Miracle-dz/UniFAR-FTUs huggingface dataset:
Administration of mircoRNA‐135b‐reinforced exosomes derived from MSCs ameliorates glucocorticoid‐induced osteonecrosis of femoral head (ONFH) in rats

Exosomes were found to exert a therapeutic effect in the treatment of osteonecrosis of the femoral head (ONFH), while miR‐135b was shown to play an important role in the development of ONFH. In this study, we investigated the effects of concomitant administration of exosomes and miR‐135b on the treatment of ONFH. A rat mode of ONFH was established. TEM, Western blotting and nanoparticle analysis were used to characterize the exosomes collected from human‐induced pluripotent stem cell–derived mesenchymal stem cells (hiPS‐MSC‐Exos). Micro‐CT was used to observe the trabecular bone structure of the femoral head. Real‐time PCR, Western blot analysis, IHC assay, TUNEL assay, MTT assay and flow cytometry were performed to detect the effect of hiPS‐MSC‐Exos and miR‐135b on cell apoptosis and the expression of PDCD4/caspase‐3/OCN. Moreover, computational analysis and luciferase assay were conducted to identify the regulatory relationship between PDCD4 mRNA and miR‐135b. The hiPS‐MSC‐Exos collected in this study displayed a spheroidal morphology with sizes ranging from 20 to 100 nm and a mean concentration of 1 × 1012 particles/mL. During the treatment of ONFH, the administration of hiPS‐MSC‐Exos and miR‐135b alleviated the magnitude of bone loss. Furthermore, the treatment of MG‐63 and U‐2 cells with hiPS‐MSC‐Exos and miR‐135b could promote cell proliferation and inhibit cell apoptosis. Moreover, PDCD4 mRNA was identified as a virtual target gene of miR‐135b. HiPS‐MSC‐Exos exerted positive effects during the treatment of ONFH, and the administration of miR‐135b could reinforce the effect of hiPS‐MSC‐Exos by inhibiting the expression of PDCD4.
A Telemonitoring and Hybrid Virtual Coaching Solution “CAir” for Patients with Chronic Obstructive Pulmonary Disease: Protocol for a Randomized Controlled Trial

Background Chronic obstructive pulmonary disease (COPD) is one of the most common disorders in the world. COPD is characterized by airflow obstruction, which is not fully reversible. Patients usually experience breathing-related symptoms with periods of acute worsening and a substantial decrease in the health-related quality-of-life. Active and comprehensive disease management can slow down the progressive course of the disease and improve patients’ disabilities. Technological progress and digitalization of medicine have the potential to make elaborate interventions easily accessible and applicable to a broad spectrum of patients with COPD without increasing the costs of the intervention. Objective This study aims to develop a comprehensive telemonitoring and hybrid virtual coaching solution and to investigate its effects on the health-related quality of life of patients with COPD. Methods A monocentric, assessor-blind, two-arm (intervention/control) randomized controlled trial will be performed. Participants randomized to the control group will receive usual care and a CAir Desk (custom-built home disease-monitoring device to telemonitor disease-relevant parameters) for 12 weeks, without feedback or scores of the telemonitoring efforts and virtual coaching. Participants randomized to the intervention group will receive a CAir Desk and a hybrid digital coaching intervention for 12 weeks. As a primary outcome, we will measure the delta in the health-related quality of life, which we will assess with the St. George Respiratory Questionnaire, from baseline to week 12 (the end of the intervention). Results The development of the CAir Desk and virtual coach has been completed. Recruitment to the trial started in September 2020. We expect to start data collection by December 2020 and expect it to last for approximately 18 months, as we follow a multiwave approach. We expect to complete data collection by mid-2022 and plan the dissemination of the results subsequently. Conclusions To our knowledge, this is the first study investigating a combination of telemonitoring and hybrid virtual coaching in patients with COPD. We will investigate the effectiveness, efficacy, and usability of the proposed intervention and provide evidence to further develop app-based and chatbot-based disease monitoring and interventions in COPD. Trial Registration ClinicalTrials.gov identifier: NCT04373070; https://clinicaltrials.gov/ct2/show/NCT04373070 International Registered Report Identifier (IRRID) DERR1-10.2196/20412
Amyloid, prions, and other protein aggregates

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Anterior Cingulate Cortex in Addiction: New Insights for Neuromodulation

Substance use disorder (SUD) is characterized by compulsive use of addictive substances with considerable impact on both the medical system and society as a whole. The craving of substances leads to relapse in the majority of patients within one year of traditional treatments. In recent decades, neuromodulation approaches have emerged as potential novel treatments of SUD, but the ideal neural target remains contentious.
Assessing knowledge of genomic concepts among Canadian nursing students and faculty

