Miracle-dz/UniFAR-FTUs huggingface dataset:
S100A12 facilitates osteoclast differentiation from human monocytes

Osteoclasts play a critical role not only in bone homeostasis but also in inflammatory osteolysis, such as that occurring in inflammatory arthritis and systemic inflammation. In both inflammation conditions, inflammatory cytokines like Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α induce RANKL expression in osteoblasts, but the roles of these cytokines in osteoclast activation remain unclear. S100A12, an S100 family member, is a low-molecular-weight calcium-binding protein. Although it has a pro-inflammatory role, its effects on osteoclast differentiation have been unclear. Here we examined the direct effects of S100A12 on human osteoclasts in vitro. S100A12 facilitated osteoclast formation in the presence of RANKL, as judged by the cells’ morphology and elevated expression of osteoclast-related molecules, including NFATc1, ACP5, CALCR, and ITGβ3. In addition, S100A12 administration markedly enhanced the osteoclasts’ bone resorption ability, consistent with their increased expression levels of CTSK and CA2. Blocking RAGE and TLR4 cancelled the effects of S100A12. Our results indicate that S100A12 is a potential therapeutic target for inflammatory osteolysis.
R2s for Correlated Data: Phylogenetic Models, LMMs, and GLMMs

Many researchers want to report an R2 to measure the variance explained by a model. When the model includes correlation among data, such as phylogenetic models and mixed models, defining an R2 faces two conceptual problems. (i) It is unclear how to measure the variance explained by predictor (independent) variables when the model contains covariances. (ii) Researchers may want the R2 to include the variance explained by the covariances by asking questions such as “How much of the variance is explained by phylogeny? ” Here, I investigate three R2s for phylogenetic and mixed models. A least-squares R2ls is an extension of the ordinary least-squares R2 that weights residuals by variances and covariances estimated by the model; it is closely related to R2glmm proposed by Nakagawa & Schielzeth (2013). The conditional expectation R2ce is based on “predicting” each residual from the remaining residuals of the fitted model. The likelihood ratio R2lr was first used by Cragg & Uhler (1970) for logistic regression, and here is used with the standardization proposed by Nagelkerke (1991). These three R2s are formulated as partial R2s, making it possible to compare the contributions of mean components (regression coefficients in phylogenetic models and fixed effects in mixed models) and variance components (phylogenetic correlations and random effects) to the fit of models. The properties of the R2s for phylogenetic models were assessed using simulations for continuous and binary response data (phylogenetic generalized least squares and phylogenetic logistic regression). Because the R2s are designed broadly for any model for correlated data, the R2s were also compared for LMMs and GLMMs. R2ls, R2ce, and R2lr all have good performance, and each has advantages and disadvantages for different applications. These R2s are computed in the R package rr2 (https://github.com/arives/rr2). [Binomial regression, coefficient of determination, non-independent residuals, phylogenetic model, pseudo-likelihood]
Expected challenges of implementing universal pertussis vaccination during pregnancy in Quebec: a cross-sectional survey.

BACKGROUND Vaccination of all pregnant women with an acellular pertussis-containing vaccine (tetanus, diphtheria, pertussis [Tdap]) was recently recommended in Canada, ideally between 27 and 32 weeks of gestation. This study aimed to describe the existing model of prenatal care in Quebec and determine to what extent maternal vaccination against pertussis could be integrated into this model. METHODS In Quebec, health care is organized around Local Community Service Centres (LCSCs) that serve specific geographic areas. For each of 158 LCSCs (98.1% of LCSCs in the province), we invited 1 nurse or manager involved in prenatal care to participate in a cross-sectional Web-based survey. The structure of prenatal care visits and potential integration of maternal Tdap vaccination into the existing model were documented and compared according to urbanization level, determined with the use of census data. RESULTS A completed survey was obtained for 127 LCSCs (response rate 80.4%). Only 13 (10.2%) and 14 (11.0%) LCSCs offered on-site visits with a nurse for the majority of pregnant women during the second and third trimesters, respectively. A significantly higher proportion of rural LCSCs than urban LCSCs offered on-site visits to pregnant women in the third trimester (13 [18%] v. 1 [2%]) (p = 0.003). In at least 50 LCSC service areas (39.4%), vaccines were not available in most medical clinics offering prenatal care. INTERPRETATION Given the current situation in Quebec, implementing universal maternal Tdap vaccination may be challenging, which may result in suboptimal vaccine coverage among pregnant women. As other Canadian provinces may face similar issues, a priority will be to evaluate province-based implementation models to develop efficient ways to provide maternal Tdap vaccination across Canada.
Deep part induction from articulated object pairs

