bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome‐level genome assembly and functional characterization of terpene synthases provide insights into the volatile terpenoid biosynthesis of Wurfbainia villosa
Authors: Yang Peng , Zhao Hai‐Ying , Wei Jie‐Shu , Zhao Yuan‐Yuan , Lin Xiao‐Jing , Su Jing , Li Fang‐Ping , Li Meng , Ma Dong‐Ming , Tan Xu‐Kai , Liang Hui‐Lin , Sun Ye‐Wen , Zhan Ruo‐Ting , He Guo‐Zhen , Zhou Xiao‐Fan , Yang Jin‐Fen
Published: September 2022

Wurfbainia villosa is a well‐known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high‐quality chromosome‐level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein‐coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole‐genome duplication event prior to the W. villosa–Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS‐a and TPS‐b subfamilies, showed that most of these WvTPSs are multi‐product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.
La intermediación en los sistemas de innovación agroindustrial
Authors: Guarin Manrique Leidy Dayhana , Martínez Ardila Hugo Ernesto
Published: September 2022

Atendiendo a la importancia que los sistemas de innovación agroindustrial están tomando en los países en vía de desarrollo, tal como Colombia (territorio de vocación agrícola por naturaleza), se presenta un acercamiento a su concepto y a la importancia que representa la intermediación en la transferencia de conocimiento y tecnología entre los diversos actores de la cuádruple hélice que conforman a este tipo de sistema sectorial.  Es así que se ha realizado una búsqueda de literatura en Google Scholar, Scopus y Web of Science, así como resultados de otras investigaciones enfocadas a estudiar el rol de los agentes intermediarios en los procesos de innovación relacionados con el agro.
Numerical Evaluation of an Efficient Deep-Water Mooring Configuration Designed to Allow a Fast Identification of Failure Events
Authors: Kochem Rodrigo Moretti , Correa Fabrício Nogueira , Jacob Breno Pinheiro
Published: September 2022

This work proposes a taut-leg deep-water mooring configuration with buoys, designed specifically to allow a quick and easy visual identification of the rupture of any mooring line of the system. This addresses one of the main concerns of the offshore oil and gas industry: the significant number of events of mooring line failure that has been recently observed in actual operations in deep and ultra-deep water scenarios; field experience indicates that, in current spread-mooring systems, several weeks may pass until a failure is detected. The proposed configuration also presents the additional advantages of reducing the mooring radius and the tensions on the top of the lines. The configuration is evaluated and compared with a standard taut-leg system, considering the same base case study of a typical deep-water FPSO, and using up-to-date numerical methods implemented into an in-house fully coupled nonlinear time-domain dynamic analysis tool. The results indicated that the proposed configuration provided significant improvements in the cost and performance of the mooring system, in terms of line lengths, mooring radii, tensions, and offsets; and confirmed that the buoy emerges and reaches the surface in the event of a line rupture, irrespective of the point where the line has broken. This indicates that the resulting configuration is a promising technical alternative to traditional standard taut-leg systems in deep and ultra-deep water scenarios.
Study on Integration of Retired Lithium-Ion Battery With Photovoltaic for Net-Zero Electricity Residential Homes
Authors: Alhadri Muapper , Zakri Waleed , Farhad Siamak
Published: September 2022

The behavior of a retired lithium-ion battery (LIB) from its first-life in an electric aircraft (EA) to its second-life in a solar photovoltaic (PV) system for a net-zero electricity residential home is studied. The first part of this study presents the design and sizing of a battery energy storage system (BESS), made from retired LIBs, to store a portion of the PV generation for a typical home in Ohio. The home is connected to the grid, but the net electricity usage from the grid in one year is zero. The purpose of the BESS is to peak shaving, power arbitrage, reduce the home dependency on the grid, and increase the economic benefits. The sizing is determined based on the hourly data of the PV system generation, ambient temperature, irradiation, and home demand electricity. In the second part of this study, the retired LIB degradation rate and its remaining useful life in the BESS are estimated using an adopted empirical LIB model. The model includes the capacity-fade for both first-life and second-life of the LIB under various duty cycles. It is shown that the retired LIB from its first-life is still suitable to be used in the PV grid-tied battery (PVGB) system for another 10 years. The results of this study can potentially reduce the LIB cost for electric vehicles (EVs) and EAs because the retired LIBs from these applications still have value to serve for other applications such as PVGB systems for residential homes.
A functional regression analysis of vessel source level measurements from the Enhancing Cetacean Habitat and Observation (ECHO) database
Authors: MacGillivray Alexander O. , Ainsworth Laurie M. , Zhao Joanna , Dolman Joshua N. , Hannay David E. , Frouin-Mouy Héloïse , Trounce Krista B. , White Derek A.
Published: September 2022

