bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPACT OF THE COVID-19 PANDEMIC ON THE ONCOLOGICAL PRACTICE
Authors: Kaprin A. D. , Gameeva E. V. , Polyakov A. A. , Kornietskaya A. L. , Rubtsova N. A. , Fedenko A. A.
Published: July 2020

Detailed, systematic review of the world literature data, including all aspects that reflect the impact of the COVID-19 pandemic on the oncological practice was conducted. The information sources were taken from Pubmed, MedLine, Scopus, Web of Science, and RSCI systems. The data from retrospective and prospective clinical trials have been analyzed. This review presents current data on the impact of COVID-19 on cancer patients, mortality and prognosis of cancer patients infected with COVID-19, treatment options for COVID-19, as well as the case report of the cancer patient with rare atypical COVID-19 course of disease. To date, the groups of increased risk of being infected with a new coronavirus have been identified. These groups include cancer patients. Despite the pandemic, treatment of cancer patients must be continued, since the presence of a tumor process does not allow the therapy to be delayed. The world cancer community is actively continuing to develop recommendations for optimal management of cancer patients in the context of the pandemic. The most relevant of them are described in this article.
THE INFLAMMATORY STATUS AND LYMPH NODE METASTASES IN NON-SMALL CELL LUNG CANCER
Authors: Pismenny D. S. , Savelieva O. E. , Zavyalova M. V. , Rodionov E. O. , Tashireva L. A. , Tuzikov S. A. , Pankova O. V. , Perelmuter V. M.
Published: July 2020

Introduction. The development of inflammation is characterized by changes in blood hematology parameters and indices. Various inflammatory parameters are used to assess the inflammatory status (IS) during cancer treatment. Recent studies have revealed a relationship between tumor progression and the presence of chronic inflammation. Consequently, there have been many attempts to predict the risk of tumor recurrence and distant metastases, as well as patient’s survival assessing the various inflammatory markers. The relationship between IS parameters and lymph node metastasis remains poorly understood in non-small cell lung cancer (NSCLC).

Material and Methods. The prospective study included 35 patients with NSCLC (T1–4N0–2M0). Seventeen patients received 2–3 cycles of neoadjuvant chemotherapy (NAC). A leukocyte formula was determined in the peripheral blood and inflammatory indices, such as neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), lymphocytes to monocytes ratio (LMR) and systemic immuno-inflammatory index (SII) were calculated. In addition, the concentrations of fibrinogen, C-reactive protein (CRP) and cortisol were evaluated.

Results. NAC alone did not significantly change the parameters of patients’ IS. Lymph node metastases were associated with changes in parameters indicating the enhanced IS. In the group of patients who did not receive NAC, lymph node metastasis was associated with fibrinogen blood levels (cut-off value 5.35 g/L), PLR index value (cut-off value 7.18) and cortisol blood concentration (cut-off value 414 nmol/mL). The confidence level was χ2 =10.118; р=0.018. In the group of patients who received NAC, lymph node metastasis was associated with the leukocyte count (cut-off value 7.1×109 /L), PLR index value (cut-off value is 7.18) and CRP blood concentration (cut-off value is 8.5 mg/L). The confidence level was χ2 =8.193; р=0.042.

Conclusion. Risk of lymph node metastasis in NSCLC is associated with IS. Parameters of IS can be used to predict the risk of lymph node metastases.
ASSOCIATION OF THE COMBINATION OF STEMNESS GENE AMPLIFICATIONS AND COPY NUMBER ABERRATIONS OF WNT-SIGNALING GENES IN BREAST TUMORS WITH METASTASIS
Authors: Litviakov N. V. , Ibragimova M. K. , Tsyganov M. M. , Deriusheva I. V. , Pevsner A. M. , Garbukov E. Yu. , Doroshenko A. V. , Slonimskaya E. M.
Published: July 2020

We studied the association between the presence of 2 or more stemness gene amplifications as well as copy number aberrations (CNAs) of WNT signaling genes in residual breast tumor and metastasis. WNT pathway genes associated with metastasis were identified.

Material and Methods. The study included 30 patients with breast cancer, who had 2 or more stemness gene amplifications in the residual tumor after neoadjuvant chemotherapy. Fifteen of the thirty patients developed hematogenous metastases; they constituted a group with metastases, the remaining 15 patients entered the second group without metastases. The tumor DNA was examined using a CytoScanHD Array microarray (Affymetrix, USA).

Results. By subtracting amplification and deletion frequencies in 852 cytobands between groups with metastases and without metastases, 21 cytobands were identified with the largest difference in deletion and amplification frequencies. They contain 19/150 of WNT genes (12 activators: SKP1, WNT8A, MAPK9, CCND3, FZD9, WNT8B, CCND1, PLCB2, PRKCB, FZD2, WNT3, WNT9B and 7 negative regulators: GSK3B, APC, CSNK2B, SFRP5, BTRC, TCF7L2, CSNK2A2). A point system was developed: when amplifying WNT-signaling activators or deletion of negative regulators, one point was added to the total score, and vice versa when deleting WNT-signaling activators or amplification of negative regulators, one point was taken from the total amount. It was shown that 93% (14/15) of patients with metastases had a total score higher than 0, while 93% (14/15) of patients without metastases had a total score of zero or less than zero. The differences between the groups were statistically significant according to the two-sided Fisher test with a high level of confidence probability (p=0.000003) and the log-rank test (p=0.00004) when assessing non-metastatic survival by the Kaplan-Mayer method.

