bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravitreal Aflibercept injection with Panretinal photocoagulation versus early Vitrectomy for diabetic vitreous hemorrhage: randomized clinical trial
Authors: Abd Elhamid Ahmed Hosni , Mohamed Ahmed Abd El Alim , Khattab Abeer Mohamed
Published: April 2020

Background

To compare efficacy and safety of intravitreal aflibercept (IVA) injection with panretinal photocoagulation (PRP) versus early vitrectomy for diabetic vitreous hemorrhage (VH).

Methods

Prospective, randomized study that included 34 eyes with diabetic VH. They were divided into two groups, Group Ι (17 eyes) received three successive IVA injections followed by PRP and group ΙΙ (17 eyes) for whom early vitrectomy was done. Follow up was carried out after one, two, three, six and nine months. The primary outcome measure was change in the mean best corrected visual acuity (BCVA) after nine months, secondary outcome measures were mean duration of clearance of VH and rate of recurrent hemorrhage with any additional treatment in both groups. Complications were reported.

Results

There was no statistically significant difference regarding initial demographic criteria between both groups. The mean final log MAR BCVA was statistically better than the initial BCVA in both groups (0.51 ± 0.20, 1.17 ± 0.48 for group I and 0.48 ± 0.18, 1.44 ± 0.44 for group II,P < 0.001). There was no statistically significant difference between both groups regarding the mean final Log Mar BCVA (0.51 ± 0.20 for group I, 0.48 ± 0.18 for group II,p ≥ 0.05), the mean duration of clearance of VH was 7.8 ± 1.8 weeks, 5 days for group I and II respectively. PRP was completely done for all eyes in group I after three months. The difference in the recurrence rate between group I (29.4%) and group II (11.8%) was statistically significant (p < 0.05). Vitrectomy was done for three eyes (17.6%) due to recurrent non-resolving VH in group I. late recurrent VH occurred in two eyes (11.8%) in group II, IVA was given with complete clearance of the hemorrhage. No vision threatening complications were reported in both groups.

Conclusion

Both intravitreal injection of aflibercept followed by PRP and early vitrectomy are effective and safe modalities for treatment of diabetic vitreous hemorrhage. Early vitrectomy leads to faster vision gain with less incidence of recurrence than intravitreal injection.

Trial registration

Randomized clinical trial under the number ofNCT04153253on November 6, 2019 “Retrospectively registered”.
Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report
Authors: Miura Gen , Baba Takayuki , Iwase Takehito , Ohde Hisao , Kanda Atsuhiro , Saito Wataru , Ishida Susumu , Yamamoto Shuichi
Published: April 2020

Background

Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye.

Case presentation

Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind.

Conclusions

As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.
In situ split plus portal vein ligation (ISLT) – a salvage procedure following inefficient portal vein embolization to gain adequate future liver remnant volume prior to extended liver resection
Authors: Lehwald-Tywuschik Nadja , Vaghiri Sascha , Schulte am Esch Jan , Alaghmand Salman , Klosterkemper Yan , Schimmöller Lars , Lachenmayer Anja , Ashmawy Hany , Krieg Andreas , Topp Stefan A. , Rehders Alexander , Knoefel Wolfram Trudo
Published: April 2020

Background

Right extended liver resection is frequently required to achieve tumor-free margins. Portal venous embolization (PVE) of the prospective resected hepatic segments for conditioning segments II/III does not always induce adequate hypertrophy in segments II and III (future liver remnant volume (FLRV)) for extended right-resection. Here, we present the technique of in situ split dissection along segments II/III plus portal disruption to segments IV-VIII (ISLT) as a salvage procedure to overcome inadequate gain of FLRV after PVE.

Methods

In eight patients, FLRV was further pre-conditioned following failed PVE prior to hepatectomy (ISLT-group). We compared FLRV changes in the ISLT group with patients receiving extended right hepatectomy following sufficient PVE (PVEres-group). Survival of the ISLT-group was compared to PVEres patients and PVE patients with insufficient FLRV gain or tumor progress who did not receive further surgery (PVEnores-group).

Results

Patient characteristics and surgical outcome were comparable in both groups. The mean FLRV-to-body-weight ratio in the ISLT group was smaller than in the PVEres-group pre- and post-PVE. One intraoperative mortality due to a coronary infarction was observed for an ISLT patient. ISLT was successfully completed in the remaining seven ISLT patients. Liver function and 2-year survival of ~ 50% was comparable to patients with extended right hepatectomy after efficient PVE. Patients who received a PVE but who were not subsequently resected (PVEnores) demonstrated no survival beyond 4 months.