Measurements of the source levels of 9880 passes of 3188 different large commercial ships from the Enhancing Cetacean Habitat and Observation (ECHO) program database were used to investigate the dependencies of vessel underwater noise emissions on several vessel design parameters and operating conditions. Trends in the dataset were analyzed using functional regression analysis, which is an extension of standard regression analysis and represents a response variable (decidecade band source level) as a continuous function of a predictor variable (frequency). The statistical model was applied to source level data for six vessel categories: cruise ships, container ships, bulk carriers, tankers, tugs, and vehicle carriers. Depending on the frequency band and category, the functional regression model explained approximately 25%–50% of the variance in the ECHO dataset. The two main operational parameters, speed through water and actual draft, were the predictors most strongly correlated with source levels in all of the vessel categories. Vessel size (represented via length overall) was the design parameter with the strongest correlation to underwater radiated noise for three categories of vessels (bulkers, containers, and tankers). Other design parameters that were investigated (engine revolutions per minute, engine power, design speed, and vessel age) had weaker but nonetheless significant correlations with source levels.
Mechanical and vibro-acoustic performance of sandwich panel with perforated honeycomb cores
Authors: Kang Ludi , Liu Bilong , An Fengyan , Wei Dapeng
Published: September 2022

The effect of perforating the honeycomb walls of a honeycomb sandwich panel on the dynamic bending stiffness and sound transmission loss of the panel is investigated. The dynamic bending stiffness and sound transmission loss of several sandwich panels with different cores are calculated using a semi-analytical method, and the static bending stiffness and flatwise stiffness of these structures are also analyzed with the finite element method. Furthermore, the influences of the honeycomb shape, the hole shape of the perforated honeycomb wall, the number of perforations, and the wall thickness on the vibro-acoustic and mechanical properties of the sandwich panel are investigated. The results show that the static mechanical performance of the sandwich panel quickly reaches a high level when the ratio of honeycomb wall thickness to length t/l is about 5.3 × 10−3 and a square hole in the honeycomb wall can bring superior characteristics of “high static and low dynamic properties,” significantly improving the sound insulation of the sandwich panel. This study makes an effective reference for the optimized design of the innovative sandwich structure in practical applications.
In Science Journals
Authors: Ash Caroline , Stajic Jelena , Vignieri Sacha , Yeston Jake , Szuromi Phil , Whelan Robert , Malo Courtney S. , Alderton Gemma , Lopez Bianca , Jiang Di , Hines Pamela J. , Smith H. Jesse , Kelly Priscilla N. , Smith Keith T. , Osborne Ian S. , Erkes Dan A. , VanHook Annalisa M.
Published: September 2022

Highlights from the
Science
family of journals
In Other Journals
Authors: Grocholski Brent , Scanlon Seth Thomas , Alderton Gemma , Ash Caroline , Ray L. Bryan , McCartney Melissa , Osborne Ian S.
Published: September 2022

Editors’ selections from the current scientific literature
RecT Affects Prophage Lifestyle and Host Core Cellular Processes in Pseudomonas aeruginosa
Authors: Long Xiang , Zhang Hanhui , Wang Xiaolong , Mao Daqing , Wu Weihui , Luo Yi
Published: September 2022

Multidrug-resistant and metabolically versatile
P. aeruginosa
are difficult to eradicate by anti-infective therapy and frequently lead to significant morbidity and mortality. This study characterizes a putative recombinase (RecT) encoded by a prophage of a clinical
P. aeruginosa
strain isolated from severely burned patients, altering prophage lifestyle and host core cellular processes.
Avatar Mice Underscore the Role of the T Cell-Dendritic Cell Crosstalk in Ebola Virus Disease and Reveal Mechanisms of Protection in Survivors
Authors: Rottstegge Monika , Tipton Tom , Oestereich Lisa , Ruibal Paula , Nelson Emily V. , Olal Catherine , Port Julia R. , Seibel Johan , Pallasch Elisa , Bockholt Sabrina , Koundouno Fara Raymond , Boré Joseph Akoi , Rodríguez Estefanía , Escudero-Pérez Beatriz , Günther Stephan , Carroll Miles W. , Muñoz-Fontela César
Published: September 2022

