bluuebunny/crossref_metadata_2025 huggingface dataset:
Detección de la adulteración de la leche mediante sensor óptico
Authors: Velásquez Yaneris , Ventura Rubén , Villarreal Mitzela , Campos Alfredo
Published: September 2021

La adulteración de la leche mediante la adición de agua es una práctica utilizada actualmente para aumentar su volumen y así reducir los costos de producción, lo cual deriva en una problemática que afecta mayormente a países en vías de desarrollo y es importante mitigar. A raíz de esta situación se realizan investigaciones con el fin de crear una herramienta que permita detectar estas anomalías de manera sencilla y rápida. En este trabajo de investigación se modeló un sensor óptico basado en una película delgada nanométrica de oro utilizando el software Matlab 2020, con el cuál se simuló la reflectancia de un haz de luz en función del ángulo incidente en presencia de leche pura y en presencia de leche con distintos porcentajes de dilución en agua. Conjuntamente se realizó un estudio de la determinación del espesor óptimo del sensor para obtener la máxima sensibilidad. Se puede afirmar que, según la data simulada, el sensor muestra alta sensibilidad al detectar pequeñas diluciones de agua, además se obtuvo que el espesor óptimo de la película delgada para aumentar la sensibilidad es de 90 nm. Este trabajo brinda información importante para tener en cuenta a la hora de la construcción de un sensor óptico de este tipo. Además, este sensor es una herramienta muy prometedora, ya que su ejecución tiene como objetivo dar resultados precisos y de calidad.
Oral health care for a young drug user
Authors: Camargo Lucas Lucena , Antoniassi Junior Gilmar
Published: September 2021

Objetivo: desenhar os cuidados com a saúde bucal de um jovem usuário de drogas, acerca da autoimagem em virtude do método terapêutico aplicado no atendimento odontológico, realizado na Clínica Escola de uma Faculdade Privada em uma cidade de médio porte do interior do Estado de Minas Gerais, Brasil. Materiais e Métodos: trata-se de uma pesquisa intervenção de observação participante de natureza qualitativa do tipo estudo de caso, que fez uso do método intervencionista, sendo realizada em uma Clínica Escola de Odontologia de uma Faculdade Privada. O caso foi selecionado de modo intencional a partir do atendimento da Clínica de Triagem e o direcionamento para o atendimento da Clínica Integrada, devido à complexidade da condição de saúde bucal em decorrência do uso de drogas. O estudo foi submetido para apreciação Ética através do CAEE: 40362620.2.0000.8078. Trata-se de um paciente com idade de 19 anos aqui denominado como T, de classe social baixa, ensino médio incompleto, exercendo atividade laboral como barbeiro, residente com os pais em um bairro periférico da cidade. Como instrumento de coleta de dados utilizou do registro de fotográfico, prontuário, diário de campo e entrevista episódica. Para as análises de dados foram utilizados métodos de abordagem qualitativa. Considerações: pode-se considerar positivamente que a evolução do plano de tratamento estabelecido transcorreu positivamente a favor da intervenção terapêutica estabelecida em decorrência do comportamento apresentado pelo paciente, demonstrando assim, a satisfação do paciente com os resultados no âmbito da condição da saúde bucal, bem como, a estética e a autoestima.
Selenyum, Su Ürünleri ve Sağlık
Authors: KOCATEPE Demet , BÜYÜKKOL Derya , ÖZTÜRK Gözde
Published: September 2021

Selenyum; endokrin, bağışıklık ve kardiyovasküler sistem gibi birçok sistemin işlevini destekler. Tüm eser mineraller gibi vücudun düzgün çalışması için gereklidir. Selenyum insan sağlığı için önemli olan ancak fazla alındığında insanlar için de zararlı olabilecek bir eser elementtir. Selenyum ihtiyacı, kalsiyum ve demir gibi vücuda daha çok miktarlarda gerekli olan minerallerden daha az seviyededir. Bu nedenle de bir mikro besin olarak adlandırılır. Diğer birçok besinde de olduğu gibi, selenyuma verilen biyolojik yanıt cinsiyete ve yaşa göre farklılık gösterir. İnsanlar genellikle selenyumu mahsul ve hayvansal ürünlerle ve bazen de fonksiyonel yiyecekler veya takviyeler olarak alırlar. Selenyum, E vitamini ile sinerjist olarak çalışır. Su ürünlerinin selenyum açısından zengin gıdalar arasında gelmektedir. Sadece balık değil kabuklu su ürünleri de içerdikleri minerallerden dolayı günlük besin alımında önemli bir yeri vardır.
Modeling the seasonal variability of phytoplankton in the subarctic northeast Pacific Ocean
Authors: Zhang HR , Wang Y , Xiu P , Chai F
Published: September 2021

