Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-asthmatic effect of nitric oxide metallo-donor FOR811A [cis-[Ru(bpy)2(2-MIM)(NO)](PF6)3] in the respiratory mechanics of Swiss mice

We aimed at evaluating the anti-asthmatic effect of cis-[Ru(bpy)2(2-MIM)(NO)](PF6)3 (FOR811A), a nitrosyl-ruthenium compound, in a murine model of allergic asthma. The anti-asthmatic effects were analyzed by measuring the mechanical lung and morphometrical parameters in female Swiss mice allocated in the following groups: untreated control (Ctl+Sal) and control treated with FOR811A (Ctl+FOR), along asthmatic groups untreated (Ast+Sal) and treated with FOR811A (Ast+FOR). The drug-protein interaction was evaluated by in-silico assay using molecular docking. The results showed that the use of FOR811A in experimental asthma (Ast+FOR) decreased the pressure-volume curve, hysteresis, tissue elastance, tissue resistance, and airway resistance, similar to the control groups (Ctl+Sal; Ctl+FOR). However, it differed from the untreated asthmatic group (Ast+Sal, p<0.05), indicating that FOR811A corrected the lung parenchyma and relaxed the smooth muscles of the bronchi. Similar to control groups (Ctl+Sal; Ctl+FOR), FOR811A increased the inspiratory capacity and static compliance in asthmatic animals (Ast+Sal, p<0.05), showing that this metallodrug improved the capacity of inspiration during asthma. The morphometric parameters showed that FOR811A decreased the alveolar collapse and kept the bronchoconstriction during asthma. Beyond that, the molecular docking using FOR811A showed a strong interaction in the distal portion of the heme group of the soluble guanylate cyclase, particularly with cysteine residue (Cys141). In summary, FOR811A relaxed bronchial smooth muscles and improved respiratory mechanics during asthma, providing a protective effect and promising use for the development of an anti-asthmatic drug.
The closure issue related to liquid–cell mass transfer and substrate uptake dynamics in biological systems

An original dynamic model for substrate uptake under transient conditions is established and used to simulate a variety of biological responses to external perturbations. The actual uptake and growth rates, treated as cell properties, are part of the model variables as well as the substrate concentration at the cell–liquid interface. Several regulatory loops inspired by the structure of the glycolytic chain are considered to establish a set of ordinary differential equations. The uptake rate evolves so as to reach an equilibrium between the cell demand and the environmental supply. This model does not contain any of the usual algebraic closure laws relating to the instantaneous uptake, growth rates, and the substrate concentration, nor does it enforce the continuity of mass fluxes at the liquid–cell interface. However, these relationships are found in the steady‐state solution. Previously unexplained experimental observations are well reproduced by this model. Also, the model structure is suitable for further coupling with flux‐based metabolic models and fluid‐flow equations.
De novo synthesis of pH-responsive, self-assembled, and targeted polypeptide nano-micelles for enhanced delivery of doxorubicin

Doxorubicin (DOX) is a commonly used anticancer drug, but it is inefficient as a therapeutic due to a lack of targeting. Peptide-tuned self-assembly of DOX offers a strategy to improve targeting for greater efficacy. In this work, we designed and prepared an amphiphilic tumor cell-targeting peptide, P14 (AAAAFFFHHHGRGD), able to encapsulate DOX by self-assembly to form tumor cell-targeting and pH-sensitive nano-micelles. The results showed a critical P14-micelle concentration of 1.758 mg l−1 and an average particle size of micelles of 121.64 nm, with entrapment and drug-loading efficiencies of 28.02% ± 1.35% and 12.06% ± 0.59%, respectively. The prepared micelles can release 73.52 ± 1.27% DOX within 24 h in pH 4.5 medium, and the drug cumulative release profile of micelles can be described by the first-order model. Compared with free DOX, the micelles exhibited an increased ability to inhibit tumor cell growth and cause tumor apoptosis in vitro, with IC50 values of DOX and P14-DOX micelles against human breast cancer cells (MCF-7) of 0.91 ± 0.07 and 0.75 ± 0.06 μg ml−1, respectively, and cellular apoptotic rates of DOX and P14-DOX micelles of 70.3% and 42.4%, respectively. Cellular uptake experiments revealed high concentrations of micelles around and inside MCF-7 cells, demonstrating that micelles can target tumor cells. These results indicate the excellent potential for the application of this amphiphilic peptide as a carrier for small-molecule drugs and suggest a strategy for the design of effective anti-tumor drugs.
Detrimental effects of intrahospital transport on cerebral metabolism in patients suffering severe aneurysmal subarachnoid hemorrhage.