Abstract Objectives Contemporary nurses require genomic literacy to engage in genomics-informed health care. Little is known about the genomic literacy of undergraduate nursing students and faculty in many countries. Concept inventories can be used to assess levels of knowledge and inform curriculum development. Methods The 31-item Genomic Nursing Concept Inventory (GNCI) was administered to undergraduate nursing students (n=207) and faculty (n=13) in a school of nursing with two sites in western Canada. Results Scores on the GNCI were low and comparable to those of US students and faculty. Six student characteristics were associated with total score on the GNCI. Conclusions Both students and faculty need to increase their knowledge of genomics. Mandates from national nursing organizations and international collaboration are needed to develop and implement foundational genomics content for undergraduate curricula to enable graduates to engage in genomics-informed health care.
Between-group difference in mean values or changes in pain intensity? Evaluating the distribution of change from baseline in a neuropathic cancer pain clinical trial.

Ann Palliat Med 2020;9(6):4398-4402 | http://dx.doi. org/10.21037/apm-20-930 When evaluating pain relief in pain research, both betweengroup differences in mean values and changes in pain intensity (absolute or relative values) are recommended (1). However, there is no consensus on which one is superior, thereby causing a few challenges such as difficulty in comparing multiple research views and differences in sample size calculations, resulting in different results within a single study. Our recent studies (2,3) have also yielded different results within a single study, making interpretation difficult. One such study of ours, the DIRECT study, which was a multicenter double-blinded randomized placebo-controlled two-parallel group trial, investigated the efficacy of duloxetine for cancer-related neuropathic pain (CNP) nonresponsive or intolerant to opioidpregabalin combination therapy. In that study, duloxetine was commenced at a dose of 20 mg once daily. On day-3, the degree of pain relief was evaluated using the Pain Relief Scale (4). Patients who reported complete or substantial relief continued to receive the same dose while the dose was increased to 40 mg for the remaining patients. The primary endpoint was a comparison of pain intensity [Brief Pain Inventory (BPI)-item 5] (5) at day-10 in both groups. Seventy eligible patients were enrolled and randomized, and 65 participants completed the study. Among the 70 patients, 67 were evaluable: 34 in group duloxetine (Group D) and 33 in group placebo (Group P). There were no primary endpoint data for one patient in each group. Of the 67 evaluable subjects, 32 patients (94.1%) in Group D and 29 patients (87.9%) in Group P completed the protocol treatment on day-10. Twenty-two patients (63%) of patients in Group D and 23 patients (66%) of those in Group P increased the dose to 40 mg per day. Three different types of analyses were applied revealing the following results. Firstly, in the complete case (CC) analysis, BPI-item 5 on day-10 was 4.03 [90% confidence interval (CI): 3.33–4.74] for Group D and 4.88 (90% CI: 4.37–5.38) for Group P (P=0.053). Secondly, in the sensitivity analysis using baseline observation carried forward (BOCF) (6), average pain scores on day-10 were 4.06 (90% CI: 3.37–4.74) for Group D and 4.91 (90% CI: 4.41–5.41) for Group P (P=0.04). BOCF is based on the assumption that the pain returns to the baseline state if treatment is stopped because neuropathic cancer pain is unlikely to improve in the natural course during this short period. Hence, we imputed missing data on day-10 with the score from day-0. However, responder analysis, comparing the percentages of patients with clinically meaningful pain reduction (≥30% and ≥50%), showed different results. On the tenth day, 15 patients (44.1%) in Group D and 6 patients (18.2%) in Group P reported pain improvement ≥30% (P=0.02) whereas 11 patients (32.4%) in Group D and 1 patient (3%) in Group Editorial Commentary
Investigation of Outbreaks of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae in Three Neonatal Intensive Care Units Using Whole Genome Sequencing

Infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are on a constant rise and are a noted cause of outbreaks in neonatal intensive care units (NICUs). We used whole genome sequencing (WGS) to investigate the epidemiology of consecutive and overlapping outbreaks caused by ESBL-KP in NICUs in three hospitals in close proximity. Clonality of 43 ESBL-KP isolates from 40 patients was determined by BOX-PCR. Short-read sequencing was performed on representative isolates from each clone. The dominant clones from each NICU were sequenced using long-read sequencing. Bioinformatics methods were used to define multilocus sequence type (MLST), analyze plasmid content, resistomes, and virulence factors. In each NICU, we found a unique dominant clone (ST985, ST37, and ST35), each belonging to a distinct sequence type (ST), as well as satellite clones. A satellite strain in NICU-2 (ST35) was the dominant strain in NICU-3, where it was isolated four weeks later, suggesting transmission. NICU-1- and NICU-2-dominant strains had blaCTX-M-15 carried on a similar transposable element (Tn3-ISEcp1) but at different locations: on a plasmid and on the chromosome, respectively. We concluded that the overlapping ESBL-KP outbreaks were a combination of clonal transmission within NICUs, possible transposable element transmission between NICUs, and repeated importation of ESBL-KP from the community.
Clinical Behavior of Ceramic, Hybrid and Composite Onlays. A Systematic Review and Meta-Analysis

