bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging T2WI hyperintense foci number and the prognosis of adenomyosis after high‐intensity focused ultrasound treatment
Authors: Du Cheng‐chao , Wang Yu‐qi , Qu Da‐cheng , Jiang Liu‐peng , Yu Xin , Zhou Hong‐gui 
Published: January 2021

AbstractObjectiveTo investigate the relationship between the number of hyperintense foci of T2‐weighted imaging (T2WI) and the efficacy of high‐intensity focused ultrasound (HIFU) in the treatment of adenomyosis.MethodsThis prospective cohort study enrolled 102 patients with adenomyosis. Participants were classified into two groups: 50 patients in whom the number of hyperintense foci on magnetic resonance imaging (MRI) T2WI was more than five were placed in the >5 group and 52 patients in whom the number of hyperintense foci on MRI T2WI was five or fewer were placed in the ≤5 group. Uterine fibroid symptoms (UFS) and visual analog scale (VAS) scores were recorded as indicators for the course of adenomyosis treatment.ResultsAmong the enrolled patients, 84 received HIFU treatment and were followed up. At 6, 12, 24, and 36 months after HIFU treatment, the UFS score of women in the >5 group was higher than that of the patients in the ≤5 group (P < 0.05). The ablation rate of MRI T2WI in the hyperintense foci ≤5 group was higher than the hyperintense foci >5 group (P < 0.05).ConclusionNumber of MRI T2WI hyperintense foci is a factor affecting the ablation rate and the clinical efficacy of HIFU treatment in women with adenomyosis. It is likely to be a predictor of the efficacy of HIFU in adenomyosis treatment.
An Early Attempt at a Core, Common Set of Loss‐Driven Systems Engineering Principles
Authors: Winstead Mark 
Published: January 2021

ABSTRACTPrinciples articulate the basic concepts guiding a discipline. Michael Watson observed “Principles are accepted truths that apply throughout a discipline. These truths serve as a guide to the application of the discipline.” To paraphrase Watson: “loss driven” systems engineering principles are accepted truths applying throughout the loss driven systems engineering discipline, guiding its application.What might these principles be for loss driven systems engineering? A starting point is looking for commonality and similarities among principles previously articulated for safety, security, resilience, and critical infrastructure protection and recovery. Where core principles appear unique to a specialty, the questions become: is there something more fundamental, more abstract, ultimately unifying across specialties? Can re‐expressing these unique specialty principles transcend specialties?This paper summarizes background for core principles among loss driven specialties. This background results from a review process identifying obvious commonalities among principles. This review identifies “new” transcendent principles and presents a first draft of core principles for loss driven systems engineering. Once assessed, the review process itself proposes potential next steps for maturing the loss driven systems engineering principle set.
Harmonizing the Domains of Loss‐Driven Systems Engineering
Authors: Willett Keith D. 
Published: January 2021

ABSTRACTSystem characteristics include what it is (structure, state), what it does (function, behavior), where it resides (environment, containing whole), what it uses (resources, energy source, raw material), what it contains (content), and why it exists (value delivery). An adversity produces a disturbance that can induce stress in a system so it may suffer some loss within one or more of these characteristics. Loss‐driven systems engineering (LDSE) is an approach to address systemic loss in all forms helping ensure value delivery. LDSE domains include reliability, sustainability, survivability, risk management, resistance, resilience, agility, safety, and security which all work in harmony to avoid, withstand, and recover from loss. Traditional systems engineering treats these as separate domains with varying degrees of detail, rigor, and results. LDSE proposes consolidating these domains for a comprehensive, cohesive, and consistent approach to address system loss. This paper establishes interrelationships among the LDSE domains to harmonize role, fit, function, and impact among the domains focusing on sustaining value‐delivery.
Analytical study of carbon dioxide equivalent emission from agricultural drain surfaces — a case study from Egypt*
Authors: Khairy Wael , Salem Mariam , Saber Gamal 
Published: January 2021