The crosstalk between dendritic cells and T cells marks the transition between innate and adaptive immune responses, and it constitutes an important checkpoint in EVD. In this study, we present a mouse avatar model in which T cell and dendritic cell interactions from a specific donor can be studied during EVD.
Complete Genome Sequence of Cluster C Mycobacteriophage McGee
Authors: Nsa Imade Y. , Odunsi Ayodeji A. , Okorie Chioma V. , Bamisaye Seun D. , Abass Rashidat O. , Amadi Dennis O. , Ebitigha Joshua E. , Kadiri Oluwafemi O. , Makinwa Temidayo M. , Olaiya Solape O. , Oluwafemi Josephine O. , Owoeye Tomilayo L. , Sekoni Zainab A. , Olubajo Abisoye F. , Egwuatu Tenny O. G. , Oyetibo Ganiyu O. , Ilori Matthew O.
Published: September 2022

Mycobacteriophage McGee is a myovirus isolated from a wet soil sample collected at Manassas, VA, using
Mycobacterium smegmatis
mc
2
155. McGee has a genome 156,008 bp long, containing 237 protein-coding genes, 31 tRNA genes, and 1 transfer-messenger RNA (tmRNA) gene. McGee shares high gene content similarity to phages in actinobacteriophage cluster C1.
Analysis of Recombinant Characteristics Based on 949 PRRSV-2 Genomic Sequences Obtained from 1991 to 2021 Shows That Viral Multiplication Ability Contributes to Dominant Recombination
Authors: Cui Xingyang , Xia Dasong , Huang Xinyi , Sun Yue , Shi Mang , Zhang Jianqiang , Li Ganwu , Yang Yongbo , Wang Haiwei , Cai Xuehui , An Tongqing
Published: September 2022

Recombination is an important driver of the genetic shifts that are tightly linked to the evolution of RNA viruses. Viral recombination contributes substantially to the emergence of new variants, alterations in virulence, and pathogenesis.
Heterophase Synthesis of Humic Substances at Low Substrate Concentrations and Flow-Through Conditions
Authors: Zavarzina A. G. , Demin V. V. , Belova O. V. , Leontievsky A. A. , Lisov A. V.
Published: September 2022

Abstract—

Humic substances (HS) are heterogeneous and polydisperse compounds formed in soils, sediments and waters during the decay and transformation of organic residues (the process called humification). The role of extracellular free-radical condensation reactions (secondary synthesis) in the formation of HS is a subject of debate. Here we have studied the formation of HS from a mixture of monomers under the dynamic conditions and at low substrate concentrations in the presence of laccase from the fungusCoprinus comatusF-2940. Laccase was immobilized on kaolinite modified with aluminum hydroxide. We have investigated some properties of the enzyme, reactivity of phenolic acids and amino acids in the presence of laccase. The optimum of 2.6-dimethoxyphenol (2.6-DMP) oxidation by free laccase was at pH 6.0. Upon immobilization, it shifted to the acidic region (pH 4.4), the thermal stability decreased, however the kinetic parameters of 2.6-DMP oxidation remained unchanged. In terms of reactivity (% of substrate conversion by free laccase) the individual phenolic acids formed a series: caffeic (72) > ferulic (53) > gallic = syringic (43) > protocatechuic (5.5) > vanillic = p-hydroxybenzoic (0). In the mixture of phenolic acids, gallic acid was most efficiently oxidized (50%), while the other acids were oxidized in comparable amounts (13–17%). The conversion of phenolic acids increased in the presence of lysine. When a mixture of gallic, protocatechuic, syringic, ferulic acids (0.01 mM each) and lysine (0.02 mM) was passed through a flow-through microcolumn, immobilized laccase effectively oxidized the phenolic acids, the reaction products bound to the mineral phase, staining it dark. According to high performance liquid chromatography, the molecular weights of compounds extracted from the mineral phase did not exceed 900 Da, thus fulvic acid-like substances were formed. Results of the study suggest an important role of free-radical heterophase reactions in the formation of the molecular composition of the liquid phase and organo-mineral complexes.
Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study
Authors: Furumaya Alicia , Haring Martijn P D , van Rosmalen Belle V , Klompenhouwer Anne J , Besselink Marc G , de Man Robert A , IJzermans Jan N M , Thomeer Maarten G J , Kramer Matthijs , Coolsen Mariëlle M E , Tushuizen Maarten E , Schaapherder Alexander F , de Haas Robbert J , Duiker Evelien W , Kazemier Geert , van Delden Otto M , Verheij Joanne , Takkenberg R Bart , Cuperus Frans J C , De Meijer Vincent E , Erdmann Joris I
Published: September 2022

Introduction

Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease.

Methods and analysis

A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course.

Ethics and dissemination

The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal.

