Miracle-dz/UniFAR-FTUs huggingface dataset:
Erenumab and OnabotulinumtoxinA Combination Therapy for the Prevention of Intractable Chronic Migraine without Aura: A Retrospective Analysis

Abstract Erenumab is a monoclonal antibody that mediates calcitonin-gene-related peptide (CGRP), a pro-inflammatory polypeptide implicated in migraine pathology, by targeting its receptor. To date, no clinical trial has evaluated combination therapy with both erenumab and onabotulinumtoxinA therapy for the treatment of chronic migraine. We conducted a retrospective chart review of 78 patients to investigate if the addition of erenumab to patients with chronic migraines receiving onabotulinumtoxinA had a decrease in their total monthly headache days (MHDs) and monthly migraine days (MMD). At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 ± 8.7 and mean MMDs were 15.8 ± 8.3, and 65 patients (83.3%) failed at least three preventative therapies. Our results demonstrated a significant reduction in MHDs and MMDs at 30- (-6.8 MHDs; p < 0.001, −7.0 MMDs; p < 0.001), 60- (-7.2 MHDs; p < 0.001, −6.7 MMDs; p < 0.001), and 90 days (-8.1 MHDs; p < 0.001, −7.4 MMDs; p < 0.001). Thus, the results of this study suggest favorable outcomes with the addition of erenumab to patients who were still suffering while receiving onabotulinumtoxinA therapy. Additional investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers.
Prevalence of and lifestyle factors associated with metabolic syndrome determined using multi-level models in Chinese adults from a cross-sectional survey

Abstract People living in the same area are more likely to experience similar socioeconomic characteristics, which leads to cluster effect and influences the generalizability of data regarding metabolic syndrome (MetS). However, previous studies did not consider or adjust for the cluster effect of living circumstances. The aim of this study was to determine the prevalence of MetS and associated lifestyle factors in Chinese adults 18 to 80 years of age, using multi-level generalized estimation equation (GEE). The participants came from a large-scale cross-sectional population survey. A total of 28,062 participants underwent all the blood tests. Participants meeting at least 3 of the 5 diagnostic criteria were defined as having MetS. Multi-level GEE was used to evaluate the relationship between MetS and lifestyle covariates to control the cluster effect of living circumstances. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of each relationship. A total of 65.70% of the participants had at least 1 clinical feature of MetS, and 2926 were diagnosed with MetS (prevalence 14.03%). 32.74%, 18.93%, 10.25%, 3.25%, and 0.53% of the participants had 1, 2, 3, 4, and 5 components, respectively. The prevalence of MetS in men (12.31%) was lower than in women (15.57%). After controlling for the cluster effect of living circumstances, many demographic and lifestyle characteristics were associated with MetS. Overweight (OR = 1.670, 95%CI: 1.600–1.743), obesity (OR = 2.287, 95% CI: 2.136–2.449), current alcohol consumption (OR = 1.053, 95% CI: 1.020–1.086), physical labor (OR=1.070, 95% CI: 1.040–1.101), a high-salt diet (OR=1.040, 95% CI: 1.009–1.071), hyperuricemia (OR=1.264, 95% CI: 1.215–1.316), short sleep duration (OR=1.032, 95% CI: 1.009–1.055), and a family history of cardiovascular disease (OR=1.065, 95% CI: 1.019–1.113), or cerebrovascular disease (OR=1.055, 95% CI: 1.007–1.104) increased the risk of MetS. The risk of MetS increased 6.9% (OR = 1.069, 95% CI: 1.053–1.085) with each 5% increase in body fat percentage. MetS has become a serious public health challenge in China. Many lifestyle factors have been found to be closely associated with MetS, including obesity, a high-salt diet, alcohol consumption, and short sleep duration. Therefore, changes in lifestyle are very important for adults to reduce the prevalence of MetS.
Experimental and Theoretical Studies of a Spirostannole and Formation of a Pentaorganostannate †

A new spirostannole, 1,1′,3,3′-tetrakis(5-methylthiophen-2-yl)-4,4′,5,5′,6,6′,7,7′-octahydro-2,2′-spirobi[benzo[c]stannole] (4), is synthesised and the molecular structure is compared with the optimised geometry from DFT calculations. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are twice degenerated and show a small HOMO–LUMO energy gap of 3.2 eV. In addition, cyclic voltammetry measurements are conducted and three redox processes are observed. Absorption and emission spectra show maxima at λabs,max 436 nm and λem,max 533 nm, respectively. Spirostannole 4 is a strongly absorbing material, but an extremely weak emitter in solution at 295.15 K. However, when the solution is cooled from 280 to 80 K, the emission becomes visible. The reaction of spirostannole 4 with methyllithium is monitored by NMR spectroscopy at 238.15 K. The 119Sn{1H} NMR signal shifts from −36.0 (4) to −211.0 ppm, which is indicative of the formation of the lithium pentaorganostannate 5. The complex is thermally instable at 295.15 K, but insights into the molecular structure and electronic behaviour are obtained by DFT and TD-DFT calculations.
Strategies for Microbial Decontamination of Fresh Blueberries and Derived Products