Conclusion

Despite extended embolization of segments I and IV-VIII, ISLT should be considered if hypertrophy was not adequate. Liver function and overall survival after ISLT was comparable to patients with trisectionectomy after efficient PVE.
Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study
Authors: Koguchi Dai , Murakami Yasukiyo , Ikeda Masaomi , Dobashi Masato , Ishii Junichiro
Published: April 2020

Background

Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC.

Methods

We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy.

Results

Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL.

Conclusion

Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.
Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging
Authors: Chen Junchen , Zhang Chen , Guo Yanxiu , Chang Xiaohong , Ma Ruiqiong , Ye Xue , Cheng Hongyan , Li Yi , Cui Heng
Published: April 2020

Background

To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance.

Methods

The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging.

Results

In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs.

Conclusions

COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.
Long-term survival and costs following extracorporeal membrane oxygenation in critically ill children—a population-based cohort study
Authors: Fernando Shannon M. , Qureshi Danial , Tanuseputro Peter , Dhanani Sonny , Guerguerian Anne-Marie , Shemie Sam D. , Talarico Robert , Fan Eddy , Munshi Laveena , Rochwerg Bram , Scales Damon C. , Brodie Daniel , Thavorn Kednapa , Kyeremanteng Kwadwo
Published: April 2020

Background

Extracorporeal membrane oxygenation (ECMO) is used to provide temporary cardiorespiratory support to critically ill children. While short-term outcomes and costs have been evaluated in this population, less is known regarding long-term survival and costs.

Methods

Population-based cohort study from Ontario, Canada (October 1, 2009 to March 31, 2017), of pediatric patients (< 18 years of age) receiving ECMO, identified through the use of an ECMO procedural code. Outcomes were identified through linkage to provincial health databases. Primary outcome was survival, measured to hospital discharge, as well as at 1 year, 2 years, and 5 years following ECMO initiation. We evaluated total patient costs in the first year following ECMO.

Results

We analyzed 342 pediatric patients. Mean age at ECMO initiation was 2.9 years (standard deviation [SD] = 5.0). Median time from hospital admission to ECMO initiation was 5 days (interquartile range [IQR] = 1–13 days). Overall survival to hospital discharge was 56.4%. Survival at 1 year, 2 years, and 5 years was 51.5%, 50.0%, and 42.1%, respectively. Among survivors, 99.5% were discharged home. Median total costs among all patients in the year following hospital admission were $147,957 (IQR $70,571–$300,295). Of these costs, the large proportion were attributable to the inpatient cost from the index admission (median $119,197, IQR $57,839–$250,675).

Conclusions

Children requiring ECMO continue to have a significant in-hospital mortality, but reassuringly, there is little decrease in long-term survival at 1 year. Median costs among all patients were substantial, but largely reflect inpatient hospital costs, rather than post-discharge outpatient costs. This information provides value to providers and health systems, allowing for prognostication of short- and long-term outcomes, as well as long-term healthcare-related expenses for pediatric ECMO survivors.
Problems and Prospects of Organizing a Counselor's Practice for Students of the Faculty of Preschool Pedagogy and Psychology of MPSU
Authors: Semenova Tatiana
Published: April 2020

The author describes the experience of organizing and conducting a summer teaching counselor practice at the faculty of preschool pedagogy and psychology of the Moscow State Pedagogical University (MPSU) as a social and pedagogical innovation, analyzes the problems and highlights the prospects for the implementation of the module «basics of counselor activity».

The purpose of the study: the study of opinions of students of Faculty of preschool pedagogy and psychology Moscow State Pedagogical University (MSPU) relative to years of teaching leader practices for consolidation and analysis of their experience; identification of problems and definition of prospects of the organization and conduct of this practice, the dissemination of pedagogical experience.

Research problem:

1. study of the opinion of students of the faculty of preschool pedagogy and psychology of MPSU regarding the organization and conduct of summer pedagogical leader practice;

2. identification of the attitude of students of the faculty of preschool pedagogy and psychology to the study of the module "Basics of leadership activity";

3. justification of the need to study the module "Basics of leadership activities" and include leadership practice in the curriculum of students' training, identifying problems and determining the prospects for its organization and implementation.
Resonator fiber-optic gyro with intensity error suppression using a bias-sampling compensation technique
Authors: Shang Kejun , Lei Ming , Fang Yuan , Yu Huaiyong , Zhang Lizhe
Published: April 2020

