bluuebunny/crossref_metadata_2025 huggingface dataset:
Avaliação do estado nutricional de adultos acompanhados pelo sistema de vigilância alimentar e nutricional entre os anos de 2009 e 2019
Authors: Soares Tamires da Cunha , Vilarinho Maria de Fátima Sousa Barros , Dias Thaline Milany da Silva , Chaves Wenicios Ferreira , Soares Ticianne da Cunha , Lima Vanessa Moreira de , Cardoso Bruna Emanuele Pereira , Câmara Gabriel Barbosa , Martins Victor Brito Dantas , Silva Franciely Alves da
Published: March 2021

A modificação do padrão econômico em todo o mundo tem sido associada à transição nutricional. Nesse cenário, percebe-se a necessidade de monitoramento regular do estado nutricional da população. Avaliar o estado nutricional de adultos acompanhados pelo Sistema de Vigilância Alimentar e Nutricional (SISVAN) entre os anos de 2009 e 2019. Materiais e Método: Estudo epidemiológico com coleta de dados secundários provenientes do SISVAN Web. As variáveis consideradas neste estudo foram sexo masculino e feminino, faixa etária entre 20 e 60 anos e estado nutricional de indivíduos em todo o Brasil. O número de adultos acompanhados pelo SISVAN no período estudado foi de 9.962.669. No sexo feminino, o baixo peso, bem como os três extratos da obesidade, foram mais prevalentes em 2009 e menos em 2019, a maior porcentagem de eutrofia ocorreu em 2009 e a menor em 2016, o sobrepeso esteve mais presente em 2015 e menos em 2009. No sexo masculino, menor e maior prevalência de baixo peso ocorreu em 2018 e 2014, respectivamente. O estado de eutrofia foi percebida em 2009 e menos em 2016, o sobrepeso obteve maior porcentagem em 2019 e em menor em 2009. Quanto aos três níveis de obesidade, percebeu-se maior porcentagem em 2016 e menor em 2009. Não houve diferença estatística entre os sexos e ao longo dos anos. Percebeu-se crescimento do sobrepeso e obesidade, em detrimento do baixo peso e eutrofia nessa população. Esses achados demonstram a necessidade da implementação de políticas públicas de incentivo à alimentação saudável.
Peningkatan Produktivitas Ramuan Herbal Di Kelurahan Gadel Kecamatan Tandes Kota Surabaya Dengan Penerapan Manajemen Produksi Administrasi Dan Pemasaran
Authors: Yanto Erwan Arist , Ermawati Yuli , Nanda Aditya Surya
Published: March 2021

Ditengah merebaknya Covid â€“ 19 atau virus Corona berbagai produk herbal laris manis di pasaran tak terkecuali produk UMKMÂ  minuman ramuan herbal tradisional ikut terdongkrak. Momentum ini harus di manfaat sebaik mungkin oleh pelaku usaha. Mitra kami adalah Ibu Sunarti yang lebih dikenal dengan panggilan Bu Yanto, berdomisili di Kelurahan Gadel, Kecamatan Tandes, Kota Surabaya. Beliau menitipkan ramuan herbalnya di toko â€“ toko kelontongÂ Â  sekitar yang memiliki lemari pendingin. Karena keterbatasan ramuan herbal yang hanya menjual produk sinom, keterbatasan administrasi pembukuan, keterbatasan IPTEK dan permodalan membuat ibu Sunarti tidak berani memperluas pasar. Padahal semangat dan potensi produk ramuan herbal sangat menjanjikan. Solusi yang di berikan yang pertama yaitu dengan melakukan uji coba penambahan varian produk. Kedua, memberikan pendampingan dan pelatihan manajemen keuangan dan usaha, Ketiga, memberikan pendampingan dan pelatihan manajemen pemasaran, baik secara offline ( pelabelan, brosur, kartu nama dan konsinyasi ) maupun online ( sosial media, marketplace ) untuk meningkatkan jangkauan pasar. Metode yang di gunakan adalah pendampingan personal terhadap mitra. Rencana yang akan dilakukan oleh tim adalah dengan memberikan pelatihan untuk manajemen usaha mereka ( mulai dari proses pengelolaan produksi, pembukuan sederhana,Â  pemasaran efektif dan inspirasi pengusaha sukses ) dengan mendatangkan para pakar yang kompeten untuk mendongkrak usaha mereka. Setelah itu tim akan mengawal mitra untuk membuat label yang modern dan menarik dengan merek yang mereka ciptakan. Kemudian mendampingi mitra dalam memasarkan produk secara offline dan online agar jangkauan pasar lebih luas. Dengan begitu diharapkan pendapatan dan kesejahteraan mitra akan meningkat.Â Â Â
Pelatihan Kejuruan Pengolahan Hasil Pertanian Balai Latihan Kerja Sorong
Authors: Zain Evi Mufrihah , Andjar Febry Jein , Devi Devi
Published: March 2021

