bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Faktor Pemberian Imunisasi Rubella di Kelurahan Wakangka Kabupaten Buton
Authors: Andriani Rininta , Wahyuddin Wahyuddin , Darmawan Agus
Published: November 2020

Rubella disease is a contagious disease that can be prevented by immunization. This disease is characterized by the appearance of a rash and mild fever or similar to other viral diseases such as measles and scarlet fever. Rubella is more common in adults than in children. In adults, 70% of cases of rubella disease cause arthritis or atrophy and joint pain. This study aims to determine the relationship of knowledge, attitudes and religion in the administration of rubella immunization in Wakangka Village, Kapontori District. This type of research is quantitative analytic observational approach is a study that explains the relationship between variables through hypothesis testing. The number of samples was 72 people. Samples were taken using simple random sampling technique. Data analysis using univariate and bivariate analysis using chi square test is to see the relationship between variables. The results showed knowledge with a value of p = 0,000 (α <0.05), maternal attitudes with a value of p = 0,000 (α <0.05), and religion with a value of p = 0.995 (α> 0.05). The conclusion in this study is that there is a relationship between knowledge and attitudes with the provision of Rubella Immunization, but there is no relationship between religion and Rubella immunization. It is recommended that people who have children aged 5 months to 15 years be rubella immunized to avoid being recorded.
Apakah Kegel Exercise Berpengaruh terhadap Pengeluaran Urine Ibu Post Partum Pervaginam?
Authors: Ernawati Ernawati , PH Livana
Published: November 2020

The childbirth II causes an excessive emphasis on the pelvic floor muscles, so that the weakness of the pelvic floor muscles occurs and results in a disruption in the urging system. With Kegel exercise techniques that have a function to tighten the pubococcygeus muscles, as a bladder supporter, will reduce the disruption in the system of urging. This study aims to determine the benefits of Kegel exercise on vaginal post partum urine output. Quantitative research with interventional/experimental, urine output dependent variable and Kegel exercise independent variable. After doing research at BPM Farida Gumilir Cilacap the period of December. The results of the study showed that no exercise kegel benefit to the production of urine post a delivery in BPM Farida Gumilir Cilacap. BPM and Puskesmas can make the results of this research as input materials in providing care for the mother of Nifas, to further improve the quality of service and approach to patients maternity, NIFAS and society in general to support the restoration of the condition of the mother Nifas.
Heavy metal resistance in Marinobacter adhaerens HP15 supports colonization of transparent exopolymer particles during its interaction with diatoms
Authors: Will V , Stahl A , Ullrich MS
Published: November 2020

Marine diatoms and heterotrophic bacteria play a crucial role in the oceanic carbon cycle as they form aggregates that sink and transport biomass down in the water column. Polysaccharides are a major component of these aggregates and can bind heavy metal cations. Therefore, both organism groups might also be important for the vertical or micro-scale distribution of heavy metals in the ocean. Our model organism for diatom-bacteria interactions, Marinobacter adhaerens HP15, possesses 2 operons coding for heavy metal efflux pumps of the czcCBA type that are responsible for zinc resistance in this bacterium. The goal of this study was to elucidate the role of zinc resistance in M. adhaerens HP15 during its interaction with the diatom Thalassiosira weissflogii. For this, an HP15 mutant deficient in both czcCBA gene clusters was used in diatom co-cultivation experiments with or without zinc stress. When zinc was added to the co-cultures, the release of Alcian Blue-stainable particles increased 10-fold compared to assays without zinc. Both M. adhaerens HP15 wild-type and ΔczcCBA.1/2 mutant colonized the aggregates, and the percentage of bacteria attaching to transparent exopolymer particles (TEP) increased significantly under zinc stress. In the assays with zinc, HP15 wild-type had a higher cell density inside the aggregates than the mutant, although the zinc concentrations inside TEP were comparable. As TEP can bind and thus enrich heavy metals, resistance against them may help M. adhaerens HP15 to colonize aggregates. These results suggest that heavy metal resistance can be beneficial for bacteria during TEP- and aggregate-associated lifestyles.
Wszystko płynie, czyli o pochodzeniu mieszkańców parafii Wawrzeńczyce / Everything flows, or the origins of the inhabitants of Wawrzeńczyce parish
Authors: Wyżga Mateusz
Published: November 2020

The text introduces the specificity of genealogical research in the context of regional and local histories. The author draws attention to the impermanence of the names of the lower social strata. In addition, the text contains a catalogue of some of the oldest known names of residents of the Wawrzeńczyce, in today’s Kraków district. The realities of life in the Wawrzeńczyce parish in the pre-industrial period, the functioning of social networks, and professional activity are discussed.
Pałacu w Igołomi dzieje najnowsze / The manor house in Igołomia and its later history
Authors: Tunia Krzysztof , Woźny Marzena
Published: November 2020