Conclusion. Nineteen WNT signaling genes were identified. Copy number aberrations of these genes in combination with stemness gene amplifications in residual tumors were associated with metastasis. A new highly effective prognostic factor for breast cancer was identified.
LOSS OF HETEROZYGOSITY IN THE BRCA1 AND BRCA2 LOCUS IN BREAST CANCER
Authors: Tsyganov M. M. , Ibragimova M. K. , Pevzner A. M. , Litviakov N. V.
Published: July 2020

One of the factors of variability of malignant neoplasms is the loss of heterozygosity (LOH). The biological meaning of LOH, in relation to carcinogenesis, is associated with the inactivation of heterozygous loci of pathogenetically significant genes. Thus, the aim of this work was to study BRCA1/2 LOH in breast tumors.

Material and Methods. The study included 122 patients with stage IIAIIIC breast cancer. DNA was isolated from 122 biopsy samples of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). To assess the status of LOH, microarray analysis was performed on high-density DNA chips from Affymetrix CytoScanTM HD Array. To process the results of microchipping, we used the Chromosome Analysis Suite 3.3 program (Affymetrix, USA).

Results. The loss of heterozygosity in the BRCA1 gene was found to be associated with response to NAC. It was shown that in 59 patients LOH in the BRCA1gene was associated with an objective response to treatment (p=0.005). The presence of LOH in the studied genes was associated with a favorable prognosis. The 5-year non-metastatic survival rates were 75 % and 100 % in patients with LOH in the BRCA1 and BRCA2 genes, respectively (log-rank test: p=0.003 and p=0.05, respectively).

Conclusion. The phenomenon of LOH in the BRCA1/2 genes was shown to be associated with response to NACT. BRCA1/2. Further studies are needed to evaluate the frequency of BRCA1/2 LOH after NAC for choosing and changing treatment tactics.
Pictures and Words: Allegorical and Persuasive Cartography
Authors: Mrgić Jelena
Published: July 2020

This paper aims to present a novel approach to map analysis, treating all ‘map-like’ drawings as icono-texts, according to premises postulated in modern cartographical theory by Brian Harley and his successors in this field. It is not just ‘deconstructing’ which takes place, but further interpretations are stimulated by probing questions not only of authorship (often unknown), but also of the social, cultural, and religious environment. Making an allegorical map and text was a difficult task, an intellectual endeavor, which demanded that the author carefully choose the symbols that would outlive the material. In this paper, the Fool’s Cap Map of the World is presented as an example of icono-textual analysis, by bringing together the most popular literary works and their illustrations – Erasmus Desiderius, Sebastian Brandt, and Hieronymus Bosch. The double masks of the author – the pseudonym “Epichtonius Cosmopolites”, with its denunciation of nationality, and the jester’s costume, were chosen as the means of conveying unpleasant truths about the state of the world, France, and/or the Netherlands. Human hybris, Suberbia and Vanitas were the primal sins, by which they were all blinded, waging wars for pieces of land and worldly goods. Therefore, the fool’s malade is melancholy, strictly reserved for male intellectuals – Ficino, Dürer, Shakespeare, Bright and Burton. On the other hand, it would seem as if the female primal sin were vanity, which brings the puritan Bunyan and Anglican Thackeray into this polyphonic interpretation. Their works did, however, show that’'vanitas’ is present among both genders and is an everlasting human trait, now heavily exploited as a ’cash crop’ par excellence. Since all knowlegde is situated, I feel the need to say that I am finishing this paper in self-quarantine due to the ’new plague’ pandemic, wondering if the people in this mad and greedy world would contemplate how all is nothing, and whether the survivors would be better, i.e. more human, acting with more empathy, regardless of the perpetually announced Apocalypse. This remains to be witnessed.
The Construction of the Neoliberal Self in Belgrade Psychotherapeutic Practice
Authors: Vukomanović Bogdan
Published: July 2020

The processes of neoliberalization and European integration in Serbia have been underway for some time, and in addition to their effect on certain elements of the social structure such as the family, the economy, political life etc., their impact is also evident in the way that Serbian citizens perceive themselves and their position in this environment. Due to reduced social protection, the withdrawal of the state from the public sphere, and increasing financial and employment insecurity, individuals are obliged to assume responsibility for their lives and to engage in self-improvement with the aim of personal development and the finding of new survival strategies. Through interviews with psychotherapists and persons who have used the services of private psychotherapy, this paper looks at the relationship between private psychotherapeutic practice in Belgrade as a technique for self-improvement and the construction of the self in its clients, and then relates it to the broader socio-economic context in which the respondents live and work. The findings suggest that with regard to its clients, private psychotherapeutic practice mirrors the emphasis on independence, autonomy and responsibility for one's life and life decisions, which are typical features of the entrepreneurial self characteristic of the period of post-socialist neoliberalization.
Tracking Agriculture-Induced Fertility Among Yorùbá Farmers of Southwestern Nigeria
Authors: Motunrayo Ibrahim Fausat
Published: July 2020

The dynamics of agricultural production in African peasant economies featured human fertility in no small measure. The role of increased fertility in agricultural productivity is explained by opposing ideologies, yet, African perspectives on increased fertility for agricultural production, in the current social climate, are seemingly deficient. Using a triangulation of qualitative methods, this work explores agriculture-induced fertility among Yorùbá farmers of Southwestern Nigeria. The findings clearly and dominantly indicate that the option of increasing fertility deliberately through polygyny, for improved agricultural production has tremendously diminished. Instead, concerns over optimum child development, which can hardly be guaranteed with continued agriculture-induced fertility, are stressed. This shows that Yorùbá farmers’ disposition towards increasing fertility is dictated by pecuniary circumstances, thereby accentuating the rationality of Yorùbá culture and its people.
Kratko proljeće anarhije
Authors: Zebić Enis
Published: July 2020

