bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the use of individualised patient‐reported outcome measures in eating disorders: Validation of the Psychological Outcome Profiles
Authors: Austin Amelia , Potterton Rachel , Flynn Michaela , Richards Katie , Allen Karina , Grant Nina , Glennon Danielle , Mountford Victoria A. , Franklin‐Smith Mary , Schelhase Monique , Jones William R. , Serpell Lucy , Mahoney Kate , Brady Gaby , Nunes Nicole , Kali Kuda , Connan Frances , Schmidt Ulrike
Published: January 2021

Rationale

Psychotherapies for eating disorders (EDs) are routinely assessed using standardised patient‐reported outcome measures (PROMs). PROMs have been criticised for their lack of patient centeredness and clinical utility. The Psychological Outcome Profiles (PSYCHLOPS) is an individualised PROM that allows patients to specify their own outcomes.

Aims

(1) To validate the use of the PSYCHLOPS in ED treatment, and (2) to identify patient concerns beyond those measured by common ED PROMs.

Methods

Two hundred and seventy‐eight emerging adult patients, presenting with a first‐episode ED (aged 16–25, illness duration <3 years) completed the PSYCHLOPS and two standardised ED PROMs (the EatingDisorder Examination Questionnaire [EDE‐Q] and the Clinical Impairment Assessment Questionnaire [CIA]) at four time points across 12 months. Psychometrics of the PSYCHLOPS were assessed quantitatively against the EDE‐Q and CIA. Content analysis assessed unique patient concerns identified by PSYCHLOPS.

Results

The PSYCHLOPS had adequate to good psychometric properties. A total of 53.3% of participants reported a concern not addressed by the EDE‐Q or the CIA, the most common being depression/anxiety, academic problems, treatment concerns and disturbed sleep.

Discussion

PROMs can be complemented by the PSYCHLOPS to identify problems specific to an individual's context. As ED patients are typically ambivalent about change, understanding their concerns is vital in building motivation for change.
Clinical and genomic characterization of patients diagnosed with the provisional entity acute myeloid leukemia with BCR‐ABL1, a Swedish population‐based study
Authors: Orsmark‐Pietras Christina , Landberg Niklas , Lorenz Fryderyk , Uggla Bertil , Höglund Martin , Lehmann Sören , Derolf Åsa , Deneberg Stefan , Antunovic Petar , Cammenga Jörg , Möllgård Lars , Wennström Lovisa , Lilljebjörn Henrik , Rissler Marianne , Fioretos Thoas , Lazarevic Vladimir Lj
Published: January 2021

Acute myeloid leukemia (AML) with t(9;22)(q34;q11), also known as AML with BCR‐ABL1, is a rare, provisional entity in the WHO 2016 classification and is considered a high‐risk disease according to the European LeukemiaNet 2017 risk stratification. We here present a retrospective, population‐based study of this disease entity from the Swedish Acute Leukemia Registry. By strict clinical inclusion criteria we aimed to identify genetic markers further distinguishing AML with t(9;22) as a separate entity. Twenty‐five patients were identified and next‐generation sequencing using a 54‐gene panel was performed in 21 cases. Interestingly, no mutations were found in NPM1, FLT3, or DNMT3A, three frequently mutated genes in AML. Instead, RUNX1 was the most commonly mutated gene, with aberrations present in 38% of the cases compared to around 10% in de novo AML. Additional mutations were identified in genes involved in RNA splicing (SRSF2, SF3B1) and chromatin regulation (ASXL1, STAG2, BCOR, BCORL1). Less frequently, mutations were found in IDH2, NRAS, TET2, and TP53. The mutational landscape exhibited a similar pattern as recently described in patients with chronic myeloid leukemia (CML) in myeloid blast crisis (BC). Despite the concomitant presence of BCR‐ABL1 and RUNX1 mutations in our cohort, both features of high‐risk AML, the RUNX1‐mutated cases showed a superior overall survival compared to RUNX1 wildtype cases. Our results suggest that the molecular characteristics of AML with t(9;22)/BCR‐ABL1 and CML in myeloid BC are similar and do not support a distinction of the two disease entities based on their underlying molecular alterations.
Ceramic exchange networks in the south‐central Tuxtla Mountains, southern Veracruz, Mexico
Authors: Venter Marcie L. , Pierce Daniel , Glascock Michael D.
Published: January 2021

