bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortalidade por acidente ou sinistros de motocicleta nas regiões do Brasil: análise temporal 2016 a 2020
Authors: Fidelis Fernando Antônio Pedrosa , Araújo Karina Conceição Gomes Machado de , Martins Filho Paulo Ricardo Saquete
Published: May 2022

Este estudo teve como objetivo analisar a mortalidade por acidentes ou sinistros nas regiões do Brasil, no período de 2016 a 2020. Para isso, foi realizada uma coleta de dados secundários sobre os acidentes com motocicletas no Brasil ocorridos entre 2016 e 2020 onde as informações foram coletadas do Sistema de Informação sobre Mortalidade (SIM), do Departamento de Informática do Sistema Único de Saúde (DATASUS). As variáveis levantadas foram: óbitos por região, faixa etária, sexo e raça. Essas informações estão disponíveis através do endereço eletrônico. Os dados obtidos pelo TABNET/DATASUS foram tabulados e analisados no Excel versão 2019. Os resultados mostraram que durante o período estudado ocorreram 58.660 óbitos em decorrência de acidentes envolvendo motocicletas, deste 23.469 (40%) ocorreram na região Nordeste, sendo entre a faixa etária que obteve o maior número de óbitos foi 20 e 29 anos e do sexo masculino. Portanto, ficou claro a necessidade de investir na educação, pois as pessoas precisam entender que as regras de trânsito existem para obedecer e o respeito à vida é o fator mais importante para ajudar a reduzir o número desses casos. Perante estes fatores, é necessário mais investimento em ações de melhoria da qualidade das vias públicas para melhorar a segurança das pessoas que as utilizam e dos motociclistas que nelas transitam diariamente.
Caracterização físico-química de queijo Minas Artesanal da microrregião do cerrado
Authors: Lopes Iris Maria de Araújo , Rocha Guilherme Franco , Mota Guiomar Magela da , Silva Laura Aparecida Corrêa da , Castro Renata de Oliveira , Melo Cláudia Maria Tomás
Published: May 2022

Este trabalho teve como objetivo fazer a caracterização físico-química do queijo Minas Artesanal de um produtor do município de Cruzeiro da Fortaleza, da microrregião do Cerrado. O queijo Minas Artesanal se distingue de outros queijos produzidos no Brasil pela adição do “pingo” no leite cru e prensagem manual, que proporcionam características singulares no aroma, sabor, odor e textura.  As análises fisico-químicas garantem ao produtor e ao consumidor a segurança do alimento. A caracterização físico química deste produto  garante que ele esteja de acordo com os padrões descritos na legislação, evitando assim fraudes ou adulterações de produtos que podem ser altamente prejudiciais à saúde humana. Para as análises físico-químicas utilizou-se uma unidade de um lote de Queijo Minas Artesanal do Cerrado, do município de Cruzeiro da Fortaleza, com 03 dias de fabricação. Foi deterrminada a composição centesimal em base úmida, considerando umidade, lipídeos, proteínas e cinzas. Além disso, foram avaliadas acidez titulável e presença de amido. Observou-se que os percentuais médios de umidade e cinzas encontrados foram de 44,71% e 3,195% respetivamente; ao passo que o valor verificado para lipídios e proteinas foram, respectivamente, 27,66 % e  21,33 %. A presença de amido foi negativa e a média encontrada de acidez titulável em ácido lático foi de 0,225%. Concluiu-se que o queijo analisado atende aos parâmetros mínimos determinados pela legislação brasileira, destacando-se que as diferenças encontradas em relação a literatura são principalmente devido a fatores externos e não padronizados.
Caracterização das infecções relacionadas à assistência à saúde em uma unidade de terapia intensiva do Acre
Authors: Dourado Eduardo de Souza , Bezerra Ruth Canuto , Medeiros Phietra Beatriz Bezerra de , Tavares Vanessa Victoria Alnert Vieira , Costa Vanessa Holanda de Souza Ribeiro da , Conceição Matilde da Silva , Souza Christopher Wando da Silva , Nunes Eryckson Araújo , Costa Ruth Silva Lima da
Published: May 2022

Indivíduos hospitalizados estão sujeitos à ocorrência de Infecções Relacionadas à Assistência a Saúde (IRAS), responsáveis pelo aumento de gastos públicos e impacto no tempo de internação. Objetivo: analisar casos de Infecções Relacionadas à Assistência à Saúde         em pacientes assistidos em uma Unidade de Terapia Intensiva do Acre. Métodos: estudo epidemiológico, retrospectivo, realizado em um Hospital de Urgência e Emergência do Acre, no ano de 2019. Os dados foram coletados através das fichas de notificação da comissão de controle da infeccção hospitalar da unidade, organizados em tabelas      e analisados por meio da estatística descritiva. Resultados: a maior ocorrência se deu no sexo masculino (66%). Não foi possível   avaliar a média de idade dos indivíduos, pois essa informação estava ausente em 32% das fichas de notificação, bem como em 26% delas, não haviam informações acerca do motivo da internação, porém observou-se que a topografia mais incidente entre os casos identificados, foram as internações por acidentes e violências (24%). A ventilação mecânica foi realizada na maioria dos pacientes (59%) e a Pseudomonas aeruginosa foi o principal patógeno encontrado (39%). O material biológico mais frequente para isolamento do patógeno foi       a secreção traqueal (70%). Acerca do desfecho clínico, em (61%) das fichas essa informação também estava ausente, no entanto frente ao que foi possível avaliar (31%) dos indivíduos evoluíram para óbito. Conclusão: As Infeccções Relacionadas á Assistencia á Saúde, são uma realidade atual dentro das unidades de terapia intensivas, acometendo um número significativo de individuos no Acre, sendo importante que se implementem medidas que possam mudar essa realidade, bem como é urgente que haja melhoria dos registros nas fichas de notificação para que seja possível a realização de avaliações mais concretas.
Campos Verdes-GO e o garimpo de esmeraldas: território, desenvolvimento local e desterritorialidade
Authors: Pasqualetto Antonio , Matsuura Fudio , Ferreira Ubirajara de Lima
Published: May 2022

