bluuebunny/crossref_metadata_2025 huggingface dataset:
Comportamento ingestivo e padrões de deslocamento de novilhas de corte em Tifton 85 com diferentes níveis de suplementação
Authors: Martini Ana Paula Machado , Moura Amanda Farias de , Borchate Daniele , Adams Sander Martinho , Silva Mauren Burin da , Cocco Joziane Michelon , Cattelam Jonatas , Mello Fernanda Cristina Breda de , Brondani Ivan Luiz , Alves Filho Dari Celestino
Published: December 2020

Objetivou-se identificar quais as variáveis do comportamento ingestivo, padrões de deslocamento e parâmetros produtivos da pastagem explicam a maior parte dos resultados entre os níveis de suplementação ofertados a novilhas terminadas em Tifton 85 (Cynodon dactylon). Utilizou-se a análise de componentes principais para identificar quais variáveis foram relevantes. Na análise, oito variáveis, tempo de pastejo, tempo de ócio, número de estações alimentares/dia, tempo em cada estação, taxa de bocado/dia, massa e oferta de lâminas foliares e relação folha:colmo, explicaram 80,5% da variação dos resultados. Novilhas exclusivamente em pastagem tiveram maior tempo de pastejo e taxa de bocado/dia e menor tempo em ócio. Novilhas que receberam 0,4% de peso corporal de suplemento visitaram maior número de estações alimentares, enquanto novilhas que receberam 1,2% de suplemento permaneceram mais tempo em cada estação alimentar. No primeiro período de avaliação, as novilhas tiveram maior tempo de pastejo, número de estações alimentares/dia, taxa de bocado, massa e oferta de lâminas foliares. O nível 0,8% de suplemento, não influenciou as variáveis avaliadas. Os padrões de deslocamento e o comportamento ingestivo de novilhas recebendo ou não suplemento são influenciadas pelas características estruturais do pasto.
Estudo anatômico do padrão labial entre mães e filhas do Nordeste brasileiro
Authors: Silva Aline Vasconcelos , Costa Ananda Lobo Pedreira , Silva Mona Lisa Cordeiro Asselta da , Oliveira Millena Barroso , Paranhos Luiz Renato , Franco Ademir , Marques Jeidson Antônio Morais , Musse Jamilly de Oliveira
Published: December 2020

Objetivo: Avaliar o padrão de herança queiloscópico, transmitido de mãe para filha, e sua aplicabilidade na identificação humana. Metodologia: Tratou-se de um estudo transversal de natureza qualitativa e quantitativa, elaborado de acordo com o Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). A amostra foi composta por 30 acadêmicas de Odontologia da Universidade Estadual de Feira de Santana (UEFS), e suas respectivas mães. O método consistiu em três etapas: mensuração da espessura labial, classificação das comissuras dos lábios e avaliação do padrão sulcular, seguindo a classificação de Suzuki e Tsuchihashi. Os dados foram analisados estatisticamente utilizando testes Qui-quadrado de Pearson e Exato de Fisher. Resultados: As características labiais mais prevalentes foram a presença de lábios mistos, grossos/muito grossos e da comissura labial disposta horizontalmente. Na avaliação do padrão sulcular prevaleceram os sulcos tipo I (linhas verticais completas) e I’ (linhas verticais incompletas). A espessura e o tipo de comissura labial apresentaram maior potencial de transmissão de mãe para filhas, quando comparado aos tipos de sulcos labiais. Conclusão: A análise dos lábios evidenciou algumas características que apresentam maior semelhança entre mães e filhas, sendo o padrão das impressões labiais a característica de menor semelhança entre os descendentes estudados.
Implicações do perfil preditivo clínico da neuropatia sensorial periférica induzida por oxaliplatina para o cuidado de enfermagem no câncer da topografia gastrointestinal: estudo observacional descritivo
Authors: Pires Lívia Márcia Vidal , Fuly Patrícia dos Santos Claro
Published: December 2020

