Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination Treatment With Inhibitors of ERK and Autophagy Enhances Antitumor Activity of Betulinic Acid in Non–small-Cell Lung Cancer In Vivo and In Vitro

Aberrant activation of the Ras–ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non–small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Mitogen-activated protein kinases, and especially ERK that facilitates cancer cell survival, are also activated by BA treatment. As such, in the presence of ERK inhibitors (ERKi), lung cancer cells are much more sensitive to BA. However, the dual treatment of BA and ERKi results in increased protective autophagy and AKT phosphorylation. Accordingly, inhibition of AKT has a highly synergistic anticancer effect with co-treatment of BA and ERKi. Notably, autophagy inhibition by hydroxychloroquine (HCQ) increases the response of lung cancer cells to BA in combination with ERKi. In vivo, the three-drug combination (BA, ERKi, and HCQ), resulted in superior therapeutic efficacy than single or dual treatments in the xenograft mouse model. Thus, our study provides a combined therapy strategy that is a highly effective treatment for patients with NSCLC.
Sleep-Related Breathing Problem Trajectories Across Early Childhood and Academic Achievement-Related Performance at Age Eight

Background: Childhood sleep disordered breathing (SDB) has been linked to poorer academic performance; however, research has not investigated the extent improvement in SDB may alter outcomes across key academic skills. This study aimed to investigate if children's early SDB status could predict later academic outcomes, and if an improvement in SDB status across the early childhood years would coincide with better, later performance in key academic skills related to reading, numeracy, and listening comprehension. Methods: Eighty five case children with an SDB symptom score >25 (maximum 77) were matched to 85 control children (score <12) at recruitment (age 3). SDB severity (symptom history and clinical assessment) was evaluated at ages 3, 4, 6, and 8 years and performance on individually-administered academic skills assessed at age 8 (91% retention from age 3). Case children were categorized into “improved” or “not-improved” groups based on SDB trajectories over the 5 years. Contributions of SDB status and trajectory group to academic performance were determined using regression analysis adjusted for demographic variables. Results: History of SDB from age 3 predicted significantly poorer performance on some key academic skills (oral reading and listening skills) at age 8. Children whose SDB improved (45%) performed better in oral reading fluency than those whose SDB did not improve, but difficulties with specific tasks involving oral language (listening retell) remained when compared to controls. Conclusion: Findings support links between early SDB and worse academic outcomes and suggest key academic areas of concern around oral language. Findings highlight the need for child mental health professionals to be aware of children's sleep problems, particularly SDB (past and present), when assessing potential barriers to children's achievement, to assist with appropriate and timely referrals for evaluation of children's sleep difficulties and collaborative evaluation of response to intervention for sleep difficulties.
Lodgepole Pine Bole Wood Density and Decay Rate 1, 11, and 22 Years After Felling in Central Montana, United States

Estimates of dead and down woody material (DWM) biomass are important for nutrient cycling, wildlife habitat assessment, fire effects and climate change science. Most methods used to sample woody material initially assess volume then estimates of wood density are used to convert volume to biomass. To assess initial wood density and decomposition rate, this study examined in situ wood density of lodgepole pine logs at the Tenderfoot Creek Experimental Forest (TCEF), central Montana, United States, 1, 11, and 22 years after felling. Mean wood density decreased from 0.39 to 0.27 g cm–3 over 22 years and the single exponential decay rate was k = 0.012 yr–1 1 and 11-years post-felling and 0.022 yr–1 11 and 22 years post-felling. A common 5-category decay classification system was evaluated for estimating wood density by decay class, which identified significant difference in three of four observed classes.
Musical and Bodily Predictors of Mental Effort in String Quartet Music: An Ecological Pupillometry Study of Performers and Listeners

Music performance can be cognitively and physically demanding. These demands vary across the course of a performance as the content of the music changes. More demanding passages require performers to focus their attention more intensity, or expend greater “mental effort. ” To date, it remains unclear what effect different cognitive-motor demands have on performers' mental effort. It is likewise unclear how fluctuations in mental effort compare between performers and perceivers of the same music. We used pupillometry to examine the effects of different cognitive-motor demands on the mental effort used by performers and perceivers of classical string quartet music. We collected pupillometry, motion capture, and audio-video recordings of a string quartet as they performed a rehearsal and concert (for live audience) in our lab. We then collected pupillometry data from a remote sample of musically-trained listeners, who heard the audio recordings (without video) that we captured during the concert. We used a modelling approach to assess the effects of performers' bodily effort (head and arm motion; sound level; performers' ratings of technical difficulty), musical complexity (performers' ratings of harmonic complexity; a score-based measure of harmonic tension), and expressive difficulty (performers' ratings of expressive difficulty) on performers' and listeners' pupil diameters. Our results show stimulating effects of bodily effort and expressive difficulty on performers' pupil diameters, and stimulating effects of expressive difficulty on listeners' pupil diameters. We also observed negative effects of musical complexity on both performers and listeners, and negative effects of performers' bodily effort on listeners, which we suggest may reflect the complex relationships that these features share with other aspects of musical structure. Looking across the concert, we found that both of the quartet violinists (who exchanged places halfway through the concert) showed more dilated pupils during their turns as 1st violinist than when playing as 2nd violinist, suggesting that they experienced greater arousal when “leading” the quartet in the 1st violin role. This study shows how eye tracking and motion capture technologies can be used in combination in an ecological setting to investigate cognitive processing in music performance.
Comparison of Shear Wave Elastography and Dynamometer Test in Muscle Tissue Characterization for Potential Medical and Sport Application