Objetivou-se analisar a descoberta de esmeraldas, a ocupação do território e o surgimento da cidade de Campos Verdes, marcado pelo desenvolvimento econômico local no auge da exploração de esmeraldas e posteriormente, a sua decadência e o esvaziamento da cidade. O arcabouço teórico desta pesquisa teve como fundamento os conceitos de território e desterritorialidade e suas dinâmicas, bem como, o de desenvolvimento local. Assim, foi realizada pesquisa descritiva, de caráter qualitativo e pesquisa de campo, com aplicação de questionários, a fim de observar como as populações dessas localidades percebem historicamente o território e o desenvolvimento econômico local – ou não – oriundo do garimpo. Os resultados demonstraram que o garimpeiro, devido ao caráter temporal das minas de exploração, rompe com a lógica de fixação no território, gerando esvaziamento das cidades e regiões quando o garimpo entra em crise. Esses processos levam ao questionamento da noção de desenvolvimento associada à atividade mineradora, já que esta apresenta caráter predatório e de alto risco ambiental, incompatíveis com o desenvolvimento sustentável.
Nietzsche e a construção do diagnóstico da temporalidade moderna tardia: o apequenamento do último homem nos mecanismos impessoais do trabalho moderno
Authors: Menezes Dalila Miranda , Cabral João Edson Gonçalves , Brito Marilha Vieira de , Paiva Iara Tâmara Pessoa , Oliveira Neto João Evangelista de
Published: May 2022

Seria possível identificarmos em nossas ações contemporâneas traços vinculadores com processos históricos mais amplos que ainda estariam em curso? Por mais que consideremos a especificidade de nossas vivências contemporâneas não é possivel deixar de reconhecer coincidências preocupantes que nos vinculam aos tipos humanos avaliados pela crítica do olhar reflexivo de certas tradições filosóficas, aqui circunscrita à filosofia nietzscheana. O objetivo deste artigo é nos servimos da análise de algumas passagens em Nietzsche para nos auxiliar na tarefa de desvelarmos o significado do modo pueril de vida contemporâneo, afeito a uma tacanha doutrina da felicidade e da virtude que uniformizam suas ações e retiram suas possibilidades de desenvolverem uma direção própria segundo as exigências de suas singularidades. Nietzsche denominou seus contemporâneos como os “últimos homens”, aqueles que, segundo Zaratustra, “não sabem o que é amor, o que é criação, o que é anseio, mas dizem que inventaram a felicidade”, ou aqueles que “reduziram o trabalho a um passatempo, desistiram do que é penoso, conquistaram segurança e conforto, consideram que todos são iguais e vivem para os pequenos prazeres”. Quais caminhos percorre Nietzsche para compor seu juízo e apresentar este tipo humano rebaixado? Nós nos serviremos de dois fatos recentes e completamente distantes em sua localização geográfica e em sua dimensão política ocorridos, nos anos de 2021 e 2022, para ilustrar nossa condição contemporânea similar de apequenamento: o que a brincadeira de um grupo de crianças pode ter relação com o resultado das eleições presidenciais francesas?
The role of the family and formal education in the development of the broken home child's thought and morals
Authors: Dayani Prihatini Septi , Haryono Haryono
Published: May 2022

Education is a broader process of increasing knowledge, insight and process of shaping a broader character and mind-set. Formal education can transform one's self into a more disciplined, know - the - rules and limditations of doing things. With formal education we can raise awareness of a thing that can sometimes lead one toward something that is wrong. Education can also help a person to become critical in his or her thinking. Education can help a person change his weaknesses into strengths. In the world of education there is a great deal of implied meaning and purpose, hope and goals to achieve. One dof the professions that play a major role in education is teachers. Teachers are a milestone in the success and development of education. Education is especially important for children who receive little love from their parents and for children who are victims of a parent's divorce.
PEMBENTUKAN HABITUASI LITERASI BACA TULIS SISWA MELALUI GERAKAN LITERASI SEKOLAH DI SDN INPRES 1 NARU SAPE
Authors: Waluyati Ida , Nurhidayatika Nurhidayatika , Irfan Irfan , Ahdiyanti Istika
Published: May 2022

