Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Analyses of Multi-Locus Sequence Typing Data Reveal Geographic Differentiation, Hybridization, and Recombination in the Cryptococcus gattii Species Complex

Cryptococcus gattii species complex (CGSC) is a basidiomycete haploid yeast and globally distributed mammalian pathogen. CGSC is comprised of six distinct lineages (VGI, VGII, VGIII, VGIV, VGV, and VGVI); however, the geographical distribution and population structure of these lineages is incompletely described. In this study, we analyze published multi-locus sequence data at seven loci for 566 previously recorded sequence types (STs) encompassing four distinct lineages (VGI, VGII, VGIII, and VGIV) within the CGSC. We investigate indicators of both clonal dispersal and recombination. Population genetic analyses of the 375 STs representing 1202 isolates with geographic information and 188 STs representing 788 isolates with ecological source data suggested historically differentiated geographic populations with infrequent long-distance gene flow. Phylogenetic analyses of sequences at the individual locus and of the concatenated sequences at all seven loci among all 566 STs revealed distinct clusters largely congruent with four major distinct lineages. However, 23 of the 566 STs (4%) each contained alleles at the seven loci belonging to two or more lineages, consistent with their hybrid origins among lineages. Within each of the four major lineages, phylogenetic incompatibility analyses revealed evidence for recombination. However, linkage disequilibrium analyses rejected the hypothesis of random recombination across all samples. Together, our results suggest evidence for historical geographical differentiation, sexual recombination, hybridization, and both long-distance and localized clonal expansion in the global CGSC population.
Chaotic classical and half-classical adiabatic reactions: geometric magnetism and deterministic friction

We study the dynamics of a heavy (slow) classical system coupled, through its position, to a classical or quantal light (fast) system, and derive the first-order velocity-dependent corrections to the lowest adiabatic approximation for the reaction force on the slow system. If the fast dynamics is classical and chaotic, there are two such first-order forces, corresponding to the antisymmetric and symmetric parts of a tensor given by the time integral of the force–force correlation function of the fast motion for frozen slow coordinates. The antisymmetric part is geometric magnetism, in which the ‘magnetic field’ is the classical limit of the 2-form generating the quantum geometric phase. The symmetric part is deterministic friction, dissipating slow energy into the fast chaos; previously found by Wilkinson, this involves the same correlation function as governs the fluctuations and drift of the adiabatic invariant. In the ‘half-classical’ case where the fast system is quantal with a discrete spectrum of adiabatic states, the only first-order slow force is geometric magnetism; there is no friction. This discordance between classical and quantal fast motion is explained in terms of the clash between the semiclassical and adiabatic limits. A generalization of the classical case is given, where the slow velocity, as well as position, is coupled to the fast motion; to first order, the symplectic form in the lowest-order hamiltonian dynamics is modified.
Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study)

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0–93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.
The first‐order reliability method of predicting cumulative mass flux in heterogeneous porous formations

Previous studies have proposed the first‐order reliability method (FORM) as an approach to quantitative stochastic analysis of subsurface transport. Most of these considered only simple analytical models of transport in homogeneous media. Studies that looked at more‐complex, heterogeneous systems found FORM to be computationally demanding and were inconclusive as to the accuracy of the method. Here we show that FORM is poorly suited for computing point concentration cumulative distribution functions (cdfs) except in the case of a constant or monotonically increasing solute source. FORM is better equipped to predict transport in terms of the cumulative mass flux across a control surface. As a demonstration, we use FORM to estimate the cumulative mass flux cdf in two‐dimensional, random porous media. Adjoint sensitivity theory is employed to minimize the computational burden. In addition, properties of the conductivity covariance and distribution are exploited to improve efficiency. FORM required eight times less CPU time than Monte Carlo simulation to generate the results presented. The accuracy of FORM is found to be minimally affected by the size of the initial solute body and the solute travel distance. However, the accuracy is significantly influenced by the degree of heterogeneity, providing an accurate estimate of the cdf when there is mild heterogeneity (σInK = 0.5) but a less accurate estimate when there is stronger heterogeneity (σ1nK = 1.0).
Long-Term SMN- and Ncald-ASO Combinatorial Therapy in SMA Mice and NCALD-ASO Treatment in hiPSC-Derived Motor Neurons Show Protective Effects

