bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Public-Private Partnership in the Healthcare Management System
Authors: Ovcharova Natalia , Grabowska Monika
Published: June 2022

This article states that the private sector and the government can resolve contradictions and bridge interaction gaps through a public-private partnership due to complementing each other functionally. The study aims to determine the elements of public-private partnership development in healthcare and primary conditions for further forming an effective environment for implementing the principles of public-private partnership in healthcare management. This investigation examined the public-private partnership state worldwide and in Ukraine and the prospects for its development in the context of healthcare reform. It was noted that cooperation between the public and private sectors is becoming increasingly social. However, the current practice does not show effectiveness in achieving certain goals. The properties and differences in realizing social public-private partnership projects were investigated. The risks and problems in the implementation of public-private partnerships in healthcare were identified. The authors developed the structural and target model for ensuring the development of public-private partnerships in healthcare. It was determined that the basic conditions contributing to the successful implementation of public-private partnership projects in healthcare should include the factors as follows: political willpower to promote the development and support of public-private partnership; legislative and regulatory system to attract private sector funding; availability of feasible and effective projects and mechanisms for their selection; availability of information and staff needed for project implementation. The findings substantiated that state budget support is essential in reducing the risks of a private partner at the initial stage of public-private partnership development. The world experience showed that state funding of public-private partnership projects in healthcare might vary depending on the project life cycle stage. Given the importance of improving the funding of public-private partnerships, especially in terms of state budget funding for health projects, key elements and possible areas for improvement were identified.
State Policy for the Private Healthcare Sector Development of Ukraine
Authors: Kolotilina Olena , Lomko Vitalii , Prasol Lesya
Published: June 2022

The need to ensure quality and comprehensive healthcare at the world standard level determines the establishment and importance of private medicine in the healthcare system. It forms the task to reform, develop, and implement targets for private medicine. This article aims to investigate the measures by state policy in promoting private medical services. The methodological basis of this study is the dialectical method of scientific knowledge, system approach, and methods of logistic analysis. The empirical research involved retrospective, structural and comparative analyses. To achieve the study goal, the following tasks were solved: 1) determination of the theoretical basis of the state policy in private healthcare based on scientific background; 2) the analysis of the state policy in Ukrainian healthcare; 3) identification of the role of private medicine in the health care system; 4) the comprehensive analysis of the medical institution activities on the example of a private clinic «L-MED Clinic»; 5) determination of the connection between the effectiveness of activities and the marketing activities in promoting medical services. is study determined the importance of private medicine in the healthcare system of Ukraine. Private treatment and prevention facilities relieve the burden on public hospitals and clinics. The main competitive advantages of private healthcare institutions include availability, sufficient admission time, responsibility and organized attitude to the treatment process, quality diagnosis, full-range medical services, courtesy and attentive staff, comfortable and pleasant interior, etc. Based on the findings, the authors provided practical recommendations for improving the state policy, state regulation of private medical activity, and implementing the best world practices of branching out of the health care sector. The obtained results could be useful to the Ministry of Health of Ukraine, the Ministry of Social Policy of Ukraine, the Cabinet of Ministers of Ukraine, and the Verkhovna Rada of Ukraine in state regulation of healthcare reformation in Ukraine.
Vegetative Propagation of Ratibida columnifera (Nutt.) Wooton & Standl.
Authors: Hopkins Kaitlin A. , Arnold Michael A. , Hall Charles R. , Pemberton Brent , Palma Marco A.
Published: June 2022

Variation in floral characteristics and growth habits within the native range of the North American wildflower Ratibida columnifera (Nutt.) Wooton & Standl. suggest potential for breeding and selection efforts to develop improved cultivars for commercial and residential landscapes. Toward that end, experiments in vegetative propagation were performed to enable perpetuation of unique germplasm. Stem development stage, applications of auxin, genotypic variation, and the effects of bottom heat applications were assessed to determine impacts on rooting percentages and adventitious root system quality measures. Younger apical stem sections rooted more readily and produced better quality root systems than more lignified basal stem cuttings. Optimal rooting percentages and rooted cutting quality ranged from 0.10% to 0.30% IBA (indole-3-butyric acid) quick dips, with 0.30% being optimal for most genotypes. Application of 26 °C bottom heat improved rooting ability in both cool and warm seasons compared with ambient and bottom heat of 32 °C. Bottom heat of 32 °C improved most rooting measures over ambient during the cool season, but not during the warm season. The degree of improvement in adventitious rooting associated with various developmental stage, auxin quick dips, and bottom heating varied among accessions of R. columnifera, suggesting that adventitious rooting characteristics should be evaluated as a selection criterion for cultivar development within this species.
Master integrals contributing to two-loop leading colour QCD helicity amplitudes for top-quark pair production in the gluon fusion channel
Authors: Chaubey Ekta
Published: June 2022

