bluuebunny/crossref_metadata_2025 huggingface dataset:
New ibuprofen derivatives with thiazolidin-4-one scaffold with improved pharmaco-toxicological profile
Authors: Vasincu Ioana-Mirela , Apotrosoaei Maria , Constantin Sandra Madalina , Butnaru Maria , Vereștiuc Liliana , Lupusoru Catalina-Elena , Buron Frederic , Routier Sylvain , Lupascu Dan , Tauser Roxana-Georgiana , PROFIRE LENUȚA
Published: November 2020

Background
Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen.
Methods
For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used.
Results
The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 µg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models.
Conclusions
The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.
Knowledge, attitude and practice of health care workers on measuring adult vitamin D level, diagnosis of deficiency, and management of consequent health conditions in three ecologies of Ethiopia: A cross-sectional study
Authors: Mekonnen Wubegzier , Feleke Yeweyenhareg , Desalegn Yakob , Tarekegne Getahun , Lambisso Biruk , Haidar Jemal , Zewede Tewabech
Published: November 2020

Background: Vitamin D is essential for health and its shortage exacerbate overall mortality. Health care workers (HCWs) need to educate on its uses and sources although studies indicate their low level of practice. The main aim of this study is therefore to assess the knowledge, attitude and practice of measuring adult vitamin D status, diagnosis of deficiency and managing health consequences among HCWs in Ethiopia.Methods: This study was conducted in three ecologies covering lowland, midland and highland districts. A total of 405 health care workers with different levels were interviewed. Tablets were used for data collection to archive in a cloud server. Data were exported to Stata version 14 software for cleaning and analysis. Rates were computed and Chi-square test was used to compare differences between the two groups. Binary logistic regression was used to measure the strength, direction and significance of association between different covariates and the practice of HCWs.Result: The level of knowledge, positive attitude and good practice in measuring adult vitamin D status, diagnosis of deficiency and managing health consequences among HCWs was 210(51.8%), 261(63.5%) and 195(47.4%) respectively. The odds of good practice in the provision of adult vitamin D service were AOR=6.87: 95% CI (3.57, 13.21) and AOR= 2.20: 95% CI (1.23, 3.92) times higher among HCWs in Addis Ababa and highlands compared with those working in lowlands. Good practice among clinicians was AOR=4.26: 95% CI (1.48, 12.25) times higher compared with those working in leadership positions. The likelihood was AOR=1.96: 95% CI (1.19, 3.23) times higher among those with good knowledge compared with those with poor knowledge. Besides, good practice in adult vitamin D service provision was AOR=2.30: 95% CI (1.40, 3.78) times higher among those with positive attitude compared with those who had negative attitude.Conclusions: A little over half of HCWs have good knowledge and close to two-third of them has positive attitude while less than half of them have good practice on adult vitamin D deficiency. Besides, HCWs residential ecology, clinical position, knowledge and attitude is associated with good practice on adult vitamin D. It is essential to provide rigorous and continues training for HCWs focusing on their deployment ecology.
Perspectives of family physicians towards access to lung cancer screening for individuals living with low income – a qualitative study
Authors: Sayani Ambreen , Vahabi Mandana , O’Brien Mary Ann , Liu Geoffrey , Hwang Stephen W. , Selby Peter , Nicholson Erika , Lofters Aisha
Published: November 2020

Background: Individuals living with low income are less likely to participate in lung cancer screening (LCS) with low-dose computed tomography. Family physicians (FPs) are typically responsible for referring eligible patients to LCS; therefore, we sought to understand their perspectives on access to lung cancer screening for individuals living with low income in order to improve equity in access to LCS. Methods: A theory-informed thematic analysis was conducted using data collected from 11 semi-structured interviews with FPs recruited from three primary care sites in downtown Toronto. Data was coded using the Systems Model of Clinical Preventative Care as a framework and interpretation was guided by the synergies of oppression analytical lens. Results: Four overarching themes describe FP perspectives on access to LCS for individuals living with low income: the degree of social disadvantage that influences lung cancer risk and opportunities to access care; the clinical encounter, where there is often a mismatch between the complex health needs of low income individuals and structure of health care appointments; the need for equity-oriented health care, illustrated by the neglect of structural origins of health risk and the benefits of a trauma-informed approach; and finally, the multiprong strategies that will be needed in order to improve equity in health outcomes. Conclusion: An equity-oriented and interdisciplinary team based approach to care will be needed in order to improve access to LCS, and attention must be given to the upstream determinants of lung cancer in order to reduce lung cancer risk.
Salting-Out Induced Liquid-Liquid Microextraction for Alogliptin Benzoate Determination in Human Plasma by HPLC/UV
Authors: Hammad Sherin Farouk , Abdallah Inas , Bedair Alaa , Mansour Fotouh
Published: November 2020

