bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol
Authors: Gao Lin-rui , Wang Xin , Han Weiming , Deng Wei , Li Chen , Wang Xiaomin , Zhao Yidian , Ni Wenjie , Chang Xiao , Zhou Zongmei , Deng Lei , Wang Wenqing , Liu Wenyang , Liang Jun , Zhang Tao , Bi Nan , Wang Jianyang , Zhai Yirui , Feng Qinfu , Lv Jima , Li Ling , Xiao Zefen 
Published: May 2020

Abstract
Background: Since the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8–2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC.Methods: This two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA–IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5–6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial.Discussion: In unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated.Trial registration: clinicaltrials.gov (NCT03308552, November 1, 2017).
Sepsis and septic shock in COVID-19: a scoping review of the research data
Authors: Lakoh Sulaiman , JIBA Darlinda F. , BALDEH Mamadu , VANDY Alren O. , BENYA Hassan , LADO Marta , SEVALIE Stephen , YENDEWA George A. , SAHR Foday 
Published: May 2020

Abstract
Background

Sepsis is a major contributor to global mortality with an estimated 700, 000 sepsis-related deaths annually. As sepsis is an acute complication of COVID-19, the ongoing pandemic can increase its global burden. Despite this, there is still limited research evidence on COVID-19 and sepsis. In this scoping review, we described the research data on sepsis and septic shock among patients with COVID-19.
Methods

We adapted Arksey and O’Malley framework by reviewing relevant studies published on medRxiv, PubMed, and Google Scholar between January 01, 2020, and April 16, 2020, on sepsis and septic shock with the publication language restriction to English. The findings included the prevalence and outcome of COVID-19 patients with sepsis or septic shock, sepsis criteria, laboratory data, and the treatment given to COVID patients.
Results

Of the 16 eligible articles included in this review, 13 (81.2%) were conducted in China. With the exception of one article, the research work for all the articles was conducted in adult patients. The articles were retrospective studies (12, 75%), case reports (3, 18.8%) and prospective observational studies (1,6.2%). The estimated prevalence of sepsis and septic shock range from 6.8–100% and 4–28.9%, respectively. Serum lactate, platelets, C-reactive protein, white cell counts, and procalcitonin were elevated in 24.5%, 6.2%, 31.2%, 62.5%, 43.8% and 37.5% of the articles, respectively. Bacterial cultures were documented in 4(25%) of the eligible articles. 12 (75%) and 11 (68.8%) articles documented the use of antivirals and antibiotics, respectively. Other antimicrobials used among COVID-19 patients were hydroxychloroquine (1,6.3%), chloroquine (1, 6.3%), and unspecified antifungal drugs (2, 12.5%). Supportive therapies like oxygen therapy, mechanical ventilation, and fluid therapy were documented in 12(75%), 13 (81.3%), and 2 (12.5%) articles, respectively. The highest and lowest mortality among the study participants is 29.8% (134) and 5.4% (12), respectively.
Conclusion

There is a paucity of data in the literature on sepsis in COVID-19 despite its high burden among the COVID-19 patient population resulting in a high rate of antimicrobial use that is not backed by clearly documented microbiology laboratory support. Research is needed to understand the burden of sepsis in COVID-19.
Nutritional Quality of Beverages Available in Vending Machines in Health and Social Care Institutions: Do We Really Want Such Offers?
Authors: Rozman Urška , Mis Nataša Fidler , Kupirovič Urška Pivk , Pravst Igor , Kocbek Primož , Strauss Maja , Turk Sonja Šostar 
Published: May 2020

Abstract
Background Vending machines represent one way of offering food, but they are overlooked in the efforts to improve people’s eating habits. The aim of our study was to analyse the variety and nutritional values of beverages offered in vending machines in social and health care institution in Slovenia.Methods The available beverages were quantitatively assessed using traffic light profiling and the model for nutrient profiling used by Food Standards Australia New Zealand. Vending machines in 188 institutions were surveyed, resulting in 3046 different beverages consisting of 162 unique product labels.Results Between 51% and 54% of beverages were categorized as unhealthy with regard to sugar content. Water accounted for only 13.7% of all beverages in vending machines. About 82% of beverages in vending machines were devoted to sugar-sweetened beverages, the majority (58.9%) presented in 500 ml bottles. The average sugar content and average calories in beverages sold in vending machines are slightly lower than in beverages sold in food stores.Conclusions We suggest that regulatory guidelines should be included in the tender conditions for vending machines in health and social care institutions, to ensure healthy food and beverage choices.
CAMBRIDGE ANALYTICA: ESCÂNDALO, LEGADO E POSSÍVEIS FUTUROS PARA A DEMOCRACIA
Authors: Fornasier Mateus De Oliveira , Beck Cesar 
Published: May 2020

