Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective.

BACKGROUND Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC. METHODS A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (ClinicalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained. RESULTS In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of $55,285 and $61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure. CONCLUSIONS In a US healthcare setting, durvalumab was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.
Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.
Methods for Social Media Monitoring Related to Vaccination: Systematic Scoping Review

Background Social media has changed the communication landscape, exposing individuals to an ever-growing amount of information while also allowing them to create and share content. Although vaccine skepticism is not new, social media has amplified public concerns and facilitated their spread globally. Multiple studies have been conducted to monitor vaccination discussions on social media. However, there is currently insufficient evidence on the best methods to perform social media monitoring. Objective The aim of this study was to identify the methods most commonly used for monitoring vaccination-related topics on different social media platforms, along with their effectiveness and limitations. Methods A systematic scoping review was conducted by applying a comprehensive search strategy to multiple databases in December 2018. The articles’ titles, abstracts, and full texts were screened by two reviewers using inclusion and exclusion criteria. After data extraction, a descriptive analysis was performed to summarize the methods used to monitor and analyze social media, including data extraction tools; ethical considerations; search strategies; periods monitored; geolocalization of content; and sentiments, content, and reach analyses. Results This review identified 86 articles on social media monitoring of vaccination, most of which were published after 2015. Although 35 out of the 86 studies used manual browser search tools to collect data from social media, this was time-consuming and only allowed for the analysis of small samples compared to social media application program interfaces or automated monitoring tools. Although simple search strategies were considered less precise, only 10 out of the 86 studies used comprehensive lists of keywords (eg, with hashtags or words related to specific events or concerns). Partly due to privacy settings, geolocalization of data was extremely difficult to obtain, limiting the possibility of performing country-specific analyses. Finally, 20 out of the 86 studies performed trend or content analyses, whereas most of the studies (70%, 60/86) analyzed sentiments toward vaccination. Automated sentiment analyses, performed using leverage, supervised machine learning, or automated software, were fast and provided strong and accurate results. Most studies focused on negative (n=33) and positive (n=31) sentiments toward vaccination, and may have failed to capture the nuances and complexity of emotions around vaccination. Finally, 49 out of the 86 studies determined the reach of social media posts by looking at numbers of followers and engagement (eg, retweets, shares, likes). Conclusions Social media monitoring still constitutes a new means to research and understand public sentiments around vaccination. A wide range of methods are currently used by researchers. Future research should focus on evaluating these methods to offer more evidence and support the development of social media monitoring as a valuable research design.
Timely Control of Gastrointestinal Eubiosis: A Strategic Pillar of Pig Health

The pig gastrointestinal tract (GIT) is an open ecosystem in which microorganisms and their host are mutually involved and continually adapt to different factors and problems which may or may not be host dependent or due to the production system. The aim of the present review is to highlight the factors affecting the GIT microbial balance in young pigs, focusing on the pre- and post-weaning phases, to define a road map for improving pig health and the production efficiency of the food chain. Birth and weaning body weight, physiological maturation, colostrum and milk (composition and intake), genetic background, environmental stressors and management practices, antibiotic use and diet composition are considered. Overall, there is a lack of knowledge regarding the effect that some factors, including weaning age, the use of creep feed, the composition of the colostrum and milk and the use of antibiotics, may have on the gut microbiome of piglets. Furthermore, the information on the gut microbiome of piglets is mainly based on the taxonomy description, while there is a lack of knowledge regarding the functional modification of the microbiota, essential for the exploitation of microbiota potential for modulating pig physiology.
Screening and Genetic Network Analysis of Genes Involved in Freezing and Thawing Resistance in DaMDHAR—Expressing Saccharomyces cerevisiae Using Gene Expression Profiling

