bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pegylated recombinant human arginase 1 induces autophagy and apoptosis via the ROS-activated AKT/mTOR pathway in bladder cancer cells
Authors: Zhao Zhuyun , Zhang Peng , Li Wei , Wang Dengchuan , Ke Changneng , Liu Yueming , Ho James Chung-Man , Cheng Paul Ning-Man , Xu Shi 
Published: June 2020

Abstract
Background
Bladder cancer is one of the dominant cancers worldwide, especially for male. Currently, the therapeutical regimen of bladder cancer is based on surgery, radiation therapy, chemotherapy and immunotherapy, but the clinical outcome is still needed to improve. Recombinant human arginase (rhArg, BCT-100) is a novel agent to show great anticancer effect on arginine auxotrophic tumor. However, the effect of rhArg on bladder cancer still remains unclear.
Methods
A panel of six bladder cancer cell lines (BIU-87, EJ-1, J82, SCaBER, T24 and 5637) was employed to assess the anticancer effect of BCT-100 in vitro by MTT assay. T24 nude mice xenograft models were established to evaluate the anticancer effect of BCT-100 in vivo. Protein level (argininosuccinate synthetase 1 (ASS1), ornithine transcarbamylase, cleaved-PARP, PEG, Survivin, p62, Beclin-1, LC3B, p-AKT, p-mTOR) was detected by Western blot. Intracellular, serum and intratumoral arginine concentrations were examined by ELISA. Apoptotic rate, H2O2 and mitochondrial membrane depolarization were tested by flow cytometer. Immunoflorescence on ki67 and TUNEL assay were applied to identify cellular and tumoral apoptotic events.
Results
BCT-100 displayed anticancer effects on bladder cancer cells in vitro and in vivo. The expression of ASS1 varies in different bladder cancer cell lines, and ornithine transcarbamylase is almost deficient except weakly expressed in SCaBER cell line. Knockdown ASS1 in BIU-87 cells could enhance the cytotoxicity induced by BCT-100. Intracellular arginine level was sharply decreased followed by apoptotic events. Futhermore, BCT-100 induced H2O2 production and mitochondrial membrane depolarization, leading to cytochrome c and smac released from mitochondria to cytosol. The expression of LC3B and Becllin-1 was up-regulated, while p62 was down-regulated in a time dependent manner. Autophagic flux was also observed upon BCT-100 treatment. Besides, the phosphorylation of AKT/mTOR pathway was suppressed in a time dependent fashion in BCT-100-treated T24 cells. N-Acetyl-L-cystein reduced the apoptosis and autophagy induced by BCT-100, while CQ, MK-2206 and rapamycin potentiated the apoptosis triggered by BCT-100.
Conclusions
The present study demonstrated that BCT-100 induced autophagy and apoptosis via ROS mediated AKT/mTOR signaling pathway in bladder cancer cells.
Assessing training needs in infectious disease management at major ports, airports and ground-crossings in Europe
Authors: de Rooij Doret , Belfroid Evelien , Hadjichristodoulou Christos , Mouchtouri Varvara A. , Raab Jörg , Timen Aura 
Published: June 2020

