bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation
Authors: Li Yanhong , Wang Jing , Ma Yanchao , Du Wenjia , Feng Haijun , Feng Kai , Li Guangjie , Wang Shuanke 
Published: November 2020

Abstract
Background
Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation.

Methods
Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo.

Results
WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor.

Conclusion
Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway.

Graphical abstract
What is the size of Australia’s sexual minority population?
Authors: Wilson Tom , Temple Jeromey , Lyons Anthony , Shalley Fiona 
Published: November 2020

AbstractObjectivesThe aim is to present updated estimates of the size of Australia’s sexual minority adult population (gay, lesbian, bisexual, and other sexual minority identities). No estimate of this population is currently available from the Australian Bureau of Statistics, and very little is available from other sources. We obtained data on sexual minority identities from three data collections of two national surveys of recent years. Combining averaged prevalence rates from these surveys with official Estimated Resident Population data, we produce estimates of Australia’s sexual minority population for recent years.ResultsAccording to percentages averaged across the three survey datasets, 3.6% of males and 3.4% of females described themselves with a minority sexual identity. When applied to Estimated Resident Populations, this gives a sexual minority population at ages 18 + in Australia of 599,500 in 2011 and 651,800 in 2016. Population estimates were also produced by sex and broad age group, revealing larger numbers and higher sexual minority percentages in the younger age groups, and smaller numbers and percentages in the oldest age group. Separate population estimates were also prepared for lesbian, gay, bisexual, and other sexual minority identities.
Predictors of short-term thrombocytopenia after transcatheter aortic valve implantation: a retrospective study at a single Japanese center
Authors: Yamada Yasutaka , Miura Daisuke , Takamori Ayako , Nogami Eijiro , Yunoki Junji , Sakaguchi Yoshiro 
Published: November 2020

Abstract
Objective
Thrombocytopenia is common after transcatheter aortic valve implantation (TAVI) and is associated with mortality and major complications, although the underlying mechanisms are unclear. This retrospective single-center study aimed to identify factors associated with the decrease in platelet count (DPC) after TAVI in Japanese patients. Patients with severe aortic valve stenosis who underwent transfemoral TAVI between March 2014 and August 2019 were grouped according to DPC values of < 50% or ≥ 50% (DPC = 100% × [baseline platelet count–nadir platelet count]/[baseline platelet count]). Multivariable logistic regression analysis was performed to identify factors associated with a DPC of ≥ 50%.

Results
Among the 131 patients who underwent transfemoral TAVI, 74 patients (56%) had a DPC of ≥ 50%, and 57 patients (44%) had a DPC of < 50%. Significant risk factors for a DPC of ≥ 50% were older age, lower body mass index (BMI), and use of balloon-expandable valves (BEV). The multivariable analysis revealed that a DPC of ≥ 50% was independently predicted by low BMI (adjusted odds ratio: 0.884, 95% confidence interval: 0.785–0.997; P = 0.039) and BEV use (adjusted odds ratio: 3.014, 95% confidence interval: 1.003–9.056; P = 0.045). Platelet count monitoring after TAVI, especially when using BEV devices, is essential for Japanese patients with low BMI.
TREM2 Alzheimer’s variant R47H causes similar transcriptional dysregulation to knockout, yet only subtle functional phenotypes in human iPSC-derived macrophages
Authors: Hall-Roberts Hazel , Agarwal Devika , Obst Juliane , Smith Thomas B. , Monzón-Sandoval Jimena , Di Daniel Elena , Webber Caleb , James William S. , Mead Emma , Davis John B. , Cowley Sally A. 
Published: November 2020

Abstract
Background
TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. TREM2 signalling via SYK aids phagocytosis, chemotaxis, survival, and changes to microglial activation state. In AD mouse models, knockout (KO) of TREM2 impairs microglial clustering around amyloid and prevents microglial activation. The R47H mutation is proposed to reduce TREM2 ligand binding. We investigated cell phenotypes of the R47H mutant and TREM2 KO in a model of human microglia, and compared their transcriptional signatures, to determine the mechanism by which R47H TREM2 disrupts function.

Methods
We generated human microglia-like iPSC-macrophages (pMac) from isogenic induced pluripotent stem cell (iPSC) lines, with homozygous R47H mutation or TREM2 knockout (KO). We firstly validated the effect of the R47H mutant on TREM2 surface and subcellular localization in pMac. To assess microglial phenotypic function, we measured phagocytosis of dead neurons, cell morphology, directed migration, survival, and LPS-induced inflammation. We performed bulk RNA-seq, comparing significant differentially expressed genes (DEGs; p < 0.05) between the R47H and KO versus WT, and bioinformatically predicted potential upstream regulators of TREM2-mediated gene expression.