The cryoprotection of cell activity is a key determinant in frozen-dough technology. Although several factors that contribute to freezing tolerance have been reported, the mechanism underlying the manner in which yeast cells respond to freezing and thawing (FT) stress is not well established. Therefore, the present study demonstrated the relationship between DaMDHAR encoding monodehydroascorbate reductase from Antarctic hairgrass Deschampsia antarctica and stress tolerance to repeated FT cycles (FT2) in transgenic yeast Saccharomyces cerevisiae. DaMDHAR-expressing yeast (DM) cells identified by immunoblotting analysis showed high tolerance to FT stress conditions, thereby causing lower damage for yeast cells than wild-type (WT) cells with empty vector alone. To detect FT2 tolerance-associated genes, 3′-quant RNA sequencing was employed using mRNA isolated from DM and WT cells exposed to FT (FT2) conditions. Approximately 332 genes showed ≥2-fold changes in DM cells and were classified into various groups according to their gene expression. The expressions of the changed genes were further confirmed using western blot analysis and biochemical assay. The upregulated expression of 197 genes was associated with pentose phosphate pathway, NADP metabolic process, metal ion homeostasis, sulfate assimilation, β-alanine metabolism, glycerol synthesis, and integral component of mitochondrial and plasma membrane (PM) in DM cells under FT2 stress, whereas the expression of the remaining 135 genes was partially related to protein processing, selenocompound metabolism, cell cycle arrest, oxidative phosphorylation, and α-glucoside transport under the same condition. With regard to transcription factors in DM cells, MSN4 and CIN5 were activated, but MSN2 and MGA1 were not. Regarding antioxidant systems and protein kinases in DM cells under FT stress, CTT1, GTO, GEX1, and YOL024W were upregulated, whereas AIF1, COX2, and TRX3 were not. Gene activation represented by transcription factors and enzymatic antioxidants appears to be associated with FT2-stress tolerance in transgenic yeast cells. RCK1, MET14, and SIP18, but not YPK2, have been known to be involved in the protein kinase-mediated signalling pathway and glycogen synthesis. Moreover, SPI18 and HSP12 encoding hydrophilin in the PM were detected. Therefore, it was concluded that the genetic network via the change of gene expression levels of multiple genes contributing to the stabilization and functionality of the mitochondria and PM, not of a single gene, might be the crucial determinant for FT tolerance in DaMDAHR-expressing transgenic yeast. These findings provide a foundation for elucidating the DaMDHAR-dependent molecular mechanism of the complex functional resistance in the cellular response to FT stress.
Hépatite virale B lors d´une campagne de dépistage en population générale au Bénin: séroprévalence et facteurs associés

Introduction l´hépatite B est un problème mondial de santé publique. Le but de cette étude était de déterminer la prévalence et les facteurs associés au portage du virus de l´hépatite B (VHB) à l´occasion d´un dépistage de masse dans plusieurs localités réparties sur le territoire béninois. Méthodes il s´agissait d´une étude transversale descriptive et analytique avec une collecte prospective de données. Cette collecte avait eu lieu du 20 au 28 juillet 2019 à l´occasion d´un dépistage volontaire gratuit de l´hépatite B organisé au Bénin par les Club Rotary sur 23 sites répartis sur tout le territoire national. Un test rapide d´orientation diagnostique avait été utilisé pour la détection de l´Antigène HBs. Résultats en tout, 9035 volontaires étaient inclus, pour la plupart de nationalité Béninoise (99%), avec un âge médian de 27 ans, dont 51,1% de célibataires et principalement des écoliers, élèves ou étudiants (37,9%). La séroprévalence du VHB était de 6% (545/9035) [IC95%, 5%-6, 5%]. Les facteurs associés au portage de l´Ag HBs étaient, en analyse univariée: l´âge, le sexe, le statut matrimonial, le niveau d´étude, la profession et les antécédents de diabète, de scarification et d´hépatite C; et en analyse multivariée: le sexe, l´âge, et le niveau d´étude. Conclusion la séroprévalence du VHB est de 6% dans la population étudiée. L´infection par le VHB semble toucher volontiers les sujets de sexe masculin, âgés de plus de 17 ans, et ayant un niveau d´étude secondaire.
A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.
Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents

Abstract Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.
Leukocyte cell‐derived chemotaxin 2 promotes the development of nonalcoholic fatty liver disease through STAT‐1 pathway in mice

Nonalcoholic fatty liver disease (NAFLD), whose pathogenesis remains unelucidated, has become an increasingly prevalent disease globally requiring novel treatment strategies. This study aims to explore the role of leukocyte cell‐derived chemotaxin 2 (LECT2), one of the known hepatokines, in the development of NAFLD.
Lower Predation with Increasing Altitude in the Mesquite Lizard Sceloporus grammicus

Abstract. We evaluated differential predation pressure on the lizard Sceloporus grammicus at 3 sampling sites along a high-mountain gradient, using 3 methods of assessment: attacks on plasticine lizard models, frequency of lizard tail autotomy, and estimation of the richness of potential predators. We placed a total of 720 lizard models at each sampling site (2600, 3100, and 4150 m asl) on 6 d during the reproductive season and on 6 d during the nonreproductive season. Each day we placed 60 models (n = 30 for each sex, with each sex having 10 each of 3 gular color morphotypes [gray, yellow, and orange]) at lizards' previously observed basking sites. Additionally, we conducted 20 mark-recapture sampling visits at each site from 2014 to 2019 to determine the number of individuals with tail autotomy; we also made observations to estimate the richness of potential predators and supplemented our observations with information from the available literature. We expected (1) an inverse effect of altitude on predation pressure due to a possible decrease in the richness of potential predators with altitude, and (2) differential predation pressure according to sex and gular morphotype due to differential behavioral and morphological conspicuity. Our findings support a decrease in predation pressure with altitude according to our 3 methods of assessment. However, we did not find evidence for an effect of sex or color of gular morphotype on predation pressure, neither from the number of attacks on the plasticine models nor from the frequency of tail autotomy. Lower predation with increasing altitude could be due to the following combined effects: lower richness of predators, lower visibility of lizards because of less contrast of their bodies with the substrate, and reduced locomotor, foraging, and social movements due to thermal restriction.
Vegetation Patterns in Waisoi Primary Rainforest, Southeast Viti Levu, Fiji1