Penelitian ini bertujuan untuk mempelajari bagaimana caraÂ  memanfaatkan sumberdaya alam untuk dihasilkan menjadi bahan pangan, mengolah bahan mentah menjadi berbagai macam produk yang bermanfaat dan untuk meningkatkan dampak perekonomian masyarakat, Penelitian iniÂ  menggunakan beberapa metode pendekatan yaitu pelatihan dan penyuluhan yang dilakukan di Balai Latihan Kerja Sorong. Pada umumnya masyarakat selalu menginginkanÂ  sesuatu yang berbeda, tidak terkecuali dengan hal kuliner atau makanan. Hasil olahan labu kuning dapat di olah menjadi beberapa makanan yaitu cake labu kuning , kue lumpur labu kuning , puding labu kuning ,karena di kota sorong sendiri pengolahan labu kuning biasanya hanya sebagai sayuran. Kesimpulannya melalui kegiatan pelatihan pengolahan labu kuning dapat menciptakan berbagai makanan yang mempunyai banyak varian yang dapat dikonsumsi. Â
Influencia de la interacción dinámica suelo-estructura en el mecanismo de colapso y nivel de desempeño de edificaciones de hormigón armado.
Authors: Corratgé Yzaguirre Zenayda , Martínez Cid Janet Otmara , Cobelo Cristiá Willian
Published: March 2021

En el presente artículo se analiza la influencia de la consideración de la interacción dinámica suelo-estructura (IDSE) en el comportamiento estructural de una edificación de diez niveles de hormigón armado con tipología mixta sometida a carga sísmica. Para ello se implementó el método estático no lineal push-over mediante el software ETABS V17. La IDSE es incorporada a través de los modelos de Pais & Kausel y Sargsian, considerándose las características de dos tipos de suelos: rígido y arcilla blanda contemplados en la NC 46:2017 [1]. Como principales resultados se observa, al incluir la IDSE, un aumento en los valores de desplazamiento en el tope de la edificación y de derivas por piso y una disminución de los valores de cortante basal para los cuales se alcanzan la fluencia global de la estructura y el mecanismo de colapso respectivamente. Adicionalmente, el nivel de desempeño de esta se aleja de lo recomendado por las normas.
Andrei Sakharov’s research work and modern physics
Authors: Altshuler B L
Published: March 2021

We follow the work carried out by Andrei Sakharov in both research and engineering, from the first domestic thermonuclear charges to fundamental physics. We emphasize the current status of the research fields recognized to have originated in Sakharov’s work: controlled fusion, magnetic cumulation and magnetic explosion generators, induced gravity, cosmological ‘Sakharov’ (baryonic acoustic) oscillations, and baryon asymmetry of the Universe. Another subject that unexpectedly gained momentum in the 21st century is the model of a pulsating universe, which was among Sakharov’s ideas. Other subjects that were dear to him, such as quantum cosmology and the anthropic principle, are also currently at the forefront of science.
Exogenous application of potassium improves the drought tolerance in chickpea
Authors: Sattar Abdul , Sher Ahmad , Ijaz Muhammad , Kashif Muhammad , Suleman Muhammad , Ali Muhammad Usman , Abbas Aown , Mahboob Asif
Published: March 2021

Drought is one of the major agricultural problems which cause losses to crop productivity. It is a worldwide problem and prevails in many parts of the world as a major threat to agriculture. Potassium (K) is considered to be an essential nutrient that plays an important role in growth, development and defense response in the plant under stressful conditions. This work investigated the effects of K in drought tolerance of chickpea seedlings by examining growth, photosynthetic performance, total osmo-regulation substance contents and antioxidative enzymes subjected to drought stress. The drought stress impaired the growth (root and shoot dry weight, root: shoot ratio, seedlings biomass), water relations, photosynthetic attributes, transpiration rate and chlorophyll contents and anti-oxidants activity of chickpea seedlings. Nonetheless, the foliar application K improved the growth, water relations, photosynthetic attributes, transpiration rate, chlorophyll contents and anti-oxidative activity of chickpea under drought conditions. Moreover, an increase in antioxidant enzyme activity and accumulation of osmoprotectants (proline, soluble protein and soluble sugar) was noted under stressed conditions, which was more pronounced in chickpea which experienced of K application. To conclude that, foliar application of K mitigated the adverse effect of drought, K was proved to be even more effective in alleviating the adverse effect of drought stress on chickpea.
AŞI KABULÜNÜ ETKİLEYEN FAKTÖRLERİN BELİRLENMESİNE YÖNELİK BİR ARAŞTIRMA
Authors: YALMAN Fuat
Published: March 2021