Results
R47H modified surface expression and shedding of TREM2, but did not impair TREM2-mediated signalling, or gross phenotypes that were dysregulated in the TREM2 KO (phagocytosis, motility, survival). However, altered gene expression in the R47H TREM2 pMac overlapped by 90% with the TREM2 KO and was characterised by dysregulation of genes involved with immunity, proliferation, activation, chemotaxis, and adhesion. Downregulated mediators of ECM adhesion included the vitronectin receptor αVβ3, and consequently, R47H TREM2 pMac adhered weakly to vitronectin compared with WT pMac. To counteract these transcriptional defects, we investigated TGFβ1, as a candidate upstream regulator. TGFβ1 failed to rescue vitronectin adhesion of pMac, although it improved αVβ3 expression.

Conclusions
The R47H mutation is not sufficient to cause gross phenotypic defects of human pMac under standard culture conditions. However, overlapping transcriptional defects with TREM2 KO supports the hypothesised partial loss-of-function effects of the R47H mutation. Furthermore, transcriptomics can guide us to more subtle phenotypic defects in the R47H cells, such as reduced cell adhesion, and can be used to predict targets for therapeutic intervention.
Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature
Authors: Lawal Tokunbor A. , Todd Joshua J. , Witherspoon Jessica W. , Bönnemann Carsten G. , Dowling James J. , Hamilton Susan L. , Meilleur Katherine G. , Dirksen Robert T. 
Published: November 2020

AbstractTheRYR1gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 andRYR1variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then,RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders.RYR1variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression.RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically,RYR1-RM-affected individuals were diagnosed based on morphologic features observed in muscle biopsies including central cores, cores and rods, central nuclei, fiber type disproportion, and multi-minicores. However, these histopathologic features are not always specific toRYR1-RM and often change over time. As additional phenotypes were associated withRYR1variations (including King-Denborough syndrome, exercise-induced rhabdomyolysis, lethal multiple pterygium syndrome, adult-onset distal myopathy, atypical periodic paralysis with or without myalgia, mild calf-predominant myopathy, and dusty core disease) the overlap among diagnostic categories is ever increasing. With the continuing emergence of new clinical subtypes along theRYR1disease spectrum and reports of adult-onset phenotypes, nuanced nomenclatures have been reported (RYR1- [related, related congenital, congenital] myopathies). In this narrative review, we provide historical highlights ofRYR1research, accounts of the main diagnostic disease subtypes and proposeRYR1-related disorders (RYR1-RD) as a unified nomenclature to describe this complex and evolving disease spectrum.
MyoSight—semi-automated image analysis of skeletal muscle cross sections
Authors: Babcock Lyle W. , Hanna Amy D. , Agha Nadia H. , Hamilton Susan L. 
Published: November 2020

AbstractBackgroundManual analysis of cross-sectional area, fiber-type distribution, and total and centralized nuclei in skeletal muscle cross sections is tedious and time consuming, necessitating an accurate, automated method of analysis. While several excellent programs are available, our analyses of skeletal muscle disease models suggest the need for additional features and flexibility to adequately describe disease pathology. We introduce a new semi-automated analysis program, MyoSight, which is designed to facilitate image analysis of skeletal muscle cross sections and provide additional flexibility in the analyses.ResultsWe describe staining and imaging methods that generate high-quality images of immunofluorescent-labelled cross sections from mouse skeletal muscle. Using these methods, we can analyze up to 5 different fluorophores in a single image, allowing simultaneous analyses of perinuclei, central nuclei, fiber size, and fiber-type distribution. MyoSight displays high reproducibility among users, and the data generated are in close agreement with data obtained from manual analyses of cross-sectional area (CSA), fiber number, fiber-type distribution, and number and localization of myonuclei. Furthermore, MyoSight clearly delineates changes in these parameters in muscle sections from a mouse model of Duchenne muscular dystrophy (mdx).ConclusionsMyoSight is a new program based on an algorithm that can be optimized by the user to obtain highly accurate fiber size, fiber-type identification, and perinuclei and central nuclei per fiber measurements. MyoSight combines features available separately in other programs, is user friendly, and provides visual outputs that allow the user to confirm the accuracy of the analyses and correct any inaccuracies. We present MyoSight as a new program to facilitate the analyses of fiber type and CSA changes arising from injury, disease, exercise, and therapeutic interventions.
Consistent independent low-rank matrix analysis for determined blind source separation
Authors: Kitamura Daichi , Yatabe Kohei 
Published: November 2020