Abstract
Background: The implementation of core capacities as stated in the International Health Regulations (IHR) is far from complete, and, as the COVID-19 pandemic shows, the spreading of infectious diseases through points of entry (POEs) is a serious problem. To guide training and exercises, we performed a training needs assessment on infectious disease management among professionals at European POE. Methods: We disseminated a digital questionnaire to representatives of designated airports, ports, and ground-crossings in Europe. Topics were derived from the IHR core capacities for POEs. Based on the importance (4-point Likert scale) and training needs (4-point Likert scale), we identified the topics with the highest priority for training. These results were put in further perspective using prior experience (training <3 year, exercise <5 years, events <5 years). Also, preferences for training methodologies were assessed. Results: Fifty questionnaires were included in the analyses, representing 50 POEs from 19 European countries. Importance is high for 26/30 topics, although scores widely vary among respondents. Topics with a high training need (16/30) are amongst others the handling of ill travelers; using and composing the public health emergency contingency plan, and public health measures. Respondents from ports and airports attribute equal importance to most topics, but respondents from ports showed higher training needs on 75% of the topics. POEs are unevenly and generally little experienced. The most preferred training methods were presentations. Simulation is the preferred methodology for training the handling of ill or exposed travelers. Conclusions: The European workforce at designated ports, airports and ground-crossings has a different level of experience and perceives varying importance of the topics assessed in our study. We identified the topics on which training is required. We call for European collaboration between POEs to agree upon the importance of infectious disease management, and to jointly build a trained and prepared workforce that is ready to face the next crisis.
Psychological consequences of COVID-19 pandemic in Italian MS patients: signs of resilience?
Authors: Capuano Rocco , Altieri Manuela , Bisecco Alvino , d'Ambrosio Alessandro , Docimo Renato , Buonanno Daniela , Matrone Federica , Giuliano Federica , Tedeschi Gioacchino , Santangelo Gabriella , Gallo Antonio 
Published: June 2020

Abstract
Background: Anxiety, depression and reduction of quality of life (QoL) are common in people with multiple sclerosis (pwMS). Fear of getting sick from COVID-19, government’s lockdown and the imposed social distancing might have an impact on psychological distress and QoL. Objectives: The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.Methods: 67 pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation (at T0) and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Bonferroni correction for multiple comparisons was applied.Results: BDI-II and STAI-Y1 scores did not change between T0 and T1, whereas the satisfaction on sexual function subscale of MsQoL-54 was significantly higher at T1 (p<0.001).Conclusions: This is the first study that evaluated mood and QoL levels before and during the lockdown due to COVID-19 pandemic in pwMS. No worsening of anxiety and depression levels was found. Contrariwise, some improvements were noted on QoL, the most reliable regarding the sexual satisfaction.
Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study
Authors: Laskar Monjur Ahmed , Choudhury Manabendra Dutta 
Published: June 2020

Abstract
Background: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. Papain-like protease (PLpro) of SARS CoV-2 is an important target of COVID-19 because it is a multifunctional cysteine protease essential for coronaviral replication. Large numbers of phytochemicals with varied chemical structures isolated from medicinal plants have been shown to possess antiviral activity. Some of these phytochemicals have been chosen on the basis of literature survey for this study. Reported inhibitors of the papain-like protease are taken as control and for QSAR study.Methods: Three dimensional structure of target was downloaded from Protein Data Bank and docked with phytochemicals & inhibitors by using software FlexX. Inhibitors of the papain-like protease were taken from binding database and QSAR analysis was performed by using EasyQSAR software.Results: Six phytochemicals: Baicalin, Rutin, Biopterin, Licoleafol, Luteolin and Quercetin shows stable bonding pattern with the target in compare to known inhibitors as it shows least score in docking, forms maximum number of hydrogen bonds with the active residues of the receptor. The predicted IC50 values of the phytochemicals are also better than the known inhibitors.Conclusion: Based on present observation of docking score of both phytochemicals and known inhibitors, IC50 value of known inhibitors and predicted IC50 of phytochemicals, we suggests above mentioned six phytochemicals may be the Papain-like protease (PLpro) targeted potent drug leads against Covid-19.
Outpatient management or hospitalization of patients with proven or suspected SARS-CoV-2 infection: The HOME-CoV rule.
Authors: D. Douillet , R. Mahieu , V. Boiveau , Y.-M. Vandamme , A. Armand , F. Morin , D. Savary , V. Dubée , C. Annweiler , P.-M. Roy 
Published: June 2020