Study registration

NL8231—10 December 2019; Netherlands Trial Register.
Effectiveness of linkage to care and prevention interventions following HIV self-testing: a global systematic review and meta-analysis protocol
Authors: Bain Luchuo Engelbert , Amu Hubert , Dowou Robert Kokou , Memiah Peter , Agbor Valirie Ndip
Published: September 2022

Introduction

Early identification of persons living with HIV (PLWH) is crucial to institute timely treatment to prevent HIV-related morbidity and mortality. The convenience, flexibility and confidentiality of HIV self-testing enhance the acceptability of HIV testing and early detection of PLWH. However, persons who tested positive after a self-test are more likely to present late for treatment. This review seeks to evaluate the effectiveness of interventions to improve linkage to care and prevention after self-testing.

Methods and analysis

We will search PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Global Health Library, ClinicalTrials.gov and current controlled trials for all randomised and non-randomised studies published from 1 January 2010 to 31 July 2022 without language restriction. Two review authors will independently screen and select articles (based on the eligibility criteria for this review), extract data and assess the risk of bias in the included studies. Study-specific estimates will be converted to log risk ratios and weighted by the inverse of the variance of the log risk ratio before pooling into a fixed-effect model. The Cochrane’s Q χ2test and the I2statistic will be used to assess and quantify heterogeneity in the included studies, respectively. The Egger’s test and funnel plots will be used to assess publication bias. Sensitivity analysis will be conducted using leave-one-out analysis to assess the impact of outliers on the overall summary intervention effect.

Ethics and dissemination

No ethical clearance is needed for the current study as it will be based on already published articles. We will publish the findings of this study in international peer-reviewed journals and present them at conferences.
Cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture–recapture
Authors: Ramos Pedro Lima , Santana Rui , Marques Ana Patricia , Sousa Ines , Rocha-Sousa Amandio , Macedo Antonio Filipe
Published: September 2022

Objectives

The aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal.

Setting

Information about people with VI was obtained from primary care centres, blind association (ACAPO) and from hospitals (the PCVIP study) in the Northwest of Portugal during a period spanning years 2014–2015. Causes of VI were obtained from hospitals.

Participants

Administrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20° were investigated. Capture–recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources.

Primary and secondary outcome measures

Log-linear models were used to estimate the crude prevalence and the category specific prevalence of VI.

Results

Crude prevalence of VI was 1.97% (95% CI 1.56% to 2.54%), and standardised prevalence was 1% (95% CI 0.78% to 1.27%). The age-specific prevalence was 3.27% (95% CI 2.36% to 4.90%), older than 64 years, 0.64% (95% CI 0.49% to 0.88%), aged 25–64 years, and 0.07% (95% CI 0.045% to 0.13%), aged less than 25 years. The female-to-male ratio was 1.3, that is, higher prevalence among females. The five leading causes of VI were diabetic retinopathy, cataract, age-related macular degeneration, glaucoma and disorders of the globe.

Conclusions

The prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterise temporal changes in prevalence of VI in Portugal.
Association of area-level education with the regional growth trajectories of rates of antibacterial dispensing to patients under 3 years in Norway: a longitudinal retrospective study
Authors: Svalestuen Sigbjørn , Svendsen Kristian , Eggen Anne Elise , Småbrekke Lars
Published: September 2022

Objective

To examine the association between area-level education and the local growth trajectories in antibacterial dispensing rates in Norwegian municipalities among children under 3 years old.

Design

Retrospective, longitudinal study using individual primary care prescription data from the Norwegian Prescription Database for the period 2006–2016. Data were collected on the date of dispensing, the type and amount of antibiotic, the patient’s age, sex and municipality of residence and linked to municipality-level statistics on education available from Statistics Norway. We used multilevel growth curve modelling, with a linear trend variable modelled as a random effect and a cross-level interaction between linear trends and the proportion of the population in the municipality having received a university or college education.

Setting

The local government level in Norway. The sample includes all municipalities over the study period.

Outcome measure

Number of dispensed antibacterial prescriptions per 100 children in individual primary care by municipality and year.

Results

We identified a significant negative linear trend in the square root of the dispensing rate for children under 3 years old during the period. This trend varied between municipalities. A negative cross-level interaction term between population education levels and random trends showed that municipalities with an average level of population education saw a reduction in their square root dispensing rates of −0.053 (95% CI −0.066 to −0.039) prescriptions per 100 children. Each additional percentage point in population education contributed a further −0.0034 (95% CI −0.006 to –0.001) reduction to the square root dispensing rate.