The subarctic northeast Pacific Ocean (SNEP) is a high-nitrate, low-chlorophyll region where, due to iron (Fe) limitation, chlorophyll a (chl a) concentration is persistently low throughout the year despite abundant nitrate. Observations from a Biogeochemical-Argo float (BGC-Argo) deployed in the SNEP in 2012 show prominent variations in chl a in the upper ocean (0-150 m). Chl a peaks in late summer and autumn at a value >3�times that in winter; these observations at a fine resolution can help us disentangle the mechanisms driving the full seasonal cycle of phytoplankton. A one-dimensional physical-biogeochemical coupled model was applied at OSP to investigate the factors driving phytoplankton dynamics in the SNEP. Seasonal variability of chl a in the upper layer is reproduced by the model; results are reasonably comparable to the BGC-Argo observations in 2012 near OSP. Phytoplankton growth is limited in winter by the deep mixed layer, which reduces light availability; light gradually increases later in the year due to shoaling of the mixed layer and increasing solar radiation. In spring and early summer, Fe limitation restricts phytoplankton growth, especially diatoms, and grazing pressure on small phytoplankton from overwintering microzooplankton inhibits accumulation of phytoplankton biomass. Chl a accumulates throughout the summer, peaking in late summer and autumn as mesozooplankton consume microzooplankton, which reduces microzooplankton grazing on phytoplankton. Although the model study was restricted to the seasonal pattern of BGC-Argo observations in 2012, it nevertheless fully describes seasonal variability in chl a in the SNEP and is crucial to understanding mechanisms underlying phytoplankton dynamics in high-nitrate, low-chlorophyll regions.
Physical development and individual metabolic parameters in various forms of congenital epidermolysis bullosa depending on supplementation treatment
Authors: Pronina I. Yu. , Murashkin N. N. , Makarova S. G. , Fisenko A. P. , Semikina E. L. , Epishev R. V. , Leonova M A.
Published: September 2021

Congenital epidermolysis bullosa (CEB) is a group of rare genetic diseases of varying severity, which are characterized with the formation of blisters on the skin and/or mucous membranes with minor trauma. In this case, the clinical course of the disease in some cases is aggravated by the development of malnutrition, which further worsens the quality of life of patients.

Aim of the study. To assess the physical development and laboratory findings of nutritional status in children with simple (SCEB) and dystrophic forms of CEB (DCEB).

Methods and materials. The study included children with SCEB and DCEB at the age of 8 months to 18 years old, treated at the National Medical Research Centre of Children's Health (Moscow, Russia) from January 2018 to January 2019. Anthropometric parameters were assessed in all patients, and a biochemical blood test was performed for total calcium, phosphorus, albumin, and magnesium. Data are presented using the median (Me) and quartiles of 25 % and 75 % [Q25; Q75], as well as the mean (M) and 95 % confidence interval (95 % CI) for variables with a normal distribution.

Results. A total of 87 children were included in the study, 70 with DCEB and 17 with SCEB. There were no differences in sex and age between the groups. According to the results of the study, all anthropometric parameters (WAZ, HAZ and BAZ) in children with DCEB were statistically significantly lower (p < 0.001) than in children with SCEB. Although in both forms of CEB the averaged values of WAZ, HAZ and BAZ turned out to be within the normal range, in children with DCEB, a decrease in HAZ less than -2 was noted in 22 children (31%). Moderate protein-energy malnutrition (-3 < BAZ < -2) was detected in 29 patients (41 %), while 20 of them (29%) were diagnosed with severe protein-energy malnutrition (BAZ < -3). Biochemical parameters were within the reference values, however, the levels of albumin and total calcium were statistically significantly reduced in children with DCEB compared with SCEB children (p < 0.001 and p = 0.005, respectively). Hypoalbuminemia was observed in 64 %, and hypocalcemia in 9 % of DCEB children.

Conclusion. All anthropometric values in children with DCEB were lower than in children with SCEB. The study of albumin and total calcium level in the blood of children with DCEB can reveal preclinical forms of malnutrition.
Development of information and educational environment that promotes spread of sustainable lifestyle changes through adherence to principles of healthy nutrition
Authors: Simkalova L. M. , Bokova E. A. , Ivanov G. E. , Gavrilin A. A.
Published: September 2021

Healthy nutrition is the most important component of the quality of life of the population. Disorders of the nutritional structure lead to the development of alimentary-dependent diseases, including cardiovascular, oncological, diabetes mellitus, obesity, osteoporosis, etc., that are the main causes of premature mortality of the population of economically developed countries, including Russia. This is due, among other things, to the low level of knowledge of the population about the principles of healthy nutrition. In order to eliminate the existing gap in the competence of the population on healthy nutrition, the Centre for Hygienic education of the population of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Moscow, as a part of the implementation of the federal project ‘Formation of a system of motivation of citizens to a healthy lifestyle, including healthy nutrition and rejection of bad habits' (‘Strengthening the Public Health'), which is a part of the national project ‘Demography', conducts systematic activities aimed at creating and maintaining an information and educational environment.
Role of vitamin D in patients with cardiac arrhythmias (atrial fibrillation). Personalization of nutrition
Authors: Balashova N. V. , Gulia L. D. , Beniya R. M. , Orlova S. V. , Nikitina E. A.
Published: September 2021