Abstract
In the context of the COVID-19 pandemic and overloaded hospitals, a central issue is the need to define reliable and consensual criteria for hospitalization or outpatient management in mild cases of COVID-19. Our aim was to define an easy-to-use clinical rule aiming to help emergency physicians in hospitalization or outpatient management decision-making for patients with suspected or confirmed SARS-CoV-2 infection (the HOME-CoV Rule). The Delphi method was used to reach a consensus of a large panel of 51 experts: emergency physicians, geriatricians, infectious disease specialists, and ethical consultants. A preliminary list of eligible criteria was compiled based on a literature review. Four rounds of anonymized expert consultations were performed. The experts were asked to score each item as relevant, possibly relevant and non-relevant, as major or minor, and to choose the cut-off. They were also able make suggestions and remarks. Eight criteria constituting the HOME-CoV were selected: six correspond to the severity of clinical signs, one to the clinical course (clinically significant worsening within the last 24 hours), and the last corresponds to the association of a severe comorbidity and an inadequate living context. Hospitalization is deemed necessary if a patient meets one or more of the criteria. In the end, 94.4% of the experts agreed with the defined rule. Thanks to the Delphi method, an absolute consensus was obtained of a large panel of experts on the HOME-CoV rule, a decision-making support mechanism for clinicians to target patients with suspected or confirmed COVID-19 requiring hospitalization.Trial registration: NCT04338841
Feasibility of Relative Strain Index (RSI) for the Assessment of Heat Stress in Outdoor Environments: Case Study in Three Different Climates of Iran
Authors: Asghari Mehdi , Ghalhari Gholamabbas Fallah , Abbasinia Marzieh , Shakeri Fahimeh , Tajik Reza , Ghannadzadeh Mohammad Javad 
Published: June 2020

Objectives:
Different indices are used to evaluate heat stress in outdoor environments. This study was aimed at examining the applicability of the Relative Strain Index (RSI) to the assessment of heat stress in several climates of Iran.

Methods:
Based on the Köppen classification, three different climates were studied. Arak, Bandar Abbas, and Sari were selected as representative of semi-arid and cold climates, hot and dry, and Mediterranean, respectively. The data recorded by the meteorological organization, including air temperature, relative humidity and air velocity were surveyed during 15-year period in three different climates. The RSI index was calculated by the formula. Also, the Wet Bulb Globe Temperature (WBGT) index was computed using a model presented by the Australian Bureau of Meteorology (ABM). Data were analyzed using SPSS v.22, descriptive statistics, Pearson correlation coefficient, and linear regression.

Results:
The mean RSI index in summer of the 15 years in Arak was 0.033 ± 0.33, in Bandar Abbas 0.54 ± 0.6 and for Sari was 0.17 ± 0.05. A high correlation was found between environmental variables and RSI index in three different climates. As well, there was a positive and significant correlation between both RSI and WBGT indices in three different climates (R2>0.96).

Conclusion:
The RSI index is a simple and empirical index and can be used for the evaluation of heat stress along with other indices. The index estimates the situation more than expected to be stressful in warm and dry conditions. So, it is not a useful index for hot and dry climates such as Bandar Abbas.
The Politics of Campus Free Speech in Canada and the United States
Authors: Newman* Stephen L. 
Published: June 2020

Ontario Premier Doug Ford and US President Donald Trump have something in common: both recently issued directives to colleges and universities intended to promote free speech on campus. Premier Ford’s came first. In August 2018, shortly after winning the provincial election, Ford required all colleges and universities in the province to devise policies upholding free speech on their campuses in line with a minimum standard prescribed by his government. The policies were to be in place no later than January 1, 2019. Failure to comply would result in a reduction of operating grant funding from the province. President Trump’s executive order concerning “free inquiry” on American campuses was issued in March 2019. The order states that it is the policy of the federal government to encourage institutions of higher learning “to foster environments that promote open, intellectually engaging, and diverse debate, including through compliance with the First Amendment for public institutions and compliance with stated institutional policies regarding freedom of speech for private institutions.”1 Colleges and universities that fail to do so are threatened with the loss of federal research and education grants.

