bluuebunny/crossref_metadata_2025_split huggingface dataset:
FXR expression in a rat model of hilar cholangiocarcinoma
Authors: Zhang Meng-yu , Wang Jie-ping , he Kai , Xia Xian-ming 
Published: May 2020

Abstract
Background: To develop a rat model of hilar cholangiocarcinoma and detect Farnesyl X receptor (FXR) expression in hilar cholangiocarcinoma tissues of this model, in order to provide a new method for the treatment of hilar cholangiocarcinoma.Methods: Forty male Wistar rats (body weight, 185 ± 5 g) were randomly divided into two groups (n = 20 each) as follows: The control group was fed a standard diet, and the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe. Every day note the rats’ mental state, diet, and fur condition. At 4 weeks, one rat of the experimental group was sacrificed, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of FXR in hilar cholangiocarcinoma and normal hilar bile duct tissues.Results: From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with controls. After 6 weeks, we detected hilar cholangiocarcinoma in 17 rats (85%) in the experimental group. In the experimental group, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those of the control group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The FXR/Gapdh mRNA ratio in hilar cholangiocarcinoma and normal hilar bile duct tissues differed markedly. Light microscopy revealed a granular pattern of FXR expression which reacted with the anti-FXR antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with >10% positive cells were designated positive,Sections with <10% positive cells were designated negative. Each group included 4,800 cells. In the experimental group, 1,196 cells (24.9%) were positive and 3,538 cells (73.7%) were positive in the control group, and this difference was statistically significant.Conclusion: FXR expression significantly decreased in hilar cholangiocarcinoma of rats than in those of controls, suggesting that drugs targeting FXR may be a new strategy for hilar cholangiocarcinoma.
Timing of immune checkpoint inhibitors for metastatic patients over 75 years of age: the earlier the better
Authors: Landre Thierry , Guetz Gaetan Des , Chouahnia Kader , Fossey-Diaz Virginie , Culine Stéphane 
Published: May 2020

Abstract
Background The impact of ageing on Immune Checkpoint Inhibitors (ICIs) effectiveness remains controversial. However, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We focused our study on patients over 75 and looked at the potential impact of timing in the use of ICIs. Methods We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumors. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients (< 75 years). Hazard ratios (HRs) with their 95% confidence interval (CI) were collected and pooled. Results Fifteen phase III studies evaluating anti-PD-1(nivolumab or pembrolizumab), anti-PD-L1 (atezolizumab or avelumab) or anti-CTLA-4 (ipilimumab) were included. Patients were enrolled for Non-Small-Cell-Lung-Cancer, Renal-Cell-Carcinoma, Melanoma, Head-and-Neck-Squamous-Cell-Carcinoma or Gastric Cancer. Eight studies assessed treatment in first-line setting and seven in the second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 youngers. In first-line setting, HRs for death were 0.78 (95% CI: 0.61-0.99) in patients ≥75 years versus 0.84 (95% CI: 0.71-1.00) in younger. In second line setting, HRs for death were 1.02 (95% CI: 0.77-1.36) in patients ≥75 years versus 0.68 (95% CI: 0.61-0.75) in younger with a statistically significant difference observed between subgroups (p interaction = 0.009). Conclusions ICIs appears to be effective in patients over 75 years of age. However, the survival benefit is mainly observed in first-line treatment.
Effectiveness of a phantom based learning model for medical students to achieve ultrasound-guided vascular access – a prospective study
Authors: Jagoda Philippe , Stroeder Jonas , Buecker Arno , Gawlitza Joshua , Frenzel Felix , Raczeck Paul 
Published: May 2020

Abstract
Background:
This prospective study evaluated the learning curve of inexperienced medical students in successfully establishing an ultrasound guided vessel access.

Methods:
Medical students (n=11) with no experience in ultrasound imaging were asked to perform an ultrasound- guided vessel access simulated by a gelatin based phantom model. Success rates and time of procedures were measured. Afterwards, every student underwent peer-teaching with both theoretical information given and practical training skills applied. Then, every student had to perform the very same procedure again and results were compared in a prior- to post-teaching scenario with paired t-test.