Despite advances in the diagnosis and treatment of various forms of cardiac arrhythmias, atrial fibrillation (AF) remains a serious problem in the internal medicine clinic, especially acute in gerontology. Prevention of the development of cardiac arrhythmias is an important medical and social task. Adequate nutrition plays an important role in the cardiovascular diseases prophylaxis. At the same time, a deficiency of vitamins and minerals, including vitamin D, can create a pathogenetic basis for the development of arrhythmias. Experimental and clinical studies have demonstrated the effect of vitamin D on the mechanisms underlying the formation of AF. Screening for vitamin D deficiency in cardiac patients should become routine. Correcting vitamin D deficiencies must be personalized. Further clinical trials are needed to investigate the clinical endpoints (morbidity and mortality) of vitamin D supplementation in arrhythmology.
β-hydroxy-β-methylbutyrate: role and prospects applications in gerontology
Authors: Nikitina E. A. , Orlova S. V. , Pigareva Yu. A. , Magomedova Kh. A.
Published: September 2021

The problem of population aging in developed countries poses new challenges for the medical community. Sarcopenia is one of the most common problems that decrease the quality of life of older people and increase the risk of disability and death. Currently, several dietary approaches to the prevention and correction of sarcopenia have been developed. Hydroxymethyl butyrate is one of the innovative substances designed to optimize the diet of elderly patients, primarily those with a sedentary lifestyle or on bed rest.
Bone Regeneration in Load-Bearing Segmental Defects, Guided by Biomorphic, Hierarchically Structured Apatitic Scaffold
Authors: Kon Elizaveta , Salamanna Francesca , Filardo Giuseppe , Di Matteo Berardo , Shabshin Nogah , Shani Jonathan , Fini Milena , Perdisa Francesco , Parrilli Annapaola , Sprio Simone , Ruffini Andrea , Marcacci Maurilio , Tampieri Anna
Published: September 2021

The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and 3D porous structure effective in guiding and sustaining new bone formation and vascularization in large bone defects. In the present study, biomorphic calcium phosphate bone scaffolds (GreenBone™) featuring osteon-mimicking, hierarchically organized, 3D porous structure and lamellar nano-architecture were implanted in a critical cortical defect in sheep and compared with allograft. Two different types of scaffolds were tested: one made of ion-doped hydroxyapatite/β-tricalcium-phosphate (GB-1) and other made of undoped hydroxyapatite only (GB-2). X-ray diffraction patterns of GB-1 and GB-2 confirmed that both scaffolds were made of hydroxyapatite, with a minor amount of β-TCP in GB-1. The chemical composition analysis, obtained by ICP-OES spectrometer, highlighted the carbonation extent and the presence of small amounts of Mg and Sr as doping ions in GB-1. SEM micrographs showed the channel-like wide open porosity of the biomorphic scaffolds and the typical architecture of internal channel walls, characterized by a cell structure mimicking the natural parenchyma of the rattan wood used as a template for the scaffold fabrication. Both GB-1 and GB-2 scaffolds show very similar porosity extent and 3D organization, as also revealed by mercury intrusion porosimetry. Comparing the two scaffolds, GB-1 showed slightly higher fracture strength, as well as improved stability at the stress plateau. In comparison to allograft, at the follow-up time of 6 months, both GB-1 and GB-2 scaffolds showed higher new bone formation and quality of regenerated bone (trabecular thickness, number, and separation). In addition, higher osteoid surface (OS/BS), osteoid thickness (OS.Th), osteoblast surface (Ob.S/BS), vessels/microvessels numbers, as well as substantial osteoclast-mediated implant resorption were observed. The highest values in OS.Th and Ob. S/BS parameters were found in GB-1 scaffold. Finally, Bone Mineralization Index of new bone within scaffolds, as determined by micro-indentation, showed a significantly higher microhardness for GB-1 scaffold in comparison to GB-2. These findings suggested that the biomorphic calcium phosphate scaffolds were able to promote regeneration of load-bearing segmental bone defects in a clinically relevant scenario, which still represents one of the greatest challenges in orthopedics nowadays.
Micelles Based on Lysine, Histidine, or Arginine: Designing Structures for Enhanced Drug Delivery
Authors: Xie Li , Liu Rong , Chen Xin , He Mei , Zhang Yi , Chen Shuyi
Published: September 2021

Natural amino acids and their derivatives are excellent building blocks of polymers for various biomedical applications owing to the non-toxicity, biocompatibility, and ease of multifunctionalization. In the present review, we summarized the common approaches to designing and constructing functional polymeric micelles based on basic amino acids including lysine, histidine, and arginine and highlighted their applications as drug carriers for cancer therapy. Different polypeptide architectures including linear polypeptides and dendrimers were developed for efficient drug loading and delivery. Besides, polylysine- and polyhistidine-based micelles could enable pH-responsive drug release, and polyarginine can realize enhanced membrane penetration and gas therapy by generating metabolites of nitric oxide (NO). It is worth mentioning that according to the structural or functional characteristics of basic amino acids and their derivatives, key points for designing functional micelles with excellent drug delivery efficiency are importantly elaborated in order to pave the way for exploring micelles based on basic amino acids.
Physical Cues of Matrices Reeducate Nerve Cells
Authors: Luo Yiqian , Li Jie , Li Baoqin , Xia Yuanliang , Wang Hengyi , Fu Changfeng
Published: September 2021