A Oxaliplatina é um medicamento utilizado  no tratamento de pacientes oncológicos, principalmente com câncer de colón retal metastático. Porém, ela pode promover o desenvolvimento da Neuropatia Sensorial Periférica (NSP). O objetivo deste estudo é descrever o perfil da preditividade clínica de desenvolvimento da NSP em pacientes expostos à Oxaliplatina, para apoio à prática segura do cuidado de enfermagem nessa toxicidade. A pesquisa foi realizada entre os meses de agosto de 2019 e Março de 2020, com 29 pacientes em tratamento quimioterápico ambulatorial na Central de Quimioterapia Adulto da unidade I do Instituto Nacional de Câncer José Alencar Gomes da Silva, que utilizaram a Oxaliplatina para tratamento de neoplasia na topografia do trato gastrointestinal, sob os protocolos CAPOX e FOLFOX, com idade  igual ou superior a 18 anos completos. Foi verificada a prevalência dos fatores clínicos preditivos em ordem decrescente, apontam Diabetes tipo II, Etilismo e Obesidade. O perfil de pacientes que detêm maiores características preditoras de desenvolvimento da NSP induzida por Oxaliplatina é feminino, com idade maior que 60 anos e tão importante quanto a apresentação de comorbidades é a dose cumulativa ao qual estão expostos, suficientes para apresentar manifestações neuropáticas em dose média de 780 mg/m². O reconhecimento dos fatores preditivos, o uso de instrumentos para mensuração  do grau de severidade da Neuropatia e a descrição dos eventos agudos e crônicos podem fornecer apoio ao manejo da toxicidade da Oxaliplatina.
Artefatos para o cuidado de usuários com lesões crônicas de pele na atenção primária à saúde com base em princípios da gestão da clínica
Authors: Cordova Fernanda Peixoto , Santin Jaine , Barros Andre Phylippe Dantas , Pereira Carolina Simões , Paskulin Lisiane Manganelli Girardi , Duarte Êrica Rosalba Mallmann , Kaiser Dagmar Elaine , Ferreira Gímerson Erick
Published: December 2020

Neste estudo, propõe-se a produção de artefatos para o cuidado de usuários com lesões crônicas de pele na atenção primária à saúde (APS). Empreendeu-se pesquisa de natureza aplicada, abordagem qualitativa, com ancoragem teórica em princípios da gestão da clínica e sistematizada metodologicamente com base em técnicas e ferramentas de experimentação do design. A análise do conteúdo produzido integra dados de revisão integrativa da literatura, e de diálogos em grupos focais, envolvendo a equipe multiprofissional da APS. Desta análise, emergiram quatro categorias temáticas, nas quais são apresentados os respectivos artefatos produzidos, com vistas à qualificação do cuidado na APS a usuários com lesões crônicas de pele: mapa conceitual, com representação gráfica que permite uma visão geral das atribuições da equipe; algoritmo de atendimento para apoio a decisões clínicas, monitoramento e avaliação do cuidado; briefing que reúne as principais condutas terapêuticas de recurso mínimo e/ou opção de coberturas especiais fundamentais ao manejo clínico e social; e estrutura de registro para emprego de padrões de monitoramento, avaliação e suporte à decisão nas ações de cuidado. A pesquisa contribui para a implementação de princípios da gestão da clínica nos serviços de APS, na medida em que favorece a incorporação de práticas baseadas em evidências, bem como a orientação das ações clínicas compartilhadas e interprofissionais, com base nas necessidades de usuários com lesões crônicas de pele, e em padrões de qualidade e segurança, com foco no empreendimento de melhores práticas ao usuário no encontro com o serviço.
Recent updates on the management of autoimmune hepatitis
Authors: Komori Atsumasa
Published: December 2020

Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence of AIH has been observed worldwide, along with a relative increase in the percentage of male patients. AIH is characterized and diagnosed based on serum biochemistry and liver histology: elevated aminotransferases and serum immunoglobulin G (IgG), the presence of serum anti-nuclear antibody or anti-smooth muscle antibody, and interface lympho-plasmacytic hepatitis. Clinical manifestations differ among disease subtypes with distinct time-frames, i.e., AIH with a chronic insidious onset, and acute-onset AIH (the diagnosis of which is often challenging due to the lack of typical serum findings). The absence of disease-specific biomarkers or histological findings may expand the disease phenotype into drug-induced AIH-like liver injury. Corticosteroids and azathioprine are recommended first-line treatments for AIH. The complete normalization of aminotransferases and serum IgG is an essential treatment response to ensure long-term overall survival. An incomplete response or intolerance to these drugs is considered an indication for second-line treatment, especially with mycophenolate mofetil. Life-long maintenance treatment is required for the majority of patients, but the few who achieve prolonged and stringent biochemical remission with lower alanine aminotransferase and IgG within the normal range may be able to discontinue the medications. In the future, the quality of life of AIH patients should be managed by personalized medicine, including the appropriate selection and dosing of first-line therapy and perhaps alternating with potential therapeutics, and the prediction of the success of treatment withdrawal.
Transteritoriálne správne akty v podmienkach Európskej únie a Slovenskej republiky
Authors: Jakab Radomír , Seman Tibor , Jančát Lukáš
Published: December 2020