Penelitian ini bertujuan untuk mengkaji pembentukan habituasi literasi baca tulis siswa melalui Gerakan Literasi Sekolah (GLS) di SDN INPRES 1 NARU SAPE. Penelitian ini menggunakan pendekatan kualitatif dengan metode deskriptif analitis. Teknik pengumpulan data dengan cara wawancara mendalam dan observasi langsung. Teknik pemilihan informan dilakukan dengan tehnik purposive sampling. informan yang di pilih adalah 4 orang siswa, kepala sekolah, penanggung jawab pelaksanaan literasi dan 2 orang guru. Uji validitas data menggunakan triangangulasi metode dan triangulasi sumber. Analisis data menggunakan analisis Cresswell yang terdiri dari tahapan: menyiapkan data, mengeksplorasi data, mengkoding data, mendeskripsikan melalui narasi dan menginterpretasi data atau memaknai data. Hasil penelitian menunjukan bahwa pembentukan habituasi literasi baca tulis siswa melalui GLS dilakukan melalui tiga fase. Habituasi ialah bentuk pembiasaan yang dilakukan melalui pengalaman dan pengajaran. Kegiatan literasi melalui GLS sengaja dilakukan oleh pihak sekolah untuk membentuk siswa yang literat dengan harapan siswa mampu meraih prestasi yang akan memperkuat posisi SDN INPRES 1 NARU sebagai sekolah rujukan. Rangkaian proses pembentukan habituasi di mulai dengan pemahaman kognitif kemudian akan menyatu dengan gagasan pikiran sebelumnya dan di pelajari dalam waktu yang lama dan panjang hingga diekspresikan menjadi perilaku yang terpola. Pembentukan habituasi baca tulis siswa melalui GLS yaitu, fase pertama, dilakukan dengan memberi pemahaman pada siswa melalui pikirannya melalui sosialisasi dan dibenturkan dengan idealisme sekolah sebagai penggeraknya. Fase kedua, yaitu siswa diberikan latihan sebagai bentuk pembudayaan yaitu melalui (1) tahap pembiasaan yang terdiri dari kegiatan 15 menit membaca sebelum pembelajaran dan penciptaan lingkungan fisik yang literat yaitu pojok baca, taman baca serta perpustakaan sekolah, (2) tahap pengembangan melalui kegiatan talkshow atau seminar literasi , (3) tahap pembelajaran yaitu produk tulisan yang dihasilkan siswa. Fase ketiga, yaitu terpola, yaitu siswa memiliki bentuk kesadaran dalam hal literasi dan manfaatnya, sehingga kegiatan literasi yang dibiasakan di sekolah dilakukan siswa ketika berada diluar sekolah, seperti keaktifan siswa dalam berdiskusi bersama guru maupun teman baik didalam maupun luar pembelajaran dan mengikutsertakan tulisannya dalam ajang perlombaan.
Efektivitas Teknik Self-Control Strategies Untuk Mengurangi Perilaku Off Task Pada Peserta Didik SMA
Authors: Nurhayati Nurhayati , Khairunnisa Khairunnisa , Nurmaya Alya , Indah Sulistia
Published: May 2022

Perilaku off task siswa adalah perilaku siswa yang tidak memperhatikan, mengalami kebingungan atau gagal dalam menyelesaikan tugas di dalam kelas. Tujuan penelitian ini untuk melihat bahwa self-control strategies dapat menurunkan perilaku off task peserta didik. Peneltian ini menggunakan instrument lembar monitoring.   Analisis data menggunanakan statistik persentase. Hasil penelitian ini menunjukkan bahwa perilaku off task yang dimunculkan oleh keempat subjek dalam penelitian ini sangat signifikan, baik hasil analisis data frekuensi maupun durasi. Penurunan perilaku off task siswa dilihat dari data baseline (fase A) sebelum treatmen diberikan, dibandingkan dengan data treatmen (fase B) dan perilaku dipertahankan agar tidak kembali lagi pada fase maintenance (fase C). Berdasarkan hasil penelitian ini menunjukkan bahwa penggunaan selfcontrol strategies dalam konseling kelompok mampu mengurangi frekuensi sebanyak 70,58 %, dan menurunkan durasi perilaku off task sebesar 78,57 %.
Anadolu Ağızlarında Kişi Betimlemeleri İle İlgili Söz Varlığı Üzerine Bir İnceleme: Bitlis Merkez Ağzı Örneği
Authors: PARLAKPINAR Murat
Published: May 2022

Ağızlardaki söz varlığıyla ilgili yapılan çalışmalar incelendiğinde çalışmaların daha çok çeşitli yöre ağızlarında geçen hayvan, bitki, giyecek, araç-gereç, meyve vb. adlarının incelenmesi konularında yoğunluk kazandığı görülmektedir. Ne var ki Türkçenin söz varlığı bakımından zenginliğini ve ifade gücünü göstermesi bakımından önemli sayılabilecek olan betimleme sözcükleri bahse pek konu olmamıştır. Betimleme genel anlamı ile tasarlamak, göz önünde canlandırmak, bir şeyi söz ya da yazı ile anlatmak demektir. Betimlemede özellikle varlıkların kendilerine özgü özellikleri üzerinde durulur ve bu belirleyici özelliklerin, niteleme sözcükleri ile anlatılması söz konusudur. İnsanla ilgili betimleme ruhsal betimleme ve fiziksel betimleme olmak üzere ikiye ayrılır. İnsanların gözle görülmeyen iyi kalplilik, alçak gönüllülük, sevecenlik, çalışkanlık, karamsarlık, kıskançlık, kendini beğenmişlik vb. özelliklerinin anlatılmasına ruhsal betimleme; kişilerin gözle görülen; boyu, kilosu, yüz şekli, ten ve saç rengi, kılık kıyafeti ile ilgili özelliklerinin ayrıntılı olarak anlatılmasına ise fiziksel betimleme denir. Anadolu ağızları dikkatli bir nazarla incelendiğinde kişilerin fiziksel ve ruhsal özelliklerini anlatmada kullanılan zengin bir söz varlığıyla karşılaşılmaktadır. Bu çalışmada Anadolu ağızlarının bu anlamdaki zenginliğine dikkat çekmek, Bitlis merkez ağzında kullanılan fiziksel ve ruhsal betimleme ile ilgili söz varlığını ortaya koyarak ağız çalışmalarına katkıda bulunmak amaçlanmıştır.
A Dose-Response Investigation of a Micronized Porous Ceramic Particle to Improve the Health and Performance of Post-weaned Pigs Infected With Salmonella enterica Serotype Typhimurium
Authors: Davis Emily M. , Wallace Kayla P. , Cruz Penn Michael J. , Petry Amy L. , Broadway Rand , Burdick Sanchez Nicole C. , Carroll Jeffery A. , Ballou Michael A.
Published: May 2022