Architecturally dominating Igołomia village in Kraków district on the Vistula River is a neoclassical manor house with an English-style park surrounding it, erected at the beginning of the 19th century. After several changes of ownership, in 1950 it was taken over by the Polish Academy of Arts and Sciences for the purposes of its Archaeological Museum. For several years, the manor house served as a base for excavation research in Igołomia and the surrounding area, including the production center of “grey ware”, wheel-made pottery of the Roman period, and a project known as the Millennium research, aimed at exploring the beginnings of the Polish state and thus celebrating its 1000-year anniversary. In 1954, the manor house came into the possession of the Institute of the History of Material Culture of the Polish Academy of Sciences (now the Institute of Archaeology and Ethnology of the PAS). After renovation in the 1960s, an Archaeological Laboratory was organised there, which became the basis for ongoing research on the prehistoric settlement of the nearby west Lesser Poland loess upland and archaeological excavations in many other, sometimes distant, areas.
The Inquiries of British Liberals İnto the Destiny of Muslim and Turkish Inhabitants of the Balkans in the Late Nineteenth and Early Twentieth Centuries
Authors: ÇİÇEK Nazan
Published: November 2020

This study delineates the image of Muslims and Turks in Ottoman “European Turkey” as perceived and constructed by the two influential opinion-forming Liberal British periodicals, namely the Contemporary Review and the Fortnightly Review, between the years of 1865-1923. Being a part of the intellectual influence of modern European nationalism repertoire over the Balkans, the convictions of British journal writers indisputably played a crucial role as a source of both inspiration and vindication in the formation and consolidation of Balkan nationalist ideals and practices. By exploring the literary treatment of Muslim and Turkish inhabitants of the Balkans by these prominent British periodicals this study aims to better understand and contextualize the processes of expulsion, assimilation or accommodation that the Muslim and Turkish population faced after the Ottoman power was partly or completely dismantled in the region and was replaced by successor Balkan nation-states which as essentially ethnic polities saw their Muslim minorities as “aliens” and monumental reminders of the “Ottoman yoke”.
Naming an unknown animal: the case of the sloth (Folivora)
Authors: Berrens Dominik
Published: November 2020

The sloth (Folivora) is a mammal from Central and South America that struck the early modern ( c.1500–1800) European naturalists as especially odd. Hence, descriptions and depictions of this animal featured in many texts from this period. Apart from its physiognomy and its behaviour, the naming of the sloth was discussed in detail, and scholars came up with various names and etymologies for the animal. Several European and Amerindian languages were involved in this complex naming process, while Latin played a decisive role as the lingua franca in establishing a scholarly discourse. The paper focuses on written sources from the sixteenth and seventeenth centuries; it tries to reconstruct how the given names and their etymologies were connected to the perceived behaviour and the physiognomy, and what this might tell us about the conceptions behind these. The results are compared to similar findings from anthropology and ethnobiology.
NAZOPALATİN KANAL KİSTLERİ - 3 OLGU SUNUMU VE LİTERATÜR DERLEMESİ
Authors: BOĞAÇ Pembe , ONAY KARAKAŞ Ferah , TOPRAK Mehmet Emin , YENEL Selda
Published: November 2020

Nazopalatin kanal kisti ya da diğer adıyla insiziv kanal kisti, nazopalatin kanalın embriyolojik kalıntılarından meydana gelir. Gelişimsel, epitelyal ve non-odontojenik bir kisttir. Palatinal ön bölgede orta hatta lokalize olup genellikle rutin radyografik muayene sırasında tespit edilir. Bu yazıda kliniğimizde opere edilen üç adet nazopalatin kanal kisti olgusu bildirilmiş ve bu kist tipinin tanı, tedavi ve özellikleriyle ilgili literatür derlemesine yer verilmiştir.
Euthanasia In The Side Of Theological View
Authors: Ming David
Published: November 2020

Everyone can comment on life and death as the saying written by Goerge Arnold, but that does not mean that everyone can comment on living people being invited to be killed. A person's death is not a human right to determine it but God, the Creator and Protector of the whole nature, including humans who have been planned in the line of life and death. Therefore, when euthanasia arises between the medical and legal circles, then this is not something that can be forced to exist, especially as long as it is discussed without having a strong and clear basis. The author will explain what is Euthanasia? The question of Euthanasia's historical problems, the pros and cons of euthanasia, and Euthanasia's theological criticism. The author uses a descriptive method of literature and gets research results as follows: Viewed from the aspect of human rights is a moral breakdown that needs to be evaluated again whether euthanasia is in accordance with human rights values ​​because human rights values ​​essentially deny the existence of euthanasia. Also seen from the religious aspect, euthanasia is never justified. Law 6: "Do not kill" can not be laughed anymore means that refusing euthanasia.
LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2
Authors: Cheng Wenfang , Shi Xiuling , Lin Mingqiang , Yao Qiwei , Ma Jiayu , Li Jiancheng
Published: November 2020

Background

Accumulating evidence has suggested that aberrant expression of long non-coding RNAs (lncRNAs) may contribute to cancer progression in association with radioresistance. The current study aimed to identify the potential role of lncRNA MAGI2-AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells.

Methods and Results

Initially, we detected high expression of HOXB7 from microarray-based gene expression profiling of esophageal cancer. Then, we identified the interactions among MAGI2-AS3, HOXB7, and EZH2 by dual-luciferase reporter gene assay, RNA pull-down assay, RIP assay and ChIP assay. HOXB7 was highly-expressed, while MAGI2-AS3 was poorly-expressed in esophageal cancer tissues and cells. The effect of MAGI2-AS3 and HOXB7 on esophageal cancer cell proliferation and apoptosis as well as tumorigenicity of radioresistant cells was examined by gain- and loss-of-function experiments. Interestingly, MAGI2-AS3 down-regulated HOXB7 through interaction with EZH2, which promoted cell apoptosis and inhibited proliferation and radio-resistance. Besides, down-regulation of MAGI2-AS3 exerted a promoting effect on these malignant phenotypes.