Our study situates the classic period center Matacanela, located in southern Veracruz, Mexico, within the context of shifting regional political‐economic systems. Specifically, we assess the potential for utilizing neutron activation analysis (NAA) of pottery in the study of changing interactions through a focus on three ceramic wares: Coarse Orange, Fine Orange, and Coarse Brown. NAA identified four compositional groups, suggesting that Matacanela selectively utilized ceramics from a variety of sources, but the center's inhabitants overwhelming used ceramics that were only occasionally exploited by their contemporaries in the nearby Catemaco and Tepango valleys. Instead, the center's primary ceramic exchange partners were in the southern Tuxtlas foothills. This divergent pattern of ceramic exchange parallels earlier obsidian exploitation differences that revealed participation in the networks of the western Tuxtla uplands as well as the southern foothills and centers within eastern Olman. The findings of this study contribute to (1) the geological characterization of ceramic resources used by ancient Gulf lowland societies, (2) to the comparative ceramic database in a region that was an important nexus for diverse cultural traditions spanning Mesoamerican prehistory, and (3) the refinement of our knowledge relevant to the divergent strategies employed by groups.
Petrology and geochemistry of mafic plugs associated with the Semri Group of the Vindhyan Supergroup in the eastern part of the Son valley, Central India: Implications for bimodal volcanism
Authors: Mageswarii G. , Mishra Meenal , Shrivastava Jaya Prakash
Published: January 2021

The intrabasinal felsic pyroclastics and rhyolite in the lower part of Semri Group of Vindhyan Supergroup are intruded by 3–11 m thick mafic plugs. These mafic bodies intrude Kajrahat Limestone of Semri Group. Earlier studies pertaining to these dykes are restricted to petrography; however, geochemical data on these rocks are lacking. Ca‐plagioclase, augite, and enstatite‐bearing dolerites show sub‐alkaline nature with basaltic andesitic (52–56% SiO2) composition. They exhibit moderate incompatible trace elemental enrichment, characterized by enriched LREE and depleted HREE [(La/Yb)N = 3.5–5.7] contents akin to those reported from the intraplate continental rift‐related basalts. Moreover, high Ba, Th, U together with the low Nb, Ta, and Ti values suggests crustal contamination. Chondrite‐normalized REE patterns and trace element ratios when compared to continental rift basalts show similarity with them. Th/Ta and La/Yb discriminant diagram represents mixed sources and characterizes the occurrence in the sub‐continental lithosphere. High La/Nb, La/Ta ratios, and positive Eu anomaly indicate that the basalt was derived from a depleted mantle source but mixed with crustal components. It is further supported by the ratios of Yb/Ta, Nb/Ta, and Zr/Hf indicating crustal contamination. In this article, we report the petrological and geochemical characteristics for the bimodal volcanics in order to understand their magma source and implications on tectonic setting in the lower part of Vindhyan Basin.
Psychomotor processing and functional decline in Parkinson's disease predicted by the Purdue Pegboard test
Authors: Hinkle Jared T. , Pontone Gregory M.
Published: January 2021

Background

The Purdue Pegboard test (PPT) assesses upper‐extremity dexterity and motor skills. We hypothesized that PPT skill would predict functional and cognitive decline in Parkinson's disease (PD), independent of observer‐rated measures of motor impairment.

Methods

We utilized data from 399 PD participants enrolled in the deprenyl and tocopherol antioxidative therapy of Parkinsonism trial. Unified Parkinson Disease Rating Scale (UPDRS) metrics, neuropsychological assessments, and clinical rating scales were extracted for analysis with multivariate linear mixed‐effects and generalized estimating equation regression models.

Results

In multivariate logistic regression, higher baseline and time‐varying PPT scores predicted better visual processing speed and attention throughout longitudinal follow‐up. No similarly strong associations were found for tests of memory, nonvisual attention, phonemic fluency, or set‐shifting. Independently of observer‐rated motor impairment (UPDRS part III), PPT performance was significantly associated with changes in activities of daily living (ADL) function measured with UPDRS part II. Low baseline PPT score (≤10th percentile) doubled the relative risk of later ADL dysfunction (≥90th percentile).

Conclusions

PPT impairment selectively predicted declining psychomotor processing speed in PD. The domain‐specificity of this association may reflect correlated pathophysiological changes in top‐down visual and motor control pathways. PPT also predicted increasing ADL dysfunction after adjusting for objective measures of motor impairment. We suggest that PPT scores may be prognostically useful for predicting cognitive changes and ADL dysfunction, which have dramatic impacts on both patient and caregiver quality of life. Furthermore, simple task‐based assessments like the PPT could be investigated for remote assessment in PD.
Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein–Barr virus DNA
Authors: Wei Zhi‐Gong , Hu Xiao‐Lin , He Yan , Guan Hui , Wang Jing‐Jing , He Ling , Mu Xiao‐Li , Liu Zhe‐Ran , Li Rui‐Dan , Peng Xing‐Chen
Published: January 2021

Background

To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein–Barr virus (EBV) DNA level.