The behavior of nerve cells plays a crucial role in nerve regeneration. The mechanical, topographical, and electrical microenvironment surrounding nerve cells can activate cellular signaling pathways of mechanical transduction to affect the behavior of nerve cells. Recently, biological scaffolds with various physical properties have been developed as extracellular matrix to regulate the behavior conversion of nerve cell, such as neuronal neurite growth and directional differentiation of neural stem cells, providing a robust driving force for nerve regeneration. This review mainly focused on the biological basis of nerve cells in mechanical transduction. In addition, we also highlighted the effect of the physical cues, including stiffness, mechanical tension, two-dimensional terrain, and electrical conductivity, on neurite outgrowth and differentiation of neural stem cells and predicted their potential application in clinical nerve tissue engineering.
The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction
Authors: Kugler Elisabeth C. , Greenwood John , MacDonald Ryan B.
Published: September 2021

The neurovascular unit (NVU) is a complex multi-cellular structure consisting of endothelial cells (ECs), neurons, glia, smooth muscle cells (SMCs), and pericytes. Each component is closely linked to each other, establishing a structural and functional unit, regulating central nervous system (CNS) blood flow and energy metabolism as well as forming the blood-brain barrier (BBB) and inner blood-retina barrier (BRB). As the name suggests, the “neuro” and “vascular” components of the NVU are well recognized and neurovascular coupling is the key function of the NVU. However, the NVU consists of multiple cell types and its functionality goes beyond the resulting neurovascular coupling, with cross-component links of signaling, metabolism, and homeostasis. Within the NVU, glia cells have gained increased attention and it is increasingly clear that they fulfill various multi-level functions in the NVU. Glial dysfunctions were shown to precede neuronal and vascular pathologies suggesting central roles for glia in NVU functionality and pathogenesis of disease. In this review, we take a “glio-centric” view on NVU development and function in the retina and brain, how these change in disease, and how advancing experimental techniques will help us address unanswered questions.
Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma
Authors: Dong Bo , Wu Chunli , Huang Lan , Qi Yu
Published: September 2021

Lymph node metastasis is a major factor that affects prognosis in patients with lung adenocarcinoma (LUAD). In some cases, lymph node metastasis has already occurred when the primary tumors are still small (i.e., early T stages), however, relevant studies on early lymph node metastasis are limited, and effective biomarkers remain lacking. This study aimed to explore new molecular biomarker for early lymph node metastasis in LUAD using transcriptome sequencing and experimental validation. Here, we performed transcriptome sequencing on tissues from 16 matched patients with Stage-T1 LUAD (eight cases of lymph node metastasis and eight cases of non-metastasis), and verified the transcriptome profiles in TCGA, GSE68465, and GSE43580 cohorts. With the bioinformatics analysis, we identified a higher abundance of M0 macrophages in the metastatic group using the CIBERSORT algorithm and immunohistochemistry (IHC) analysis and the enrichment of the epithelial–mesenchymal transition (EMT) pathway was identified in patients with higher M0 infiltration levels. Subsequently, the EMT hallmark gene SPP1, encoding secreted phosphoprotein 1 (SPP1), was identified to be significantly correlated with macrophage infiltration and M2 polarization, and was determined to be a key risk indicator for early lymph node metastasis. Notably, SPP1 in the blood, as detected by enzyme-linked immunosorbent assay (ELISA) showed a superior predictive capability for early lymph node metastasis [area under the curve (AUC) = 0.74]. Furthermore, a long non-coding RNA (lncRNA, AC037441), negatively correlated with SPP1 and macrophage infiltration, had also been identified and validated to be involved in the regulation of early lymph node metastasis. In conclusion, we revealed the potential role of macrophages in lymph node metastasis and identified the macrophage-related gene SPP1 as a potential biomarker for early lymph node metastasis in LUAD.
Large Scale Identification of Osteosarcoma Pathogenic Genes by Multiple Extreme Learning Machine
Authors: Zhao Zhipeng , Shi Jijun , Zhao Guang , Gao Yanjun , Jiang Zhigang , Yuan Fusheng
Published: September 2021