OBJECTIVE Intrahospital transport for CT scans is routinely performed for neurosurgical patients. Particularly in the sedated and mechanically ventilated patient, intracranial hypertension and blood pressure fluctuations that might impair cerebral perfusion are frequently observed during these interventions. This study quantifies the impact of intrahospital patient transport on multimodality monitoring measurements, with a particular focus on cerebral metabolism. METHODS Forty intrahospital transports in 20 consecutive patients suffering severe aneurysmal subarachnoid hemorrhage (SAH) under continuous intracranial pressure (ICP), brain tissue oxygen tension (pbtO2), and cerebral microdialysis monitoring were prospectively included. Changes in multimodality neuromonitoring data during intrahospital transport to the CT scanner and the subsequent 10 hours were evaluated using linear mixed models. Furthermore, the impact of risk factors at transportation, such as cerebral vasospasm, cerebral hypoxia (pbtO2 < 15 mm Hg), metabolic crisis (lactate-pyruvate ratio [LPR] > 40), and transport duration on cerebral metabolism, was analyzed. RESULTS During the transport, the mean ICP significantly increased from 7.1 ± 3.9 mm Hg to 13.5 ± 6.0 mm Hg (p < 0.001). The ICP exceeded 20 mm Hg in 92.5% of patients; pbtO2 showed a parallel rise from 23.1 ± 13.3 mm Hg to 28.5 ± 23.6 mm Hg (p = 0.02) due to an increase in the fraction of inspired oxygen during the transport. Both ICP and pbtO2 returned to baseline values thereafter. Cerebral glycerol significantly increased from 71.0 ± 54.9 µmol/L to 75.3 ± 56.0 µmol/L during the transport (p = 0.01) and remained elevated for the following 9 hours. In contrast, cerebral pyruvate and lactate levels were stable during the transport but showed a significant secondary increase 1-8 hours and 2-9 hours, respectively, thereafter (p < 0.05). However, the LPR remained stable over the entire observation period. Patients with extended transport duration (more than 25 minutes) were found to have significantly higher levels of cerebral pyruvate and lactate as well as lower glutamate concentrations in the posttransport period. CONCLUSIONS Intrahospital transport and horizontal positioning during CT scans induce immediate intracranial hypertension and an increase in cerebral glycerol, suggesting neuronal injury. Afterward, sustained impairment of neuronal metabolism for several hours could be observed, which might increase the risk of secondary ischemic events. Therefore, intrahospital transport for neuroradiological imaging should be strongly reconsidered and only indicated if the expected benefit of imaging results outweighs the risks of transportation.
Novel Antimuscarinic Antidepressant-like Compounds with Reduced Effects on Cognition