We discuss the analytic structure of the master integrals relevant for computing the complete set of leading-colour analytic helicity amplitudes for top-quark pair production via gluon fusion at two loops in QCD. This includes corrections due to massive fermion loops
which give rise to integrals involving elliptic curves. We also elaborate on the structure of singularities that play an important role in the numerical evaluation of the iterated integrals and their analytic continuation.
Double Virtual Contributions for Massless 2 -> 3 Scattering in NNLO QCD
Authors: Sotnikov Vasily
Published: June 2022

We review the recent advances in
the calculation of two-loop QCD corrections for massless five-point
scattering that paved the way for their broad phenomenological applications
in calculation of NNLO QCD predictions.
We first discuss the construction of a transcendental function basis which facilitates derivation of compact analytic
representations for two-loop amplitudes and enables their fast and stable
numerical evaluation over physical phase space. We then present the recent
calculations of the leading-color two-loop corrections for hadroproduction of
three photons and three jets.
On the discrepancy between the FOPT and CIPT approaches for hadronic tau spectral function moments
Authors: Hoang André , Regner Christoph
Published: June 2022

The discrepancy between the FOPT and CIPT approaches for hadronic
\tauτ
spectral function moments constitutes the major theoretical uncertainty
for strong coupling determinations from tau decay data. We show the
discrepancy can be analytically understood since the Borel
representations – which have been assumed to be identical for both
approaches previously – differ in the presence of IR renormalons. This
implies that the OPE condensate corrections are different for both
approaches and that the discrepancy may eventually be reconciled. In the
talk we explain the difference and some mathematical aspects of of the
FOPT and CIPT Borel representations and show numerical results.
NLO QCD corrections for off-shell $t\bar{t}b\bar{b}$
Authors: Lupattelli Michele
Published: June 2022

We present a full off-shell NLO QCD calculation of
pp \rightarrow e^+ \nu_e b \mu^- \bar{\nu}_\mu \bar{b} b \bar{b} + Xpp→e+νebμ−ν‾μb‾bb‾+X.
Results are obtained using the Helac-Nlo Monte Carlo framework. We
discuss a comparison to previous results and to experimental
measurements. We also investigate the contribution of the initial states
involving bb-quarks
and we introduce two bb-jet
tagging schemes.
Proving the dimension-shift conjecture
Authors: Britto Ruth , Jehu Guy , Orta Andrea
Published: June 2022

We prove the conjecture made by Bern, Dixon, Dunbar, and Kosower that
describes a simple dimension shifting relationship between the one-loop
structure of \mathcal{N}=4𝒩=4
MHV amplitudes and all-plus helicity amplitudes in pure Yang-Mills
theory. The proof captures all orders in dimensional regularisation
using unitarity cuts, by combining massive spinor-helicity with
Coulomb-branch supersymmetry. The form of these amplitudes can be given
in terms of pentagon and box integrals using a generalised
DD-dimensional
unitarity technique which captures the full amplitude to all
multiplicities.
A new Wilson line-based classical action for gluodynamics
Authors: KAKKAD HIREN , Kotko Piotr , Stasto Anna
Published: June 2022

We develop a new classical action that in addition to
\mathrm{MHV}MHV
vertices contains also \mathrm{N^kMHV}NkMHV
vertices, where 1\leq k \leq n-41≤k≤n−4
with nn
the number of external legs. The lowest order vertex is the four-point
MHV vertex – there is no three point vertex and thus the amplitude
calculation involves fewer vertices than in the CSW method. The action
is obtained by a canonical transformation of the Yang-Mills action in
the light-cone gauge, where the field transformations are based on
Wilson line functionals.
Rethinking the role of pioglitazone in modern diabetology as a cardiorenoprotective agent
Authors: Salukhov V. V. , Kovalevskaya E. A.
Published: June 2022

