bluuebunny/crossref_metadata_2025_split huggingface dataset:
QSAR, molecular docking, and design of novel 4-(N,N-diarylmethyl amines) Furan-2(5H)-one derivatives as insecticides against Aphis craccivora
Authors: Isyaku Yusuf , Uzairu Adamu , Uba Sani , Ibrahim Muhammad Tukur , Umar Abdullahi Bello 
Published: March 2020

Abstract
Background
Aphis craccivora has many plant hosts, though it seemingly forechoice to groups of bean family. Other plants it hosts are families of Solanaceae, Rosaceae, Malvaceae, Chenopodiaceae, Caryophyllaceae, Ranunculaceae, Cucurbitaceae, Brassicaceae, and Asteraceae.

Result
A computational study was carried out on a series of twenty compounds of novel 4-(N,N-diarylmethylamines) furan-2(5H)-one derivatives against Aphis craccivora insect. Optimization of the compounds was performed with the aid of Spartan 14 software using DFT/B3LYP/6-31G** quantum mechanical method. Using PaDel descriptor software to calculate the descriptors, Generic Function Approximation (GFA) was employed to generate the model. Model 1 found to be the optimal out of four models generated which has the following statistical parameters; R2 = 0.871489, R2adj = 0.83644, cross-validated R2 = 0.790821, and external R2 = 0.550768. Molecular docking study occurred between the compounds and the complex crystal structure of the acetylcholine (protein AChBP) (PDB CODE 2zju) in which compound 13 was identified to have the highest binding energy of − 8.4 kcalmol−1. Statistical analyses, such as variance inflation factor, mean effect, and the applicability domain, were conducted on the model. This compound has a strong affinity with the macromolecular target point of the A. craccivora (2zju) producing H-bond and as well the hydrophobic interaction at the target point of amino acid residue. Molecular docking gave an insight into the structure-based design of the new compounds with better activity against A. craccivora in which three compounds A, B, and C were designed and discovered to be of high quality and have greater binding affinity compared to the one obtained from the literature.

Conclusion
The QSAR model was generated by the employment of Genetic Function Approximation (GFA). The model was found to be robust and possessed a good statistical parameter. Furthermore, a molecular docking study was performed to get an idea for structure-based design in which three (3) compounds A, B, and C were designed and were found to be more active than the template (compound 13, i.e., the one with highest docking score). QSAR model was developed to give an insight into the ligand/template-based design of computer-aided drug design.
Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study
Authors: Abrahão Renata , Perdomo Sandra , Pinto Luis Felipe Ribeiro , Nascimento de Carvalho Flávia , Dias Fernando Luis , de Podestá José Roberto V. , Ventorin von Zeidler Sandra , Marinho de Abreu Priscila , Vilensky Marta , Giglio Raul Eduardo , Oliveira José Carlos , Mineiro Matinair Siqueira , Kowalski Luiz P. , Ikeda Mauro K. , Cuello Mauricio , Munyo Andres , Rodríguez-Urrego Paula A. , Hakim José Antonio , Suarez-Zamora David Alfonso , Cayol Federico , Figari Marcelo Fernando , Oliver Javier , Gaborieau Valerie , Keogh Ruth H. , Brennan Paul , Curado Maria Paula ,   on behalf of the InterCHANGE Group
Published: March 2020

PURPOSE Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.
First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors
Authors: Hassan Raffit , Blumenschein George R. , Moore Kathleen N. , Santin Alessandro D. , Kindler Hedy L. , Nemunaitis John J. , Seward Shelly M. , Thomas Anish , Kim Stella K. , Rajagopalan Prabhu , Walter Annette O. , Laurent Dirk , Childs Barrett H. , Sarapa Nenad , Elbi Cem , Bendell Johanna C. 
Published: March 2020

