Miracle-dz/UniFAR-FTUs huggingface dataset:
Peri‐procedural code status for transcatheter aortic valve replacement: Absence of program policies and standard practices

Little is known about policies and practices for patients undergoing Transcatheter Aortic Valve Replacement (TAVR) who have a documented preference for Do Not Resuscitate (DNR) status at time of referral. We investigated how practices across TAVR programs align with goals of care for patients presenting with DNR status.
Harnessing the benefits of diversity to address socio-environmental governance challenges

Solving complex problems, from biodiversity conservation to reducing inequality, requires large scale collective action among diverse stakeholders to achieve a common goal. Research relevant to meeting this challenge must model the interaction of stakeholders with diverse cognitive capabilities and the complexity of the problem faced by stakeholders to predict the success of collective action in various contexts. Here, we build a model from first principles of cognitive abilities, diversity, and socio-environmental complexity to identify the sets of conditions under which groups most effectively engage in collective action to solve governance problems. We then fit the model to small groups, U.S. states, and countries. Our model illustrates the fundamental importance of understanding the interaction between cognitive abilities, diversity, and the complexity of socio-environmental challenges faced by stakeholders today. Our results shed light on the ability of groups to solve complex problems and open new avenues of research into the interrelationship between cognition, institutions, and the environments in which they co-evolve.
Functional and biological heterogeneity of KRASQ61 mutations

Missense mutations at the three hotspots in the guanosine triphosphatase (GTPase) RAS—Gly12, Gly13, and Gln61 (commonly known as G12, G13, and Q61, respectively)—occur differentially among the three RAS isoforms. Q61 mutations in KRAS are infrequent and differ markedly in occurrence. Q61H is the predominant mutant (at 57%), followed by Q61R/L/K (collectively 40%), and Q61P and Q61E are the rarest (2 and 1%, respectively). Probability analysis suggested that mutational susceptibility to different DNA base changes cannot account for this distribution. Therefore, we investigated whether these frequencies might be explained by differences in the biochemical, structural, and biological properties of KRASQ61 mutants. Expression of KRASQ61 mutants in NIH 3T3 fibroblasts and RIE-1 epithelial cells caused various alterations in morphology, growth transformation, effector signaling, and metabolism. The relatively rare KRASQ61E mutant stimulated actin stress fiber formation, a phenotype distinct from that of KRASQ61H/R/L/P, which disrupted actin cytoskeletal organization. The crystal structure of KRASQ61E was unexpectedly similar to that of wild-type KRAS, a potential basis for its weak oncogenicity. KRASQ61H/L/R-mutant pancreatic ductal adenocarcinoma (PDAC) cell lines exhibited KRAS-dependent growth and, as observed with KRASG12-mutant PDAC, were susceptible to concurrent inhibition of ERK-MAPK signaling and of autophagy. Our results uncover phenotypic heterogeneity among KRASQ61 mutants and support the potential utility of therapeutic strategies that target KRASQ61 mutant–specific signaling and cellular output. Description Comparison of Gln61 (Q61) mutations in KRAS reveals a potential therapeutic opportunity. A portrait of rare RAS mutants Mutations in the RAS family of proteins promote various cancers, of which mutations at Gln61 (also referred to as Q61) are relatively and unexpectedly rare in KRAS. Huynh et al. compared the structural, biochemical, and biological effects of Gln61 mutations in KRAS (see also Sealover and Kortum). The Q61E mutant had weaker metabolic activity and induced greater cell adhesion and less motility than the other mutants, thus potentially explaining the relative rarity of this mutant. Nonetheless, other aspects made Gln61 mutant KRAS pancreatic cancer cells susceptible to the same inhibitors that are currently in trials to treat tumors dependent on the more common KRAS mutants. The findings may both broaden and differentiate treatment strategies for these rarer mutant KRAS–driven tumors.
The CLP and PREP protease systems coordinate maturation and degradation of the chloroplast proteome in Arabidopsis thaliana.