* Associate Professor, Department of Politics, Faculty of Liberal Arts and Professional Studies, York University where he teaches political theory.1 Andy Thomason, “Here’s What Trump’s Executive Order on Free Speech Says”, The Chronicle of Higher Education (21 March 2019), online: <chronicle.com/article/Heres-Wat-Trumps-Executive/245943?cid+bn&utm_medium=en&cid=bn>. An executive order is a directive issued by the President of the United States in his capacity as head of the executive branch and has the force of law. Trump’s executive order on campus free speech is reproduced in its entirety online.
Academic Freedom, Canadian Labour Law and the Scope of Intra-Mural Expression
Authors: Lynk* Michael 
Published: June 2020

The Murray Library is the central library at the University of Saskatchewan. In January 2013, the Library Dean announced that ten support staff in the University’s library system, including several working at the Murray Library, were to be laid off. All were women. After each staff member had been individually informed by the Dean that she was being laid off, she was told to collect her possessions and was then immediately escorted off the campus property. The layoffs were part of a University-wide cost cutting measure, which would ultimately result in 40 layoffs among the support staff across the campus. The support staff were unionized, in a bargaining unit represented by the Canadian Union of Public Employees.
The University librarians were also unionized, in a separate bargaining unit represented by the University of Saskatchewan Faculty Association. In the librarians’ collective agreement was a broadly drafted provision protecting academic freedom. Among other things, the provision guaranteed the right of the unionized librarians “…to criticize the University and the Association without suffering censorship or discipline.” This provision did not contain any language which would restrict the scope of its protection to reasonable or responsible comments. This right of faculty and librarians to criticize the university leadership is known, among the various features that make up academic freedom, as the freedom of intra-mural expression.1

* Associate Professor, Faculty of Law, Western University, London, Ontario, where he teaches labour law, human rights law, and constitutional law.1 See generally Matthew Finkin & Robert Post, For the Common Good: Principles of American Academic Freedom (New Haven, Connecticut: Yale University Press, 2009), ch 5.
Production Of L-Glutamic Acid As A Function Of Urease Activity By Corynebacterium glutamicum X680 Using Agro-Based Raw Materials
Authors: Subhadeep Ganguly  
Published: June 2020

Urease catalyzes hydrolysis of urea. The present investigation was undertaken to investigate the urease activity and its optimization during L-glutamic acid fermentation by a biotin auxotroph Corynebacterium glutamicum X680 using urea as the principal nitrogen source. Another interesting part of this study was to investigate the efficiency of this microorganism for utilization of indigenous raw materials (such as hydrolysates of cassava starch, rice bran and wheat bran) as a cheap carbon sources instead of glucose. Among different raw materials, hydrolysate of cassava starch appeared to be the most suitable. However, the production efficiency is significantly less (p<0.01) with cassava starch compared to glucose. When the medium is supplemented with equivalent amount of (10g%) cassava starch hydrolysate, the L-glutamic acid accumulation was reported to be 18.2mg/ml with maximum urease activity (0.18U/mg protein) with pH7 at 300C.Thus, among the different agro-based wastes were examined, cassava starch hydrolysate appeared to be the best alternative of glucose to minimize L- glutamic acid production cost.
Colorimetric Sensing of Hg2+ and Fe3+ Ions in aqueous solution using Green Synthesized Silver Nanoparticles
Authors: Pinaki Mandal  , Samir Maji  
Published: June 2020

Plant extracts have a very important role for the synthesis of different nanoparticles due to its reducing capability, availability and nontoxicity. Biosynthesized silver nanoparticles were investigated for colorimetric sensing of metal ions at different concentrations. Aqueous leaf extract of Plumeria alba was used as bio reduction to synthesize stable Silver nanoparticles (AgNPs). A possible interaction between AgNPs and metal ions at different concentrations was proposed on the basis of UV-Vis spectral analysis. The produced silver nanoparticles were characterised by different technique which includes UV–vis spectroscopy and transmission electron microscopy (TEM). The intensity of the localized surface plasmon absorption band at 438 nm in UV-visible spectrum confirmed the presence of silver nanoparticles. TEM analysis showed the spherical and irregular particles shape and size of nanoparticles ranging from 20 to 100 nm. Metal ion sensing properties of these AgNPs in aqueous solution has been explored. In the detection of different metal ions using these green synthesized AgNPs, the promising colorimetric response was observed with naked eyes and spectroscopic changes were examined by using a UV-Visible spectrophotometer. The colorimetric sensor studies showed selective sensing of Fe3+ and potentially hazardous Hg2+ ions in aqueous medium with a limit of detection of about 0.2 mM concentrations. This method may be applied as low cost and high potential colorimetric sensor for the selective recognition and monitoring of Hg2+ and Fe3+ ions in biological, pharmaceutical samples as well as in water.
Komunikasi Interpersonal Santri
Authors: Munir Muhammad , Latifah Lailatul 
Published: June 2020