PURPOSE This phase I study, which to our knowledge is the first-in-human study of this kind, investigates the safety, tolerability, pharmacokinetics, and clinical activity of anetumab ravtansine, an antibody–drug conjugate of anti-mesothelin antibody linked to maytansinoid DM4, in patients with advanced, metastatic, or recurrent solid tumors known to express the tumor-differentiation antigen mesothelin. PATIENTS AND METHODS This phase I, open-label, multicenter, dose-escalation and dose-expansion study of anetumab ravtansine enrolled 148 adult patients with multiple solid tumor types. Ten dose-escalation cohorts of patients with advanced or metastatic solid tumors (0.15-7.5 mg/kg) received anetumab ravtansine once every 3 weeks, and 6 expansion cohorts of patients with advanced, recurrent ovarian cancer or malignant mesothelioma received anetumab ravtansine at the maximum tolerated dose once every 3 weeks, 1.8 mg/kg once per week, and 2.2 mg/kg once per week. RESULTS Forty-five patients were enrolled across the 10 dose-escalation cohorts. The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg once every 3 weeks or 2.2 mg/kg once per week. Thirty-two patients were enrolled in the 6.5 mg/kg once-every-3-weeks, 35 in the 1.8 mg/kg once-per-week, and 36 in the 2.2 mg/kg once-per-week expansion cohorts. The most common drug-related adverse events were fatigue, nausea, diarrhea, anorexia, vomiting, peripheral sensory neuropathy, and keratitis/keratopathy. There were no drug-related deaths. Anetumab ravtansine pharmacokinetics were dose proportional; the average half-life was 5.5 days. Among 148 patients with mesothelioma or ovarian, pancreatic, non–small-cell lung, and breast cancers, 1 had a complete response, 11 had partial responses, and 66 had stable disease. High levels of tumor mesothelin expression were detected in patients with clinical activity. CONCLUSION Anetumab ravtansine exhibited a manageable safety and favorable pharmacokinetic profile with encouraging preliminary antitumor activity in heavily pretreated patients with mesothelin-expressing solid tumors. The results allowed for the determination of recommended doses, schedules, and patient populations for anetumab ravtansine in phase II studies.
Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago
Authors: Sommer Phillip , Lukovic Elvedin , Fagley Eliot , Long Dustin R. , Sobol Julia B. , Heller Katherine , Moitra Vivek K. , Pauldine Ronald , O’Connor Michael F. , Shahul Sajid , Nunnally Mark E. , Tung Avery 
Published: March 2020

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named coronavirus disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020.
In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.
Control of translation elongation in health and disease
Authors: Knight John R. P. , Garland Gavin , Pöyry Tuija , Mead Emma , Vlahov Nikola , Sfakianos Aristeidis , Grosso Stefano , De-Lima-Hedayioglu Fabio , Mallucci Giovanna R. , von der Haar Tobias , Smales C. Mark , Sansom Owen J. , Willis Anne E. 
Published: March 2020

ABSTRACT
Regulation of protein synthesis makes a major contribution to post-transcriptional control pathways. During disease, or under stress, cells initiate processes to reprogramme protein synthesis and thus orchestrate the appropriate cellular response. Recent data show that the elongation stage of protein synthesis is a key regulatory node for translational control in health and disease. There is a complex set of factors that individually affect the overall rate of elongation and, for the most part, these influence either transfer RNA (tRNA)- and eukaryotic elongation factor 1A (eEF1A)-dependent codon decoding, and/or elongation factor 2 (eEF2)-dependent ribosome translocation along the mRNA. Decoding speeds depend on the relative abundance of each tRNA, the cognate:near-cognate tRNA ratios and the degree of tRNA modification, whereas eEF2-dependent ribosome translocation is negatively regulated by phosphorylation on threonine-56 by eEF2 kinase. Additional factors that contribute to the control of the elongation rate include epigenetic modification of the mRNA, coding sequence variation and the expression of eIF5A, which stimulates peptide bond formation between proline residues. Importantly, dysregulation of elongation control is central to disease mechanisms in both tumorigenesis and neurodegeneration, making the individual key steps in this process attractive therapeutic targets. Here, we discuss the relative contribution of individual components of the translational apparatus (e.g. tRNAs, elongation factors and their modifiers) to the overall control of translation elongation and how their dysregulation contributes towards disease processes.
A murine model demonstrates capsule-independent adaptive immune protection in survivors of Klebsiella pneumoniae respiratory tract infection
Authors: Twentyman Joy , Morffy Smith Catherine , Nims Julia S. , Dahler Aubree A. , Rosen David A. 
Published: March 2020