Skeletal muscle status and its dynamic follow up are of particular importance in the management of several diseases where weight and muscle mass loss and, consequently, immobilization occurs, as in cancer and its treatment, as well as in neurodegenerative disorders. But immobilization is not the direct result of body and muscle mass loss, but rather the loss of the maximal tension capabilities of the skeletal muscle. Therefore, the development of a non-invasive and real-time method which can measure muscle tension capabilities in immobile patients is highly anticipated. Our aim was to introduce and evaluate a special ultrasound measurement technique to estimate a maximal muscle tension characteristic which can be used in medicine and also in sports diagnostics. Therefore, we determined the relationship between the results of shear wave elastography measurements and the dynamometric data of individuals. The measurements were concluded on the m. vastus lateralis. Twelve healthy elite athletes took part in our preliminary proof of principle study—five endurance (S) and seven strength (F) athletes showing unambiguously different muscle composition features, nine healthy subjects (H) without prior sports background, and four cancer patients in treatment for a stage 3 brain tumor (T). Results showed a high correlation between the maximal dynamometric isometric torque (Mmax) and mean elasticity value (E) for the non-athletes [(H + T), (r = 0.795)] and for the athletes [(S + F), (r = 0.79)]. For the athletes (S + F), the rate of tension development at contraction (RTDk) and E correlation was also determined (r = 0.84, p < 0.05). Our measurements showed significantly greater E values for the strength athletes with fast muscle fiber dominance than endurance athletes with slow muscle fiber dominance (p < 0.05). Our findings suggest that shear wave ultrasound elastography is a promising method for estimating maximal muscle tension and, also, the human skeletal muscle fiber ratio. These results warrant further investigations with a larger number of individuals, both in medicine and in sports science.
Diversity and Disease: The Effects of Coral Diversity on Prevalence and Impacts of Stony Coral Tissue Loss Disease in Saint Thomas, U.S. Virgin Islands

Stony coral tissue loss disease (SCTLD) was first observed in St. Thomas, U.S. Virgin Islands (USVI) in January 2019. This disease affects at least 20 scleractinian coral species; however, it is not well understood how reef diversity affects its spread or its impacts on reef ecosystems. With a large number of susceptible species, SCTLD may not follow the diversity-disease hypothesis, which proposes that high species diversity is negatively correlated with disease prevalence. Instead, SCTLD may have a higher prevalence and a greater impact on reefs with higher coral diversity. To test this, in 2020 we resampled 54 sites around St. Thomas previously surveyed in 2017 or 2019 by the National Oceanic and Atmospheric Administration National Coral Reef Monitoring Program. These sites represented a variety of species diversity values [categorized into poor (<12 spp. rich.) and rich (≥12 spp. rich.)] in multiple disease zones (Endemic: disease present ≥ 9 months; Epidemic: disease present 2–6 months; Control and Emergent: disease present no disease/<2 months). We hypothesized that, contrary to the diversity-disease hypothesis, sites with high species diversity (as measured by species richness or Simpson’s index) would have higher disease prevalence within the epidemic zone, and that high species diversity sites would have a greater impact from disease within the endemic zone. Results indicated a significant positive relationship between disease prevalence and diversity in the epidemic zone, and a similar trend in the endemic zones. Additionally, a negative relationship was seen between pre-outbreak diversity and loss of diversity and coral cover within the endemic zone. This supports the hypothesis that higher diversity predicts greater disease impact and suggests that SCTLD does not follow the diversity-disease hypothesis. Within the epidemic zone, the species with the highest SCTLD prevalence were Dendrogyra cylindrus, Colpophyllia natans, and Meandrina meandrites, while in the endemic zone, Diploria labyrinthiformis, Pseudodiploria strigosa, Montastraea cavernosa, and Siderastrea siderea had the highest SCTLD prevalence. Understanding the relationship between species diversity and SCTLD will help managers predict the most vulnerable reefs, which should be prioritized within the USVI and greater Caribbean region.
High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration

Placentas from preeclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels with reduced expression of aquaporin 3 (AQP3). However, whether TNF-α modulates AQP3 expression remains to be elucidated. We hypothesize that elevated levels of TNF-α reduce AQP3 expression and negatively impact trophoblastic cell migration. Spontaneously hypertensive rats (SHRs) and Wistar rats (14–16 weeks) were divided into hypertensive and normotensive groups, respectively. Systolic blood pressure (SBP) was measured, and animals mated. In a third group, pregnant SHRs were treated with a TNF-α antagonist, etanercept (0.8 mg/kg, subcutaneously) on days 0, 6, 12, and 18 of pregnancy. Placentas were collected on the 20th day of pregnancy. Human placental explants, from normotensive pregnancies, were incubated with TNF-α (5, 10, and 20 ng/ml) and/or etanercept (1 μg/ml). Swan 71 cells were incubated with TNF-α (10 ng/ml) and/or etanercept (1 μg/ml) and subjected to the wound healing assay. AQP3 expression was assessed by Western blot and TNF-α levels by ELISA. SBP (mmHg) was elevated in the hypertensive group, and etanercept treatment reduced this parameter. Placental TNF-α levels (pg/ml) were higher in the hypertensive group. AQP3 expression was reduced in the hypertensive group, and etanercept treatment reversed this parameter. Explants submitted to TNF-α exposition displayed reduced expression of AQP3, and etanercept incubation reversed it. Trophoblastic cells incubated with TNF-α showed decreased cell migration and reduced AQP3 expression, and etanercept incubation ameliorated it. Altogether, these data demonstrate that high TNF-α levels negatively modulate AQP3 in placental tissue, impairing cell migration, and its relationship in a pregnancy affected by hypertension.
A Robust Prognostic Gene Signature Based on eRNAs-Driven Genes in Prostate Cancer

Prostate cancer (PCa) is the second most common malignancy in men, but its exact pathogenetic mechanisms remain unclear. This study explores the effect of enhancer RNAs (eRNAs) in PCa. Firstly, we screened eRNAs and eRNA -driven genes from The Cancer Genome Atlas (TCGA) database, which are related to the disease-free survival (DFS) of PCa patients;. screening methods included bootstrapping, Kaplan–Meier (KM) survival analysis, and Pearson correlation analysis. Then, a risk score model was established using multivariate Cox analysis, and the results were validated in three independent cohorts. Finally, we explored the function of eRNA-driven genes through enrichment analysis and analyzed drug sensitivity on datasets from the Genomics of Drug Sensitivity in Cancer database. We constructed and validated a robust prognostic gene signature involving three eRNA-driven genes namely MAPK15, ZNF467, and MC1R. Moreover, we evaluated the function of eRNA-driven genes associated with tumor microenvironment (TME) and tumor mutational burden (TMB), and identified remarkable differences in drug sensitivity between high- and low-risk groups. This study identified a prognostic gene signature, which provides new insights into the role of eRNAs and eRNA-driven genes while assisting clinicians to determine the prognosis and appropriate treatment options for patients with PCa.
Insulin-Like Peptides and Cross-Talk With Other Factors in the Regulation of Insect Metabolism

The insulin-like peptide (ILP) and insulin-like growth factor (IGF) signalling pathways play a crucial role in the regulation of metabolism, growth and development, fecundity, stress resistance, and lifespan. ILPs are encoded by multigene families that are expressed in nervous and non-nervous organs, including the midgut, salivary glands, and fat body, in a tissue- and stage-specific manner. Thus, more multidirectional and more complex control of insect metabolism can occur. ILPs are not the only factors that regulate metabolism. ILPs interact in many cross-talk interactions of different factors, for example, hormones (peptide and nonpeptide), neurotransmitters and growth factors. These interactions are observed at different levels, and three interactions appear to be the most prominent/significant: (1) coinfluence of ILPs and other factors on the same target cells, (2) influence of ILPs on synthesis/secretion of other factors regulating metabolism, and (3) regulation of activity of cells producing/secreting ILPs by various factors. For example, brain insulin-producing cells co-express sulfakinins (SKs), which are cholecystokinin-like peptides, another key regulator of metabolism, and express receptors for tachykinin-related peptides, the next peptide hormones involved in the control of metabolism. It was also shown that ILPs in Drosophila melanogaster can directly and indirectly regulate AKH. This review presents an overview of the regulatory role of insulin-like peptides in insect metabolism and how these factors interact with other players involved in its regulation.
A Review on Development of Ceramic-Graphene Based Nanohybrid Composite Systems in Biological Applications