O texto traz um referencial acerca do caso da empresa Cambridge Analytica (C.A). Foram demonstradas, ao longo do artigo, as causas que levaram ao escândalo ocorrido, o legado deixado a partir disso e as possibilidades de futuro para a referida empresa. São mencionados ainda os pontos que levaram a C.A a cometer erros que custaram sua reputação. O artigo aborda ainda que o ocorrido com a empresa poderá acontecer com diversos outros setores, necessitando, portanto, de ações preventivas capazes de trabalhar e modificar pontos falhos. O texto é finalizado a partir da observação acerca da Fake News – tema amplamente mencionado no passado-recente e sobre a Deep Fake - tema do futuro-imediato. A importância do conhecimento acerca desses termos próximo das eleições a serem realizadas no ano de 2020 identifica que o eleitor brasileiro ainda precisa compreender melhor a questão da escolha consciente a fim de promover a boa manutenção do Estado Democrático de Direito, sendo essas questões um aprendizado ensinado a partir da análise do exemplo do escândalo da CA O estudo é feito por meio de uma pesquisa de natureza descritiva, com método hipotético-dedutivo, sendo um estudo de caso de abordagem qualitativa e transdisciplinar, com técnica bibliográfico-documental.
Evaluation of Blood Oxidant/Antioxidant Changes and Testicular Toxicity after Subacute Exposure to Cadmium in Albino Rats: Therapeutic Effect of Nigella sativa Seed Extracts
Authors: Uchendu Ikenna Kingsley , Okoroiwu Henshaw Uchechi 
Published: May 2020

Aim and Objective:
Cells and tissues of the body are prone to oxidative damage as a
result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying
ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect
of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress
and testicular toxicity in albino rats.

Materials and Methods:
Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly
grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal
administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose
MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group
E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment
was administered to group A (Normal control). The oxidative state of the blood was assessed by
measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was
assessed by measuring serum testosterone level using ELISA. The testes were harvested for
histopathological examination.

Results:
The results showed that cadmium induced a marked elevation in the level of MDA, and a
decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant
alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the
testes showed that cadmium significantly induced testicular injury, which was however
ameliorated by the seed extract of N. sativa.

Conclusion:
We conclude that N. sativa seed extract is potentially testiculoprotective and
attenuates oxidative stress against harmful chemical toxins such as cadmium.
Bioanalytical Method Validation of an RP-HPLC Method for Determination of Rifampicin in Liver Perfusion Studies
Authors: Izat Nihan , Kaplan Ozan , Celebier Mustafa , Sahin Selma 
Published: May 2020

Background:
The number of validated quantification methods for rifampicin, a prototypical Oatp inhibitor, in biological rat samples was limited.

Objective:
This study was conducted to validate a modified reversed-phase liquid chromatographic method for the determination of rifampicin in rat liver tissue according to the current ICH M10 Bioanalytical Method Validation Draft Guideline (2019) for application to samples of in situ rat liver perfusion studies.

Methods:
Liver tissue samples were obtained from recirculatory in situ rat liver perfusion studies. The
analysis was performed on a C18 column with a mobile phase composed of 0.05 M phosphate buffer
(pH 4.58): acetonitrile (55:45, v/v). The assay was validated for selectivity, calibration curve and
range, matrix effect, carry-over, accuracy and precision, reinjection reproducibility, and stability.

Results:
he method was considered selective and stable, without having carry-over and matrix effects.
The calibration curve was linear (R2: 0.9983) within the calibration range (0.5-60 ppm). Accuracy and
precision values fulfilled the required limits. Liver concentrations of rifampicin in liver tissue, obtained
after 60 min perfusion with 10 μM and 50 μM of rifampicin, were 45.1 ± 11.2 and 313.4 ± 84.4 μM,
respectively.

Conclusion:
The bioanalytical method validation was completed and the method was successfully applied for the determination of rifampicin in rat liver tissue.
Determination of Free Amino Acids in Banlangen Granule and its Fractions by Solid Phase Extraction Combined with Ion-pair Hig-h Perfor mance Liquid Chromatography using a Corona-charged Aerosol Detector (SPE-HPLC-CAD)
Authors: Qian Xiuyu , Nie Lixing , Dai Zhong , Ma Shuangcheng 
Published: May 2020

Background:
Banlangen granules are broad-spectrum effective antiviral drugs, and have a
large clinical demand in China. Free amino acid is one of the main antiviral active ingredients of Banlangen
granules. The pre-processing of samples by the existing pre-column derivatization reversed-
HPLC method is complicated. Therefore, the determination of free amino acids (AAs) by underivatized
ion-pair HPLC-CAD is advantageous for simplifying the preparation process and improving sensitivity.