Thiazolidinediones are insulin sensitizers – a class of antidiabetic drugs that reducing insulin resistance, convincingly improve glycemic control in patients with type 2 diabetes. In addition to glucose-reducing action, a representative of this class – pioglitazone in studies demonstrates other pleiotropic effects associated with a decrease in blood pressure, a decrease in the level of pro-inflammatory cytokines and prothrombotic factors, correction of dyslipidemia and improving the state of the vascular wall. In accordance with these anti-atherogenic and metabolic effects of pioglitazone in patients with confirmed cardiovascular diseases, he reduced the frequency of development of large atherosclerotic events in prospective randomized clinical studies (studies of PROactive and IRIS), as well as in meta-analyses of all published studies of pioglitazone. Pioglitazone reduces albuminuria and proteinuria, mortality from all causes and cardiovascular events in patients with diabetes and chronic kidney disease. In other studies, the intake of pioglitazone was associated with mobilization of fat from liver in patients with non-alcoholic fatty liver disease with an improvement in its function and a positive effect on fibrosis. This article also provides an analysis of unwanted phenomena that were noted during the study of pioglitazone. The identified weight increase, swelling, bone fractures of the limbs, have a rare frequency of occurrence and dose-dependent nature. Indeed, when using low doses of pioglitazone (7.5–30 mg/day), the ratio of benefit/risk for the drug seems very favorable. At the same time, the benefits of pioglitazone with a significant improvement in cardiovascular and cerebrovascular outcomes are higher with secondary than with primary prevention in patients with both 2TDM and prediabetes/insulin resistance, most likely due to positive effects on atherosclerosis
Replacement of prolonged-acting octreotide with lanreotide autogel 120 mg in patients with Acromegaly in real clinical practice
Authors: Tsoy U. A. , Kravchuk E. N. , Dalmatova A. B. , Belousova L. V. , Grineva E. N.
Published: June 2022

Introduction. In the cases of neurosurgery failure in acromegaly treatment, drug therapy with somatostatin analogues (SSA) octreotide or lanreotide is indicated. The effectiveness of SSA is limited by the presence of resistance, there is an opinion that in some cases it can be overcome by replacing one drug with another.

Aim. Own experience analysis of transferring acromegaly patients from therapy with long-acting octreotide to lanreotide autogel 120 mg.

Materials and methods. The case histories of acromegaly patients who were recommended to replace long-acting octreotide therapy with lanreotide therapy 120 mg were analyzed. GH and insulin-like growth factor-1 (IGF-1) dynamics was evaluated at least 6 months after the replacement of the drug. The target value for GH was considered to be less than 2.5 micrograms/l, for IGF-1 – an excess of no more than 30% of the upper normal limit.

Results. 24 patients were transferred to lanreotide therapy 120 mg. Of the 19 patients with insufficient reduction of GH and IGF-1 on prolonged-acting octreotide therapy at a dose of 40 mg every 28 days (OCT40) the prescription of lanreotide 120 mg every 28 days (LAN120) led to the target values of both GH and IGF-1 in 4 (21%) cases. These patients had no more than a twofold excess of IGF-1, and the level of GH was less than 2.5 mcg/l on the background of OCT 40 therapy. In 6 (32%) patients, IGF-1 levels normalized or decreased, but GH remained outside the target values. In 9 (47%) cases, the replacement of the SSA did not lead to a significant positive dynamics in the levels of GH and IGF-1. The effects of lanreotide therapy 120 mg in another five patients initially treated with octreotide 20 mg are also described.

Conclusions. Replacement of OCT4 with LAN120 may be effective in some patients with acromegaly. A slight increase in the level of IGF-1 together with the target values of GH before replacing the SSA may be the predictor of success.
Features of the intestinal microbiome in patients with thyroid diseases
Authors: Solovev M. V. , Raevskiy K. P. , Sorokin A. N.
Published: June 2022

Introduction. Today the search and development of new methods for diagnosing organic or functional pathology of the thyroid gland with an asymptomatic or clinically nonspecific course is an urgent task of endocrinology and therapy. The functioning of the thyroid gland and the state of the human intestinal microbiome are dynamically interrelated. One of the considered promising methods is mass spectrometry of microbial markers of the human intestinal microbiota.

The purpose of the study. To study the microbial spectrum and characteristics of the biotic environment of the intestine in patients with thyroid diseases.

Materials and methods. 21 patients were examined (8 men and 13 women, median age 40.5 [31.75; 54] years, respectively; 15 with thyroid disease, 6 without thyroid disease). In addition to the standard clinical and laboratory-instrumental examination, patients, colon contents were examined by chromatography-mass spectrometry of microbial materials. The work used descriptive non-parametric statistics with subsequent interpretation. Mean values of indicators and their variance are presented as median, upper and lower quartiles. In relation to representatives of the fecal microbiota, in addition to absolute values, the frequency of occurrence of the microorganism within the reference range, moderate or pronounced deviations was taken into account. The determination of the statistical significance of differences in the relative frequency value was carried out using Fisher’s exact test. The presentation of the results is implemented in the form of range diagrams, compactly depicting a one-dimensional probability distribution, tables. Results. Differences in the composition of the microbiota of the control group and the experimental group for Alcaligenes spp., Staphylococcus spp., Megamonas hypermegale, Peptostreptococcus anaerobius were revealed.