For SMA patients with only two SMN2 copies, available therapies might be insufficient to counteract lifelong motor neuron (MN) dysfunction. Therefore, additional SMN-independent compounds, supporting SMN-dependent therapies, might be beneficial. Neurocalcin delta (NCALD) reduction, an SMA protective genetic modifier, ameliorates SMA across species. In a low-dose SMN-ASO-treated severe SMA mouse model, presymptomatic intracerebroventricular (i.c.v.) injection of Ncald-ASO at postnatal day 2 (PND2) significantly ameliorates histological and electrophysiological SMA hallmarks at PND21. However, contrary to SMN-ASOs, Ncald-ASOs show a shorter duration of action limiting a long-term benefit. Here, we investigated the longer-term effect of Ncald-ASOs by additional i.c. v. bolus injection at PND28. Two weeks after injection of 500 µg Ncald-ASO in wild-type mice, NCALD was significantly reduced in the brain and spinal cord and well tolerated. Next, we performed a double-blinded preclinical study combining low-dose SMN-ASO (PND1) with 2× i.c. v. Ncald-ASO or CTRL-ASO (100 µg at PND2, 500 µg at PND28). Ncald-ASO re-injection significantly ameliorated electrophysiological defects and NMJ denervation at 2 months. Moreover, we developed and identified a non-toxic and highly efficient human NCALD-ASO that significantly reduced NCALD in hiPSC-derived MNs. This improved both neuronal activity and growth cone maturation of SMA MNs, emphasizing the additional protective effect of NCALD-ASO treatment.
Addressing Critical Issues Related to Storage and Stability of the Vault Nanoparticle Expressed and Purified from Komagataella phaffi

The vault nanoparticle is a eukaryotic assembly consisting of 78 copies of the 99-kDa major vault protein. They generate two cup-shaped symmetrical halves, which in vivo enclose protein and RNA molecules. Overall, this assembly is mainly involved in pro-survival and cytoprotective functions. It also holds a remarkable biotechnological potential for drug/gene delivery, thanks to its huge internal cavity and the absence of toxicity/immunogenicity. The available purification protocols are complex, partly because they use higher eukaryotes as expression systems. Here, we report a simplified procedure that combines human vault expression in the yeast Komagataella phaffii, as described in a recent report, and a purification process we have developed. This consists of RNase pretreatment followed by size-exclusion chromatography, which is far simpler than any other reported to date. Protein identity and purity was confirmed by SDS-PAGE, Western blot and transmission electron microscopy. We also found that the protein displayed a significant propensity to aggregate. We thus investigated this phenomenon and the related structural changes by Fourier-transform spectroscopy and dynamic light scattering, which led us to determine the most suitable storage conditions. In particular, the addition of either trehalose or Tween-20 ensured the best preservation of the protein in native, soluble form.
Impact of COVID-19 Pandemic Lockdown on Migraine Patients in Latin America

The coronavirus (COVID-19) pandemic, confinement, fear, lifestyle changes, and worldwide health care impacted almost all diseases. Reports from countries outside Latin America revealed differences in migraine patients. In this study, we describe and compare the immediate changes in migraine symptoms associated with COVID-19 quarantine in patients from Argentina, Mexico, and Peru. An online survey was conducted from May to July 2020. The survey was answered by 243 migraine patients, with questions related to sociodemographic data, quarantine conditions, changes in working conditions, physical activity, coffee intake, healthcare access, acute migraine medication use, symptoms of anxiety, depression, and fear of COVID-19. The results show that 48.6% of migraine patients experienced worsened symptoms, 15.6% improved, and 35.8% remained unchanged. Worsening migraine symptoms were associated with staying at home during the lockdown. Intake of analgesics was associated with an increase in migraine symptoms of 18 times relative to those who did not increase their intake. Migraine symptoms improved when the number of sleep hours was increased, and we observed an improvement when patients decreased analgesic intake. The uncertainty about the end of the pandemic, the news, and social media are three items that contributed to the worsening of migraine symptoms in patients in the three investigated countries. Confinement during the first pandemic wave in Latin America harmed migraine patients who stayed home during the lockdown.
Parasomnias in Pregnancy