Increasing consumption of blueberries is associated with appreciation of their organoleptic properties together with their multiple health benefits. The increasing number of outbreaks caused by pathogenic microorganisms associated with their consumption in the fresh state and the rapid spoilage of this product which is mainly caused by moulds, has led to the development and evaluation of alternatives that help mitigate this problem. This article presents different strategies ranging from chemical, physical and biological technologies to combined methods applied for microbial decontamination of fresh blueberries and derived products. Sanitizers such as peracetic acid (PAA), ozone (O3), and electrolyzed water (EOW), and physical technologies such as pulsed light (PL) and cold plasma (CP) are potential alternatives to the use of traditional chlorine. Likewise, high hydrostatic pressure (HHP) or pulsed electrical fields (PEF) successfully achieve microbial reductions in derivative products. A combination of methods at moderate intensities or levels is a promising strategy to increase microbial decontamination with a minimal impact on product quality.
The association between parent-reported child disaster reactions and posttraumatic stress disorder in parent survivors of disasters and terrorism.

BACKGROUND Disaster studies establishing an association between parent and child disaster reactions usually discuss results in terms of the influence of parents on their children. This study explores a complementary interpretation of this association by focusing on the potential influence of children on their parents. METHODS Investigations of 5 disasters and terrorist events included a combined sample of 556 survivor parents and their 1,066 children. Structured diagnostic interviews were administered to survivor parents to obtain diagnostic assessment of pre- and post-disaster psychiatric disorders. Parent survivors also provided information about their own demographics and disaster experiences and about each child's demographics, disaster-related experiences, and disaster reactions (posttraumatic stress symptoms, behavior changes, increased school behavior problems, and decline in grades). RESULTS The results revealed an association of parent posttraumatic stress disorder with parent injury in the disaster, parent lifetime pre-disaster psychiatric disorder, parent direct exposure to disaster trauma, and each of 4 child disaster outcomes. CONCLUSIONS The analysis suggests the potential for child factors to influence survivors' reactions. Clinicians should query survivors about their children's reactions and ascertain the need for services for the children. Future research should examine the potential that children's reactions influence parent outcomes.
Silencing Orco Impaired the Ability to Perceive Trail Pheromones and Affected Locomotion Behavior in Two Termite Species

Abstract Sophisticated social behaviors in termite colonies are mainly regulated via chemical communication of a wide range of pheromones. Trail pheromones play important roles in foraging behavior and building tunnels and nests in termites. However, it is almost unclear how termites perceive trail pheromones. Here, we cloned and sequenced of olfactory co-receptor (Orco) genes from the two termites Reticulitermes chinensis Snyder (Isoptera: Rhinotermitidae) and Odontotermes formosanus (Shiraki) (Isoptera:Termitidae), and then examined their responses to trail pheromones after silencing Orco through RNA interference (RNAi). We found that Orco knockdown impaired their ability to perceive trail pheromones and resulted in the disability of following pheromone trails in the two termite species. Our locomotion behavior assays further showed that Orco knockdown significantly decreased the distance and velocity in the two termite species, but significantly increased the angular velocity and turn angle in the termite R. chinensis. These findings strongly demonstrated that Orco is essential for termites to perceive their trail pheromones, which provides a potential way to control termite pests by damaging olfactory system.
Duration of antiretroviral therapy among people living with HIV and incidence of hypertension in Ghana