Pojem transteritoriálny správny akt je vo vede správneho práva relatívne novým, a to najmä v podmienkach Slovenskej republiky. Svoju praktickú uplatniteľnosť má v súvislosti s uplatňovaním práva Európskej únie (aj medzinárodného práva). Jeho podstata spočíva v tom, že účinky takéhoto správneho aktu vydaného v rámci jedného členského štátu presahujú územie tohto členského štátu, t.j. majú účinky aj v iných členských štátoch, resp. vo všetkých členských štátoch Európskej únie bez toho, aby podliehali procesu jeho uznania. Cieľom monografie je zhrnutie výsledkov skúmania tohto typu správnych aktov, vymedzenie jeho charakteristických znakov a jeho účinkov, skúmanie možností procesnej obrany pred pôsobením jeho účinkov zo strany dotknutého štátu, prípadne posúdenie možností unifikácie postupu členských štátov Európskej únie v prípade potreby procesnej obrany voči účinkom transteritoriálnych správnych aktov. V rámci monografie sú taktiež analyzované jednotlivý typy transteritoriálnych správnych aktov aplikujúcich sa v podmienkach Európskej únie a Slovenskej republiky, ktoré sú kategorizované podľa stanovených kritérií.
Electrode-less Measurement of Cell Layers Impedance
Authors: KRŮŠEK J. , ĎAĎO S.
Published: December 2020

This paper is devoted to yet unpublished electrode-less methods (ELM) of cell layers impedance measurement based on transformer principle. The main advantage of ELM is elimination uncertainties caused by interface between electrodes and measured electrolyte. The method of avoiding distortion caused by non-ideal transformer transfer function (“deconvolution”) and errors caused by residual voltage is described. The modification of original transformer based method allowing to measure an impedance of inserted object is proposed. Results of several calibration measurements confirming the proper function of ELM including example of transepithelial resistance of cells layer are presented. Crucial parts of measuring system and recommendation for their realization are included.
Renal Changes in the Early Stages of Diet-Induced Obesity in Ovariectomized Rats
Authors: AMARAL L. S. B. , SILVA J. A. , TRINDADE T. M. , RIBAS W. B. D. , MACEDO C. L. , COIMBRA T. M. , BELO N. O. , MAGALHÃES A. C. M. , SOARES T. J.
Published: December 2020

The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-kB), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-kB.
Physiological Response to Whole-Body Vibration in Athletes and Sedentary Subjects
Authors: GOJANOVIC B. , FEIHL F. , GREMION G. , WAEBER B.
Published: December 2020

Whole-body vibration (WBV) is a new exercise method, with good acceptance among sedentary subjects. The metabolic response to WBV has not been well documented. Three groups of male subjects, inactive (SED), endurance (END) and strength trained (SPRINT) underwent a session of side-alternating WBV composed of three 3-min exercises (isometric half-squat, dynamic squat, dynamic squat with added load), and repeated at three frequencies (20, 26 and 32 Hz). VO2, heart rate and Borg scale were monitored. Twenty-seven healthy young subjects (10 SED, 8 SPRINT and 9 END) were included. When expressed in % of their maximal value recorded in a treadmill test, both the peak oxygen consumption (VO2) and heart rate (HR) attained during WBV were greatest in the SED, compared to the other two groups (VO2: 59.3 % in SED vs 50.8 % in SPRINT and 48.0 % in END, p<0.01; HR 82.7 % in SED vs 80.4 % in SPRINT and 72.4 % in END, p<0.05). In conclusions, the heart rate and metabolic response to WBV differs according to fitness level and type, exercise type and vibration frequency. In SED, WBV can elicit sufficient cardiovascular response to benefit overall fitness and thus be a potentially useful modality for the reduction of cardiovascular risk.
‘In search of lost time’, ‘friendship and archaeology’: a personal reminiscence of Ludovic Mann, Joseph Harrison Maxwell and George Applebey – my father
Authors: Applebey George
Published: December 2020

In this paper, I will reflect on my personal memories of Ludovic Mann, friend and mentor to my late father George Applebey, whose archaeological career is also a focus of the paper. They both worked together on Mann's most famous excavations at Knappers Farm, and the nearby painting of the Cochno Stone rock-art panel. However, these are only two examples of their long-term collaboration and friendship, and this paper will explore the broader context within which they worked. This will include consideration of other collaborators, such as J Harrison Maxwell, part of the ‘Ludovic Group’ in the first half of the twentieth century. The important role that all three men played in the development of Scottish archaeology is noted. The paper concludes with developments following Mann's death in 1955 including George Applebey's emergence as a noted amateur archaeologist in his own right, and the fate of the Mann and Applebey collections.
The past in the past and the present: a study of deep time and the city
Authors: Stewart Edward
Published: December 2020