Resonator fiber-optic gyros (RFOGs) are one of the most promising
candidates for next-generation inertial rotation sensors. The
frequency servo loop is used to lock the laser frequency to the
resonance frequency of fiber ring resonator via adjusting the laser
diode current, which increases accompanying intensity variation and
induces RFOG drift. RFOG output compensation using a bias-sampling
technique is proposed to suppress intensity error. The linear
relationship between the RFOG output and bias is verified by theory
and experimental results, and the bias-sampling compensation technique
by monitoring the bias signal is analyzed in detail. With the
compensation technique, intensity error is significantly suppressed,
and the RFOG bias stability is effectively improved from 127.2 to
7.4 deg/h, which demonstrates tactical-grade performance.
Two-dimensional simulation of near-longitudinally pumped dye laser amplifiers
Authors: Yang Qiunan , Zhang Xiaowei , An Zhenjie
Published: April 2020

Simulations of near-longitudinally pumped dye laser amplifiers are demonstrated in this paper. We developed a two-dimensional model that considers the amplified spontaneous emission (ASE). The influence of the angle between the input beam and pump beam on the extraction efficiency, ASE, and heating process of the amplifiers is investigated. It was found that for the main amplifiers with high pump and input powers, both the extraction efficiency and the ASE are insensitive to variations in the pump angle. However, for preamplifiers with a low input power, the increase in the angle causes a more significant loss in efficiency and a higher ASE generation. For the heating caused by light, the influence of the pump angle is insignificant. The results suggest that near-longitudinal pumping is appropriate for main amplifiers but not for preamplifiers.
Application of resilience assessment grid in production of aircraft components
Authors: Sekeľová Frederika , Lališ Andrej
Published: April 2020

The paper evaluates an application of the resilience measuring tool Resilience Assessment Grid (RAG) in the aircraft components production. For the purpose of the evaluation a specific RAG model for a change process is created. The paper contains a description of change process and the approval process of the engineering change proposal. Paper describes BPMN and FRAM models created to support model RAG and which both clarify relations among the functions inside the management of change process. The paper presents a possible approach for the Resilience Assessment Grid model creation. The outcome is a creation of a change process profile in a company producing aircraft components in which change process and approval of the engineering proposed change is managed, and a recording of a current state of four  process potentials that can be used by the company management to develop wider safety awareness among employees.
Wpływ kultury politycznej na proces funkcjonowania demokracji w Polsce w latach 2006–2018
Authors: Tyrała Marek
Published: April 2020

Celem artykułu jest charakterystyka procesu funkcjonowania demokracji w Polsce w ciągu ostatniej dekady. Główna hipoteza badawcza postawiona w artykule brzmi: Kultura polityczna ma kluczowy wpływ na proces funkcjonowania demokracji w Polsce. Celem autora była charakterystyka procesu rywalizacji politycznej oraz czynników określających (warunkujących) proces konsolidacji demokracji. Tekst ma charakter interdyscyplinarny, problem badawczy został przeanalizowany z perspektywy politologicznej, socjologicznej i filozoficznej. Weryfikując hipotezę postawioną w pracy, zauważono, iż występuje duże prawdopodobieństwo, że to właśnie niska kultura polityczna ma negatywny wpływ na funkcjonowanie demokracji w Polsce. Próba analizy problemu badawczego może wnieść istotny wkład w dalsze badanie procesu funkcjonowania demokracji w Polsce.
Effect of State Immunization Information System Centralized Reminder and Recall on HPV Vaccination Rates
Authors: Szilagyi Peter , Albertin Christina , Gurfinkel Dennis , Beaty Brenda , Zhou Xinkai , Vangala Sitaram , Rice John , Campbell Jonathan D. , Whittington Melanie D. , Valderrama Rebecca , Breck Abigail , Roth Heather , Meldrum Megan , Tseng Chi-Hong , Rand Cynthia , Humiston Sharon G. , Schaffer Stanley , Kempe Allison
Published: April 2020

BACKGROUND:

Although autodialer centralized reminder and recall (C-R/R) from state immunization information systems (IISs) has been shown to raise childhood vaccination rates, its impact on human papillomavirus (HPV) vaccination rates is unclear.

METHODS:

In a 4-arm pragmatic randomized controlled trial across 2 states, we randomly selected practices representative of the specialty (pediatrics, family medicine, and health center) where children received care. Within each practice, patients 11 to 17.9 years old who had not completed their HPV vaccine series (NY: N = 30 616 in 123 practices; CO: N = 31 502 in 80 practices) were randomly assigned to receive 0, 1, 2, or 3 IIS C-R/R autodialer messages per vaccine dose. We assessed HPV vaccine receipt via the IIS, calculated intervention costs, and compared HPV vaccine series initiation and completion rates across study arms.

RESULTS:

In New York, HPV vaccine initiation rates ranged from 37.0% to 37.4%, and completion rates were between 29.1% and 30.1%, with no significant differences across study arms. In Colorado, HPV vaccine initiation rates ranged from 31.2% to 33.5% and were slightly higher for 1 reminder compared with none, but vaccine completion rates, ranging from 27.0% to 27.8%, were similar. On adjusted analyses in Colorado, vaccine initiation rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.07 and 1.04, respectively); completion rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.02 and 1.03, respectively).