Understanding the differential rates of incident hypertension among People Living with HIV (PLWH) based of duration of exposure to combination antiretroviral therapy (cART) may provide insights into the pathogenesis of hypertension in this population. Utilizing the dataset of a prospective study conducted at a Ghanaian tertiary medical center, we evaluated factors associated with incident hypertension among PLWH previously naïve to cART before study enrollment (cART newly prescribed group, n = 221) versus PLWH established on cART for at least a year (cART established group, n = 212). New‐onset hypertension was diagnosed as clinic BP > 140/90 mmHg on two separate clinic visits over 12‐month follow‐up. Cox proportional hazards regression models were used to assess factors associated with incident hypertension. Mean age of new versus cART established was 41.1 ± 8.2 versus 45.1 ± 8.6 years (p < .001), with more women in the cART established group (68.3 vs. 82%, p = .0009). There were 105 (24.3%) episodes of incident hypertension over 328 person‐years follow‐up (PYFU), incidence rate of 320.1 (95% CI: 263.1‐385.9)/1000 PYFU, with higher rates in new versus cART established (476.6/1000 PYFU vs. 222.8/1000 PYFU, p = 0.0002). Overall, age by increasing decile (aHR 0.76; 95% CI: 0.59‐0.98), log HIV‐1 viral load (aHR 1.16; 1.04‐1.35), and use of tenofovir (aHR 1.66; 1.04‐2.64) were associated with incident hypertension. While CD4 counts, age, BMI, pre‐diabetes, and urban/peri‐urban residency were independently associated with hypertension in the cART established group; no independent predictors were identified among the cART newly prescribed group. Further studies to explore the potential mechanisms underlying incidence of hypertension in PLWH are warranted.
Ameliorative Effect of Linalool in Cisplatin-Induced Nephrotoxicity: The Role of HMGB1/TLR4/NF-κB and Nrf2/HO1 Pathways

Background: The monoterpene linalool is a well-known essential oil component produced by several aromatic plants. Cisplatin is a widely used anticancer drug that produces many side effects, particularly nephrotoxicity. Here, we aimed to inspect linalool’s protective activity against cisplatin-induced nephrotoxicity and explore part of the underlying mechanisms. Methods: Male Wistar rats were given linalool (50 and 100 mg/kg/day orally) for 15 days; then challenged with cisplatin (8 mg/kg) on the 12th day. Renal function parameters, oxidative stress, inflammatory and apoptotic markers, and toll-like receptor pathway gene, and protein expressions were investigated. Histopathology, immunohistochemistry, and cell-line mediated cytotoxicity assays were conducted. Results: Linalool ameliorated kidney function after cisplatin challenge and managed all oxidation system parameters including GSH, SOD, CAT, MDA, NADPH, and particularly the Nrf2-mediated pathway markers. Linalool decreased TLR4, MYD88 and TRIF gene and protein expressions; diminished related inflammatory mediators such as TNF-α, IL-1β, IL-6, and NF-κB; and down-regulated HMBG1. Linalool mitigated cisplatin-induced apoptotic markers such as caspase 3, caspase 9, and Bax expression, and boosted the anti-apoptotic Bcl2 expression. Linalool potentiated the cytotoxic effect of cisplatin when investigated on HeLa and PC3 human cancer cell lines. Conclusion: Linalool could protect against cisplatin-induced kidney function and tissue damage.
Caregiver experience and perceived acceptability of a novel near point-of-care early infant HIV diagnostic test among caregivers enrolled in the PMTCT program, Myanmar: A qualitative study

Background The majority of HIV infection among children occurs through mother-to-child transmission. HIV exposed infants are recommended to have virological testing at birth or 4–6 weeks of age but challenges with centralized laboratory-based testing in Myanmar result in low testing rates and delays in result communication and treatment initiation. Decentralized point-of-care (POC) testing when integrated in prevention of mother-to-child transmission of HIV (PMTCT) services, can be an alternative to increase coverage of early infant diagnosis (EID) and timely engagement in HIV treatment and care. Aim This paper aims to explore experiences of caregivers of HIV-exposed infants enrolled in the PMTCT program in Myanmar and the perceived acceptability of point-of-care EID testing compared to conventional centralised laboratory-based testing. Methods This is a sub-study of the cluster randomised controlled stepped-wedge trial (Trial registration number: ACTRN12616000734460) that assessed the impact of near POC EID testing using Xpert HIV-1 Qual assay in four public hospitals in Myanmar. Caregivers of infants who were enrolled in the intervention phase of the main study, had been tested with both Xpert and standard of care tests and had received the results were eligible for this qualitative study. Semi-structured interviews were conducted with 23 caregivers. Interviews were audio recorded, transcribed verbatim and translated into English. Thematic data analysis was undertaken using NVivo 12 Software (QSR International). Results The majority of caregivers were satisfied with the quality of care provided by PMTCT services. However, they encountered social and financial access barriers to attend the PMTCT clinic regularly. Mothers had concerns about community stigma from the disclosure of their HIV status and the potential consequences for their infants. While medical care at the PMTCT clinics was free, caregivers sometimes experienced financial difficulties associated with out-of-pocket expenses for childbirth and transportation. Some caregivers had to choose not to attend work (impacting their income) or the adult antiretroviral clinic in order to attend the paediatric PMTCT clinic appointment. The acceptability of the Xpert testing process was high among the caregiver participants and more than half received the Xpert result on the same day as testing. Short turnaround time of the near POC EID testing enabled the caregivers to find out their infants’ HIV status quicker, thereby shortening the stressful waiting time for results. Conclusion Our study identified important access challenges facing caregivers of HIV exposed infants and high acceptability of near POC EID testing. Improving the retention rate in the PMTCT and EID programs necessitates careful attention of program managers and policy makers to these challenges, and POC EID represents a potential solution.
Gut microbiota ecology: Biodiversity estimated from hybrid neutral-niche model increases with health status and aging