Bu çalışmanın temel amacı, aşı kabulünü etkileyen faktörleri ve bu faktörler arasındaki yapısal ilişkileri tespit etmektir. Araştırmanın evrenini Zonguldak ili oluşturmaktadır. Zonguldak il merkezinde ikamet eden ve sağlık hizmetlerini kullanan genç, orta ve ileri yaş grubu her bir birey, araştırma birimi olarak kabul edilmiştir. Değerlendirmeye alınan ve verilerin analizinde kullanılan toplam anket sayısı ise 400 dür. Verilerin analizinde SPSS ve AMOS paket programları kullanılmıştır. Araştırmada açıklayıcı faktör analizi (AFA) ve doğrulayıcı faktör analizi (DFA) teknikleri kullanılarak faktörler belirlenmiştir. Açıklayıcı ve doğrulayıcı faktör analizleri ile elde edilen bulgular, modelin geçerliliğinin sağlandığını göstermektedir. Açıklayıcı faktör analizi ile ortaya konulan yapı geçerliliği, doğrulayıcı faktör analizi ile de teyit edilmiştir. Geçerlilik ve güvenilirliğin sağlanması; aşı kabulünü etkileyen faktörler arasındaki yapısal ilişkinin varlığını göstermektedir. Ayrıca geçerlilik ve güvenilirlik sağlandığından dolayı, “aşı kabulünü etkileyen faktörler arasındaki ilişki ölçeği”, aşı kabulünü etkileyen faktörler arasındaki ilişkileri ve beklentileri ölçmek için rehber ölçek olarak kullanılabilir.
PENGARUH EFIKASI DIRI, MOTIVASI BELAJAR DAN MINAT BACA TERHADAP HASIL BELAJAR SPEAKING SISWA KELAS X
Authors: Hardianti Novilia , Marpaung Marlin P.
Published: March 2021

The use of English in communication becomes important nowadays in facing the challenges of globalization. Mainly in education, English is one of the school subjects that helps students in preparing their abilities to be part of global citizens. Speaking skills in English subject is one of way in preparing the students, meanwhile learn English also becomes one of the challenges for students.This research is is a quantitative research which aimed to identify the influence of self efficacy, learning motivation and reading interest of the students to their learning outcomes of speaking skill. Data collection was carried out by distributing 3 questionnaires to a population of grade X students, as well as doing some interview to grade X students. The data obtained were further processed and examined by conducting multiple regression analysis tests and determining contributions through R-Square values. The population in this research consists of 76 students. On the results of the analysis, self-efficacy had positive influence on learning outcomes of speaking. Learning motivation had positive influence on learning outcomes of speaking. The last, the coefficient of reading interest had positive influence of reading interest on speaking learning outcomes. These results are based on the R-Square value of the three variables silmutantly have a strong influence on learning outcomes of speaking skills.

Penggunaan bahasa Inggris dalam berkomunikasi dirasakan penting dalam menghadapai tantangan global sekarang ini. Terkhusus dalam dunia pendidikan, Bahasa Inggris menjadi salah satu matapelajaran yang membantu siswa sebagai bentuk persiapan untuk membekali kemampuan dan kecakapan siswa menjadi bagian dari warga global. Keterampilan berbicara “speaking skill” dalam bahasa Inggris juga menjadi salah satu tantangan bagi para sisw. Penelitian ini bersifat kuantitatif dengan tujuan untuk mengidentifikasi pengaruh efikasi diri, motivasi belajar dan minat baca terhadap hasil belajar speaking siswa. Pengumpulan data dilakukan dengan penyebaran tiga kuesioner kepada populasi siswa kelas X, pemberian pertanyaan wawancara kepada siswa kelas X, serta nilai hasil belajar speaking siswa. Data yang diperoleh selanjutnya dianalisis dengan melakukan analisis regresi berganda serta menentukan kontribusi melalui nilai R-Square. Populasi siswa terdiri dari 76 siswa. Berdasarkan hasil analisis yang diperoleh yakni bahwa koefisien efikasi diri berpengaruh positif terhadap hasil belajar speaking. Koefisien motivasi belajar berpengaruh positif terhadap hasil belajar speaking. Terakhir yakni koefisien minat baca berpengaruh positif minat baca terhadap hasil belajar speaking. Berdasarkan nilai R-Square, maka ketiga variabel diatas diperoleh nilai secara simultan berpengaruh kuat terhadap hasil belajar speaking.
Towards a Sustainable Vector-Control Strategy in the Post Kala-Azar Elimination Era
Authors: Garlapati Rajesh , Iniguez Eva , Serafim Tiago D. , Mishra Prabhas K. , Rooj Basab , Sinha Bikas , Valenzuela Jesus G. , Srikantiah Sridhar , Bern Caryn , Kamhawi Shaden
Published: March 2021

Visceral leishmaniasis (VL) is a potentially deadly parasitic disease. In the Indian sub-continent, VL is caused byLeishmania donovaniand transmittedviathe bite of an infectedPhlebotomus argentipesfemale sand fly, the only competent vector species in the region. The highest disease burden is in the northern part of the Indian sub-continent, especially in the state of Bihar. India, Bangladesh, and Nepal embarked on an initiative, coordinated by World Health Organization, to eliminate VL as a public health problem by the year 2020. The main goal is to reduce VL incidence below one case per 10,000 people through early case-detection, prompt diagnosis and treatment, and reduction of transmission using vector control measures. Indoor residual spraying, a major pillar of the elimination program, is the only vector control strategy used by the government of India. Though India is close to its VL elimination target, important aspects of vector bionomics and sand fly transmission dynamics are yet to be determined. To achieve sustained elimination and to prevent a resurgence of VL, knowledge gaps in vector biology and behavior, and the constraints they may pose to current vector control methods, need to be addressed. Herein, we discuss the successes and failures of previous and current vector-control strategies implemented to combat kala-azar in Bihar, India, and identify gaps in our understanding of vector transmission towards development of innovative tools to ensure sustained vector control in the post-elimination period.
Impacts of the Wetland Environment on Demographic Development During the Neolithic in the Lower Yangtze Region—Based on Peat and Archaeological Dates
Authors: Shao Konglan , Zhang Jianping , He Keyang , Wang Can , Lu Houyuan
Published: March 2021