Conclusions. The development of thyroid gland pathology is accompanied by significant deviations in the composition of the fecal microbiota, determined by mass spectrometry of microbial markers. In persons with thyroid pathology, in the absence of clinically significant external influences on the intestinal microbiome, a pronounced decrease in the level of Alcaligenes spp., Staphylococcus spp., is detected, a tendency to a decrease in the level of Megamonas hypermegale, Peptostreptococcus anaerobius is determined. Further differentiated study of the composition of the intestinal microbiome in patients with thyroid diseases is required, depending on the nosological affiliation and the nature of the endocrine dysfunction.
Special considerations in the therapeutic education of elderly with diabetes mellitus type 2
Authors: Balashova A. V. , Glinkina I. V. , Pavlova M. G. , Oderiy A. V. , Fadeev V. V.
Published: June 2022

Diabetes self-management education (DSME) is an essential part of effective and safe treatment of chronic conditions such as diabetes mellitus (DM). Though the data on DSME effectiveness in elderly are limited, all patients should be educated regardless of age. The form of learning and education program may vary depending on the clinical situation and the patient’s characteristics. Age-related problems, so-called geriatric syndromes, determinant heterogeneity of elderly diabetic population. Geriatric syndromes should be taken into account to choose proper treatment goals and optimal education programs. Functional dependency, cognitive decline, depression, sarcopenia, malnutrition and polypharmacy seems to be most important in the education context. The development of geriatric education program with a broad focus on solving both diabetic and age-related problems and its implementation on a wider range of institutions may be useful to improve diabetes self-management education of elderly in clinical practice. It is also necessary to initiate clinical studies to evaluate DSME effectiveness in elderly not only from the generally accepted diabetological criteria, but also considering its impact on age-related problems.
Comparison efficacy of different regimens of insulin therapy in patients with type 2 diabetes and morbid obesity
Authors: Maloletkina E. S. , Gurova O. Y. , Glinkina I. V. , Amosova M. V. , Shyman Zh. Zh. , Khaykina I. A. , Kalashnikova M. F. , Fadeev V. V.
Published: June 2022

Introduction. In type 2 diabetes mellitus, an inevitable decrease in the secretion of  β-cells of the pancreas occurs, which requires the  initiation of  insulin therapy. Currently, there have been no studies evaluating the  features of  insulin therapy in patients with diabetes type 2 and morbid obesity.

Objective. To compare the effectiveness of different insulin therapy regimens in patients with type 2 diabetes mellitus and morbid obesity. Materials and methods. 140  patients with diabetes type  2 and morbid obesity were included in  a 24-week prospective, non-blinded, randomized clinical study. The patients were divided into 4  groups: 1  – received basic-bolus insulin therapy in combination with metformin (n = 40); 2 – used prandial insulin in combination with metformin (n = 40); 3 – basal insulin in combination with empagliflozin and metformin (n = 30); 4 – received prandial insulin in combination with empagliflozin and metformin (n = 30). Initially, after 12 and 24 weeks, the level of HbA1c, fasting plasma glucose and during the day, body weight, daily insulin doses, frequency of hypoglycemia, and albumin in daily urine were assessed.

Results. After 24 weeks of treatment, there was no statistically significant difference in the achieved HbA1c level between the groups (p = 0.65); in groups 3 and 4, there was a statistically significant decrease in body weight, daily doses of insulin and frequency of hypoglycemia compared to the first and second treatment groups (p = 0.029, p < 0.001 and p < 0,001, respectively); also registered a decrease in albumin in daily urine by 27% during the study period compared with the first and second treatment groups (p = 0.044).