Results:
After theoretical and practical teaching lessons all students were able to successfully establish an ultrasound-guided vascular access. Prior to teaching sessions, only 4 out of 11 students managed to successfully perform the procedure. Success rate rose from 36.4% to 100%. Mean number of attempts were 2.5 +- 1.3 before, and 1.2 +- 0.4 after teaching (p < 0.05). Overall time to successful guide wire placement improved from 291+-8 seconds to 151+-37 seconds (p<0.05).

Conclusions:
In a gelatin based phantom model for ultrasound-guided vascular access medical students demonstrate significantly improved practical puncture skills and thus a steep learning curve.
Molecular docking of natural compounds from tulsi (Ocimum sanctum) and neem (Azadirachta indica) against SARS-CoV-2 protein targets
Authors: Kumar Arun 
Published: May 2020

Abstract
Background: Antiviral activity of tulsi and neem extracts are widely reported. Selected natural compounds from tulsi and neem were hence screened for their efficacy against SARS-CoV-2 targets. Materials and Methods: Using molecular docking tools, the binding efficacy of natural compounds from tulsi and neem were tested against three key SARS-CoV-2 targets i.e., 1) surface glycoprotein (6VSB) responsible for viral attachment, 2) RNA dependent RNA polymerase (6M71) responsible for viral replication and 3) main protease (6Y84) responsible for viral replication. Results: Methyl eugenol, oleanolic acid and ursolic acid had high binding efficacy against surface spike glycoprotein and RNA polymerase of SARS-CoV-2. Epoxyazadiradione, Gedunin, Methyl eugenol, Oleanolic acid and Ursolic acid showed high binding efficacy against the main protease of SARS-CoV-2. Binding efficacy of natural compounds from tulsi and neem was superior to that of the standard drugs Lopinavir/Ritonavir and Remdesivir. Conclusion: Natural compounds from tulsi and neem have high binding efficacy against SARS-CoV-2 targets involved in viral attachment and replication, hence will be useful in the management of infection caused by SARS-CoV-2.
COVID-19 may present with an itchy erythematous papular rash: a case report
Authors: Serafini Alice , Kurotschka Peter K. , Bertolani Mariabeatrice , Riccomi Silvia 
Published: May 2020

Abstract
Background: the most commonly reported clinical manifestations of Coronavirus Disease (COVID- 19) are: fever, fatigue, dry cough, anorexia, myalgias, dyspnoea and sputum production. Other, rarer, manifestations include headache, sore throat, rhinorrhoea, nausea, diarrhoea and olfactory or taste disorders. Two recent small-scale studies suggest the possibility of a skin rash being a clinical presentation of the disease. The purpose of our case report is to bring attention to an atypical presentation of the disease (skin rash) and reflect on the importance of the correct identification of COVID-19 suspicious symptoms as part of the crucial activity of case-finding in primary care.Case presentation: the patient is an Italian 32 years old female nurse who has had several close contacts to COVID-19 cases during her working shifts. On the 13 th March 2020 she developed an itchy erythematous papular rash sparing only her sparing only her face, scalp and abdomen. One week later she developed fever and diarrhoea. During the first week of remote assessment carried out by her General Practitioner (GP), she gradually developed a dry cough, intermittent fever and diarrhoea. At the time of article submission (31 days after the symptoms onset), she has not completely recovered and is still suffering of a dry cough, headache, fatigue and, occasionally, diarrhoea.Conclusions: this study suggest that skin manifestations could be an early presentation of COVID-19 and, during outbreaks, they should be taken into proper account by primary care providers as possibly caused by Sars-Cov-2. Early identification of COVID-19 patients is a crucial part of the strategy of case detection and case isolation, which has shown to be crucial in the reduction of incidence and COVID-19-related mortality. Further research is needed to establish frequency, symptoms, signs, pathogenesis and role in case detection of skin manifestations in COVID-19 patients.
Clinical features and laboratory findings of SARS-CoV-2 infection in hospitalized patients
Authors: Wang Lijuan , Zhang Yuanyuan , Du Yan , Xu Yunfang , Jing Yang , Wu Jing , Zhang Jingqi , Yue Ming , Liu Xingxiang , Dong Chen 
Published: May 2020

