Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of c-Raf Stability through the CTLH Complex

c-Raf is a central component of the extracellular signal-regulated kinase (ERK) pathway which is implicated in the development of many cancer types. RanBPM (Ran-Binding Protein M) was previously shown to inhibit c-Raf expression, but how this is achieved remains unclear. RanBPM is part of a recently identified E3 ubiquitin ligase complex, the CTLH (C-terminal to LisH) complex. Here, we show that the CTLH complex regulates c-Raf expression through a control of its degradation. Several domains of RanBPM were found necessary to regulate c-Raf levels, but only the C-terminal CRA (CT11-RanBPM) domain showed direct interaction with c-Raf. c-Raf ubiquitination and degradation is promoted by the CTLH complex. Furthermore, A-Raf and B-Raf protein levels are also regulated by the CTLH complex, indicating a common regulation of Raf family members. Finally, depletion of CTLH subunits RMND5A (required for meiotic nuclear division 5A) and RanBPM resulted in enhanced proliferation and loss of RanBPM promoted tumour growth in a mouse model. This study uncovers a new mode of control of c-Raf expression through regulation of its degradation by the CTLH complex. These findings also uncover a novel target of the CTLH complex, and suggest that the CTLH complex has activities that suppress cell transformation and tumour formation.
A Comprehensive Model of Factors Associated With Capability to “Live Well” for Family Caregivers of People Living With Mild-to-Moderate Dementia

Introduction: Understanding key influences on outcomes for caregivers of people with dementia is hampered by inconsistent conceptualization and measurement of outcomes and limited evidence about the relative impact of different variables. We aimed to address these issues. Methods: We analyzed data from 1283 caregivers of community-dwelling individuals with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life cohort study. We generated a “living well” latent factor from measures of quality of life, satisfaction with life, and well-being. We used structural equation modelling to derive latent variables for 7 domains reflecting caregivers’ perceptions of their personal resources and experiences, and to examine the associations with caregivers’ perceptions of their capability to “live well. ” Results: The domain of psychological characteristics and psychological health was most strongly related to living well [2.53; 95% confidence interval (CI), 2.08-2.97], followed by physical fitness and physical health (1.48; 95% CI, 1.04-1.91) and experiencing caregiving (1.34; 95% CI, 0.99-1.70). Social capitals, assets and resources (0.68; 95% CI, 0.35-1.00) and relationship with the person with dementia (−0.22; 95% CI, −0.41 to −0.03) had smaller, significant associations. Social location (0.28; 95% CI, −0.33 to 0.89) and managing everyday life with dementia (0.06; 95% CI, −0.15 to 0.28) were not significantly associated with living well. Discussion: These findings demonstrate the importance of supporting caregivers’ psychological and physical health and their ability to develop and maintain positive coping strategies, as well as enabling them to maintain vital social capitals, assets and resources.
The mystery of the origins of Cebus albifrons malitiosus and Cebus albifrons hypoleucus: mitogenomics and microsatellite analyses revealed an amazing evolutionary history of the Northern Colombian white-fronted capuchins

Abstract Knowledge of the genetic units of species is fundamental to the conservation of biodiversity. This is true for all regions, including the Neotropics where the Earth has its greatest diversity, including roughly 34% of primate species, a group that has almost 60% of its taxa threatened with extinction. The untufted (gracile) capuchins are medium-sized Neotropical primates, traditionally classified in four species: Cebus albifrons, C. capucinus, C. olivaceus, and C. kaapori. They have a very confusing intra-specific systematics with a large number of fragmented and isolated populations throughout their geographical distributions. We sequenced a large sample of gracile capuchins, including all of the recognized species, to offset the paucity of phylogenic and phylogeographic data regarding this group and to try to understand their phylogeny and evolution. A set of 189 gracile and robust capuchins were sequenced for their mitogenomes whereas another set of 394 gracile and robust capuchins were sequenced at two individual mitochondrial genes (mtCOI-COII). Additionally, 41 Colombian gracile capuchins were geno typified at eight nuclear DNA microsatellites. Our main findings are as follows: (1) Nineteen different groups of gracile capuchin were detected with the mitogenomics data set and more than twenty significant groups and sub-groups were identified with the mtCOI-COII genes; (2) The temporal splits of the older gracile capuchin haplogroups expanded between 2 and 4 million years ago (MYA), during the Pliocene; (3) The two most northern taxa of Colombian C. albifrons (malitiosus and hypoleucus) are the same taxon (C. a. hypoleucus) as was claimed by Cabrera. This taxon represents an old colonization event from the Amazon to current northern Colombia. It is intensely hybridized (evidence from both mitochondrial and nuclear genes) with a haplogroup of C. capucinus (H3) and also has an influx of robust capuchins; (4) Three different and independent migrations of C. albifrons from the Amazon arrived to northern Colombia giving rise to C. a. hypoleucus (including malitiosus), C. a versicolor (including leucocephalus, cesarae, and pleei), and C. a. adustus; (5) On the Caribbean island of Trinidad, two different gracile capuchin taxa exist, one autochthonous, which could correspond to a fourth migration into northwestern South America (C. a. trinitatis) and probably another one, introduced more recently (C. olivaceus brunneus); (6) The values of the genetic distance analyses, the inexistence of reciprocal mitochondrial monophylia for many clades of gracile capuchins and the strong hybridization detected with nuclear microsatellites, especially among hypoleucus (malitiosus), C. capucinus-H3, versicolor, and cesarae, support that all the gracile capuchins belong to one unique superspecies: C. capucinus (senior name for all the gracile capuchins).
Construction fatality due to electrical contact in Ontario, Canada, 1997-2007.