AbstractIndependent low-rank matrix analysis (ILRMA) is the state-of-the-art algorithm for blind source separation (BSS) in the determined situation (the number of microphones is greater than or equal to that of source signals). ILRMA achieves a great separation performance by modeling the power spectrograms of the source signals via the nonnegative matrix factorization (NMF). Such a highly developed source model can solve the permutation problem of the frequency-domain BSS to a large extent, which is the reason for the excellence of ILRMA. In this paper, we further improve the separation performance of ILRMA by additionally considering the general structure of spectrograms, which is calledconsistency, and hence, we call the proposed methodConsistent ILRMA. Since a spectrogram is calculated by an overlapping window (and a window function induces spectral smearing called main- and side-lobes), the time-frequency bins depend on each other. In other words, the time-frequency components are related to each other via the uncertainty principle. Such co-occurrence among the spectral components can function as an assistant for solving the permutation problem, which has been demonstrated by a recent study. On the basis of these facts, we propose an algorithm for realizing Consistent ILRMA by slightly modifying the original algorithm. Its performance was extensively evaluated through experiments performed with various window lengths and shift lengths. The results indicated several tendencies of the original and proposed ILRMA that include some topics not fully discussed in the literature. For example, the proposed Consistent ILRMA tends to outperform the original ILRMA when the window length is sufficiently long compared to the reverberation time of the mixing system.
Can technology optimise the pre-operative pathway for elective hip and knee replacement surgery: a qualitative study
Authors: Sharif Faraz , Rahman Ammar , Tonner Emma , Ahmed Hanad , Haq Iqraa , Abbass Rami , Asinger Shad , Sbai Magda 
Published: November 2020

AbstractBackgroundAn ageing population has resulted in a rise in the number of hip and knee replacement surgeries in the UK. The pre-operative pathway is plagued with issues causing long delays and cancellations. Virtual healthcare technologies have a growing evidence base to help solve these issues. One problem of implementing these technologies is the resistance to change mentality from healthcare professionals. By getting their opinions on the place of these technologies within the pre-operative pathway, a united front can be formed to help deliver change.MethodsSixteen semi-structured interviews were conducted with key stakeholders within the orthopaedic pre-operative pathway at Imperial College Healthcare NHS Trust. General topics included the different technologies that could be used within the pathway, their uses and associated benefits and problems. Interviews were audio-recorded, before being manually transcribed and then analysed to form categories and themes.ResultsVarious uses, benefits and problems were identified by healthcare professionals for each modality of technology. E-forms were seen as a high reward, low-risk intervention. Remote patient monitoring and teleconsultations had their bonuses, but feasibility was a primary concern. Web-based interventions were seen as an intervention of the past, whereas virtual reality was seen as perhaps being ahead of its time. M-health was very positively viewed due to its all-encompassing nature. Digital illiteracy emerged as a consistent problem for most technologies.ConclusionsCurrent literature, the results from this study and technology trends within society highlight both M-health and E-forms as the 2 most promising virtual healthcare technologies for use in the pre-operative pathway for orthopaedics. Areas such as pre-operative assessment, triaging and prehabilitation are prime candidates for virtual intervention. Future research should also consider including patient opinions on any proposed interventions, as well as taking into account barriers to implementation.
Characterization of the materials and techniques of a birthday inscribed lacquer plaque of the Qing Dynasty
Authors: Zheng Liping , Wang Liqin , Zhao Xing , Yang Jiali , Zhang Mengxia , Wang Yunfu 
Published: November 2020