CONCLUSIONS:

IIS-based C-R/R for HPV vaccination did not improve HPV vaccination rates in New York and increased vaccination rates slightly in Colorado.
Mathematical modelling of cumulative erosion ratio for suffusion in soils
Authors: Xu Zhenhao , Lin Peng , Xing Huilin , Wang Jing
Published: April 2020

Internal erosion induced by suffusion is a progressive process that can have negative consequences for dams, foundations and tunnel projects. The erosion ratio (denoting the ratio of the weight of cumulative eroded soils to the total weight of soils) is an important parameter in characterising this process, reflecting variations in porosity and hydraulic conductivity during suffusion. In this study, an erosion equation expressing the variation in the erosion ratio with respect to the hydraulic gradient and time is derived under arbitrary hydraulic loading conditions. This equation is based on investigations into the influence of both the hydraulic gradient and of time on the process of soil erosion. The derived erosion equation is applied in a case study and the results are compared with existing test data. It is shown that the expression proposed in this paper is in good agreement with observations. Finally, the influences of the hydraulic loading history and an erosion rate coefficient on the soil erosion process are discussed.
¿Es la política internacional, una intención de integración o desintegración? Y ¿la ciudadanía? Análisis del caso de la “transición” del socialismo al “capitalismo globalizado”
Authors: Vélez Gallego Gabriela
Published: April 2020

Este artículo de refl exión es un llamado a pensar por qué los países socialistas o comunistas ingresaron a las ideologías capitalistas; para ello, parte de un análisis que resalta el momento histórico en el que se da el desarrollo tecnológico, el cual adquiere un auge al considerar que quien tiene la información tiene el poder y analiza el hecho de que si hay globalización, entonces se debe promover el ciudadano global. Ante este reto de la educación de formar para la ciudadanía global, se pregunta: ¿a qué tipo de ciudadano y a qué tipo de ciudadanía apunta la globalización? Por último, se analiza el deber ser de los organismos internacionales en cuanto a su compromiso de garantizar la estabilidad política global, el cual no ha sido así, por las actuaciones que ha mostrado en sus intervenciones y da a conocer las realidades del socialismoeste y su ingreso al capitalismo-occidente.
Una reflexión sobre las raíces teórico-jurídicas del derecho de la competencia en Colombia
Authors: Hernandez Collazos Freddy , Latorre Iglesias Edimer
Published: April 2020

En el marco de la reflexividad, este artículo propone una analísis de las bases teoricas que le dan le dan un sustento deontológico al derecho de la competencia en el ordenamiento jurídico colombiano; reconociendo el impacto de la globalización como un fenómeno cultural, inmerso en la economía de los diferentes países, el cual ha facilitado el intercambio continuo de productos, la competencia en los mercados, pero bajo ciertos requerimientos y restricciones que promuevan la calidad sin afectar la equidad en las relaciones de producción y permitan la intervención de organismos nacionales e internacionales, veedores de la eficacia, transparencia de las negociaciones y garantes de la proteccion de los derechos de los consumidores y sociedad en general. Para lograr tal objetivo, se plantearon metodologías hermenéuticas, basándose en el análisis del Derecho Económico y por último, se señalaron los desafíos del derecho de la competencia para América Latina.

 

AbstractThis article searching to analyze the theories about deontical argument tothe competitive law, in the Colombia legal system, but it's must to think over the impact globalization cultural phenomenon, inside of the economic countries. Also, it's situation has allowed the echanged products' the competitive in the Market, buyt according to laws and others requirements and certify the quality, without damage the production relationals and it's easy the participation international and national institution, the care and protection the users andsociety right. Additionally, in this investigation for to obtain this objective to methodology interpretation it based in the Economy Law and the competition law's for Latin America.
EDITORIAL
Authors: Editor Editor
Published: April 2020

Editorial
Stink Bug Population in Cotton Plantations with Different Plant Spacings
Authors: Lima Júnior Izidro dos Santos de , Degrande Paulo Eduardo , Melo Elmo Pontes de , Piletti Lígia Maria Maraschi da Silva , Viegas Neto Antonio Luiz
Published: April 2020

