bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of 42 kDa chitinase of Trichoderma asperellum (Ta-CHI42) from a synthetic gene in Escherichia coli
Authors: Luong Nguyen Ngoc , Tien Nguyen Quang Duc , Huy Nguyen Xuan , Tue Nguyen Hoang , Man Le Quang , Sinh Duong Duc Hoang , Van Thanh Dang , Chi Duong Thi Kim , Hoa Phung Thi Bich , Loc Nguyen Hoang 
Published: August 2021

Abstract
Chitinases are enzymes that catalyze the degradation of chitin, a major component of the cell walls of pathogenic fungi and cuticles of insects, gaining increasing attention for the control of fungal pathogens and insect pests. Production of recombinant chitinase in a suitable host can result in a more pure product with less processing time and a significantly larger yield than that produced by native microorganisms. The present study aimed to express the synthetic chi42 gene (syncodChi42), which was optimized from the chi42 gene of Trichoderma asperellum SH16, in Escherichia coli to produce 42 kDa chitinase (Ta-CHI42); then determined the activity of this enzyme, characterizations and in vitro antifungal activity as well as its immunogenicity in mice. The results showed that Ta-CHI42 was overexpressed in E. coli. Analysis of the colloidal chitin hydrolytic activity of purified Ta-CHI42 on an agar plate revealed that this enzyme was in a highly active form. This is a neutral chitinase with pH stability in a range of 6–8 and has an optimum temperature of 45°C with thermal stability in a range of 25–35°C. The chitinolytic activity of Ta-CHI42 was almost completely abolished by 5 mM Zn2+ or 1% SDS, whereas it remained about haft under the effect of 1 M urea, 1% Triton X-100 or 5 mM Cu2+. Except for ions such as Mn2+ and Ca2+ at 5 mM that have enhanced chitinolytic activity; 5 mM of Na+, Fe2+ or Mg2+ ions or 1 mM EDTA negatively impacted the enzyme. Ta-CHI42 at 60 U/mL concentration strongly inhibited the growth of the pathogenic fungus Aspergillus niger. Analysis of western blot indicated that the polyclonal antibody against Ta-CHI42 was greatly produced in mice. It can be used to analyze the expression of the syncodChi42 gene in transgenic plants, through immunoblotting assays, for resistance to pathogenic fungi.
The “Chinese Expert Consensus on the Clinical Application of the Chinese Modified Triplet Combination with Irinotecan (CPT-11), Oxaliplatin (LOHP), Continuous Infusion 5-Fluorouracil, and Leucovorin for Colorectal Cancer”
Authors: Deng Yanhong ,   Chinese Southwest Oncology Group - the Committee of Colorectal Cancer
Published: August 2021

Abstract
Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardization and rational application of FOLFOXIRI regimen by clinicians in China, the “Chinese Expert Consensus on the Clinical Application of the Chinese Modified Triplet Combination with Irinotecan (CPT-11), Oxaliplatin (LOHP), Continuous Infusion 5-Fluorouracil, and Leucovorin for Colorectal Cancer” was formulated by the Committee of Colorectal Cancer in Chinese Southwest Oncology Group. Based on the mechanism underlying the combined three drugs and toxicity profile, the dosage of Chinese modified FOLFOXIRI (cmFOLFOXIRI) regimen and the management of adverse reactions are proposed. This consensus recommended that the FOLFOXIRI regimen be used in neoadjuvant, conversion, and palliative therapy for colorectal cancer under specific conditions. This consensus aimed to drive the application of cmFOLFOXIRI in the field of colorectal cancer in order to bring benefits to colorectal cancer patients.
Whole-Genome Sequencing of a 900-Year-Old Human Skeleton Supports Two Past Migration Events from the Russian Far East to Northern Japan
Authors: Sato Takehiro , Adachi Noboru , Kimura Ryosuke , Hosomichi Kazuyoshi , Yoneda Minoru , Oota Hiroki , Tajima Atsushi , Toyoda Atsushi , Kanzawa-Kiriyama Hideaki , Matsumae Hiromi , Koganebuchi Kae , Shimizu Kentaro K , Shinoda Ken-ichi , Hanihara Tsunehiko , Weber Andrzej , Kato Hirofumi , Ishida Hajime 
Published: August 2021