At present, the main treatment methods of osteosarcoma are chemotherapy and surgery. Its 5-year survival rate has not been significantly improved in the past decades. Osteosarcoma has extremely complex multigenomic heterogeneity and lacks universally applicable signal blocking targets. Osteosarcoma is often found in adolescents or children under the age of 20, so it is very important to explore its genetic pathogenic factors. We used known osteosarcoma-related genes and computer algorithms to find more osteosarcoma pathogenic genes, laying the foundation for the treatment of osteosarcoma immune microenvironment-related treatments, so as to carry out further explorations on these genes. It is a traditional method to identify osteosarcoma related genes by collecting clinical samples, measuring gene expressions by RNA-seq technology and comparing differentially expressed gene. The high cost and time consumption make it difficult to carry out research on a large scale. In this paper, we developed a novel method “RELM” which fuses multiple extreme learning machines (ELM) to identify osteosarcoma pathogenic genes. The AUC and AUPR of RELM are 0.91 and 0.88, respectively, in 10-cross validation, which illustrates the reliability of RELM.
Isotope-Dilution Gas Chromatography-Mass Spectrometry Method for the Selective Detection of Nicotine and Menthol in E-Cigarette, or Vaping, Product Liquids and Aerosols
Authors: Pérez José J. , Watson Clifford H. , Blount Benjamin C. , Valentín-Blasini Liza
Published: September 2021

We developed a quantitative method for analyzing nicotine and menthol in e-cigarette, or vaping, products (EVPs). These products may adversely impact health through inhalational exposure to addictive and harmful chemicals. The presence of unknown substances in do-it-yourself e-liquids, counterfeits, or unregulated products may increase exposure to harmful chemicals, as underscored by the 2019 EVP use-associated lung injury (EVALI) outbreak. To minimize these risks, it is important to accurately quantify nicotine and menthol in e-liquids and aerosol emissions to evaluate EVP authenticity, verify product label accuracy, and identify potentially hazardous products. We developed a simple, versatile, high-throughput method using isotope-dilution gas chromatography-mass spectrometry for quantifying nicotine and menthol concentrations in both e-liquid contents and machine-generated aerosol emissions of EVPs. Rigorous validation has demonstrated that the method is specific, precise (CV<2.71%), accurate (percent error ≤7.0%), and robust. Linear calibration ranges from 0.01 to 1.00 mg/ml for both analytes was achieved, corresponding to expected analyte levels in e-liquids and machine-generated EVP aerosols. Limits of detection (LODs) in the final 10-ml sample extract were 0.4 μg/ml for nicotine and 0.2 μg/ml for menthol. The method was used to analyze aerosol emissions of 141 EVPs associated with the 2019 EVALI outbreak; detectable levels of nicotine (2.19–59.5 mg/g of aerosol) and menthol (1.09–10.69 mg/g of aerosol) were observed in 28 and 11%, respectively, of the samples analyzed. Nicotine was not detected in any of the tetrahydrocannabinol (THC), cannabidiol (CBD), or oil-based products, while menthol (2.95 mg/g of aerosol) was only detected in one of these products (THC-labeled). The analytical method can be used to quantify nicotine and menthol concentrations in the e-liquids and aerosols from a range of EVPs, and these findings highlight a difference between e-cigarette and other vaping products.
Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States
Authors: Zhai Yinghong , Ye Xiaofei , Hu Fangyuan , Xu Jinfang , Guo Xiaojing , Cao Yang , Lin Zhen , Zhou Xiang , Guo Zhijian , He Jia
Published: September 2021

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.

Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.

Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.

Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1–Q3: 4–85 days) for ischemic heart disease, with the longest time being 68 days (Q1–Q3: 21–139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).

Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
Trace Element (Fe, Co, Ni and Cu) Dynamics Across the Salinity Gradient in Arctic and Antarctic Glacier Fjords
Authors: Krause Jana , Hopwood Mark J. , Höfer Juan , Krisch Stephan , Achterberg Eric P. , Alarcón Emilio , Carroll Dustin , González Humberto E. , Juul-Pedersen Thomas , Liu Te , Lodeiro Pablo , Meire Lorenz , Rosing Minik T.
Published: September 2021

Around the Greenlandic and Antarctic coastlines, sediment plumes associated with glaciers are significant sources of lithogenic material to the ocean. These plumes contain elevated concentrations of a range of trace metals, especially in particle bound phases, but it is not clear how these particles affect dissolved (<0.2 µm) metal distributions in the ocean. Here we show, using transects in 8 glacier fjords, trends in the distribution of dissolved iron, cobalt, nickel and copper (dFe, dCo, dNi, dCu). Following rapid dFe loss close to glacier outflows, dFe concentrations in particular showed strong similarities between different fjords. Similar dFe concentrations were also observed between seasons/years when Nuup Kangerlua (SW Greenland) was revisited in spring, mid- and late-summer. Dissolved Cu, dCo and dNi concentrations were more variable and showed different gradients with salinity depending on the fjord, season and year. The lack of consistent trends for dCu and dNi largely reflects less pronounced differences contrasting the concentration of inflowing shelf waters with fresher glacially-modified waters. Particles also made only small contributions to total dissolvable Cu (dCu constituted 83 ± 28% of total dissolvable Cu) and Ni (dNi constituted 86 ± 28% of total dissolvable Ni) within glacier plumes. For comparison, dFe was a lower fraction of total dissolvable Fe; 3.5 ± 4.8%. High concentrations of total dissolvable Fe in some inner-fjord environments, up to 77 µM in Ameralik (SW Greenland), may drive enhanced removal of scavenged type elements, such as Co. Further variability may have been driven by local bedrock mineralogy, which could explain high concentrations of dNi (25–29 nM) and dCo (6–7 nM) in one coastal region of west Greenland (Kangaatsiaq). Our results suggest that dissolved trace element distributions in glacier fjords are influenced by a range of factors including: freshwater concentrations, local geology, drawdown by scavenging and primary production, saline inflow, and sediment dynamics. Considering the lack of apparent seasonality in dFe concentrations, we suggest that fluxes of some trace elements may scale proportionately to fjord overturning rather than directly to freshwater discharge flux.
The Opportunities and Challenges of Integrating Population Histories Into Genetic Studies for Diverse Populations: A Motivating Example From Native Hawaiians
Authors: Chiang Charleston W. K.
Published: September 2021