Conclusion

Taken together, our results reveal the potential role of MAGI2-AS3 over-expression in controlling esophageal cancer resistance to radiotherapy by down-regulating HOXB7, this providing a candidate biomarker for resistance to radiotherapy.
Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling
Authors: Zhang Wen-jun , Hu Ce-gui , Luo Hong-liang , Zhu Zheng-ming
Published: November 2020

The pathological mechanism of colon cancer is very complicated. Therefore, exploring the molecular basis of the pathogenesis of colon cancer and finding a new therapeutic target has become an urgent problem to be solved in the treatment of colon cancer. ATP plays an important role in regulating the progression of tumor cells. P2 × 7 belongs to ATP ion channel receptor, which is involved in the progression of tumors. In this study, we explored the effect and molecular mechanism of ATP-mediated P2 × 7 receptor on the migration and metastasis of colon cancer cells. The results showed that ATP and BzATP significantly increased the inward current and intracellular calcium concentration of LOVO and SW480 cells, while the use of antagonists (A438079 and AZD9056) could reverse the above phenomenon. We found that ATP promoted the migration and invasion of LOVO and SW480 cells and is dose-dependent on ATP concentration (100–300 μM). Similarly, BzATP (10, 50, and 100 μM) also significantly promoted the migration and invasion of colon cancer cells in a concentration-dependent manner. While P2 × 7 receptor antagonists [A438079 (10 μM), AZD9056 (10 μM)] or P2 × 7 siRNA could significantly inhibit ATP-induced colon cancer cell migration and invasion. Moreover,in vivoexperiments showed that ATP-induced activation of P2 × 7 receptor promoted the growth of tumors. Furthermore, P2 × 7 receptor activation down-regulated E-cadherin protein expression and up-regulated MMP-2 mRNA and concentration levels. Knocking down the expression of P2 × 7 receptor could significantly inhibit the increase in the expression of N-cadherin, Vimentin, Zeb1, and Snail induced by ATP. In addition, ATP time-dependently induced the activation of STAT3 via the P2 × 7 receptor, and the STAT3 pathway was required for the ATP-mediated invasion and migration. Our conclusion is that ATP-induced P2 × 7 receptor activation promotes the migration and invasion of colon cancer cells, possibly via the activation of STAT3 pathway. Therefore, the P2 × 7 receptor may be a potential target for the treatment of colon cancer.
Organotypic Modeling of the Tumor Landscape
Authors: Haykal Maria M. , Nahmias Clara , Varon Christine , Martin Océane C. B.
Published: November 2020

Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal cells, including endothelial cells, adipocytes, immune and nerve cells, and a stromal compartment composed of extracellular matrix, cancer-associated fibroblasts and mesenchymal cells. Tumorigenesis is a dynamic process with constant interactions occurring between the tumor cells and their surroundings. Even though all connections have not yet been discovered, it is now known that crosstalk between actors of the microenvironment drives cancer progression. Taking into account this complexity, it is important to develop relevant models to study carcinogenesis. Conventional 2D culture models fail to represent the entire tumor microenvironment properly and the use of animal models should be decreased with respect to the 3Rs rule. To this aim,in vitroorganotypic models have been significantly developed these past few years. These models have different levels of complexity and allow the study of tumor cells alone or in interaction with the microenvironment actors during the multiple stages of carcinogenesis. This review depicts recent insights into organotypic modeling of the tumor and its microenvironment all throughout cancer progression. It offers an overview of the crosstalk between epithelial cancer cells and their microenvironment during the different phases of carcinogenesis, from the early cell autonomous events to the late metastatic stages. The advantages of 3D over classical 2D orin vivomodels are presented as well as the most promising organotypic models. A particular focus is made on organotypic models used for studying cancer progression, from the less complex spheroids to the more sophisticated body-on-a-chip. Last but not least, we address the potential benefits of these models in personalized medicine which is undoubtedly a domain paving the path to new hopes in terms of cancer care and cure.
The Crystallinity Control of Polymer Donor Materials for High-Performance Organic Solar Cells
Authors: Qiu Dingding , Adil Muhammad Abdullah , Lu Kun , Wei Zhixiang
Published: November 2020

Bulk heterojunction (BHJ) organic solar cells (OSCs) can be regarded as one of the most promising energy generation technologies for large-scale applications. Despite their several well-known drawbacks, the devices where polymers are employed as the donor are still leading the OSC universe in terms of performance. Such performance generally depends upon various critical factors such as the crystallinity of the material, the crystallization process during the film formation, and also the final film morphology. Despite a few reviews on the structure of the polymer donor materials and device performance, not enough attention has been paid toward the crystallinity problem. Herein, the structure and crystallinity of the representative polymer donor materials and the corresponding device properties have been briefly reviewed. Furthermore, several typical methods for controlling the crystallinity of materials have been summarized and illustrated as well. Moreover, the obstacles lying in the way of successful commercialization of such polymer solar cells have been systematically discussed. The in-depth interpretation of the crystallinity of the polymer donors in this article may stimulate novel ideas in material design and device fabrication.
Microbes in Tumoral In Situ Tissues and in Tumorigenesis
Authors: Feng Xue , Han Lu , Ma Sijia , Zhao Lanbo , Wang Lei , Zhang Kailu , Yin Panyue , Guo Lin , Jing Wei , Li Qiling
Published: November 2020