Studentski prosvjedi 1968. bili su traumatska tema za cijelog kasnijeg trajanja jugoslavenskog socijalizma. Prvo, zato što je po prvi puta netko masovno marksističkom frazeologijom osporio isključivi monopol vlasti Saveza komunista, drugo, zato što je 1968. na ulicu iznijela (poznate i bolne!) strukturne probleme sustava, treće, što je vlast represijom i demagogijom eutanazirala studentski pokret i četvrto – što problemi koje su isticali »šezdesetosmaši« nisu razriješeni sve do propasti jugoslavenskog socijalizma, a priličnim dijelom su toj propasti i kumovali. Fenomen šezdesetosme dio je svojevrsne nečiste savjesti jugoslavenske nomenklature i u tom kontekstu treba interpretirati izravnu i meku represiju nad sudionicima i simpatizerima šezdesetosme, uključujući i »slučaj« raspuštanja uredništva zagrebačkog Studentskog lista 1978. godine.
Onkraj nauka kršćanskoga
Authors: Mikulić Ivana , Senković Željko
Published: July 2020

Hrvatska je književna kultura u 18. stoljeću obilježena stilskim pluralizmom, s tim da se najčešće ističe njezin prosvjetiteljski karakter s naglašenom didaktičkom (odgojnom, moralističkom, katoličkom) i utilitarističkom dimenzijom. Austrijski katekizam temeljna je knjiga školskog vjeronauka od 1777. do 1847. godine u cijeloj Habsburškoj Monarhiji te ima važnu ulogu u odgoju djece, ali i cijele obitelji, odnosno društvene zajednice u duhu jozefinističke politike. Navedena tematika razmatra se u perspektivi Immanuela Kanta kojemu je bilo važno istaknuti opasnosti u koje fetišizacija crkvenih normi može voditi te razviti kritičke momente slobode i odgoja. Izostanak prosvjetiteljstva u hrvatskim zemljama Habsburške Monarhije kompleksno je uvjetovan: od religijskog otpora promjenama u društvenom i političkom smislu, do zaostalosti i neobrazovanosti velikog dijela stanovništva, što je odgovaralo hrvatskom plemstvu i kleru.
Review on the monograph of the authors Yu. K. Zaitsev and O. M. Moskalenko “Philosophical and Methodological Principles of Subject Architectonics of Contemporary Political Economy”
Authors: Maslov Anatolii
Published: July 2020

Review on the monograph of the authors Yu. K. Zaitsev and O. M. Moskalenko “Philosophical and Methodological Principles of Subject Architectonics of Contemporary Political Economy” (the Book I of the monograph “Contemporary Political Economy as a Theoretical Basis of Economic Development of the Society”)
Madencilik Sektöründe İş Sağlığı ve Güvenliği Yönetimi için Veri Entegrasyonu Uygulaması
Authors: ERKAYAOĞLU Mustafa
Published: July 2020

Madencilik endüstrisi, iş sağlığı ve güvenliği açısından değerlendirildiğinde, farklı mühendislik alanlarını ve bunlara bağlı riskleri kapsamaktadır. Günümüzde, teknoloji alanında yaşanan gelişmeler, madencilik endüstrisini mevcut donanım ve yazılımlar aracılığıyla, üretim, ekipmanların bakım/onarım durumu, maliyet, çevresel koşullar ve en önemlisi iş sağlığı ve güvenliği konusunda, veri toplayabilecek duruma getirmiştir. Bu çalışmada, iş sağlığı ve güvenliği ile ilgili farklı kaynaklardan elde edilen verilerin entegre edildiği bir uygulama sunulmaktadır. Veri entegrasyonu uygulamasında kullanılan, vaka çalışması sonucunda ekipman sağlığı ile ilgili güvensiz durum kayıtlarının, farklı ekipler ve taşıma işlemleri için incelenebileceği ortaya konmuştur. Özellikle vardiya başlangıçlarının, iş sağlığı ve güvenliği ile ilgili olayların yaşanabileceği bir zaman aralığı olduğu belirlenmiştir. Veri görselleştirmesi, analiz kabiliyeti açısından sınırlı olup, günümüzde kullanılan bilgi görselleri ve modern görselleştirme araçlarına rağmen, veri içerisindeki yapılar karmaşık hale gelebilmektedir. Belirli olayların sebepleri incelenirken, veri madenciliği gibi daha sistematik yöntemlerin kullanılması önerilmektedir.
Fabrication and Characterization of CuO Nanostructures: Applications in Electrocatalytic Hydrogen Production
Authors: BARAN AYDIN Evrim
Published: July 2020

Hydrogen which is a renewable and sustainable form of energy to replace fossil fuels has been has been attracted great interest because of clean emission and high conversion efficiencies. To make water electrolyzer more profitable and economical, the selection of electrodes having low overpotentials, low- cost and stable with well electrocatalytic activity is required. In this study, CuO nanostructures were fabricated by chemical techniques. The morphologies and structures of CuO nanostructures were studied in detail by FE-SEM, BET, and XRD. Three different morphologies of CuO (Nanorod, nanoflake and nano-flower nanostructures) were synthesized. The contact angle measurements were carried out to state the surface properties of the synthesized materials. The cathodic polarization, open circuit potential-time measurements, impedance measurements and Mott-Schottky analysis were carried out in 1M KOH solution to determine the electrocatalytic performance of electrodes in hydrogen formation reaction. Besides, energy consumption efficiencies of electrodes for alkaline electrolysis were investigated.
Heat Conduction Analysis of Two-Dimensional Anisotropic Plate
Authors: YARIMPABUÇ Durmuş , CİHAN Ertuğrul , ÇELEBİ Kerimcan , EKER Mehmet
Published: July 2020