Cities have an immortal quality in the minds of their inhabitants, enduring over the span of their lifetimes, ever changing yet familiar as every new stratigraphic relationship in the city's fabric is thrust, hacked or crammed into the centuries and millennia of anthropogenic stratum that shaped the place to that point. What role does this deep time play in the lives of the shoppers, commuters, dwellers, and workers who interact with the largely invisible urban prehistoric landscape? This paper reports on experiential landscape research focused on a possible prehistoric site in Glasgow, the Camphill enclosure, in Queen's Park. An account of the site has been provided detailing the academic histories from antiquarian rediscovery to the present, current interactions, and a phenomenology-based interpretative narrative of past. The paper concludes with a critique of the research undertaken highlighting the limitations of both the methods and practices and some thoughts on deep time in urban places.
A Binary Logistic Regression Model for Prediction of Feed Conversion Ratio of Clarias gariepinus From Feed Composition Data
Authors: OLUWATOSİN ADEKUNLE Familusi
Published: December 2020

Aquaculture in developing countries faces a lot of challenges that are barely being addressed. With feed taking nearly 70% of the total production cost, it becomes imperative to develop means of optimizing how research is conducted into feed development. Feed conversion ratio as a measure of feed quality can be used to quantify in retrospect the appropriateness of feed fed to livestock, particularly, Clarias gariepinus. From the study, binary logistic regression can in simple terms, determine if prospective feed will perform below or above the acceptable level of 1.5, based on its composition and proximate analysis values. Data from similar experiments are normalized and split into train and testing data to fit a logistic regression model, three numerical optimizers were used including liblinear, Newton-CG, SAG and accuracy of the models were compared using the confusion matrix, and Jaccard similarity score. An accuracy value of 0.8 was observed in the model regardless of the numerical optimizer, this indicates the appropriateness of the model in predicting either high or low FCR for feed types. The probability of prediction showed disparity among liblinear and SAG/Newton-CG solvers. Liblinear solver showed close probabilities in predicting if values will be 1 or 0. While a similar prediction was made by all solvers, this indicates a possible affinity for error when the solver is used. This is also indicated with a logloss of 0.65 as compared to 0.51 in both SAG and Newton-CG solvers.
Rancang Bangun Robot Three wheeled Omnidirectional Dengan Konfigurasi Mikrokontroler Master-Slave
Authors: Rochmanto Raditya Artha , Muslim M. Aziz , Rif’an Mochammad
Published: December 2020

Three wheeled omnidirectional robot has been used in industries and academics fields because its ability to move freely and simultaneously both rotation and translation. Free movement in this robot is assisted by omni wheel which consists of wheels and rollers. So, the movement of this robot is a combination of wheel and roller rotation. At present, the task given to the mobile robot is increasingly complex, so it makes microcontroller’s workload heavier. A microcontroller’s workload could be lightened by master-slave configuration to divide the microcontroller’s tasks. The wheel rotating speed control system uses a pid controller to obtain a fast and stable wheel speed response. The PID parameters, kp,ki,kd were obtained by using the hand tuning method. The testing results shown the average error of robot direction is 4,3750 and the direction of the robot’s face changed 5.750.
PENGARUH HUTANG JANGKA PENDEK DAN UKURAN PERUSAHAAN TERHADAP PROFITABILITAS PADA PT WIDJAYA DJAYA INDAH DI KOTA BATAM
Authors: Efriyenty Dian
Published: December 2020

This study aims to examine the effect of short-term debt and firm size on profitability at PT Widjaya Djaya Indah, located in Batam City. This research uses quantitative methods. The data collection technique in this study used a saturated sample technique, namely using the entire data obtained. The data analysis method used is descriptive analysis, classic assumption test which includes normality test, multicolonierity test, heterocedastity test and autocorrelation test, hypothesis test which includes t test, f test, determination coefficient test and multiple linear regression. The sample used is 60 financial statement data from PT Widjaya Djaya Indah and the research objects used are the current ratio (X1), company size (X2), and return on assets (Y). The data in this study were processed using SPSS version 21. The results of the F test processing in this study indicate that simultaneously there is a positive and significant effect between the current ratio and company size on return on assets at PT Widjaya Djaya Indah. And the t test results show that the current ratio has a positive and significant effect on return on assets while company size has a negative and significant effect on return on assets.
Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
Authors: Veiga-Lopez Almudena , Sethuraman Visalakshi , Navasiolava Nastassia , Makela Barbara , Olomu Isoken , Long Robert , van de Wetering Koen , Martin Ludovic , Aranyi Tamas , Szeri Flora
Published: December 2020

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.
Resistance Mechanisms of Anti-angiogenic Therapy and Exosomes-Mediated Revascularization in Cancer
Authors: Zeng Ye , Fu Bingmei M.
Published: December 2020