The increase in cotton plant population by decreasing the spacing between rows cause some changes in phenotypical characteristics of cotton plants, such as decrease in number of leaves per plant, low-development leaves, and great soil shading. Stink bugs of the Pentatomidae family that migrate from soybean crops seem to benefit from the cotton narrow-row planting system. The objective of the present work was to evaluate adult and nymph stink bug populations in cotton plantations under three plant spacing. The experiment was conducted in the 2010/2011 cotton season at the Experimental Farm of the Federal University of Grande Dourados, in Dourados, MS, Brazil. A randomized block experimental design was used, with three cotton growing systems and eight replications, totaling 24 plots. The cotton growing systems were selected based on spacing between planting rows (0.22, 0.45, and 0.90 m). Five evaluations were conducted to survey the stink bug populations, with two samples per plot. The number of nymphs and adults of Euschistus heros and Edessa meditabunda was counted. The spacing between cotton planting rows affects stink bug populations of the species Euschistus heros and Edessa meditabunda. Increases in cotton plant density decrease the occurrence of stink bug in the plantation. The stink bug population is greater in cotton plantations with spacing of 0.90 m between planting rows.
Diagnostic value of the Epstein-Barr virus serological markers in patients with nasopharyngeal carcinoma in cases of undetectable primary tumor location
Authors: Gurtsevitch V. E. , Senyuta N. B. , Lomaya M. V. , Ignatova A. V. , Dushenkina T. E. , Repkina I. A. , Pavlovskaya A. I. , Mudunov A. M.
Published: April 2020

The goal of this work was to describe a method for diagnosis of the non-keratinizing nasopharyngeal carcinoma (nNPC) in cases of the undetectable primary tumor location. The method is based on evaluation of IgG and IgA antibody levels to the capsid (VCA) and early antigens (EA) of the Epstein-Barr virus (EBV). The diagnosis of nNPC is established by a so-called decision rule. The latter was created by mathematical processing of the method of multifactor analysis of the results of anti-EBV antibody testing of 72 patients with clinically and morphologically confirmed nNPC and 72 patients with other head and neck benign tumors (OHNT) not associated with EBV, which were tested as a control group. The diagnostic value of the decision rule which was tested in the group of 77 patients with confirmed nNPC and 231 patients of a control group was high. The numbers of false negative and false positive cases were equal to 5.2% (4/77) and 6.5% (17/231), respectively. Among 32 patients with undetectable primary tumors the decision rule was able to identify 11 cases of nNPC. This diagnosis later was confirmed by morphological and instrumental methods of study. Only in two cases, false negative result was obtained (2/32; 6.3%) indicating that the serological diagnostics of nNPC with the decision rule is highly specific but not exact. Thus, the data obtained allowed us to conclude that the serological testing of EBV specific antibody evaluated by the decision rule can be recommended as an important test supplementing the standard methods of pdNPC diagnostics including cases with undetected primary tumor location.
Genetic aspects of HPV infection detection in tumor and adjacent tissues of patients with laryngeal squamous cell carcinoma
Authors: Dvoryaninova O. Yu. , Nikitina E. G. , Bychkov V. A. , Litviakov N. V.
Published: April 2020

The article describes methods for the human papillomavirus (HPV) detection in tumor and adjacent (morphologically intact) tissues of patients with laryngeal squamous cell carcinoma (LSSC) in terms of viral pathogenesis. Comparative evaluation of the principles and techniques for HPV detection was performed. Advantages and disadvantages of the HPV detection methods are described. Approaches for DNA and HPV oncoproteins E6-E7 identification are substantiated. The results of our research into the qualitative and quantitative detection of HPV in the tumor and adjacent tissues of patients with Lssc are described. The research was conducted using commercial test systems Amplisens HPV HR screen-titre-FL and Amplisens HPV HR genotype-FL. Based on these results we developed the algorithm of HPV detection in samples of tumor tissue of patients with Lssc. The need for typing HPV-positive tissue samples with low concentration of HPV DNA was discussed.
Severe fever with thrombocytopenia syndrome: the disease, caused by the novel phlebovirus
Authors: Sizikova T. E. , Lebedev V. N. , Pantukhov V. B. , Borisevich S. V.
Published: April 2020

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a new virus (SFTS virus) reported to be endemic to central and northeastern parts of China. SFTS virus, which is classified into the genus Phlebovirus (the Bunyaviridae family), is suspected to be a tick-borne virus owing to evidence in two species of ticks: Haemaphysalis longicornis and Rhipicephalus microplus. SFTS virus is detected among many species of domestic animals in China. The clinical symptoms of SFTS include fever, thrombocytopenia, leucocytopenia, gastrointestinal symptoms, neural symptoms, bleeding tendency. The fatality rate of SFTS is 6-30%. Person-to-person transmission of SFTS virus is possible through blood contact. Clinical and epidemiological studies of SFTS, the cases of SFTS outside China, person-to-person transmission of SFTS virus, evolutionary and molecular analysis of the emergent SFTS virus, and risk assessment of human infection with a novel phlebovirus are considered in this review.
POXVIRUS DISEASE OF SQUIRRELS (POXVIRIDAE, CHORDOPOXVIRINAE, SQPV - SQUIRREL POXVIRUS)
Authors: Borisevich S. V. , Stovba L. F. , Paveliev D. I.
Published: April 2020