Salting-out induced liquid-liquid microextraction method has been developed for plasma sample treatment before determination of alogliptin by high performance liquid chromatography with UV detection. Several parameters were optimized to achieve maximum enrichment, including type of extractant, volume of extractant, type of anion, type of cation, salt amount and pH. The optimum conditions were attained using 500 µL of acetonitrile, added to 1 mL of aqueous sample containing 250 mg of sodium chloride at pH 12. An RP-HPLC method was developed and validated according to the International Conference on Harmonization guidelines M10. The method was linear in the concentration range of 0.1 to 50 µg/mL (correlation coefficient= 0.997). The limit of detection was 19 ng/mL and limit of quantitation was 60 ng /mL. The method was accurate and precise with an average % recovery of 99.7% and a % relative standard deviation ranging between 1.5 and 2.5. These results showed that the salting-out induced liquid-liquid microextraction methods could be better than other sample preparation protocols in terms of sensitivity, easiness, solvent consumption and waste reduction.
Universal adversarial attacks on deep neural networks for medical image classification
Authors: Hirano Hokuto , Minagi Akinori , Takemoto Kazuhiro
Published: November 2020

Background. Deep neural networks (DNNs) are widely investigated in medical image classification to achieve ﻿automated support for clinical diagnosis. It is necessary to evaluate the robustness of medical DNN tasks against adversarial attacks, as high-stake decision-making will be made based on the diagnosis. Several previous studies have considered simple adversarial attacks. However, the vulnerability of DNNs to more realistic and higher risk attacks, such as universal adversarial perturbation (UAP), which is a single perturbation that can induce DNN failure in most classification tasks has not been evaluated yet.Methods. We focus on three representative DNN-based medical image classification tasks (i.e., skin cancer, referable diabetic retinopathy, and pneumonia classifications) and investigate their vulnerability to the seven model architectures of UAPs.Results. We demonstrate that DNNs are vulnerable to both nontargeted UAPs, which cause a task failure resulting in an input being assigned an incorrect class, and to targeted UAPs, which cause the DNN to classify an input into a specific class. The almost imperceptible UAPs achieved > 80% success rates for nontargeted and targeted attacks. The vulnerability to UAPs depended very little on the model architecture. Moreover, we discovered that adversarial retraining, which is known to be an effective method for adversarial defenses, increased DNNs’ robustness against UAPs in only very few cases.Conclusion. Unlike previous assumptions, the results indicate that DNN-based clinical diagnosis is easier to deceive because of adversarial attacks. Adversaries can cause failed diagnoses at lower costs (e.g., without consideration of data distribution); moreover, they can affect the diagnosis. The effects of adversarial defenses may not be limited. Our findings emphasize that more careful consideration is required in developing DNNs for medical imaging and their practical applications.
Comparison with tube core and Magill forceps for nasotracheal intubation: a randomized controlled trial
Authors: Hu Rui , Niu Jingyi , Wu Lining , Sun Hao , Sun Peng , Huang Jiaying , Yu Junma
Published: November 2020

Background: Magill forceps are frequently used to complete the process of nasotracheal intubation (NTI). We aimed to identify a tube core that could facilitate the NTI process conveniently without Magill forceps. Methods: Sixty patients with no differences between the two groups (30 per group) with regard to demographic data were enrolled in our study. In Group M, the wire-reinforced tracheal tube was inserted into the trachea using Magill forceps. However, in Group T, a tube core bent to the physiological curve of the nasal cavity lubricated with aseptic liquid paraffin was inserted into the tracheal tube, and the tube core was then withdrawn after the tracheal tube was advanced through the glottis under direct vision. Results: All NTIs were completed successfully, and no Magill forceps were used in Group T. There was a significant difference in total NTI time between the two groups (Group M, 59.7 (5.1) sec vs Group T, 52.4 (3.1) sec). Mild epistaxis was observed in 6 patients in Group M and 5 patients in Group T (6/30 vs 5/30, respectively). There was no presence of damaged oral tissue or damage to the teeth in either group. Conclusion: We conclude that using the tube core, which is a disposable sterilised stylet, for NTI is a convenient choice. Trial registrations: This clinical research was registered at the Chinese Clinical Trial Registry (www.Chictr.org.cn, ChiCTR1900027387).
Genome-wide survey of the phosphofructokinase family in cassava and functional characterization in response to oxygen-deficient stress
Authors: Wang Haiyan , Zhao Pingjuan , Shen Xu , Xia Zhiqiang , Zhou Xincheng , Chen Xin , Lu Cheng , Wang Wenquan
Published: November 2020