Abstract
Recent studies on paleogenomics have reported some Paleolithic and Neolithic genomes that have provided new insights into the human population history in East and Northeast Asia. However, there remain some cases where more recent migration events need to be examined to elucidate the detailed formation process of local populations. Although the area around northern Japan is one of the regions archaeologically suggested to have been affected by migration waves after the Neolithic period, the genetic source of these migrations are still unclear. Thus, genomic data from such past migrant populations would be highly informative to clarify the detailed formation process of local populations in this region. Here, we report the genome sequence of a 900-year-old adult female (NAT002) belonging to the prehistoric Okhotsk people, who have been considered to be the past migrants to northern Japan after the Neolithic period. We found a close relationship between NAT002 and modern Lower Amur populations and past admixture events between the Amur, Jomon, and Kamchatka ancestries. The admixture dating suggested migration of Amur-related ancestry at approximately 1,600 BP, which is compatible with the archaeological evidence regarding the settlement of the Okhotsk people. Our results also imply migration of Kamchatka-related ancestry at approximately 2,000 BP. In addition, human leukocyte antigen (HLA) typing detected the HLA-B*40 allele, which is reported to increase the risk of arthritis, suggesting the genetic vulnerability of NAT002 to hyperostosis, which was observed around her chest clavicle.
Demographic History of the Brown Bear (Ursus arctos) on Hokkaido Island, Japan, Based on Whole-Genomic Sequence Analysis
Authors: Endo Yu , Osada Naoki , Mano Tsutomu , Masuda Ryuichi 
Published: August 2021

Abstract
Previous studies of the brown bear (Ursus arctos) on Hokkaido Island, Japan, have detected three geographically distinct subpopulations representing different mitochondrial lineages and shown that gene flow between subpopulations has occurred due to male-biased dispersal. In this study, we determined whole-genomic sequences for six Hokkaido brown bears and analyzed these data along with previously published genomic sequences of 17 brown bears from other parts of the world. We found that the Hokkaido population is genetically distinct from the other populations, keeping genetic diversity higher than the endangered populations in western Europe but lower than most populations on the continents. A reconstruction of historical demography showed no increase in population size for the Hokkaido population during the Eemian interglacial period (130,000–114,000 years ago). In a phylogenetic analysis of the autosomal data, the Hokkaido population formed a clade distinct from North American and European populations, showing that it has maintained genetic diversity independently from continental populations following geographical isolation on the island. This autosomal genetic similarity contrasts with the geographically separate mitochondrial lineages on Hokkaido and indicates the occurrence of male-driven gene flow between subpopulations.
Association Between Physical Activity, Quadriceps Muscle Performance, and Biological Characteristics of Very Old Men and Women
Authors: Varesco Giorgio , Coudy-Gandilhon Cécile , Lapole Thomas , Decourt Alice , Gueugneau Marine , Barthélémy Jean-Claude , Roche Frédéric , Bechet Daniel , Féasson Léonard , Rozand Vianney 
Published: August 2021