Methods

Propensity score matching (PSM) method was used to create well‐balanced cohorts. Kaplan–Meier method and Cox proportional hazards models were performed to conduct survival analysis.

Results

Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3‐year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004).

Conclusions

NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.
Pattern separation beyond the hippocampus: Ahigh‐resolution whole‐braininvestigation of mnemonic discrimination in healthy adults
Authors: Nash Michelle I. , Hodges Cooper B. , Muncy Nathan M. , Kirwan C. Brock
Published: January 2021

Episodic memory depends on the computational process of pattern separation in order to establish distinct memory representations of similar episodes. Studies of pattern separation in humans rely on mnemonic discrimination tasks, which have been shown to tax hippocampal‐dependent pattern separation. Although previous neuroimaging research has focused on hippocampal processing, little is known about how other brain regions, known to be involved in recognition memory performance, are involved in mnemonic discrimination tasks. Conversely, neuroimaging studies of pattern separation with whole‐brain coverage lack spatial resolution to localize activation to hippocampal subfields. In this study, 48 healthy young adult participants underwent whole‐brain high‐resolution functional MRI (fMRI) scanning while completing a mnemonic discrimination task. A priori region‐of‐interest analyses revealed activation patterns consistent with pattern separation in distinct hippocampal subregions, particularly in the subiculum. Connectivity analyses revealed a network of cortical regions consistent with the memory retrieval network where fMRI activation was correlated with hippocampal activation. An exploratory whole‐brain analysis revealed widespread activation differentially associated with performance of the mnemonic discrimination task. Taken together, these results suggest that a network of brain regions contribute to mnemonic discrimination performance, with the hippocampus and parahippocampal cortex as a hub in the network displaying clear signals consistent with pattern separation and regions such as the dorsal medial prefrontal cortex particularly important for successful lure discrimination.
Radiative flow of MHD non‐Newtonian fluid by utilizing the updated version of heat flux model under Joule heating
Authors: Sohail Muhammad , Alrabaiah Hussam , Nazir Umar
Published: January 2021

This exploration reports the analysis of thermal and species transportation to yields manifesting non‐Newtonian material flowing over the linear stretching sheet. Phenomena of heat transport are presented via Cattaneo–Christov heat flux definition. Mass transportation is modeled by engaging the traditional Fick's second law with updated model of mass flux including the species relaxation time. Moreover, Joule heating and radiation contribution to thermal transmission are also considered. The significant contribution of diffusion‐thermo and thermos‐diffusion is engaged in thermal and species transmission. Physical depiction of the considered scenario is modeled via boundary layer approximation. Similarity analysis has been made to transfigure the system of modeled partial differential equations into respective ordinary differential equations. Afterwards, transformed physical expressions are computed for the momentum, thermal, and species transportation inside the boundary layer.
Effect of outline curvature degree on heat transfer and flow characteristics inside dimpled tubes and spirally grooved tubes
Authors: Zhang Liang , Xiong Wei , Liang Zheng
Published: January 2021

The flow behaviors and heat transfer characteristics have been studied inside the dimpled tubes and spirally grooved tubes with different curvature degrees, which is considered for the first time within the influence factors. A three‐dimensional numerical simulation by periodic boundary conditions is performed to model the fully developed flow of dimpled and grooved sections to acquire the finer mesh and more accurate results. In addition, the dimple and groove outlines with different curvature degrees are generated by polynomial functions. Effects of curvature degrees for dimpled tubes and spirally grooved tubes on flow, heat transfer, and comprehensive performances are discussed. The results indicate that the influence of curvature degrees for dimpled tubes exhibit an opposite behavior when compared with those for spirally grooved tubes. On the whole, all performance factors increase with the growing curvature degree for dimpled tubes but decrease with the increasing curvature degree for spirally grooved tubes. By comparing different curvature degrees, the maximum ranges of heat transfer enhancement are 1.50–2.22 and 2.54–2.82, respectively, for dimpled and grooved tubes with respect to Re. Thermal and hydraulic fields are considered to analyze the mechanism of heat transfer enhancement. The analysis shows that the way the dimple changes thermohydraulic properties differs from the way the groove changes the properties.
Long term high frequency sediment observatory in an alpine catchment: The Arc‐Isère rivers, France
Authors: Thollet Fabien , Rousseau Christophe , Camenen Benoit , Boubkraoui Stephane , Branger Flora , Lauters François , Némery Julien
Published: January 2021

