Miracle-dz/UniFAR-FTUs huggingface dataset:
Affordable Prices Without Threatening the Oncological R&D Pipeline—An Economic Experiment on Transparency in Price Negotiations

The high prices of innovative medicines endanger access to care worldwide. Sustainable prices need to be affordable while sufficiently incentivizing research and development (R&D) investments. A proposed solution is increased transparency. Proponents argue that price and R&D cost confidentiality are drivers of high prices. On the contrary, supporters of confidentiality claim that confidentiality enables targeted discounts which make treatments affordable; moreover, pharmaceutical companies argue that R&D investments would suffer with more transparency. Despite the political relevance, limited empirical evidence exists on the effects of transparency regulations. We contribute to fill this gap with an experiment where we replicate the EU pharmaceutical market in a laboratory setting. In a randomized controlled study, we analyzed how participants, 400 students located in four European countries, negotiated in the current system of Price Secrecy in comparison with innovative bargaining settings where either prices only (Price Transparency) or prices and R&D costs (Full Transparency) were made transparent to buyers. We found that Price transparency had no statistically significant effect on average prices or number of patients treated and made R&D investments significantly smaller (−16.86%; P: 0.0024). On the other hand, Full Transparency reduced prices (−26%; P: 0.0004) and held the number of patients constant at the level of Price Secrecy. It produced price convergence between countries with low and high health budgets, and, despite lower prices, had no effect on R&D investments. Our findings provide novel evidence that combining price and R&D cost transparency could be an effective policy to contribute to sustainable medicine prices. See related article by Franzen et al. (Cancer Discov 2022;12:299–302).
Financial literacy, financial inclusion and participation of individual on the Ghana stock market

Abstract This paper examines the impact of financial literacy and financial inclusion on stock market participation in Ghana. It employs a sample of 1,966 respondents across the 10 regions of Ghana for the year 2018. We employ biprobit models to estimate the influence of financial literacy on financial inclusion, while robust probit models are used to independently analyse the effect of financial literacy and financial inclusion on stock market participation as well as their joint effect. We find the following results: first, financial literacy positively influences financial inclusion. Second, the study does not support previous findings that financial literacy is not a determinant of stock market participation in Ghana. Third, financial inclusion through using an account to save significantly affects stock market participation. Finally, the interaction of financial literacy and financial inclusion on stock market participation provides evidence of no significant effect.
Selective glycerol oxidation to glyceric acid under mild conditions using Pt/CeO2–ZrO2–Fe2O3/SBA-16 catalysts

ABSTRACT Effective glyceric acid production from glycerol was demonstrated under mild conditions in an open-air system at room temperature in the absence of base or oxygen gas flow by employing a Pt/CeO2–ZrO2–Fe2O3/Santa Barbara Amorphous No. 16 (SBA-16) catalyst. At a low loading amount of CeO2–ZrO2–Fe2O3 (16 wt%Ce0.64Zr0.16Fe0.20O2−δ/SBA-16), the oxygen release and storage abilities and high acidity of the catalyst afforded a high glyceraldehyde yield, owing to the enhancement of the oxidation ability of the Pt activator and the acceleration of the desorption of glyceraldehyde. The increase in CeO2–ZrO2–Fe2O3 loading amount further improved the oxygen release and storage abilities and lowered the catalyst acidity induced by crystallite growth and particle aggregation. The high oxygen release and storage abilities, as well as the low acidity, contributed to the high glyceric acid yield; the highest activity for glyceric acid production was obtained for the 7 wt%Pt/40 wt%Ce0.64Zr0. 16Fe0.20O2−δ/SBA-16 catalyst. The glyceric acid yield increased up to 68.2% after 10 h of reaction in atmospheric air at 30°C.
Investigation on antibacterial activity of α-Fe2O3 / ZnO nanocomposites against Gram-positive and Gram-negative bacteria

ABSTRACT In this study, α-Fe2O3/ZnO nanocomposites were synthesized by co-precipitation and solvothermal methods. The morphology, structure, and properties were characterized by FTIR, XRD, FESEM, EDS, and TEM techniques. The XRD patterns showed that the nanocomposite included rhombohedral haematite (α-Fe2O3), hexagonal zincite (ZnO), and cubic franklinite (ZnFe2O4). TEM images revealed the formation of rod-shaped particles with an average diameter of 18 nm and length of 125.82 nm. The quantity of Fe, Zn, and O was obtained to be 12.92%, 9.26%, and 77.82%, respectively. To investigate the effect of the zinc oxide concentration on antibacterial properties, α-Fe2O3/ZnO nanocomposite FZ0.5, FZ1.5, and FZ2.5 were prepared. The antibacterial properties against Staphylococcus aureus, and Escherichia coli bacteria were investigated. α-Fe2O3/ZnO had an efficient antibacterial activity on Gram-positive bacterial strains, and nanocomposites with higher zinc levels demonstrated a more efficient antibacterial activity. The effect of calcination temperature on the antibacterial activity of the sample was also studied . Graphical abstract
Perceived identity threat and organizational cynicism in the recursive relationship between psychological contract breach and counterproductive work behavior