Abstract
The aim of the study was to evaluate the association between physical activity, knee extensors (KE) performance (ie, isometric strength and fatigability), and biological parameters (ie, muscle structural, microvascular, and metabolic properties) in healthy very old men and women. Thirty very old adults (82 ± 1 years, 15 women) performed an isometric Quadriceps Intermittent Fatigue (QIF) test for the assessment of KE maximal force, total work (index of absolute performance), and fatigability. Muscle biopsies from the vastus lateralis muscle were collected to assess muscle fibers type and morphology, microvasculature, and enzymes activity. Correlation analyses were used to investigate the relationships between physical activity (steps/day, actimetry), KE performance, and biological data for each sex separately. Men, compared to women, showed greater total work at the QIF test (44 497 ± 8 629 Ns vs 26 946 ± 4 707 Ns; p &lt; .001). Steps per day were correlated with total work only for women (r = 0.73, p = .011). In men, steps per day were correlated with the percentage (r = 0.57, p = .033), shape factor (r = 0.75, p = .002), and capillary tortuosity of type IIX fibers (r = 0.59, p = .035). No other relevant correlations were observed for men or women between steps per day and biological parameters. Physical activity level was positively associated with the capacity of very old women to perform a fatiguing test, but not maximal force production capacity of the KE. Physical activity of very old men was not correlated with muscle performance. We suggest that very old women could be at higher risk of autonomy loss and increasing the steps per day count could provide a sufficient stimulus for adaptations in less active women.
Frequency-dependent anisotropy due to non-orthogonal sets of mesoscale fractures in porous media
Authors: Shuai Da , Stovas Alexey , Zhao Yang , Huang Xingxing , He Lingyi 
Published: August 2021

SUMMARY
The monoclinic medium with a horizontal symmetry plane is gradually being studied for seismic anisotropy characterization. The principle goal of this paper is to investigate the effect of fracture parameters (azimuth angle, density, aspect ratio, scale) on the exact and approximate monoclinic anisotropy parameters. We derive the monoclinic porous media based on the Chapman model which accounts for the wave-induced fluid flow and give the expressions of the Thomsen-style anisotropy parameters (nine orthorhombic anisotropy parameters: VP0, VS0, ϵ1, ϵ2, γ1, γ2, δ1, δ2, δ3, three exact monoclinic parameters: ζ1, ζ2, ζ3 and three approximate monoclinic parameters: $\widetilde{\zeta _{1}}, \widetilde{\zeta _{2}}, \widetilde{\zeta _{3}}$). The dependence of Thomsen-style anisotropy parameters associated with azimuth angle between two fracture sets is analysed. The orthorhombic anisotropy parameters and monoclinic anisotropy parameters have the same period (π) on the azimuth angle between two fracture sets. The exact and approximate monoclinic anisotropy parameters responsible for the rotation of the P-wave NMO ellipse have a similar trend versus the azimuth angle, while those responsible for the rotation of the S1- and S2-wave NMO ellipses have significant discriminations. The influence of fracture density, aspect ratio, and scale on the monoclinic parameters are also analysed. The monoclinic anisotropy parameters responsible for the rotation of the P-wave NMO ellipse decrease with fracture density and aspect ratio increasing from 0 to 0.1, while those responsible for the rotation of S1- and S2-wave NMO ellipses increase with the fracture parameters. The fracture density has a bigger influence on the monoclinic anisotropy parameters than the fracture aspect ratio. When saturated with different fluids (water and CO2), the monoclinic parameters have a similar behaviour versus the azimuth angle between two fracture sets.
Key role of a structural water molecule for the specificity of 14F7—An antitumor antibody targeting the NeuGc GM3 ganglioside
Authors: Bjerregaard-Andersen Kaare , Abraha Fana , Johannesen Hedda , Oscarson Stefan , Moreno Ernesto , Krengel Ute 
Published: August 2021

Abstract
Tumor-associated glycolipids such as NeuGc GM3 are auspicious molecular targets in antineoplastic therapies and vaccine strategies. 14F7 is a monoclonal IgG1 with high clinical potential in cancer immunotherapy as it displays extraordinary specificity for NeuGc GM3, while it does not recognize the very similar, ubiquitous NeuAc GM3. Here we present the 2.3 Å crystal structure of the 14F7 antigen-binding domain (14F7 scFv) in complex with the NeuGc GM3 trisaccharide. Modeling analysis and previous mutagenesis data suggest that 14F7 may also bind to an alternative NeuGc GM3 conformation, not observed in the crystal structure. The most intriguing finding, however, was that a water molecule centrally placed in the complementarity-determining region directly mediates the specificity of 14F7 to NeuGc GM3. This has profound impact on the complexity of engineering in the binding site and provides an excellent example of the importance in understanding the water structure in antibody–antigen interactions.
Accounting for country- and time-specific values in the economic evaluation of health-related projects relevant to low- and middle-income countries
Authors: Lomas James , Claxton Karl , Ochalek Jessica 
Published: August 2021