Cancerous tumors are severe diseases affecting human health that have a complicated etiology and pathogenesis. Microbes have been considered to be related to the development and progression of numerous tumors through various pathogenic mechanisms in recent studies. Bacteria, which have so far remained the most studied microbes worldwide, have four major possible special pathogenic mechanisms (modulation of inflammation, immunity, DNA damage, and metabolism) that are related to carcinogenesis. This review aims to macroscopically summarize and verify the relationships between microbes and tumoral in situ tissues from cancers of four major different systems (urinary, respiratory, digestive, and reproductive); the abovementioned four microbial pathogenic mechanisms, as well as some synergistic pathogenic mechanisms, are also discussed. Once the etiologic role of microbes and their precise pathogenic mechanisms in carcinogenesis are known, the early prevention, diagnosis, and treatment of cancers would progress significantly.
Land-Use Changes and the Effects of Oil Palm Expansion on a Peatland in Southern Thailand
Authors: Srisunthon Prapawadee , Chawchai Sakonvan
Published: November 2020

Tropical peatlands are one of the largest reservoirs of terrestrial organic carbon. However, present-day tropical peat swamp forests are under threat by anthropogenic disturbances and have already been widely degraded. Anthropogenic pressures on peatland ecosystems have resulted in ecological and biogeochemical changes and the release of carbon to the atmosphere. In Southeast Asia, the conversion of peatlands to oil palm plantations has accelerated significantly during the last 2 decades. This research analyzed direct and indirect land-use changes (DLUC and ILUC) that have been associated with oil palm expansion and anthropogenic impacts in the Princess Sirindhorn Wildlife Sanctuary (PSWS), Narathiwat, southern Thailand. Our analysis is based on land-use and land-cover data of the Land Development of Thailand from two different periods: 2000–2009 and 2009–2016. For the purpose of comparison, the data were reclassified into 12 types of land use: oil palm, para rubber, paddy field, abandoned paddy field, orchard, other agriculture lands, wetlands and peatlands, mangrove, evergreen forest, water area, build-up area, and unused area. In addition, the area of net change due to DLUC and ILUC was calculated, and carbon stock changes were estimated from above- and below-ground biomass and soil organic carbon. The results show that the total oil palm plantation area has increased from 0.04% in 2000 to 6.84% in 2016, because of a Thai government policy promoting the use of biodiesel and increasing capacity of palm oil production in 2005. Paddy field, evergreen forest, wetlands, and peatlands were the main areas being replaced. The clearance of natural forest greatly increased in the period of 2000–2009. The ILUC indicates that the expansion of oil palm plantations invades other croplands (paddy field, para rubber, and orchard). The results demonstrate that the conversion of natural landscapes (evergreen forest, mangrove, wetlands, and peatlands) to oil palm plantations at Princess Sirindhorn Wildlife Sanctuary area had a negative effect, with carbon stock changes of 4 million Mg C during 2000–2016 (0.25 million Mg C/year). Given the significance of carbon stock changes arising from land-use changes, this research highlights the need for sustainable land-use management and long-term monitoring.
Cardiometabolic Risk in First Episode Psychosis Patients
Authors: Smith Jo , Griffiths Lisa A. , Band Marie , Horne Dominic
Published: November 2020

Previous research in patients with schizophrenia in European and USA population groups has demonstrated a high prevalence of metabolic syndrome and disease progression (~35%–40%) and increased risk for cardiovascular disease and long-term mortality. Limited research has determined the prevalence of existing cardiometabolic risk factors at onset of a first episode psychosis. This cross-sectional study presents a clinical overview of the cardiometabolic risk profile in young people with first episode psychosis in the UK. Forty-six participants (72% male) clinically diagnosed with first episode psychosis (n = 25), schizophrenia (n = 13), bipolar disorder (n = 4), unspecified non-organic psychosis (n = 2) or acute psychotic episode (n = 2) with < 6 months Duration of Untreated Psychosis (DUP; mean 33.4 ± 37.2 days) were assessed for anthropometric, health risk behaviors and clinical measurements including resting heart rate, blood pressure, blood lipids, glycated hemoglobin, and prolactin. Overall, participants (aged 18–37 years) had a high prevalence of cardiometabolic risk factors due to: elevated values for BMI (73%) and abdominal adiposity (50%), blood pressure (47% prehypertensive; 23% hypertensive), resting heart rate (43%); hypercholesterolemia (32%); suboptimal HDL-C levels (36%); and hypertriglyceridemia (40%). Participants also self-reported poor health risk habits including smoking (55%), alcohol use (39%), substance use (18%), poor diet (52%), and sedentary behavior (29%). Young people with psychosis are at increased risk for cardiometabolic disorders due to elevated clinical markers and health risk behaviors. Physical health interventions (including health behavior advice) are needed early in the treatment process to address this increased risk for cardiometabolic disorders in individuals recently diagnosed with psychosis.
A Review of Proton Conductivity in Cellulosic Materials
Authors: Selyanchyn Olena , Selyanchyn Roman , Lyth Stephen M.
Published: November 2020