Abstract
In this study, in order to analyze the materials and techniques used for the production of the inscribed plaques, multi-analytical scientific approach, including optical microscopy (OM), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM–EDS), X-ray diffraction (XRD), micro-attenuated total reflection Fourier transform infrared spectroscopy (μ-ATR-FTIR), and micro-Raman spectroscopy (μ-Raman), were used to explore the materials and techniques utilized to create the “Chun Rong Xuan Mao” birthday inscribed plaque of the Qing Dynasty. The results showed that the plaque was made of cypress wood and decorative parts consisting of the surface lacquer layers, plaster lacquer layers and primer lacquer layers. Chinese lacquer was the principal material used in the surface lacquer layers; gypsum and Chinese lacquer were the materials used in the plaster lacquer layers; and the primer lacquer layers was composed of Chinese lacquer, calcite, and mixed pigments by cinnabar and minium. The surface lacquer layers of the inscribed plaque were lacquered black. Gypsum lacquer plaster has been commonly used in the ground layer of lacquerware in modern history. This study confirmed the existence of technology to make lacquerware using gypsum lacquer plaster in the Bashu area during the late Qing Dynasty. Moreover, this study not only provides new findings regarding the traditional production of inscribed plaques and offers technical support for the protection and restoration of such plaques but also has great significance to exploring the history of ancient techniques of lacquering and decorating lacquerware.
The feasibility of a Comprehensive Resilience-building psychosocial Intervention (CREST) for people with dementia in the community: protocol for a non-randomised feasibility study
Authors: Casey Dympna , Gallagher Niamh , Devane Declan , Woods Bob , Murphy Kathy , Smyth Siobhán , Newell John , Murphy Andrew W. , Clarke Charlotte , Foley Tony , Timmons Fergus , Dröes Rose-Marie , O’Halloran Martin , Windle Gill , Irving Lupton Kate , Domegan Christine , O’Shea Eamon , Dolan Pat , Doyle Priscilla 
Published: November 2020

AbstractBackgroundA dementia diagnosis can prevent people from participating in society, leading to a further decline in cognitive, social and physical health. However, it may be possible for people with dementia to continue to live meaningful lives and continue to participate actively in society if a supportive psychosocial environment exists. Resilience theory, which focuses on strengthening personal attributes and external assets in the face of serious challenges, may provide a scaffold on which an inclusive multifaceted psychosocial supportive environment can be built. This protocol paper describes a study to determine the feasibility of conducting a multifaceted complex resilience building psychosocial intervention for people with dementia and their caregivers living in the community.MethodsThis is a non-randomised feasibility study. Ten participants with dementia and their primary caregivers living in the community will be recruited and receive the CREST intervention. The intervention provides (a) a 7-week cognitive stimulation programme followed by an 8-week physical exercise programme for people with dementia and (b) a 6-week educational programme for caregivers. Members of the wider community will be invited to a dementia awareness programme and GP practices to a dementia training workshop. Trained professionals will deliver all intervention components. Outcomes will assess the feasibility and acceptability of all study processes. The feasibility and acceptability of a range of outcomes to be collected in a future definitive trial, including economic measurements, will also be explored. Finally, social marketing will be used to map a route toward stigma change in dementia for use in a subsequent trial. Quantitative feasibility outcome assessments will be completed at baseline and after completion of the 15-week intervention while qualitative data will be collected at recruitment, baseline, during and post-intervention delivery.ConclusionThis feasibility study will provide evidence regarding the feasibility and acceptability of a comprehensive multifaceted psychosocial intervention programme for people with dementia and their caregivers (CREST). The results will be used to inform the development and implementation of a subsequent RCT, should the findings support feasibility.Trial registrationISRCTN25294519Retrospectively registered 07.10.2019
25 vs. 27-gauge micro-incision vitrectomy surgery for visually significant macular membranes and full-thickness macular holes: a retrospective study
Authors: Brown Gordon T. , Pugazhendhi Sangeethabalasri , Beardsley Robert M. , Karth John W. , Karth Peter A. , Hunter Allan A. 
Published: November 2020

AbstractBackgroundTo evaluate visual and safety outcomes for 25-gauge (25G) and 27-gauge (27G) micro-incision vitrectomy platforms (MIVS) for the treatment of epiretinal membrane and full-thickness macular holes.MethodsRetrospective analysis of all patients who underwent internal limiting membrane (ILM) peel surgery from January 2017 through December 2018. 207 cases met the eligibility criteria for inclusion. Primary endpoint was post-operative Best-Corrected Distance Visual Acuity (BCVA) at 6 months.ResultsFor all patients combined, mean logMAR BCVA improved from 0.57 (± 0.40) to 0.37 (± 0.36) post-operatively (p < 0.001). For 25G ERMs, logMAR BCVA improved from 0.51 (± 0.28) to 0.30 (± 0.25) post-operatively (p < 0.001). For 27G ERMs, logMAR BCVA improved from 0.33 (± 0.28) to 0.28 (± 0.27) post- operatively (p = 0.15). For 25G FTMHs, logMAR BCVA improved from 0.87 (± 0.48) to 0.51 (± 0.44) post-operatively (p < 0.001). For 27G FTMHs, logMAR BCVA changed from 0.89 (± 0.47) to 0.96 (± 0.60).ConclusionFinal visual outcomes improved for both 25G and 27G ERM groups and the 25G FTMH group. Both 25G and 27G were safe and well tolerated MIVS platforms for the treatment of ERM and FTMH.