There is a well-recognized need to include diverse populations in genetic studies, but several obstacles continue to be prohibitive, including (but are not limited to) the difficulty of recruiting individuals from diverse populations in large numbers and the lack of representation in available genomic references. These obstacles notwithstanding, studying multiple diverse populations would provide informative, population-specific insights. Using Native Hawaiians as an example of an understudied population with a unique evolutionary history, I will argue that by developing key genomic resources and integrating evolutionary thinking into genetic epidemiology, we will have the opportunity to efficiently advance our knowledge of the genetic risk factors, ameliorate health disparity, and improve healthcare in this underserved population.
Organelle Genome Variation in the Red Algal Genus Ahnfeltia (Florideophyceae)
Authors: Kim Hocheol , Yang Ji Hyun , Bustamante Danilo E. , Calderon Martha S. , Mansilla Andres , Maggs Christine A. , Hansen Gayle I. , Yoon Hwan Su
Published: September 2021

The agarophyte Ahnfeltia (Ahnfeltiales, Rhodophyta) is a globally widespread genus with 11 accepted species names. Two of the most widespread species in this genus, A. plicata and A. fastigiata, may have diverged genetically due to past geographic changes and subsequent geographic isolation. To investigate this genomic and genetic diversity, we generated new plastid (ptDNAs) and mitochondrial genomes (mtDNAs) of these Ahnfeltia species from four different regions (A. plicata - Chile and UK and A. fastigiata - Korea and Oregon). Two architecture variations were found in the Ahnfeltia genomes: in ptDNA of A. fastigiata Oregon, the hypothetical pseudogene region was translocated, likely due to recombination with palindromic repeats or a gene transfer from a red algal plasmid. In mtDNA of A. fastigiata Korea, the composition of the group II intronic ORFs was distinct from others suggesting different scenarios of gain and loss of group II intronic ORFs. These features resulted in genome size differences between the two species. Overall gene contents of organelle genomes of Ahnfeltia were conserved. Phylogenetic analysis using concatenated genes from ptDNAs and mtDNAs supported the monophyly of the Ahnfeltiophycidae. The most probable individual gene trees showed that the Ahnfeltia populations were genetically diversified. These trees, the cox1 haplotype network, and a dN/dS analysis all supported the theory that these Ahnfeltia populations have diversified genetically in accordance with geographic distribution.
Histopathologic Features of Antibody Mediated Rejection: The Banff Classification and Beyond
Authors: Cornell Lynn D.
Published: September 2021

Antibody mediated rejection (ABMR) in the kidney can show a wide range of clinical presentations and histopathologic patterns. The Banff 2019 classification currently recognizes four diagnostic categories: 1. Active ABMR, 2. Chronic active ABMR, 3. Chronic (inactive) ABMR, and 4. C4d staining without evidence of rejection. This categorization is limited in that it does not adequately represent the spectrum of antibody associated injury in allograft, it is based on biopsy findings without incorporating clinical features (e.g., time post-transplant, de novo versus preformed DSA, protocol versus indication biopsy, complement inhibitor drugs), the scoring is not adequately reproducible, and the terminology is confusing. These limitations are particularly relevant in patients undergoing desensitization or positive crossmatch kidney transplantation. In this article, I discuss Banff criteria for these ABMR categories, with a focus on patients with pre-transplant DSA, and offer a framework for considering the continuum of allograft injury associated with donor specific antibody in these patients.
Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome
Authors: Huang Lixing , Qiao Ying , Xu Wei , Gong Linfeng , He Rongchao , Qi Weilu , Gao Qiancheng , Cai Hongyan , Grossart Hans-Peter , Yan Qingpi
Published: September 2021