The cholinergic nervous system has been implicated in mood disorders, evident in the fast-onset antidepressant effects of scopolamine, a potent muscarinic antagonist, in clinical studies. One prominent disadvantage of the use of scopolamine in the treatment of depression is its detrimental effects on cognition, especially as such effects might aggravate cognitive deficits that occur with depression itself. Thus, the identification of antimuscarinic drugs that are free of such detrimental effects may provide an important avenue for the development of novel therapeutics for the management of depression. The present data in rats indicate that a historical muscarinic antagonist, L-687,306, and a muscarinic antagonist of our own design, CJ2100, were as or more effective than scopolamine in antagonizing both the bradycardic effects of the muscarinic agonist arecoline in cardiovascular studies and its discriminative stimulus and rate-decreasing effects in behavioral studies. Additionally, both novel muscarinic antagonists were as effective as scopolamine in decreasing immobility in the forced swim test, a preclinical indicator of potential antidepressant activity. However, at equieffective or even larger doses, they were considerably less disruptive than scopolamine in assays of cognition-related behavior. All three drugs displayed high specificity for the mAChRs with few off-target binding sites, and CJ2100 showed modest affinity across the mAChRs when compared with L-687,306 and scopolamine. These data emphasize the dissimilar pharmacological profiles that are evident across antimuscarinic compounds and the potential utility of novel antagonists for the improved treatment of depression. SIGNIFICANCE STATEMENT Some clinical studies with the muscarinic antagonist scopolamine document its ability to produce antidepressant effects in patients with mood disorders; however, scopolamine also has well known adverse effects on both autonomic and centrally mediated physiological functions that limit its therapeutic use. This study characterizes the cardiovascular and discriminative stimulus effects of two novel muscarinic antagonists, L-687,306 and CJ2100, that produce antidepressant-like effects in a rodent model (forced swim test) without affecting touchscreen-based cognitive performance (titrating psychomotor vigilance and delayed matching-to-position).
Raman scattering studies on nanocrystalline BaTiO3 Part I—isolated particles and aggregates

BaTiO3 powders with various crystallite sizes, which were prepared through microemulsion-mediated synthesis, were thoroughly studied by Raman spectroscopy. Clear evidence for the presence of the tetragonal phase was found for ultrafine powders with an average crystallite size above 30 nm. The lifetime of phonons that are specifically assigned to the tetragonal phase decreased with decreasing crystallite size below a critical size of 100 nm. In particles as fine as 100 nm, the short mean free path of phonons, mainly due to internal pressure, causes decoupling of the coupled A1 (TO) phonons and a diffuse phase transition behaviour (TC = 115 °C). Coupled A1(TO) phonons, which give a spectral dip at around 180 cm−1 and a lesser extent of diffuseness, were revealed for powders consisting of particles as large as 0.17 µm (TC = 123 °C). Further coarsening upon annealing induced the formation of aggregates, resulting in the shift of phase transition points to higher temperatures for the rhombohedral to orthorhombic and the orthorhombic to tetragonal transitions and to lower temperatures for the tetragonal to cubic transition, respectively. Phase stability in powders is discussed by considering possible factors such as internal pressure in isolated particles and internal stress in aggregates. Copyright © 2007 John Wiley & Sons, Ltd.
Societal Costs of a Measles Outbreak

We estimate the economic burden of a measles outbreak from a societal perspective, including public health response costs, direct medical costs, and productivity losses. BrightcoveDefaultPlayer10.1542/6227458861001PEDS-VA_2020-027037 Video Abstract BACKGROUND AND OBJECTIVES: Between December 31, 2018, and April 26, 2019, 72 confirmed cases of measles were identified in Clark County. Our objective was to estimate the economic burden of the measles outbreak from a societal perspective, including public health response costs as well as direct medical costs and productivity losses of affected individuals. METHODS: To estimate costs related to this outbreak from the societal perspective, 3 types of costs were collected or estimated: public health response (labor, material, and contractor costs used to contain the outbreak), direct medical (third party or patient out-of-pocket treatment costs of infected individuals), and productivity losses (costs of lost productivity due to illness, home isolation, quarantine, or informal caregiving). RESULTS: The overall societal cost of the 2019 Clark County measles outbreak was ∼$3.4 million ($47 479 per case or $814 per contact). The majority of the costs (∼$2.3 million) were incurred by the public health response to the outbreak, followed by productivity losses (∼$1.0 million) and direct medical costs (∼$76 000). CONCLUSIONS: Recent increases in incident measles cases in the United States and across the globe underscore the need to more fully understand the societal cost of measles cases and outbreaks and economic consequences of undervaccination. Our estimates can provide valuable inputs for policy makers and public health stakeholders as they consider budget determinations and the substantial value associated with increasing vaccine coverage and outbreak preparedness as well as the protection of society against vaccine-preventable diseases, such as measles, which are readily preventable with high vaccination coverage.
The Missing Expression Level–Evolutionary Rate Anticorrelation in Viruses Does Not Support Protein Function as a Main Constraint on Sequence Evolution