Conclusions. Administration of iSGLT-2 in combination with both basal and prandial insulin in patients with diabetes type 2 and morbid obesity has advantages over the basic-bolus regimen and the regimen of multiple prandial injections, despite the comparable efficacy.
Influence of gut microbiota on the development of insulin resistance
Authors: Demidova T. Yu. , Lobanova K. G. , Shevtsova N. S. , Korotkova T. N. , Kochina A. S.
Published: June 2022

Insulin resistance (IR) is an important problem of humanity, which leads to development of many metabolic disorders. Сurrently the pathogenic mechanism of the development of IR is not completely investigated. Nevertheless, there are some hypotheses explaining the development of this condition. These include such hypotheses as the hypothesis of thrifty genotype, thrifty phenotype, hormonal, stress, good and bad calories, chronic metabolic inflammation, microbiotic and integrated model suggested by Professor Rainer Straub. In this article, the microbiotic theory will be considered in detail, explaining the mechanism of the development of peripheral tissue insensitivity to insulin in dysbiosis due to amplification of transmission by proinflammatory molecules from the intestine to the bloodstream and activation of systemic inflammation, disruption of the “gut-brain-periphery” mechanism and impaired receptor interactions of active intestinal metabolites of the gut microbiota (GM) at the level of cells of metabolic organs. The value of this theory is that its factors affect all links in the pathogenesis of the development of IR, reflected in the integrated model of Professor Straub. In this review the influence of GM and metabolic processes of human body on the development of IR will be considered in detail, data from clinical studies about the influence of GM (its composition, active metabolites, individual bacterial strains) on the development of IR and the role of chronic metabolic inflammation in this process will also be presented. In addition, attention will be paid to bidirectional effects of GM and metformin, as well as to data from clinical studies on changes in GM in healthy people and people with IR under the influence of metformin and how GM affects the pharmacokinetics of this drug. The possibility of IR correction through the use of dietary fiber will also be considered.
Metformin in prediabetes: key mechanisms for the prevention of diabetes and cardiometabolic risks
Authors: Babenko A. Yu.
Published: June 2022

Today, prediabetes is regarded by the world medical community as early diabetes mellitus. The accumulated research evidence shows that prediabetes is characterized by a spectrum of complications that are similar to those of diabetes mellitus, which means that the deterioration of cardiovascular prognosis starts already at the stage of prediabetes. In the current timeframe, metformin is actually the only drug that is widely prescribed for the treatment of prediabetes to prevent type 2 diabetes mellitus and cardiovascular diseases associated with insulin resistance and hyperinsulinemia. Meanwhile, metabolically unhealthy obesity characterized by hyperinsulinemia and insulin resistance is associated with a significantly unfavourable course of prediabetes, as well as the highest risk of developing both type 2 diabetes mellitus and cardiovascular diseases, development/ progression of chronic kidney disease. The theme of this review is the priority of metformin for the management of the most prognostically unfavourable phenotypes of prediabetes. The review is also devoted to the description of the most significant mechanisms that provide effects of metformin underlying the management of key disorders that determine the unfavourable prognosis of prediabetes. In particular, it sets forth the role of unhealthy nutrition, its effects on the development of imbalance of the composition of gut microbiota, which, in turn, entails a cascade of metabolic disorders underlying the development of metabolic ill health. The review sets forth the key role of metformin as a drug that protects against the development of these disorders. The information presented in this review will be useful to personalize the choice of both the scope and nature of interventions in patients with different phenotypic characteristics.
Short- and long-term outcomes from the upfront high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation in diffuse large B-cell lymphoma
Authors: Koviazin A. K. , Filatova L. V. , Zyuzgin I. S. , Artemyeva A. S. , Motalkina M. S. , Chudinovskikh Yu. A. , Dobrovolskaya E. V. , Volchenkov S. A. , Polyatskin I. L. , Shalaev S. A. , Ishmatova I. V. , Zverkova A. A. , Burda D. S. , Elkhova S. S. , Semiglazova T. Yu.
Published: June 2022

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).

Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.

Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.

Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p < 0.001). Early relapse served as an independent negative prognostic factor in OS (p < 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p < 0.001, LR - p < 0.001 in control group and ER - p < 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had >1 extranodal site with lung involvement (p < 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of >1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.

Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or >1 extranodal sites with lung involvement.
Adjuvant immunotherapy of operable non-small cell lung cancer: achievements and treatment prospects
Authors: Denisova E. S. , Laktionov K. K. , Ardzinba M. A. , Reutova E. V.
Published: June 2022