Interpersonal Communication can occur in place, namely in boarding schools. If Interpersonal Communication doesnâ€™t effectively do, there will be awkwardness in Communication. The phenomenon that occurs in santri in pesantren is closed Communication with seniors. Because it is awkward that makes interpersonal Communication of students becomes inappropriate because there is a sense that is embedded in students to senior students, as well as senior students of prestige to greet and give greetings to junior students. This research approach is a phenomenological study, while this type of research is qualitative. While interviews, observations and documentation are methods of collecting data. They consisted of Al-Amien Prenduan students and An-Nurriyah Surabaya students. Because this boarding schools has a strict discipline and found the difference. While data reduction, synthesis, compiling working hypotheses are as data analysis. Triangulation and extension of participation as checking the validity of the data. The results of this study are interpersonal Communication of junior and senior santri, the social behavior of junior and senior santri, social interaction of junior santri and senior santri, the doctrine of senior santri to junior santri, fanatic of junior santri and senior santri, bullying of junior santri and senior santri.

Komunikasi interpersonal dapat terjadi di manapun termasuk pondok pesantren. Jika Komunikasi Interpersonal tidak dilakukan secara efektif maka akan terjadi kecanggungan dalam berkomunikasi, umumnya fenomena komunikasi yang terjadi antar santri di pesantren adalah komunikasi tertutup. Hal ini dikarenakan rasa canggung antara santri senior dan santri junior dalam berinteraksi, santri senior gengsi untuk menyapa dan memberikan sapaan kepada santri junior. Pendekatan penelitian ini adalah studi fenomenologi dengan menggunkan jenis penelitian kualitatif. Pengumpulan data menggunakan wawancara, observasi dan dokumentasi. Sedangkan reduksi data dan sintesisasi digunakan sebagai analisis data. Selain itu menggunakan triangulasi dan perpanjangan keikutsertaan untuk pengecekan keabsahan data. Hasil dari penelitian ini menggambarkan komunikasi interpersonal santri junior dan santri senior, perilaku sosial santri junior dan santri senior, intraksi sosial santri junior dan santri senior, doktrin santri senior kepada santri junior, fanatik santri junior dan santri senior, serta bullying santri junior dan santri senior.
ANALISIS PENYELESIAN SENGKETA INTERNAL LEMBAGA NEGARA (STUDI KASUS PELANTIKAN PIMPINAN DEWAN PERWAKILAN DAERAH REPUBLIK INDONESIA PERIODE 2017-2019)
Authors: Nugraha Yanzah Bagas , Budisetyowati Dwi Andayani 
Published: June 2020

The establishment of the Regional Representative Council of the Republic of Indonesia so called Dewan Perwakilan Daerah (DPD-RI) at least has two objectives. The first is to enhance justice for the people in the region. Secondly, to expanding and increasing the participation of local communities in national life. The process to form this state institution is done by amending the 3rd amendment of the 1945 Constitution of the Republic Indonesia. However, in doing that amendment there was an internal conflict within the body of DPD-RI involving the old and the new leaders of this institution last year. The length of leadership tenure which was initially made 5 years was amended to became 2.5 years. The different length of leadership tenure was then canceled by the Supreme Court and it was decided to be the same as other institution such as The People’s Consultative Assembly and The House of Representative in that the leadership tenure should be in accordance with the electoral cycle of 5 years. However, although the regulation of DPD-RI has been canceled, the Supreme Court keeps sending its representative to guide the oath of position of the new DPD-RI leadership. The only regulation that has been introduced by the state was regulation toward conflict between state institutions and this conflict can merely be resolved by the Constitutional Court. Therefore, there is an urgent need for the state to seek solution to solve this problem to prevent the same thing happened to other state institution in the future.