Object functionality is often expressed through part articulation - as when the two rigid parts of a scissor pivot against each other to perform the cutting function. Such articulations are often similar across objects within the same functional category. In this paper we explore how the observation of different articulation states provides evidence for part structure and motion of 3D objects. Our method takes as input a pair of unsegmented shapes representing two different articulation states of two functionally related objects, and induces their common parts along with their underlying rigid motion. This is a challenging setting, as we assume no prior shape structure, no prior shape category information, no consistent shape orientation, the articulation states may belong to objects of different geometry, plus we allow inputs to be noisy and partial scans, or point clouds lifted from RGB images. Our method learns a neural network architecture with three modules that respectively propose correspondences, estimate 3D deformation flows, and perform segmentation. To achieve optimal performance, our architecture alternates between correspondence, deformation flow, and segmentation prediction iteratively in an ICP-like fashion. Our results demonstrate that our method significantly outperforms state-of-the-art techniques in the task of discovering articulated parts of objects. In addition, our part induction is object-class agnostic and successfully generalizes to new and unseen objects.
Mutant MRPS5 affects mitoribosomal accuracy and confers stress‐related behavioral alterations

The 1555 A to G substitution in mitochondrial 12S A‐site rRNA is associated with maternally transmitted deafness of variable penetrance in the absence of otherwise overt disease. Here, we recapitulate the suggested A1555G‐mediated pathomechanism in an experimental model of mitoribosomal mistranslation by directed mutagenesis of mitoribosomal protein MRPS5. We first establish that the ratio of cysteine/methionine incorporation and read‐through of mtDNA‐encoded MT‐CO1 protein constitute reliable measures of mitoribosomal misreading. Next, we demonstrate that human HEK293 cells expressing mutant V336Y MRPS5 show increased mitoribosomal mistranslation. As for immortalized lymphocytes of individuals with the pathogenic A1555G mutation, we find little changes in the transcriptome of mutant V336Y MRPS5 HEK cells, except for a coordinated upregulation of transcripts for cytoplasmic ribosomal proteins. Homozygous knock‐in mutant Mrps5 V338Y mice show impaired mitochondrial function and a phenotype composed of enhanced susceptibility to noise‐induced hearing damage and anxiety‐related behavioral alterations. The experimental data in V338Y mutant mice point to a key role of mitochondrial translation and function in stress‐related behavioral and physiological adaptations.
Weight Reduction Goal Achievement Among Veterans With Mental Health Diagnoses

BACKGROUND: Despite the use of weight management programs among veterans, the impact of mental health diagnoses on weight reduction goal achievement is unknown. AIMS: We aimed to describe the prevalence and association of mental health diagnoses with a 5% weight reduction goal achievement. METHODS: Logistic regression was used to describe the association between mental health diagnoses and weight reduction goal achievement at 6, 12, and 24 months among 402 veterans enrolled in a weight management program. RESULTS: More than 43% of veterans had a mental health diagnoses, with depressive disorders, posttraumatic stress disorder (PTSD), and substance use disorders being the most prevalent. At all three times, simply having a mental health diagnosis was not associated with weight reduction goal achievement. Specific diagnoses were associated with a greater likelihood of achieving weight reduction goals at 12 months (PTSD and Drug Use Disorder) and 24 months (Anxiety Disorder and Other Mental Health Diagnosis). CONCLUSION: The findings suggest that unhealthy weight is quite common for individuals with mental health diagnoses; however, weight reduction goal achievement may be equally likely for those with and without mental health diagnoses. The prevalence of mental health diagnoses among veterans seeking weight reduction suggests that psychiatric nurses should be aware of this common comorbidity.
Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions

Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several advantages including low cost and reduced adverse effects led to consider light emitting diodes (LED) and even daylight as an alternative to use PDT to treat accessible lesions. In this study we examined the capacity of OR141, a recently identified non-porphyrin photosensitizer (PS), to exert significant cytotoxic effects in various models of skin lesions and tumors upon white light activation. Using different cancer cell lines, we first identified LED lamp as a particularly suited source of light to maximize anti-proliferative effects of OR141. We then documented that OR141 diffusion and light penetration into tumor spheroids both reached thresholds compatible with the induction of cell death deep inside these 3D culture models. We further identified Arlasove as a clinically suitable solvent for OR141 that we documented by using Franz cells to support significant absorption of the PS through human skin. Finally, using topical but also systemic administration, we validated growth inhibitory effects of LED-activated OR141 in mouse skin tumor xenograft and precancerous lesions models. Altogether these results open clinical perspectives for the use of OR141 as an attractive PS to treat superficial skin malignant and non-malignant lesions using affordable LED lamp for photoactivation.
La calidad de los objetos de aprendizaje. Una aplicación de la plantilla GEHOA