ABSTRACT
Klebsiella pneumoniae represents a growing clinical threat, given its rapid development of antibiotic resistance, necessitating new therapeutic strategies. Existing live-infection models feature high mortality rates, limiting their utility in the study of natural adaptive immune response to this pathogen. We developed a preclinical model of pneumonia with low overall mortality, in which previously exposed mice are protected from subsequent respiratory tract challenge with K. pneumoniae. Histologic analyses of infected murine lungs demonstrate lymphocytic aggregates surrounding vasculature and larger airways. Initial exposure in RAG1 knockout mice (lacking functional B and T cells) failed to confer protection against subsequent K. pneumoniae challenge. While administration of isolated K. pneumoniae capsule was sufficient to provide protection, we also found that initial inoculation with K. pneumoniae mutants lacking capsule (Δcps), O-antigen (ΔwecA) or both conferred protection from subsequent wild-type infection and elicited K. pneumoniae-specific antibody responses, indicating that non-capsular antigens may also elicit protective immunity. Experiments in this model will inform future development of multivalent vaccines to prevent invasive K. pneumoniae infections.
Redox-Active α-Diimine Complexes of Early Transition Metals: From Bonding to Catalysis
Authors: Mashima Kazushi 
Published: March 2020

Abstract
It is an intrinsic nature that early transition metals favorably adopt their highest oxidation state with d0 configuration. We have been interested in early transition metal complexes bearing redox active α-diimine ligands for introducing redox processes at the metal center through reversible interconversion among possible coordination modes, i.e., a neutral 1,4-diaza-1,3-diene form A, a monoanionic form B, and dianionic ene-diamido forms, σ2-enediamido form C and σ2,π-enediamido form D. In this context, we continuously investigated synthesis of a series of α-diimine complexes of group 3, 5 and 6 metals by implementing two synthetic methodologies, (1) a salt-metathesis protocol by treating ligand-supported metal precursors with the alkali metal salts of α-diimines and (2) a salt-free protocol by applying organosilicon compounds, such as 3,6-di(trimethylsilyl)-1,4-cyclohexadiene (abbrev. Si-CHD) and 1,4-di(trimethylsilyl)-2-methyl-cyclohexa-2,4-diene (abbrev. Si-Me-CHD) together with 1,4-di(trimethylsilyl)-2,5-dimethyl-1,4-dihydropyrazine (abbrev. Si-Me2-DHP) and 1,4-di(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine (abbrev. Si-Me4-DHP), for reducing homoleptic chlorides and imide chlorides of early transition metals in the presence of α-diimine ligands. This account thus summarizes the author’s achievements on bonding and reactivity of various α-diimine complexes of group 3, group 5, and group 6 metals as well as their catalytic performance.
How Economically Significant Are Unused Capacity Costs? A Large-Scale Empirical Analysis
Authors: Ederhof Merle , Nagar Venky , Rajan Madhav 
Published: March 2020

This study uses a confidential Census sample of 151,900 U.S. manufacturing plant-years from 1974 to 2011 to investigate the impact of excluding the cost of unused capacity from key financial indicators, namely, product costs and gross margins. We estimate the magnitude of unused capacity cost as a percentage of sales to be about 4.8%, which for Compustat manufacturing firms in 2011 amounts to $142 billion (by comparison, the well-researched topic of research and development expenses totals to $223 billion). We find that excluding the cost of unused capacity decreases product costs by approximately 6% and increases gross margins by around 26%. These magnitudes are economically significant and pervasive across industries and over time. Excluding the cost of unused capacity also smooths the time-series variation in unitized product costs and gross margins, with the standard deviation of gross margins declining (significantly) by 5%. Additional analyses indicate the presence of congestion and other costs at high capacity utilization levels, as predicted by the operations literature. This paper was accepted by Suraj Srinivasan, accounting.
THE ELEMENTAL COMPOSITION OF THE VEGETATIVE ORGANS OF SORTS REGAL AIR AND SPEAK TO ME OF HEMEROCALLIS HYBRIDA
Authors: Sedel'nikova Lyudmila Leonidovna , Chankina Ol'ga Vasil'yevna 
Published: March 2020

The data on the content of 22 chemical elements in the leaves and rhizomes of Hemerocallis hybrida plants of the Speak to me and Regal Air varieties growing in soil-ecological conditions of the forest-steppe zone of Western Siberia are presented. The General regularities of accumulation and distribution of macro- and microelements in leaves and rhizomes of plants of two varieties of daylilies are established: excess of the content of many microelements (vanadium, chromium, nickel, rubidium) in rhizomes in comparison with leaves. It was revealed that the concentration of chemical elements in plants differed both in organs and between varieties. The peculiarity of the mineral composition of the Regal Air variety was the excess of the total content of trace elements in 1.5–3 times compared to the variety Speak to me. Concentrations of individual elements in the leaves and rhizomes of daylilies differed significantly. It is shown that in both varieties in the leaves the amount of bromine was 4 times higher than in rhizomes, strontium – 1.5–1.8 times. The concentration of toxicant elements in the phytomass of Hemerocallis hybrida varieties was significantly lower than permissible concentration, which makes it possible to use them for medicinal purposes.
DEVELOPMENT OF A METHOD FOR HYDROLYTIC CLEAVAGE OF MOLECULES SAPONINS – DERIVATIVES OF QUILLAJA ACID
Authors: Mironenko Natal'ya Vladimirovna , Shkutina Irina Viktorovna , Brezhneva Tat'yana Aleksandrovna , Selemenev Vladimir Fedorovich 
Published: March 2020