A new taxon of the subfamily Chordopoxvirinae that may represent a new genus of smallpox viruses is considered in this review. The distribution of gray squirrels (Sciurus carolinensis) throughout the UK during the 20th century and the decrease in the population of red squirrels (Sciurus vulgaris) is one of the most well-documented cases of ecological change of local fauna by the introduced species. The tendency to expand the distribution of the smallpox virus from Great Britain to the Western part of Europe has been noted. The genetic peculiarities of the genome of the poxvirus of squirrels, which determine its biological properties, as well as evolutionary relationships with other poxviruses, are separately described. Determination of the size of the genome by restriction analysis, sequencing of the whole genome, determination of the content of G/C nucleotide pairs, and functional mapping of the majority of genes made it possible to construct a phylogenetic tree. Phylogenetic analysis shows that this is a new representative of the subfamily Chordоpoxvirinae located between the viruses of the molluscum contagiosum and parapoxviruses. Serological and molecular biological methods are used to reveal and identify the causative agent of smallpox. The use of electron microscopy is limited in grey squirrels, due to the absence of organ damage and reproduction of the virus. Identification of the DNA of the causative agent of poxvirus of squirrels based on the use of different types of polymerase chain reaction (nested and in real time) overcomes all these limitations.
CROSS-PROTECTIVE PROPERTIES OF AN INFLUENZA VACCINE BASED ON HBC4M2E RECOMBINANT PROTEIN
Authors: Tsybalova L. M. , Stepanova L. A. , Shuklina M. A. , Petrov S. V. , Kovaleva A. A. , Potapchuk M. V. , Shaldzhan A. A. , Zabrodskaya Y. A. , Egorov V. V.
Published: April 2020

One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.
EPSTEIN-BARR VIRUS AND NASOPHARYNGEAL CARCINOMA: VIRAL MARKERS FOR DIAGNOSTICS AND ASSESSMENT OF CLINICAL STATUS OF PATIENTS
Authors: Kondratova V. N. , Lomaya M. V. , Ignatova A. V. , Dushenkina T. E. , Smirnova K. V. , Mudunov A. M. , Lichtenstein A. V. , Gurtsevitch V. E. , Senyuta N. B.
Published: April 2020

The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of China and the countries of Southeast Asia, and later in the rest of the world, has served as a basis for the widespread use of EBV serological markers for the diagnosis of this form of tumor. In recent years, the use of a test based on the quantitative determination of the EBV DNA concentration in the blood plasma of uNPC patients for early detection and monitoring of the disease has become widespread in endemic regions. In non-endemic regions, such studies virtually have not been carried out, and moreover, the comparative evaluation of the significance of two viral markers, serological and EBV DNA load in the bloodstream of uNPC patients, for diagnostics and evaluation of the therapeutic effect was not investigated. The aim of this study was to compare the clinical value of two serological markers and plasma EBV DNA load in uNPC patients from non-endemic region (Russia). The obtained results indicate that IgA antibodies to the viral capsid antigen (IgA/VCA) and plasma EBV DNA concentration can be successfully used for the diagnosis of uNPC, while IgG/VCA antibodies have no practical significance as an uNPC marker. In addition, it was found that plasma EBV DNA load is more sensitive marker of uNPC than IgA/VCA titers because DNA copy numbers reflect more accurately the effect of the therapy and the clinical state of patients at the stages of remission or relapse. It was shown for the first time that in the non-endemic region the simultaneous evaluation of IgA/VCA antibody levels and the plasma EBV DNA loads are the most effective markers for the diagnostics of uNPC. However, we believe, that it is more practical to use IgA/VCA antibody levels for uNPC screening, and plasma EBV DNA copies - for monitoring of the disease.
ANALYSIS OF THE QUALITY OF NATIONAL VACCINE AGAINST RUBELLA
Authors: Unasova T. N. , Binyatova A. S. , Phadeykina O. V. , Sarkisyan K. A. , Movsesyants A. A. , Ignatyev G. M. , Volkova R. A. , Tereshkina N. V. , Sidorenko E. S. , Ilyasova T. N. , Sukhanova L. L.
Published: April 2020