Resumen. El presente trabajo describe el proceso de evaluación, por parte de expertos desde el punto de vista tecnológico y pedagógico, de un Objeto de Aprendizaje (OA) para un curso de Cálculo Inicial de la Facultad de Ingeniería de la Universidad Nacional de Mar del Plata. Para la evaluación se utilizó la plantilla GEHOA (Guía de Evaluación Heurística para Objetos de Aprendizaje) combinada con la observación de experto/usuario, la cual complementó cualitativamente la evaluación numérica. Este enfoque metodológico pretende enriquecer la calidad técnica y pedagógica del OA y generar mejores recursos educativos digitales con el fin de promover instancias de producción de conocimientos en los estudiantes. En particular, a partir de la evaluación realizada a este OA, surgieron los aspectos favorables y desfavorables, y las modificaciones que son necesarias realizar antes de su implementación.
Influences of addition of malic acid or citric acid, Lactobacillus plantarum and their mixtures on fermentation quality, proteolysis and fatty acid composition of ensiled alfalfa

ABSTRACT The aim of this study was to evaluate the effect of two organic acids [malic acid (MA) and citric acid (CA)], Lactobacillus plantarum (LP) and their mixtures on the fermentation of alfalfa silage. The wilted and chopped alfalfa was ensiled in vacuum-sealed plastic bags (200–230 g per bag) with following additives: 0.5% distilled water (control), 0.5% DL-MA, 0.5% CA, LP (1 · 106 cfu/g), 0.5% DL-MA plus LP (MA+LP) or 0.5% CA plus LP (CA+LP) (application rates based on fresh weight). Each treatment had four replicates and was stored at room temperature. After 60 d of ensiling, decreases in pH, non-protein N (NPN) and increases in lactic acid were observed in all additive-treated silages (p < 0.01). Compared with treatment LP, higher pH and lower lactic acid concentrations were observed after MA or CA addition (p < 0.05) and further application of MA or CA together with LP did not promote lactic acid fermentation in ensiled alfalfa. Furthermore, additives decreased the proportion of saturated fatty acids and increased the proportion of polyunsaturated fatty acids in ensiled alfalfa, with the highest level in CA-treated silages (p < 0.05). Although MA and CA were not as effective as LP in improving silage fermentation quality, treatments MA+LP and CA+LP were more effective in decreasing silage NPN, and CA was most effective in inhibiting biohydrogenation of fatty acids in ensiled alfalfa.
Halophytism: What Have We Learnt From Arabidopsis thaliana Relative Model Systems?1[OPEN]

Halophytes are able to thrive in salt concentrations that would kill 99% of other plant species, and identifying their salt-adaptive mechanisms has great potential for improving the tolerance of crop plants to salinized soils. Much research has focused on the physiological basis of halophyte salt tolerance, whereas the elucidation of molecular mechanisms has traditionally lagged behind due to the absence of a model halophyte system. However, over the last decade and a half, two Arabidopsis (Arabidopsis thaliana) relatives, Eutrema salsugineum and Schrenkiella parvula, have been established as transformation-competent models with various genetic resources including high-quality genome assemblies. These models have facilitated powerful comparative analyses with salt-sensitive Arabidopsis to unravel the genetic adaptations that enable a halophytic lifestyle. The aim of this review is to explore what has been learned about halophytism using E. salsugineum and S. parvula. We consider evidence from physiological and molecular studies suggesting that differences in salt tolerance between related halophytes and salt-sensitive plants are associated with alterations in the regulation of basic physiological, biochemical, and molecular processes. Furthermore, we discuss how salt tolerance mechanisms of the halophytic models are reflected at the level of their genomes, where evolutionary processes such as subfunctionalization and/or neofunctionalization have altered the expression and/or functions of genes to facilitate adaptation to saline conditions. Lastly, we summarize the many areas of research still to be addressed with E. salsugineum and S. parvula as well as obstacles hindering further progress in understanding halophytism.
Benefits of Centralized ECG Reading in Clinical Oncology Studies

Background Many clinical trials of investigational oncologic agents utilize electrocardiogram (ECG) machine measurements of QTc, for inclusion/exclusion and dosing decisions, though their reliability in this setting has not been established. Methods We compared the digital ECG machine QTc measurements with those obtained by a centralized ECG core lab on more than 270,000 consecutive ECGs collected from 299 clinical oncology trials. Results The mean difference between the ECG machine measurements and the central measured QTcF was 1.8 ± 15.7 milliseconds. In addition, 29.7% of ECGs with an ECG machine-measured QTcF >450 milliseconds had a centrally measured QTcF <450 milliseconds, 44.6% of ECGs with an ECG machine-measured QTcF >470 milliseconds had a centrally measured QTcF <470 milliseconds, and 77.2% of ECGs with an ECG machine-measured QTcF >500 milliseconds had a centrally measured QTcF <500 milliseconds. The likelihood of a large discrepancy between the ECG machine- and centrally measured value for QTcF increased at both the high and low ends of the range of ECG machine QTcF measurements. Conclusions While on average ECG machine-measured QTcF values were very similar to the central core lab measurements; there were very significant discrepancies which will have important implications for patient recruitment for clinical oncology trials as well as for patient safety during dosing with new oncologic agents. Reliance on ECG machine QTc measurements during clinical oncology trials may lead to unnecessary exclusion of patients as well as unneeded treatment interruptions.
A qualitative study exploring views and experiences of people with stroke undergoing transcranial direct current stimulation and upper limb robot therapy