A network of peptidases governs proteostasis in plant chloroplasts and mitochondria. This study demonstrates strong genetic and functional interactions in Arabidopsis thaliana between the chloroplast stromal CLP chaperone-protease system and the PREP1,2 peptidases dually localized to chloroplast stroma and the mitochondrial matrix. Higher order mutants defective in CLP or PREP proteins were generated and analyzed by quantitative proteomics and N-terminal proteomics (TAILS). Strong synergistic interactions were observed between the CLP protease system (clpr1-2, clpr2-1, clpc1-1, clpt1, clpt2) and both PREP homologs (prep1, prep2) resulting in embryo lethality or growth and developmental phenotypes. Synergistic interactions were observed even when only one of the PREP proteins was lacking, suggesting that PREP1 and PREP2 have divergent substrates. Proteome phenotypes were driven by the loss of CLP protease capacity, with little impact by the PREP peptidases. Chloroplast N-terminal proteomes showed that many nuclear encoded chloroplast proteins have alternatively processed N-termini in prep1prep2, clpt1clpt2 and prep1prep2clpt1clpt2. Loss of chloroplast protease capacity interferes with stromal processing peptidase (SPP) activity due to folding stress and low levels of accumulated cleaved cTP fragments. PREP1,2 proteolysis of cleaved cTPs is complemented by unknown proteases. A model for CLP and PREP activity within a hierarchical chloroplast proteolysis network is proposed.
Commonalities and specialties in photosynthetic functions of PROTON GRADIENT REGULATION5 variants in Arabidopsis

Abstract The PROTON GRADIENT REGULATION5 (PGR5) protein is required for trans-thylakoid proton gradient formation and acclimation to fluctuating light (FL). PGR5 functionally interacts with two other thylakoid proteins, PGR5-like 1 (PGRL1) and 2 (PGRL2); however, the molecular details of these interactions are largely unknown. In the Arabidopsis (Arabidopsis thaliana) pgr5-1 mutant, the PGR5G130S protein accumulates in only small amounts. In this work, we generated a knockout allele of PGR5 (pgr5-Cas) using CRISPR-Cas9 technology. Like pgr5-1, pgr5-Cas is seedling-lethal under FL, but photosynthesis and particularly cyclic electron flow, as well as chlorophyll content, are less severely affected in both pgr5-Cas and pgrl1ab (which lacks PGRL1 and PGR5) than in pgr5-1. These differences are associated with changes in the levels of 260 proteins, including components of the Calvin–Benson cycle, photosystems II and I, and the NDH complex, in pgr5-1 relative to the wild type (WT), pgr5-Cas, and pgrl1ab. Some of the differences between pgr5-1 and the other mutant lines could be tentatively assigned to second-site mutations in the pgr5-1 line, identified by whole-genome sequencing. However, others, particularly the more pronounced photosynthetic defects and PGRL1 depletion (compared to pgr5-Cas), are clearly due to specific negative effects of the amino-acid substitution in PGR5G130S, as demonstrated by complementation analysis. Moreover, pgr5-1 and pgr5-Cas plants are less tolerant to long-term exposure to high light than pgrl1ab plants. These results imply that, in addition to the previously reported necessity of PGRL1 for optimal PGR5 function, PGR5 is required alongside PGRL1 to avoid harmful effects on plant performance.
Book Reviews: Generating Referring Expressions

This book describes the author's research on the automatic generation of referring expressions in English. The work is encapsulated in EPICURE, a natural language generation system that produces cookery recipes from three basic sets of data structures: a set of entities corresponding to the ingredients of the target recipe; a set of planning operators that describe the necessary cooking actions and their effects on the dish; and a model of thecook's capabilities. The recipes produced by EPICURE are composed of two ordered structures: a list of the required basic ingredients and another of the basic preparatory (e.g., soaking, draining, peeling) and cooking actions (e.g., saut6ing, simmering, boiling) to be carried out on them. Given the focus of the w o r k the recipes themselves are rather simple in that they do not, for example, contain explanations of why particular actions are to be performed, and thus do not involve the types of complex sentences often found in action-oriented discourses (e.g., sentences with means-, rationale-, or purpose-clauses). The sophistication of the text lies squarely in the way in which pronouns, anaphoric definite noun phrases, and one-anaphoric phrases are used to pick out complex entities in the discourse. The organization of the book closely follows what one would normally expect of a doctoral thesis, from which it is drawn (Edinburgh 1989); contrary to what is usual in such cases, this organization works well here. Chapter 1 presents a brief description of the class of referring expressions under consideration, the foundations of the work carried out, and an overview of EPICURE. It provides an excellent introduction to the book, set in terms that are easily accessible to nonlinguists or non-computer scientists. Chapter 2 introduces the notions of entities and outlines the complexities that underlie a typical ingredients list:
Rational torsion of prime order in elliptic curves over number fields