Anti-angiogenic therapies (AATs) have been widely used for cancer treatment. But the beneficial effects of AATs are short, because AAT-induced tumor revascularization facilitates the tumor relapse. In this mini-review, we described different forms of tumor neovascularization and revascularization including sprouting angiogenesis, vessel co-option, intussusceptive angiogenesis, and vasculogenic mimicry, all of which are closely mediated by vascular endothelial growth factor (VEGF), angiopoietins, matrix metalloproteinases, and exosomes. We also summarized the current findings for the resistance mechanisms of AATs including enhancement in pro-angiogenic cytokines, heterogeneity in tumor-associated endothelial cells (ECs), crosstalk between tumor cells and ECs, masking of extracellular vesicles, matrix stiffness and contributions from fibroblasts, macrophages and adipocytes in the tumor microenvironment. We highlighted the revascularization following AATs, particularly the role of exosome stimulating factors such as hypoxia and miRNA, and that of exosomal cargos such as cytokines, miRNAs, lncRNAs, and circRNAs from the tumor ECs in angiogenesis and revascularization. Finally, we proposed that renormalization of tumor ECs would be a more efficient cancer therapy than the current AATs.
Carbon Allocation in Multi-Product Steel Mills That Co‐process Biogenic and Fossil Feedstocks and Adopt Carbon Capture Utilization and Storage Technologies
Authors: Biermann Maximilian , Montañés Rubén M. , Normann Fredrik , Johnsson Filip
Published: December 2020

This work investigates the effects of carbon allocation on the emission intensities of low-carbon products cogenerated in facilities that co‐process biogenic and fossil feedstocks and apply the carbon capture utilization and storage technology. Thus, these plants simultaneously sequester CO2 and synthesize fuels or chemicals. We consider an integrated steel mill that injects biomass into the blast furnace, captures CO2 for storage, and ferments CO into ethanol from the blast furnace gas. We examine two schemes to allocate the CO2 emissions avoided [due to the renewable feedstock share (biomass) and CO2 capture and storage (CCS)] to the products of steel, ethanol, and electricity (generated through the combustion of steel mill waste gases): 1) allocation by (carbon) mass, which represents actual carbon flows, and 2) a free-choice attribution that maximizes the renewable content allocated to electricity and ethanol. With respect to the chosen assumptions on process performance and heat integration, we find that allocation by mass favors steel and is unlikely to yield an ethanol product that fulfills the Renewable Energy Directive (RED) biofuel criterion (65% emission reduction relative to a fossil comparator), even when using renewable electricity and applying CCS to the blast furnace gas prior to CO conversion into ethanol and electricity. In contrast, attribution fulfills the criterion and yields bioethanol for electricity grid intensities <180 gCO2/kWhel without CCS and yields bioethanol for grid intensities up to 800 gCO2/kWhel with CCS. The overall emissions savings are up to 27 and 47% in the near-term and long-term future, respectively. The choice of the allocation scheme greatly affects the emissions intensities of cogenerated products. Thus, the set of valid allocation schemes determines the extent of flexibility that manufacturers have in producing low-carbon products, which is relevant for industries whose product target sectors that value emissions differently. We recommend that policymakers consider the emerging relevance of co‐processing in nonrefining facilities. Provided there is no double-accounting of emissions, policies should contain a reasonable degree of freedom in the allocation of emissions savings to low-carbon products, so as to promote the sale of these savings, thereby making investments in mitigation technologies more attractive to stakeholders.
Natural Clinopyroxene Reference Materials for in situ Sr Isotopic Analysis via LA-MC-ICP-MS
Authors: Zhao Han , Zhao Xin-Miao , Le Roux P. J. , Zhang Wen , Wang Hao , Xie Lie-Wen , Huang Chao , Wu Shi-Tou , Yang Jin-Hui , Wu Fu-Yuan , Yang Yue-Heng
Published: December 2020