Abstract Background: Neurorehabilitation technologies used mainly in research such as robot therapy (RT) and transcranial direct current stimulation (tDCS) can promote upper limb motor recovery after stroke. Understanding the feasibility and efficacy of stroke rehabilitation technologies for upper limb impairments is crucial for effective implementation in practice. Small studies have explored views of RT by people with stroke; however experiences of people receiving tDCS in combination with RT have never been explored. Objective: To explore views and experiences of people with sub-acute and chronic stroke that had previously taken part in a randomised controlled trial involving tDCS and RT for their impaired upper limb. Methods: An interview study includes open and closed questions. Face-to-face interviews were audio recorded. Open-ended question responses were transcribed and analyzed using thematic analysis; closed questions were analyzed using descriptive analysis. Results: Participants felt that RT was enjoyable (90%) and beneficial for their affected arm (100%). From the open question data, it was found that the intervention was effective for the impaired arm especially in the sub-acute stage. Main reported concerns were that tDCS caused painful, itching and burning sensations and RT was sometimes tiring and difficult. Participants recommended that future research should focus on designing a more comfortable method of tDCS and develop a robot that promotes hand movements. Conclusions: This study provides new knowledge about the benefits and barriers associated with these technologies which are crucial to the future effective implementation of these tools in practice.
Reliability and validity of the Hebrew version of the Nijmegen Continuity Questionnaire for measuring patients' perceived continuity of care in oral anticancer therapy

To assess the validity and reliability of the Nijmegen Continuity Questionnaire in Hebrew (NCQ-H) for measuring patients' perceived continuity of care in the multiprovider setting of oral anticancer therapy (OACT). Following forward-backward translation of the original instrument into Hebrew, the NCQ-H was administered to adult cancer patients in five oncology centres in Israel, 2-3 months after initiation of OACT (either targeted, hormonal or chemotherapy). Confirmatory factor analysis and Cronbach's alpha were used to assess the validity and reliability of the NCQ-H respectively. A total of 135 patients completed the questionnaire. The postanalysis models for measuring "personal continuity with care provider" (eight items for each provider: the oncology specialist and the primary care physician), and "team/cross-boundary continuity" (four items for each setting: within the oncology team, and between the oncology specialist and the primary care physician) showed good fit for the observed data (root-mean-square error of approximation (RMSEA) = 0.02; RMSEA = 0.015; for each model respectively). Cronbach's alpha was 0.79-0.95 for all subscales. Conclusions. This study provides preliminary evidence for the reliability and validity of the NCQ-H in assessing cancer patients' experience with continuity of care and for its usability in the context of OACT.
Interaction between step-to-step variability and metabolic cost of transport during human walking

ABSTRACT Minimizing the metabolic cost of transport can affect selection of the preferred walking speed. While many factors can affect metabolic cost of transport during human walking, its interaction with step-to-step variability is unclear. Here, we aimed to determine the interaction between metabolic cost of transport and step length variability during human walking at different speeds. In particular, two aspects of step length variability were analyzed: the amount of variations (‘variations’) and the organization of the step-to-step fluctuations (‘fluctuations’). Ten healthy, young participants walked on a treadmill at five speeds, ranging from 0.75 to 1.75 m s−1. Metabolic cost of transport, step length variations (coefficient of variation) and step length fluctuations (quantified via detrended fluctuation analysis) were calculated. A mixed-model ANOVA revealed that variations and walking speed were strong predictors of metabolic cost of transport (R2=0.917, P<0.001), whereas fluctuations were not. Preferred walking speed (1.05±0.20 m s−1) was not significantly different from the speed at which metabolic cost of transport was minimized (1.04±0.05 m s−1; P=0.792), nor from the speed at which fluctuations were most persistent (1.00±0.41 m s−1; P=0.698). The minimization of variations occurred at a faster speed (1.56±0.17 m s−1) than the preferred walking speed (P<0.001). Step length variations likely affect metabolic cost of transport because greater variations are indicative of suboptimal, mechanically inefficient steps. Fluctuations have little or no effect on metabolic cost of transport, but still may relate to preferred walking speed. Summary: Overall step length variations, but not the organization of fluctuations, may predict changes in energy cost during walking.