Background: Glycolytic pathway is common in all plant organs, especially in oxygen-deficient tissues. Phosphofructokinase (PFK) is a rate-limiting enzyme in the glycolytic pathway and catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Cassava (Manihot esculenta) root is a huge storage organ with low amount of oxygen. However, less is known about the functions of PFK from M. esculenta (MePFK). We conducted a systematic analysis of MePFK genes to explore the function of the MePFK gene family under hypoxic stress.Results: We identified 13 MePFK genes and characterised their sequence structure. The phylogenetic tree divided the 13 genes into two groups: nine were MePFKs and four were pyrophosphate-fructose-6-phosphate phosphotransferase (MePFPs). We confirmed by green fluorescent protein fusion protein expression that MePFK03 and MePFPA1 were localised in the chloroplast and cytoplasm, respectively. The expression profiles of the 13 MePFKs detected by quantitative reverse transcription polymerase chain reaction revealed that MePFK02, MePFK03, MePFPA1, MePFPB1 and MePFPA2 displayed higher expression in leaves, root and flower. The expression of MePFK03, MePFPA1 and MePFPB1 in tuber root increased gradually with plant growth. We confirmed that hypoxia occurred in the cassava root, and the concentration of oxygen was sharply decreasing from the outside to the inside root. The expression of MePFK03, MePFPA1 and MePFPB1 decreased with the decrease in the oxygen concentration in cassava root. Waterlogging stress treatment showed that the transcript level of PPi-dependent MePFP and MeSuSy were up-regulated remarkably and PPi-dependent glycolysis bypass was promoted. Conclusion: A systematic survey of phylogenetic relation, molecular characterisation, chromosomal and subcellular localisation and cis-element prediction of MePFKs were performed in cassava. The expression profiles of MePFKs in different development stages, organs and under waterlogging stress showed that MePFPA1 plays an important role during the growth and development of cassava. Combined with the transcriptional level of MeSuSy, we found that pyrophosphate (PPi)-dependent glycolysis bypass was promoted when cassava was under waterlogging stress. The results would provide insights for further studying the function of MePFKs under hypoxic stress.
Comparison of intraocular pressure among individuals with systemic hypertension and those with normal blood pressure
Authors: Parajuli Sanket , Shrestha Pooja , Shrestha Jeevan kumar
Published: November 2020

Background
Systemic blood pressure, by far is one of the most important factors that can have an effect on intraocular pressure. There is a limited set of studies regarding the effects of increased blood pressure on intraocular pressure. As for our knowledge, this study was first of its kind in Nepal. We have tried to compare the intraocular pressure (IOP) among patients with systemic hypertension and those with normal blood pressure.
Methods
A hospital based prospective case control study was conducted from March 2017 to March 2018 in the outpatient department of the department of ophthalmology in Dhulikhel hospital. A total of 100 patients with hypertension were included in case group (hypertensive group) and 100 cases with no systemic or ocular disease were included in control group (normotensive group). Mean intraocular pressures were calculated and compared along with the different range of blood pressure levels.
Results
Mean age of patients was 49.03 years in hypertensive group and 47.53 years in Normotensive group. Mean IOP of right eye in those with hypertension was 16.10 mmHg and in left eye was 15.8 mmHg. Similarly mean IOP of right eye in normotensive group was 15.8 mmHg and left eye was 16.2 mmHg. The difference between mean of IOP of hypertensive and normotensive individuals were not statistically significant. The prevalence of ocular hypertension in this study population was found to be 7.5% in that age group. The prevalence of primary open angle glaucoma (POAG) in this study population was found to be 1.5%.
Conclusion
There was no statistically significant difference in IOP between hypertensive and normotensive individuals. There was statistically significant difference in IOP in hypertensive with controlled BP and hypertensive with uncontrolled BP indicating that high BP may be associated with high IOP.
Stomatin modulates adipocyte differentiation through ERK pathway and regulates lipid droplet growth and function
Authors: Wu Shao-Chin , Lio Yuan-Ming , Lee Jui-Hao , Chen Chin-Yau , Chen Tung-Wei , Liu Hong-Wen , Lian Wei-Nan , Lin Wei-Ju , Yang Chih-Yung , Tung Chien-Yi , Lin Chi-Hung
Published: November 2020

Controlling fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), are closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of the lipid raft, participate in adipogenesis and lipogenesis by preferentially recruiting effectors, such as perilipin for LD fusion or transporters for fatty acid uptake. Adipocyte-like cells having increased stomatin expressions exhibit higher levels of fatty acid uptake and LD growth or enlargements. Moreover, transgenic mice fed with a high-fat diet showed increased stomatin expression that facilitated progression of obesity and caused insulin resistance and hepatic impairments. Conversely, inhibitions of stomatin by gene knockdown or pharmacological treatments could block not only LD growth but also adipogenic differentiation through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involved ERK signaling; however, an alternate pathway also exist. Amongst various anti-obesity measures, stomatin serves as another potential therapeutic target.
First report of the stubby-root nematode Nanidorus minor infecting Paspalum vaginatum, seashore paspalum grass in Georgia, USA
Authors: Jagdale Ganpati B. , Forghani Fereidoun , Martin Katherine , Hajihassani Abolfazl , Martinez-Espinoza Alfredo Dick
Published: November 2020