The objective was to investigate the effects of supplementing increasing concentrations of PowerGuard (PG), a micronized ceramic particle, to weaned pigs on health and performance following a Salmonella enterica serotype Typhimurium infection. Forty barrows were transported to the USDA facility in Liberty, TX, USA. Pigs were randomly assigned to one of five treatments (n = 8): (1) uninfected control (CON), no Salmonella typhimurium (ST) and no PG treatment; (2) infected control (ST), infected with ST but no PG treatment; (3) PG0.05, infected with ST and supplemented with 0.05% PG; (4) PG0.25, infected with ST and supplemented with 0.25% PG; and (5) PG0.50, infected with ST and supplemented with 0.5% PG. All pigs were enrolled at 21.5 ± 1.33 days of age and did not differ in initial BW (1.98 ± 0.09 kg). Pigs were anesthetized to insert temperature recording devices into the abdominal cavity. Pigs were offered feed and water ad libitum. Pigs in ST, PG0.05, PG0.25, and PG0.50 were infected orally with 1.75 × 107 colony-forming units of Salmonella typhimurium on day 7. Pig body weights and peripheral blood samples were collected on days 0, 7, 10, 14, and 21. Pigs were harvested on day 21 and ileum and liver samples were collected for histopathological analyses. There was no treatment difference for final BW (P ≥ 0.201). There was a tendency (P = 0.087) for a treatment difference in the fecal score; ST and PG0.50 had more loose fecal scores than CON and PG0.25. There was a treatment × time interaction for intraperitoneal temperature (P < 0.0001); PG0.05, PG0.25, and PG0.50 had attenuated febrile responses during the acute post-infection period compared with ST. There was a treatment × time interaction for total leukocyte counts (P = 0.007); PG treatments reduced leukocytosis post-infection compared with ST. Supplementing PG0.25 improved many health and performance variables when pigs were infected with Salmonella Typhimurium. Furthermore, supplementing PG0.05 attenuated the febrile response and many hematological variables. However, supplementing PG0.5 did not improve many aspects of health or performance. Therefore, supplementing PowerGuard between 0.05 and 0.25% of the diet may play a role in protecting weaned pigs from disease caused by Salmonella.
Optimal Timing of Ovulation Triggering to Achieve Highest Success Rates in Natural Cycles—An Analysis Based on Follicle Size and Oestradiol Concentration in Natural Cycle IVF
Authors: Helmer Anja , Magaton Isotta , Stalder Odile , Stute Petra , Surbek Daniel , von Wolff Michael
Published: May 2022

Introduction

Timing of ovulation triggering is essential in infertility treatments including treatments based on natural menstrual cycles. However, data on follicle size and oestradiol (E2) concentration are limited. Therefore, the model of natural cycle IVF (NC-IVF) was applied to provide more detailed information on these parameters to better schedule the optimal time for triggering ovulation.

Materials and Methods

A retrospective cross-sectional analysis of 606 monofollicular NC-IVF cycles was performed at a university-based IVF centre from 2016 to 2019. Follicle size and E2 and LH serum concentrations were evaluated on day -5 to 0 (day 0 = day of oocyte retrieval). Ovulation was triggered if follicle size was 14–22 mm. Patients with irregular cycles, endometriosis >II°, cycles with azoospermia or cryptozoospermia and cycles with inconsistent data were excluded. All parameters were analysed inter- and intraindividually, and associations of the parameters were evaluated. Associations were adjusted for age, cause of infertility and number of previous transfers.

Results

The mean age of women undergoing NC-IVF was 35.8 ± 4.0 years. Follicle size increased by 1.04 ± 0.03 mm, and E2 concentration by 167 ± 11.0 pmol/l per day.

Based on a multivariate adjusted mixed model with follicle size, E2 and their interaction, the number of retrieved oocytes was associated with E2 concentration (aOR 1.91, 95% CI: 1.03–3.56; p = 0.040). Maturity of oocytes was associated not only with E2 concentration (aOR 2.01, 95% CI: 1.17–3.45; p = 0.011) but also with follicle size (aOR 1.27, 95% CI: 1.01–1.60; p = 0.039), as was the interaction of both parameters (aOR 0.96, 95% CI: 0.93–0.99; p = 0.017).

LH surge was calculated to start in 25% of cases at an E2 level of 637 pmol/l, in 50% of cases at 911 pmol/l and in 75% of cases at an E2 level of 1,480 pmol/l.

The live birth rate per follicle aspiration cycle was (non-significantly) higher in cycles with follicles sizes at the time of oocyte retrieval of 18–22 mm (7.7%–12.5%) versus in cycles with follicles sizes of 14–17 mm (1.6%–4.3%).