AbstractMethane emission is usually converted into equivalent carbon dioxide (CO2e) in order to compare it with other sectoral emissions. Estimation of methane from ‘agricultural drain surfaces’ is not accounted for in most of the derivation methods. This research paper dealt with the estimation of CO2e emission from ‘surfaces of the agricultural drains network in Egypt’ and then estimated the projected future CO2e emission loads trend for the period 2046–2065. CO2e emission was estimated using general circulation models for climate change under expected temperature variation in the coming decades. Annual average total CO2e emission loads from the BHD surface and its surrounding areas to the atmosphere were about 3790 t eq. CO2e yr‾¹ for the period 2046–2065. The ‘additional’ total emission of CO2e from the agriculture drainage network surface in relation to total emissions from the agricultural sector in Egypt was about 13.8%. It also accounted for about 1.4% of overall CO2e emission in Egypt. This research paper, furthermore, developed a methane indicative emission map for the Egyptian agricultural drainage network for the period 2046–2065, through which it is possible to estimate CO2e emission loads at any segment on any agricultural drain in Egypt during the period 2046–2065.
E‐transparency and government budgetary corruption: A social marketing and transformation case from Nigeria
Authors: Olarewaju Tolu , Rufai Ibrahim , Gallage Samanthika 
Published: January 2021

AbstractThis article shows how Information and Communication Technology (ICT), incorporating social media, can lead to accountability and transparency in a government's budget. Specifically, it examined how a Non‐Governmental Organization (NGO) used ICT to foster citizenship engagement in the Nigerian government budgetary process. The article, using abductive reasoning, presents four citizen empowerment stages and four social marketing transition stages through which government budget transparency can be improved and corruption reduced. A model was also inferred that can help lessen the exclusivity around the government budget to encourage dialog and openness around the government budget in similar contexts. Furthermore, this article shows that the social transformative role for NGOs using ICT to increase government budget transparency and reduce corruption is a process that happens over time.
Improving Bone Health by Optimizing the Anabolic Action of Wnt Inhibitor Multitargeting
Authors: Choi Roy B , Bullock Whitney A , Hoggatt April M , Loots Gabriela G , Genetos Damian C , Robling Alexander G 
Published: January 2021

ABSTRACTSclerostin antibody (romosozumab) was recently approved for clinical use in the United States to treat osteoporosis. We and others have explored Wnt‐based combination therapy to disproportionately improve the anabolic effects of sclerostin inhibition, including cotreatment with sclerostin antibody (Scl‐mAb) and Dkk1 antibody (Dkk1‐mAb). To determine the optimal ratio of Scl‐mAb and Dkk1‐mAb for producing maximal anabolic action, the proportion of Scl‐mAb and Dkk1‐mAb were systematically varied while holding the total antibody dose constant. A 3:1 mixture of Scl‐mAb to Dkk1‐mAb produced two to three times as much cancellous bone mass as an equivalent dose of Scl‐mAb alone. Further, a 75% reduction in the dose of the 3:1 mixture was equally efficacious to a full dose of Scl‐mAb in the distal femur metaphysis. The Scl‐mAb/Dkk1‐mAb combination approach was highly efficacious in the cancellous bone mass, but the cortical compartment was much more subtly affected. The osteoanabolic effects of Wnt pathway targeting can be made more efficient if multiple antagonists are simultaneously targeted. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
A computational method to simulate global conformational changes of proteins induced by cosolvent
Authors: Tanimoto Shoichi , Tamura Koichi , Hayashi Shigehiko , Yoshida Norio , Nakano Haruyuki 
Published: January 2021