We found that Nanidorus spp. was pathogenic to seashore paspalum (Paspalum vaginatum) turfgrass as its population increased from 100 to 2,080 nematodes per pot 180 days after inoculation under greenhouse conditions. Morphological measurements of adult females were similar to those described for N. minor. Molecular analysis also confirmed the morphological identification by targeting three different regions of the genomic DNA. Three primer pairs targeting 18S rDNA (360F/932R), 28S rDNA (D2A/D3B) and ITS1 rDNA (BL18/5818) were used in singleplex PCR. Forward and reverse sequences of each individual primer set were then subjected to multiple alignment and the complimentary sequences were assembled into a consensus sequence. Upon nucleotide blast on the NCBI website, they were all confirmed to be N. minor. A one-step multiplex PCR method using specific primers and a fragment size of 190 bp also confirmed the identity of N. minor. To the best of our knowledge, this is the first report of N. minor infecting seashore paspalum turfgrass in Georgia.
Influence of lithium chloride on the apoptosis of endotheliocytes in systemic inflammatory response syndrome in patients with severe multiple injury. A retrospective study
Authors: Kuzovlev Artem N. , Grebenchikov O. A. , Meshkov M. A. , Dolgikh V. T. , Prokofiev M. D. , Shpichko N. P. , Ershov A. V.
Published: November 2020

Objectives. The goal is to study the effect of lithium chloride on the intensity of endotheliocytes apoptosis in a monolayer in vitro under the action of blood serum of patients with the syndrome of systemic inflammatory response in severe multiple trauma.
Materials and methods. We used toxic blood serum of 5 patients with severe multiple trauma. As controls we used blood serum of 5 healthy donors. In different series of the experiment EA.hy926 endothelial cells were incubated with blood serum of a healthy person (control), with blood serum of patients with systemic inflammatory response syndrome in severe multiple trauma. Lithium chloride was added to the cell samples at final concentrations of 0.01, 0.1, 1, 10 mmol/L. After incubation the cells were removed with trypsin-versen solution fixed with 70 % ethanol and stained with propidium iodide. Cells containing fragmented genomic DNA were analyzed by flow cytometry.
Results. It was revealed that toxic serum suppressed GSK-3β phosphorylation in endotheliocytes and also caused the splitting of VE-cadherin, a decrease in the amount of claudine and actin, initiating the destruction of intercellular contacts of the endothelial monolayer and apoptosis of endotheliocytes. Incubation of a monolayer of endotheliocytes with lithium chloride at a concentration of 1.0 mmol/l and higher almost completely prevented the dismantling of claudine, actin and VE-cadherin, and also reduced the intensity of apoptosis of endotheliocytes by more than 2 times. It was found that preincubation with lithium chloride at a concentration of 1 mmol/L not only prevented the inactivation of GSK-3β, but even stimulated its phosphorylation.
Conclusion. Lithium chloride prevents the dismantling of claudine and VE-cadherin in the intercellular contacts, reduces the number of apoptotic cells in the monolayer of the endothelial cells of the EA.hy926 line under the action of the blood serum of patients with a systemic inflammatory response syndrome in severe multiple trauma, which may indicate a protective effect of the drug on endothelial barrier. The results of this investigation suggest that the protective effect of lithium chloride on endothelium is realized via GSK-3β phosphorylation.
Evaluation of the need of perioperative antibiotic prophylaxis at endoscopic operations in bariatric surgery. An observational study
Authors: Prudkov A. I. , Anferov I. D. , Anferov D. I. , Fyodorova K. E. , Mezenina Ya. M. , Struikhin A. S. , Nishnevich E. V. , Rudnov Vladimir A.
Published: November 2020

Purpose of the study. To determine the need for perioperative antibiotic prophylaxis in video endoscopic operations in bariatric surgery. Materials and methods. The observational study included 152 patients who underwent sleeve gastrectomy for morbid obesity — 94 (61.84 %), gastric bypass surgery — 21 (13.82 %), mini-gastric bypass surgery — 31 (20.40 %) or gastric banding — 6 (3.94 %) in the absence of PAP. All surgical interventions were performed by one team of surgeons. The average duration of the operation was 140.69 ± 35.57 minutes. The overwhelming majority of patients belonged to the average age — 44.0 ± 8.5 years (from 23 to 64 years). The average body mass index (BMI) of all patients at the time of admission was 46.57 ± 7.12. Results. It was found that the development of infections of the surgical site (SSI) without the use of antibiotics in the perioperative period was absent, the frequency of presumed infections was 4.0 % (6 out of 151). Moreover, only in 1 case, an anastomotic leak was diagnosed, in 6 cases the focus of infection was not established and antibiotics (cefoperazone / sulbactam or cefepime, or ceftriaxone) were prescribed empirically for 2–3 days based on an increase in the number of blood leukocytes and a rise in body temperature above normal values. An increase in body temperature and an increase in the number of blood leukocytes in the initial state was associated with grade 4 on the ASA scale and an operation duration of more than 180 minutes. Conclusion. During endovideoscopic surgeries for morbid obesity, perioperative antibiotic prophylaxis is justified only in patients belonging to the 4th class on the ASA scale and the estimated duration of surgery is more than 3 hours.
Molecular Diagnosis of FLT3 Mutations in Acute Myeloid Leukemia Patients
Authors: Zaikova E.K. , Belotserkovskaya Ekaterina Vasil’evna , Zaytsev D.V. , Petukhov A.V. , Fedorova O.A. , Motorin D.V. , Ivanov V.V. , Zaritskey A.Yu. , Girshova L.L.
Published: November 2020