Cellulose is derived from biomass and is useful in a wide range of applications across society, most notably in paper and cardboard. Nanocellulose is a relatively newly discovered variant of cellulose with much smaller fibril size, leading to unique properties such as high mechanical strength. Meanwhile, electrochemical energy conversion in fuel cells will be a key technology in the development of the hydrogen economy, but new lower cost proton exchange membrane (PEM) materials are needed. Nanocellulose has emerged as a potential candidate for this important application. In this review we summarize scientific developments in the area of cellulosic materials with special emphasis on the proton conductivity, which is the most important parameter for application in PEMs. We cover conventional cellulose and nanostructured cellulose materials, polymer composites or blends, and chemically modified cellulose. These developments are critically reviewed, and we identify interesting trends in the literature data. Finally, we speculate on future directions for this field.
First Spatial Distribution Analysis of Male Sea Turtles in the Southern Gulf of Mexico
Authors: Cuevas Eduardo , Putman Nathan F. , Uribe-Martínez Abigail , López-Castro Melania C. , Guzmán-Hernández Vicente , Gallegos-Fernández Sandra A. , Liceaga-Correa María de los Ángeles , Trujillo-Córdova Jorge A. , González-Díaz-Mirón Raúl de Jesús , Negrete-Phillipe Ana , Acosta-Sánchez Héctor H. , Martínez-Portugal Rosa C. , López-Hernández Martha , Huerta-Rodríguez Patricia , Silver Jim
Published: November 2020

In the Gulf of Mexico, the bulk of published studies for sea turtles have focused on northern (United States) waters where economic resources are centered, with fewer studies in the southern portion of the basin, resulting in significant knowledge gaps in these underrepresented areas. Similarly, publications on adult sea turtles are dominated by research on females that come ashore to nest and can be readily studied (e.g., through the collection of biological samples and the application of satellite-telemetry devices), whereas information on adult male sea turtles is scarce. The goal of this paper is to begin filling these knowledge gaps by synthesizing available data on adult male sea turtles in the southern Gulf of Mexico. We used satellite-telemetry, boat- and drone-based surveys, and stranding records combined with ocean circulation modeling to better understand the spatial distribution of male loggerhead (Caretta caretta), green (Chelonia mydas), hawksbill (Eretmochelys imbricata), and Kemp’s ridley (Lepidochelys kempii) sea turtles in the southern Gulf of Mexico. These spatially explicit analyses will provide context for opportunistically collected data on male sea turtles and better contribute to the management and restoration of sea turtle populations that use the Gulf of Mexico. Moreover, this synthesis can serve as a launching point for directed studies on male sea turtles in this region.
Emerging Molecular Targets for the Treatment of Refractory Sarcoidosis
Authors: Boleto Gonçalo , Vieira Matheus , Desbois Anne Claire , Saadoun David , Cacoub Patrice
Published: November 2020

Sarcoidosis is a multisystem granulomatous disease of unknown origin that has variable clinical course and can affect nearly any organ. It has a chronic course in about 25% of patients. Corticosteroids (CS) are the cornerstone of therapy but their long-term use is associated with cumulative toxicity. Commonly used CS-sparing agents include methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil. Twenty to forty percentage of sarcoidosis patients are refractory to these therapies or develop severe adverse events. Therefore, additional and targeted CS-sparing agents are needed for chronic sarcoidosis. Macrophage activation, interferon response, and formation of the granuloma are mainly mediated by T helper-1 responses. Different pro-inflammatory cytokines such as interleukin (IL)-8, IL-12, IL-6, and tumor necrosis factor-alpha (TNF-α) have been shown to be highly expressed in sarcoidosis-affected tissues. As a result of increased production of these cytokines, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is constitutively active in sarcoidosis. Several studies of biological agents that target TNF-α have reported their efficacy and appear today as a second line option in refractory sarcoidosis. Some case series report a positive effect of tocilizumab an anti-IL-6 monoclonal antibody in this setting. More recently, JAK inhibition appears as a new promising strategy. This review highlights key advances on the management of chronic refractory sarcoidosis. Novel therapeutic strategies and treatment agents to manage the disease are described.
Identification of a Stable Hydrogen-Driven Microbiome in a Highly Radioactive Storage Facility on the Sellafield Site
Authors: Ruiz-Lopez Sharon , Foster Lynn , Boothman Chris , Cole Nick , Morris Katherine , Lloyd Jonathan R.
Published: November 2020