Conclusion

The study contributes to an optimization of infertility treatments involving natural cycles. The study gives guidance about the number of days required after follicle monitoring to schedule the optimal time for triggering ovulation.
Severe Hypoglycemia Caused by a Giant Borderline Phyllodes Tumor of the Breast: A Case Report and Literature Review
Authors: Liu Yaoxia , Zhang Min , Yang Xudan , Zhang Min , Fan Zhen , Li Yi , Wang Tao , Chen Ping
Published: May 2022

A case of hypoglycemic coma caused by a giant borderline phyllodes tumor of the breast has been described. The patient, a 63-year-old woman, was admitted with recurrent unconsciousness. She had a giant breast tumor with decreased blood glucose, insulin, and C-peptide. The patient’s hypoglycemia resolved rapidly after resection of the breast tumor. Pathological examination indicated a borderline phyllodes tumor of the breast, and immunohistochemistry suggested high expression of insulin-like growth factor-2 (IGF-2) in the tumor tissue. A literature review is also included to summarize the clinical characteristics of such patients and to serve as a unique resource for clinical diagnosis and treatment of similar cases.
Exposed and Sequestered Antigens in Testes and Their Protection by Regulatory T Cell-Dependent Systemic Tolerance
Authors: Harakal Jessica , Qiao Hui , Wheeler Karen , Rival Claudia , Paul Alberta G. A. , Hardy Daniel M. , Cheng C. Yan , Goldberg Erwin , Tung Kenneth S. K.
Published: May 2022

Continuous exposure of tissue antigen (Ag) to the autoantigen-specific regulatory T cells (Treg) is required to maintain Treg-dependent systemic tolerance. Thus, testis autoantigens, previously considered as sequestered, may not be protected by systemic tolerance. We now document that the complete testis antigen sequestration is not valid. The haploid sperm Ag lactate dehydrogenase 3 (LDH3) is continuously exposed and not sequestered. It enters the residual body (RB) to egress from the seminiferous tubules and interact with circulating antibody (Ab). Some LDH3 also remains inside the sperm cytoplasmic droplets (CD). Treg-depletion in the DEREG mice that express diphtheria toxin receptor on the Foxp3 promoter results in spontaneous experimental autoimmune orchitis (EAO) and Ab to LDH3. Unlike the wild-type male mice, mice deficient in LDH3 (wild-type female or LDH3NULLmales) respond vigorously to LDH3 immunization. However, partial Treg depletion elevated the wild-type male LDH3 responses to the level of normal females. In contrast to LDH3, zonadhesin (ZAN) in the sperm acrosome displays properties of a sequestered Ag. However, when ZAN and other sperm Ag are exposed by vasectomy, they rapidly induce testis Ag-specific tolerance, which is terminated by partial Treg-depletion, leading to bilateral EAO and ZAN Ab response. We conclude that some testis/sperm Ag are normally exposed because of the unique testicular anatomy and physiology. The exposed Ag: 1) maintain normal Treg-dependent systemic tolerance, and 2) are pathogenic and serve as target Ag to initiate EAO. Unexpectedly, the sequestered Ags, normally non-tolerogenic, can orchestratede novoTreg-dependent, systemic tolerance when exposed in vasectomy.
Safety and Efficacy of Combined Intramuscular/Intranasal RAZI-COV PARS Vaccine Candidate Against SARS-CoV-2: A Preclinical Study in Several Animal Models
Authors: Banihashemi Seyed Reza , Es-haghi Ali , Fallah Mehrabadi Mohammad Hossein , Nofeli Mojtaba , Mokarram Ali Rezaei , Ranjbar Alireza , Salman Mo , Hajimoradi Monireh , Razaz Seyad Hossein , Taghdiri Maryam , Bagheri Mohsen , Dadar Maryam , Hassan Zuhair Mohammad , Eslampanah Mohammad , Salehi Najafabadi Zahra , Lotfi Mohsen , Khorasani Akbar , Rahmani Fereidoon
Published: May 2022

Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×106 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P<0.01). Middle and high doses of RAZI-COV PARS vaccine significantly induced a robust and quick immune response from the third-week post-immunization. Histopathological studies on vaccinated hamsters showed that the challenge with SARS-CoV-2 did not induce any modifications in the lungs. The protection of the hamster was documented by the absence of lung pathology, the decreased virus load in the lung, rapid clearance of the virus from the lung, and strong humoral and cellular immune response. These findings confirm the immunogenicity and efficacy of the RAZI-COV PARS vaccine. Of the three tested vaccine regimens, the middle dose of the vaccine showed the best protective immune parameters. This vaccine with heterologous prime-boost vaccination method can be a good candidate to control the viral infection and its spread by stimulating central and mucosal immunity.
Based on Gene Expression Analysis: Low-Density Neutrophil Expression Is a Characteristic of the Fast Responders Treated With Guselkumab for Psoriasis
Authors: Lu Jiajing , Wang Yu , Li Ying , Zhong Xiaoyuan , Gong Yu , Ding Yangfeng , Yu Ning , Shi Yuling
Published: May 2022