Wetlands were important resources for the hunting–gathering and early farming communities in coastal areas in the Neolithic. However, the relationship between the development of the wetland environment and the human population remains unclear due to the lack of successive wetland environmental changes throughout the Holocene in coastal areas. Here, the summed probability distributions (SPD) of radiocarbon dates of peat were used as an indicator and combined with archaeological radiocarbon dates to reconstruct the wetland environmental and demographic changes during the Neolithic in the lower Yangtze region. The results showed that the shifts in demographic centers and population development were related to wetland environment with peat formation. The first shift of the demographic center was from the hilly regions to the coastal plain and occurred during ca. 8,300–8,000 cal yr BP, which might be caused by the attractiveness of survival resources offered by the coastal wetland environment and the 8.2 ka event. The second shift occurred from the Ningshao Plain to the Taihu region and might be attributed to the widespread waterlogged environment in the Ningshao Plain. The peak of demographic development coincided with the peak of peat formation during the middle Holocene in the lower Yangtze region, indicating that the wetland environment facilitated changes in human societies. The formation of peat might be related to the sea-level and El Niño-Southern Oscillation events; however, further studies are required for deep comprehension. The present study is an attempt at identifying the past impacts of the wetland environment on demographic development and can form the basis for a more comprehensive understanding of the interactions between the humans and their living environment.
Identification and Analysis of Potential Key Genes Associated With Hepatocellular Carcinoma Based on Integrated Bioinformatics Methods
Authors: Li Zhuolin , Lin Yao , Cheng Bizhen , Zhang Qiaoxin , Cai Yingmu
Published: March 2021

Background

Hepatocellular carcinoma (HCC) is a type of primary liver tumor with poor prognosis and high mortality, and its molecular mechanism remains incompletely understood. This study aimed to use bioinformatics technology to identify differentially expressed genes (DEGs) in HCC pathogenesis, hoping to identify novel biomarkers or potential therapeutic targets for HCC research.

Methods

The bioinformatics analysis of our research mostly involved the following two datasets: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). First, we screened DEGs based on the R packages (limma and edgeR). Using the DAVID database, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were carried out. Next, the protein-protein interaction (PPI) network of the DEGs was built in the STRING database. Then, hub genes were screened through the cytoHubba plug-in, followed by verification using the GEPIA and Oncomine databases. We demonstrated differences in levels of the protein in hub genes using the Human Protein Atlas (HPA) database. Finally, the hub genes prognostic values were analyzed by the GEPIA database. Additionally, using the Comparative Toxicogenomics Database (CTD), we constructed the drug-gene interaction network.

Results

We ended up with 763 DEGs, including 247 upregulated and 516 downregulated DEGs, that were mainly enriched in the epoxygenase P450 pathway, oxidation-reduction process, and metabolism-related pathways. Through the constructed PPI network, it can be concluded that the P53 signaling pathway and the cell cycle are the most obvious in module analysis. From the PPI, we filtered out eight hub genes, and these genes were significantly upregulated in HCC samples, findings consistent with the expression validation results. Additionally, survival analysis showed that high level gene expression of CDC20, CDK1, MAD2L1, BUB1, BUB1B, CCNB1, and CCNA2 were connected with the poor overall survival of HCC patients. Toxicogenomics analysis showed that only topotecan, oxaliplatin, and azathioprine could reduce the gene expression levels of all seven hub genes.

Conclusion

The present study screened out the key genes and pathways that were related to HCC pathogenesis, which could provide new insight for the future molecularly targeted therapy and prognosis evaluation of HCC.
Transgenic Expression of Human C-Type Lectin Protein CLEC18A Reduces Dengue Virus Type 2 Infectivity in Aedes aegypti
Authors: Cheng Lie , Liu Wei-Liang , Tsou Yun-Ting , Li Jian-Chiuan , Chien Chia-Hao , Su Matthew P. , Liu Kun-Lin , Huang Ya-Lang , Wu Shih-Cheng , Tsai Jih-Jin , Hsieh Shie-Liang , Chen Chun-Hong
Published: March 2021

The C-type lectins, one family of lectins featuring carbohydrate binding domains which participate in a variety of bioprocesses in both humans and mosquitoes, including immune response, are known to target DENV. A human C-type lectin protein CLEC18A in particular shows extensive glycan binding abilities and correlates with type-I interferon expression, making CLEC18A a potential player in innate immune responses to DENV infection; this potential may provide additional regulatory point in improving mosquito immunity. Here, we established for the first time a transgenic Aedes aegypti line that expresses human CLEC18A. This expression enhanced the Toll immune pathway responses to DENV infection. Furthermore, viral genome and virus titers were reduced by 70% in the midgut of transgenic mosquitoes. We found significant changes in the composition of the midgut microbiome in CLEC18A expressing mosquitoes, which may result from the Toll pathway enhancement and contribute to DENV inhibition. Transgenic mosquito lines offer a compelling option for studying DENV pathogenesis, and our analyses indicate that modifying the mosquito immune system via expression of a human immune gene can significantly reduce DENV infection.
Short-Term Thinning Influences the Rhizosphere Fungal Community Assembly of Pinus massoniana by Altering the Understory Vegetation Diversity
Authors: Liu Size , Yin Haifeng , Li Xiangjun , Li Xianwei , Fan Chuan , Chen Gang , Feng Maosong , Chen Yuqin
Published: March 2021