Conclusions

Municipalities in which a larger proportion of the local population have high educational achievements have been more successful in reducing antibacterial dispensing rates in children under 3 years old. Adopting area-level strategies and addressing local community disadvantages may help to optimise practices and prescribing patterns across local communities.
Develop an ADR prediction system of Chinese herbal injections containing Panax notoginseng saponin: a nested case–control study using machine learning
Authors: Wu Xing-Wei , Zhang Jia-Ying , Chang Huan , Song Xue-Wu , Wen Ya-Lin , Long En-Wu , Tong Rong-Sheng
Published: September 2022

Objective

This study aimed to develop an adverse drug reactions (ADR) antecedent prediction system using machine learning algorithms to provide the reference for security usage of Chinese herbal injections containing Panax notoginseng saponin in clinical practice.

Design

A nested case–control study.

Setting

National Center for ADR Monitoring and the Electronic Medical Record (EMR) system.

Participants

All patients were from five medical institutions in Sichuan Province from January 2010 to December 2018.

Main outcomes/measures

Data of patients with ADR who used Chinese herbal injections containing Panax notoginseng saponin were collected from the National Center for ADR Monitoring. A nested case–control study was used to randomly match patients without ADR from the EMR system by the ratio of 1:4. Eighteen machine learning algorithms were applied for the development of ADR prediction models. Area under curve (AUC), accuracy, precision, recall rate and F1 value were used to evaluate the predictive performance of the model. An ADR prediction system was established by the best model selected from the 1080 models.

Results

A total of 530 patients from five medical institutions were included, and 1080 ADR prediction models were developed. Among these models, the AUC of the best capable one was 0.9141 and the accuracy was 0.8947. According to the best model, a prediction system, which can provide early identification of patients at risk for the ADR of Panax notoginseng saponin, has been established.

Conclusion

The prediction system developed based on the machine learning model in this study had good predictive performance and potential clinical application.
Impact of conventional lipid-lowering therapy on circulating levels of PCSK9: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Luo Jichang , Huang Tianze , Xu Ran , Wang Xue , Yang Yutong , Li Long , Zhang Xiao , Zhang Yinhang , Yang Renjie , Wang Jie , Yang Hai , Ma Yan , Yang Bin , Wang Tao , Jiao Liqun
Published: September 2022

Introduction

Conventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3, are essential to the management of dyslipidaemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased cardiovascular risk. This review aims to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.

Methods and analysis

This protocol is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger’s test.

Ethics and dissemination

Ethics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal.

Patient and public involvement

No patient or members of the general public are involved.

PROSPERO registration number

CRD42022297942.
Protocol for the Tessa Jowell BRAIN MATRIX Platform Study
Authors: Watts Colin , Savage Joshua , Patel Amit , Mant Rhys , Wykes Victoria , Pohl Ute , Bulbeck Helen , Apps John , Sharpe Rowena , Thompson Gerard , Waldman Adam D , Ansorge Olaf , Billingham Lucinda
Published: September 2022

Introduction

Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK National Health Service resources to support research that is patient centric and attractive to both academic and commercial investors.

Methods and analysis

The TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for patients with glioma. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in patients with glioma from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological–molecular diagnosis using whole-genome sequencing and epigenomic classification. Secondary outcome measures include those that are process centred, patient centred and framework based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients.

Ethics and dissemination

The study will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland and stated in the respective participating countries’ laws governing human research, and Good Clinical Practice. The protocol was initially approved on 18 February 2020 by West Midlands – Edgbaston Research Ethics Committee; the current protocol (v3.0) was approved on 15 June 2022. Participants will be required to provide written informed consent. A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The results of this study will be disseminated through national and international presentations and peer-reviewed publications. Manuscripts will be prepared by the Study Management Group and authorship will be determined by mutual agreement.

Trial registration number

NCT04274283, 18-Feb-2020;ISRCTN14218060, 03-Feb-2020.
A systematic review of adeno-associated virus gene therapies in neurology: the need for consistent safety monitoring of a promising treatment
Authors: Horton Rebecca H , Saade Dimah , Markati Theodora , Harriss Elinor , Bönnemann Carsten G , Muntoni Francesco , Servais Laurent
Published: September 2022