The heat conduction of a two dimensional anisotropic plate with non-homogeneous general boundary conditions is solved by using ANSYS Fluent in the cartesian coordinate system. It is assumed that the thermal conductivity and heat generation of the material arbitrarily change in the direction of the two space variables. Under these conditions, a variable coefficient differential equation is obtained. Analytical solutions of such equations cannot be obtained except for some simple material functions. The variable coefficient differential equation, which includes the heat conduction coefficient and volumetric heat generation depending on the two space variables and non-homogeneous boundary conditions, is handled numerically by ANSYS Fluent user-defined function (UDF). The accuracy of the numerical method is demonstrated by comparing analytical and numerical solutions using simple material functions.
Elektrodepolanmış Nanokompozit Kaplamalarda Elektrolit Bileşenlerinin Etkisi
Authors: ÜNAL Ersin , YAŞAR Abdulkadir , KARAHAN İsmail Hakkı
Published: July 2020

Bu çalışmada, nikel esaslı alaşım ve nanokompozit kaplamalar elektrokimyasal depolama metodu ile paslanmaz çelik altlık üzerine üretilmiştir. Watts tipi nikel banyosuna bor kaynağı olarak trimetilamin boran (TMAB) ilave edilerek Ni-B alaşım kaplama elde edilmiş, daha sonra buna ilave olarak banyoya titanyum diborür (TiB2) seramik nano parçacıkları ilave edilerek nanokompozit kaplama elde edilmiştir. Elektrolit bileşenlerinin kaplama özelliklerine etkilerini incelemek amacıyla elektrokimyasal, mikrosertlik, korozyon dayanımı ve yüzey morfolojileri açısından analizler yapılmıştır. Yapılan incelemeler sonucunda her banyo bileşeninin morfoloji, sertlik ve korozyon dayanımı gibi özellikleri ciddi miktarda etkilediği görülmektedir. Genel olarak yüzey morfolojiler pürüzsüz olmakla birlikte, nanokompozit kaplamanın yüzeyinin daha kaba olduğu optik resimlerden anlaşılmaktadır. Ana yapıya bor elementi ilavesi mikro sertliği yaklaşık %38 oranında artırırken, TiB2 takviyesiyle birlikte saf nikele göre %140, Ni-B alaşımına göre %75 oranında iyileşme olmasına sebep olmuştur. Bor takviyesi korozyon dayanımını azaltırken, TiB2 takviyesi korozyon dayanımında artışa neden olmuştur.
Ağ Elemanı Özelliklerinin Sayısal Model Sonuçları Üzerine Etkisinin Belirlenmesi
Authors: ŞİMŞEK Oğuz , İŞLEK Hüseyin , AKÖZ M. Sami
Published: July 2020

Gelişen teknolojiyle birlikte bilgisayar yazılımları, karmaşık mühendislik problemlerin çözümünde oldukça sık kullanılmaya başlanmıştır. Kullanılan bu yazılımlardan elde edilen sonuçların doğruluğunun test edilmesi için fiziksel model deneyleri yapılmakta ve elde edilen sonuçlar, sayısal model sonuçları ile karşılaştırılmaktadır. Sayısal model sonuçları üzerinde, ağ yapısı özellikleri, kullanılan türbülans modeli, iterasyon sayısı ve adımı büyüklüğü gibi parametrelerin etkili olduğu bilinmektedir. Bu çalışmada, eğrisel geniş başlıklı savak üzerinden geçen akımın sayısal modellemesinde farklı geometrik özelliklere sahip çözüm ağları tasarlanmıştır. Akımı idare eden temel denklemlerin çözümü, sonlu hacimler yöntemine dayalı ANSYS-Fluent yazılımıyla gerçekleştirilmiştir. Sayısal hesaplamalarda, Reynolds Ortalamalı Navier Stokes (RANS) denklemlerine dayalı çözüm yapan Renormalization Group k-ε (RNG) türbülans modeli ve su-hava arakesitinin belirlenmesinde ise Akışkan Hacimleri Yöntemi kullanılmıştır. Sayısal olarak elde edilen su yüzü ve hız profilleri, deneysel sonuçlar ile karşılaştırılarak optimum çözüm ağının tipi ve boyutu belirlenmiştir. Ayrıca, hız profilleri üzerinde duvar yakını fonksiyonlarının etkileri araştırılmıştır. Deneysel ve farklı ağ yapıları kullanılarak elde edilen sayısal hız profillerinin karşılaştırılmasından, çok küçük elemanlardan oluşan hesaplama ağı yapısının sayısal model sonuçları üzerinde önemli ölçüde iyileştirme yapmadığı belirlenmiştir.
Framework conditions to design sustainable business models for decentralised water treatment technologies in Viet Nam for international technology providers
Authors: Fritz Mona , Hohmann Claudia , Tettenborn Felix
Published: July 2020