BACKGROUND Electrical contact is a leading cause of occupational fatality in the construction industry. However, research on the factors that contribute to electricity-related fatality in construction is limited. OBJECTIVES To characterize, using an adapted Haddon's Matrix, the factors that contribute to electricity-related occupational fatalities in the construction industry in Ontario, Canada. METHODS Coroner's data on occupational electricity-related fatalities between 1997-2007 in the construction industry were acquired from the Ontario Ministry of Labour. Using an adapted Haddon's Matrix, we characterized worker, agent, and environmental characteristics of electricity-related occupational fatalities in the province through a narrative text analysis. RESULTS Electrical contact was responsible for 15% of all occupational fatalities among construction workers in Ontario. Factors associated with said occupational fatalities included direct contact with electrical sources, lower voltage sources, and working outdoors. CONCLUSIONS This study provides a profile of electricity-related occupational fatalities among construction workers in Ontario, and can be used to inform safety regulations.
Effect of Calcium Precursor on the Bioactivity and Biocompatibility of Sol-Gel-Derived Glasses

This study investigated the impact of different calcium reagents on the morphology, composition, bioactivity and biocompatibility of two-component (CaO-SiO2) glasses produced by the Stöber process with respect to their potential application in guided tissue regeneration (GTR) membranes for periodontal repair. The properties of the binary glasses were compared with those of pure silica Stöber particles. The direct addition of calcium chloride (CC), calcium nitrate (CN), calcium methoxide (CM) or calcium ethoxide (CE) at 5 mol % with respect to tetraethyl orthosilicate in the reagent mixture gave rise to textured, micron-sized aggregates rather than monodispersed ~500 nm spheres obtained from the pure silica Stöber synthesis. The broadening of the Si-O-Si band at ~1100 cm−1 in the infrared spectra of the calcium-doped glasses indicated that the silicate network was depolymerised by the incorporation of Ca2+ ions and energy dispersive X-ray analysis revealed that, in all cases, the Ca:Si ratios were significantly lower than the nominal value of 0.05. The distribution of Ca2+ ions was also found to be highly inhomogeneous in the methoxide-derived glass. All samples released soluble silica species on exposure to simulated body fluid, although only calcium-doped glasses exhibited in vitro bioactivity via the formation of hydroxyapatite. The biocompatibilities of model chitosan-glass GTR membranes were assessed using human MG63 osteosarcoma cells and were found to be of the order: CN < pure silica ≈ CC << CM ≈ CE. Calcium nitrate is the most commonly reported precursor for the sol-gel synthesis of bioactive glasses; however, the incomplete removal of nitrate ions during washing compromised the cytocompatibility of the resulting glass. The superior bioactivity and biocompatibility of the alkoxide-derived glasses is attributed to their ease of dissolution and lack of residual toxic anions. Overall, calcium ethoxide was found to be the preferred precursor with respect to extent of calcium-incorporation, homogeneity, bioactivity and biocompatibility.
Factors Influencing Quality of Life in Breast Cancer Patients Six Months after the Completion of Chemotherapy