The use of nuclear power has been a significant part of the United Kingdom’s energy portfolio with the Sellafield site being used for power production and more recently reprocessing and decommissioning of spent nuclear fuel activities. Before being reprocessed, spent nuclear fuel is stored in water ponds with significant levels of background radioactivity and in high alkalinity (to minimize fuel corrosion). Despite these challenging conditions, the presence of microbial communities has been detected. To gain further insight into the microbial communities present in extreme environments, an indoor, hyper-alkaline, oligotrophic, and radioactive spent fuel storage pond (INP) located on the Sellafield site was analyzed. Water samples were collected from sample points within the INP complex, and also the purge water feeding tank (FT) that supplies water to the pond, and were screened for the presence of the 16S and 18S rRNA genes to inform sequencing requirements over a period of 30 months. Only 16S rRNA genes were successfully amplified for sequencing, suggesting that the microbial communities in the INP were dominated by prokaryotes. Quantitative Polymerase Chain Reaction (qPCR) analysis targeting 16S rRNA genes suggested that bacterial cells in the order of 104–106 mL–1 were present in the samples, with loadings rising with time. Next generation Illumina MiSeq sequencing was performed to identify the dominant microorganisms at eight sampling times. The 16S rRNA gene sequence analysis suggested that 70% and 91% from of the OTUs samples, from the FT and INP respectively, belonged to the phylum Proteobacteria, mainly from the alpha and beta subclasses. The remaining OTUs were assigned primarily to the phyla Acidobacteria, Bacteroidetes, and, Cyanobacteria. Overall the most abundant genera identified were Hydrogenophaga, Curvibacter, Porphyrobacter, Rhodoferax, Polaromonas, Sediminibacterium, Roseococcus, and Sphingomonas. The presence of organisms most closely related to Hydrogenophaga species in the INP areas, suggests the metabolism of hydrogen as an energy source, most likely linked to hydrolysis of water caused by the stored fuel. Isolation of axenic cultures using a range of minimal and rich media was also attempted, but only relatively minor components (from the phylum Bacteroidetes) of the pond water communities were obtained, emphasizing the importance of DNA-based, not culture-dependent techniques, for assessing the microbiome of nuclear facilities.
Effects of Bacterial Supplementation on Black Soldier Fly Growth and Development at Benchtop and Industrial Scale
Authors: Kooienga Emilia M. , Baugher Courtney , Currin Morgan , Tomberlin Jeffery K. , Jordan Heather R.
Published: November 2020

Historically, research examining the use of microbes as a means to optimize black soldier fly (BSF) growth has explored few taxa. Furthermore, previous research has been done at the benchtop scale, and extrapolating these numbers to industrial scale is questionable. The objectives of this study were to explore the impact of microbes as supplements in larval diets on growth and production of the BSF. Three experiments were conducted to measure the impact of the following on BSF life-history traits on (1) Arthrobacter AK19 supplementation at benchtop scale, (2) Bifidobacterium breve supplementation at benchtop scale, and (3) Arthrobacter AK19 and Rhodococcus rhodochrous 21198 as separate supplements at an industrial scale. Maximum weight, time to maximum weight, growth rate, conversion level of diet to insect biomass, and associated microbial community structure and function were assessed for treatments in comparison to a control. Supplementation with Arthrobacter AK19 at benchtop scale enhanced growth rate by double at select time points and waste conversion by approximately 25–30% with no impact on the microbial community. Predicted gene expression in microbes from Arthrobacter AK19 treatment was enriched for functions involved in protein digestion and absorption. Bifidobacterium breve, on the other hand, had the inverse effect with larvae being 50% less in final weight, experiencing 20% less conversion, and experienced suppression of microbial community diversity. For those tested at the industrial scale, Arthrobacter AK19 and R. rhodochrous 21198 did not impact larval growth differently as both resulted in approximately 22% or more greater growth than those in the control. Waste conversion with the bacteria was similar to that recorded for the control. Diets treated with the supplemental bacteria showed increased percent difference in predicted genes compared to control samples for functions involved in nutritional assimilation (e.g., protein digestion and absorption, energy metabolism, lipid metabolism). Through these studies, it was demonstrated that benchtop and industrial scale results can differ. Furthermore, select microbes can be used at an industrial scale for optimizing BSF larval production and waste conversion, while others cannot. Thus, targeted microbes for such practices should be evaluated prior to implementation.
NGS-Based S. aureus Typing and Outbreak Analysis in Clinical Microbiology Laboratories: Lessons Learned From a Swiss-Wide Proficiency Test
Authors: Dylus David , Pillonel Trestan , Opota Onya , Wüthrich Daniel , Seth-Smith Helena M. B. , Egli Adrian , Leo Stefano , Lazarevic Vladimir , Schrenzel Jacques , Laurent Sacha , Bertelli Claire , Blanc Dominique S. , Neuenschwander Stefan , Ramette Alban , Falquet Laurent , Imkamp Frank , Keller Peter M. , Kahles Andre , Oberhaensli Simone , Barbié Valérie , Dessimoz Christophe , Greub Gilbert , Lebrand Aitana
Published: November 2020

Whole genome sequencing (WGS) enables high resolution typing of bacteria up to the single nucleotide polymorphism (SNP) level. WGS is used in clinical microbiology laboratories for infection control, molecular surveillance and outbreak analyses. Given the large palette of WGS reagents and bioinformatics tools, the Swiss clinical bacteriology community decided to conduct a ring trial (RT) to foster harmonization of NGS-based bacterial typing. The RT aimed at assessing methicillin-susceptible Staphylococcus aureus strain relatedness from WGS and epidemiological data. The RT was designed to disentangle the variability arising from differences in sample preparation, SNP calling and phylogenetic methods. Nine laboratories participated. The resulting phylogenetic tree and cluster identification were highly reproducible across the laboratories. Cluster interpretation was, however, more laboratory dependent, suggesting that an increased sharing of expertise across laboratories would contribute to further harmonization of practices. More detailed bioinformatic analyses unveiled that while similar clusters were found across laboratories, these were actually based on different sets of SNPs, differentially retained after sample preparation and SNP calling procedures. Despite this, the observed number of SNP differences between pairs of strains, an important criterion to determine strain relatedness given epidemiological information, was similar across pipelines for closely related strains when restricting SNP calls to a common core genome defined by S. aureus cgMLST schema. The lessons learned from this pilot study will serve the implementation of larger-scale RT, as a mean to have regular external quality assessments for laboratories performing WGS analyses in a clinical setting.
Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibodies in Egyptian Convalescent Plasma Donors
Authors: Gomaa Mokhtar R. , Kandeil Ahmed , Mostafa Ahmed , Roshdy Wael H. , Kayed Ahmed E. , Shehata Mahmoud , Kutkat Omnia , Moatasim Yassmin , El Taweel Ahmed , Mahmoud Sara H. , Kamel Mina Nabil , Abo Shama Noura M. , El Sayes Mohamed , El-Shesheny Rabeh , Bakheet Osama H. , Elgohary Mohamed A. , Elbadry Mohamed , Nassif Naguib N. , Ahmed Salwa H. , Abdel Messih Ibrahim Y. , Kayali Ghazi , Ali Mohamed A.
Published: November 2020