Counterproductive work behavior toward the organization (CWB-O) or supervisor (CWB-S) is commonly treated as a consequence of psychological contract breach (PCB). However, drawing from Self-Consistency Theory, the authors in this article argue that the PCB–CWB relationship is recursive through two mediating mechanisms: self-identity threat and organizational cynicism. Furthermore, the authors predict that the relationship between feelings of violation and CWB-O (or CWB-S) would depend on the extent to which the victim attributed blame to the organization (or supervisor). Using weekly and daily survey data, the study found that identity threat was a stronger mediator for recursive CWB–PCB relationships. Moreover, it was found that PCB related positively to violation feelings, which in turn related positively to CWB-O and CWB-S over time. As predicted, the former was moderated by organizational blame attributions, whereas the latter was moderated by supervisor blame attributions. The authors discuss the theoretical implications and propose novel practical implications based on these reciprocal findings.
Fluoroquinolone Persistence in Escherichia coli Requires DNA Repair despite Differing between Starving Populations

When faced with nutritional deprivation, bacteria undergo a range of metabolic, regulatory, and biosynthetic changes. Those adjustments, which can be specific or independent of the missing nutrient, often alter bacterial tolerance to antibiotics. Here, using fluoroquinolones, we quantified Escherichia coli persister levels in cultures experiencing starvation from a lack of carbon (C), nitrogen (N), phosphorous (P), or magnesium (Mg2+). Interestingly, persister levels varied significantly based on the type of starvation as well as fluoroquinolone used with N-starved populations exhibiting the highest persistence to levofloxacin, and P-starved populations exhibiting the highest persistence to moxifloxacin. However, regardless of the type of starvation or fluoroquinolone used, DNA repair was required by persisters, with ∆recA and ∆recB uniformly exhibiting the lowest persistence of the mutants assayed. These results suggest that while the type of starvation and fluoroquinolone will modulate the level of persistence, the importance of homologous recombination is consistently observed, which provides further support for efforts to target homologous recombination for anti-persister purposes.
A journey toward the heaven of chemical fidelity of intermolecular force fields

Alongside the evolution of density functional theory into a new era led by the dispersion‐corrected hybrid density functional theory approaches, formulation of a new generation of intermolecular potentials has also taken the center stage. An ideal potential formulation should desirably possess simplicity of functional forms, physically meaningful parameters, separability of various terms into atomic‐level contributions, computational tractability, ability to capture non‐additivity of interactions, transferability across different chemical species, and crucially, chemical fidelity in terms of reproducing the benchmark data. The Lennard‐Jones potential, one of the popular intermolecular pair potentials for performing large‐scale simulations fails to capture the intricate features of molecular interactions. Woven around the central theme of anisotropy in the nature of intermolecular interactions, herein, we describe various landmark contributions in the quest for chemical fidelity of empirical potential formulations that include (i) incorporation of the anisotropic nature of exchange‐repulsion and dispersion contributions, (ii) multipolar description of the dispersion terms, (iii) damping functions to provide an accurate description of the asymptotes, and (iv) transferability of intermolecular interaction terms. We illustrate the nuances of intermolecular force field development in the context of modeling the non‐covalent interactions governing the (i) binding of atoms and molecules with carbon nanostructures, (ii) molecular aggregates of polycyclic aromatic hydrocarbons, and (iii) interlayer interactions in layered nanostructures. We exemplify the hierarchy of empirical potentials by depicting them on the various rungs of the Jacob's ladder equivalent of density functional theory for the intermolecular force fields. Finally, we discuss some possible futuristic directions in intermolecular force field development.
Structure, People, and Relationships: A Multidimensional Method to Assess Museum Resilience