Abstract: The vegetation composition and structure of “pristine” primary lowland rainforest in Waisoi, south Viti Levu, Fiji were assessed quantitatively by recording all trees with a diameter at breast height > 1 cm within sample plots covering the topographic range of the Waisoi area. The tree flora comprised 78 recognizable taxa, 68 of which were recorded to species. Of these 68 species, 61% were endemic. Four forest types were evaluated; “River Flat,” “Slope,” “Ridge,” and “Quasi-montane. ” Differences in stem density, species richness, and diversity were observed across the forest types. The River Flat and Quasi-montane forest types were distinct from each other and from Slope and Ridge forests. Canopy structure was characterized for each of these forest types and illustrated with profile diagrams.
A Noninvasive Genetic Technique Using Guano for Identification of Corynorhinus townsendii (Townsend's Big-Eared Bat) Maternity Roosts

Abstract. The use of DNA from fecal samples can allow for a better understanding of the ecology of a species without capturing and handling the animals. This is particularly useful for cryptic and elusive animals, such as bats. Being able to identify critical habitat, such as maternity roosts, for bat species in areas where they depend on abandoned mines that could be slated for closure is necessary to enact appropriate protections for such roosts. In particular, Corynorhinus townsendii commonly uses abandoned mines for maternity roosts. Further, maternity roosts are difficult to identify through visual surveys when only one or a few surveys are performed before mine closures. We have developed a method for identification of C. townsendii maternity roosts that uses fecal DNA extracted from fresh guano collected from plastic sheeting placed at a mine entrance. We provide a multiplex PCR assay to amplify a control region fragment found only in C. townsendii, as well as a Y-linked protein (DBY) to detect male C. townsendii DNA. The purpose of this study was to identify a temporal shift in the presence of male C. townsendii bats, which can be useful to identify a maternity roost. This method allows for noninvasive identification of critical habitat for this species and reduces the effort and safety risk of entering mines on the part of biologists.
High-pressure proton disorder in brucite

Abstract In this paper we explore the structure and physical properties of brucite over a wide range of pressures with density functional theory using the variable cell-shape plane wave pseudopotential method in the local density (LDA) and generalized gradient (GGA) approximations. We probe the energetics underlying the structure and dynamics of the proton sub-lattice by performing a series of constrained and unconstrained static calculations based on an energetically stable √3×√3×1 super-cell wherein proton locations are related to the 6i Wyckoff sites as opposed to the ideal 2d site. The displacement of the hydrogen atom from the threefold axis increases with increasing pressure. This means that even in the absence of thermal energy, the protons are frustrated and would be expected to exhibit long-range disorder akin to a spin glass. To shed light on the dynamic nature of the proton hopping between the 6i-like sites, we determined the activation energy barrier for such jumps. We found that the energy barrier increases with compression, possibly indicating a transition from dynamic proton disorder at lower pressures to static disorder at higher pressure. We have also investigated the possibility of proton jumps across the interlayer, by determining the potential energy well along the O···O vector. We infer that proton jumps across the interlayer are either severely limited or highly cooperative since we did not find any evidence for a double well along the O···O vector. The absence of a double well along the O···O vector, the evolution of O-H···O distances with compression, and the gradual transition to a symmetric O-H···O configuration, all argue for weak hydrogen bonding in brucite.
NSF AI Institute for Research on Trustworthy AI in Weather, Climate, and Coastal Oceanography (AI2ES)

We introduce the National Science Foundation (NSF) AI Institute for Research on Trustworthy AI in Weather, Climate, and Coastal Oceanography (AI2ES). This AI institute was funded in 2020 as part of a new initiative from the NSF to advance foundational AI research across a wide variety of domains. To date AI2ES is the only NSF AI institute focusing on environmental science applications. Our institute focuses on developing trustworthy AI methods for weather, climate, and coastal hazards. The AI methods will revolutionize our understanding and prediction of high-impact atmospheric and ocean science phenomena and will be utilized by diverse, professional user groups to reduce risks to society. In addition, we are creating novel educational paths, including a new degree program at a community college serving underrepresented minorities, to improve workforce diversity for both AI and environmental science.
Ergonomic Redesign of the Coca Cola Freestyle Machine Graphical User Interface to Improve Accessibility

The purpose of this research is to redesign the graphical user interface of the Coca Cola Freestyle machine to improve its usability for individuals with visual impairments. The proposed design included a feature to increase text and button size. Also, the drink selection process was reordered. In this study, the original display and the redesign were implemented on a touchscreen laptop to emulate the actual process. Ten subjects with normal and impaired vision were recruited respectively and were randomly assigned to complete a drink selection task in using either the “Original” GUI or a “Redesign” created by the authors (n=5). User feedback was collected and analyzed. The drink dispensing task completion time was recorded and analyzed using two-way ANOVA and Tukey pairwise comparison. It was concluded that the original design was easier to navigate in terms of icon position, but the redesign was preferred because of its flexibility to change the text size.