Abstract
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a new emerging public health crisis to the world. However, data are still limited on the clinical features and laboratory findings in COVID-19 patients.Methods: Medical records including demographics characteristics, clinical features, laboratory findings and radiological materials of 66 hospitalized COVID-19 patients were collected between Jan 23 and Mar 9, 2020. Symptoms/signs with potential association with the disease severity were analyzed.Results: Of 66 hospitalized COVID-19 patients, the male-to-female ratio was 44:22. There were eight cases potentially exposed to one single patient. The most common initial symptoms of SARS-CoV-2 infection were fever (77.3%) and cough (74.2%). Compared to those with non-severe infection, the severe patients were more likely to be older (62.6 ± 15.1 vs 46.9 ± 13.3 years. P = 0.001) and with more infected lobes. As the results shown, higher initial (on admission) and peak (during hospitalization) counts of lymphocyte were inversely associated with the severe SARS-CoV-2 infection (both OR: 0.01 every 1´109/L decrease). However, the elevated initial neutrophil counts (OR: 1.63 every 1´109/L increase), initial and peak levels of LDH (OR: 1.02 and 1.01 every 1 U/L increase), peak levels of CRP (OR: 1.03 every 1 mg/L increase), AST (OR: 1.06 every 1 U/L increase) and ALT (OR: 1.02 every 1 U/L increase) were significantly associated with COVID-19 severity.Conclusion: Our present study indicated that fever and cough were the most common initial symptoms of SARS-CoV-2 infection, and the virus could be efficiently spread by person-to-person transmission. In addition, lymphocyte and neutrophil counts, and serum levels of AST, ALT, CRP and LDH should be useful for the evaluation on COVID-19 severity.
DIREITO PENAL COMO INSTRUMENTO IDEOLÓGICO PATRIARCAL
Authors: POLI Beatriz Capalbo , GERA Marcos Silvestre 
Published: May 2020

Desenvolve-se uma análise sobre o poder ideológico patriarcal por intermédio do Direito Penal, como forma de manter seu status e poder. Objetiva-se trazer à luz do bom-senso o assunto, destacando os processos de naturalização - apresentar como naturais processos decorrentes de ações humanas, portanto, históricas -, e universalização - apresentar como universais os valores da classe dominante de uma sociedade, estendendo seus valores às outras, de forma sutil, como se fossem igualmente importantes para todas as classes sociais - que conceitos provenientes da ideologia patriarcal passaram por meio do Direito Penal, que atua como emissor e receptor destes. Apesar das alterações e revogações de dispositivos prejudiciais às mulheres e conquistas de novos direitos para sua proteção; o legado ideológico dos conceitos machistas e patriarcais, que estão ou estiveram presentes no Direito Brasileiro, continuam, até a atualidade, podendo ser demonstrado pelo número crescente de casos de crimes contra mulheres, bem como pela opinião popular que continua em grande medida culpando a vítima pelas mais diversas atrocidades praticadas em detrimento dela. Ou seja, as mudanças acontecem pela pressão dos movimentos sociais, entretanto, não há o pleno entendimento dos reais motivos dessas demandas, gerando alterações no macro, sem haver entendimento de base, para que de fato haja uma mudança na mentalidade do senso comum, a caminho do bom senso. Através dos métodos dedutivo bibliográfico e histórico, esclarece-se os assuntos relativos ao tema da pesquisa, visando a superação da naturalização da ideologia. Palavras-chave: Poder ideológico patriarcal. Direito Penal. Machismo. Feminismo.
JUSTIÇA FISCAL: UMA ANÁLISE DA APLICAÇÃO DO PRINCÍPIO DA CAPACIDADE CONTRIBUTIVA A LUZ DO IPVA
Authors: FARACO Gabriel Araujo 
Published: May 2020