AbstractA computational method to investigate the global conformational change of a protein is proposed by combining the linear response path following (LRPF) method and three‐dimensional reference interaction site model (3D‐RISM) theory, which is referred to as the LRPF/3D‐RISM method. The proposed method makes it possible to efficiently simulate protein conformational changes caused by either solutions of varying concentrations or the presence of cosolvent species by taking advantage of the LRPF and 3D‐RISM. The proposed method is applied to the urea‐induced denaturation of ubiquitin. The LRPF/3D‐RISM trajectories successfully simulate the early stage of the denaturation process within the simulation time of 300 ns, whereas no significant structural change is observed even in the 1 μs standard MD simulation. The obtained LRPF/3D‐RISM trajectories reproduce the mechanism of the urea denaturation of ubiquitin reported in previous studies, and demonstrate the high efficiency of the method.
The involvement of nuclear factor‐κB in astroprotection against ischemia‐reperfusion injury by ischemia‐preconditioned neurons
Authors: Wu Xiao‐Mei , Qian Christopher , Jiang Fei , Bao Yu‐Xin , Qian Zhong‐Ming , Ke Ya 
Published: January 2021

AbstractIschemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)‐induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor‐κB (NF‐κB) in cell survival and adaption to oxidative stress, we hypothesized that NF‐κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes. Here, we investigated the effects of IP neurons on NF‐κB activation, cell viability, reactive oxygen species (ROS), expression of antioxidant enzymes, erythropoietin (EPO), and tumor necrosis factor α (TNF‐α), in the presence or absence of BAY11‐7082 (an NF‐κB inhibitor), anti‐EPO, and anti‐TNF‐α antibodies, in astrocytes treated with or without I/R. We found that IP neurons could keep NF‐κB activation at a relatively higher but beneficial level, and in turn, upregulated the activity of antioxidant enzymes and hence enhanced cell viability and reduced ROS in I/R treated astrocytes. The results collectively indicated that IP neurons are able to significantly inhibit the I/R‐induced NF‐κB overactivation, probably via EPO and TNF‐α, being essential for IP neuron‐induced astroprotection under the conditions of I/R. We concluded that NF‐κB‐mediated antioxidative stress is one of the mechanisms by which IP neurons protect astrocytes against I/R injury.
Natural ghrelin in advanced cancer patients with cachexia, a case series
Authors: Blum David , de Wolf‐Linder Susanne , Oberholzer Rolf , Brändle Michael , Hundsberger Thomas , Strasser Florian 
Published: January 2021

AbstractBackgroundNatural ghrelin, a peptide growth hormone secretagogue, has a therapeutic potential in cachexia. We designed a dose‐finding trial of subcutaneous natural ghrelin to improve nutritional intake (NI) in advanced cancer patients.MethodsAdvanced cancer patients with cachexia management (symptom management, physiotherapy, nutritional, and psychosocial support) started with ghrelin at 32 μg/kg body weight, followed by 50% dose increases. Patients self‐injected ghrelin twice daily for 4 days followed by a wash‐out period. After reaching the primary endpoint, maximal NI (minimal dose for maximal NI), a maintenance period followed during which patients injected 10 doses of ghrelin per week. Safety parameters, NI, and cachexia outcomes (symptoms, narratives, muscle mass, and strength) were measured over 6 weeks.ResultsTen patients with metastatic solid tumours were included, and six (100% male, mean age 61.8 ± 8.5 SD) received ghrelin. Minimal dose for maximal NI was reached in four patients. Three patients reached the end‐of study visit. Ghrelin was well tolerated with variable results on appetite and eating‐related symptoms but a positive effect in the narratives. Mean Functional Assessment of Appetite & Cachexia Therapy score was 6.8 points lower at final measurement compared with baseline, t(5) = 5.98, P < .01. Muscle mass was stable in two patients and increased in one patient, and muscle strength was stable in three patients. Subjective tolerability was high. Patients showed a fluctuating trajectory, and median survival was 88 days (51–412 days).ConclusionsGhrelin was safe in advanced patients with cancer cachexia without dose‐limiting toxicity and well tolerated. The intervention was very complex, and the number of patients included was small. There was a positive effect on nutritional intake and patient narratives.
Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge?
Authors: Vogel Robert , Savage John , Muzard Julien , Della Camera Giacomo , Vella Gabriele , Law Alice , Marchioni Marianne , Mehn Dora , Geiss Otmar , Peacock Ben , Aubert Dimitri , Calzolai Luigi , Caputo Fanny , Prina‐Mello Adriele 
Published: January 2021

