Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamical Boolean Modeling of Immunogenic Cell Death

As opposed to the standard tolerogenic apoptosis, immunogenic cell death (ICD) constitutes a type of cellular demise that elicits an adaptive immune response. ICD has been characterized in malignant cells following cytotoxic interventions, such as chemotherapy or radiotherapy. Briefly, ICD of cancer cells releases some stress/danger signals that attract and activate dendritic cells (DCs). The latter can then engulf and cross-present tumor antigens to T lymphocytes, thus priming a cancer-specific immunity. This series of reactions works as a positive feedback loop where the antitumor immunity further improves the therapeutic efficacy by targeting cancer cells spared by the cytotoxic agent. However, not all chemotherapeutic drugs currently approved for cancer treatment are able to stimulate bona fide ICD: some commonly used agents, such as cisplatin or 5-fluorouracil, are unable to activate all features of ICD. Therefore, a better characterization of the process could help identify some gene or protein candidates to target pharmacologically and suggest combinations of drugs that would favor/increase antitumor immune response. To this end, we have built a mathematical model of the major cell types that intervene in ICD, namely cancer cells, DCs, CD8+ and CD4+ T cells. Our model not only integrates intracellular mechanisms within each individual cell entity, but also incorporates intercellular communications between them. The resulting cell population model recapitulates key features of the dynamics of ICD after an initial treatment, in particular the time-dependent size of the different cell types. The model is based on a discrete Boolean formalism and is simulated by means of a software tool, UPMaBoSS, which performs stochastic simulations with continuous time, considering the dynamics of the system at the cell population level with appropriate timing of events, and accounting for death and division of each cell type. With this model, the time scales of some of the processes involved in ICD, which are challenging to measure experimentally, have been predicted. In addition, our model analysis led to the identification of actionable targets for boosting ICD-induced antitumor response. All computational analyses and results are compiled in interactive notebooks which cover the presentation of the network structure, model simulations, and parameter sensitivity analyses.
Evaluation of the Distribution and Elimination of Balanced Isotonic Crystalloid, 5% Hypertonic Saline, and 6% Tetrastarch 130/0.4 Using Volume Kinetic Modeling and Analysis in Healthy Conscious Cats

This prospective, randomized, blinded, interventional cross-over study investigated the distribution, elimination, plasma volume expansion, half-life, comparative potency, and ideal fluid prescription of three commonly prescribed intravenous (IV) fluids in 10 healthy conscious cats using volume kinetic analysis that is novel to veterinary medicine. Each cat received 20 mL/kg of balanced isotonic crystalloid (PLA), 3.3 mL/kg of 5% hypertonic saline (HS), and 5 mL/kg of 6% tetrastarch 130/0.4 (HES) over 15 min on separate occasions. Hemoglobin concentration, red blood cell count, hematocrit, heart rate, and blood pressure were measured at baseline, 5, 10, 15, 20, 30, 40, 50, 60, and every 15 min until 180 min. Urine output was estimated every 30 min using point-of-care bladder ultrasonography. Plasma dilution derived from serial hemoglobin concentration and red blood cell count served as input variables for group and individual fluid volume kinetic analyses using a non-linear mixed effects model. In general, the distribution of all IV fluids was rapid, while elimination was slow. The half-lives of PLA, HS, and HES were 49, 319, and 104 min, respectively. The prescribed fluid doses for PLA, HS, and HES resulted in similar peak plasma volume expansion of 27–30% potency of HS was 6 times higher than PLA and 1.7 times greater than HES, while HES was 3.5 times more potent than PLA. Simulation of ideal fluid prescriptions to achieve and maintain 15 or 30% plasma volume expansion revealed the importance of a substantial reduction in infusion rates following initial IV fluid bolus. In conclusion, volume kinetic analysis is a feasible research tool that can provide data on IV fluid kinetics and body water physiology in cats. The rapid distribution but slow elimination of IV fluids in healthy conscious cats is consistent with anecdotal reports of fluid overload susceptibility in cats and warrants further investigation.
Comparison of Different Methods for Spatial Downscaling of GPM IMERG V06B Satellite Precipitation Product Over a Typical Arid to Semi-Arid Area