Lung cancer is one of the most common malignant tumors with the highest mortality, with about 85% of cases of the disease being non-small cell lung cancer. To date, adjuvant chemotherapy based on platinum preparations remains the standard of treatment for patients with radically operated stage II or III non-small cell lung cancer. However, a large proportion of patients still have a risk of developing a recurrence of lung cancer even after complete resection of the tumor. That is why there is a need to search for new methods of treatment of early stages of NSCLC, which will minimize the likelihood of postoperative relapses and improve survival in a potentially curable group of patients. Already today, clinical trials are beginning to advance the treatment of non-small cell lung cancer in the early stages beyond the standard cytotoxic chemotherapy. Immunotherapy, represented by immune checkpoint inhibitors, is being investigated in an increasing number of clinical trials in patients with operable NSCLC at early stages, gradually enriching existing treatment methods. At the same time, some issues related to adjuvant immunotherapy have yet to be considered. The choice of the drug, the use of monotherapy or combined treatment regimens remain unclear. This review examines the progress of research aimed at improving adjuvant therapy through the inclusion of immune checkpoint inhibitors in the treatment of early stages of resectable non-small cell lung cancer. Adjuvant immunotherapy can improve relapse-free survival in individual patients with resectable lung cancer, and current or planned studies using biomarkers and immunotherapy may also ultimately lead to an improvement in the overall survival of this group of patients.
Nivolumab with Ipilimumab in the treatment of refractory hepatocellular carcinoma
Authors: Khagazheeva M. N. , Dzhanyan I. A. , Breder V. V. , Laktionov K. K.
Published: June 2022

HCC is considered refractory when it comes to progression during treatment with TKIs (sorafenib, lenvatinib). The combined immunotherapy of nivolumab with ipilimumab was studied in the one cohort of CheckMate-040 study, excluding immunotherapy-naive patients. The question of choosing an immunotherapy option in the presence of several options remains open. Like separate issue remains the prospect of using immunotherapeutic combinations after progression on immunotherapy. We present a long history of treatment of a patient with advanced HCC, which has been observed for 8 years at the Blokhin National Medical Research Center of Oncology. The example of this clinical observation shows the result of a multidisciplinary individual approach to the treatment of advanced HCC with the background of hepatitis C virus without liver cirrhosis (Child -Pugh A), stage BCLC-C. During this period of time, the patient received 5 lines of antitumor therapy, which were repeatedly supplemented with TACE procedures, radiation therapy and surgical treatment, with oligometastatic progression. The longest period of therapy without progression was recorded with the use of Nivolumab 240 mg in the 3rd line for 18 months, without clinically significant toxicity. The disease progressed with damage of the brain substance, one-stage microsurgical removal of metastases was performed, followed by EBRT. 4-line TKI therapy was not long-term. Due to the lack of a potential therapy option, it was recommended to resume therapy with anti-PD-1 with the addition of anti-CTLA-4, which gave its objective effect. Since November 2021 patient received 4 courses of Nivolumab 1 mg/kg + ipilimumab 3 mg/kg once every 3 weeks, and a partial effect was achieved (-42% according to RECIST 1.1). Then we performed nivolumab 240 mg IV every 2 weeks — which the patient continues to the present time.
Long-term disease control in a patient with ALK-positive non-small cell lung cancer
Authors: Berezina G. I. , Laktionov K. K. , Reutova E. V. , Ardzinba M. S. , Borisova T. N. , Utkina V. L.
Published: June 2022

Non-small cell lung cancer is a very heterogeneous group of diseases. When choosing an effective patient management strategy, an oncologist focuses on the stage of the disease, the morphological form of the tumor, as well as its molecular genetic markers. Most of the targeted mutations in lung cancer today are in adenocarcinoma. The standard for detecting this type of cancer in 2022 is the determination of mutations in the EGFR genes (18-21 exons) and BRAF (V600E), translocations of the ALK and ROS1 genes, and determination of PD-L1 status regardless of gender, age, and history of smoking. Often, lung cancer is detected in the advanced stages, but the detection of ALK gene translocation can give the patient a high chance of a longer life expectancy and long-term control of the disease. In this article, on the example of a clinical case of a patient with ALK-positive lung adenocarcinoma, a multidisciplinary approach to the management of cancer patients, long-term control of the disease with the use of the second-generation targeted medication alectinib, as well as treatment options for disease progression are demonstrated.
Experience in correcting skin radiation reactions with basic care products. Clinical observation
Authors: Akhtemzyanov A. R. , Pinyaeva S. M. , Nikolaeva E. N. , Emileva T. E.
Published: June 2022

Radiation therapy (RT) is one of the main methods of treatment of malignant tumors. More than 70% of patients with malignant tumors of various localizations require RT as part of their combination treatment. Cutaneous reactions can occur in up to 95% of patients during or after their treatment. Clinically, cutaneous radiation reactions are manifested by hyperemia, edema, burning and itching of the skin, which cause significant discomfort to patients and reduce their quality of life, especially if these processes are localized on the exposed parts of the body. Also in some localizations of malignant tumors together with RT are used antitumor drugs, which, in turn, increases the frequency of skin toxicity and worsens the clinical picture. Timely detection of the above symptoms, their adequate comprehensive therapy with the use of basic skin care products can significantly reduce or eliminate their manifestations. This article presents the clinical experience of using La Roche-Posay products during radiotherapy and chemoradiotherapy (the patients gave their informed consent for the publication of the clinical observations).
Key differences between anti-PD-1/PD-L1 inhibitors
Authors: Zhukova N. V. , Orlova R. V. , Kaledina E. A. , Naymushina P. A. , Malkova A. M. , Beliak N. P.
Published: June 2022

Indications  to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors  showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors  (CPI) in the future may allow  to solve the problem of rechallenge  and reintroduction after management of severe IRAEs.
Immunotherapy of advanced hepatocellular carcinoma: case report and literature review
Authors: Menshikov K. V. , Sultanbaev A. V. , Musin Sh. I. , Menshikova I. A. , Abdeev R. R. , Sultanbaeva N. I. , Nigmatullin V. G. , Popova E. V.
Published: June 2022

Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.

At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.
Identification of Neural Progenitor Cell-associated Chemoradiotherapy Resistance
Gene Set (ARL4C, MSN, TNFAIP6) for Prognosis of Glioma
Authors: Yang Yongchang , Xu Xing , Xie Yang , Liu Yancheng , Ning Chunlan , Ai Yiding , Lv Chao , Wei Haotian , Ge Xianglian , Yi Tailong , Piao Yongjun , Wang Xiaoguang , Jin Xun
Published: June 2022

Background:

Glioma is the most common malignant intracranial tumor with high lethality. Despite surgery combined with chemoradiotherapy, the prognosis for patients with glioma remains poor. This is primarily due to acquired chemoradiotherapy resistance. Therefore, to improve the prognosis of glioma, further study into the mechanism of chemoradiotherapy resistance is needed.

Objective:

This study aimed to (1) evaluate the prognosis of patients with glioma by using a prognostic risk score model constructed by chemoradiotherapy resistance genes, (2) provide new targets and directions for precise treatment of glioma, and (3) discuss the tumor heterogeneity of tumor cells.

Methods:

According to therapy class and overall survival (OS), we identified 53 genes associated with glioma chemoradiotherapy resistance in The Cancer Genome Atlas Glioblastoma (TCGA GBM) database. Considering the improtant role of chemoradiotherapy resistance-related genes in the prognosis of glioma, we preliminarily screened and identified vital prognostic factors among these genes by using Cox regression model of absolute contraction and selection operators in the TCGA GBM lower-grade glioma (TCGA GBMLGG) dataset. Next, the heterogeneity of the chemoradiotherapy resistance-associated genes in different glioma cells was revealed by single-cell sequencing in the GSE117891 cohort.

Results:

A prognostic risk score model consisting of three genes (ARL4C, MSN, TNFAIP6) was constructed. The expression of this model was high in glioma neural progenitor cells (NPCs) and low in glioma oligodendrocytes. The OS rates were significantly lower in the high- vs low-risk group.

Conclusion:

Our 3 gene risk score complements current glioma diagnosis and provides a novel insight into chemoradiotherapy resistance mechanisms for the prognosis of patients with glioma.
A Network Pharmacology Approach for Uncovering the Mechanism of
'Kouchuangling' in Radiation-induced Oral Mucositis Treatment
Authors: Li Bo , Sheng Pei , Xie Jing , Wu Yuqing , Xia Xiaotong , Wu Mianhua
Published: June 2022

Background:

Radiation-induced oral mucositis (RIOM) is an intractable inflammatory
disease whose pathogenesis needs to be clarified. “Kouchuangling” (KCL), a traditional Chinese
medicine formula, is composed of Lonicerae Japonicae Flos, Radix Paeoniae Rubra, and Radix
Sanguisorbae. Although all of them are Chinese folk medicines which have long been utilized for
ameliorating inflammation, the mechanism of KCL to RIOM remains unclear.

Purpose:

To predict the active ingredients of KCL and identify the mechanism of KCL on RIOM.

Material and Methods:

We identified the chemical ingredients in KCL using TCM Systems
Pharmacology (TCMSP), TCM@Taiwan, PubChem, and SuperPred databases and used the oral
bioavailability (OB), drug-like properties (DL) and Degree of compounds for screening. Targets
for oral mucositis were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic
Target Database (TTD), PharmGKB, and DrugBank databases. Cytoscape 3.7.0 was used to
visualize the compound-target-disease network for KCL and RIOM. The biological processes of
target gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways
were analyzed using DAVID.