This article proposes a multidimensional method for measuring and evaluating museum resilience holistically. The research highlights the lack of a framework for understanding the level of resilience in museums and the contribution of museums to resilience. To this end, a model is presented based on three enabling dimensions, namely, structure, people, and relationships. The model is applied to the museums of the Marche region’s “seismic crater” (Italy). Qualitative information and data drawn from the regional authority’s Museum Information System were evaluated using exploratory analysis techniques. On the basis of a cluster analysis, four categories of museums are identified according to their degree of resilience. The results suggest that human resources is an area that is commonly in need of upgrading. Nevertheless, the evidence on the heterogeneity of the clusters in terms of structure and relationships calls for a diversified approach to identifying priorities, investments, and public policies.
Potential response of single successive constant-current-driven electrolytic hydrogen bubbles spatially separated from the electrode

In gas-evolving electrolytic processes, the presence of bubbles can heavily alter the mass transport of gaseous products and can induce severe overpotential penalties at the electrode through the action of bubble coverage (hyperpolarization) and electrolyte constriction (Ohmic shielding). However, bubble formation can also alleviate the overpotential by lowering the concentration of dissolved gas in the vicinity of the electrode. In this study, we investigate the latter by considering the growth of successive hydrogen bubbles driven by a constant current in alkaline-water electrolysis and their impact on the half-cell potential in the absence of hyperpolarization. The bubbles nucleate on a hydrophobic cavity surrounded by a ring microelectrode which remains free of bubble coverage. The dynamics of bubble growth does not adhere to one particular scaling law in time, but undergoes a smooth transition from pressure-driven towards supply-limited growth. The contributions of the different bubble-induced phenomena leading to the rich behaviour of the periodic fluctuations of the overpotential are identified throughout the different stages of the bubble lifetime, and the influence of bubble size and applied current on the concentration and Ohmic overpotential components is quantified. We find that the efficiency of gas absorption, and hence the concentration-lowering effect, increases with increasing bubble size and also with increasing current. However, the concentration-lowering effect is always eventually countered and overcome by the effect of Ohmic shielding as the bubble size outgrows and eclipses the electrode ring beneath.
The Sharp Spikes of Poverty: Financial Scarcity Is Related to Higher Levels of Distress Intensity in Daily Life

Although income is an important predictor of life satisfaction, the precise forces that drive this relationship remain unclear. We propose that financial resources afford individuals a path to reducing the distressing impact of everyday hassles, thereby increasing one’s life satisfaction. More specifically, we hypothesize that financial scarcity is associated with greater distress intensity in everyday life. Furthermore, we propose that lower perceived control helps explain why financial scarcity predicts higher distress intensity and lower life satisfaction. We provide evidence for these hypotheses in a 30-day daily diary study (522 participants, 13,733 observations). A second study (N = 376) further suggests that, although everyone relies on social support to ease stress, financial scarcity shrinks the sense one can use economic resources to reduce the adverse impact of daily hassles. Although money may not necessarily buy happiness, it reduces the intensity of stressors experienced in daily life—and thereby increases life satisfaction.
Clarifying Work Values Through Seasonal Employment: An Instrumental Case Study of Summer Camp Employment

Emerging adults need opportunities to clarify their work values. Although researchers have examined how transitions and work experiences influence emerging adults’ work values and job choices, less is known about how seasonal employment shapes work values. Using the theory of work adjustment as a guide, we conducted semi-structured interviews with 20–27 year olds (n = 76; mage = 22.03, SD = 1.82) to understand how their seasonal employment at summer camps influenced their work values. We found that seasonal camp employment aligned with and helped participants clarify their desire for dynamic work that makes a difference and that offers a supportive social environment with adequate work-life balance. Our findings suggest that seasonal employment affords emerging adults important opportunities to discover, reinforce, and prune work values in a temporary employment setting. We conclude by discussing implications for emerging adults’ career development and offer suggestions for career counselors.
Inhibitory IL-10-producing CD4+ T cells develop in a T-bet-dependent manner and facilitate cytomegalovirus persistence via coexpression of arginase-1

Inhibitory CD4+ T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity, but the mechanisms that underpin the development of such regulatory networks in vivo have remained obscure. To address this knowledge gap, we performed a comprehensive functional, phenotypic, and transcriptomic analysis of IL-10-producing CD4+ T cells induced by chronic infection with murine cytomegalovirus (MCMV). We identified these cells as clonally expanded and highly differentiated TH1-like cells that developed at sites of viral persistence in a T-bet-dependent manner and coexpressed arginase-1 (Arg1), which promotes the catalytic breakdown of L-arginine. Mice lacking Arg1-expressing CD4+ T cells exhibited more robust antiviral immunity and were better able to control MCMV. Conditional deletion of T-bet in the CD4+ lineage suppressed the development of these inhibitory cells and also enabled better immune control of MCMV. Collectively, these data elucidated the ontogeny of IL-10-producing CD4+ T cells and revealed a previously unappreciated mechanism of immune regulation, whereby viral persistence was facilitated by the coexpression of Arg1.
Glycoengineering of Darbepoetin-α in CHO-DG44 Cells through Overexpression of α-2,3-sialyl-transferase and CMP-sialic Acid Transporter