Objectives: Pregnancy is often associated with reduced sleep quality and an increase in sleep disorders, such as restless leg syndrome, obstructive sleep apnea, and insomnia. There are few studies investigating the prevalence of parasomnias in pregnancy, although they may be expected to be a significant problem, as disturbed sleep in this time period in addition to these sleep disorders may trigger parasomnia episodes. Methods: We conducted a survey using an online questionnaire focusing on a comparison of the prevalence of parasomnias in three time periods: 3 months before pregnancy, during pregnancy, and 3 months after delivery. We also inquired about psychiatric and neurological comorbidities, current anxiety and depression symptoms, and pregnancy complications. Results: A total of 325 women (mean age 30.3 ± 5.3 years) participated in the online survey. The overall number of reported parasomnias increased during pregnancy compared to the 3 months before pregnancy (p < 0.001) and decreased after childbirth (p < 0.001). Specifically, we found a significant increase in sleepwalking (p = 0.02) and night terrors (p < 0.001), as well as in vivid dreams (p < 0.001) and nightmares (p < 0.001) during pregnancy. A similar significant increase during pregnancy was reported for head explosion (p < 0.011). In contrast, the number of episodes of sleep paralysis increased after delivery (p = 0.008). At the individual level, an increase in the severity/frequency of individual parasomnia episodes was also observed during pregnancy. Participants whose vivid dreams/nightmares persisted after delivery had higher BDI-II and STAI-T scores. Our data also suggest a significant impact of migraines and other chronic pain, as well as complications during pregnancy, on the presence of parasomnia episodes in our cohort. Conclusions: We have shown that the prevalence of parasomnias increases during pregnancy and needs to be targeted, especially by non-pharmacological approaches. At the same time, it is necessary to inquire about psychiatric and neurological comorbidities and keep in mind that more sleep disorders may be experienced by mothers who have medical complications during pregnancy.
Pore‐Scale Modeling of Nonwetting‐Phase Residual in Porous Media

The complexity of the formation and removal of nonwetting-phase residual in porous media provides a significant challenge to the development of theories needed to advance more effective aquifer remediation schemes. Constitutive theories are required to overcome theoretical deficiencies in describing behaviors such as the formation, dissolution, and mobilization of residual. Current macroscopic approaches are often unable to capture adequately the complexity of such processes; in these cases, pore-scale research should provide the necessary conceptual and quantitative basis for constitutive theory development. This work contributes to these efforts by investigating factors affecting residual in strongly wet, capillary-dominated systems. Porous media are modeled as three-dimensional networks of pore bodies and throats. A random network approach is developed, which provides stochastic geometry and variable connectivity. Immiscible displacement occurs via piston-displacement and film-flow mechanisms. Residual ganglia become trapped during imbibition. Wetting-phase continuity is maintained during drainage, disallowing the entrapment of wetting-phase ganglia. Results show that pore- scale geometric parameters significantly affect residual saturation, the ganglia-volume distribution, and nonwetting-wetting-phase interfacial area. Thus constitutive theory of residual should incorporate pore-scale knowledge to be valid for a wide range of conditions and porous media types. Comparison with quantitative experimental ganglia- volume distributions yields good agreement with the data trends but poor quantitative agreement. These results indicate the need for further experimental comparisons with theoretical results, linking macroscale and microscale theory and experiment.
Improved hydrogenerator field winding thermal monitoring

A new monitoring method for determination of average hydrogenerator field winding temperature is introduced in order to increase the robustness of the temperature measurement system using the classic U-I method. The classic approach is prone to error due to brush voltage drop, especially when field voltage is low. Developed thermal model is based on field current and cold cooling air temperature measurements, as well on temperatures acquired from digital temperature sensors mounted across the field winding. To monitor the rotor temperature for generators with brushless excitation where field voltage and current measurements are not accessible, a mathematical model was developed to estimate the average field winding temperature based on the existing temperature monitoring of the cooling medium and mounted sensors. Importance of the proposed approach arises from the foreseen widespread use of brushless generators in distributed generation. The developed models were compared and their sensitivity was examined thoroughly.
The explanatory factors of disclosures related to the discount rates by listed entities in Portugal