Using convalescent plasma as immunotherapy is an old method for treatment of infectious diseases. Several countries have recently allowed the use of such therapy for the treatment of COVID-19 patients especially those who are critically ill. A similar program is currently being tested in Egypt. Here, we tested 227 plasma samples from convalescent donors in Egypt for neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a microneutralization (MN) assay. A third of the tested samples did not have antibody titers and 58% had titers between 1:10 and 1:80. Only 12% had titers >1:160. We also compared MN assays using different virus concentrations, plaque reduction neutralization (PRNT) assays, and a chemiluminescence assay that measures immunoglobulin G (IgG) binding to N and S proteins of SARS-CoV-2. Our results indicated that a MN assay using 100 TCID50/ml provides comparable results to PRNT and allows for high throughput testing.
LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p
Authors: Bu Lu-Lu , Xie Ying-Yu , Lin Dan-Yu , Chen Ying , Jing Xiu-Na , Liang Yan-Ran , Peng Su-Dan , Huang Kai-Xun , Tao En-Xiang
Published: November 2020

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD. Our previous study found that exogenous α-Syn induced the downregulation of lncRNA-T199678 in SH-SY5Y cells via a gene microarray analysis. This finding suggested that lncRNA-T199678 might have a potential pathological role in the pathogenesis of PD. This study aimed to explore the influence of lncRNA-T199678 on α-Syn-induced dopaminergic neuron injury. Overexpression of lncRNA-T199678 ameliorated the neuron injury induced by α-Syn via regulating oxidative stress, cell cycle, and apoptosis. Studies indicate lncRNAs could regulate posttranscriptional gene expression via regulating the downstream microRNA (miRNA). To discover the downstream molecular target of lncRNA-T199678, the following experiment found out that miR-101-3p was a potential target for lncRNA-T199678. Further study showed that the upregulation of lncRNA-T199678 reduced α-Syn-induced neuronal damage through miR-101-3p in SH-SY5Y cells and lncRNA-T199678 was responsible for the α-Syn-induced intracellular oxidative stress, dysfunction of the cell cycle, and apoptosis. All in all, lncRNA-T199678 mitigated the α-Syn-induced dopaminergic neuron injury via targeting miR-101-3p, which contributed to promote PD. Our results highlighted the role of lncRNA-T199678 in mitigating dopaminergic neuron injury in PD and revealed a new molecular target for PD.
Escalate and De-Escalate Therapies for Intracranial Pressure Control in Traumatic Brain Injury
Authors: Battaglini Denise , Anania Pasquale , Rocco Patricia R. M. , Brunetti Iole , Prior Alessandro , Zona Gianluigi , Pelosi Paolo , Fiaschi Pietro
Published: November 2020

Severe traumatic brain injury (TBI) is frequently associated with an elevation of intracranial pressure (ICP), followed by cerebral perfusion pressure (CPP) reduction. Invasive monitoring of ICP is recommended to guide a step-by-step “staircase approach” which aims to normalize ICP values and reduce the risks of secondary damage. However, if such monitoring is not available clinical examination and radiological criteria should be used. A major concern is how to taper the therapies employed for ICP control. The aim of this manuscript is to review the criteria for escalating and withdrawing therapies in TBI patients. Each step of the staircase approach carries a risk of adverse effects related to the duration of treatment. Tapering of barbiturates should start once ICP control has been achieved for at least 24 h, although a period of 2–12 days is often required. Administration of hyperosmolar fluids should be avoided if ICP is normal. Sedation should be reduced after at least 24 h of controlled ICP to allow neurological examination. Removal of invasive ICP monitoring is suggested after 72 h of normal ICP. For patients who have undergone surgical decompression, cranioplasty represents the final step, and an earlier cranioplasty (15–90 days after decompression) seems to reduce the rate of infection, seizures, and hydrocephalus.
Neurological Associations of COVID-19—Do We Know Enough: A Tertiary Care Hospital Based Study
Authors: Kushwaha Suman , Seth Vaibhav , Bapat Prateek , R KiranGowda , Chaturvedi Monali , Gupta Renu , Bhattar Sonali , Maheshwari Siddharth , Anthony Aldrin
Published: November 2020