Psoriasis is a worldwide chronic inflammatory skin disease. The treatment of disease is usually designed according to its severity. In this research, RNA-seq was performed on 37 patients with psoriasis treated with guselkumab before and after treatment, and the patients were divided into fast responder and slow responder according to PASI score to analyze the differentially expressed genes (DEGs) between them. Moreover, The biological mechanism of psoriasis was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and Gene Set Enrichment Analysis (GSEA) analysis. And then, this protein-protein interaction network was constructed and 17 DEGs including IL-1β, CXCL8, S100A12 and MMP9 were analyzed by GSVA. DEGs were detected by GO and KEGG analysis of target genes, which were primarily associated with immune response, neutrophil activation, neutrophil degranulation. GSEA reminded that fast responders were mainly involved in low-density neutrophils and abundant NK cells. And the GSVA showed that the DEGs were down-regulated after the early stage of the fast responder and the reverse in the slow responder by GSVA analysis. On the whole, these results indicated that these DEGs may serve as a psoriasis potential diagnostic and predictive biomarkers after been treated by guselkumab.
Mechanosurveillance: Tiptoeing T Cells
Authors: Göhring Janett , Schrangl Lukas , Schütz Gerhard J. , Huppa Johannes B.
Published: May 2022

Efficient scanning of tissue that T cells encounter during their migratory life is pivotal to protective adaptive immunity. In fact, T cells can detect even a single antigenic peptide/MHC complex (pMHC) among thousands of structurally similar yet non-stimulatory endogenous pMHCs on the surface of antigen-presenting cells (APCs) or target cells. Of note, the glycocalyx of target cells, being composed of proteoglycans and bulky proteins, is bound to affect and even modulate antigen recognition by posing as a physical barrier. T cell-resident microvilli are actin-rich membrane protrusions that puncture through such barriers and thereby actively place the considerably smaller T-cell antigen receptors (TCRs) in close enough proximity to APC-presented pMHCs so that productive interactions may occur efficiently yet under force. We here review our current understanding of how the plasticity of T-cell microvilli and physicochemical properties of the glycocalyx may affect early events in T-cell activation. We assess insights gained from studies on T-cell plasma membrane ultrastructure and provide an update on current efforts to integrate biophysical aspects such as the amplitude and directionality of TCR-imposed mechanical forces and the distribution and lateral mobility of plasma membrane-resident signaling molecules into a more comprehensive view on sensitized T-cell antigen recognition.
Microplastics in Demersal Sharks From the Southeast Indian Coastal Region
Authors: Janardhanam Madhuvandhi , Sivakumar Priya , Srinivasan Gomathi , Sivakumar Rekha , Marcus Priscilla Niranjani , Balasubramaniam Sujatha , Rajamanickam Krishnamurthy , Raman Thiagarajan , Singaram Gopalakrishnan , Harikrishnan Thilagam
Published: May 2022

Microplastic (MPs) contamination has emerged as a serious worldwide issue. Human activity, commercial enterprises, and fishing are concentrated around the seashore, causing high levels of MPs contamination in coastal and marine organisms. When it comes to their vulnerability to MPs ingestion, sharks are least studied organism. The objective of this study is to investigate MPs accumulation in sharks collected from the Southeast Indian coastal zone (Bay of Bengal). We present evidence of MPs ingestion in demersal sharks caught by the trawlers during trawling operations in marine waters beyond a depth of 80 m in the Southeast India coast. Shark samples were also checked for any gender or size differences in contaminant loading. Gill and gut (digestive tract) were examined in 40 sharks and 82.5% of samples contained at least one MP particle. The average number of MP particles was found to be 4.67 items per individual shark; the gastrointestinal tract showed more MPs than the gills. The majority of the MPs were blue and pale white followed by black and transparent particles with diameters ranging from 0.5 to 2 mm. The fibre fragments were prevalent in the intestines of the shark. Fourier Transform Infrared (FT-IR) spectroscopy revealed that the bulk of polymers were polypropylene (PP), polyacrylamides (PA), and polyethylene (PE). MPs contamination poses an unknown level of harm to shark species. The present study revealed the first scientific data of MPs and associated fibre ingestion in shark species in their habitat in the Bay of Bengal.
Comparing Two Neurodevelopmental Disorders Linked to CK2: Okur-Chung Neurodevelopmental Syndrome and Poirier-Bienvenu Neurodevelopmental Syndrome—Two Sides of the Same Coin?
Authors: Ballardin Demetra , Cruz-Gamero Jose M. , Bienvenu Thierry , Rebholz Heike
Published: May 2022

In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by de novo missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.
Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies
Authors: Just Mie Kristine , Gram Hjalte , Theologidis Vasileios , Jensen Poul Henning , Nilsson K. Peter R. , Lindgren Mikael , Knudsen Karoline , Borghammer Per , Van Den Berge Nathalie
Published: May 2022