Until recently Rubella has been a wide spread infection. Thanks to vaccination against rubella, taking part in the global elimination program of “manageable infections” of WHO and adoption of the program “Elimination of measles and rubella in Russian Federation” the morbidity index of rubella has reached the sporadic level. One of the determining conditions of rubella elimination is application of high-quality vaccines that satisfy international standards. In Russian Federation, foreign rubella vaccines certified in our country were used for several years. In 2008, the commercial production of domestic vaccine began. It is widely known that the required quality of immunobiological medications is achieved using adequate production conditions and standard technological process. That is why during the production of domestic rubella vaccine, all the rules and requirements of Russian regulatory authorities and international recommendations are followed. In this article, a retrospective analysis of domestic vaccine against rubella according to laboratory options of quality in 2012-2017 is given. The results of the analysis show that the medication demonstrates stable high quality that is indicative of secure production technologies.
ON MODERN APPROACHES TO CREATION OF A SINGLE-CYCLE VACCINE AGAINST TICK-BORNE ENCEPHALITIS
Authors: Lashkevich V. A. , Karganova G. G.
Published: April 2020

In Russia, about 2000 people get tick-borne encephalitis (TBE) every year. Almost none of them are vaccinated. For the prevention of TBE, inactivated vaccines (IVTBE) are used. IVTBE are safe and protect from TBE not less than 95% of vaccinated. The disadvantages of IVTBE are the need for numerous intramuscular injections by medical personnel, the high cost of vaccination and the vaccination refusals. A new vaccine against TBE should not be inferior to IVTBE in its safety and efficacy, should cause long-term immunity after a single application, and, preferably, be effective after oral administration. Currently, genetic engineering methods for producing replication-defective (single-cycle) flaviviruses that can serve as the basis for creating new types of safe vaccines similar in many characteristics to classic live vaccines based on attenuated strains of viruses have been proposed. The possibility of infecting humans with TBE by the use of milk of naturally infected animals, as well as the experience of using experimental live TBE vaccines, are prerequisites for the creation of a safe oral single-dose TBE vaccine.
CYTOTOXIC PROPERTIES OF TRITERPENE SAPONIN TAUROSID SX1 AND ITS EFFECT ON HUMAN IMMUNODEFICIENCY VIRUS AND INFLUENZA VIRUS INFECTION IN MICE
Authors: Krivorutchenko Yu. L. , Nosik D. N. , Maligina V. Yu. , Lobach O. A. , Andronovskaja I. B. , Kirsanova M. A. , Grishkovets V. I.
Published: April 2020

Triterpene saponin Taurosid Sx1 purified from leaves of the plant Crimean Ivy Hedera taurica Carr. (Araliaceae) was evaluated for its cytotoxic activity against lymphoblastoid cell lines MT-4, Jurkat-tat, U937, and human peripheral blood monocytes. The ability of saponin to influence HIV-1 replication was studied as well. In addition, the ability of Taurosid Sx1 to increase survival of mice infected with influenza virus А/WSN/1/33(H1N1) and its capacity for strengthening the immune responses in mice immunized with the influenza vaccine Grippol® have been studied. Taurosid Sx1 has been shown to inhibit MT-4 cell line at 25 μg ml-1 concentration, IC50 33,3 μmol l-1 (MTT assay). The saponin concentration of 5 μg ml-1 was non-toxic for all the cell lines studied and demonstrated a moderate inhibitory effect on HIV p24 production in Jurkat-tat cells. In the lower concentrations Taurosid Sx1 did not stimulate HIV p24 production. It was shown that oral administration of 200 μg Taurosid Sx1 to the influenza virus infected mice caused 1.5-fold increase in their survival. Taurosid Sx1 given orally amplified immunopotentiating ability of an intramusculary administered subunit influenza vaccine. Antibody production was significantly higher in animals fed Taurosid Sx1 after primary or secondary immunizatuion. In mice given 2 doses of vaccine, from 1 to 3 weeks apart, feeding 200 μg saponin resulted in 2 to 10-fold enhancement in production of anti-H1, anti-H3, and anti-inluenza type B hemagglutinin antibodies. Thus, Taurosid Sx1 can be considered as low-toxic promising immunopotentiating agent uncapable of enhancing HIV-1 replication.
CONSTRUCTION OF MOSAIC HBC PARTICLES PRESENTING CONSERVATIVE FRAGMENTS OF M2 PROTEIN AND HEMAGGLUTININ OF INFLUENZA A VIRUS
Authors: Blokhina E. A. , Ravin N. V.
Published: April 2020