The neurotrophic potential of SARS-CoV-2 virus is manifesting as various neurological disorders in the present pandemic. Nervous system involvement can be due to the direct action of the virus on the brain tissue or due to an indirect action through the activation of immune-mediated mechanisms. This study will discuss the detailed systematically evaluated clinical profile and relevant investigations and outcome of 14 laboratory confirmed SARS-CoV-2 positive patients presenting with neurological signs and symptoms. The patients were further categorized into confirmed, probable, and possible neurological associations. The probable association was found in meningoencephalitis (n = 4), stroke (n = 2), Guillain-Barré syndrome (n = 1), and anosmia (n = 1). The other six patients had coexisting neurological diseases with SARS-CoV-2. One patient with a large artery stroke succumbed to the illness due to respiratory complication. Memory impairment as a sequela is present during follow up of one encephalitis patient. Presently the early recognition and diagnosis of neurological manifestations remains a challenge for clinicians as the SARS-CoV-2 related neurological manifestations are in evolution. A long-term correlation study of clinical profile, radiological and laboratory investigations, along with neuropathological studies is needed to further understand the pathophysiology behind the SARS-CoV-2 neurological manifestations. Further understanding will facilitate timely recognition, therapeutic intervention, and possible prevention of long-term sequalae.
Screening for Fabry Disease in Young Strokes in the Australian Stroke Clinical Registry (AuSCR)
Authors: Malavera Alejandra , Cadilhac Dominique A. , Thijs Vincent , Lim Joyce Y. , Grabsch Brenda , Breen Sibilah , Jan Stephen , Anderson Craig S.
Published: November 2020

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficiency or absence of alpha-galactosidase A (α-GAL A) enzyme, where stroke can be a serious complication. The aim of this study is to determine the feasibility of centralized screening for FD, among young stroke adults registered in the national Australian Stroke Clinical Registry (AuSCR).

Methods: The study was conducted in young (age 18 – 55 years) survivors of acute stroke of unknown etiology registered in AuSCR at hospitals in Queensland, Tasmania, New South Wales, and Victoria during 2014 – 2015; and who, at the 3-month outcome assessment, agreed to be re-contacted for future research. Descriptive analyses of case identification from responses and specific enzyme and DNA sequencing analyses were conducted for α-galactosidase A (α-GLA) from dried blood spot (DBS) testing.

Results: Of 326 AuSCR-identified patients invited to participate, 58 (18%) provided consent but six were subsequently unable to provide a blood sample and two later withdrew consent to use their data. Among the remaining 50 participants (median age 53 years [48 – 56 years]; 47% female), 67% had experienced an acute ischemic stroke. All males (n = 27) had an initial screen for α-GLA enzyme activity of whom seven with low enzyme levels had normal secondary α-GLA gene analysis. All females (n = 23) had genetic analysis, with one shown to have a pathogenic c.352C>T p.(Arg118Cys) missense mutation of the α-GLA gene for FD.

Conclusions: These findings provide logistical data for embedding a process of automated central stroke registry screening for an additional case-finding tool in FD.
The ADNP Syndrome and CP201 (NAP) Potential and Hope
Authors: Gozes Illana
Published: November 2020

Activity-dependent neuroprotective protein (ADNP) syndrome, also known as Helsmoortel-Van Der Aa syndrome, is a rare condition, which is diagnosed in children exhibiting signs of autism. Specifically, the disease is suspected when a child is suffering from developmental delay and/or intellectual disability. The syndrome occurs when one of the two copies of the ADNP gene carries a pathogenic sequence variant, mostly a de novo mutation resulting in loss of normal functions. Original data showed that Adnp+/− mice suffer from learning and memory deficiencies, muscle weakness, and communication problems. Further studies showed that the ADNP microtubule-interacting fragment NAP (called here CP201) resolves, in part, Adnp deficiencies and protects against ADNP pathogenic sequence variant abnormalities. With a clean toxicology and positive human adult experience, CP201 is planned for future clinical trials in the ADNP syndrome.
On the Relationship Between White Matter Structure and Subjective Pain. Lessons From an Acute Surgical Pain Model
Authors: Torrecillas-Martínez Laura , Catena Andrés , O'Valle Francisco , Solano-Galvis César , Padial-Molina Miguel , Galindo-Moreno Pablo
Published: November 2020

Background: Pain has been associated with structural changes of the brain. However, evidence regarding white matter changes in response to acute pain protocols is still scarce. In the present study, we assess the existence of differences in brain white matter related to pain intensity reported by patients undergoing surgical removal of a mandibular impacted third molar using diffusion tensor imaging (DTI) analysis.

Methods: 30 participants reported their subjective pain using a visual analog scale at three postsurgical stages: under anesthesia, in pain, and after the administration of an analgesic. The diffusion data were acquired prior to surgery.

Results: DTI analysis yielded significant positive associations of fractional anisotropy in white matter areas related to pain processing (corticospinal tract, corona radiata, corpus callosum) with the differences in pain between the three postsurgery stages. Extent and location of these associations depended on the magnitude of the subjective pain differences. Tractography analysis indicated that some pain–tract associations are significant only when pain stage is involved in the contrast (posterior corona radiata), while others (middle cerebellar peduncle, pontine crossing) are only when anesthesia is involved in the contrast.

Conclusions: The association of white matter fractional anisotropy and connectivity, measured before the pain stages, with subjective pain depends on the magnitude of the differences in pain scores.