O presente trabalho tem como objetivo abordar os princípios tributários trazidos pela Constituição Federal de 1998, no Título VI, da Tributação e do Orçamento, Capitulo I, do Sistema Tributário Nacional, Seção II, das limitações ao poder de tributar e analisar a aplicação no caso concreto destes princípios, especialmente o Princípio da Capacidade Contributiva e se estes realmente operam como mecanismos de defesa do contribuinte frente a atuação do Estado no campo do direito tributário. É necessário esclarecer que o modelo de tributação de um país deve buscar atingir vários objetivos, às vezes conflitantes. O primeiro desses objetivos é arrecadar para financiar políticas públicas, em segundo lugar, os tributos de um país devem gerar o mínimo de distorções econômicas que prejudicam o crescimento. Por fim, a tributação deve contribuir para melhorar a distribuição de renda do país. No presente trabalho, o foco será a aplicabilidade dos referidos princípios da cobrança do Imposto sobre Propriedades de Veículos Automotores – IPVA. Assim, serviços essenciais à população, como educação, saúde, moradia e segurança, considerados direitos fundamentais pela Constituição Federal de 1988, são muito mal prestados aos cidadãos, embora a administração pública seja remunerada (e muito bem) para oferecê-los com boa qualidade a todos.
RESPONSABILIDADE CIVIL DA ADMINISTRAÇÃO PELA QUALIDADE DA ALIMENTAÇÃO
Authors: BARBOSA Guilherme Gumiero , ROCHA Manoel Ilson Cordeiro 
Published: May 2020

Este trabalho destina-se a propagação do direito à alimentação escolar, bem como rapidamente demonstrar o que seria uma alimentação de qualidade. Dada a necessidade de muitos alunos da Rede Pública de ensino em ter uma alimentação oferecida na escola, fala-se em alimentação fornecida pela administração pública, logo, administração presta um serviço para a comunidade, desta forma é responsável por aquilo que fornece. Quando presta esse serviço de forma ineficiente há que se falar em responsabilidade civil da administração, já que seria responsável diretamente pelos serviços por seus agentes prestados. Interessante expor, que não se faz necessária a ilicitude da conduta praticada, mas simplesmente que esta conduta causou efetivo dano a outrem. O corpo discente no Brasil, tem reconhecidamente o direito à alimentação escolar, porém não basta apenas fornecer, mas sim fornecer com qualidade, respeitando as necessidades nutricionais diárias de cada faixa etária.
The problem of refusal from immunodiagnosis of tuberculosis: results of a multi-center sociological study
Authors: Kazykina T. N. , Sterlikov S. A. , Borisova E. S. , Gripekina N. V. , Dolzhenko E. N. , Elenkina Zh. V. , Kozlova L. V. , Maliev B. M. , Fadeev P. A. , Khorotetto V. A. 
Published: May 2020

The objective: to study the reasons for the refusal of legally authorized representatives of children to conduct mass immunodiagnosis of tuberculosis using a representative sample of population and to outline possible ways to change this negative situation.Subjects and methods: A cross-sectional multi-center study was conducted. In 8 regions of the Russian Federation, the survey was conducted in 1,059 legally authorized representatives of children refusing to undergo mass immunodiagnostics of tuberculosis. The following main reasons for refusal were found out: fear of side effects and complications (32.6%), distrust in the quality of the test (29.7%), lack of understanding of the need to examine a child for tuberculosis. 72.2% of respondents demonstrated poor awareness of the problem of tuberculosis – they denied this problem or associated it with a different social environment, which was fertile ground for negative information received through various channels. To solve this problem, it is necessary to intensify health education in various groups of the population, including work with religious communities. Additional resources can be used such as targeted social advertisements, which will allow covering with health education propaganda of 33.1% of people who do not want to receive information about tuberculosis, expanding the regulation for the use of alternative methods of screening for tuberculosis.The authors state that they have no conflict of interests.
Hacia una explicación naturalizada del problema filosófico de las otras mentes
Authors: Gòmez Tabares Anyerson Stiths , Ospina José Fernando , Micolta Henao Andres Felipe 
Published: May 2020

En este artículo se pretende mostrar que el tratamiento de algunos problemas tradicionales de la filosofía de mente, para el caso de este trabajo, el problema de las otras mentes, debe articularse a una visión naturalista del mundo, y en coherencia con ello, al estudio empírico de las ciencias cognitivas, de tal manera que, la reflexión meta-teórica propia de la filosofía soporte sus principios metafísicos, epistemológicos y lógicos desde el andamiaje de la evidencia empírica.
Se intentará utilizar una metodología naturalista basada en la revisión de teorías científicas con evidencia empírica en el campo de la neurociencia cognitiva, la etología y la psicología cognitiva sobre el problema filosófico de las otras mentes y de cómo el constructo científico de teoría de la mente (ToM) puede aportar a su solución o reformulación. Esto supone, ciertamente, una re-evaluación del problema filosófico, sus argumentos e intentos de solución, resultado de una naturalización fructífera anclada a una visión teleológica de la evolución cognitiva-social del ser humano y otras especies.
Human activity impact on surface water quality in semi-arid regions: a case study of Aïnzeda lake (North-East Algeria)
Authors: Mebarkia Abdelhafid , Boufekane Abdelmadjid 
Published: May 2020