Virus-like HBc particles formed as a result of the self-assembly of the nuclear antigen of the hepatitis B virus can be used as a highly immunogenic carrier for the presentation of foreign epitopes when creating recombinant vaccines. We use this vehicle to create influenza vaccines based on the conservative antigens of the influenza virus, the extracellular domain of the transmembrane protein M2 (M2e) and the fragment of the second subunit of hemagglutinin (HA2). Presentation on the surface of HBc particles should improve the immunogenicity of these peptides. Using genetic engineering techniques, we obtained a fusion protein in which the HA2 sequence is attached to the N-terminus of the HBc antigen, and the M2e peptide is included in the immunodominant loop region exposed on the surface of HBc particle. The hybrid protein expressed in Escherichia coli and purified under denaturing conditions formed virus-like HBc particles after refolding in vitro. Refolding of this protein in the presence of a previously denatured HBc antigen carrying no inserts resulted in formation of mosaic virus-like particles. The developed method will allow construction of mosaic HBc particles carrying different target epitopes of the influenza virus by combining the corresponding modified HBc proteins, which opens the possibility of creating vaccines with a wider spectrum of protection.
PROBLEMS OF ISOLATION, IDENTIFICATION AND ANTIGENIC CHARACTERIZATION OF RECENT HUMAN A(H3N2) INFLUENZA VIRUSES
Authors: Petrova P. A. , Konovalova N. I. , Danilenko D. M. , Vasilieva A. D. , Eropkin M. Yu.
Published: April 2020

Human A (H3N2) influenza viruses are distinguished by a high rate of evolution and regularly cause epidemics around the world. Their ability to adapt and to escape from the host's immune response and to change their receptor specificity is very high. Over the past 20 years, these viruses have lost the ability to agglutinate red blood cells of chickens and turkeys and have practically ceased to propagate in chicken embryos - the main source of influenza vaccines. Isolation of viruses in the MDCK cell culture led to the selection of strains that lose one of the potential glycosylation sites. Many of the A (H3N2) strains have acquired mutations in neuraminidase, which distort the results of antigenic analysis in the hemagglutination inhibition test - the cornerstone method for the analysis of the match between viral isolates circulating in human population to strains selected for the influenza vaccines. In this regard, the characteristics of the antigenic properties of influenza A (H3N2) viruses by traditional methods become poorly informative, and the selection of vaccine strains of this subtype is erroneous, which is reflected in the discrepancy between vaccine and circulating A (H3N2) viruses in recent years (2013-2014, 2014 -2015, 2015-2016). The search, development and implementation of new algorithms for the isolation and antigen analysis of influenza A (H3N2) viruses are extremely urgent.
INFLUENCE OF INGARON ON THE DYNAMICS OF INTERFERON-α AND -γ PRODUCTION AND ON THE MANIFESTATION OF CLINICAL SYMPTOMS IN PATIENTS WITH CHRONIC VIRUS EРSTHTEIN-BARR INFECTION
Authors: Rakityanskaya I. A. , Ryabova T. S. , Kalashnikova A. A.
Published: April 2020

Introduction. Patients with chronic herpes virus infection develop impaired IFN-α and IFN-γ products due to secondary immunodeficiency, which leads to impaired elimination of the intracellular virus and the development of chronic recurrent infection. It has been shown that IFN-γ is a potent immunoregulatory cytokine and has an antiviral effect. The aim of the study is to study the effect of Ingaron therapy on the dynamics of IFN-α and IFN-γ production and the clinical picture in patients with chronic Epstein-Barr virus infection (ChEBVI). Material and methods. 32 patients with ChEBVI were examined. The average age of patients was 35.06 ± 1.60 years. There were 22 women, 10 men. Serum IFN-α and IFN-γ, spontaneous and induced cytokine production in blood lymphocyte cultures were determined. As an inducer of IFN-α products, the Newcastle disease virus was used (obtained in the LA Tarasevich State Medical Institute, St. Petersburg) with an infectious titer of 8 lg EID / 0.2 ml in a volume of 8 μl per well, as an inducer of IFN-γ products, phytohemagglutinin (PanEco, Russia) was used at a dose of 10 µg / ml. The quantitative content of cytokines was determined in the serum and supernatant of a 24-hour whole blood culture using enzyme-linked immunosorbent assay (ELISA) using test systems (Vector Best, Russia). Results. It was shown that the content of IFN-γ decreased (P = 0.013) after Ingaron therapy in patients with initially high levels of induced IFN-γ (4435.64 ± 1343.50 pg/ml). In patients with initially low levels of induced IFN-γ (234.25 ± 34 , 31 pg / ml) the content of IFN-γ increased (P = 0.002). Ingaron leads to an increase in spontaneous and serum IFN-γ production in patients. Conclusions. Conducting Ingaron therapy with ChEBVI is shown independently of the initial production of IFN-γ-induced lymphocyte culture. Ingaron is recommended for the treatment of patients with ChEBVI at a dose of 500,000 IU with a course dose of 10 or more injections.