Fish is considered as a supreme model for clarifying the evolution and regulatory mechanism of vertebrate immunity. However, the knowledge of distinct immune cell populations in fish is still limited, and further development of techniques advancing the identification of fish immune cell populations and their functions are required. Single cell RNA-seq (scRNA-seq) has provided a new approach for effective in-depth identification and characterization of cell subpopulations. Current approaches for scRNA-seq data analysis usually rely on comparison with a reference genome and hence are not suited for samples without any reference genome, which is currently very common in fish research. Here, we present an alternative, i.e. scRNA-seq data analysis with a full-length transcriptome as a reference, and evaluate this approach on samples fromEpinephelus coioides-a teleost without any published genome. We show that it reconstructs well most of the present transcripts in the scRNA-seq data achieving a sensitivity equivalent to approaches relying on genome alignments of related species. Based on cell heterogeneity and known markers, we characterized four cell types: T cells, B cells, monocytes/macrophages (Mo/MΦ) and NCC (non-specific cytotoxic cells). Further analysis indicated the presence of two subsets of Mo/MΦ including M1 and M2 type, as well as four subsets in B cells, i.e. mature B cells, immature B cells, pre B cells and early-pre B cells. Our research will provide new clues for understanding biological characteristics, development and function of immune cell populations of teleost. Furthermore, our approach provides a reliable alternative for scRNA-seq data analysis in teleost for which no reference genome is currently available.
The Era of Antimicrobial Peptides: Use of Hepcidins to Prevent or Treat Bacterial Infections and Iron Disorders
Authors: Barroso Carolina , Carvalho Pedro , Nunes Magda , Gonçalves José F. M. , Rodrigues Pedro N. S. , Neves João V.
Published: September 2021

The current treatments applied in aquaculture to limit disease dissemination are mostly based on the use of antibiotics, either as prophylactic or therapeutic agents, with vaccines being available for a limited number of fish species and pathogens. Antimicrobial peptides are considered as promising novel substances to be used in aquaculture, due to their antimicrobial and immunomodulatory activities. Hepcidin, the major iron metabolism regulator, is found as a single gene in most mammals, but in certain fish species, including the European sea bass (Dicentrarchus labrax), two different hepcidin types are found, with specialized roles: the single type 1 hepcidin is involved in iron homeostasis trough the regulation of ferroportin, the only known iron exporter; and the various type 2 hepcidins present antimicrobial activity against a number of different pathogens. In this study, we tested the administration of sea bass derived hepcidins in models of infection and iron overload. Administration with hamp2 substantially reduced fish mortalities and bacterial loads, presenting itself as a viable alternative to the use of antibiotics. On the other hand, hamp1 seems to attenuate the effects of iron overload. Further studies are necessary to test the potential protective effects of hamp2 against other pathogens, as well as to understand how hamp2 stimulate the inflammatory responses, leading to an increased fish survival upon infection.
Metabolomics of Healthy and Stony Coral Tissue Loss Disease Affected Montastraea cavernosa Corals
Authors: Deutsch Jessica M. , Jaiyesimi Olakunle A. , Pitts Kelly A. , Houk Jay , Ushijima Blake , Walker Brian K. , Paul Valerie J. , Garg Neha
Published: September 2021

Stony coral tissue loss disease, first observed in Florida in 2014, has now spread along the entire Florida Reef Tract and on reefs in many Caribbean countries. The disease affects a variety of coral species with differential outcomes, and in many instances results in whole-colony mortality. We employed untargeted metabolomic profiling ofMontastraea cavernosacorals affected by stony coral tissue loss disease to identify metabolic markers of disease. Herein, extracts from apparently healthy, diseased, and recoveredMontastraea cavernosacollected at a reef site near Ft. Lauderdale, Florida were subjected to liquid-chromatography mass spectrometry-based metabolomics. Unsupervised principal component analysis reveals wide variation in metabolomic profiles of healthy corals of the same species, which differ from diseased corals. Using a combination of supervised and unsupervised data analyses tools, we describe metabolite features that explain variation between the apparently healthy corals, between diseased corals, and between the healthy and the diseased corals. By employing a culture-based approach, we assign sources of a subset of these molecules to the endosymbiotic dinoflagellates, Symbiodiniaceae. Specifically, we identify various endosymbiont- specific lipid classes, such as betaine lipids, glycolipids, and tocopherols, which differentiate samples taken from apparently healthy corals and diseased corals. Given the variation observed in metabolite fingerprints of corals, our data suggests that metabolomics is a viable approach to link metabolite profiles of different coral species with their susceptibility and resilience to numerous coral diseases spreading through reefs worldwide.
Bearing Capacity of Hollow GFRP Pipe-Concrete-High Strength Steel Tube Composite Long Columns Under Eccentrical Compression Load
Authors: Ji Jing , Zeng Wen , Wang Ruili , Ren Hongguo , Zhang Lei , Liu Yuchen , Jiang Liangqin , He Lingjie , Lin Yubo , Yu Chenyu
Published: September 2021