Clinopyroxene is a major host mineral for lithophile elements in the mantle lithosphere, and therefore, its origin is vital for constraints on mantle evolution and melt generation. In situ Sr isotopic measurement of clinopyroxene has been available since the recent development of laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) in the 2000s. Therefore, there is an increasing demand for natural clinopyroxene reference materials for Sr isotope microanalysis. In this contribution, we present six natural clinopyroxene reference materials from South Africa (JJG1424) and China (YY09-47, YY09-04, YY09-24, YY12-01, and YY12-02) for Sr isotope microanalysis. The Sr content of these clinopyroxenes ranges from 50 to 340 μg g−1, which covers most natural clinopyroxene compositions. Homogeneity of these potential reference materials were investigated and evaluated in detail over a 2-year period using 193-nm nanosecond and 257-nm femtosecond laser systems coupled to either a Neptune or Neptune Plus MC-ICP-MS. Additionally, the major and trace element of these clinopyroxenes were examined by electron probe microanalyzer (EPMA) as well as solution and laser ICP-MS. The in situ87Sr/86Sr values obtained for the six natural clinopyroxene reference materials agree well with data obtained using the thermal ionization mass spectrometer (TIMS) method. The Sr isotopic stability and homogeneity of these clinopyroxenes make them potential reference materials for in situ Sr microanalysis to correct instrumental fractionation or as quality control materials for analytical sessions. The new Sr isotope data provided here might be beneficial for microbeam analysis in the geochemical community.
A Multi-Method Approach for Quantification of In- and Exfiltration Rates from the Subterranean Estuary of a High Energy Beach
Authors: Grünenbaum Nele , Ahrens Janis , Beck Melanie , Gilfedder Benjamin Silas , Greskowiak Janek , Kossack Michael , Massmann Gudrun
Published: December 2020

Accurate SGD (submarine groundwater discharge) mass export calculations require detailed knowledge of the spatial and temporal variability in SGD rates. In coastal aquifers, SGD includes a terrestrial freshwater component as well as a saline component originating from circulating seawater. Representative field measurements of SGD rates are difficult to conduct, because SGD is often patchy, diffuse, and temporally variable, especially under tidal influence and high wave activity. In this study, a combination of lysimeters, seepage meters, temperature sensors, pore water radon, and numerical modeling was used to estimate the volumes of infiltrating seawater and exfiltrating groundwater in the intertidal zone of a mesotidal, high energy beach on Spiekeroog Island, northern Germany. Additionally, a 3D-laser scanner was used over short (days) and medium time scales (months) to determine changes in beach topography. The results showed net water infiltration above mean sea level (MSL) and net exfiltration below MSL. Water exchange rates fluctuated between 0.001 and 0.61 m day−1, showing similar ranges within the multiple method approaches. The beach topography was subject to strong fluctuation caused by waves, currents, wind driven erosion and sedimentation, even over short time scales. A comparison of extrapolated in- and exfiltrating water volumes along a beach transect from the mean high water to mean low water line at different times highlights the variability of total in or outflow. The results show that exchange rates depend on beach topography, which in turn changes significantly over time.
Oxidation-Specific Epitopes in Non-Alcoholic Fatty Liver Disease
Authors: Hendrikx Tim , Binder Christoph J.
Published: December 2020

An improper balance between the production and elimination of intracellular reactive oxygen species causes increased oxidative stress. Consequently, DNA, RNA, proteins, and lipids are irreversibly damaged, leading to molecular modifications that disrupt normal function. In particular, the peroxidation of lipids in membranes or lipoproteins alters lipid function and promotes formation of neo-epitopes, such as oxidation-specific epitopes (OSEs), which are found to be present on (lipo)proteins, dying cells, and extracellular vesicles. Accumulation of OSEs and recognition of OSEs by designated pattern recognition receptors on immune cells or soluble effectors can contribute to the development of chronic inflammatory diseases. In line, recent studies highlight the involvement of modified lipids and OSEs in different stages of the spectrum of non-alcoholic fatty liver disease (NAFLD), including inflammatory non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Targeting lipid peroxidation products shows high potential in the search for novel, better therapeutic strategies for NASH.
Experimental Study of Freeze-Thaw/Water Compound Erosion and Hydraulic Conditions as Affected by Thawed Depth on Loessal Slope
Authors: Wang Wei , Li Zhanbin , Yang Rui , Wang Tian , Li Peng
Published: December 2020

Freeze-thaw cycles have significant influences on slope erosion processes. In this study, simulated rainfall laboratory experiments were implemented to investigate erosion processes and the relationship between the soil loss rate and hydraulics conditions under different thawed depths and rainfall intensities. The results indicated that linear regression could be used to describe the relationship between the soil loss rate and runoff time. Soil loss rate, as measured by the curve slope k (represented the increase rate in the soil loss rate), generally increased with runoff time over different thawed depths across all rainfall intensities. The k values generally increased with rainfall intensity from 0.6 to 1.2 mm/min, with the exception of the 4 cm thawed slope, for which the k values initially increased before decreasing with rainfall intensity from 0.6 to 1.2 mm/min. The mean soil loss rate and range also increased with thawed depth under the same rainfall intensity. Finally, the interaction of rainfall intensity and thawed depth had the greatest effect on soil loss rate, while stream erosion power was the hydraulic parameter that exhibited the best soil loss rate prediction performance. The results presented herein improve the understanding of the response of freeze-thaw/water compound erosion to hydraulic conditions.
MiRNA-Mediated Subpathway Identification and Network Module Analysis to Reveal Prognostic Markers in Human Pancreatic Cancer
Authors: Liu Yuejuan , Cui Yuxia , Bai Xuefeng , Feng Chenchen , Li Meng , Han Xiaole , Ai Bo , Zhang Jian , Li Xuecang , Han Junwei , Zhu Jiang , Jiang Yong , Pan Qi , Wang Fan , Xu Mingcong , Li Chunquan , Wang Qiuyu
Published: December 2020

Background

Pancreatic cancer (PC) remains one of the most lethal cancers. In contrast to the steady increase in survival for most cancers, the 5-year survival remains low for PC patients.