The expansion of water-intensive industrial activities and the impacts of climate change are jeopardising the sufficiency of safe drinking water in several Southeast Asian countries. One is Viet Nam, where geogenic arsenic contamination further limits the availability of freshwater resources with a simultaneous increase in water demand. Innovative and sustainable water treatment technologies are required to meet these challenges. Equally, we assume that the provision of safe drinking water requires tailored business models (BMs). In this study, we focus on the key stakeholders and framework conditions to design tailored BMs providing safe drinking water to the low-income and middle-income population in Viet Nam. We consider decentralised technologies to be suitable due to their lower investment costs for implementation and the avoidance of strong path dependencies. We therefore conducted a literature review and interviews with international experts in the domain of decentralised water treatment technologies. Our results show that relevant aspects include a lack of financial resources, specific characteristics associated with Vietnamese culture, e.g. the importance of relationships and trust in the business domain, lack of education and vocational training, market saturation suggesting co-operation with existing water suppliers, lack of suitable partners, and deficiencies in the institutional environment.
Data analytics in control and operation of municipal wastewater treatment plants: qualitative analysis of needs and barriers
Authors: Eerikäinen S. , Haimi H. , Mikola A. , Vahala R.
Published: July 2020

This study aims to identify barriers and needs for the application of data analytics in municipal wastewater treatment. The study was conducted through a series of interviews with stakeholders involved in instrumentation, control, and automation of wastewater treatment plants. Opportunities and limitations observed by different stakeholders were assessed with a thematic analysis. Thematic analysis enabled a broader consideration of social and organizational aspects related to process control, operation, and maintenance. Identified key barriers for applying data analytics included laborious instrumentation maintenance, unstable control loops, and deficient customization of digital tools for users at wastewater treatment plants. Development needs include easier data processing tools, quality assurance of instrumentation, and controller tuning. Results indicate that the perceived potential of data analytics is highly dependent on the performance of underlying physical and digital systems, as well as the control strategies and operating environment of the plant. Despite the barriers, users and developers see many potential applications for data analytics and expect them to have a central role in the control and operation of wastewater treatment plants in the future.
Possibilities of treating skin lesions in the graft versus host disease using the Pulsavac Plus wound repair system
Authors: Aliev T. Z. , Kirgizov K. I. , Belysheva T. S.
Published: July 2020

This article describes the experience of using the Pulsavac Plus debridement system for atraumatic treatment of the skin in one of the forms of graft versus host diseases after allogeneic hematopoietic stem cell transplantation.
Secondary T-cell lymphoblastic lymphoma in a child after anticancer therapy for neuroblastoma: clinical case
Authors: Toshina Yu. K. , Dinikina Yu. V. , Egorov A. S. , Smirnova A. Yu. , Belogurova M. B.
Published: July 2020

Neuroblastoma (NB) is the most common extra-cranial solid tumor in infants with the most heterogeneous clinical course to compare with other malignant diseases. Due to intensive multimodal anticancer treatment there are an increased number of survivors and issues related to long-term effects are becoming increasingly important. One of them is the risk of secondary malignant neoplasms. This article represents a clinical case of T-cell lymphoblastic leukemia in a child aged 2 years and 5 months who received combined antitumor therapy for NB with an intermediate risk group under the age of one year. We observed literature data to investigate the incidence of second malignant neoplasms in patients with NB for the period from 1948 to 2018 and analyzed risk factors.
Treatment problem of anephric patients with Wilms tumor
Authors: Izmozherova R. I. , Kuleva S. A. , Ivanova S. V. , Gumbatova E. D. , Senchurov E. M. , Osipov A. I. , Sarychev S. A. , Trofimova A. G. , Faseeva N. D. , Mikhailova E. A. , Borokshinova K. M.
Published: July 2020

Bilateral nephroblastoma is rare and is about 5 % of the total number of patients. The modern strategy of treatment children with bilateral Wilms tumor requires a comprehensive approach. An important task is to preserve as much of the renal parenchyma as possible, which will be sufficient for normal kidney function and development of the child. However, in subtotal kidney damage organ-preserving treatment is not always possible. In this case, the only curative option is bilateral nephrectomy followed by continuous renal replacement therapy. To date, the literature describes isolated cases of adjuvant chemotherapy in children on peritoneal dialysis. The article presents a clinical case of specific therapy with topotecan for a child after bilateral nephrectomy, a carrier of peritoneal dialysis catheter on the background of progression of the underlying disease.
Retinoblastoma: a patient’s story
Authors: Yarovoy A. A. , Ushakova T. L. , Golubeva O. V. , Levashov I. A. , Mikhailova S. N. , Yarovaya V. A. , Polyakov V. G.
Published: July 2020

Relevance. Development and application of novel treatment methods for patients with retinoblastoma (Rb) is a great task since it may provide higher rates of eye salvage and reduce adverse effects of current therapy.

Aim of the study was to represent the history of Rb eye-sparing treatment in Russia and worldwide through the one clinical case.

Materials and methods. A child was treated by systemic chemotherapy, plaque brachytherapy using non-described techniques, cryotherapy and external beam radiotherapy. Intravitreal chemotherapy was approached for treatment of vitreous seeding. Vitreoretinal surgery with melphalan irrigation was successfully performed after failure of vitreous hemorrhage conservative treatment and parents’ refusal to indicated enucleation. The child died from CNS disseminated esthesioneuroblastoma.

Results. The use of various treatment modalities helped to save the single eye.