Background. FLT3 gene is an important prognostic molecular marker in acute myeloid leukemia (AML). However, the detection of FLT3 mutations presents a challenge. Aim. To compare techniques used for the detection of FLT3 mutations, and to develop a test-system based on polymerase chain reaction (PCR) for quick and reliable determination of FLT3 mutation status. Materials & Methods. Bone marrow samples obtained from AML patients were subjected to examination. To detect FLT3-ITD and FLT3-TKD mutations PCR was performed with subsequent agarose gel electrophoresis visualization. The results were verified by Sanger sequencing. The data obtained using our test-system were compared with widely applied commercial kit ‘FLT3 Mutation Assay for Gel Detection’ by Invivoscribe. Results. To determine the FLT3 mutation status a PCR test was developed. This technique was validated on 22 bone marrow samples obtained from AML patients. FLT3-ITD mutation was detected in 4 patients, 3 patients showed FLT3-TKD mutation. In 1 patient both mutations were identified. These results fully corresponded to the molecular genetic analysis of FLT3, performed by ‘FLT3 Mutation Assay for Gel Detection’. The chosen technique was validated using Sanger sequencing data analysis. Conclusion. The article offers the review of all existing FLT3 mutation screening techniques and describes the experience of developing the PCR test for FLT3-ITD and FLT3-TKD mutation detection. The chosen technique is affordable and easy to use compared with the others. This study can be used as a guide for both doctors and researchers.
Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice
Authors: Lepik K.V. , Volkov N.P. , Mikhailova N.B. , Kondakova E.V. , Tsvetkova L.A. , Zalyalov Yu.R. , Lepik Ye.Ye. , Fedorova L.V. , Beinarovich A.V. , Demchenkova M.V. , Smykova O.G. , Kotselyabina P.V. , Moiseev I.S. , Baikov V.V. , Afanasyev B.V.
Published: November 2020

Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/re-fractory classic Hodgkin's lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria. Results. The study included 42 patients with relapsed/re-fractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22-43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2-99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3-49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4-79.1 %) vs. 25.2 % (95% CI 10.46-43.1 %) in patients who did not reach CR (p = 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8-37.5 %) vs. 68 % (95% CI 35.9-86.8 %) in their absence (p = 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3-4 were observed in 19.1 % of patients. Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.
Efficient Transduction of T-Lymphocytes by Lentiviral Particles in Oncoimmunological Studies
Authors: Zaikova E.K. , Levchuk K.A. , Pozdnyakov D.Yu. , Daks A.A. , Zaritskey A.Yu. , Petukhov A.V.
Published: November 2020

Aim. To compare different methods of lentivirus concentration in order to select the best way of providing high-level transduction for generating laboratory CAR-T cells. Materials & Methods. Concentration of lentiviral supernatant was carried out by 4 methods: ultrafiltration, ultracentrifugation, polyethylene glycol (PEG), water-soluble non-ionic polymer, precipitation method, and ion-exchange chromatography. Functional viral titer was determined by mCherry reporter protein expression in the transduced HeLa cell line as well as by rapid immunochromatographic (IC) tests. Physical titer was determined by ELISA. Transduction efficiency of healthy donor’s T-lymphocytes was assessed by flow cytometry with respect to signal intensity of reporter protein FusionRed. Functional activity of generated anti-CD19 CAR-T was evaluated by microscopy after co-cultivation with CD19-HeLa cell line as well as subsequent cytokine testing. Results. Lentivirus purification and concentration by ultrafiltration provided the greatest number of transduced cells, i.e. 84.7 %. Methods of ultracentrifugation, PEG precipitation, and ion-exchange chromatography yielded 56.08 %, 74.22 %, and 21.05 % of T-cell transduction, respectively. Results of rapid IC tests were comparable (г = 0.91) with cell line titer data. The mean T-cell transduction efficiency was 59.55 % ± 2.94 %, and its maximum reached 76.26 %. Conclusion. The focus was laid on optimization of CAR-T cell production during the generation of lentiviral vectors and their purification. Ultrafiltration was selected as the best method of lentiviral supernatant concentration to efficiently transduce T-lymphocytes and to generate functional CAR-T cell population.
Comorbidity and Personalized Treatment of Multiple Myeloma in Real Clinical Practice
Authors: Skvortsova N.V. , Kovynyov I.B. , Khalzov K.V. , Nechunaeva I.N. , Pospelova T.I.
Published: November 2020