Adeno-associated virus (AAV) gene therapies are generating much excitement in the rare disease field, particularly for previously untreatable neurological conditions. Efficacy has been claimed for several gene therapy products and the number of trials is rapidly increasing. However, reports of severe treatment-related adverse reactions are emerging, including death. There is still insufficient knowledge about their aetiology, prevention and treatment. We therefore undertook to systematically review publicly available data on AAV gene therapies in order to collate existing information on both safety and efficacy. Here, we review emerging efficacy reports of these novel therapies, many of which show promise. We also collate an increasing number of adverse reactions. Overwhelmingly, these results make a case for unified reporting of adverse events. This is likely to be critical for improving the safety of these promising treatments.
Understanding the value of non-specific abnormal capillary dilations in presence of Raynaud’s phenomenon: a detailed capillaroscopic analysis
Authors: Pacini Greta , Pogna Andrea , Pendolino Monica , Pizzorni Carmen , Carmisciano Luca , Gotelli Emanuele , Sulli Alberto , Paolino Sabrina , Schenone Carlotta , Smith Vanessa , Cutolo Maurizio
Published: September 2022

Background

Nailfold videocapillaroscopy (NVC) non-specific abnormalities may be present in subjects with isolated Raynaud’s phenomenon (RP) before the potential transition to systemic sclerosis (SSc) specific microvascular alterations (‘scleroderma pattern’). This study aims to investigate NVC non-specific abnormalities, notably capillary dilations, in RP patients, as possible forerunners of the ‘scleroderma pattern’.

Methods

A 10-year retrospective NVC-based investigation evaluated 55 RP patients sorted into 3 sex-matched and age-matched groups according to clinical evolution: 18 later developing SSc (cases), 19 later developing other connective tissue disease and 18 maintaining primary RP at long-term follow-up (controls). All patients had a basal NVC showing non-specific abnormalities, namely non-specific >30 µm dilated capillaries (30–50 μm diameter). Sequential NVCs were longitudinally evaluated using current standardised approach. Statistical analysis assessed the risk for developing a ‘scleroderma pattern’.

Results

Significantly larger capillary diameters were observed in cases versus controls both at basal NVC and during follow-up NVC (p=<0.05 to <0.001). Interestingly, controls showed stable NVC non-specific abnormalities over the study follow-up. The number of >30 µm dilated capillaries/mm at basal NVC was the strongest single predictor of ‘scleroderma pattern’ evolution with 24% increased risk per each dilated capillary (OR 1.24, 95% CI 1.17,1.32). Additionally, a tree-based analysis suggested the efferent (venous) diameter of the most dilated capillary on basal NVCas a variable of interest to identify patients maintaining primary RP.

Conclusion

This is the first study to describe an NVC ‘prescleroderma signature’ to potentially identify RP patients later developing a ‘scleroderma pattern’.
Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies
Authors: Asfar Taghrid , Jebai Rime , Li Wei , Oluwole Olusanya Joshua , Ferdous Tarana , Gautam Prem , Schmidt Michael , Noar Seth M , Lindblom Eric N , Eissenberg Thomas , Bursac Zoran , Vallone Donna , Maziak Wasim
Published: September 2022

Objectives

This umbrella review aims to summarise the evidence about electronic nicotine delivery systems’ (ENDS) risk and safety health profile to inform ENDS health communication strategies.

Data sources and study selection

Six databases were searched for systematic reviews presenting evidence on ENDS-related health effects. Ninety reviews divided into five categories were included: toxicity=20, health effects=40, role in smoking cessation=24, role in transition to combustible cigarettes (CCs)=13 and industry marketing claims=4.

Data extraction

Findings were synthesised in narrative summaries. Meta-analyses were conducted by study type when appropriate. Quality assessment was conducted using the Measurement Tool to Assess Systematic Reviews. The Institute of Medicine’s Levels of Evidence Framework was used to classify the evidence into high-level, moderate, limited-suggestive and limited-not-conclusive.

Data synthesis

We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes serious injuries due to explosion or poisoning; increases smoking cessation in clinical trials but not in observational studies; increases CC initiation; and exposure to ENDS marketing increases its use/intention to use. Evidence was moderate for ENDS association with mental health and substance use, limited-suggestive for cardiovascular, and limited-not-conclusive for cancer, ear, ocular and oral diseases, and pregnancy outcomes.

Conclusions

As evidence is accumulating, ENDS communication can focus on high-level evidence on ENDS association with toxicity, nicotine addiction, respiratory disease, ENDS-specific harm (explosion, poisoning) and anti-ENDS industry sentiment. Direct comparison between the harm of CCs and ENDS should be avoided.