AbstractThe measurement of physicochemical properties of polydisperse complex biological samples, for example, extracellular vesicles, is critical to assess their quality, for example, resulting from their production and isolation methods. The community is gradually becoming aware of the need to combine multiple orthogonal techniques to perform a robust characterization of complex biological samples. Three pillars of critical quality attribute characterization of EVs are sizing, concentration measurement and phenotyping. The repeatable measurement of vesicle concentration is one of the key‐challenges that requires further efforts, in order to obtain comparable results by using different techniques and assure reproducibility. In this study, the performance of measuring the concentration of particles in the size range of 50–300 nm with complementary techniques is thoroughly investigated in a step‐by step approach of incremental complexity. The six applied techniques include multi‐angle dynamic light scattering (MADLS), asymmetric flow field flow fractionation coupled with multi‐angle light scattering (AF4‐MALS), centrifugal liquid sedimentation (CLS), nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (TRPS), and high‐sensitivity nano flow cytometry (nFCM). To achieve comparability, monomodal samples and complex polystyrene mixtures were used as particles of metrological interest, in order to check the suitability of each technique in the size and concentration range of interest, and to develop reliable post‐processing data protocols for the analysis. Subsequent complexity was introduced by testing liposomes as validation of the developed approaches with a known sample of physicochemical properties closer to EVs. Finally, the vesicles in EV containing plasma samples were analysed with all the tested techniques. The results presented here aim to shed some light into the requirements for the complex characterization of biological samples, as this is a critical need for quality assurance by the EV and regulatory community. Such efforts go with the view to contribute to both, set‐up reproducible and reliable characterization protocols, and comply with the Minimal Information for Studies of Extracellular Vesicles (MISEV) requirements.
At least half of the leapfrog fullerene graphs have exponentially many Hamilton cycles
Authors: Kardoš František , Mockovčiaková Martina 
Published: January 2021

AbstractA fullerene graph is a 3‐connected cubic planar graph with pentagonal and hexagonal faces. The leapfrog transformation of a planar graph produces the dual of the truncation of the given graph. A fullerene graph is a leapfrog if it can be obtained from another fullerene graph by the leapfrog transformation. We prove that leapfrog fullerene graphs on vertices have at least Hamilton cycles.
Seymour's second‐neighborhood conjecture from a different perspective
Authors: Bouya Farid , Oporowski Bogdan 
Published: January 2021

AbstractSeymour's Second‐Neighborhood Conjecture states that every directed graph whose underlying graph is simple has at least one vertex such that the number of vertices of out‐distance two from is at least as large as the number of vertices of out‐distance one from it. We present alternative statements of the conjecture in the language of linear algebra.
The feasibility and safety in using acetaminophen with fentanyl for pain control after liver resection with regards to liver function: A prospective single‐center pilot study in Japan
Authors: Hidaka Masaaki , Ohyama Kaname , Hara Takanobu , Soyama Akihiko , Adachi Tomohiko , Kamada Natsu , Nakashima Mikiro , Ichinomiya Taiga , Hara Tetsuya , Eguchi Susumu 
Published: January 2021

AbstractIntroductionAcetaminophen has been widely used as an analgesic agent after various types of surgery. However, acetaminophen may sometimes induce severe liver dysfunction, which can occasionally lead to the need for liver transplantation. The aim of this study was to assess the feasibility and efficacy of administering acetaminophen to patients after liver resection (LR).Patients and methodsThe prospective study included 50 patients who underwent the following procedures: partial LR (n = 21) and more than one section LR (n = 29). Pain control was provided with continuous intravenous fentanyl and acetaminophen every 6 hours (within 2 days). We analyzed the liver function and blood concentration of acetaminophen at 1 and 3 days after LR using high performance liquid chromatography (HPLC), and investigated the results of partial and more than one section LR, and also examined the degree of liver fibrosis.ResultsThe alanine transaminase level on postoperative days 1, 5, and 7 and total bilirubin on postoperative days 1 to 5 after LR in patients with more than one section LR was significantly higher than the levels in patients with partial resection. No patients developed liver failure. The blood concentration of acetaminophen by HPLC was significantly elevated in patients with resection of more than one section in comparison to the partial resection group.ConclusionThe safety of acetaminophen was evaluated in Japanese patients who underwent different types of LR with different degrees of liver fibrosis.
Catalyst‐free facile and efficient one‐pot synthesis of densely functionalized pyrroles and α‐amino ketones
Authors: Vanga Sivarama Krishna Reddy , Bollikolla Hari Babu , Peruri V. V. Satyanarayana 
Published: January 2021