Abstract
Economic evaluation of health-related projects requires principles and methods to address the various trade-offs that need to be made between costs and benefits, across sectors and social objectives, and over time. Existing guidelines for economic evaluation in low- and middle-income countries embed implicit assumptions about expected changes in the marginal cost per unit of health produced by the healthcare sector, the consumption value of health and the appropriate discount rates for health and consumption. Separating these evaluation parameters out requires estimates for each country over time, which have hitherto been unavailable. We present a conceptual economic evaluation framework that aims to clarify the distinct roles of these different evaluation parameters in evaluating a health-related project. Estimates for each are obtained for each country and in each time period, based on available empirical evidence. Where existing estimates are not available, for future values of the marginal cost per unit of health produced by the healthcare sector, new estimates are obtained following a practical method for obtaining projected values. The framework is applied to a simple, hypothetical, illustrative example, and the results from our preferred approach are compared against those obtained from other approaches informed by the assumptions implicit within existing guidelines. This exposes the consequences of applying such assumptions, which are not supported by available evidence, in terms of potentially sub-optimal decisions. In general, we find that applying existing guidelines as done in conventional practice likely underestimates the value of health-related projects on account of not allowing for expected growth in the marginal cost per unit of health produced by the healthcare sector.
Body Caudal Undulation Measured by Soft Sensors and Emulated by Soft Artificial Muscles
Authors: Schwab Fabian , Lunsford Elias T , Hong Taehwa , Wiesemüller Fabian , Kovac Mirko , Park Yong-Lae , Akanyeti Otar , Liao James C , Jusufi Ardian 
Published: August 2021

Abstract
We propose the use of bio-inspired robotics equipped with soft sensor technologies to gain a better understanding of the mechanics and control of animal movement. Soft robotic systems can be used to generate new hypotheses and uncover fundamental principles underlying animal locomotion and sensory capabilities, which could subsequently be validated using living organisms. Physical models increasingly include lateral body movements, notably back and tail bending, which are necessary for horizontal plane undulation in model systems ranging from fish to amphibians and reptiles. We present a comparative study of the use of physical modeling in conjunction with soft robotics and integrated soft and hyperelastic sensors to monitor local pressures, enabling local feedback control, and discuss issues related to understanding the mechanics and control of undulatory locomotion. A parallel approach combining live animal data with biorobotic physical modeling promises to be beneficial for gaining a better understanding of systems in motion.
Effective Kummer Theory for Elliptic Curves
Authors: Lombardo Davide , Tronto Sebastiano 
Published: August 2021

Abstract
Let $E$ be an elliptic curve defined over a number field $K$, let $\alpha \in E(K)$ be a point of infinite order, and let $N^{-1}\alpha $ be the set of $N$-division points of $\alpha $ in $E(\overline {K})$. We prove strong effective and uniform results for the degrees of the Kummer extensions $[K(E[N],N^{-1}\alpha ): K(E[N])]$. When $K=\mathbb Q$, and under a minimal (necessary) assumption on $\alpha $, we show that the inequality $[\mathbb Q(E[N],N^{-1}\alpha ): \mathbb Q(E[N])] \geq cN^2$ holds for a positive constant $c$ independent of both $E$ and $\alpha $.
Integrable Systems on Singular Symplectic Manifolds: From Local to Global
Authors: Cardona Robert , Miranda Eva 
Published: August 2021