We present a dataset on to the Arc‐Isère long‐term environmental research observatory, which is part of the Rhône Basin Long Term Environmental Research Observatory. This alpine catchment located in the French Alps is characterized by high Suspended Particulate Matter (SPM) in anthropogenized valleys. Suspended Sediment Concentrations (SSC) naturally observed in the river are very high, ranging from a few tens of milligrams per litre at low flow to tens of grams per litre during major natural hydrological events (floods, debris flows) or river dam hydraulic flushes. One research objective related to this site is to better understanding the SSC dynamics along the river using a system of nested catchments (Arvan, Arc, and Isère) in order to assess both temporal and spatial dynamics. The data allow the quantification of fine sediment yields and also the evaluation of possible morphological changes due to fine sediment deposition or resuspension. Additionally, the observatory database support studies on contaminants (either dissolved or particulate contaminants). Our monitoring includes six stations with high frequency (2–30 min) streamflow, SSC measurement using turbidity sensors, and associated automatic sampling. Discharge is measured via water level measurements and a rating curve. The oldest station (Grenoble‐campus) started recording discharge and concentration data from April 2006 while others stations were built between 2009 and 2011. Data are available in an online data website called ‘Base de Données des Observatoires en Hydrologie’ (Hydrological observatory database, https://bdoh.irstea.fr/ARC-ISERE/) with a DOI reference for the dataset. The hydrological and sediment transport time series are stored, managed and made available to a wide community with unfettered access in order to be used at their full extent. This database is used as a data exchange tool for both scientists and operational end‐users and there is an associated online tool to compute integrated fluxes.
Establishment and characterization of murine models of asthma and subcutaneous immunotherapy for Humulus pollen allergy
Authors: Xi Guang P. , Zhang Qian , Yin Jia
Published: January 2021

Introduction

Humulus pollen is an important cause of allergic asthma in East Asia. There have been some murine models for Humulus pollen allergy established by intraperitoneal (IP) sensitization and nasal drip stimulation, but they were not comprehensive enough. Here, we used atomized inhalation for challenge and compared the subcutaneous (SC) and IP sensitization routes to determine the optimal method to establish a model of asthma induced by Humulus pollen. Subsequently, we tried to develop a rapid subcutaneous immunotherapy (SCIT) model for Humulus allergy.

Methods

BALB/c Mice were sensitized through the SC or IP route, with respective reference to previously established sensitization methods and allergen dosing, and challenged with nebulized Humulus pollen extract to induce asthma. To compare the two sensitization methods, airway hyperresponsiveness (AHR), inflammatory cell infiltration, allergen‐specific serum immunoglobulin (Ig)E (sIgE) levels, cytokine levels, and lung histopathology were assessed. The effects of SCIT (once every other day for 16 days) on airway inflammation, AHR, sIgE, and allergen‐specific serum IgG2a (sIgG2a) levels were evaluated by using the model established in this study.

Results

Although mice sensitized by the SC or IP routes both showed AHR and airway inflammation, the SC route elicited significantly higher levels of sIgE, eosinophil inflammation, and T helper type 2 cytokines, compared with the IP route. SCIT in the treatment group significantly reduced the titers of sIgE, enhanced the titers of sIgG2a, and effectively alleviated pulmonary inflammation and AHR, compared with the vehicle group.

Conclusions

The SC route can be used to establish a murine model of Humulus pollen allergy that recapitulates the characteristics of clinical allergic asthma. Short‐term SCIT can significantly improve symptoms and pathophysiology in asthmatic mice.
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

Objective

To 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.

Methods

This 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.

Results

Among 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).

Conclusion

Number 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.
A rare case of ectopic pregnancy: Posterior ectopic pregnancy of the iliac vessels
Authors: Shi Qiaorui , Wang Xue , Wang Xiaohui
Published: January 2021

Synopsis

Posterior iliac vasculature pregnancy is an extremely dangerous condition; however, surgical treatment can achieve a positive outcome through the cooperation of a multidisciplinary team.
An Early Attempt at a Core, Common Set of Loss‐Driven Systems Engineering Principles
Authors: Winstead Mark
Published: January 2021

Principles 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

System 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

Methane 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

This 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

Sclerostin 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

A 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

Ischemic 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

Background

Natural 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.