Objective:
To better optimize AAs analysis methods, here a sensitive SPE-HPLC-CAD method with a
better resolution was established for the determination of underivatized AAs in Banlangen Granule for
the first time.

Method:
The analytes were separated only by HPLC using a Hypercarb column with gradient elution of solvent A (20
mM nonafluorovaleric Acid in water) and solvent B (0.3% trifluoroacetic acid in acetonitrile-0.3% trifluoroacetic acid
in water (1:9, v/v)) at a flow rate of 0.15 mL/min. N2 gas pressure and evaporation temperature of CAD were held at a
constant 58.6 psi and 60 ℃, respectively.

Results:
This method was linear over the respective concentration range of six amino acids. The precision, accuracy,
stability and recovery were satisfactory in all samples examined. And the method was successfully applied to
determination of free amino acids in Banlangen granules and its fractions. The total contents of six amino acids in 28
batches of Banlangen Granule were between 1.36 mg/g-11.62 mg/g.

Conclusion:
The proposed method could be a simple, accurate and sensitive alternative approach for the determination
of free AAs in Banlangen Granule.
Effect of surgery-first orthognathic approach on oral health-related quality of life:
Authors: Yao Ke , Zhu Guanyin , Chen Miao , Zhang Bo , Wu Yongzhi , Li Peilin 
Published: May 2020

ABSTRACT

Objectives
To systematically evaluate the effect of the surgery-first approach (SFA) on oral health-related quality of life (OHRQoL) in patients with dentofacial deformities.

Materials and Methods
An electronic database search and hand search of selected journals and references were carried out. Studies investigating the OHRQoL of patients receiving SFA with or without a control group were included. The risk of bias was assessed by the Cochrane risk of bias tool in randomized clinical trials (RCTs) and the Newcastle-Ottawa Scale in non-RCTs.

Results
A total of seven articles met the eligible criteria and were included, of which six were cohort studies and one was an RCT, and six assessed the OHRQoL of the SFA with conventional orthodontic–surgical treatment (COST) as a control and one without. A total of 214 patients were examined, with sample sizes in studies ranging from 9 to 50. A total of 3 articles successfully measured the OHRQoL both before and after treatment in both the SFA and conventional orthodontic–surgical treatment groups. A total of six cohort studies were classified as low to moderate risk of bias, and the RCT was classified as high.

Conclusions
The SFA could improve the OHRQoL of patients with dentofacial deformities similar to conventional orthodontic–surgical treatment at the end of complete treatment. In addition, it increases OHRQoL immediately at the beginning of treatment without a deterioration.
Aortocoronary conduits may show a different inflammatory response - comparative study at transcript level
Authors: Nawrocki Mariusz J. , Kałużna Sandra , Jopek Karol , Hutchings Greg , Perek Bartłomiej , Jemielity Marek , Malińska Agnieszka , Kempisty Bartosz , Mozdziak Paul , Nowicki Michał 
Published: May 2020

Abstract
Coronary artery bypass grafting (CABG), together with percutaneous coronary intervention (PCI), are both still the most efficient procedures for myocardial revascularization to treat advanced coronary artery disease (CAD). Donor blood vessels used in CABG are usually the internal thoracic artery (ITA) and saphenous vein (SV). The importance of inflammation and inflammatory pathways in graft patency is well established. Nevertheless, not all molecular mechanisms underlying the inflammatory process appear to be clear. Employing the expressive microarray approach to analyze the transcriptome of both venous and arterial grafts, five GO BP terms has been selected: “cellular response to interferon-gamma”, “inflammatory response”, “interferon-gamma-mediated signaling pathway”, “response to interferon-gamma” and “positive regulation of inflammatory response”. This study aimed to evaluate potential molecular factors that could be characteristic markers for both SV and ITA conduits.

Running title: Aortocoronary conduits may show a different inflammatory response
New molecular markers involved in immune system homeostasis and hemopoietic organ development are differentially regulated during oocytes in vitro maturation
Authors: Moncrieff Lisa , Kocherova Ievgeniia , Bryja Artur , Kranc Wiesława , Perek Joanna , Celichowski Piotr , Kulus Magdalena , Kempisty Bartosz , Mozdziak Paul , Jeseta Michal 
Published: May 2020