In this work we propose an index to estimate the gut microbiota biodiversity using a modeling approach with the aim of describing its relationship with health and aging. The gut microbiota, a complex ecosystem that links nutrition and metabolism, has a pervasive effect on all body organs and systems, undergoes profound changes with age and life-style, and substantially contributes to the pathogenesis of age-related diseases. For these reasons, the gut microbiota is a suitable candidate for assessing and quantifying healthy aging, i.e. the capability of individuals to reach an advanced age, avoiding or postponing major age-related diseases. The importance of the gut microbiota in health and aging has been proven to be related not only to its taxonomic composition, but also to its ecological properties, namely its biodiversity. Following an ecological approach, here we intended to characterize the relationship between the gut microbiota biodiversity and healthy aging through the development a parsimonious model of gut microbiota from which biodiversity can be estimated. We analysed publicly available metagenomic data relative to subjects of different ages, countries, nutritional habits and health status and we showed that a hybrid niche-neutral model well describes the observed patterns of bacterial relative abundance. Moreover, starting from such ecological modeling, we derived an estimate of the gut microbiota biodiversity that is consistent with classical indices, while having a higher statistical power. This allowed us to unveil an increase of the gut microbiota biodiversity during aging and to provide a good predictor of health status in old age, dependent on life-style and aging disorders.
miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts

Increasing evidence has suggested a critical role for endothelial‐to‐mesenchymal transition (EndoMT) in a variety of pathological conditions. MicroRNA‐200c‐3p (miR‐200c‐3p) has been implicated in epithelial‐to‐mesenchymal transition. However, the functional role of miR‐200c‐3p in EndoMT and neointimal hyperplasia in artery bypass grafts remains largely unknown. Here we demonstrated a critical role for miR‐200c‐3p in EndoMT. Proteomics and luciferase activity assays revealed that fermitin family member 2 (FERM2) is the functional target of miR‐200c‐3p during EndoMT. FERMT2 gene inactivation recapitulates the effect of miR‐200c‐3p overexpression on EndoMT, and the inhibitory effect of miR‐200c‐3p inhibition on EndoMT was reversed by FERMT2 knockdown. Further mechanistic studies revealed that FERM2 suppresses smooth muscle gene expression by preventing serum response factor nuclear translocation and preventing endothelial mRNA decay by interacting with Y‐box binding protein 1. In a model of aortic grafting using endothelial lineage tracing, we observed that miR‐200c‐3p expression was dramatically up‐regulated, and that EndoMT contributed to neointimal hyperplasia in grafted arteries. MiR‐200c‐3p inhibition in grafted arteries significantly up‐regulated FERM2 gene expression, thereby preventing EndoMT and reducing neointimal formation. Importantly, we found a high level of EndoMT in human femoral arteries with atherosclerotic lesions, and that miR‐200c‐3p expression was significantly increased, while FERMT2 expression levels were dramatically decreased in diseased human arteries. Collectively, we have documented an unexpected role for miR‐200c‐3p in EndoMT and neointimal hyperplasia in grafted arteries. Our findings offer a novel therapeutic opportunity for treating vascular diseases by specifically targeting the miR‐200c‐3p/FERM2 regulatory axis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Life Cycle Sustainability Performance Assessment Method for Comparison of Civil Engineering Works Design Concepts: Case Study of a Bridge

Standardized and transparent life cycle sustainability performance assessment methods are essential for improving the sustainability of civil engineering works. The purpose of this paper is to demonstrate the potential of using a life cycle sustainability assessment method in a road bridge case study. The method is in line with requirements of relevant standards, uses life cycle assessment, life cycle costs and incomes, and environmental externalities, and applies normalization and weighting of indicators. The case study involves a short-span bridge in a design-build infrastructure project, which was selected for its generality. Two bridge design concepts are assessed and compared: a concrete slab frame bridge and a soil-steel composite bridge. Data available in the contractor’s tender phase are used. The two primary aims of this study are (1) to analyse the practical application potential of the method in carrying out transparent sustainability assessments of design concepts in the early planning and design stages, and (2) to examine the results obtained in the case study to identify indicators in different life cycle stages and elements of the civil engineering works project with the largest impacts on sustainability. The results show that the method facilitates comparisons of the life cycle sustainability performance of design concepts at the indicator and construction element levels, enabling better-informed and more impartial design decisions to be made.
Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.