AbstractAn efficient catalyst‐free one‐pot three‐component synthesis of penta‐substituted pyrroles has been successfully developed. A variety of penta‐substituted pyrroles were straightforwardly synthesized from good to excellent yields (78%–93%) by using easily accessible starting materials under mild conditions. This protocol also provided α‐amino ketones in good yields (87%–98%) without column chromatography.
Mass spectrometry in the study of molecular complexes between 5‐fluorouracil and catechins
Authors: Moracci Laura , Crotti Sara , Traldi Pietro , Agostini Marco 
Published: January 2021

Abstract5‐Fluorouracil (5FU) is a widely employed antineoplastic agent that acts as antimetabolite. However, 5FU activity is strongly reduced against a subset of cancer cells called cancer stem cells (CSCs), which are believed to be responsible for chemoresistance and tumour recurrence. It was found that epigallocatechin‐3‐gallate (EGCG), the most abundant catechin present in green tea extract, suppresses CSCs grown in various cancers. This chemosensitizing effect of EGCG was investigated in 5FU‐resistant (5FUR) CRC cells, showing that EGCG enhances 5FU‐induced cytotoxicity. However, the real mechanism of an improved 5FU chemosensitivity in the presence of EGCG was not evaluated. Considering the capability of catechins to form bimolecular noncovalent complexes, in the present study, the interaction of catechins and 5FU was studied by different mass spectrometric approaches. The ESI(+) and ESI(−) spectra of [5FU‐catechin] mixtures were studied, showing the formation of protonated and deprotonated bimolecular complexes, whose nature was confirmed by MS/MS experiments (product and precursor ion scans). To exclude the possible origin of these species as ESI artefacts, a further series of experiments were performed by high‐resolution liquid chromatography–mass spectrometry. By this approach, bimolecular complexes have been detected at retention times different from those of free 5FU and catechins, proving their presence in the original solution. Analogous studies were performed on 5FU‐green tea extract mixtures, showing that 5FU leads to complexes not only with EGCG but also with other catechins. These molecular species, differently to free 5FU drug alone, would in principle possess a new biological activity and could be an explanation of the described activity cited above.
Hydrogen–deuterium exchange mass spectrometry identifies spatially distinct antibody epitopes on domain III of the Zika virus envelope protein
Authors: Adhikari Jagat , Zhao Haiyan , Fernandez Estefania , Huang Yining , Diamond Michael S. , Fremont Daved H. , Gross Michael L. 
Published: January 2021

AbstractZika virus (ZIKV) has become a global public health concern because it causes fetal microcephaly and other neurological complications in humans. Currently, there are no approved treatments or vaccines for ZIKV infection. We describe here the epitopes for six monoclonal antibodies (mAbs) that bind to domain III of the envelope protein of ZIKV, some of which have therapeutic potential. We show that by using hydrogen–deuterium exchange mass spectrometry (HDX‐MS), we can identify three spatially distinct epitopes for the six mAbs investigated. The HDX‐MS approach identified epitopes for three mAbs that agreed well with previously reported X‐ray crystallography data. The HDX‐MS determined epitopes for the other three anti‐ZIKV mAbs, for which there were no crystal structures, and the epitopes were confirmed by structure‐guided mutagenesis and biolayer interferometry competition binding assay. Our results have implications for the design of vaccine and antibody therapeutics against ZIKV and demonstrate the use of HDX‐MS as a rapid and valid approach for epitope mapping.