Abstract
The growth and maturation of the oocyte is a dynamic process which requires a variable supply of hormones, growth factors and energy. These needs are met partially by the surrounding somatic cells and the cumulus-oocyte complex, which communicate bi-directionally via gap junctions. Identifying and analyzing protein expression in the oocyte can provide insight in its development and growth. Further, like bone marrow stem cells, if relevant marker genes are found in oocytes, there is a potential for the oocyte to be manipulated into becoming hemopoietic stem cells. In this study, porcine oocytes were isolated and subjected to microarray analysis to compare the oocyte gene expression in vivo and in vitro maturation (IVM). Genes identified belonged to both ‘hemopoietic or lymphoid organ development’(GO:0048534) and ‘immune system development’ (GO:0002520), and the markers can be used to identify several activities such as cell migration, neurogenesis and proliferation. The following are the identified genes and all were downregulated after IVM to varying degrees: ID2, VEGFA, TGFBR3, INHBA, CDK6, BCL11A, MYO1E, ITGB1, EGR1, NOTCH2, SPTA1, KIT and TPD52. Our results should provide new markers to further investigate oocyte development and growth regulation.

Running title: Markers of hemopoietic organ development
Cell-based approaches in drug development – a concise review
Authors: Kocherova Ievgeniia , Kempisty Bartosz , Hutchings Greg , Moncrieff Lisa , Dompe Claudia , Janowicz Krzysztof , Petitte Jim , Shibli Jamil A. , Mozdziak Paul 
Published: May 2020

Abstract

In vitro models represent an alternative technique to in vivo or ex vivo studies in the drug development process. Cell-based assays are used to measure the level of proliferation and toxicity, as well as activation of signalling pathways and changes in morphology in cultivated cells. The studies conducted in vitro are aimed to estimate the newly synthesised drugs’ ability to permeate biological barriers and exert their therapeutic or cytotoxic effects. However, more than half of all studied drugs fail in the second or third phase of clinical trials due to a lack of confirmed efficacy. About a third of drugs fail because of safety issues, such as unacceptable levels of toxicity. To reduce attrition level in drug development, it is crucial to consider the implementation of translational phenotypic assays as well as to decipher various molecular mechanisms of action for new molecular entities. In this review, we summarise the existing cell-based methods most frequently used in the studies on drugs, taking into account their advantages and drawbacks.

Running title: Cell-based approaches in drug development
Bronchial Asthma: Current Trends in Treatment
Authors: Palova R , Adamcakova J , Mokra D , Mokry J 
Published: May 2020

Abstract
Asthma is a heterogenous disease which pathophysiology is still poorly understood. Asthma was traditionally divided into allergic (extrinsic) and non-allergic (intrinsic) types, while patients with allergic type responded better to corticosteroids. Since 2013 the definition of asthma has changed. Recently, better insight into clinical consi -derations and underlying inflammatory phenotypes has been gained. Defining these phenotypes has already led to more specific clinical trials and, therefore, to more personalized and successfully targeted therapy. For future, much more effort is put in identifying new phenotype-specific biomarkers which could be helpful in stratification of heterogeneous patients with asthma.
Brachial Plexopathy as an Unusual First Sign of a Head and Neck Cancer: Case Report
Authors: Surova V , Slavik P , Calkovsky V , Hajtman A. 
Published: May 2020

Abstract
Malignancies in the ENT (Ear, Nose, and Throat) area are mostly manifested by dysphagia, dysphonia, dyspnea, throat swelling, and other “traditional” head and neck symptoms. Sporadically, a primary tumor or metastasis can reach such a size and it can be localized in such an area in which it can cause the pathology of the brachial plexus. If this appears first, differential diagnosis may be more difficult.
In this article the authors review current literature knowledge and present the case of this unusual sign of a head and neck cancer at the Clinic of Otorhinolaryngology and Head and Neck Surgery, Jessenius Faculty of Medicine, Comenius University, and Martin University Hospital, Martin, Slovakia.
HPLC method development for fampridine using Analytical Quality by Design approach
Authors: Kovács Béla , Boda Francisc , Fülöp Ibolya , Székely-Szentmiklósi István , Kelemen Éva Katalin , Kovács-Deák Boglárka , Székely-Szentmiklósi Blanka 
Published: May 2020

Abstract
Offering a systematic and multivariate analysis of the analytical procedure, development and validation of HPLC methods using Quality by Design approach are in the limelight of current research trends. A new, experimental design-aided HPLC method for fampridine was developed and preliminarily validated according to current in-force international guidelines for linearity, accuracy, robustness and precision.
The method offers a high throughput sample analysis, with an elution time of 2.9 minutes, and signal detection without excipient interference performed at 262 nm. The method proved to be linear between 1–15 µg mL−1 (R2
= 0.9996). The mean recovery was found to be 98.7 ± 1.9 % in the tested range of 2.5–7.5 µg mL−1. Low RSD values (< 1 %) were obtained for both model, intra- and inter-day precision. The limit of detection and limit of quantification were 0.24 and 0.78 µg mL−1, resp. The method proved to be applicable for active substance assay in a pharmaceutical dosage form.