A systematic review and meta-analysis was performed to analyze the survival of onlay restorations in the posterior region, their clinical behavior according to the material used (ceramic reinforced with lithium disilicate, conventional feldspathic ceramic or reinforced with leucite; hybrid materials and composite), possible complications, and the factors influencing restoration success. The systematic review was based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, without publication date or language restrictions. An electronic search was made in the PubMed, Scopus, Embase, and Cochrane databases. After discarding duplicate publications and studies that failed to meet the inclusion criteria, the articles were selected based on the population, intervention, comparison, outcome (PICO) question. The following variables were considered in the qualitative and quantitative analyses: restoration survival rate (determined by several clinical parameters), the influence of the material used upon the clinical behavior of the restorations, and the complications recorded over follow-up. A total of 29 articles were selected for the qualitative analysis and 27 for the quantitative analysis. The estimated restoration survival rate was 94.2%. The predictors of survival were the duration of follow-up (beta = −0.001; p = 0.001) and the onlay material used (beta = −0.064; p = 0.028). Composite onlays were associated with a lower survival rate over time. Onlays are a good, conservative, and predictable option for restoring dental defects in the posterior region, with a survival rate of over 90%. The survival rate decreases over time and with the use of composite as onlay material.
Treatment strategies in ischaemic left ventricular dysfunction: a network meta-analysis.

OBJECTIVES The optimal revascularization strategy for patients with ischaemic left ventricular systolic dysfunction (iLVSD) remains controversial. We aimed to compare percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical therapy (MT) in a network meta-analysis. METHODS All randomized controlled trials and observational studies comparing any combination of PCI, CABG and MT in patients with iLVSD were analysed in a frequentist network meta-analysis (generic inverse variance method). Primary outcome was mortality at longest available follow-up. Secondary outcomes were cardiac death, stroke, myocardial infarction (MI) and repeat revascularization (RR). RESULTS Twenty-three studies were included (n = 23 633; 4 randomized controlled trials). Compared to CABG, PCI was associated with higher mortality [incidence rate ratio (IRR) 1.32, 95% confidence interval (CI) 1.13-1.53], cardiac death (IRR 1.65, 95% CI 1.18-2.33), MI (IRR 2.18, 95% CI 1.70-2.80) and RR (IRR 3.75, 95% CI 2.89-4.85). Compared to CABG, MT was associated with higher mortality (IRR 1.52, 95% CI 1.26-1.84), cardiac death (IRR 3.83, 95% CI 2.12-6.91), MI (IRR 3.22, 95% CI 1.52-6.79) and RR (IRR 3.37, 95% CI 1.67-6.79). Compared to MT, PCI was associated with lower cardiac death (IRR 0.43, 95% CI 0.24-0.78). CABG ranked as the best revascularization strategy for mortality, cardiac death, MI and RR; MT ranked as the strategy associated with the lowest incidence of stroke. Left ventricular ejection fraction, year of study, use of drug-eluting stents did not affect relative treatment effects. CONCLUSIONS CABG appears to be the best therapy for iLVSD, although mainly based on observational data. Definitive randomized controlled trials comparing CABG and PCI in iLVSD are required. PROSPERO REGISTRATION ID 132414.
Evaluation of Anticancer and Antimicrobial Activity of Arborinine from Glycosmis pentaphylla

Abstract The natural product arborinine, isolated from the plant Glycosmis pentaphylla was evaluated for its anticancer activity against five human cancer cell lines viz. human colon cancer cell line COLO-205, human ovarian cancer cell line OVCAR-3, human cervical cancer cell line SiHa, human breast cancer cell lines T-47D and MDA-MB-435 by SRB assay. The results were compared against a standard anticancer drug Adriamycin. Arborinine shows good activity on COLO-205, OVCAR-3 and T-47D with GI50 value <10 μg/ml in all the three experiments. It also shows mild to moderate antimicrobial activity against Staphylococcus aureus, Klebsiella pneumonia, Bacillus subtilis and Candida albicans strains in Agar well diffusion method.
The relationship between perceived support and depression in spousal care partners: a dyadic approach