Aim. To study incidence and structure of comorbidity in multiple myeloma (MM) patients depending on their age; to determine its effect on overall survival, efficacy, and safety of the first-line therapy in real clinical practice. Materials & Methods. Overall, 369 patients with newly diagnosed MM were enrolled in the trial from January 2012 to December 2017. Among them there were 134 men and 235 women hospitalized at the Unit of Hematology in the Novosibirsk Municipal Clinical Hospital No. 2. Median age of patients was 67 years (range 32-82 years). Results. The analyzed patients were divided into three age groups: the first group of young/middle age (32-59 years) (n = 105), the second group of elderly patients (6074 years) (n = 186), and the third group of old age (> 75 years) (n = 78). In each patient prior to chemotherapy the comorbidity spectrum was identified and CIRS-G, CCI, and MCI comorbidity scores were calculated. Patients with newly diagnosed MM in real clinical practice prove to have high and increasing with age comorbidity incidence (91 % in patients of young/middle age, 97,7 % and 100 % in patients of elderly and old age, respectively). Comorbidity significantly reduces overall survival (OS) of MM patients. Important OS predictors are rhythm and conduction disorder (odds ratio, OR, 2.762; p < 0.002), chronic pancreatitis (OR 1.864; p < 0.001), exogenous constitutive obesity (OR 1.948; p < 0.002), chronic obstructive pulmonary disease (OR 2.105; p < 0.021), chronic kidney disease, stage С4-С5 (OR 2.255; p < 0.003), and chronic heart failure, functional class II (OR 1.915; p < 0.002). Highest importance in predicting OS, efficacy, and tolerance to chemotherapy in MM patients is attached to MCI score (OR 3.771; p < 0.001). MM patients with high risk by MCI are characterized by lower rate and depth of response to the first-line therapy, shorter time before the first relapse, higher incidence of non-hematologic toxicity of grade > 3, and therapy withdrawal or drug dose reduction.
Mantle Cell Lymphoma: History, Current Principles of Diagnosis, and Treatment (Literature Review)
Authors: Tumyan Gayane Sepugovna
Published: November 2020

Mantle cell lymphoma (MCL) is a heterogeneous disease with a broad spectrum of clinical manifestations from rare indolent cases requiring no immediate treatment to aggressive fast-proliferating tumors. Differences in clinical behavior are rooted in molecular grounds which in the latest edition of WHO hematopoietic and lymphoid tissue tumor classification formed the basis for dividing MCL into two variants: classical (in most cases) and indolent. In last decades, our insight into biology and disease development mechanisms has been considerably enhanced. Further, it will help to risk stratify patients not only according to clinical factors (MIPI) but also taking into account molecular and biological properties of tumor (Ki-67 proliferation index, ТР53, NOTCH1, and NOTCH2 mutations, complex karyotype, and unmutated IGHV status). Treatment algorithms based on intensive chemotherapy with high-dose cytarabine and autologous hematopoietic stem cell transplantation with further rituxi-mab maintenance therapy ensure long-term monitoring of the disease in many MCL patients. The use of new “chemo-free” regimens and rational combinations (bortezomib, BTK inhibitors, lenalidomide, and venetoclax) offers the hope of a departure from conventional chemotherapy for a certain part of patients. Novel drugs with unique modes of action enabled, to some extent, to deconstruct the stigma of MCL fatality.
Intermediate Results of Prospective, Randomized, Comparative Study of NHL BFM-90 and СНОЕР Efficacy in Primary ALK-Positive Anaplastic LargeCell Lymphoma
Authors: Gorenkova Liliya Gamilevna , Kravchenko S.K. , Klebanova E.E. , Kovrigina A.M. , Sychevskaya K.A. , Gemdzhian E.G. , Nesterova E.S. , Mangasarova Ya.K. , Magomedova A.U. , Misyurin A.V. , Sidorova Yu.V. , Obukhova T.N.
Published: November 2020