Methods

We describe a new pipeline that can be used to identify prognostic molecular biomarkers by identifying miRNA-mediated subpathways associated with PC. These modules were then further extracted from a comprehensive miRNA-gene network (CMGN). An exhaustive survival analysis was performed to estimate the prognostic value of these modules.

Results

We identified 105 miRNA-mediated subpathways associated with PC. Two subpathways within the MAPK signaling and cell cycle pathways were found to be highly related to PC. Of the miRNA-mRNA modules extracted from CMGN, six modules showed good prognostic performance in both independent validated datasets.

Conclusions

Our study provides novel insight into the mechanisms of PC. We inferred that six miRNA-mRNA modules could serve as potential prognostic molecular biomarkers in PC based on the pipeline we proposed.
Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
Authors: Salum Kaio Cezar Rodrigues , de Souza Guilherme Orofino , Abreu Gabriella de Medeiros , Campos Junior Mário , Kohlrausch Fabiana Barzotto , Carneiro João Regis Ivar , Nogueira Neto José Firmino , Magno Fernanda Cristina C. Mattos , Rosado Eliane Lopes , Palhinha Lohanna , Maya-Monteiro Clarissa Menezes , Cabello Giselda Maria Kalil de , Cabello Pedro Hernán , Bozza Patrícia Torres , Zembrzuski Verônica Marques , da Fonseca Ana Carolina Proença
Published: December 2020

Background

The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity.

Methods

This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0–11 years), 19 patients in the adolescence/youth-onset group (12–21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject’s DNA was assessed using automated Sanger sequencing.

Results

Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity.

Conclusion

This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.
Macrophages in Organ Transplantation
Authors: Ordikhani Farideh , Pothula Venu , Sanchez-Tarjuelo Rodrigo , Jordan Stefan , Ochando Jordi
Published: December 2020

Current immunosuppressive therapy has led to excellent short-term survival rates in organ transplantation. However, long-term graft survival rates are suboptimal, and a vast number of allografts are gradually lost in the clinic. An increasing number of animal and clinical studies have demonstrated that monocytes and macrophages play a pivotal role in graft rejection, as these mononuclear phagocytic cells recognize alloantigens and trigger an inflammatory cascade that activate the adaptive immune response. Moreover, recent studies suggest that monocytes acquire a feature of memory recall response that is associated with a potent immune response. This form of memory is called “trained immunity,” and it is retained by mechanisms of epigenetic and metabolic changes in innate immune cells after exposure to particular ligands, which have a direct impact in allograft rejection. In this review article, we highlight the role of monocytes and macrophages in organ transplantation and summarize therapeutic approaches to promote tolerance through manipulation of monocytes and macrophages. These strategies may open new therapeutic opportunities to increase long-term transplant survival rates in the clinic.
Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer
Authors: Davies Sarah I. , Barrett John , Wong Susan , Chang Mark Jesse , Muranski Pawel J. , Brownell Isaac
Published: December 2020

Virus positive Merkel cell carcinoma (VP-MCC) is an aggressive but immunogenic skin malignancy driven by Merkel cell polyomavirus (MCPyV) T antigen (TAg). Since adoptive T cell transfer (ACT) can be effective against virus-driven malignancies, we set out to develop a methodology for generating MCPyV TAg specific T cells. MCPyV is a common, asymptomatic infection and virus-exposed healthy donors represent a potential source of MCPyV TAg specific T cells for ACT. Virus specific T cells were generated using monocyte-derived dendritic cells (moDCs) pulsed with MCPyV TAg peptide libraries and co-cultured with autologous T cells in supplemented with pro-inflammatory and homeostatic cytokines for 14 days. Specific reactivity was observed predominantly within the CD4+T cell compartment in the cultures generated from 21/46 random healthy donors. Notably, responses were more often seen in donors aged 50 years and older. TAg specific CD4+T cells specifically secreted Th1 cytokines and upregulated CD137 upon challenge with MCPyV TAg peptide libraries and autologous transduced antigen presenting cells. Expanded T cells from healthy donors recognized epitopes of both TAg splice variants found in VP-MCC tumors, and minimally expressed exhaustion markers. Our data show that MCPyV specific T cells can be expanded from healthy donors using methods appropriate for the manufacture of clinical grade ACT products.
Sensitivity of a Satellite Algorithm for Harmful Algal Bloom Discrimination to the Use of Laboratory Bio-optical Data for Training
Authors: Martinez-Vicente Victor , Kurekin Andrey , Sá Carolina , Brotas Vanda , Amorim Ana , Veloso Vera , Lin Junfang , Miller Peter I.
Published: December 2020