PROSPERO registration number

CRD42021241630.
From maximum force to the field equations of general relativity and implications
Authors: Kenath Arun , Schiller Christoph , Sivaram C.
Published: September 2022

There are at least two ways to deduce Einstein’s field equations from the principle of maximum force [Formula: see text] or from the equivalent principle of maximum power [Formula: see text]. Tests in gravitational wave astronomy, cosmology, and numerical gravitation confirm the two principles. Apparent paradoxes about the limits can all be resolved. Several related bounds arise. The limits illuminate the beauty, consistency and simplicity of general relativity from an unusual perspective.
A note on proper conformal vector fields of Bianchi type-I perfect fluid space-times in f(R,T) gravity
Authors: Mehmood A. B. , Hussain Fiaz , Ramzan M. , Faryad M. , Khan M. Jamil , Malik S.
Published: September 2022

The purpose of this paper is to investigate proper conformal vector fields (CVFs) of Bianchi type-I perfect fluid space-times in the [Formula: see text], [Formula: see text] theory of gravity, where [Formula: see text] and [Formula: see text] are the Ricci scalar and the trace of energy–momentum tensor, respectively. To seek the proper CVFs, we perform a classification of the space-times by imposing different restrictions on the space-time components. The whole classification consists of 12 cases. By studying each case thoroughly, we conclude that in the [Formula: see text], [Formula: see text] theory of gravity, the overall dimension of CVFs for the Bianchi type-I space-times turns out to be 3, 4, 5 and 15.
A simple Gödel-type universe
Authors: Boskoff Wladimir-Georges
Published: September 2022

Einstein’s field equations not only allow realistic solutions, but also allow exotic ones. In the first class, there are solutions describing FLRW universe, black holes and the gravitational waves. In the second class, we point out de Sitter and Anti-de Sitter universes without matter, wormholes solutions and Gödel universe without time. In this paper, we are interested in finding out a simpler example of Gödel-type universe. The road to the desired result passes through a spacetime without matter and time at the same time, whose texture is “flicked” by planar gravitational waves. This example allows us to create a simpler Gödel-type universe.
Nonlinear Causal Relationship Between Economic Policy Uncertainty and Macroeconomic Variables in Selected Emerging Market Economies
Authors: Adjei Abigail Naa Korkor , Tweneboah George , Junior Peterson Owusu
Published: September 2022

This paper sought to close the gap on the inconsistent findings on the causal relationship between uncertainty and business cycles. We investigate the causal relationship between economic policy uncertainty (EPU) and business cycles in six emerging market economies, during the period January 1999 to December 2018. We significantly contribute to the literature by adopting a robust nonlinear causality test and the maximal overlap discrete wavelet transform that transforms the series into multilevel wavelet and scaling coefficients. The empirical findings are thus presented in short-, medium-, and long-term dynamics, which correspond to investors’ different time horizons. We further introduce new variables which significantly alter our understanding of the inconsistent findings between EPU and business cycles. We record a handful of evidence to prove that EPU is both a cause and effect of business cycle fluctuations, except for India that records a one-way causality from business cycles to EPU. These findings are significant because they provide investors and policymakers with information on the causal relationship between EPU and business cycles over time and across frequencies, which can be used to improve policy formulations and investment strategies across time horizons. Furthermore, the findings aid in explaining the inconsistent findings in the literature.
Solution for Simple Classical Systems Using SCILAB
Authors: Kumar Naik Bikash
Published: September 2022

The use of computers as a learning tool has been a time-tested method, which can attract the interest and motivation of students to solve any complicated system easily. Scilab is an open-source computational software package that provides various tools to simulate and solve problems in classical mechanics.

In this paper, two types of classical mechanics problems are solved. Under kinematics section, we solve the Projectile motion considering air resistance and particle falling under the action of gravity, with resistive force dependence on different exponents of velocity. Similarly, under the waves superposition section, we solve the two sinusoidal waves superimposed to give a Lissajous pattern and superposition of two or more waves using Scilab software for a better understanding of the classical problems by visualization of graphs, as Scilab has 2D and 3D plotting facilities.
Multitask Balanced and Recalibrated Network for Medical Code Prediction
Authors: Sun Wei , Ji Shaoxiong , Cambria Erik , Marttinen Pekka
Published: September 2022

Human coders assign standardized medical codes to clinical documents generated during patients’ hospitalization, which is error prone and labor intensive. Automated medical coding approaches have been developed using machine learning methods, such as deep neural networks. Nevertheless, automated medical coding is still challenging because of complex code association, noise in lengthy documents, and the imbalanced class problem. We propose a novel neural network, called the Multitask Balanced and Recalibrated Neural Network, to solve these issues. Significantly, the multitask learning scheme shares the relationship knowledge between different coding branches to capture code association. A recalibrated aggregation module is developed by cascading convolutional blocks to extract high-level semantic features that mitigate the impact of noise in documents. Also, the cascaded structure of the recalibrated module can benefit learning from lengthy notes. To solve the imbalanced class problem, we deploy focal loss to redistribute the attention on low- and high-frequency medical codes. Experimental results show that our proposed model outperforms competitive baselines on a real-world clinical dataset called the Medical Information Mart for Intensive Care (MIMIC-III).
Nickel Doping Manipulation towards Developing High-Performance Cathode for Proton Ceramic Fuel Cells
Authors: Liang Mingzhuang , Liu Dongliang , Zhu Yijun , Zhou Wei , Yang Guangming , Ran Ran , Shao Zongping
Published: September 2022