Abstract Objectives Caregiving within a spousal partnership marks a novel relationship stage for couples. Caregiving introduces new stressors and affects couples’ ability to cope, and potentially alters perceptions of emotional support. Prior research on older married couples illustrates how perceived support not only affects an individual’s mental health, but also that of their partner. To date, the dyadic relationship between emotional support and mental health is largely unexamined among caregiving partners, where support expectations may differ. Method Actor partner interdependence models using linear mixed modeling were applied to data from spouses where one partner received caregiving within the 2014 and 2016 waves of the Health and Retirement Study. We examined the cross-sectional and lagged associations between perceived emotional support and strain from a spouse on actor and partner depression scores, as well as whether one was the caregiver or the care recipient moderated associations. Results More positive perceptions of support were associated with lower depression scores for oneself (b= −0.55, p < 0.001) and one’s partner (b= −0.24, p < 0.001). Actor effects—how one’s own perceptions of support associate with one’s own depressive symptomology—were stronger for care recipients than for caregivers (b= −0.83, p < 0.001 v. b= −0.26, p < 0.05). Higher perceptions of strain were also associated with higher depression scores for oneself (b = 0.57, p < 0.001) and one’s partner (b = 0.39, p < 0.001), associations that remained even in lagged models. Conclusions The observation of both actor and partner effects in this study suggests opportunities to improve care recipient outcomes through intervention with caregivers or both members of the care dyad.
Agronomic characterization of citrandarin fruits and seeds

In citrus cultivation, rootstocks are of fundamental importance and affect several characteristics of the variety used as canopy. Despite the great diversity within Citrus and related genera, the production of rootstocks in Brazil is restricted to a small number of varieties, making the citrus culture vulnerable to the appearance of phytosanitary problems. The aim of this study was to agronomically characterize fruits and seeds of seven citrandarins [Citrus sunki (Hayata) hort. ex Tanaka x Poncirus trifoliata cv. Rubidoux (L.) Raf. ], obtained by controlled crossing. The orchard was installed in randomized blocks, with three replicates, in the municipality of Cordeirópolis, SP, where 20 fruits were collected in each replicate, obtained from free pollination of seven citrandarins, Swingle citrumelo and Rangpur lime. The following variables were evaluated: fruit mass, height, diameter, total number of seeds and percentage of viable seeds per fruit; number of embryos per seed, mass of one thousand seeds, number of seeds in 1.0 kg, final emergence rate, number of seedlings per seed, polyembryony rate, emergence speed index and seedling height at 60 days after sowing. For fruit size, the highest values were obtained for Swingle citrumelo. For number of embryos per seed, seedlings obtained through seed and polyembryony, citrandarin TSxPT 245 showed the highest values. Although citrandarin fruits had smaller size than fruits from commercial Rangpur lime and Swingle citrumelo rootstocks, characteristics related to seeds such as viability, polyembryony and emergence rate, were similar or superior, and can be considered potential new rootstocks for the production of citrus plants.
Understanding Human–Nature Connections Through Landscape Socialization

Understanding the landscape socialization underpinning the human–nature relationship is essential because it can contribute to assisting us to reconnect with nature. Reconnecting to nature is increasingly recognized as positively contributing to health and well-being. This study aimed to understand people’s connections with nature through landscape socialization under different land use policies. The study assumed that social values, as perceived by residents, facilitates their landscape socialization. Using a questionnaire measuring sense of community and the Social Values for Ecosystem Services application as analytical tools, the study assessed how residents with varying educational attainment, sense of community, and grounded occupation differ in identifying with conservation- and recreation-oriented policy interventions. The results demonstrated the role of landscape socialization in how people connect with nature, and the landscape socialization as a result of long-term policy interventions may exert substantial effects on residents’ social values across various spatial scales. The results deepen the general understanding of system leverage points for creating inner connections to nature which can aid sustainability transformation.
Insights into the Function and Evolution of Taste 1 Receptor Gene Family in the Carnivore Fish Gilthead Seabream (Sparus aurata)

A plethora of molecular and functional studies in tetrapods has led to the discovery of multiple taste 1 receptor (T1R) genes encoding G-protein coupled receptors (GPCRs) responsible for sweet (T1R2 + T1R3) and umami (T1R1 + T1R3) taste. In fish, the T1R gene family repertoires greatly expanded because of several T1R2 gene duplications, and recent studies have shown T1R2 functional divergence from canonical mammalian sweet taste perceptions, putatively as an adaptive mechanism to develop distinct feeding strategies in highly diverse aquatic habitats. We addressed this question in the carnivore fish gilthead seabream (Sparus aurata), a model species of aquaculture interest, and found that the saT1R gene repertoire consists of eight members including saT1R1, saT1R3 and six saT1R2a-f gene duplicates, adding further evidence to the evolutionary complexity of fishT1Rs families. To analyze saT1R taste functions, we first developed a stable gene reporter system based on Ca2+-dependent calcineurin/NFAT signaling to examine specifically in vitro the responses of a subset of saT1R heterodimers to L-amino acids (L-AAs) and sweet ligands. We show that although differentially tuned in sensitivity and magnitude of responses, saT1R1/R3, saT1R2a/R3 and saT1R2b/R3 may equally serve to transduce amino acid taste sensations. Furthermore, we present preliminary information on the potential involvement of the Gi protein alpha subunits saGαi1 and saGαi2 in taste signal transduction.