Methods

Advanced 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.

Results

Ten 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).

Conclusions

Ghrelin 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

The 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

A 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

Seymour'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

Introduction

Acetaminophen 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 methods

The 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.

Results

The 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.

Conclusion

The 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

An 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.
Synthesis of 13C‐labelled cutin and suberin monomeric dicarboxylic acids of the general formula HO213C‐(CH2)n‐13CO2H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28)
Authors: Schink Carina , Spielvogel Sandra , Imhof Wolfgang
Published: January 2021

13C‐labeled dicarboxylic acids HO213C‐(CH2)n‐13CO2H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28) have been synthesized as internal standards for LC‐MS and GC‐MS analysis of cutin and suberin monomer degradation by soil‐based microorganisms. Different synthetic strategies had to be applied depending on the chain length of the respective synthetic target and because of economic considerations. 13C‐labels were introduced by nucleophilic substitution of a suitable leaving group with labelled potassium cyanide and subsequent hydrolysis of the nitriles to produce the corresponding dicarboxylic acids. All new compounds are characterized by GC/MS, IR, and NMR methods as well as by elemental analysis.
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

5‐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

Zika 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.
Assessing the effects of climate variable and timescale selection on uncertainties in dryness/wetness trends in conterminous China
Authors: Ma Tianxiao , Liang Yu , Sunde Michael G. , Lau Matthew K. , Liu Bo , Wu Mia M. , He Hong S.
Published: January 2021

Analysing dryness/wetness trends, which is typically achieved by examining drought indices, is an essential approach for assessing extreme climate events. However, since there are differences among studies in terms of selected climate variables and timescales used to calculate drought indices, there is uncertainty regarding the magnitude and direction of the dryness/wetness, trend even for the same region. We used 40 years weather station data (1970–2010) and studied the uncertainties of dryness/wetness trends in conterminous China. The effects of selected climate variables, timescales and their interaction on the dryness/wetness trends were quantified by comparing the Standardized Precipitation Index, Standardized Precipitation Evapotranspiration Index (SPEI) with the Thornthwaite equation and SPEI with the Penman–Monteith equation at 3‐, 12‐ and 24‐month timescales. The results indicated that (a) higher uncertainties occurred in relatively arid and humid regions; (b) timescale tended to exaggerate the effect of climate variables, even though its effect was substantially lower than climate variables; (c) relative humidity and precipitation were the primary climate variables affecting observed dryness/wetness trend uncertainties. Since the key climate variables changed depending on the selected timescale, the role of timescale should be further examined the Inner Mongolia and Northeast regions. In general, the study results suggest that the trend analysis of dryness/wetness should include the interaction of both climate variable and timescale selection, particularly when a single drought index is used to estimate the dryness/wetness trend in diverse regions.
Parenteral Protein Decision Support System Improves Protein Delivery in Preterm Infants: A Randomized Clinical Trial
Authors: Alrifai Mhd Wael , Mulherin David P. , Weinberg Stuart T. , Wang Li , Lehmann Christoph U.
Published: January 2021

Background

Management of neonatal parenteral protein intake for preterm infants is challenging and requires daily modifications of the dose to account for the infant's postnatal age, birth weight, current weight, and the volume and protein concentration of concurrent enteral nutrition. The objective of this study was to create and evaluate the Parenteral Protein Calculator (PPC), a clinical decision support system to improve the accuracy of protein intake for preterm infants who require parenteral nutrition (PN).

Materials and Methods

We integrated the PPC into the computerized provider order entry system and tested it in a randomized controlled trial (routine or PPC). Infants were eligible if they were ≤3 days old, had a birth weight ≤1500 g, and had no inborn error of metabolism. The primary outcome was the appropriate total protein intake, defined as target protein dose ±0.5 g/kg.

Results

We randomly allocated 42 infants for 221 PN days in the control group and 211 in the PPC group. Total protein intake in the PPC group was more accurate as compared with the control group (appropriate protein dosing: odds ratio = 5.8; 95% CI, 2.7–12.4). Absolute deviation from protein target was 0.41 g/kg (0.24–0.58) lower in the PPC group.

Conclusion

The PPC improved appropriate protein dosing for premature infants receiving PN. Further studies are needed to test whether clinical decision support systems will reduce uremia and improve growth and to replicate similar findings in the cases of other PN nutrients.