An ideal cathode for proton ceramic fuel cell (PCFC) should have superior oxygen reduction reaction activity, high proton conductivity, good chemical compatibility with electrolyte and sufficient stability, thus rational design of the electrode material is needed. Here, by taking advantage of the limited solubility of nickel in perovskite lattice, we propose a new dual phase cathode developed based on nickel doping manipulation strategy. We rationally design a perovskite precursor with the nominal composition of Ba(Co0.4Fe0.4Zr0.1Y0.1)0.8Ni0.2O3−δ
(BCFZYN0.2). During high temperature calcination, a nanocomposite, composed of a B-site cation deficient and nickel-doped BCFZY perovskite main phase and nanosized NiO minor phase, is formed. The NiO nanoparticles effectively improve the surface oxygen exchange kinetics and the B-site cation deficiency structure enhances proton conductivity, thus leading to superior ORR activity of BCFZYN0.2. Furthermore, a low thermal expansion coefficient (15.3 × 10–6 K−1) is achieved, ensuring good thermomechanical compatibility the electrolyte. A peak power density of 860 mW cm−2 at 600 °C is obtained from the corresponding PCFC, and the cell operates stably for 200 h without any significant degradation. The proposing strategy, by providing a new opportunity for the development of highly active and durable PCFC cathodes, may accelerate the practical use of this technology.
Ion Transport in an Electrochemical Cell: A Theoretical Framework to Couple Dynamics of Double Layers and Redox Reactions for Multicomponent Electrolyte Solutions
Authors: Jarvey Nathan , Henrique Filipe , Gupta Ankur
Published: September 2022

Electrochemical devices often consist of multicomponent electrolyte solutions. Two processes influence the overall dynamics of these devices: the formation of electrical double layers and chemical conversion due to redox reactions. However, due to the presence of multiple length and time scales, it is challenging to simulate both processes directly from the Poisson-Nernst-Planck equations. Therefore, common modeling approaches ignore one of the processes, assume the two are independent, or extrapolate the results from reaction-free systems. To overcome these limitations, we formulate and derive an asymptotic model by solving the Poisson-Nernst-Planck equations for an arbitrary number of ions in the thin-double-layer limit. Our analysis reveals that there are two distinct timescales in the system: double-layer charging and bulk diffusion. Our model displays excellent quantitative agreement with direct numerical simulations. Further, our approach is computationally efficient and numerically stable, even for large potentials. We investigate the dynamics of charging for a binary electrolyte and three-ion system, and find that redox reactions impact the double-layer charging process at short times whereas they modify the double-layer capacitance at long times. Overall, the proposed theoretical framework advances our ability to simulate electrochemical devices that contain multiple ions and widens opportunities for future research in the field.
Finite-Element Analysis on the Tensile Membrane Effect in Geogrid Reinforced Piled Embankment under Dynamic Loading
Authors: Zhuang Yan , Wang Kangyu , Hu Shunlei , Zhang Xidong , Cui Xiaoyan
Published: September 2022

This study presented a numerical investigation of the tensile membrane effect in the geogrid reinforced piled embankment under dynamic loading. It has been found that the maximum sag of the geogrid was attained at the center of two adjacent piles, while localization of tensile force was observed at the corners of the pile caps. Under the dynamic loading, the sag and the strain of the geogrid increased when compared with the static loading, an increase of around 45.9% and 24% was, respectively, yielded for the sag and the strain of the geogrid. This increase of tension in the geogrid may mainly result from the degradation of the soil arching effect under dynamic loading. A parameter study was performed, and it showed that the tensile force in the geogrid increases with the rise of the embankment height, the clear pile spacing, and the tensile stiffness of the geogrid. However, the increase of the friction angle of the embankment fill led to a decrease in the tension in the geogrid, which may benefit from the improvement of the soil arching developed in the embankment fill. It was found that the tensile behavior of the geogrid was the most sensitive to the pile spacing. When pile spacing increased from 2.0 m to 3.0 m, the tensile force in the geogrid increased by about 248%.