Abstract
In this article, we consider integrable systems on manifolds endowed with symplectic structures with singularities of order one. These structures are symplectic away from a hypersurface where the symplectic volume goes either to infinity or to zero transversally, yielding either a $b$-symplectic form or a folded symplectic form. The hypersurface where the form degenerates is called critical set. We give a new impulse to the investigation of the existence of action-angle coordinates for these structures initiated in [34] and [35] by proving an action-angle theorem for folded symplectic integrable systems. Contrary to expectations, the action-angle coordinate theorem for folded symplectic manifolds cannot be presented as a cotangent lift as done for symplectic and $b$-symplectic forms in [34]. Global constructions of integrable systems are provided and obstructions for the global existence of action-angle coordinates are investigated in both scenarios. The new topological obstructions found emanate from the topology of the critical set $Z$ of the singular symplectic manifold. The existence of these obstructions in turn implies the existence of singularities for the integrable system on $Z$.
Clinical Cholera Surveillance Sensitivity in Bangladesh and Implications for Large-Scale Disease Control
Authors: Hegde Sonia T , Lee Elizabeth C , Islam Khan Ashraful , Lauer Stephen A , Islam Md Taufiqul , Rahman Bhuiyan Taufiqur , Lessler Justin , Azman Andrew S , Qadri Firdausi , Gurley Emily S 
Published: August 2021

Abstract

Background
A surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured.

Methods
We overlaid maps of nationally representative annual V cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and we identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies.

Results
We estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots and that 23% (25.5 million) of these individuals live in areas with the highest V cholerae infection rates.

Conclusions
The cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the country’s population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered.
Gaps Between Continuous Measurement Methods: A Longitudinal Study of Perceived Usability
Authors: Wang Yuhui 
Published: August 2021

AbstractThe available continuous measurement designs for longitudinal research on perceived usability include immediate and retrospective measurement methods. The present study was conducted to examine the gap between different continuous measurement designs. Thirty users completed a longitudinal study on typesetting software. We used two measurement methods to design three stages of testing. Each stage consists of one immediate measurement and two retrospective measurements. A long-term retrospective test was also conducted and SUS questionnaire measurements were gathered. We observed significant differences in perceived usability between participants with varying quantities of event experiences (i.e. the number of times they used the system). Within short periods of time (3 days), there may be significant differences between retrospective and immediate assessments—especially when users make negative evaluations. In the 3-day period, the user’s perceived usability retrospective evaluation is also based on the most recent experience as opposed to the most unpleasant. The recency effect is lost, however, over a long-term retrospective assessment (1 month later). This study is significant for two main reasons: (i) its unique methodology and (ii) its unprecedented level of consistency between measured results and actual user experiences. We hope that the results presented here provide a workable basis for continuous measurement design in future longitudinal studies. We found that in order to secure accurate measurements, it is necessary to set limits on the measurement time and the number of uses (events).
Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study
Authors: Khoo Saye H , Fitzgerald Richard , Fletcher Thomas , Ewings Sean , Jaki Thomas , Lyon Rebecca , Downs Nichola , Walker Lauren , Tansley-Hancock Olana , Greenhalf William , Woods Christie , Reynolds Helen , Marwood Ellice , Mozgunov Pavel , Adams Emily , Bullock Katie , Holman Wayne , Bula Marcin D , Gibney Jennifer L , Saunders Geoffrey , Corkhill Andrea , Hale Colin , Thorne Kerensa , Chiong Justin , Condie Susannah , Pertinez Henry , Painter Wendy , Wrixon Emma , Johnson Lucy , Yeats Sara , Mallard Kim , Radford Mike , Fines Keira , Shaw Victoria , Owen Andrew , Lalloo David G , Jacobs Michael , Griffiths Gareth 
Published: August 2021

Abstract

Objectives
AGILE is a Phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection.

Methods
We undertook a dose-escalating, open-label, randomized-controlled (standard-of-care) Bayesian adaptive Phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomized 2:1 in groups of 6 participants to 300, 600 and 800 mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was 25% or greater. Secondary outcomes included safety, clinical progression, pharmacokinetics and virological responses.

Results
Of 103 participants screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 300, 600 and 800 mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800 mg molnupiravir, respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild (≤grade 2). The probability of ≥30% excess toxicity over controls at 800 mg was estimated at 0.9%.

Conclusions
Molnupiravir was safe and well tolerated; a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation.