bluuebunny/crossref_metadata_2025 huggingface dataset:
Efeito da concentração inicial de frutose sobre a conservação a 5 °c do sêmen caprino
Authors: Matos-Brito B. G. , Lima I. C. S. , Pereira J. F. , Barboza F. M. , Linard M. A. B. , Aguiar G. V. , Catunda A. G. V. , Moura A. A. A. , Nunes J. F. , Campos A. C. N.
Published: February 2021

Foram coletadas 24 amostras de sêmen caprino. Cada ejaculado foi dividido em 4 alíquotas, e foram diluídas em citrato-gema de ovo (CG), TRIS-gema de ovo (TG) e água de coco industrializada-gema de ovo (ACI-G), a quarta, foi centrifugada para determinação da concentração de frutose e atividade da FLA2 no PS. O sêmen foi conservado a 5 ºC e avaliado a fresco, 2, 24 e 48 h, em cada tempo foi avaliado o vigor, motilidade e alterações morfológicas. Os reprodutores foram divididos em dois grupos: grupo I-concentração de frutose >710 mg/dL e o grupo II-concentração de frutose
Análise técnico-econômica de diferentes níveis da torta de macaúba em dietas para vacas leiteiras
Authors: Omole R. A , Obi F. L. , Ajasin L. , Okpeze C. S. , Olasehinde A. C. R. , Olasehinde D. G. , Olasehinde L. C.
Published: February 2021

O preço do leite não acompanha a tendência de alta dos insumos e a redução dos custos de produção pode permitir a eficiência econômica da atividade leiteira. Dentro deste contexto, a utilização de coprodutos, pode ser alternativa para redução dos custos da alimentação e consequentemente os de produção. Objetivou-se analisar a inclusão de diferentes níveis da torta de macaúba, obtido na cadeia do biodiesel, na dieta total de vacas Holandesas, em lactação, em substituição ao farelo de milho. Foram utilizados oito animais com peso vivo médio de 480 kg e produção média de 25 kg de leite/dia, em dois quadrados latinos 4x4, sendo quatro níveis de inclusão da torta na matéria seca (0, 10, 20 e 30 %) e quatro períodos de 21 dias, 14 de adaptação e sete dias de avaliação. Os animais foram alimentados ad libitum, com silagem de milho e concentrado, confinados em baias individuais. Avaliou-se o consumo de matéria seca total, produção de leite, custos diários e o retorno econômico das dietas. A inclusão do coproduto reduziu o consumo de matéria seca total e produção de leite, entretanto, a taxa de retorno marginal com 10 % de inclusão do coproduto foi superior aos demais tratamentos, indicando que é uma alternativa técnica e economicamente viável em substituição ao farelo de milho na dieta de vacas leiteiras.
Death as an Aesthetic Experiment
Authors:   Weimar University Bauhaus, Scholz Leander , Lipov Anatoly ,   Institute of Philosophy, Russian Academy of Sciences
Published: February 2021

The more intensely a person thinks about the final nature of life, the more he is bound to a moment in life that is limited in time. Death is a very personal and intimate process, which in most cases is not «beautiful». The reality of death in clinics, intensive care units and operating theatres is, by its human nature, cruel. The body at the «end of the road» is captured by funeral homes. Thus, death today is identical to a long path of suffering. The article is dedicated to the author's reflection on a project by the German artist Gregor Schneider, which caused sensation and fierce reaction in Western art circles and beyond the art scene, creating him a reputation as «the most terrible contemporary artist» who has violated «existing» restrictions that cannot be exceeded if we do not want to question our civilization. The artist's vision is to allow a terminally ill person to die as part of an art project that represents a confrontation with death and that can remove the horror of death. As part of the project, the dying person defines everything in advance. Instead of a mass medical procedure of the same type, death, modeled on the artist's skill, Schneider argues, will create humane places for death and contribute to the creation of a space where people can die with dignity, creating personal protection and ensuring the ethical requirement of free will and self-determination.
FracBot Technology for Mapping Hydraulic Fractures
Authors: Alshehri Abdallah A. , Martins Carlos H. , Lin Shih-Chun , Akyildiz Ian F. , Schmidt Howard K.
Published: February 2021

Miniaturized transponder systems are under development for monitoring unconventional reservoirs, mapping hydraulic fractures, and determining other wellbore parameters. These gadgets are an extension of radio-frequency identification (RFID) and are known as fracture robot (FracBot) nodes to recognize wireless underground sensor networks (WUSNs) for characterization and mapping of hydraulic breakages in unconventional reservoirs. 3D constellation maps of proppant-bed placement are generated by autonomous localization algorithms as FracBots are injected during hydraulic-fracturing operations. To investigate this model, a FracBot platform was established to explore this concept, and three basic functions have been explained. First, we have developed an innovative cross-layer communication model for magnetic-induction (MI) networks in altering underground environments, coupled with selections of coding, modulation, and power control and a geographic forwarding structure. Second, we have developed an innovative MI-based localization framework to capture the locations of the randomly deployed FracBot nodes by exploiting the exceptional properties of the MI field. Third, we have proposed an energy model for a linear FracBot network scheme that provides reasonable data rates while preserving collected energy limitations. Finally, to examine the functionalities of FracBot nodes in air, sand, and stone media, a physical MI-based WUSN test bed was implemented. Experiments indicated that the constructed FracBots can form a communication link and transfer data over amplitude-shift keying (ASK) modulation with 1.6 kbit/sec as a data rate and a minimum receiver sensitivity of −70 dBm. The performance of near-field-communication (NFC) antennas was affected by sand and stone media, which ultimately affect MI signal propagation and decrease the energy transfer. In sand or stone media, augmented mismatch between transmitter and receiver antennas was detected, leading to the decision that an advanced matching circuit design or an adaptive-frequency feature should be integrated into the FracBot design. This permits an optimal energy transmission and consistent communication link through sand and stone media.
Well Shear Associated with Conventional and Unconventional Operations: Diagnosis and Mechanisms
Authors: Ewy Russell T.
Published: February 2021

Wells are sometimes deformed due to geomechanical shear slip, which occurs on a localized slip surface, such as a bedding plane, fault, or natural fracture. This can occur in the overburden above a conventional reservoir (during production) or within an unconventional reservoir (during completion operations). Shear slip will usually deform the casing into a recognizable shape, with lateral offset and two opposite-trending bends, and ovalized cross sections. Multifinger casing caliper tools have a recognizable response to this shape and are especially useful for diagnosing well shear. Certain other tools can also provide evidence for shear deformation. Shear deformations above a depleting, compacting reservoir are usually due to slip on bedding planes. They usually occur at multiple depths and are driven by overburden bending in response to reservoir differential compaction. Shear deformations in unconventional reservoirs, for the examples studied, have been found to be caused by slip on bedding planes and natural fractures. In both cases, models, field data, and physical reasoning suggest that slip occurs primarily due to fluid pressurization of the interface. In the case of bedding plane slip, fracturing pressure greater than the vertical stress (in regions where the vertical stress is the intermediate stress) could lead to propagation of a horizontal fracture, which then slips in shear.
An Interpretable Interflow Simulated Graph Neural Network for Reservoir Connectivity Analysis
Authors: Wang Haochen , Han Jianfa , Zhang Kai , Yao Chuanjin , Ma Xiaopeng , Zhang Liming , Yang Yongfei , Zhang Huaqing , Yao Jun
Published: February 2021

Reservoir connectivity analysis plays an essential role in controlling water cut in the middle and later stages of reservoir development. The traditional analysis methods, such as well test and tracer, may result in interruption and high reservoir development costs. Analyzing connectivity through history data is an advisable alternative method because the fluctuation of data reflects interwell interference. However, most of the former data-driven methods, such as capacitance and resistance model (CRM), estimate connectivity using formulas in relatively simple forms, leading to inadequate expression for underground interwell flow. In this paper, an interpretable recurrent graph neural network (GNN) is proposed to construct an interacting process imitating the real interwell flow regularity and overcoming the weakness in previous methods. In contrast, it is formed by a deep enough neural network structure with a relatively larger number of parameters when compared with the CRM model. In detail, this method makes the first use of both rate information and bottomhole pressure (BHP) to completely describe the hidden state of wells and the energy information exchanged among them, which are then continually updated in spatial and temporal ways.

Meanwhile, a self-defined recurrent structure deals with the time lag and attenuation phenomenon as it records the residual energy from past timestamps. Finally, it calculates BHP for each production well with the manually specified production rate as extra input data. Detailed results are presented in two examples. Our proposed method shows significant advantages to other methods due to its reasonable structure and great ability to fit nonlinear mapping.
The Global Adaptation Mapping Initiative (GAMI): Part 1 – Introduction and overview of methods
Authors: Berrang-Ford Lea , Lesnikowski Alexandra , Fischer A. Paige , Siders A.R. , Mach Katharine J. , Thomas Adelle , Callaghan Max , Haddaway Neal , Kerr Rachel Bezner , Biesbroek Robbert , Bowen Kathryn , Deryng Delphine , Elliott Susan , Ford James D. , Garschagen Matthias , Gilmore Elisabeth , Harper Sherliee , Hassnoot Marjolijn , Lissner Tabea , Lwasa Shuaib , Magnan Alexandre K. , Minx Jan , Morecroft Mike , New Mark , Perez Erin Coughlan de , Reckien Diana , Simpson Nick , Singh Chandni , Stringer Lindsay , Totin Edmond , Trisos Chris , Aalst Maarten Van
Published: February 2021

Context: It is now widely accepted that the climate is changing, and that societal responses will need to be rapid and comprehensive to prevent the most severe impacts. A key milestone in global climate governance is to assess progress on adaptation. To-date, however, there has been negligible robust, systematic synthesis of progress on adaptation or adaptation-relevant responses globally. Aim: The purpose of this review protocol is to outline the methods used by the Global Adaptation Mapping Initiative (GAMI) to systematically review human adaptation responses to climate-related changes that have been documented globally since 2013 in the scientific literature. The broad question underpinning this review is: Are we adapting to climate change? More specifically, we ask ‘what is the evidence relating to human adaptation-related responses that can (or are) directly reducing risk, exposure, and/or vulnerability to climate change?’ This work responds to the recognition of the need for high-level syntheses of adaptation research to inform global and regional climate assessments.Methods: We review scientific literature 2013-2019 to identify documents empirically reporting on observed adaptation-related responses to climate change in human systems that can directly reduce risk. We exclude non-empirical (theoretical & conceptual) literature and adaptation in natural systems that occurs without human intervention. Included documents were coded across a set of questions focused on: Who is responding? What responses are documented? What is the extent of the adaptation-related response? What is the evidence that adaptation-related responses reduce risk, exposure and/or vulnerability? Once articles are coded, we conduct a quality appraisal of the coding and develop ‘evidence packages’ for regions and sectors. We supplement this systematic mapping with an expert elicitation exercise, undertaken to assess bias and validity of insights from included/coded literature vis a vis perceptions of real-world adaptation for global regions and sectors, with associated confidence assessments. Related protocols: This protocol represents Part 1 of a 5-part series outlining the phases of methods for this initiative. Part 1 provides an introduction to the Global Adaptation Mapping Initiative (GAMI) and an overview of methods.
The Global Adaptation Mapping Initiative (GAMI): Part 3 – Coding protocol
Authors: Lesnikowski Alexandra , Berrang-Ford Lea , Siders A.R. , Haddaway Neal , Biesbroek Robbert , Harper Sherilee , Minx Jan , Perez Erin Coughlan de , Reckien Diana , New Mark , Singh Chandni , Thomas Adelle , Totin Edmond , Trisos Chris , Bavel Bianca Van
Published: February 2021

Context: It is now widely accepted that the climate is changing, and that societal response will need to be rapid and comprehensive to prevent the most severe impacts. A key milestone in global climate governance is to assess progress on adaptation. To-date, however, there has been negligible robust, systematic synthesis of progress on adaptation or adaptation-relevant responses globally. Aim: The purpose of this review protocol is to outline the methods used by the Global Adaptation Mapping Initiative (GAMI) to systematically review human adaptation responses to climate-related changes that have been documented globally since 2013 in the scientific literature. The broad question underpinning this review is: Are we adapting to climate change? More specifically, we ask ‘what is the evidence relating to human adaptation-related responses that can (or are) directly reducing risk, exposure, and/or vulnerability to climate change?’ Methods: We review scientific literature 2013-2019 to identify documents empirically reporting on observed adaptation-related responses to climate change in human systems that can directly reduce risk. We exclude non-empirical (theoretical & conceptual) literature and adaptation in natural systems that occurs without human intervention. Included documents were coded across a set of questions focused on: Who is responding? What responses are documented? What is the extent of the adaptation-related response? What is the evidence that adaptation-related responses reduce risk, exposure and/or vulnerability? Once articles are coded, we conduct a quality appraisal of the coding and develop ‘evidence packages’ for regions and sectors. We supplement this systematic mapping with an expert elicitation exercise, undertaken to assess bias and validity of insights from included/coded literature vis a vis perceptions of real-world adaptation for global regions and sectors, with associated confidence assessments. Related protocols: This protocol represents Part 3 of a 5-part series outlining the phases of this initiative. Part 3 outlines the methods used to extract data on adaptation from documents (coding), as well as procedures for data quality assurance. See Figure 1.
COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance
Authors: Simonetti Michele , Zhang Ning , Harbers Luuk , Milia Maria Grazia , Nguyen Thi Thu Huong , Brossa Silvia , Bienko Magda , Sapino Anna , Sottile Antonino , Ghisetti Valeria , Crosetto Nicola
Published: February 2021

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the spread and evolution of the virus across different populations, geographical regions and species. Here, we present a streamlined workflow—COVseq—based on the CUTseq method that we previously described, which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms, from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We validated COVseq on RNA extracted from the supernatant of a SARS-CoV-2 culture as well as from 85 left-over samples from nasopharyngeal swabs, demonstrating the ability of COVseq to achieve almost complete genome coverage, including the S region encoding the spike protein. A cost analysis showed that COVseq could be used to sequence thousands of samples per week at less than 20 USD per sample. COVseq is a versatile and scalable method that can be readily applied for genomic surveillance of the ongoing pandemic and easily adapted to other pathogens such as influenza viruses.
Driving After Total Knee and Hip Arthroplasty - an Observational Study From the Perspective of Rehabilitative Orthopaedic Therapy
Authors: Lazar Tiberiu-Adrian , Edelmann Martin , Lohmann Christoph , Awiszus Friedemann
Published: February 2021

Objective: Considering the legal stipulations in Germany regarding fitness to drive a motor vehicle, the aim of this study is to find out when patients with a total knee arthroplasty (TKA) or total hip arthroplasty (THA) actually take up driving again after surgery; how the replaced joint, side, gender, place of residence and physician’s recommendations, influences the patient in making the decision to start driving again.Background: For a large proportion of the population, especially those residing in the countryside, the use of a car for daily activities is indispensable. Following a TKA or THA procedure, the overseeing physician will usually recommend refraining from driving, sometimes up to 12 weeks after surgery with a major social and economical impact on patient’s life. Methods: 92 eligible participants, contained within the frame of a prospective experimental observational study, were contacted via telephone 12 weeks after surgery and interviewed using a structured questionnaire. The answers were statistically analysed using SPSS®.Discussion: There were statistically significant differences regarding operated side, gender and place of residence. Male patients drove in the 6th and 7th postoperative week, while female patients drove in the 8th and 9th postoperative week. For 58.6% of patients the reasoning for the first post-operative drive was medical: the journey to physiotherapy or to a doctor’s appointment. TKA impaired patients the most. Patients recovering from a TKA drive considerably later. Patients recovering from a right sided TKA have an increased risk by a factor of nine, not to become an “early driver”. Female patients who underwent TKA had an increased risk by a factor of 21, of becoming a “late driver”. Conclusions: The rehabilitation following a right sided TKA proved a challenge with regard to the reuptake of driving. This should be taken into account when planning the course of therapy for patients who are driving regulary. Female patients could benefit from special training. Trial registration: DRKS00018693. Registered 20 September 2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018693
Geographically Masking Addresses to Study COVID-19 Clusters
Authors: Houfaf-Khoufaf Walid , Touya Guillaume
Published: February 2021

The spatial analysis of health data usually raises geoprivacy issues. But with the virulence of COVID-19, scientists and crisis managers do need to analyse the spatio-temporal distribution and spreading of the disease with spatially precise data. In particular, it is useful to locate each case on a map to identify clusters of cases in space and time. To allow such analyses with breach of geoprivacy, geomasking techniques are necessary. This paper experiments the geomasking techniques from the literature to solve this problem: masking the real address of positive cases while preserving the local cluster patterns. In particular, two diﬀerent approaches based on aggregation and perturbation are adapted to the geomasking of addresses in areas with diﬀerent densities of population. A new simulated crowding method is also proposed to preserve clusters as much as possible. The results show that geomasking techniques can spatially anonymize addresses while preserving clusters, and the best geomasking method depends on the use of the anonymized data.
Central metabolic responses of microorganisms to years and decades of soil warming
Authors: Söllinger Andrea , Dahl Mathilde Borg , Séneca Joana , Prommer Judith , Verbruggen Erik , Sigurdsson Bjarni , Janssens Ivan , Penuelas Josep , Urich Tim , Richter Andreas , Tveit Alexander
Published: February 2021

Microbial physiological responses to long-term warming are poorly understood. Here we applied metatranscriptomics to investigate how microorganisms react to medium-term (8 years) and long-term (>5 decades) subarctic grassland soil warming of +6 °C.
Decades, but not years, of warming induced changes in relative abundances of eukaryotic, prokaryotic, and viral transcripts and reduced functional richness. However, irrespective of the duration of warming, we observed a community-wide upregulation of central (carbon) metabolisms and cell replication in the warmed soils, whereas essential energy metabolism and protein biosynthesis complexes and pathways were downregulated. This coincided with a decrease of microbial biomass and lower soil substrate concentrations (e.g. dissolved organic carbon and phosphorus).
We conclude that permanently accelerated reaction rates at higher temperatures facilitate a downregulation of energy metabolism and protein biosynthesis, potentially freeing energy and matter for substrate acquisition and growth. This resource allocation seems to be a common response in microorganisms and allows sustaining high metabolic activities and replication rates even after decades of soil warming.
Discovery of Novel Class of Histone Deacetylase Inhibitors as Anticancer Agents
Authors: El-Awady Raafat , Salah Ekram , Hamoudi Rifat , Mazitschek Ralph , Ramadan Wafaa , Nael Manal , Elokely Khaled , Abou-Gharbia Magid , Childers Wayne , Srinivas Vunnam , Aloum Lujain , Menon Varsha , Al-Tel Taleb
Published: February 2021

Selective inhibition of histone deacetylases (HDACs) is a paramount strategy in the field of anticancer lead drug development. However, the lack of selectivity among these isozymes and the adverse side effects that arise from the inhibition of certain HDACs limits their clinical applications. Phenotypic screening of an in-house pilot library of about 70 small molecules against various HDAC isozymes led to the discovery of five compounds which displayed varying degrees of HDAC isozyme selectivity. The anticancer activities of these molecules were validated using various biological assays including transcriptomic studies. Compounds 15, 14, and 19 possessed selective inhibitory activity against HDAC5, while 28 displayed selective inhibition of HDAC1 and HDAC2. Compound 22 was found to be a selective inhibitor for HDAC3 and HDAC9. In the MCF7 breast cancer cell line the new compounds showed potent anti-proliferative activity, increased acetylation of histones and induced cells apoptosis. The new compounds’ apoptotic effects were validated through the upregulation of caspases3 and 7 and downregulation of C-MYC, BCL2, BCL3 and NFĸB genes. Furthermore, the new compounds arrested cell cycle at different phases, which was confirmed through downregulation of the CDK1, 2, 4, 6, E2F1 and RB1 proteins. Together our findings provide the foundation for the development of new chemical probes as potential lead drug candidates for the treatment of cancer.
Evaluation of Two Highly Effective Lipid-Lowering Therapies in Subjects With Acute Myocardial Infarction: A Lipidomic Analysis
Authors: Klassen Aline , Sussulini Alessandra , Derogis Priscilla , Ferreira Carlos , Lopes Aline , Cruz Elisa , Faccio Andre , Bastos Rafaela , Fontoura Stefanie , Neto Antonio , Tavares Marina , Izar Maria , Fonseca Francisco
Published: February 2021

Introduction For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low density lipoprotein - cholesterol targets, but their effects on other lipids are less reported. Objective To examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Methods Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg qd or simvastatin 40 mg combined with ezetimibe 10 mg qd during 30 days. Fasting blood samples were collected in the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Selected reaction monitoring (SRM) was used in positive and negative ionization modes with and without differential mobility spectrometry (DMS). Univariate and multivariate analyses were performed. Results Comparable classic lipid profile was observed in both groups of lipid-lowering therapies at D1 and after treatments. However, differences in other lipids were observed between groups at these time points. After treatments, main differences between groups were for lysophosphatidylcholine and triacylglycerides. Conclusion Despite similar changes in the classic lipid profile, differences in lipidomic analysis were found before and after exposure to highly effective lipid-lowering therapies in subjects after STEMI. Trial registration: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.
HDAC6/FOXP3/HNF4α axis promotes bile acids induced gastric intestinal metaplasia
Authors: Wang Na , Wu Siran , Zhang Luyao , Chen Min , Zeng Jiaoxia , Lu Guofang , Zhou Fenli , Wu Qiong , Liu Junye , Shi Yongquan
Published: February 2021

Background: Gastric intestinal metaplasia (IM) is an important precancerous lesion. Our previous study has shown that ectopic expression of HDAC6 promotes the activation of intestinal markers in bile acids (BA) induced gastric IM cells; however, the mechanism underlying how HDAC6-mediated epigenetic modifications regulate intestinal markers is not clear.Methods: RNA-sequencing (RNA-seq) was used to detect the molecular changes in GES-1 cells after HDAC6 overexpression. The potential binding sites of FOXP3 with the promoter region of HNF4α were verified by ChIP and luciferase reporter gene assays. The ChIP assay was also used to detect the histone deacetylation. The levels of mucin in gastric or intestinal mucosa were detected by AB-PAS staining. Transgenic mice were used to explore the pro-metaplastic function of DCA and HNF4α in vivo.Results: Deoxycholic acid (DCA) upregulated HDAC6 in gastric cells, which further inhibited the transcription of FOXP3. Then, FOXP3 transcriptionally inhibited HNF4α, which further inhibits the expression of downstream intestinal markers. These molecules have been shown to be clinically relevant, as FOXP3 levels were negatively correlated with HDAC6 and HNF4α in IM tissues. Transgenic mice experiments confirmed that HNF4α overexpression combined with DCA induced gastric mucosa to secrete intestinal mucus and caused an abnormal mucosal structure. Conclusions: Our findings suggest that HDAC6 reduces FOXP3 through epigenetic modification, thus forming HDAC6/FOXP3/HNF4α axis to promote gastric IM. Inhibition of HDAC6 may be a potential approach to prevent gastric IM in patients with bile reflux.
ggtreeExtra: Compact visualization of richly annotated phylogenetic data
Authors: Xu Shuangbin , Dai Zehan , Guo Pingfan , Fu Xiaocong , Liu Shanshan , Zhou Lang , Tang Wenli , Feng Tingze , Chen Meijun , Zhan Li , Wu Tianzhi , Hu Erqiang , Yu Guangchuang
Published: February 2021

We present the ggtreeExtra package for visualizing heterogeneous data with a phylogenetic tree (https://www.bioconductor.org/packages/ggtreeExtra). It supports more data types and visualization methods than other tools and has many features that are not available elsewhere. The ggtreeExtra package is a universal tool for tree data visualization. It extends the applications of phylogenetic tree in different disciplines by making more domain specific data to be available to visualize and interpret on the evolutionary context.
Asymmetric Patterns of Visual Field Loss in Primary Angle Closure Glaucoma, High Tension Glaucoma, and Normal Tension Glaucoma
Authors: Jiang Junhong , Ye Cong , Zhang Cong , Ye Wenqing , Wang Xiaoyan , Shang Xiao , Xu Xiang , Zhang Hongte , Zhang Shaodan , Zheng Jingwei , Zuo Jingjing , Hu Jingjing , Congdon Nathan , Lu Fan , Liang Yuanbo
Published: February 2021

The data directly comparing the spatial pattern of VF defects between primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) is not available. We aim to compare the asymmetric patterns of VF defects in patients with PACG, NTG and HTG across different severity levels. A total of 162 eyes of 114 patients with PACG, 111 eyes of 74 patients with HTG and 148 eyes of 102 patients with NTG were included. VF examinations were performed with standard automated perimetry (HFA, SITA-standard strategy, 24-2), and defects were categorized into 3 stages (early, moderate, and advanced) and each hemifield was divided into 5 regions according to Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. The relationship between the values of pattern standard deviation (PSD) and mean TD was assessed. In the early stage, nasal region of PACG, central region of HTG and all five regions of NTG in the superior hemifield had significantly worse mean TD than their counterparts in the inferior hemifield. In the moderate stage, three regions of NTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. In the advanced stage, central region of PACG, and central and paracentral regions of HTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. When participants were matched by age, sex and mean deviation, in PACG and HTG eyes, all 5 GHT regions in the superior hemifield had worse mean TD than that that of their inferior-hemifield counterparts; however, the differences were not statistically significant. In NTG eyes, the paracentral, nasal, arcuate 1 and arcuate 2 regions in the superior hemifield had significantly worse mean TDs than their inferior counterparts. The superior hemifield is affected more severely than the inferior hemifield in all 3 subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG compared to PACG and HTG.
Financial toxicity of cancer care in low and middle-income countries: a systematic review and meta-analysis
Authors: Donkor Andrew , Atuwo-Ampoh Vivian Della , Yakanu Frederick , Torgbenu Eric , Ameyaw Edward Kwabena , Kitson-Mills Doris , Vanderpuye Verna , Kyei Kofi Adesi , Anim-Sampong Samuel , Khader Omar , Khader Jamal
Published: February 2021

Introduction: The costs associated with cancer diagnosis, treatment and care present enormous financial toxicity. However, evidence of financial toxicity associated with cancer in low and middle-income countries (LMICs) is scarce.Aim: To identify the extent of cancer-related financial toxicity and how it has been measured in LMICs.Methods: Four electronic databases were searched to identify studies of any design that reported financial toxicity among cancer patients in LMICs. Random-effects meta-analysis was used to derive the pooled prevalence of financial toxicity. Sub-group analyses were performed according to: costs; and determinants of financial toxicity.Results: A total of 31 studies were included in this systematic review and meta-analysis. The pooled prevalence of financial toxicity was 56.96% [95% CI, 30.51, 106.32]. In sub-group meta-analyses, the financial toxicity was higher among cancer patients with household size of more than four (1.17% [95% CI, 1.03, 1.32]; p = 0.02; I2 = 0%), multiple cycles of chemotherapy (1.94% [95% CI, 1.00, 3.75]; p = 0.05; I2 = 43%) and private health facilities (2.87% [95% CI, 1.89, 4.35]; p < 0.00001; I2 = 26%). Mean medical costs per cancer patients were $2,740.18 [95% CI, $1,953.62, $3,526.74]. The ratio of cost of care to gross domestic product (GDP) per capita varied considerably across the LMICs included in this review, which ranged from 0.06 in Vietnam to 327.65 in Ethiopia.Conclusions: This study indicates that cancer diagnosis, treatment and care impose high financial toxicity on cancer patients in LMICs. Further rigorous research on cancer-related financial toxicity is needed.
Comparison of Clinical, Histological and Molecular Features of Primary Operable Breast Cancer in Patients from Kosovar and Croatian University Hospitals
Authors: Sermaxhaj Faton , Plavetić Natalija Dedić , Kulić Ana , Gozalan Ugur , Varga Ljubica Radmilović , Popović Marina , Sović Slavica , Mijatović Davor , Kurshumliu Fisnik , Bahtiri Elton , Sermaxhaj Besim
Published: February 2021

Background

The aim of this study was to explore the clinical, patohistological and molecular characteristics of primary operable breast cancer in patients from Croatia and Kosovo, in order to compare disease stage at the time of diagnosis, in country with implemented mammography screening and early diagnostic methods with country without it.
Methods

The study prospectively included 213 female patients with breast cancer (BC) ranging from 28 to 87 years of age, from which 100 from Kosovo and 113 from Croatia. Age and menopausal status of the patients were recorded before surgery. Subsequent to surgery, histopathology and immunohistochemistry analysis was carried out and data were statistically analysed. Categorical variables were compared using chi-square analysis and presented as frequencies and percentages. For non-parametric data, Mann-Whitney U test was used in order to compare means of two independent groups. A value of P < 0.05 was considered statistically significant.
Results

There were larger tumors, more patients with metastatic axillary lymph nodes and more stage III patients in Kosovo cohort. In addition, the rate of lympho-vascular invasion (LVI) and the expression of progesteron receptor (PR) were significantly higher in Kosovar patients. The other histological and immunohistochemical features were not found to be any different in the two cohorts.
Conclusions

The results of this study from two university hospitals from Croatia and Kosovo demonstrate that the BC patients in Kosovo have more advanced stage of disease at the time of diagnosis compared to Croatia.
Dysfunction of EAAT3 Enhances LPS-induced Postoperative Cognitive Dysfunction
Authors: Wang Xiaoyan , Ma Yulong , Hou Aisheng , Song Yuxiang , Sui Xin , Liu Wengang , Liu Min , Wang Yongan , Cao Jiangbei , Mi Weidong
Published: February 2021

Background: Studies have shown that excitatory amino acid transporter 3 (EAAT3) function inhibition is related to several neurodegenerative diseases. Our previous studies also found that the EAAT3 function is intimately linked to learning and memory. In this study, we examined the role of EAAT3 in postoperative cognitive dysfunction (POCD) and explored the potential benefit of riluzole against POCD. Methods: We measured EAAT3 protein expression in hippocampus of male mice at different ages. Next, we established a recombinant adeno-associated viral (rAAV)-mediated shRNA to knockdown EAAT3 expression in the hippocampus of adult male mice. And then the mice received 2μg of lipopolysaccharide (LPS) intracerebroventricular microinjection to construct the POCD model. In addition, we intraperitoneally injected 4mg/kg of riluzole 2 days before LPS microinjection for consecutive 3 days in elderly male mice. Cognitive function was assessed using a Morris water maze 24h after LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activation of EAAT3 function by riluzole. Results: We found that the expression of EAAT3 was significantly decreased in old mice and EAAT3 knockdown in hippocampus aggravated LPS-induced learning and memory deficits in adult male mice. LPS significantly inhibited hippocampal EAAT3 membrane protein expression and GluA1 protein phosphorylation level in adult male mice. Moreover, riluzole pretreatment significantly increased hippocampal EAAT3 membrane protein expression and ameliorated LPS-induced cognitive impairment in old male mice. Conclusions: Our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and riluzole may be a promising strategy for prevention and treating of POCD in the elderly people.
HPMSCs Inhibit the Expression of PD-1 in CD4+IL-10+ T Cells and Mitigate liver Damage in a GVHD Mouse Model by Regulating the Cross-talk Between Nrf2 and NF-κB Signaling Pathway
Authors: Zhang Aiping , Zhang Jiashen , Li Xiaohua , Zhang Hengchao , Xiong Yanlian , Wang Zhuoya , Zhao Nannan , Wang Feifei , Luan Xiying
Published: February 2021

Background: The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4+IL-10+ T cells and liver tissue and alleviate GVHD remains unclear. This study aimed to investigate the effect of hPMSC-mediated treatment of GVHD associated with CD4+IL-10+ T cell generation via control of redox metabolism and PD-1 expression and whether the Nrf2 and NF-κB signaling pathways were both involved in the process.Methods: A GVHD mouse model was induced using 6-8-week-old C57BL/6 and Balb/c mice, which were treated with hPMSCs. In order to observe whether hPMSCs affect the generation of CD4+IL-10+ T cells via control of redox metabolism and PD-1 expression, a CD4+IL-10+ T cell culture system was induced using human naive CD4+ T cells. The percentage of CD4+IL-10+ T cells and their PD-1 expression levels were determined in vivo and in vitro using flow cytometry, and Nrf2, HO-1, NQO1, GCLC, GCLM, and NF-κB levels were determined by western blotting, qRT-PCR, and immunofluorescence, respectively. Hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining methods were employed to analyze the changes in hepatic tissue. Results: A decreased activity of superoxide dismutase (SOD) and a proportion of CD4+IL-10+ T cells with increased PD-1 expression were observed in GVHD patients and the mouse model. Treatment with hPMSCs increased SOD activity and GCL and GSH levels in the GVHD mouse model. The percentage of CD4+IL-10+ T cells with decreased PD-1 expression, as well as Nrf2, HO-1, NQO1, GCLC, and GCLM levels, both in the GVHD mouse model and in the process of CD4+IL-10+ T cell generation, were also increased, but NF-κB phosphorylation and nuclear translocation were inhibited after treatment with hPMSCs, which was accompanied by improvement of hepatic histopathological changes.Conclusions: The findings suggested that hPMSC-mediated redox metabolism balance and decreased PD-1 expression in CD4+IL-10+ T cells were achieved by controlling the crosstalk between Nrf2 and NF-κB, which further provided evidence for application of hPMSC-mediated treatment of GVHD.
Pressure-Volume Relationship By Pharmacological Stress Cardiovascular Magnetic Resonance
Authors: Meloni Antonella , De Luca Antonio , Nugara Cinzia , Vaccaro Maria , Cavallaro Camilla , Cappelletto Chiara , Barison Andrea , Todiere Giancarlo , Grigoratos Chrysanthos , Calvi Valeria , Novo Giuseppina , Grigioni Francesco , Emdin Michele , Sinagra Gianfranco , Pepe Alessia
Published: February 2021

Background. The variation between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an index of myocardial contractility, easily obtained during routine stress echocardiography and never tested during dipyridamole stress-cardiac magnetic resonance (CMR). We assessed the ΔESPVR index in patients with known/suspected coronary artery disease (CAD) who underwent dipyridamole stress-CMR.Methods. One-hundred consecutive patients (24 females, 63.76±10.17 years) were considered. ESPVR index was evaluated at rest and stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson’s method. Results. The ΔESPVR index showed a good inter-operator reproducibility. Mean ΔESPVR index was 0.48±1.45 mmHg/mL/m2. ΔESPVR index was significantly lower in males than in females. ΔESPVR index was not correlated to rest left ventricular end-diastolic volume index or ejection fraction. Forty-six of 85 patients had myocardial fibrosis detected by the late gadolinium enhancement technique and they showed significantly lower ΔESPVR values. An abnormal stress CMR was found in 25 patients and they showed significantly lower ΔESPVR values. During a mean follow-up of 56.34±30.04 months, 24 cardiovascular events occurred. At receiver-operating characteristic curve analysis, a ΔESPVR<0.02 mmHg/mL/m2 predicted the presence of future cardiac events with a sensitivity of 0.79 and a specificity of 0.68. Conclusions. The noninvasive assessment of the ΔESPVR index during a dipyridamole stress-CMR exam is feasible and reproducible. The ΔESPVR index was independent from rest LV dimensions and function and can be used for a comparative assessment of patients with different diseases. ΔESPVR by CMR can be a useful and simple marker for additional prognostic stratification.
Umbilical Cord Mesenchymal Stem Cells for the Treatment of Atherosclerosis in a Mouse Model: A Randomized Controlled Trial
Authors: Song Yijia , Liu Gaomiyang , Shi Fei , Jiang Xiaochun , Liu Jufen , Zhang Xuejuan , Lin Qingkeng , He Falian , Li Zian , He Jie , Ruan Guangping , Pang Rongqing , Pan Xinghua , Zhu Xiangqing
Published: February 2021

BackgroundThe purpose of this study was to determine the efficacy of umbilical cord mesenchymal stem cell (UCMSC) transplantation in a mouse atherosclerosis (AS) model and explore its potential antioxidative stress and lipid metabolism regulatory effects.MethodsA mouse AS model was established by feeding ApoE-/- mice a high-fat diet, after which UCMSCs were administered by intraperitoneal injection. The treatment effect was evaluated by measuring heart size and carrying out aortic arch histological staining and blood biochemical detection of blood lipids; RT-PCR was utilized to detect the levels of autophagy-related genes, and Q-TOF was used to detect free fatty acids.ResultsAfter UCMSC treatment in a mouse model of AS: the number of aortic arch plaques, length of the heart and heart-to-weight ratio were significantly reduced. Aortic arch staining showed that UCMSC treatment reduced the degree of aortic arch intima lesions. Furthermore, serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were decreased, while the serum high-density lipoprotein cholesterol (HDL-C) level was increased The transcript levels of autophagy-related genes in the heart and liver were significantly higher in AS model mice than in control mice. Finally, the levels of phosphatidylinositol (PI) and ceramide (Cer) in the mouse plasma decreased to the level of the metabolite PI in the liver.Conclusions﻿UCMSCs increased the overall autophagy level in AS model mice, improved liver metabolic dysfunction, inhibited the formation of atherosclerotic plaques and improved the clinical symptoms of AS in the mouse model.
Lack of Changes in Preterm Delivery and Stillbirths During COVID-19 Lockdown in a European Region
Authors: Arnaez Juan , Ochoa-Sangrador Carlos , Caserío Sonia , Gutiérrez Elena Pilar , Jiménez Maria del Pilar , Castañón Leticia , Benito Marta , Peña Ana , Hernández Natalio , Hortelano Myriam , Schuffelmann Susana , Prada Maria Teresa , Gayte Pablo Diego , Villagómez Francisco Joaquín , Garcia-Alix Alfredo
Published: February 2021

Preliminary data in Europe have suggested a reduction in prematurity rates during the COVID-19 pandemic, implying that contingency measures could have an impact on prematurity rates. We designed a population-based prevalence proportion study to explore the potential link between national lockdown measures and a change in preterm births and stillbirths. Adjusted multivariate analyses did not show any decrease in preterm proportions during the lockdown period with respect to the whole pre-lockdown period or to the pre-lockdown comparison periods (2015-2019): 6.5% (95%CI 5.6-7.4), 6.6% (95%CI 6.5-6.8), and 6.2% (95%CI 5.7-6.7), respectively. Proportions of preterm live births did not change during lockdown when different gestational age categories were analyzed, nor when birthweight categories were considered. No differences in stillbirth rates among the different study periods were found: 0.33% (95%CI 0.04-0.61) during the lockdown period vs 0.34% (95%CI 0.22-0.46) during the pre-lockdown comparison period (2015-2019).ConclusionWe did not find any link between prematurity and lockdown, nor between stillbirths and lockdown. Collaborative efforts are desirable to gather more data and additional evidence on this global health issue.
Is Function-Based Resection Using Intraoperative Awake Brain Mapping Feasible and Safe for Solitary Brain Metastases Within Eloquent Areas?
Authors: Pelletier Jean-Baptiste , Moiraghi Alessandro , Zanello Marc , Roux Alexandre , Peeters Sophie , Trancart Bénédicte , Edjlali Myriam , Lechapt Emmanuele , Tauziede-Espariat Arnault , Zah-Bi Gilles , Parraga Eduardo , Chrétien Fabrice , Dezamis Edouard , Dhermain Frédéric , Pallud Johan
Published: February 2021

ObjectiveTo assess feasibility and safety of function-based resection under awake conditions for solitary brain metastasis patients.MethodsRetrospective, observational, single-institution case-control study (2014-2019). Inclusion criteria: adult patients, solitary brain metastasis, supratentorial location within eloquent areas, function-based awake resection. Case matching (1:1) criteria between metastasis group and control group (high-grade gliomas): sex, tumor location, tumor volume, preoperative Karnofsky Performance Status score, age, educational level.ResultsTwenty patients were included. Intraoperatively, all patients were cooperative, no obstacles precluded procedure from being performed. A positive functional mapping was achieved at both cortical and subcortical levels, allowing for a function-based resection in all patients. The case-matched analysis showed that intraoperative and postoperative events were similar, except for a shorter duration of the surgery (p<0.001) and of the awake phase (p<0.001) in the metastasis group. A total resection was performed in 18 cases (90%, including 10 supramarginal resections), and a partial resection was performed in two cases (10%). At three months postoperative months, none of the patients had worsening of their neurological condition or uncontrolled seizures, three patients had an improvement in their seizure control, and seven patients had a Karnofsky Performance Status score increase ≥10 points.ConclusionsFunction-based resection under awake conditions preserving the brain connectivity is feasible and safe in the specific population of solitary brain metastasis patients and allows for high resection rates within eloquent brain areas while preserving the overall and neurological condition of the patients. Awake craniotomy should be considered to optimize outcomes in brain metastases in eloquent areas.