Abstract
Water resources scarcity in Algeria, their fragility and their unequal distribution have resulted in a serious shortage, which, in spite of all the efforts, seems inevitable. This study consists of evaluating the impact of human activity on the water quality of Aïnzeda lake (NE Algeria), a typical case study of the difficulties posed by the problem of surface water quality in semi-arid regions. Principal component analysis (PCA) and the trend method were applied to interpret the physico-chemical data of monthly analyzed samples, over a 25-year period (1988–2012). The trend method results show that most chemical elements have a direct relationship with urbanization and agricultural practices in the area. The change in the watershed climatic conditions (increase of 9% in air temperature, 7% in the lake water temperature, and decrease of 8% in precipitation) is also responsible for the degradation of the water quality. The PCA shows that salinization (51.73%), and anthropogenic and agricultural pollution (13.49%) are the most significant degradation factors. These two approaches have enabled us to prove that aridity and anthropogenic or agricultural activities have a negative impact on the lake's surface water quality.
Upcoming Drifts in Bio-similars
Authors: Aggarwal Geeta , Nagpal Manju , Sharma Ameya , Puri Vivek , Dhingra Gitika Arora 
Published: May 2020

Background:
Biopharmaceuticals such as biological, medicinal products have been in
clinical use over the past three decades and have benefited the therapy of degenerative and critical
metabolic diseases. It is forecasted that the market of biologics will be going to increase at a rate of
˃ 20% per year, and by 2025, more than 50% of new drug approvals might be biological products.
The increasing utilization of the biologics necessitates cost control, especially for innovator products
that have a lengthy period of exclusive usage. As the first wave of biopharmaceuticals is expired
or set to expire, it has led to various opportunities for the expansion of bio-similars i.e. copied
versions of original biologics with same the biological activity. Development of biosimilars is expected
to promote market competition, meet worldwide demand, sustain the healthcare systems and
maintain the incentives for innovation.

Methods:
Appraisal of published articles from peer-reviewed journals, PubMed literature, latest
news and guidelines from European Medicine Agency, US Food Drug Administration (FDA) and
India were used to identify data for review.

Results:
Main insights into the quality requirements concerning biologics, the current status of
regulation of bio-similars and upcoming challenges lying for the upgrading of the marketing
authorization of biosimilars have been incorporated. Compiled literature on the therapeutic status,
regulatory guidelines and the emerging trends and opportunities of biosimilars has been thoroughly
stated.

Conclusion:
Updates on biosimilars will support to investigate the possible impact of bio-similars
on the healthcare market.
Природа открытия и модификации дираковской щели в аксионном антиферромагнитном топологическом изоляторе MnBi-=SUB=-2-=/SUB=-Te-=SUB=-4-=/SUB=-
Authors: Шикин А.М. 
Published: May 2020

Abstract The angle-resolved photoelectron spectroscopy with photoexcitation by laser radiation ( h ν = 6.3 eV) is used to study the modification of the gap open at the Dirac point in an axion antiferromagnetic topological insulator MnBi_2Te_4 at temperatures higher and lower the Néel temperature (24.5 K). The open gap is shown can have both anomalously high (62–67 meV) and significantly decreased (15–18 meV) values in various MnBi_2Te_4 samples or various areas of the same sample. In both the cases, the gap remains open above the Néel temperature. As a result of the studies, it is assumed that the difference in the widths of the gaps open at the Dirac point is related to the manifestation of the effect of fractionation of axion term θ. The gap width (62–67 meV) that correlates with the result of theoretical calculations corresponds to the state with axion term θ = π. In this case, the experimental observation of the gap at the Dirac point of 15–18 meV corresponds to the effective modulation of the axion term θ = π/4 due to the generation of many-body chiral spin fluctuations and their interaction upon laser photoexcitation.