Spatial downscaling is an effective way to obtain precipitation with sufficient spatial details. The performance of downscaling is typically determined by the empirical statistical relationships between precipitation and the used auxiliary variables. In this study, we conducted a comprehensive comparison of five empirical statistical methods for spatial downscaling of GPM IMERG V06B monthly and annual precipitation with a relatively long time series from 2001 to 2015 over a typical semi-arid to arid area (Gansu province, China). These methods included two parametric regression methods (univariate regression, or UR; multivariate regression, or MR) and three machine learning methods (artificial neural network, or ANN; support vector machine, or SVM; random forests, or RF), which were used to downscale the satellite precipitation from 0.1° (∼10 km) to 1 km spatial resolution. Five commonly used indices which were normalized differential vegetation index (NDVI), elevation, land surface temperature (LST), and latitude and longitude were selected as auxiliary variables. The downscaled results were validated using a total of 80 rain gauge station data during 2001–2015. Results showed that latitude had the overall largest correlation with IMERG annual precipitation, also evidenced by feature importance measurements in RF. The downscaled results at monthly scale were overall consistent with the results at annual scale. The machine learning-based methods had better predictive ability of the original IMERG precipitation than parametric regression methods, with larger coefficient of determination (R 2) and smaller root-mean-square error (RMSE) as well as relative root-mean-square error (RRMSE). The downscaled 1 km IMERG precipitation by parametric regression methods had obvious underestimations (positive residual errors) in the south and east of Gansu province and overestimations (negative residual errors) in the west. In addition, the validation results of parametric regression downscaling methods showed large improvements after residual correction, while the improvements were small in the machine learning-based methods. However, the interpolation algorithm included in residual correction can cause certain errors in the downscaled results due to the ignorance of precipitation spatial heterogeneity. The machine learning-based RF downscaling had the smallest residual errors and the overall best validation results, showing great potentials to provide accurate precipitation with high spatial resolution.
Enhancing Enzyme-Mediated Cellulose Hydrolysis by Incorporating Acid Groups Onto the Lignin During Biomass Pretreatment

Lignin is known to limit the enzyme-mediated hydrolysis of biomass by both restricting substrate swelling and binding to the enzymes. Pretreated mechanical pulp (MP) made from Aspen wood chips was incubated with either 16% sodium sulfite or 32% sodium percarbonate to incorporate similar amounts of sulfonic and carboxylic acid groups onto the lignin (60 mmol/kg substrate) present in the pulp without resulting in significant delignification. When Simon’s stain was used to assess potential enzyme accessibility to the cellulose, it was apparent that both post-treatments enhanced accessibility and cellulose hydrolysis. To further elucidate how acid group addition might influence potential enzyme binding to lignin, Protease Treated Lignin (PTL) was isolated from the original and modified mechanical pulps and added to a cellulose rich, delignified Kraft pulp. As anticipated, the PTLs from both the oxidized and sulfonated substrates proved less inhibitory and adsorbed less enzymes than did the PTL derived from the original pulp. Subsequent analyses indicated that both the sulfonated and oxidized lignin samples contained less phenolic hydroxyl groups, resulting in enhanced hydrophilicity and a more negative charge which decreased the non-productive binding of the cellulase enzymes to the lignin.
Inhibition of NOX4/ROS Suppresses Neuronal and Blood-Brain Barrier Injury by Attenuating Oxidative Stress After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder that can effectively induce oxidative stress responses. NADPH oxidase 4 (NOX4) is a member of the NOX family of oxidases. It is expressed in the brain normally and involved in cell signal transduction and the removal of harmful substances. In some pathological conditions, it mediates inflammation and the aging of cells. However, few studies have focused on whether NOX4 is involved in brain injury caused by ICH. Therefore, this study aimed to clarify the role of NOX4 in the pathological process that occurs after ICH and the potential mechanism underlying its role. A rat model of ICH was established by the injection of collagenase type IV, and the expression of NOX4 was then determined. Further, siRNA-mediated protein expression knockdown technology was used for NOX4 knockdown, and western immunoblotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and other molecular biological techniques were performed to assess the effects of NOX4 knockdown. Neurobiological scoring, brain water content determination, and other brain injury detection methods were also performed to assess the role of NOX4 following ICH. We found that the expression of NOX4 increased in the brains of rats after ICH, and that it was mainly expressed in neurons, astrocytes, vascular endothelial cells and microglia. Following NOX4 knockdown, the level of oxidative stress in the brain decreased considerably, the neurobehavioral scores improved, the levels of neuronal apoptosis reduced markedly, and the impairment of blood-brain barrier function was significantly ameliorated in rats with ICH. In conclusion, this study suggests that NOX4 expression is upregulated after ICH, which may cause an imbalance in the oxidative stress of relevant cells in the brain, leading to subsequent apoptosis of neurons and damage to the blood-brain barrier due to secondary brain injury following ICH.
Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