Conclusions. Intravitreal chemotherapy was introduced in Russia for the first time. Performed vitreoretinal surgery with melphalan irrigation was proved to be a safe and effective technique in case of vitreous hemorrhage in the eye with Rb. External beam therapy is associated with fatal second tumors development.
Prospects for evaluation of the minimal residual disease in the post-induction period in pediatric B-precursor acute lymphoblastic leukemia
Authors: Shervashidze M. A. , Valiev T. T. , Tupitsyn N. N.
Published: July 2020

Relevance.Currently, the assessment of the level of minimal residual disease (MRD) is the standard in evaluating the effectiveness of therapy in acute lymphoblastic leukemia (ALL) in adults and children. Although, the necessity to study MRD at the induction therapy is not in doubt, the prognostic value of MRD in the period after induction is the subject for scientific discussion. Several studies suggest that MRD-positive status after induction chemotherapy associated with poor prognosis, and the reappearance of significant level MRD during follow-up allows impending relapse to be identified and to begin appropriate therapy in low leukemic cells level.

Aim– to determine the prognostic value of post-induction MRD on overall (OS), relapse-free (RFS), and event-free (EFS) survival in children with B-precursor ALL who received program treatment at the N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia.

Materials and methods.The study included 73 pediatric patients with initial B-precursor ALL. The median age of the patients was 5.2 years (from 1 to 16 years). The treatment was according to the ALL IC-BFM 2009 protocol. MRD detected on day 15 and 33 of induction therapy, and day 78 of consolidation beginning. MRD level was determined by flow cytometry method.

Results.EFS and RFS were the same for patients with MRD-positive status on 78 day of treatment 76.8 ± 12.3 % and 96.2 ± 2.6 % for MRDnegative (p = 0.06). Detailed assessment of MRD revealed a cohort of high-risk patients with MRD-negative status on 78 day of therapy with 100 % OS (observation time – 6 years).

Conclusion.In all risk groups, patients with negative MRD status showed a better survival result, which indicates the possibility of additional stratification by risk groups not only at the induction, but also during a consolidating treatment protocol.
Results of a prospective observation on the use of a coagulation factor concentrate VIII concentrate (Octanate®) for the induction of immunological tolerance in patients with an inhibitory form of hemophilia A
Authors: Zozulya N. I. , Vdovin V. V. , Svirin P. V. , Andreeva T. A. , Shiller E. E. , Konyashina N. I. , Lavrichenko I. A. , Zalepukhina O. E. , Klimova N. I. , Konstantinova V. N. , Krasheninnikova O. A. , Petrov V. Yu. , Perina F. G. , Osmulskaya N. S. , Mironova A. V. , Popova N. A.
Published: July 2020

Relevance. Immune tolerance induction (ITI) is the only approach proven to eradicate inhibitors in hemophilia A patients. ITI with Octanate® (human VWF-stabilized FVIII) has been shown to be effective at eradicating inhibitors, even in poor-prognosis patients. Here we report interim data from two observational, prospective studies on the use of Octanate® for ITI in patients in Russia.

Purposes of research. The primary objective was to assess the efficacy of ITI. Secondary objectives included assessment of time to ITI success and inhibitor eradication.

Patients and methods. Patients of any age with any severity of hemophilia A and a FVIII inhibitor  0.6 BU/mL were eligible. The ITI regimen was at the discretion of the treating physician.

Results. The analysis included 73 patients. ITI outcomes were assessed in 63 patients who had completed the study, of whom 56 (89 %) had  1 poor prognostic factors. Inhibitor eradication was achieved by 77.1 % (37/48) of primary ITI patients and 71.4 % (45/63) of all patients, in a median of 2.4 months (range – 0.0–27.4) for both groups. Complete success was achieved by 72.9 % (35/48) of primary ITI patients in a median of 8.9 months (range – 2.4–28.0) and 66.7 % (42/63) of all patients in a median of 10.5 months (range – 2.4–28.0). No relapses were reported after complete or partial ITI success. Of the patients with  1 poor prognostic factors, 67.9 % achieved inhibitor eradication and 62.5 % complete success.

Conclusions. ITI with Octanate® in a real-world setting showed rapid and sustained success, even in patients with poor prognostic factors.
Inflammatory myofibroblastic tumors in children: literature review
Authors: Suleymanova A. M. , Kachanov D. Yu. , Imyanitov E. N. , Roshchin V. Yu. , Shamanskaya T. V. , Varfolomeeva S. R.
Published: July 2020

Inflammatory myofibroblastic tumor (IMT) is a rare type of neoplasm with undetermined biological potential. IMT can occur in both childhood and adulthood. The standard of therapy is radical surgical treatment, but for patients with inoperable/recurrent or metastatic forms of IMT, therapeutic options are very limited. This literature review describes specific clinical, morphological and biological characteristics of this neoplasm, provides modern approaches to the diagnosis and treatment of IMT.
Pyruvate kinase deficiency: epidemiology, molecular analyses and modern diagnostic approaches (literature review)
Authors: Bankole A. V. , Chernyak E. A.
Published: July 2020

Red cell pyruvate kinase deficiency is the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Pyruvate kinase is the enzyme involved in the last step of glycolysis – the transfer of a phosphate group from phosphoenolpyruvate producing the enolate of pyruvate and ATP (50 % of total energy ATP of erythrocytes). ATP deficiency directly shortened red cell lifespan. Affected red blood cells are destroyed in the splenic capillaries, leading to the development of chronic hemolytic anemia. It is an autosomal recessive disease, caused by homozygous and compound heterozygous mutations in the PKLR gene. There are no exact data on the incidence of pyruvate kinase deficiency, but the estimated frequency varies from 3: 1,000,000 to 1:20,000. The clinical features of the disease and the severity are highly variable. Diagnosis of pyruvate kinase deficiency is based on the determination of pyruvate kinase activity and molecular genetic study of the PKLR gene. The variety of clinical manifestations, possible complications, as well as the inaccessibility of diagnostic methods complicate the diagnosis.
Synthesis and Evaluation of Substituted Aryl Thiazoles With Antioxidant Potential as Gastro-sparing Anti-inflammatory Agents
Authors: Bansal Akhil , Bali Alka , Balaini Ajitesh
Published: July 2020

Background:

NSAIDs are used as first-line drugs for the treatment of various inflammatory disorders. Chronic use of NSAIDs is known to be associated with gastrointestinal and renal toxicity. Local generation of reactive oxygen species finally resulting in cellular apoptosis is one of the accepted mechanisms for NSAID-induced toxicity.