Abstract One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, because it scales with the extent of selective constraints imposed on a protein, leading to the well-known negative correlation between expression level and protein evolutionary rate (the E–R anticorrelation). Selective constraints have been hypothesized to entail the maintenance of protein function, the avoidance of cytotoxicity caused by protein misfolding or nonspecific protein–protein interactions, or both. However, empirical tests evaluating the relative importance of these hypotheses remain scarce, likely due to the nontrivial difficulties in distinguishing the effect of a deleterious mutation on a protein’s function versus its cytotoxicity. We realized that examining the sequence evolution of viral proteins could overcome this hurdle. It is because purifying selection against mutations in a viral protein that result in cytotoxicity per se is likely relaxed, whereas purifying selection against mutations that impair viral protein function persists. Multiple analyses of SARS-CoV-2 and nine other virus species revealed a complete absence of any E–R anticorrelation. As a control, the E–R anticorrelation does exist in human endogenous retroviruses where purifying selection against cytotoxicity is present. Taken together, these observations do not support the maintenance of protein function as the main constraint on protein sequence evolution in cellular organisms.
Physiologic Reserve Assessment and Application in Clinical and Research Settings in Liver Transplantation

Physiologic reserve is an important prognostic indicator. Because of its complexity, no single test can measure an individual’s physiologic reserve. Frailty is the phenotypic expression of decreased reserve and portends poor prognosis. Both subjective and objective tools have been used to measure one or more components of physiologic reserve. Most of these tools appear to predict pretransplant mortality, but only some predict posttransplant survival. Incorporation of these measures of physiologic reserve in the clinical and research settings including prediction models are reviewed, and the applicability to patient‐related outcomes are discussed. Commonly used tools, in patients with cirrhosis, that have been associated with clinical outcomes were reviewed. The strength of subjective tools lies in low‐cost, wide availability, and quick assessments at the bedside. A disadvantage of these tools is the manipulative capacity, restricting their value in allocation processes. The strength of objective tests lies in objective measurements and the ability to measure change. The disadvantages include complexity, increased cost, and limited accessibility. Heterogeneity in the definitions and tools used has prevented further advancement or a clear role in transplant assessment. Consistent use of objective tools, including the 6‐minute walk test, gait speed, Liver Frailty Index, or Short Physical Performance Battery, are recommended in clinical and research settings.
A description of three methods for the determination of the initial inert particulate chemical oxygen demand of wastewater

Three different methods are described for the determination of the initial inert particulate organics, measured in terms of COD. The methods involve experimental procedures using batch reators and are designed to differentiate residual particulate products generated by metabolic activities during the treatment processes. In the first method, the final threshold value of the particulate COD is monitored in an aerated batch reactor fed by the initial total COD. The second method uses the threshold values of the total and soluble COD in two parallel batch reactors, one fed with unfiltered and the other with filtered wastewater. The third method involves running three batch reactors, two with the wastewater to be studied and the thired with glucose. One method has been experimentally tested to assess the inert particulate fractions of domestic and textile wastewaters.
Electron spin resonance and resistivity studies of charge-ordered Bi1−xCaxMnO3

