety of physiological processes in the heart, lungs and other peripheral organs. Intriguingly, [Pyr1]-Apelin-13, a highly potent pyroglutamic form of apelin, has the potential to bind to and be degraded by angiotensin-converting enzyme 2 (ACE2). ACE2 is known to operate as a viral receptor in the early stages of severe acute respiratory coronavirus (SARS-CoV-2) infection.

Aim

This study aimed to determine if apelin protects against SARS-CoV-2 infection by inhibiting ACE2 binding to SARS-CoV-2 spike protein.

Design and methods

To determine whether [Pyr1]-Apelin-13 inhibits ACE2 binding to the SARS-CoV-2 spike protein (S protein), we performed a cell-to-cell fusion assay using ACE2-expressing cells and S protein-expressing cells and a pseudovirus-based inhibition assay. We then analyzed publicly available transcriptome data while focusing on the beneficial effects of apelin on the lungs.

Results

We found that [Pyr1]-Apelin-13 inhibits cell-to-cell fusion mediated by ACE2 binding to the S protein. In this experiment, [Pyr1]-Apelin-13 protected human bronchial epithelial cells, infected with pseudo-typed lentivirus-producing S protein, against viral infection. In the presence of [Pyr1]-Apelin-13, the level of viral spike protein expression was also reduced in a concentration-dependent manner. Transcriptome analysis revealed that apelin may control inflammatory responses to viral infection by inhibiting the nuclear factor kappa B pathway.

Conclusion

Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.
Spreading the gospel: Legitimating university rankings as boundary work
Authors: Brankovic Jelena , Ringel Leopold , Werron Tobias
Published: October 2022

The dramatic salience of university rankings is usually attributed to a number of macro-level trends, such as neoliberal ideology, the spread of audit culture, and globalization in the broadest sense. We propose that the institutionalization of university rankings cannot be fully accounted for without a better understanding of the meso-level processes that enable it. To explore these, we zoom in on an organization called IREG Observatory (whereby IREG stands for ‘International Ranking Expert Group’). Since it first emerged, in 2002, IREG has acted as a carrier of a kind of rationalized ‘faith in rankings’—a faith it has laboured to justify, diffuse, and solidify through boundary work at the intersection of technocratic, managerial, academic, and commercial spheres. Drawing on the insights gained from this particular case, the article argues that the institutionalization of university rankings is not solely a matter of universities being impelled by them but also a matter of how actors in and around the university sector collectively partake in the legitimation of the practice of ranking universities. At a more general level, our analysis potentially provides a blueprint for understanding boundary work as a meso-level process that plays an important role in the institutionalization of rankings, and other devices of evaluation.
Rating Agency Fees: Pay to Play in Public Finance?
Authors: Cornaggia Jess , Cornaggia Kimberly J , Israelsen Ryan
Published: October 2022

We examine the relationship between credit rating levels and rating agency fees in a public finance market in which rating agencies earn lower fees and face higher disclosure requirements relative to corporate bond and structured finance markets. Controlling for variation in the complexity of credit analysis at the issue level, we find evidence that rating agency conflicts of interest distort credit ratings in the municipal bond market. Unexpectedly expensive ratings are more likely downgraded, and inexpensive ratings are more likely upgraded. The relationship between credit ratings and rating agency fees is driven by issuers who lose access to AAA insurance.
10 Impact of the month of birth on the development of juvenile idiopathic arthritis among Tunisian children
Authors: Triki Wafa , Rabhi Emna , Ferjani Hanene , Ben Aissa Rania , Ben Nessib Dorra , Maatallah Kaouther , Kaffel Dhia , Hamdi Wafa
Published: October 2022

Background

Juvenile idiopathic arthritis (JIA) is the most common inflammatory disease influenced by genetic as well as environmental factors. Prior studies from Israel and USA suggested that JIA had a seasonality of birth, with birth peaking in winter and especially in January.

Objectives

The aim of the study was to evaluate the impact of month of birth and season, and the onset of JIA in Tunisian children.

Methods

We conducted a case-control study including 27 children with JIA compared with a homogeneous control group of 27 children hospitalized in a pediatric orthopedic unit for traumatic reasons and healthy for any chronic inflammatory rheumatism. Statistical differences between groups were also analyzed by non-parametrical tests.

Results

Fifty-four patients (25 females and 29 males) were enrolled. The mean age was 11.04 ± 5.58 years and the mean duration of the diseases was 5.29 ± 3,18 years. The frequency of each JIA subset was at follows: polyarticular rheumatoid factor positive (n = 2), polyarticular rheumatoid factor negative (n = 5), psoriatic arthritis (n = 1), enthesitis-related arthritis (n = 11) and oligoarthritis (n = 8). Although the majority of children with JIA were born in November (22.2%) and December (18.5%), there was no significant difference in month of birth distribution between the cases and the controls. Likewise, there was no significant correlation between season of birth and the onset of the disease (p = 0,6).

Conclusion

This study didn’t show any correlation between season and month birth, and the onset of JIA. Our result may be explained by the weather in Tunisia which is relatively warm with little variation in temperature between seasons compared with the country where they found a significant correlation. It also may be due to the limited number of our cases.