Objective:

The objective of the present study was to design and synthesize a series of 2-methane sulfonamido substituted arylthiazole derivatives by including structural features of combined antiulcer and anti-inflammatory activity utilizing as the structural core, thiazole nucleus with potential for antioxidant effect.

Methods:

Compounds were designed based on three dimensional and field similarity studies. The synthesized compounds were evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Rofecoxib and indomethacin were taken as standard drugs for comparison. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug.

Results:

The compounds 6 and 7 showed good anti-inflammatory activity comparable to the standard group and were also non ulcerogenic at the test doses. Compounds 1-7 displayed varying degrees of reducing power in the PFRAP) assay and the methanesulphonamido derivatives 4-7 showed the highest antioxidant activity (EC50 values 3.7-5.1 μmol/ml vs ascorbic acid 7.4 μmol/ml). Theoretical ADME profiling of the compounds based on selected physicochemical properties showed excellent compliance with Lipinski’s rule.

Conclusion:

A series of compounds have been designed and synthesized having dual antioxidant and anti-inflammatory activity with activities comparable to standard drugs.
Vitamin A: Modulating Effect on Breast Carcinogenesis
Authors: Nogueira Thaís R. , de Oliveira Victor A. , Pereira Irislene C. , de Carvalho Cecília Maria Resende G. , Péres-Rodrigues Gilmara , do Carmo de Carvalho e Martins Maria , de Macedo G. Frota Karoline , de Azevedo Paiva Adriana , de Jesus e Silva de Almendra Freitas Betânia
Published: July 2020

Breast cancer has a multifactorial etiology and, among the main causal factors, the dietary
profile stands out, mainly the components of the pro-inflammatory diet and their interaction with genetic
characteristics. In this sense, deciphering the molecular networks involved in the proliferation
of cancer cells in breast tissue can determine ways of action of organic compounds that modulate the
pathogenesis of cancer, such as vitamin A and analogs, as well as their possible mechanisms of modulation
of breast tumorigenesis. This is a review study conducted according to the guidelines of the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and by consulting
the PubMed and Web of Science databases including articles, published in Portuguese, English and
Spanish, in the last five years. 126 articles were obtained, of which 13 were selected for full analysis
and only 6 were included in the study for meeting the eligibility criteria. The results of the compiled
studies demonstrate the role of some retinol-binding proteins in metabolism, as well as in differentiation,
cell proliferation and inflammation. Although controversial, the results point to the use of these
proteins as possible prognostic markers. The need for further studies in humans is also emphasized in
order to assess the main effects of vitamin isoforms on tumor activity.
Endometriotic Intramyometrial Cyst –A Diagnostic Dilemma
Authors: Bhatt Anand Dineshkumar , Mishra Keeranmayee , Chavda Vishal
Published: July 2020

Background:

Endometriosis is a pathological state in which the endometrial glands and
stroma are originated at sites other than the uterine cavity. Endometriotic cystic lesions are principally
positioned in ovaries but, infrequently, can also be encountered in the myometrium. It is a
rare manifestation which poses a multitude of differential diagnoses and therapeutic options.

Case study:

A 27-year-old female patient walked into hospital complaining of severe abdominal
pain since 2 days with a medical history of dysmenorrhoea since one and a half years. On examination,
the abdomen was found to be soft with the existence of lower abdominal tenderness. An Ultrasonography
revealed a myometrial posterior wall cyst of size 4 x 4 cm with thick wall and spotted
internal echoes favoring a differential diagnosis of either an endometriotic cyst or rudimentary
horn. Both ovaries were found normal. The patient was taken for laparoscopy in which a bulge was
seen on the posterior uterine wall. It was punctured to expose a myometrial cyst with dark chocolate
colored fluid collection. The intact cyst was enucleated and sent for histopathology, which confirmed
the diagnosis of the endometriotic cyst. Upon the literature survey, it was found that only
two such cases were available in the literature on internet which described a similar pathology.

Conclusion:

Endometrioma should be considered as a probable pathology whenever myometrial
cysts are encountered. A focused transvaginal examination can be very accommodating as a diagnostic
modality to set up proper management. This case should not only make the health
careproviders rethink the etiopathogenesis of endometriosis and debate the credibility of the retrograde
menstruation hypothesis but also encourage to accurately investigate any lesion anywhere in
the body, which looks like an endometriotic chocolate cyst. In this case, it is evident that a myometrial
spot is rare but not impossible. These rare occurrences shall direct to diversify the perception
of this pathology.
Short Term Efficacy of Modified Epley’s Maneuvre Assisted by Visual Aid Dynamic Device Versus Unassisted Maneuvre for the Treatment of Posterior Canal BPPV
Authors: Patel Dhruvkumar M. , Gurumukhani Jayanti K. , Patel Mukundkumar V. , Patel Maitri M. , Patel Chilvana , Patel Harsh D. , Patel Maurvi V.
Published: July 2020

Introduction:

Modified Epley’s maneuver is the recommended treatment for the Posterior
Canal (PC) BPPV. To enhance the efficacy of this maneuver, an easy to perform visual aid
device (DizzyFIX) guided modified Epley’s maneuver was studied.