Results:

Based on OB≥30%, DL≥0.18 and Degree≥3, 24 active ingredients and 960 targets on
which the active components acted were identified. A total of 1387 targets for oral mucositis were
screened. GO enrichment and KEGG pathway analyses resulted in 43 biological processes (BPs), 3
cell components (CCs), 5 molecular functions (MFs), and 32 KEGG pathways, including leishmaniasis,
Toll-like receptor signaling, TNF signaling, and Influenza A pathways.

Conclusion:

This experiment preliminarily verified that the active ingredients of KCL play a role
in the treatment of RIOM through multiple targets and pathways, providing a reference for further
study of the pharmacological mechanism of Chinese herbal medicine.
Dysregulated YAP1/Hippo Pathway Contributes to Doxorubicin (ADM)
Resistance in Acute Myeloid Leukemia (AML)
Authors: Chen Xi , Song Yan , Huang Rui , Liu Juan
Published: June 2022

Background:

Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).

Methods:

In this study, we established two ADM-resistant cell lines (THP-1/ ADM and K562/ ADM). Then cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real time PCR were performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot.

Results:

We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM-resistance, evidenced by the increased expression in ADM-resistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding this role of YAP1 regulates AML resistance by affecting CSCs characteristics.

Conclusion:

In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM-resistance in AML. YAP1 might be novel biomarkers for treatment of drug-resistance in AML.
New Era on Combining Both Imaging and Drug Delivery to Treat Cancer
Authors: Siafaka Panoraia , Çağlar Emre Şefik , Gündoğdu Evren Atlıhan , Okur Neslihan Üstündağ
Published: June 2022

It is well documented that cancer is one of the leading causes of death worldwide. During
the pandemic, cancer screening was suspended, and only symptomatic patients were referred for
screening. It is believed that deaths related to various cancer types have increased by around 10%, and
the screening suspension was assumed as the main reason. It is well documented that the early diagnosis
of cancer is important for the outcome; last decades, the introduction of nanotechnology-based
carriers, which can serve as both imaging and therapeutic modalities, has risen. Although the combination
of imaging and drug delivery for targeting cancer is a hopeful field, it is still under investigation
and has not met clinical standards. Nanotheranostics, as they are also referred to, can combine both
imaging and delivery and improve the survival rates and overall quality of life of patients. Would cancer
patients have a chance to live a normal life if nano theranostics were incorporated into the daily
clinical oncology practice? This review tries to answer this question by providing the most current
applications of nanotheranostics targeting different types of cancer and summarizing their most significant
characteristics.
Effects of MCU-mediated Ca2+ Homeostasis on Ovarian Cancer
Cell SKOV3 Proliferation, Migration and Transformation
Authors: Zhao Lantao , Jiang Man , Tian Tian , Wang Guanqun , Mei Yingying , Fu Guangming , Zhou Na
Published: June 2022

Background:

Atlas human proteomics database showed MCU as highly
expressed in various tumor tissues, especially in ovarian cancer. Rare studies on the
role of MCU and its regulation in ovarian cancer have been reported.

Objective:

The objective of this study was to determine role of MCU in ovarian cancer
cell SKOV3 proliferation, migration, and transformation, and explore the possible
mechanism.

Methods:

MCU siRNA on lentiviral particles were stably transfected into SKOV3 cells. CCK-8 assay was performed to analyze cell proliferation. Soft-agar colony formation assay was employed to evaluate the tumorigenesis. Western blot and immunohistochemistry analyses were performed to evaluate the expression of MCU, MICU1 and phosphorylate of Akt in ovarian cancer cell and tissue specimens. Scratch assay was combined with trans-well plates assay to detect the migration ability of cancer cells. The ROS production and Ca2+ were also determined.

Results:

MCU expression was significantly higher in ovarian cancer tissues than normal
tissues. MCU silencing decreased SKOV3 cell proliferation, migration, and
transformation. ROS production was decreased after MCU silencing, depending on
disturbed Ca2+ homeostasis. MICU1 expression has been found to be decreased and
phosphorylation of Akt increased when MCU was silenced.

Conclusions:

Down-regulation of MCU inhibited SKOV3 cell proliferation, migration, and
transformation via disturbing Ca2+ homeostasis and decreasing ROS production. MICU1
and phosphorylation of Akt are associated with MCU-mediated ovarian cancer
malignancy.