The two main phytocannabinoids—delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—have been extensively studied, and it has been shown that THC can induce transient psychosis. At the same time, CBD appears to have no psychotomimetic potential. On the contrary, emerging evidence for CBD's antipsychotic properties suggests that it may attenuate effects induced by THC. Thus, we investigated and compared the effects of THC and CBD administration on emotion, cognition, and attention as well as the impact of CBD pre-treatment on THC effects in healthy volunteers. We performed a placebo-controlled, double-blind, experimental trial (GEI-TCP II; ClinicalTrials.gov identifier: NCT02487381) with 60 healthy volunteers randomly allocated to four parallel intervention groups, receiving either placebo, 800 mg CBD, 20 mg THC, or both cannabinoids. Subjects underwent neuropsychological tests assessing working memory (Letter Number Sequencing test), cognitive processing speed (Digit Symbol Coding task), attention (d2 Test of Attention), and emotional state (adjective mood rating scale [EWL]). Administration of CBD alone did not influence the emotional state, cognitive performance, and attention. At the same time, THC affected two of six emotional categories—more precisely, the performance-related activity and extraversion—, reduced the cognitive processing speed and impaired the performance on the d2 Test of Attention. Interestingly, pre-treatment with CBD did not attenuate the effects induced by THC. These findings show that the acute intake of CBD itself has no effect per se in healthy volunteers and that a single dose of CBD prior to THC administration was insufficient to mitigate the detrimental impact of THC in the given setting. This is in support of a complex interaction between CBD and THC whose effects are not counterbalanced by CBD under all circumstances.
Advanced 3D “Modeling” and “Printing” for the Surgical Planning of a Successful Case of Thoraco-Omphalopagus Conjoined Twins Separation

Background The surgical separation of two Conjoined Twins is a particularly complex operation. Surgical times are particularly long and post-operative complications are very frequent in this type of procedure. We report a clinical case of surgical separation of two thoraco-omphalopagus conjoined twins in which, thanks to the use of (3D) three dimensional technologies, we were able to significantly reduce operative times and improve clinical outcomes. Methods We performed a 3D reconstruction of the anatomical parts involved in congenital fusion using Computer Tomography (CT) images. We obtained virtual anatomical models of the patients which allowed us to estimate essential details as the residual post-operative thoracic volume as well as the exact position of resection planes for both the general separation and for the hepatic splitting procedure. Subsequently, we printed 3D anatomical models of the thoracic cage and sternum and of the liver with the plane of resection. Finally, we printed an additional 3D anatomical model of the two patients representing different organs with multiple colors and materials. Results The use of 3D printing reduced the duration of surgery by 30% with a favorable patient outcome. Two years after the operation, the patients do not present any type of deficit and have a normal life without any significant complication. Conclusion Virtual anatomical 3D models and 3D printing represent a valid technological tool to support complex surgical operations, especially in pre-surgical planning. 3D models are important tools to better understand complex anatomy and to discuss clinical cases among members of the surgical team.
Nano-acoustic resonator with ultralong phonon lifetime

Getting phonons to hang around The ideal platform for quantum-computing and quantum-sensing applications is likely to be a hybrid system that combines the best features of different components. Superconducting circuits are relatively advanced, and finding components that can control and manipulate the microwaves will be essential. MacCabe et al. explored the use of high-quality microresonators in which the acoustic environment could be engineered such that the phonon lifetime could be extended to more than 1 second. Operating at microwave frequencies of 5 gigahertz, these quantum acoustic-dynamic devices could be coupled with superconducting circuits. Science, this issue p. 840 Engineering of the acoustic environment surrounding a mechanical microresonator is used to extend phonon lifetimes. The energy damping time in a mechanical resonator is critical to many precision metrology applications, such as timekeeping and force measurements. We present measurements of the phonon lifetime of a microwave-frequency, nanoscale silicon acoustic cavity incorporating a phononic bandgap acoustic shield. Using pulsed laser light to excite a colocalized optical mode of the cavity, we measured the internal acoustic modes with single-phonon sensitivity down to millikelvin temperatures, yielding a phonon lifetime of up to τph,0≈1.5 seconds (quality factor Q=5×1010) and a coherence time of τcoh,0≈130 microseconds for bandgap-shielded cavities. These acoustically engineered nanoscale structures provide a window into the material origins of quantum noise and have potential applications ranging from tests of various collapse models of quantum mechanics to miniature quantum memory elements in hybrid superconducting quantum circuits.
Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells

The brain of adult mammals, including humans, contains neural stem cells (NSCs) located within specific niches of which the ventricular-subventricular zone (V-SVZ) is the largest one. Under physiological conditions, NSCs proliferate, self-renew and produce new neurons and glial cells. Several recent studies established that oncogenic mutations in adult NSCs of the V-SVZ are responsible for the emergence of malignant primary brain tumors called glioblastoma. These aggressive tumors contain a small subpopulation of cells, the glioblastoma stem cells (GSCs), that are endowed with proliferative and self-renewal abilities like NSCs from which they may arise. GSCs are thus considered as the cells that initiate and sustain tumor growth and, because of their resistance to current treatments, provoke tumor relapse. A growing body of studies supports that Ca2+ signaling controls a variety of processes in NSCs and GSCs. Ca2+ is a ubiquitous second messenger whose fluctuations of its intracellular concentrations are handled by channels, pumps, exchangers, and Ca2+ binding proteins. The concerted action of the Ca2+ toolkit components encodes specific Ca2+ signals with defined spatio-temporal characteristics that determine the cellular responses. In this review, after a general overview of the adult brain NSCs and GSCs, we focus on the multiple roles of the Ca2+ toolkit in NSCs and discuss how GSCs hijack these mechanisms to promote tumor growth. Extensive knowledge of the role of the Ca2+ toolkit in the management of essential functions in healthy and pathological stem cells of the adult brain should help to identify promising targets for clinical applications.
The complete mitochondrial genome of red-tailed laughingthrush (Garrulax milnei)