ABSTRACT This paper aims to identify the explanatory factors of mandatory disclosure (MD) and voluntary disclosure (VD) levels related to discount rates, based on disclosure theories. The size, leverage, profitability, and audit firms were selected from different theories, namely agency theory, signaling theory, positive accounting theory, including the political cost hypothesis, and the cost of capital theory. Furthermore, the materiality (weight of the items) and the relevance (nature) of the topic were also considered, based on the evidence already obtained in the literature. Research on disclosures related to discount rates has been assessed either as an incidental topic or from a limited-scope analysis, particularly with respect to MDs. This paper assesses this topic as its specific object of analysis for both MD and VD. The use of the discount rate has been assuming growing importance within financial reporting. Therefore, this topic should deserve particular attention from international standard-setting bodies. The understanding of the proper set of items to be disclosed and understanding the factors that explain its disclosure, aligned with the efforts to assure its compliance by legal authorities, may contribute to reducing asymmetries and increasing transparency in entities' financial reporting. This study uses the method of archival research and content analysis of consolidated reports and accounts for the year 2020 of listed entities in Euronext Lisboa. Regression models were used, having disclosure indices related to discount rates as dependent variables. This paper finds a positive association between disclosures related to discount rates and the entity’s size, as well as the materiality and the relevance, assessed by the weight of the items and the nature of the topic under assessment, respectively. It adds new explanatory factors on the VDs and MDs related to discount rates in a broader perspective of analysis.
Radical Scavenging Potential of Ginkgolides and Bilobalide: Insight from Molecular Modeling

The reactive oxygen species (ROS) scavenging capacities of ginkgolides and bilobalide, which are the peculiar constituents of the extract of Ginkgo biloba, are investigated in silico (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Unlike other popular antioxidant natural substances, the carbon backbones of these compounds are entirely aliphatic and exclusively single C–C bonds are present. The selectivity for alkoxyl radicals via hydrogen-atom transfer (HAT) is assessed; importantly, the scavenging of peroxyl radicals is also possible from a peculiar site, here labeled C10 both for ginkgolides and bilobalide. The energetics are described in detail, and the analysis discloses that the studied compounds are powerful scavengers, with thermodynamic and kinetic properties similar to those of Trolox and melatonin, and that, in addition, they display selectivity for peroxyl radicals. These are all chemical-reactivity features contributing to the therapeutic action of the extract of G. biloba.
Anomalous transport matrix for cylindrical plasmas

Transport equations are investigated for a cylindrical plasma in the presence of electrostatic fluctuations. In a weakly turbulent regime, the transport matrices that relate the anomalous particle and heat fluxes and the parallel current to the thermodynamical forces are determined by employing drift-kinetic and gyrokinetic orderings for the electrons and ions. The calculation is based on the kinetic equations for the ensemble-averaged and fluctuating distribution functions. The crucial difference with previous works is the inclusion of an extra term in the drift-kinetic equation for the fluctuating electron distribution function. This extra term, which arises from the ensemble-averaged first-order (in a Larmor radius expansion) electron distribution function, leads to the Ware pinch components of the particle and heat fluxes and a correction to the Ohmic current. Furthermore, Shaing's ansatz, which was introduced in the synthetic theory of anomalous and neoclassical transport, is shown to be connected with this extra term in the context of a turbulent plasma, and the physical meaning and the validity of this ansatz are revealed. In drift-wave turbulence, the transport matrices, expressed in an implicit form by considering the frequency of fluctuations as a parameter, are rewritten in an explicit form by determining its frequency through the dispersion relation. The Onsager symmetry is shown to be broken for this explicit form of anomalous transport matrix.
Association of weight-adjusted-waist index with asthma prevalence and the age of first asthma onset in United States adults

Objective The objective of this study was to assess whether the weight-adjusted-waist index(WWI) is associated with the prevalence of asthma and age when first asthma onset appears in US adults. Methods For analysis we selected participants from the National Health and Nutrition Examination Survey(NHANES)database between 2001 and 2018. A dose-response curve was calculated using logistic regression,subgroup analysis,and a dose-response curve. Results The study included 44480 people over the age of 20,including 6061 reported with asthma, and the increase in asthma prevalence was 15% associated with each unit increase in the WWI, after adjusting for all confounders(odds ratio(OR)=1.15,95% CI:1.11,1.20). The sensitivity analysis was performed by trichotomizing the WWI, and compared to the lowest tertile, the highest tertile WWI group displayed a 29% increase in asthma prevalence(OR=1.29,95% CI:1.19,1.40). A nonlinear correlation was found between the WWI index and the risk of asthma onset, with a threshold saturation effect indicating an inflection point of 10.53 (log-likelihood ratio test, P<0.05), as well as a positive linear correlation with age at first asthma onset. Conclusions A higher WWI index was associated with an increased prevalence of asthma and an older age of first asthma onset.