Thinning can significantly promote forest productivity and ecological function. Rhizosphere fungi play an indispensable role in regulating nutrient cycling between plants and the environment, and their community composition can positively respond to anthropogenic disturbance. However, the initial effects of thinning on rhizosphere fungal community assembly have seldom been reported. In this research, we studied the alterations in the rhizosphere fungal communities of 29-year-old Pinus massoniana in East Sichuan 2 years after three different thinning intensity treatments. In addition, the responses of fungal community and functional group composition to alterations in understory vegetation and soil physiochemical properties were analyzed. Three thinning intensities were set, which were 0 (CK), 25% (LIT), and 50% (HIT), respectively. The results suggested that the richness index and Shannon index of understory vegetation increased significantly with increasing thinning intensity. The alpha diversity indices of rhizosphere fungal community and soil physiochemical properties did not show significant differences among the three treatments. The relative abundances of 17 fungal indicator species varied regularly with increasing thinning intensity, and most of them belong to Hypocreales and Eurotiales, indicating that these two orders were potential indicators for different thinning treatments. Rhizosphere fungal community assembly was determined by deterministic process, and it was driven by the diversity of understory vegetation in the initial stage of thinning. The Simpson index and Pielou index of herbs were useful measures of the main environmental factors driving the differentiation of fungal functional group composition. Based on network analysis, thinning resulted in distinct co-occurrence patterns of rhizosphere fungal functional groups. This research elucidates the initial role of thinning in rhizosphere fungal community assembly of P. massoniana and has practical significance for the functional restoration and protection of local forest ecosystem.
Detection of Microbial Agents in Oropharyngeal and Nasopharyngeal Samples of SARS-CoV-2 Patients
Authors: Seckar Tyler , Lin Xiang , Bose Dipayan , Wei Zhi , Rohrbaugh Joseph , Collman Ronald G. , Robertson Erle S.
Published: March 2021

The novel coronavirus outbreak started in December 2019 and rapidly spread around the globe, leading to a global pandemic. Here we reported the association of microbial agents identified in oropharyngeal and nasopharyngeal samples from patients with SARS-CoV-2 infection, using a Pan-microarray based technology referred to as PathoChIP. To validate the efficiency of PathoChIP, reference viral genomes obtained from BEI resource and 25 SARS-CoV-2 positive clinical samples were tested. This technology successfully detected femtogram levels of SARS-CoV-2 viral RNA, which demonstrated greater sensitivity and specificity than conventional diagnostic techniques. Simultaneously, a broad range of other microorganisms, including other viruses, bacteria, fungi and parasites can be detected in those samples. We identified 7 viral, 12 bacterial and 6 fungal agents common across all clinical samples suggesting an associated microbial signature in individuals who are infected with SARS-CoV-2. This technology is robust and has a flexible detection methodology that can be employed to detect the presence of all human respiratory pathogens in different sample preparations with precision. It will be important for differentiating the causative agents of respiratory illnesses, including SARS-CoV-2.
High Diversity, Prevalence, and Co-infection Rates of Tick-Borne Pathogens in Ticks and Wildlife Hosts in an Urban Area in Romania
Authors: Borşan Silvia-Diana , Ionică Angela Monica , Galon Clémence , Toma-Naic Andra , Peştean Cosmin , Sándor Attila D. , Moutailler Sara , Mihalca Andrei Daniel
Published: March 2021

Despite the increasingly recognized eco-epidemiological importance of ticks as vectors for numerous zoonotic pathogens in urban areas, data regarding the pathogen diversity and co-infection rates in ticks and wildlife hosts in urban and peri-urban Romania are scanty. We aimed to establish the risk of human exposure to co-infected ticks in Cluj-Napoca, a major city in Romania. DNA was isolated from 151 questing ticks:Ixodes ricinus(n= 95),Haemaphysalis punctata(n= 53),Dermacentor reticulatus(n= 2), andDermacentor marginatus(n= 1); 222 engorged ticks:I. ricinus(n= 164),I. hexagonus(n= 36),H. punctata(n= 16),H. concinna(n= 6), and 70 tissue samples collected from wildlife hosts during 2018 in five urban, and two peri-urban sites. Using a pre-designed Fluidigm real-time PCR dynamic array, all DNA samples were individually screened for the presence of 44 vector-borne pathogens. Subsequently, conventional PCRs were performed for a selection of samples to allow validation and sequencing. In total, 15 pathogens were identified to species and 6 to genus level. In questing ticks, single infections were more common than co-infections. SevenBorreliaspp. were detected in questingI. ricinus, and three inH. punctataticks. An overall high prevalence 26.35% (95% CI: 19.46–34.22) and diversity ofBorrelia burgdorferisensu lato was seen in urban questing ticks. Other pathogens of the order Rickettsiales were present with variable prevalence. Co-infections occurred in 27.4% (95% CI: 18.72-37.48) of all infected questing ticks. In engorged ticks the overallBo. burgdorferisensu lato prevalence was 35.6% (95% CI: 29.29–42.27), with five species present. Pathogens of the order Rickettsiales were also frequently detected. We report for the first time in Romania the presence ofRickettsia aeschlimanniiandRickettsia felis. Overall, from the infected engorged ticks, 69.2% showcased co-infections. InIxodesspp., dual co-infections, namelyBorreliaspp. andAnaplasma phagocytophilum, andRickettsia helveticaandA. phagocytophilumwere the most prevalent. Given the outcome, we underline the need to establish proper tick-surveillance programs in cities and include co-infections in the management plan of tick-borne diseases in Romania.
MiR-520a-3p Inhibited Macrophage Polarization and Promoted the Development of Atherosclerosis via Targeting UVRAG in Apolipoprotein E Knockout Mice
Authors: Qi Jing Rui , Zhao Dian Ru , Zhao Li , Luo Fan , Yang Mei
Published: March 2021