Abstract In this study, the complete mitochondrial genome of Garrulax milnei was sequenced for the first time. This mitogenome is 17,871bp in length and it contains 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes, 1 control region and 1 extra pseudo-control region. The base composition of the mitochondrial genome is 29.7% A, 24.5% T, 14.2% G and 31.6% C. The phylogenetic analysis based on the 12 protein-coding genes (except for ND6 gene) showed that G. milnei clusters with other two species that belong to genus Garrulax.
An Exploratory Study of the Relative Effects of Various Protective Factors on Depressive Symptoms Among Older People

Objective: The present study investigated the relative importance of various factors found to be negatively associated with depressive symptoms in older adults and assessed the potential moderating effect of sociodemographic characteristics for each factor. Method: Depressive symptoms were measured with the Center of Epidemiological Studies Depression Scale. Psychological, social, and physical health measures relating to the following factors were also administered: personal growth, purpose in life, self-esteem, self-efficacy, social support, self-rated health, life satisfaction, and physical activity. Multivariate linear regression analysis was used to investigate the most important factors associated with depressive symptoms, and moderation analyses were employed to identify any moderating effects of sociodemographic factors. Results: Life satisfaction, self-esteem, and purpose in life were found to be negatively associated with depressive symptoms. Only one moderating effect was observed—the negative relationship between life satisfaction and depressive symptoms was significantly stronger among the younger respondents. Conclusion: These findings suggest that strategies for the prevention or amelioration of depressive symptoms across subgroups of the senior population could be optimized by focusing on enhancing life satisfaction, self-esteem, and purpose in life.
The Impact of Coping Strategies and Perceived Family Support on Depressive and Anxious Symptomatology During the Coronavirus Pandemic (COVID-19) Lockdown

The coronavirus pandemic represents a severe global crisis, affecting physical, and psychological health. Lockdown rules imposed to counteract the rapid growth of COVID-19, mainly social restrictions, have represented a risk factor for developing depressive and anxious symptoms. The research aims are to explore the effect of coping strategies and perceived social support on depressive and anxious symptomatology during the COVID-19 pandemic. Ninety-six healthy people (46 males, mean age = 39.3; SD = 16.6) completed through on-line platform: Socio-demographic questionnaire, Coping Inventory for Stressful Situations (CISS), Multidimensional Scale of Perceived Social Support (MSPSS) and Symptom Checklist-90-Revised (SCL-90-R), 3 weeks after the imposition of lockdown restrictions. SCL-90-R Depression scores showed significant positive correlation with CISS Emotion (r = 0.85; p = 0.001) and Avoidant (r = 0.34; p = 0.018), a significant negative correlation with MSPSS Family support (r = −0.43; p = 0.003). SCL-90-R Anxiety scores showed a significant positive correlation with CISS Emotion (r = 0.72; p = 0.001) and Avoidant (r = 0.35; p = 0.016). No significant correlations between both CISS Emotion and Avoidant scales with social support emerged. Two Multiple Linear Regression analysis were performed using, respectively, SCL-90-R Depression and Anxiety scores as dependent variables, and the CISS and MSPSS scales, age, and gender as predictors. The first regression model (R2 = 0.78; adjusted R2 = 0.75) revealed CISS Emotion (β = 0.83; p = 0.001) and MSPSS Family support (β = −0.24; p = 0.004) had a predictive effect on SCL-90-R Depression scores. The second regression model (R2 = 0.52; adjusted R2 = 0.472) revealed that only CISS Emotion (β = 0.71; p = 0.001) predicted the SCL-90-R Anxiety scores. In conclusion, during the COVID-19 pandemic lockdowns, coping focus on emotions seemed to increase anxious and depressive symptoms, probably due to the uncontrollable nature of the stressful event and the high emotional response. Family support which reduces the sense of loneliness had an exclusive role in mitigating depressive symptoms. These results highlight the importance of promoting psychological strategies to improve emotional regulation skills, reducing isolation from family, to prevent mood symptomatology in healthy citizens during large-scale health crises.