The possibility of hydrolytic decomposition of glycosides soap tree Qullaja. The conditions for the complete hydrolysis of saponins: a mixture of hydrochloric acid, water, ethanol in a ratio of 4 :7.35 : 6.65, heating time – at least 6 hours. The composition of the carbohydrate part of saponins was established – xylose, glucuronic acid, galactose, arabinose were identified in all hydrolysates. The analysis of the obtained fraction of aglycone – willieboy acid physico-chemical methods. Based on the calculation results of chromatographic characteristics (mobility, number and height of theoretical plates), a system for elution of aglycone of the following composition is recommended: petroleum ether–chloroform–acetone (20 : 20 : 5). By the method of potentiometric titration in a non-aqueous solvent medium, the percentage of aglycone in the selected fractions was determined-88.23%. A comparative study of the aqueous solution of aglycone and saponins by UV spectrophotometry. A decrease in the intensity of absorption bands in the 230, 290 nm region responsible for the absorption of carbonyl structures is shown. Analyzed the IR spectra of saponins and willieboy acid identified bands assigned to the vibrations of functional groups of the aglycone and the carbohydrate residue.
LiveGraph
Authors: Zhu Xiaowei , Feng Guanyu , Serafini Marco , Ma Xiaosong , Yu Jiping , Xie Lei , Aboulnaga Ashraf , Chen Wenguang 
Published: March 2020

The specific characteristics of graph workloads make it hard to design a one-size-fits-all graph storage system. Systems that support transactional updates use data structures with poor data locality, which limits the efficiency of analytical workloads or even simple edge scans. Other systems run graph analytics workloads efficiently, but cannot properly support transactions.
This paper presents LiveGraph, a graph storage system that outperforms both the best graph transactional systems and the best solutions for real-time graph analytics on fresh data. LiveGraph achieves this by ensuring that adjacency list scans, a key operation in graph workloads, are purely sequential: they never require random accesses even in presence of concurrent transactions. Such pure-sequential operations are enabled by combining a novel graph-aware data structure, the Transactional Edge Log (TEL), with a concurrency control mechanism that leverages TEL's data layout. Our evaluation shows that LiveGraph significantly outperforms state-of-the-art (graph) database solutions on both transactional and real-time analytical workloads.
Muscarinic-Dependent miR-182 and QR2 Expression Regulation in the Anterior Insula Enables Novel Taste Learning
Authors: Gould Nathaniel L. , Elkobi Alina , Edry Efrat , Daume Jonathan , Rosenblum Kobi 
Published: March 2020

AbstractIn a similar manner to other learning paradigms, intact muscarinic acetylcholine receptor (mAChR) neurotransmission or protein synthesis regulation in the anterior insular cortex (aIC) is necessary for appetitive taste learning. Here we describe a parallel local molecular pathway, where GABAAreceptor control of mAChR activation causes upregulation of miRNA-182 and quinone reductase 2 (QR2) mRNA destabilization in the rodent aIC. Damage to long-term memory by prevention of this process, with the use of mAChR antagonist scopolamine before novel taste learning, can be rescued by local QR2 inhibition, demonstrating that QR2 acts downstream of local muscarinic activation. Furthermore, we prove for the first time the presence of endogenous QR2 cofactors in the brain, establishing QR2 as a functional reductase there. In turn, we show that QR2 activity causes the generation of reactive oxygen species, leading to modulation in Kv2.1 redox state. QR2 expression reduction therefore is a previously unaccounted mode of mAChR-mediated inflammation reduction, and thus adds QR2 to the cadre of redox modulators in the brain. The concomitant reduction in QR2 activity during memory consolidation suggests a complementary mechanism to the well established molecular processes of this phase, by which the cortex gleans important information from general sensory stimuli. This places QR2 as a promising new target to tackle neurodegenerative inflammation and the associated impediment of novel memory formation in diseases such as Alzheimer’s disease.