Early detection of dense harmful algal blooms (HABs) is possible using ocean colour remote sensing. Some algorithms require a training dataset, usually constructed from satellite images with a priori knowledge of the existence of the bloom. This approach can be limited if there is a lack of in situ observations, coincident with satellite images. A laboratory experiment collected biological and bio-optical data from a culture of Karenia mikimotoi, a harmful phytoplankton dinoflagellate. These data showed characteristic signals in chlorophyll-specific absorption and backscattering coefficients. The bio-optical data from the culture and a bio-optical model were used to construct a training dataset for an existing statistical classifier. MERIS imagery over the European continental shelf were processed with the classifier using different training datasets. The differences in positive rates of detection of K. mikimotoi between using an algorithm trained with purely manually selected areas on satellite images and using laboratory data as training was overall <1%. The difference was higher, <15%, when using modeled optical data rather than laboratory data, with potential for improvement if local average chlorophyll concentrations are used. Using a laboratory-derived training dataset improved the ability of the algorithm to distinguish high turbidity from high chlorophyll concentrations. However, additional in situ observations of non-harmful high chlorophyll blooms in the area would improve testing of the ability to distinguish harmful from non-harmful high chlorophyll blooms. This approach can be expanded to use additional wavelengths, different satellite sensors and different phytoplankton genera.
Mosquito Behavior and Vertebrate Microbiota Interaction: Implications for Pathogen Transmission
Authors: Ruiz-López María José
Published: December 2020

The microbiota is increasingly recognized for its ability to influence host health and individual fitness through multiple pathways, such as nutrient synthesis, immune system development, and even behavioral processes. Most of these studies though focus on the direct effects microbiota has on its host, but they do not consider possible interactions with other individuals. However, host microbiota can change not only host behavior but also the behavior of other individuals or species toward the host. For example, microbes can have an effect on animal chemistry, influencing animal behaviors mediated by chemical communication, such as mosquito attraction. We know that host skin microbes play a major role in odor production and thus can affect the behavior of mosquitoes leading to differences in attraction to their hosts. Ultimately, the vector feeding preference of mosquitoes conditions the risk of vertebrates of coming into contact with a vector-borne pathogen, affecting its transmission, and thus epidemiology of vector-borne diseases. In this mini review, I provide an overview of the current status of research on the interaction between mosquito behavior and host skin microbiota, both in humans and other vertebrates. I consider as well the factors that influence vertebrate skin microbiota composition, such as sex, genetic makeup, and infection status, and discuss the implications for pathogen transmission.
High-Throughput Identification of Antibacterials Against Pseudomonas aeruginosa
Authors: Li Shijia , She Pengfei , Zhou Linying , Zeng Xianghai , Xu Lanlan , Liu Yaqian , Chen Lihua , Wu Yong
Published: December 2020

Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against Pseudomonas aeruginosa. A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of P. aeruginosa while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on P. aeruginosa PAO1 and P. aeruginosa ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) P. aeruginosa strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR P. aeruginosa-related infections.
Development and Optimization of Chromosomally-Integrated Fluorescent Mycobacterium tuberculosis Reporter Constructs
Authors: Kolbe Katharina , Bell Alice C. , Prosser Gareth A. , Assmann Maike , Yang Hee-Jeong , Forbes He Eun , Gallucci Sophia , Mayer-Barber Katrin D. , Boshoff Helena I. , Barry III Clifton E.
Published: December 2020

Mycobacterium tuberculosis resides in the lungs in various lesion types with unique microenvironmental conditions. This diversity is in line with heterogeneous disease progression and divergent drug efficiency. Fluorescent reporter strains can be used to decipher the micromilieu and to guide future treatment regimens. Current reporters using replicating plasmids, however, are not suitable for long-term mouse infections or studies in non-human primates. Using a combination of recombinant DNA and protein optimization techniques, we have developed reporter strains based on integrative plasmids, which exhibit stimulus-response characteristics and fluorescence intensities comparable to those based on replicating plasmids. We successfully applied the concepts by constructing a multi-color reporter strain able to detect simultaneous changes in environmental pH, Mg2+ concentrations, and protein expression levels.