The disclosure hereof is of a handtruck which includes a load support mounted on a wheel and axle assembly, with a handle unit likewise connected to said wheel and axle assembly, both pivotally related, and means to interconnect the said support and handle unit for simultaneous movement, in various adjusted positions so that the handtruck and its load may be manipulated either to maintain the load support at a generally level attitude, or to change the same depending upon the type of load to be carried thereon, the adjustment being effected by simple means which are manipulatable from the handle unit as may be necessary or desirable.
Improving the Efficiency of Runge-Kutta Methods for the Solution of BVPs for Higher-Order ODEs

Improving the E ciency of Runge-Kutta Methods for the Solution of BVPs for Higher-Order ODEs Khalid Zuberi Master of Science Graduate Department of Computer Science University of Toronto, 1996 Runge-Kutta methods are often used to solve two-point boundary value problems (BVPs) for ordinary di erential equations (ODEs.) These methods are usually applied directly to rst-order systems; to solve problems for higher-order ODEs, the di erential equations are often reduced to an equivalent rst-order system. We exploit the structure of the reduced system to construct an approximate Jacobian matrix that is signi cantly cheaper to construct for general higher order BVPs. Second-order ODEs are examined in detail, and a specialised linear system solver is suggested to provide additional computational savings. Numerical results on sample BVPs for second-order ODEs show signi cant computational savings with no loss of solution accuracy. ii Acknowledgements I would like to thank my supervisor Prof. Ken Jackson for suggesting this project and his guidance throughout this work, my second reader Tom Fairgrieve for many suggestions that improved the overall thesis, and Paul Muir for some insightful discussions. I also thank the Natural Science and Engineering Research Council for providing nancial support, and nally my wife Ameena Philips for constantly brightening my life. iii
An exploratory study of problematic shopping and problematic video gaming in adolescents

Problematic video gaming (PVG) and problematic shopping (PS) are addictive behaviors prevalent in adolescents, characterized by positive and negative reinforcement, and associated with psychosocial impairment. This study examined how PS and PVG relate in adolescents. It also examined how PS interacts with PVG in relation to health/functioning measures. Survey data from 3,657 Connecticut high-school students were evaluated. Chi-square analyses and logistic regression models were used to assess relationships between PS and measures of PVG. Interaction analyses measured effects of PS on relationships between PVG and health/functioning measures. Relative to adolescents without PS, those with PS had 8.79-fold higher odds of exhibiting PVG and were more likely to endorse gaming to relieve anxiety and impairment due to gaming. Interaction analyses revealed that in adolescents with PS, the relationships between PVG and aggressive behaviors, including fighting, serious fighting leading to physical injury, and weapon-carrying, were stronger than in adolescents without PS. PS strongly relates to PVG, and among youth reporting PS, there are stronger associations between PVG and aggressive behaviors. Prevention efforts for adolescents should consider the co-occurrence of PS and PVG. PS and PVG may be linked by negative reinforcement and propensities for aggressive and addictive behaviors, suggesting that further research should explore possible interventions targeting stress management and maladaptive coping.
Management of inflammatory bowel disease beyond tumor necrosis factor inhibitors: novel biologics and small-molecule drugs

The incidence and prevalence of inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, have increased in Asia and developing countries. In the past two decades, anti-tumor necrosis factor (TNF) agents have revolutionized the treatment of IBD, in part by decreasing the rates of complications and surgery. Although anti-TNF agents have changed the course of IBD, there are unmet needs in terms of primary and secondary non-responses and side effects such as infections and malignancies. Novel biologics and small-molecule drugs have been developed for IBD, and the medical treatment options have improved. These drugs include sphingosine-1-phosphate receptor modulators and anti-integrins to block immune cell migration, and cytokine and Janus kinase inhibitors to block immune cell communications. In this review, we discuss the approved novel biologics and small-molecule drugs, including several of those in the late stages of development, for the treatment of IBD.
Negation in Igálà

Unlike other Yoruboid languages, Igala uses a double negation syntax which combines two independent but mutually obligatory elements to generate a single semantic unit of negation. Apart from providing a description of Igala negatio nsystem, this paper, relying on instruments of minimalist grammar as propounded in Chomsky (1995, 1998, 2002), argues for a negative clause projection in which there are two separate but interdependent Neg projections – NegP1 and NegP2 - such that Nego2 takes NegP1 as complement to project NegP2. Spell-out constituent ordering derives from Nego2 n/noo attracting NegP1 to Spec-NegP2 resulting in the word order where Nego2 obligatorily ends negative clause expressions in Igala. This grammar structurally predicts that nothing follows Nego2 n/noo in the linear orderof words in Igala negative clause constructions.
Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer

Abstract Background Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC. Patients and Methods In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses. Results GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant. Conclusion GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.
Multi‐gene phylogeny of North American clear‐winged moths (Lepidoptera: Sesiidae): a foundation for future evolutionary study of a speciose mimicry complex

Sesiids are a diverse group of predominantly diurnal moths, many of which are Batesian mimics of Hymenoptera. However, their diversity and relationships are poorly understood. A multi‐gene phylogenetic analysis of 48 North American sesiid species confirmed the traditional taxonomic tribal ranks, demonstrated the paraphyly of Carmenta and Synanthedon with respect to several other genera and ultimately provided minimal phylogenetic resolution within and between North American and European groups. Character support from each gene suggested inconsistency between the phylogenetic signal of the CAD gene and that of the other four genes. However, removal of CAD from subsequent phylogenetic analyses did not substantially change the initial phylogenetic results or return Carmenta and Synanthedon as reciprocally monophyletic, suggesting that it was not impacting the overall phylogenetic signal. The lack of resolution using genes that are typically informative at the species level for other lepidopterans suggests a surprisingly rapid radiation of species in Carmenta/Synanthedon. This group also exhibits a wide range of mimicry strategies and hostplant usage, which could be fertile ground for future study.
Development of QSAR model using machine learning and molecular docking study of polyphenol derivatives against obesity as pancreatic lipase inhibitor

Abstract In developed countries and developing countries, obesity/overweight is considered a major problem, in fact, it is now recognized as a major metabolic disorder. Additionally, obesity is connected with other metabolic diseases, including cardiovascular disorders, type 2 diabetes, some types of cancer, etc. Therefore, the development of novel drugs/medications for obesity is essential. The best target for treating obesity is Pancreatic Lipase (PL), it breaks 50-70% triglycerides into monoglycerol and free fatty acids.The major aim of this in silico study is to generate a QSAR model by using Multiple Linear Regression (MLR) and to inhibit pancreatic lipase by polyphenol derivatives mainly flavonoids, plant secondary metabolites shows good inhibitory activity against PL, maybe with less unpleasant side effects.In this in silico study, a potent inhibitor was found through calculating drug likness, QSAR (Quantitative structure-activity relationship) and molecular docking. The docking was performed in Maestro 12.0 and the ADME (absorption, distribution, metabolism, and excretion) properties (drug-likeness) of compounds/ligands were predicted by the Qikprop module of Maestro 12.0. The QSAR model was developed to show the relationship between the chemical/structural properties and the compound's biological activity. We have found the best interaction between pancreatic lipase and flavonoids. The best docked compound is Epigallocatechin 3,5,-di-O-gallate with docking score −10.935 kcal/mol . All compounds also show drug-likeness activity.The developed model has satisfied all internal and external validation criteria and has square correlation coefficient (r2) 0.8649, which shows its predictive ability and has good acceptability, predictive ability, and statistical robustness. Communicated by Ramaswamy H. Sarma
Molecular mapping of quantitative trait loci for 3 husk traits using genotyping by sequencing in maize (Zea mays L.)

Abstract The maize (Zea mays L.) husk consists of multiple leaf layers and plays an important role in grain growth and development. Despite significant achievements in physiological and morphological research, few studies have focused on the detection of genetic loci underlying husk-related traits due to the lack of efficient tools. In this study, we constructed an ultra-high-density linkage map using genotyping by sequencing based on a recombinant inbred line population to estimate the genetic variance and heritability of 3 husk traits, i.e. husk length, husk width, and husk layer number in 3 field environments and the combined environment. The 3 husk traits showed broad phenotypic variation and high heritability; the broad-sense heritability (H2) was 0.92, 0.84, and 0.86. Twenty quantitative trait loci were consistently detected more than 1 environment, including 9 for husk length, 6 for husk width, and 5 for husk layer number. These loci were considered as stable quantitative trait loci. Based on the quantitative trait loci mapping in the recombinant inbred line population, qHL6 and qHN4 were detected across all environments and inferred to be reliable and major-effect quantitative trait loci for husk length and husk layer number, respectively. In addition, several predicted candidate genes were identified in the region of qHL6 and qHN4, of which 17 candidate genes potentially play a role in biological processes related to development process and energy metabolism. These results will be as a useful resource for performing functional studies aimed at understanding the molecular pathways involved in husk growth and development.