Pathogenic alpha-synuclein (asyn) aggregates are a defining feature of neurodegenerative synucleinopathies, which include Parkinson's disease, Lewy body dementia, pure autonomic failure and multiple system atrophy. Early accurate differentiation between these synucleinopathies is challenging due to the highly heterogeneous clinical profile at early prodromal disease stages. Therefore, diagnosis is often made in late disease stages when a patient presents with a broad range of motor and non-motor symptoms easing the differentiation. Increasing data suggest the clinical heterogeneity seen in patients is explained by the presence of distinct asyn strains, which exhibit variable morphologies and pathological functions. Recently, asyn seed amplification assays (PMCA and RT-QuIC) and conformation-specific ligand assays have made promising progress in differentiating between synucleinopathies in prodromal and advanced disease stages. Importantly, the cellular environment is known to impact strain morphology. And, asyn aggregate pathology can propagate trans-synaptically along the brain-body axis, affecting multiple organs and propagating through multiple cell types. Here, we present our hypothesis that the changing cellular environments, an asyn seed may encounter during its brain-to-body or body-to-brain propagation, may influence the structure and thereby the function of the aggregate strains developing within the different cells. Additionally, we aim to review strain characteristics of the different synucleinopathies in clinical and preclinical studies. Future preclinical animal models of synucleinopathies should investigate if asyn strain morphology is altered during brain-to-body and body-to-brain spreading using these seeding amplification and conformation-specific assays. Such findings would greatly deepen our understanding of synucleinopathies and the potential link between strain and phenotypic variability, which may enable specific diagnosis of different synucleinopathies in the prodromal phase, creating a large therapeutic window with potential future applications in clinical trials and personalized therapeutics.
Evaluation of Recombinant Botulinum Neurotoxin Type A1 Efficacy in Peripheral Inflammatory Pain in Mice
Authors: Oehler Beatrice , Périer Cindy , Martin Vincent , Fisher Amy , Lezmi Stéphane , Kalinichev Mikhail , McMahon Stephen B.
Published: May 2022

Well-established efficacy of botulinum neurotoxin type A (BoNT/A) in aesthetic dermatology and neuromuscular hyperactivity disorders relies on canonical interruption of acetylcholine neurotransmission at the neuromuscular junction at the site of the injection. The mechanisms and the site of activity of BoNT/A in pain, on the other hand, remain elusive. Here, we explored analgesic activity of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in a mouse model of inflammatory pain to investigate the potential role of peripheral sensory afferents in this activity. After confirming analgesic efficacy of rBoNT/A1 on CFA-induced mechanical hypersensitivity in C57Bl6J mice, we used GCaMP6s to perform in vivo calcium imaging in the ipsilateral dorsal root ganglion (DRG) neurons in rBoNT/A1 vs. vehicle-treated mice at baseline and following administration of a range of mechanical and thermal stimuli. Additionally, immunohisochemical studies were performed to detect cleaved SNAP25 in the skin, DRGs and the spinal cord. Injection of CFA resulted in reduced mechanical sensitivity threshold and increased calcium fluctuations in the DRG neurons. While rBoNT/A1 reduced mechanical hypersensitivity, calcium fluctuations in the DRG of rBoNT/A1- and vehicle-treated animals were similar. Cleaved SNAP25 was largely absent in the skin and the DRG but present in the lumbar spinal cord of rBoNT/A1-treated animals. Taken together, rBoNT/A1 ameliorates mechanical hypersensitivity related to inflammation, while the signal transmission from the peripheral sensory afferents to the DRG remained unchanged. This strengthens the possibility that spinal, rather than peripheral, mechanisms play a role in the mediation of analgesic efficacy of BoNT/A in inflammatory pain.
Lipidomics Reveals That Rice or Flour as a Single Source of Carbohydrates Cause Adverse Health Effects in Rats
Authors: Wang Siyu , Wang Wenjun , Mao Hongmei , Zhu Mingyu , Xu Zihan , Wang Jun , Zhang Xuesong , Li Baolong , Xiang Xuesong , Wang Zhu
Published: May 2022

The type of diet is very important for the maintenance of health and nutrition. How the sole source of carbohydrates from rice- or flour-based diet affect blood sugar has not been elucidated for a long time. In order to explore the effects of these diets, sixty SD rats were randomly divided into three groups: control group (C group, AIN-93, standard diet), rice diet group (R group), and flour diet group (F group). All the rats were fed for 7 weeks in total by the assigned diets for 4 weeks (stage 1, S1) and all by the AIN-93 diet for 3 weeks (stage 2, S2). The body weights of all the rats were monitored and serum samples were taken for testing blood glucose, biochemical indicators and untargeted lipidome. It was found that both rice and flour-based diets caused weight gain, but the flour diet had a significant increase in blood sugar and low-density lipoprotein (LDL), while a significant decrease in albumin (ALB) and triglycerides (TG). Twenty-three and 148 lipids were changed by lipidomics in the rice diet group and flour diet group, respectively, and two lipids showed the same changes in the two groups, all belonging to TGs, namely TG (16:0/16:0/16:1) and TG (16:0/16:1/18:2), which showed that a single diet source had a significant effect on the health of rats. Fortunately, we can recover this effect through the subsequent standard diet, allowing the rats to return to normal blood sugar, weight and biochemical indicators. A model can predict the diet types through the logistic regression method. Finally, we proposed that a single diet increased blood sugar and weight through a decrease in TGs, and blood sugar and weight returned to normal after a standard diet. Taken together, the short-term negative effects caused by a single diet can be recovered by a standard diet and further proves the importance of diet types.
Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women
Authors: Krga Irena , Corral-Jara Karla Fabiola , Barber-Chamoux Nicolas , Dubray Claude , Morand Christine , Milenkovic Dragan
Published: May 2022

Grapefruit is a rich source of flavanones, phytochemicals suggested excreting vasculoprotective effects. We previously showed that flavanones in grapefruit juice (GFJ) reduced postmenopausal women’s pulse-wave velocity (PWV), a measure of arterial stiffness. However, mechanisms of flavanone action in humans are largely unknown. This study aimed to decipher molecular mechanisms of flavanones by multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified using microarrays. Bioinformatics analyses assessed their functions, interactions and correlations with previously observed changes in PWV. GFJ modified gene and miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes suggests regulation of inflammation, immune response, cell interaction and mobility. Bioinformatics identified putative mediators of the observed nutrigenomic effect (STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone metabolites to transcription factors and cell-signaling proteins. We also observed 34 significant correlations between changes in gene expression and PWV. Moreover, global gene expression was negatively correlated with gene expression profiles in arterial stiffness and hypertension. This study revealed molecular mechanisms underlying vasculoprotective effects of flavanones, including interactions with transcription factors and gene and miRNA expression changes that inversely correlate with gene expression profiles associated with cardiovascular risk factors.