Purpose: To assess breast cancer patients’ quality of life six months after the completion of adjuvant chemotherapy, and to investigate factors affecting this. Methods: The study was conducted in one large hospital located in a major Greek city. A convenience sample of 61 breast cancer outpatients was recruited. A questionnaire, including the SF-36 scale and questions regarding demographic and clinical information, was used to collect data. Results: The mean age of the patients was 51.52 ± 12.10. The effect of age on the physical role was significant (p = 0.003). Τhe effect of menopausal status on physical role was also found to be significant (p = 0.003); this might be explained by age. Regarding the treatment type, patients who received hormone therapy in addition to surgery and chemotherapy reported a significantly higher quality of life in terms of bodily pain (p = 0.04) and vitality (p = 0.04) than patients who underwent only surgery and chemotherapy. Conclusions: Quality of life is affected by factors such as age, menopausal status, and previous therapy. Health care professionals should be more aware of the factors that influence the quality of life domains (physical role, bodily pain, vitality) within this group of cancer patients in order to meet their needs following acute treatment.
Quantitative Measurement and Evaluation of Red Blood Cell Aggregation in Normal Blood Based on a Modified Hanai Equation

The aggregation of red blood cells (RBCs) in normal blood (non-coagulation) has been quantitatively measured by blood pulsatile flow based on multiple-frequency electrical impedance spectroscopy. The relaxation frequencies fc under static and flowing conditions of blood pulsatile flow are utilized to evaluate the RBC aggregation quantitatively with the consideration of blood flow factors (RBC orientation, deformation, thickness of electrical double layer (EDL)). Both porcine blood and bovine blood are investigated in experiments, for the reason that porcine blood easily forms RBC aggregates, while bovine blood does not. The results show that the relaxation frequencies fc of porcine blood and bovine blood present opposite performance, which indicates that the proposed relaxation frequency fc is efficient to measure RBCs aggregation. Furthermore, the modified Hanai equation is proposed to quantitatively calculate the influence of RBCs aggregation on relaxation frequency fc. The study confirms the feasibility of a high speed, on-line RBC aggregation sensing method in extracorporeal circulation systems.
Machine Learning Analyses on Data including Essential Oil Chemical Composition and In Vitro Experimental Antibiofilm Activities against Staphylococcus Species

Biofilm resistance to antimicrobials is a complex phenomenon, driven not only by genetic mutation induced resistance, but also by means of increased microbial cell density that supports horizontal gene transfer across cells. The prevention of biofilm formation and the treatment of existing biofilms is currently a difficult challenge; therefore, the discovery of new multi-targeted or combinatorial therapies is growing. The development of anti-biofilm agents is considered of major interest and represents a key strategy as non-biocidal molecules are highly valuable to avoid the rapid appearance of escape mutants. Among bacteria, staphylococci are predominant causes of biofilm-associated infections. Staphylococci, especially Staphylococcus aureus (S. aureus) is an extraordinarily versatile pathogen that can survive in hostile environmental conditions, colonize mucous membranes and skin, and can cause severe, non-purulent, toxin-mediated diseases or invasive pyogenic infections in humans. Staphylococcus epidermidis (S. epidermidis) has also emerged as an important opportunistic pathogen in infections associated with medical devices (such as urinary and intravascular catheters, orthopaedic implants, etc.), causing approximately from 30% to 43% of joint prosthesis infections. The scientific community is continuously looking for new agents endowed of anti-biofilm capabilities to fight S. aureus and S epidermidis infections. Interestingly, several reports indicated in vitro efficacy of non-biocidal essential oils (EOs) as promising treatment to reduce bacterial biofilm production and prevent the inducing of drug resistance. In this report were analyzed 89 EOs with the objective of investigating their ability to modulate bacterial biofilm production of different S. aureus and S. epidermidis strains. Results showed the assayed EOs to modulated the biofilm production with unpredictable results for each strain. In particular, many EOs acted mainly as biofilm inhibitors in the case of S. epidermidis strains, while for S. aureus strains, EOs induced either no effect or stimulate biofilm production. In order to elucidate the obtained experimental results, machine learning (ML) algorithms were applied to the EOs’ chemical compositions and the determined associated anti-biofilm potencies. Statistically robust ML models were developed, and their analysis in term of feature importance and partial dependence plots led to indicating those chemical components mainly responsible for biofilm production, inhibition or stimulation for each studied strain, respectively.
Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis

Objective— Smooth muscle cells (SMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute at least 50% of atheroma foam cells. In mice, SMCs contribute fewer total lesional cells. The purpose of this study was to determine the contribution of SMCs to total foam cells in apolipoprotein E-deficient (ApoE−/−) mice, and the utility of these mice to model human SMC foam cell biology and interventions. Approach and Results— Using flow cytometry, foam cells in the aortic arch of ApoE−/− mice were characterized based on the expression of leukocyte-specific markers. Nonleukocyte foam cells increased from 37% of total foam cells in 27-week-old to 75% in 57-week-old male ApoE−/− mice fed a chow diet and were ≈70% in male and female ApoE−/− mice following 6 weeks of Western diet feeding. A similar contribution to total foam cells by SMCs was found using SMC-lineage tracing ApoE−/− mice fed the Western diet for 6 or 12 weeks. Nonleukocyte foam cells contributed a similar percentage of total atheroma cholesterol and exhibited lower expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1) when compared with leukocyte-derived foam cells. Conclusions— Consistent with previous studies of human atheromas, we present evidence that SMCs contribute the majority of atheroma foam cells in ApoE−/− mice fed a Western diet and a chow diet for longer periods. Reduced expression of ABCA1, also seen in human intimal SMCs, suggests a common mechanism for formation of SMC foam cells across species, and represents a novel target to enhance atherosclerosis regression.
Localization of TMC1 and LHFPL5 in auditory hair cells in neonatal and adult mice

The channel that governs mechanotransduction (MT) by hair cells in the inner ear has been investigated intensively for 4 decades, but its precise molecular composition remains enigmatic. Transmembrane channel‐like protein 1 (TMC1) was recently identified as a component of the MT channel, and lipoma HMGIC fusion partner‐like 5 (LHFPL5) is considered to be part of the MT complex and may functionally couple the tip link to the MT channel. As components of the MT complex, TMC1 and LHFPL5 are expected to localize at the lower end of the tip link in hair cells, a notion generally supported by previous studies on neonatal mice. However, the localization of these 2 proteins, particularly in the hair cells of adult mice, remains incompletely elucidated. Because determination of TMC1 and LHFPL5 localization at distinct developmental stages is essential for understanding their function and regulation, we used several approaches to examine the localization of these proteins in neonatal and adult hair cells in the mouse. We report several notable findings: 1) TMC1 and LHFPL5 predominantly localize at the tip of the shorter rows of stereocilia in neonatal hair cells, which largely verifies the previously published findings in neonatal hair cells; 2) LHFPL5 persists in the hair bundle of hair cells after postnatal day (P)7, which clarifies the previously reported unexpected absence of LHFPL5 after P7 and supports the view that LHFPL5 is a permanent component in the MT complex; and 3) TMC1 and LHFPL5 remain at the tip of the shorter rows of stereocilia in adult outer hair cells, but in adult inner hair cells, TMC1 is uniformly distributed in both the tallest row and the shorter rows of stereocilia, whereas LHFPL5 is uniformly distributed in the shorter rows of stereocilia. These findings raise intriguing questions regarding the turnover rate, regulation, additional functions, and functional interaction of TMC1 and LHFPL5. Our study confirms the previous findings in neonatal hair cells and reveals several previously unidentified aspects of TMC1 and LHFPL5 localization in more mature hair cells. —Li, X. , Yu, X. , Chen, X. , Liu, Z. , Wang, G. , Li, C. , Wong, E. Y. M. , Sham, M. H. , Tang, J., He, J., Xiong, W. , Liu, Z. , Huang, P. Localization of TMC1 and LHFPL5 in auditory hair cells in neonatal and adult mice. FASEB J. 33,6838–6851 (2019). www.fasebj. org
Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance–Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing

Background Mitral regurgitation (MR) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency. Methods and Results The population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR. Left ventricular systolic function significantly decreased and chamber size increased in relation to MR, paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity (P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR‐associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity (P≤0.01); impairment was greater with functional MR (P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task–based effort (B=−0.39 [95% CI, −0.62 to −0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=−1.36 [95% CI, −1.80 to −0.93]; P<0.001) and remained significant (P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction. Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR.
The Journal of the Acoustical Society of America SpEAR: An in-ear speech database in varying conditions of the audio-phonation loop

Abstract: With the rise of hearables and the advantages of using in-ear microphones with intraaural devices, accessibility to an in-ear speech database in adverse conditions is essential. Speech captured inside the occluded ear is limited in its frequency bandwidth and has an amplified low frequency content. In addition, occluding the ear canal affects speech production, especially in noisy environments. These changes to speech production have a detrimental effect on speech-based algorithms. Yet, to the authors' knowledge, there are no speech databases that account for these changes. This paper presents a Speech-in-EAR (SpEAR) database, of speech captured inside an occluded ear in noise and in quiet. The database is bilingual (in French and in English) and is intended to aid researchers in developing algorithms for intra-aural devices utilizing in-ear microphones.