Graphene-based nanocomposites constitute an interesting and promising material for various applications. Intensive progress in the development of this group of materials offers an opportunity to create new systems useful for drinking water decontamination or other biotechnological applications. Nanohybrid structures of graphene-ceramic systems can be obtained using covalent graphene surface modification with nanoparticles (NPs) of ceramic and/or co-deposition of metals with selected morphology and chemistry. The present paper systematizes the associated bio-related knowledge and inspires future development of graphene/NPs systems. Emerging knowledge and unique research techniques are reviewed within designing the required nanocomposite structure and chemical composition, development and optimization of new methods of covalent surface modification of graphene with NPs as well as analysis of mechanisms governing the formation of covalent bonding. Further, innovative research tools and methodologies are presented regarding the adjustment of functionalities of materials used for the application in drinking water decontamination or biocidal composites. This study provides a comprehensive base for rational development of more complex, hybrid graphene-based nanomaterials with various bio-functionalities that can be further applied in industrial practice.
Hotter Drought Escalates Tree Cover Declines in Blue Oak Woodlands of California

California has, in recent years, become a hotspot of interannual climatic variability, recording devastating climate-related disturbances with severe effects on tree resources. Understanding the patterns of tree cover change associated with these events is vital for developing strategies to sustain critical habitats of endemic and threatened vegetation communities. We assessed patterns of tree cover change, especially the effects of the 2012–2016 drought within the distribution range of blue oak (Quercus douglasii), an endemic tree species to California with a narrow geographic extent. We utilized multiple, annual land-cover and land-surface change products from the U.S. Geological Survey (USGS) Land Change Monitoring, Assessment and Projection (LCMAP) project along with climate and wildfire datasets to monitor changes in tree cover state and condition and examine their relationships with interannual climate variability between 1985 and 2016. Here, we refer to a change in tree cover class without a land-cover change to another class as “conditional change. ” The unusual drought of 2012–2016, accompanied by anomalously high temperatures and vapor pressure deficit, was associated with exceptional spikes in the amount of both fire and non-fire induced tree cover loss and tree cover conditional change, especially in 2015 and 2016. Approximately 1,266 km2 of tree cover loss and 617 km2 of tree cover conditional change were recorded during that drought. Tree cover loss through medium to high severity fires was especially large in exceptionally dry and hot years. Our study demonstrates the usefulness of the LCMAP products for monitoring the effects of climatic extremes and disturbance events on both thematic and conditional land-cover change over a multi-decadal period. Our results signify that blue oak woodlands may be vulnerable to extreme climate events and changing wildfire regimes. Here, we present early evidence that frequent droughts associated with climate warming may continue to affect tree cover in this region, while drought interaction with wildfires and the resulting feedbacks may have substantial influence as well. Consequently, efforts to conserve the blue oak woodlands, and potentially other vegetation communities in the Western United States, may benefit from consideration of climate risks as well as the potential for climate-fire and vegetation feedbacks.
Sustained, Multifaceted Improvements in Mental Well-Being Following Psychedelic Experiences in a Prospective Opportunity Sample

In the last 15 years, psychedelic substances, such as LSD and psilocybin, have regained legitimacy in clinical research. In the general population as well as across various psychiatric populations, mental well-being has been found to significantly improve after a psychedelic experience. Mental well-being has large socioeconomic relevance, but it is a complex, multifaceted construct. In this naturalistic observational study, a comprehensive approach was taken to assessing well-being before and after a taking a psychedelic compound to induce a “psychedelic experience. ” Fourteen measures of well-being related constructs were included in order to examine the breadth and specificity of change in well-being. This change was then analysed to examine clusters of measures changing together. Survey data was collected from volunteers that intended to take a psychedelic. Four key time points were analysed: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (N = 654, N = 315, N = 212, and N = 64, respectively). Change on the included measures was found to cluster into three factors which we labelled: 1) “Being well”, 2) “Staying well,” and 3) “Spirituality. ” Repeated Measures Multivariate Analysis of Variance revealed all but the spirituality factor to be improved in the weeks following the psychedelic experience. Additional Mixed model analyses revealed selective increases in Being Well and Staying Well (but not Spirituality) that remained statistically significant up to 2 years post-experience, albeit with high attrition rates. Post-hoc examination suggested that attrition was not due to differential acute experiences or mental-health changes in those who dropped out vs. those who did not. These findings suggest that psychedelics can have a broad, robust and sustained positive impact on mental well-being in those that have a prior intention to use a psychedelic compound. Public policy implications are discussed.