In this paper we report the temperature dependent electron spin resonance (ESR) and electrical resistivity studies on Bi(1−x)CaxMnO3 (x = 0.4, 0.45, 0.5, 0.6). The values of charge-ordering temperature TCO and Neel temperature TN estimated from ESR data are comparable to values obtained by other techniques and reported in the literature. The double integrated (DI) intensity of the ESR signal versus temperature and ln DI versus 1000/T plots have been used to get information about magnetic interactions. It is found that the magnetic phase for T > TCO is dominated by ferromagnetic (FM) correlations which can be attributed to activated Mn3+–Mn4+ hopping of a small polaron. In the temperature range TCO > T > TN, the domains of FM and antiferromagnetic (AFM) spin correlations coexist. The contribution of AFM correlations progressively increase with the increase in Ca content. The sharp change in the slope of ln DI versus 1000/T plot at ∼170–190 K indicates the onset of long-range AFM order. For T < TN, temperature independent ln DI indicates the freezing of FM microdomains/inhomogeneities in the AFM long-range ordered state. The temperature dependent resistivity data are analysed in view of the polaron model. The resistivity data analysed in view of Mott's VRH show that lnρ varies linearly with T−1/4, with a change in slope at TN. It is also found that ln ρ varies linearly with T−1/2 in the entire temperature range below TCO for all the compositions. The Griffiths phase physics may be an appropriate theoretical model for describing the ESR and resistivity data in the present system.
Defect Structure and Electrical Properties of Single‐Crystal Ba0.03Sr0.97TiO3

The electrical conductivity and thermoelectric power of single-crystalline Ba0.03Sr0. 97TiO3 were measured over a wide temperature (800° to 1100°C) and oxygen partial pressure (105 to 10-15 Pa) range. Our experimental data, like those of previous workers on nominally undoped BaTiO3 or SrTiO3, support a defect model based on doubly ionized oxygen vacancies, electrons, holes, and accidental acceptor impurities. The simultaneous measurement of electrical conductivity and thermoelectric power, together with precise experimental data obtained with an advanced thermoectric power measurement technique, enabled us to determine for the first time reliable values for the preexponential factors and the activation energies which characterize the defect equilibrium constants. These calculated values, together with the defect model, were found to give an excellent fit to the experimental data, and were used to generate the boundaries, in Po2-1/T space, of the various defect regimes.
Improved conductive atomic force microscopy measurements on organic photovoltaic materials via mitigation of contact area uncertainty

Physical processes that lead to conversion of light into electrical energy inside photovoltaic devices happen at the nanoscale. Therefore, understanding of electrical properties of photovoltaic materials at this length scale is of paramount importance for improvement of device performance. In this paper, we describe and validate a new framework for high‐resolution quantitative measurements of electrical and mechanical properties of compliant materials with sub‐100‐nm resolution. Previous approaches have generally suffered from uncertainty in the quantitative level of contact between the probe and the material being measured; the methodology presented here overcomes this obstacle. We use the broadly studied ITO/PEDOT:PSS/P3HT:PC61BM system as an example to illustrate variability of chemical composition and electrical properties of the active layer at hundred‐nanometers and micrometer length scales. Copyright © 2012 John Wiley & Sons, Ltd.
Corrigendum: Reprogramming of aerobic glycolysis in non‐transformed mouse liver with pyruvate dehydrogenase complex deficiency

The authors of the article by Patel et al. (2021) noticed an error in the funding information. The presently listed information in the paper is: Funding information: This work was supported in part by US Public Health Service Grant NS093264 (MSP). However, the correct information should read as: Funding information: This work was supported in part by US Public Health Service Grant DK20478 (MSP).
Physician Burnout: A Lifestyle Medicine Perspective

Physician burnout, as described in North America, is a multidimensional work-related syndrome that includes emotional exhaustion, depersonalization, and a low sense of accomplishment from work. More than 50% of physicians were reporting symptoms of burnout prior to the COVID-19 pandemic. This silent epidemic of burnout is bound to become less silent as the pandemic continues. Lifestyle medicine is an evidence-based discipline that describes how daily habits and health practices can affect overall health and well-being of individuals. Lifestyle Medicine can potentially play a significant role in preventing and ameliorating physician burnout. This article explores the burnout process, including the historical context, international definitions, symptoms, and imprecision of the clinical diagnosis. The systemic etiological issues are discussed, and the psychological underpinnings are explored, including physicians’ personal vulnerabilities contributing to burnout. The stress response and lifestyle medicine’s role in healthy coping are described. A prevention model for risk factor reduction is proposed, focusing on primordial, primary, secondary, and tertiary prevention. Lifestyle medicine clinicians’ role in prevention, treatment, and advocacy to ameliorate the potential for burnout is discussed along with specific recommendations.