To investigate the bearing capacity of the hollow Glass Fiber Reinforced Polymer (GFRP) pipe-concrete-steel tube composite long columns subjected to eccentrical compression load, 33 hollow GFRP pipe-concrete-steel tube composite long columns have been designed. The slenderness ratio (λ), compressive strength of concrete cube (fcu), eccentricity (e) and so on are the main parameters. Based on constitutive models for steel, GFRP and confined concrete, numerical simulation of the hollow GFRP pipe-concrete-high strength steel tube composite long columns has been carried out by using software ABAQUS. The rationality of the constitutive models and modeling method has been verified by comparing the experimental and simulated load-displacement curves. The influence of different parameters on the mechanical behavior of this kind of column has been investigated. Results show that with the increasing of t1, t2 and fcu, the ultimate eccentrical compression bearing capacity of the specimen increases. With the increasing of e, the ultimate displacement of the specimens increases, while the ultimate eccentrical compression bearing capacity decreases. The eccentricity has a significant influence on the ultimate eccentrical compression bearing capacity. With the increasing of λ, the ultimate eccentrical compression bearing capacity of the specimens gradually decreases. The specimens suffer from ductile failure. The formula of the ultimate eccentrical compression bearing capacity of the composite columns is obtained by statistical regression. The study can provide theoretical support for the application of the composite columns in practical engineering.
A Combination of N-Terminal proB-Type Natriuretic Peptide and Myoglobin Can Predict Severe Complications After Major Non-Cardiac Surgery in Elderly Patients: A Prospective Observational Cohort Study
Authors: Zhao Yi , Hao Xuechao , Zhu Yihao , Chen Mingkai , Ou Mengchan , Zhu Tao
Published: September 2021

Background: Previous studies have demonstrated that serum N-terminal proB-type natriuretic peptide (NT-proBNP) was a predictor of adverse cardiovascular outcomes after surgery. We performed a prospective study to evaluate if NT-proBNP could be a sensitive marker of overall postoperative outcomes in older patients undergoing major elective non-cardiac surgery when combined with myoglobin (MYO).

Methods: Two hundred and three adults aged ≥65 years were enrolled in the study. The American Society of Anesthesiologists (ASA) physical status of patients were I to IV. Blood samples would be taken before and 2 h after the surgery for each patients and NT-proBNP and MYO concentrations (NT-proBNP baseline/ 2 h and MYO baseline/ 2 h) of these samples would be measured immediately. The primary outcome was moderate to severe complications, which were based on the Clavien–Dindo Classification (CDC) scheme (≥CDC grade 3), and the secondary outcomes were major complications within 30 days after surgery. This study was registered at China Clinical Trial Registry (ChiCTR1900026223, http://www.chictr.org.cn/).

Results: Overall, moderate to severe complications occurred in 15 patients (7.4%) and major complications occurred in 18 patients (8.9%). Both preoperative and postoperative NT-proBNP values were independent predictors of moderate to severe complications (area under the curve (AUC), 0.820; 95% CI: 0.728, 0.912, P < 0.001; AUC, 0.785; 95% CI: 0.685, 0.885, P < 0.001). When NT-proBNP baseline and MYO-2 h were combined (NT-proBNP baseline × MYO-2 h), the predictive power was improved (AUC 0.841, 95% CI: 0.758, 0.923, P < 0.001).

Conclusions: A combination of perioperative NT-proBNP and postoperative MYO concentrations was a good predictor of postoperative complications in elderly patients who underwent major non-cardiac surgery. Using fast and dynamic tests provided by point-to-care-testing, NT-proBNP and MYO concentration measurements provided useful guidance for therapy before or soon after surgery, thus helping to reduce postoperative complications in elderly patients.
Effect of Kidney Transplantation on Accelerated Immunosenescence and Vascular Changes Induced by Chronic Kidney Disease
Authors: Ceprian Noemi , Valera Gemma , Caro Jara , Yuste Claudia , Serroukh Nadia , González de Pablos Ignacio , Oliva Carlos , Figuer Andrea , Praga Manuel , Alique Matilde , Ramirez Rafael , Morales Enrique , Carracedo Julia
Published: September 2021

Kidney transplantation is the best option for patients with end-stage renal disease. Despite the improvement in cardiovascular burden (leading cause of mortality among patients with chronic kidney disease), cardiovascular adverse outcomes related to the inflammatory process remain a problem. Thus, the aim of the present study was to characterize the immune profile and microvesicles of patients who underwent transplantation. We investigated the lymphocyte phenotype (CD3, CD4, CD8, CD19, and CD56) and monocyte phenotype (CD14, CD16, CD86, and CD54) in peripheral blood, and endothelium-derived microvesicles (annexin V+CD31+CD41–) in plasma of patients with advanced chronic kidney disease (n = 40), patients with transplantation (n = 40), and healthy subjects (n = 18) recruited from the University Hospital “12 de Octubre” (Madrid, Spain). Patients with kidney transplantation had B-cell lymphopenia, an impairment in co-stimulatory (CD86) and adhesion (CD54) molecules in monocytes, and a reduction in endothelium-derived microvesicles in plasma. The correlations between those parameters explained the modifications in the expression of co-stimulatory and adhesion molecules in monocytes caused by changes in lymphocyte populations, as well as the increase in the levels of endothelial-derived microvesicles in plasma caused by changes in lymphocyte and monocytes populations. Immunosuppressive treatment could directly or indirectly induce those changes. Nevertheless, the particular characteristics of these cells may partly explain the persistence of cardiovascular and renal alterations in patients who underwent transplantation, along with the decrease in arteriosclerotic events compared with advanced chronic kidney disease. In conclusion, the expression of adhesion molecules by monocytes and endothelial-derived microvesicles is related to lymphocyte alterations in patients with kidney transplantation.