Atherosclerosis (AS), a kind of chronic inflammatory blood vessel disease, is a main cause of cardiovascular disease, which is a leading cause of mortality around the world. Accumulation of macrophages induced by inflammation contributes to AS development. It has been indicated that microRNAs (miRNAs) are involved in the process of AS. However, the pathway and gene miRNAs targeting are poorly understood. Here we reported that miR-520a-3p was increased in mice with AS and silencing of miR-520a-3p attenuated AS process. Furthermore, inhibition of miR-520a-3p increased the expression of α-SMA and collagen. In addition, miR-520a-3p silencing inhibited the expression of M1 macrophage polarization markers and pro-inflammatory genes and promoted the M2 macrophage polarization. What’s more, forced expression of miR-520a-3p diminished IL4/IL13 induced macrophage autophagy via targeting UVRAG. Collectively, our study reveals the role of miR-520a-3p in macrophage polarization and suggests the potential of miRNA as a novel treatment target of AS.
CRISPR-CasRx Targeting LncRNA LINC00341 Inhibits Tumor Cell Growth in vitro and in vivo
Authors: Li Chunjing , Cao Yu , Zhang Li , Li Jierong , Wang Jianfeng , Zhou Yanfen , Wei Huiling , Guo Mingjuan , Liu Liang , Liu Chunxiao , Zhang Shilin , Liu Guoqing
Published: March 2021

CRISPR-CasRx technology provides a new and powerful method for studying cellular RNA in human cancer. Herein, the pattern of expression of long noncoding RNA 00341 (LINC00341) as well as its biological function in bladder cancer were studied using CRISPR-CasRx. qRT-PCR was employed to quantify the levels of expression of LINC00341 in tumor tissues along with the matched non-tumor tissues. sgRNA targeting LINC00341 or the sgRNA negative control were transiently transfected into the T24 as well as 5,637 human bladder cancer cell lines. CCK-8, ELISA as well as wound healing methods were employed to explore cell proliferation, apoptosis and migration, respectively. The tumorigenicity experiment in nude mice also performed to detect cell proliferation. The expression of p21, Bax as well as E-cadherin were assayed using western blot. The results demonstrated that LINC00341 was overexpressed in bladder cancer in contrast with the healthy tissues. The LINC00341 expression level in high-grade tumors was higher in contrast with that in low-grade tumors. The expression of linc00341 was higher relative to that of non-invasive tumors. In T24 as well as 5637-cell lines harboring LINC00341-sgRNA, inhibition of cell proliferation (in vitro and in vivo), elevated apoptosis rate and diminished migration ability. Moreover, silencing LINC00341 upregulated the expressions of p21, Bax as well as E-cadherin. Knockout of these genes could eliminate the phenotypic changes caused by sgRNA targeting LINC00341. Our data demonstrate that LINC00341 has a carcinogenic role in human bladder cancer.
Spontaneous Afferent Activity Carves Olfactory Circuits
Authors: Redolfi Nelly , Lodovichi Claudia
Published: March 2021

Electrical activity has a key role in shaping neuronal circuits during development. In most sensory modalities, early in development, internally generated spontaneous activity sculpts the initial layout of neuronal wiring. With the maturation of the sense organs, the system relies more on sensory-evoked electrical activity. Stimuli-driven neuronal discharge is required for the transformation of immature circuits in the specific patterns of neuronal connectivity that subserve normal brain function. The olfactory system (OS) differs from this organizational plan. Despite the important role of odorant receptors (ORs) in shaping olfactory topography, odor-evoked activity does not have a prominent role in refining neuronal wiring. On the contrary, afferent spontaneous discharge is required to achieve and maintain the specific diagram of connectivity that defines the topography of the olfactory bulb (OB). Here, we provide an overview of the development of olfactory topography, with a focus on the role of afferent spontaneous discharge in the formation and maintenance of the specific synaptic contacts that result in the topographic organization of the OB.
Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration
Authors: Maragkos Georgios A. , Schüpper Alexander J. , Lakomkin Nikita , Sideras Panagiotis , Price Gabrielle , Baron Rebecca , Hamilton Travis , Haider Sameah , Lee Ian Y. , Hadjipanayis Constantinos G. , Robin Adam M.
Published: March 2021

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2–4 h prior to induction to anesthesia.

Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data.

Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented.

Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4.

Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.
Contextual MEG and EEG Source Estimates Using Spatiotemporal LSTM Networks
Authors: Dinh Christoph , Samuelsson John G. , Hunold Alexander , Hämäläinen Matti S. , Khan Sheraz
Published: March 2021

Most magneto- and electroencephalography (M/EEG) based source estimation techniques derive their estimates sample wise, independently across time. However, neuronal assemblies are intricately interconnected, constraining the temporal evolution of neural activity that is detected by MEG and EEG; the observed neural currents must thus be highly context dependent. Here, we use a network of Long Short-Term Memory (LSTM) cells where the input is a sequence of past source estimates and the output is a prediction of the following estimate. This prediction is then used to correct the estimate. In this study, we applied this technique on noise-normalized minimum norm estimates (MNE). Because the correction is found by using past activity (context), we call this implementation Contextual MNE (CMNE), although this technique can be used in conjunction with any source estimation method. We test CMNE on simulated epileptiform activity and recorded auditory steady state response (ASSR) data, showing that the CMNE estimates exhibit a higher degree of spatial fidelity than the unfiltered estimates in the tested cases.
Protein and Signaling Pathway Responses to rhIL-6 Intervention Before Lobaplatin Treatment in Osteosarcoma Cells
Authors: Wang Huan , Li Bin , Yan Kang , Wu Yonghong , Wen Yanhua , Liu Yunyan , Fan Pei , Ma Qiong
Published: March 2021

Lobaplatin is a third-generation platinum-based antineoplastic agent and is widely used for osteosarcoma treatment before and after tumor removal. However, treatment failure often results from lobaplatin drug resistance. In our study, we found that SaOS-2 and SOSP-9607 osteosarcoma cells became less sensitive to lobaplatin after treatment with exogenous interleukin (IL)-6. Quantitative proteomic analysis was performed to elucidate the underlying mechanism in SaOS-2 osteosarcoma cells. Cells were divided into a control group (CG), a lobaplatin treatment group (LG), a recombinant human IL-6 (rhIL-6), and a lobaplatin treatment group (rhILG). We performed three biological replicates in each group to compare the differential protein expression between groups using a tandem mass tag (TMT) labeling technology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1,313 proteins with significant differential expression was identified and quantified. The general characteristics of the significantly enriched proteins were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein–protein interaction (PPI) analysis was conducted using IntAct and STRING. In total, 31 proteins were further verified by parallel reaction monitoring (PRM), among which ras GTPase-activating protein-binding protein 1 (G3BP1), fragile X mental retardation syndrome-related protein 1 (hFXR1p), and far upstream element-binding protein 1 (FUBP1) were significantly differentially expressed. Immunohistochemistry results showed that these three proteins are highly expressed in specimens from platinum-resistant osteosarcoma patients, while the proteins are negatively or weakly expressed in specimens from platinum-sensitive osteosarcoma patients. The immunofluorescence staining results were in accord with the immunohistochemistry staining results. siRNA knockdown of FUBP1 showed a strikingly decreased IC50 value for lobaplatin in FUBP1-silenced cells, which verified the role of FUBP1 in the drug susceptibility of osteosarcoma and the potential therapeutic value for increasing the sensitivity to lobaplatin. This is the first proteomic study on a rhIL-6 intervention before lobaplatin treatment in osteosarcoma cells.
Long Non-Coding RNAs: Role in Testicular Cancers
Authors: Bresesti Chiara , Vezzoli Valeria , Cangiano Biagio , Bonomi Marco
Published: March 2021

In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.
Adverse Events Following Administration of Anti-CTLA4 Antibody Ipilimumab
Authors: Karimi Amirali , Alilou Sanam , Mirzaei Hamid Reza
Published: March 2021

Ipilimumab, a monoclonal anti-CTLA4 antibody, paved the path for promising treatments, particularly in advanced forms of numerous cancers like melanoma. By blockading CTLA-4, ipilimumab can abolish the higher binding affinity of B7 for CTLA-4, setting CD28 free to act unlimited. This blockade can result in an amplified antitumor immune response, and thereby, boosting more effective tumor regression. However, this blockage can lead to diminished self-tolerance and yielding autoimmune complications. The current review aims to describe adverse events (AEs) following the administration of ipilimumab in different cancers as every benefit comes at a cost. We will also discuss AEs in two different categories, melanoma and non-melanoma, owing to the possible shining promises in treating non-melanoma cancers. As the melanoma settings are more studied than other cancers, it might even help predict the patterns related to the other types of cancers. This similarity also might help physicians to predict adverse events and correctly manage them in non-melanoma cancers using the extensive findings reported in the more-studied melanoma settings. Recognizing the adverse events is vital since most of the adverse events could be reverted while carefully implementing guidelines. Finally, we will also describe the observed effectiveness of ipilimumab in non-melanoma cancers. This effectiveness reveals the importance of understanding the profile of adverse events in this group, even though some have not received FDA approval yet. Further clinical trials and careful systematic reviews may be required to decipher the hidden aspects of therapies with ipilimumab and its related AEs.
Plasma Exosome-Derived Sentrin SUMO-Specific Protease 1: A Prognostic Biomarker in Patients With Osteosarcoma
Authors: Wang Li , Wu Jian , Song Shu , Chen Haining , Hu Yong , Xu Buwei , Liu Jinbo
Published: March 2021

Background

The exosomes contain many important proteins that can be used for early tumor diagnosis or patient prognosis analysis. In this study, we investigated plasma exosome-derived sentrin SUMO-specific protease 1 (SENP1) levels as a prognostic biomarker in patients with osteosarcoma.