Clinical Trial Registration

[ClinicalTrials.gov], identifier [NCT01272167].
Long-Term Clinical Benefit in EGFR-Mutant Lung Adenocarcinoma With Local Squamous Cell Carcinoma Transformation After EGFR TKI Resistance: A Case Report
Authors: Ye Junru , Ma Yutong , Ou Qiuxiang , Yan Junrong , Ye Bin , Li Yuping
Published: May 2022

The histological transformation from adenocarcinoma (ADC) to squamous cell carcinoma (SCC) is rare but recurrently occurs post TKI treatment in EGFR-mutated non-small cell lung cancer patients with a very limited number of clinical cases published. The outcome of patients after SCC onset is poor as no established treatment guidelines were available. Here we report a case who was initially diagnosed with lung ADC with EGFR L858R driver mutation and demonstrated a partial response (PR) to gefitinib for 27 months before disease progression. The rapidly progressive lung metastatic lesions were determined as an SCC histology with positive PD-L1 expression. Besides EGFR L858R, the metastatic SCC harbored the amplification of CD274 and PDCD1LG2 detected by targeted next-generation sequencing (NGS), which encode PD-L1 and PD-L2, respectively. The disease remained stable on the combination therapy of pembrolizumab plus chemotherapy for eight months until the primary ADC lesion progressed. After the failure of progressed primary ADC lesion with radiotherapy and immunotherapy, systemic ADC metastases were developed in multiple locations including kidney, liver, and chest wall with EGFR L858R mutation but negative PD-L1 expression. The patient then received the combination therapy of bevacizumab plus chemotherapy and the disease remained stable for five months. Since August 2021, afatinib has been administrated which led to a PR and the disease has remained stable up till present. This study demonstrated a primary lung ADC who developed systemic ADC metastases and local SCC transformation with distinct molecular features. The patient has achieved long-term clinical benefit upon multiple lines of chemotherapy and immunotherapy, which provided valuable insight into the treatment of advanced SCC-transformed lung ADC patients.
Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
Authors: Gan Yanglan , Hu Xin , Zou Guobing , Yan Cairong , Xu Guangwei
Published: May 2022

Accurate inference of gene regulatory rules is critical to understanding cellular processes. Existing computational methods usually decompose the inference of gene regulatory networks (GRNs) into multiple subproblems, rather than detecting potential causal relationships simultaneously, which limits the application to data with a small number of genes. Here, we propose BiRGRN, a novel computational algorithm for inferring GRNs from time-series single-cell RNA-seq (scRNA-seq) data. BiRGRN utilizes a bidirectional recurrent neural network to infer GRNs. The recurrent neural network is a complex deep neural network that can capture complex, non-linear, and dynamic relationships among variables. It maps neurons to genes, and maps the connections between neural network layers to the regulatory relationship between genes, providing an intuitive solution to model GRNs with biological closeness and mathematical flexibility. Based on the deep network, we transform the inference of GRNs into a regression problem, using the gene expression data at previous time points to predict the gene expression data at the later time point. Furthermore, we adopt two strategies to improve the accuracy and stability of the algorithm. Specifically, we utilize a bidirectional structure to integrate the forward and reverse inference results and exploit an incomplete set of prior knowledge to filter out some candidate inferences of low confidence. BiRGRN is applied to four simulated datasets and three real scRNA-seq datasets to verify the proposed method. We perform comprehensive comparisons between our proposed method with other state-of-the-art techniques. These experimental results indicate that BiRGRN is capable of inferring GRN simultaneously from time-series scRNA-seq data. Our method BiRGRN is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://gitee.com/DHUDBLab/bi-rgrn.
Long Intergenic Noncoding RNA00265 Enhances Cell Viability and Metastasis via Targeting miR-485-5p/USP22 Axis in Osteosarcoma
Authors: Chen Ting , Liu Jinxin , Zhang He , Li Jiatong , Shang Guanning
Published: May 2022

Osteosarcoma is one of the bone malignancies in children and adolescents. Long noncoding RNAs (lncRNAs) have been demonstrated to participate in osteosarcoma development and progression. Linc00265 has been shown to involve in osteosarcoma oncogenesis; however, the underlying mechanism is largely unclear. In this study, we investigated the function of linc00265 in osteosarcoma cells, including cell viability, migration and invasion. Moreover, we elucidated mechanistically the involvement of linc00265 in osteosarcoma. We found that linc00265 overexpression promoted viability, migration and invasion of osteosarcoma cells. Notably, linc00265 sponged miR-485-5p and increased the expression of USP22, one target of miR-485-5p, in osteosarcoma cells. Strikingly, linc00265 exerted its oncogenic function via regulating miR-485-5p and USP22 in osteosarcoma. Taken together, targeting linc00265 is a promising approach for treating osteosarcoma patients.