Aim. To compare NHL BFM-90 and CHOEP efficacy in adult patients with ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL). Materials & Methods. Within the period from June 2014 to December 2019 the prospective randomized comparative study at the National Research Center for Hematology in Moscow included 23 ALK+ ALCL patients. In one study arm (n = 11) CHOEP was administered, whereas the other one (n = 12) received high-dose chemotherapy (CT) according to NHL BFM-90 protocol. The median age of patients in both arms was 33 and 40 years, respectively. Results. Overall survival (OS) and event-free survival (EFS) within 3 years were 91 % in the arm receiving CHOEP (this protocol was administered to all 11 patients), and 100 % in the arm receiving NHL BFM-90 (complete remission was achieved in all patients). Due to its toxicity NHL BFM-90 was fully implemented in 9 out of 12 patients. The 3-year OS and EFS in the CHOEP and NHL BFM-90 arms are comparable, and the difference between them is not significant. Conclusion. In ALK+ ALCL treatment high-dose CT according to NHL BFM-90 protocol has no advantage in terms of the 3-year OS and EFS compared to less toxic regimen CHOEP. A larger sample of patients is required to achieve significant results, which will further lead to a final judgement on feasibility of high-dose regimens in the treatment of adult patients with ALK+ ALCL.
Clinical and Immunomorphological Characteristics of Lymphomatoid Papulosis Type E (Literature Review and Case Report)
Authors: Valiev Timur Teimurazovich , Kovrigina A.M. , Belysheva T.S.
Published: November 2020

Lymphomatoid papulosis (LP) is a rare variant of benign lym-phoproliferative disease with skin involvement. Based on clinical, morphological, and immunobiological characteristics, WHO hematopoietic and lymphoid tissue tumor classification (2016) differentiates between several LP types: А, В, С, D, Е, and with 6p25.3 rearrangement. The present article reviews the literature on clinical course, pathomorphologi-cal, immunological, and biomolecular characteristics of LP in adults and children. For the first time in the domestic literature, it provides a case report of LP, type E, in a 2-year-old child. Differential diagnosis and optimal disease management of LP are also described in detail.
New Technology Capabilities of Direct Antiglobulin Test
Authors: Poponina Elena Aleksandrovna , Butina E.V. , Iovdii A.V. , Maksimov O.D. , Zaitseva G.A. , Paramonov I.V.
Published: November 2020

Background. Direct antiglobulin test (DAT) is used to identify erythrocyte-fixed antibodies and complement components. Gel methods are applied to differentiate immunoglobulin class and subclass in positive DAT, which allows to study the nature of anemia and assess the risk of immune hemolysis. Aim. To assess the rate of positive DAT in oncohematological patients, to determine class and subclass of erythrocyte-fixed immunoglobulins, and to evaluate their contribution in hemolytic complications. Materials & Methods. In 393 oncohematological patients at the Kirov Research Institute of Hematology and Transfusiology differentiated DAT was studied using gel test with BioRad (USA) testing sets. Results. The rate of positive DAT in oncohematological patients varied for different diseases from 6.2 % to 25.2 %, in the total group it was 15.5 %. It accounted for 6.2 % in acute leukemias, 6.3 % in myelodysplastic syndrome, 10 % in chronic myeloid leukemia, 11.9 % in Hodgkin’s lymphoma, 15.4 % in chronic lymphocytic leukemia, 21 % in non-Hodgkin’s lymphoma, and 25.2 % in multiple myeloma. In multiple myeloma, acute leukemia, Hodgkin’s lymphoma, and chronic myeloid leukemia patients the positive test was associated with IgG subclasses 2 and 4. In chronic lymphocytic leukemia and non-Hodgkin’s lymphoma patients IgG1 subclass 1, IgM and C3c, C3d complement components were detected on erythrocyte surfaces. It was shown that IgG2/ IgG4 detection was not accompanied by any clinical or laboratory signs of immune hemolysis, IgG1 was responsible for destruction of erythrocytes in 50 % of cases, whereas the detection of C3c, C3d complement components was associated with hemolytic manifestations in 100 % of cases. Conclusion. Positive DAT should be interpreted in light of laboratory and clinical data. Differentiated test helps to predict hemolytic complications in oncohematological patients.
Determination of thermophysical characteristics and viscous properties of minced raw materials from pond carp
Authors: Aleksanian I. Yu. , Nugmanov A. H.-H. , Vasilievna Y. N. , Feklunova J. S.
Published: November 2020

The thermophysical characteristics and structural-mechanical properties of a functional minced fish product have been examined, the knowledge of which is necessary for thermal calculations of the developed or improved freezing units. To find the thermophysical properties, the authors used a probe method based on the thermal inertial properties of a thermocouple, which is rarely used by modern researchers, although its advantages are obvious: in particular, it allows one to determine the desired characteristics during the working process. When studying the viscous rheology of minced semi-finished products, choosing between different types of viscometers, the authors have given a detailed analysis of the principle of their operation, as a result of which it is noted that rotary viscometers are most preferable for minced fish, since they require a smaller amount of test material to achieve the required variability of shear rates in him. Low-temperature processing of raw materials from aquatic organisms, due to its high importance for aquaculture, is constantly in the field of vision of specialists connected with refrigeration technologies for storing and processing food objects. The main trends in the development of freezing technology are aimed at increasing the intensity of processes for removing heat from the objects of freezing, but it is important to ensure the safety of their consumer properties, which directly affect the choice of the applied method of carrying out the technological process. Nowadays, there are a sufficient number of freezing methods, and the choice of the method and technical means of refrigerating various food materials requires a systematic approach, the formation of which is impossible without knowledge of the thermophysical and rheological characteristics of the processing object. The use of the results obtained by the authors, together with other necessary studies, will make it possible to identify rational operating parameters for obtaining frozen minced fish pellets with specified consumer properties. These granulated products will reduce the time for the production of minced fish culinary products at catering enterprises due to the exclusion of the stage of separate defrosting of minced semi-finished product from the technological chain.
Wealth creation through corporate diversification – the bondholders’ perspective
Authors: Mammen Jan
Published: November 2020