Methods

The expression of SENP1 protein in osteosarcoma tissues and adjacent tissues was detected by immunohistochemistry (IHC). The exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. ELISA was used to detect plasma exosome-derived SENP1 levels to assess prognosis in patients with osteosarcoma.

Results

IHC showed that the positive expression rate of SENP1 in osteosarcoma tissues was 88.33%, whereas that in adjacent tissues was 46.67% (P < 0.05). Plasma exosome-derived SENP1 levels were related to tumor size, tumor location, necrosis rate, pulmonary metastasis, and surgical stage. Both disease-free survival (DFS) and overall survival (OS) were worse in patients who had higher plasma exosome-derived SENP1 levels compared with those in patients with lower plasma exosome-derived SENP1 levels (P < 0.001). The area under the receiver operating characteristic curve (AUROC) of plasma exosome-derived SENP1, as 1-year DFS and 3-year DFS prognostic biomarkers, was 0.90 (95% CI: 0.83–0.98) and 0.96 (95% CI: 0.94–0.99), respectively. As to OS, the AUROC of plasma exosome-derived SENP1 for 1-year and 3-year prediction was 0.90 (95% CI: 0.82–0.99) and 0.96 (0.93–0.98), respectively. The plasma exosome-derived SENP1 was better than plasma SENP1 as a prognostic biomarker both in DFS and OS.

Conclusions

Our findings show that the plasma exosome-derived SENP1 may serve as a novel and independent prognostic predictor in clinical applications.
Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence: A Nested Case-Control Study
Authors: Rosendahl Ann H. , Björner Sofie , Ygland Rödström Maria , Jirström Karin , Borgquist Signe , Ingvar Christian , Pollak Michael N. , Jernström Helena
Published: March 2021

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IRm) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted Ptrend=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted Ptrend=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IRm positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IRm positive tumors but not in those with IGF-IRm negative tumors (Pinteraction=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER+ tumors. Postoperative changes >10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.
Prognostic Signature of Immune Genes and Immune-Related LncRNAs in Neuroblastoma: A Study Based on GEO and TARGET Datasets
Authors: Zhong Xiaodan , Tao Ying , Chang Jian , Zhang Yutong , Zhang Hao , Wang Linyu , Liu Yuanning
Published: March 2021

Background

The prognostic value of immune-related genes and lncRNAs in neuroblastoma has not been elucidated, especially in subgroups with different outcomes. This study aimed to explore immune-related prognostic signatures.

Materials and Methods

Immune-related prognostic genes and lncRNAs were identified by univariate Cox regression analysis in the training set. The top 20 C-index genes and 17 immune-related lncRNAs were included in prognostic model construction, and random forest and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms were employed to select features. The risk score model was constructed and assessed using the Kaplan-Meier plot and the receiver operating characteristic curve. Functional enrichment analysis of the immune-related lncRNAs was conducted using the STRING database.

Results

In GSE49710, five immune genes (CDK4, PIK3R1, THRA, MAP2K2, and ULBP2) were included in the risk score five genes (RS5_G) signature, and eleven immune-related lncRNAs (LINC00260, FAM13A1OS, AGPAT4-IT1, DUBR, MIAT, TSC22D1-AS1, DANCR, MIR137HG, ERC2-IT1, LINC01184, LINC00667) were brought into risk score LncRNAs (RS_Lnc) signature. Patients were divided into high/low-risk score groups by the median. Overall survival and event/progression-free survival time were shortened in patients with high scores, both in training and validation cohorts. The same results were found in subgroups. In grouping ability assessment, the area under the curves (AUCs) in distinguishing different groups ranged from 0.737 to 0.94, better in discriminating MYCN status and high risk in training cohort (higher than 0.9). Multivariate Cox analysis demonstrated that RS5_G and RS_Lnc were the independent risk factors for overall and event/progression-free survival (all p-values <0.001). Correlation analysis showed that RS5_G and RS_Lnc were negatively associated with aDC, CD8+ T cells, but positively correlated with Th2 cells. Functional enrichment analyzes demonstrated that immune-related lncRNAs are mainly enriched in cancer-related pathways and immune-related pathways.

Conclusion

We identified the immune-related prognostic signature RS5_G and RS_Lnc. The predicting and grouping ability is close to being even better than those reported in other studies, especially in subgroups. This study provided prognostic signatures that may help clinicians to choose optimal treatment strategies and showed a new insight for NB treatment. These results need further biological experiments and clinical validation.