Sialic acid plays a very important role in determining the circulation life span of glycoprotein in various organisms. Therefore, having a high content of sialic acid is needed by glycoprotein therapeutic agents to be able to function as desired. For example, Darbepoetin (DPO), the 5 N-linked erythropoietin showed higher bioavailability and efficacy compared to 3 N-linked erythropoietin. However, in the DPO production process, the molecular weight can vary and is highly dependent on the content of sialic acid and its production host. To improve the DPO sialic acid contents in our CHO-DG44 expressing DPO, we have engineered the cells through overexpression of α-2,3-sialyl-transferase (ST) and CMP-sialic acid transporter (CST). The DPO contained in the supernatant of the engineered cells was analyzed by Western blot and characterized by using PNGase-F or neuraminidase enzyme digestions. The results showed that, two clones, overexpressing ST or CST, were obtained. The clones showed higher molecular weight of DPO as compared to DPO expressed by the parental cells, yet retained the same protein backbone. The overexpression of these two genes does not affect cell growth. This suggests that may be these cells beneficial for therapeutic glycoproteins.
A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma

Abstract Background Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs. Methods Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan–Meier method. Toxicities were assessed according to CTCAE v4.0. Results Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT. Conclusion Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.
From SARS-CoV-2 infection to COVID-19 morbidity: an in silico projection of virion flow rates to the lower airway via nasopharyngeal fluid boluses

Background: While the nasopharynx is initially the dominant upper airway infection site for SARS-CoV-2, the physiologic mechanism launching the infection at the lower airway is still not well-understood. Based on the rapidity of infection progression to the lungs, it has been hypothesized that the nasopharynx may be acting as the primary seeding zone for subsequent contamination of the lower airway via aspiration of virus-laden boluses of nasopharyngeal fluids. Methodology: To examine the plausibility of the aspiration-driven mechanism, we have computationally tracked the inhalation process in three anatomic airway reconstructions and have quantified the nasopharyngeal liquid volume transmitted to the lower airspace during each aspiration. Results: Extending the numerical trends on aspiration volume to earlier records on aspiration frequencies indicates a total aspirated nasopharyngeal liquid volume of 0.3 – 0.76 ml/day. Subsequently, for mean sputum viral load, our modeling projects that the number of virions reaching the lower airway will range over 2.1×106 – 5.3×106 /day; for peak viral load, the corresponding number hovers between 7.1×108 – 1.8×109. Conclusions: The virion transmission findings fill in a key piece of the mechanistic puzzle on the systemic progression of SARS-CoV-2, and subjectively point to health conditions like dysphagia, with proclivity to increased aspiration, as some of the potential underlying risk factors for aggressive lung infections.
Validade da velocidade crítica para a determinação dos efeitos do treinamento no limiar anaeróbio em corredores de endurance

Validity of the critical velocity for determination of the training effects on the anaerobic threshold in endurance runners. The objective of this study was to analyze the validity of the critical velocity (CV) to evaluate the anaerobic threshold (AnT), before and after two different training programs in endurance athletes. Seventeen male runners (33.4 ± 4.4 years; 62.7 ± 4.3 kg; 166.1 ± 5.0 cm) divided in two groups (G95% - N = 9 and G100% - N = 8) performed the following tests: 1) Maximum shots of 1500 and 5000 m for determination of the CV; 2) Determination of the VO2max, the speed corresponding to VO2max (vVO2max), running economy (EC), AnT and time to exhaustion (Tlim) at the intensity of 95 and 100% vVO2max. Tests were performed before and after 4 weeks of training, which was similar to both groups, except for the two days of interval training. Before training, there were no differences between AnT (17.31 ± 1.3; 17.35 ± 0.8 km/h) and CV (16.97 ± 1.1; 17.44 ± 0,9 km/h) for G95% and G100%, respectively. After training, there was an improvement in AnT (G95% = 17.98 ± 1.1; G100% = 18.11 ± 0.6 km/h) for the two groups, and in CV for G95% (G95% = 17.25 ± 1.0; G100% = 17.63 ± 0.7 km/h). In this period, the AnT was higher than the CV for the two groups. We can conclude that the validity of the CV to evaluate the AnT determined with fixed blood lactate concentration (4 mM), may be dependent on the period and/or type of training performed by endurance athletes.