Material and Methods:

This prospective, double-blind, randomized study included consecutive
patients with PC-BPPV based on clinical history, neuro-otological examination, and positive Dix-
Hallpike (DHP) test from January 2018 to March 2019 at a neurology clinic of western India. Patients
were randomly assigned treatment with either visual aid device assisted modified Epley’s
maneuver, which constituted the case group or by a placebo device guided modified Epley’s maneuver,
which constituted the control group. DizzyFIX was used as a visual aid device in the case
group. Patients were followed up at one hour and 24 hours with DHP by the blinded examiners to
observe for remission.

Results:

Out of 280 patients (140 patients in each group), 6 from the case, and 2 from the controls
were lost from the follow-up. Overall, 134 cases were compared to 138 controls. The success rate of
remission in the case and the control group at one-hour was 79.19% vs. 48.30%, respectively, with
a p-value of 0.003. Similarly, the success rate in the case and control group at 24 hours was 95.27%
vs. 80.62%, respectively, with a p-value of 0.011. At 1 hour, unadjusted Odd Ratio (OR) was 4.13,
(C.I. 95% 2.02- 8.46) and at 24 hours, it was 4.37, (C.I. 95% 1.39-13.77), which was significant
even after adjustment of co-variables (OR 4.02, C.I. 95% 2.34- 8.26) and (OR 4.11, C.I. 95% 2.30-
14.26), respectively.

Conclusion:

For short term treatment of PC-BPPV, DizzyFIX assisted modified Epley’s maneuver
is more efficacious than unassisted modified Epley’s maneuver.
Differentiation of Human Induced Pluripotent Stem Cells into Male Germ Cells
Authors: Zhao Na , Sheng Min , Wang Xia , Li Yonghui , Farzaneh Maryam
Published: July 2020

Infertility is defined as not being able to become pregnant or to conceive a child after one
year or longer of regular unprotected intercourse. Male infertility refers to a male’s inability to cause
pregnancy that can result from deficiencies in semen quality, sperm concentration, or abnormal sperm
function. Till now, there are few effective methods for the treatment of a couple with male infertility.
In the past few years, stem cell-based therapy as a promising strategy has emerged for the treatment of
male infertility. Human Pluripotent Stem Cells (hPSCs) can self-renew and differentiate into any type
of cell. Human Embryonic Stem Cells (hESCs) and induced Pluripotent Stem Cells (hiPSCs) are two
pluripotent populations that can proliferate and give rise to ectodermal, mesodermal, endodermal, and
germ cell lineages. Both undifferentiated hiPSCs and hESCs are powerful candidates for the treatment
of male infertility. Generation of male germ cells from hPSCs can provide new mechanistic insights
into the regulation of spermatogenesis and have a great opportunity for families with infertility. Therefore,
a robust, reproducible, and low-cost culture method that supports hPSCs differentiation into male
germ cells is necessary. However, very few studies have focused on the derivation of sperm-like cells
from hiPSCs and the details of hPSCs differentiation into male germ cells have not been fully investigated.
Therefore, in this review, we focus on the in vitro differentiation potential of hiPSCs into male
germ cells.
Anticancer Activity Assessment and DNA Binding Properties of Two Binuclear Platinum (II) Complexes using Spectroscopic and Molecular Simulation Approaches
Authors: Alavianmehr Mohammad M. , Ashrafi Abolfazl , Yousefi Reza , Haghighi Mohsen G. , Abolmaali Samira S. , Moosavi-Movahedi Ali A. , Rad Mohammad N.S.
Published: July 2020

Background:

Nowadays, the biological properties and anticancer activities of platinum-based drugs
and metal coordination complexes have been receiving particular attention. These compounds have revealed
clinical potential in cancer chemotherapy.

Objective:

In this research, two binuclear platinum complexes including [Pt2Cl2(bhq)2(μ-dppm)] (1) and [(p-
MeC6H4)(bhq) Pt(μ-dppm)Pt(bhq)(CF3CO2)] (2) with bhq: benzo[h] quinolone and dppm: bis(diphenylphosphino)
methane have been synthesized and evaluated for their anticancer activity against A2780 and A2780/RCIS cancer
cell lines.

Methods:

The DNA binding and interaction of AMP/GMP nucleotide with these complexes were explored by
several experimental and theoretical methods, including UV-Visible, fluorescence spectroscopic techniques and
docking analysis. These complexes have demonstrated significant anticancer properties against cisplatinsensitive
(A2780) and cisplatin-resistant (A2780/RCIS) human ovarian cancer cell lines.

Results:

The obtained results indicated that these complexes interact with DNA. Additionally, the fluorescence
emission measurements indicated that the platinum complexes binding with DNA structure occurs through nonintercalative
interaction. The molecular docking assessments have also revealed the binding of these platinum
complexes through DNA grooves. Moreover, the results have indicated that complex 1 exhibited more anticancer
activity than complex 2.

Conclusion:

The results of the DNA binding with these platinum complexes confirmed their potential antitumor
properties. The substitution of -C6H4CH3 and -CO2CF3 groups in complex 2 with two chlorine atoms in complex 1
acquired the significant improvement of the anticancer activity against the cancer cell.