The influence of corporate diversification on firm value is an important field in strategy research. Studies in strategic management and finance research have analyzed value creation through product and geographic diversification from a shareholder’s perspective. This study completes this picture by analyzing the bondholders’ perspective. It is suggested that product diversification creates value for bondholders, while geographic diversification destroys bondholder value. The hypotheses are tested on a sample of S&P 1,200 firms in 2001–2011 using a fixed-effects panel model. Drawing on prior research, bondholder value creation is measured using the Merton model. The empirical results support the hypothesis that bondholders gain value through product diversification but lose value through geographic diversification. Considering prior research results, these results show that product diversification is preferable for bondholders, while geographic diversification is preferable from a shareholder’s perspective. The opposite effects of both diversification strategies on shareholders, respectively, bondholders offer an important new perspective on corporate diversification. The results show that firms with a high level of corporate debt should struggle to justify a strategy involving geographic dispersion of activities and support a more diversified product portfolio strategy. This study also offers several avenues for investigating the bondholder’s perspective on corporate diversification in more detail.
Do Audit Fees and Characteristics of CEO Decrease Audit Delay in Mandatory IFRS Adoption?
Authors: Mawardi Rizal , Lanjarsih Laela
Published: November 2020

The research examined characteristics of CEO and audit fees on audit delay related to changes in mandatory IFRS adoption. In the setting, gender and audit fees were the level of risk tolerance, overconfidence, diligence, and monitoring intensity. As a result, these individual differences were likely to be reflected in audit delay in financial reporting decisions. Using firm data levels between 2008 and 2016 with multivariate regression, the researchers provided empirical evidence supporting the hypothesis that the characteristics of CEO and audit fees were the determinants of audit delay. There are several findings. First, the financial expertise of the CEO has more significant percentages in mandatory IFRS adoption than voluntary IFRS adoption. It is associated with a shorter delay. Second, having a female CEO and appointing a female and minority CEO will increase the likelihood that firms will issue financial reports more timely. Third, higher audit fees in mandatory than voluntary IFRS adoption can decrease audit delay.
Perovskite-Type Oxides La0.6M0.4Ni0.6Cu0.4O3 (M = Ag, Ba, Ce) towards the Oxygen Reduction Reaction (ORR) in Alkaline Medium: Structural Aspects and Electrocatalytic Activity
Authors: Lima Alan , Lima Alex , Meloni Gabriel , Santos Carla , Bertotti Mauro
Published: November 2020

In this work, La0.6M0.4Ni0.6Cu0.4O3 (M = Ag, Ba, and Ce, denoted as LANC, LBNC, and LCNC, respectively) electrocatalysts were synthesized by the Pechini method at 1023 K for two hours in air. Rietveld refinement allowed the identification of the crystallographic phases present in all oxides. The electrocatalytic performance of these oxides towards the oxygen reduction reaction (ORR) was examined in alkaline medium by rotating disk electrode (RDE) technique and scanning electrochemical microscopy (SECM) in the redox competition mode. The results indicate that the best performance was found with the LANC electrocatalyst prepared with carbon as a conducting agent (LANC/Carbon), which showed good catalytic activity towards the ORR via a pseudo fourelectron transfer pathway. The enhanced electrocatalytic activity of LANC is probably a result of the presence of a Ag phase, which improves the synergistic effect between the perovskite and carbon added to increase the conductivity, thus leading to a higher ORR performance when compared to other materials.
Comparison and Analysis of Computational Methods for Identifying N6-Methyladenosine Sites in Saccharomyces cerevisiae
Authors: Feng Pengmian , Feng Lijing , Tang Chaohui
Published: November 2020

Background and Purpose:

N6-methyladenosine (m6A) plays critical roles in a broad range of biological processes.
Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological
functions. Although experimental techniques have made substantial contributions to identify m6A, they are still
labor intensive and time consuming. As complement to experimental methods, in the past few years, a series of
computational approaches have been proposed to identify m6A sites.

Methods:

In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary
to conduct a comprehensive review and comparison of existing methods.

Results:

Since research works on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we
summarized recent progress of computational prediction of m6A sites in S. cerevisiae and assessed the performance
of existing computational methods. Finally, future directions of computationally identifying m6A sites
are presented.

Conclusion:

Taken together, we anticipate that this review will serve as an important guide for computational
analysis of m6A modifications.