2nd Type Research Articles

Helicopter turboshaft engines combustion chamber monitoring neural network method

The article proposes an innovative method for helicopter turboshaft engines’ combustion chamber monitoring based on a neural network, significantly impacting the aircraft engines’ diagnostics and monitoring subject area. This article’s main contribution is to improve defect detections’ accuracy and timeliness, which in turn contributes to the aircraft equipment operations’ reliability and safety. The developed method, leveraging an enhanced adaptive neuro-fuzzy inference system (ANFIS) neuro-fuzzy network with Sugeno-Takagi inference, significantly improves defect detection accuracy and reduces diagnostic errors, thereby enhancing the reliability and safety of flight operations. To implement it, the combustion chamber mathematical model was created based on the heat balance equation, which showed that the fuel combustion completeness coefficient is a diagnostic criterion for defects. It is mathematically substantiated that this coefficient determines combustion efficiency and directly affects thermal energy. The ANFIS with Sugeno-Takagi fuzzy inference architecture has been improved, making it possible to achieve the defects diagnosis and prediction accuracy of 99.65 %. The ANFIS neuro-fuzzy network with Sugeno-Takagi inference proposed in this work improves quality metrics for determining helicopter turboshaft engines’ combustion chamber defects, enhancing the fuel combustion completeness coefficient by 1.01 to 4.64 times. Experimental results show that optimal network training with a loss of 0.35 % is achieved in 60 epochs, which is 2.0 to 9.5 times faster than traditional algorithms (genetic algorithm, traditional backpropagation algorithm, traditional inverse gradient descending method, modified inverse gradient descending method, hybrid algorithm). The absence of hidden T-patterns in the fuel combustion completeness coefficient dynamics (the value does not exceed 10–4) is also substantiated, confirming the proposed method’s high accuracy. The accumulated heat experimental surfaces’ dependences on the dynamics and fuel consumption were obtained, which makes it possible to analyze the defects’ influence on the combustion chamber’s thermal characteristics. The proposed ANFIS network use reduces the 1st and 2nd types’ errors by 1.44…6.15 times when determining combustion chamber defects compared to other architectures and classical methods, such as the least squares method.

Influence of Solid-Phase and Melt-Quenching Na3Fe2(PO4)3 Polycrystal Production Technology on Their Structure and Ionic Conductivity

This article studies the influence of solid-phase (type 1 samples) and melt-quenching (type 2 samples) technological modes of obtaining Na3Fe2(PO4)3 polycrystals on their structures and ion-conducting properties. α-Na3Fe2(PO4)3 polycrystals of the 1st type are formed predominantly under an isothermal firing regime, and the synthesis of the 2nd type is carried out under sharp temperature gradient conditions, contributing to the formation of glassy precursors possessing a reactive and deformed structure, in which the crystallization of crystallites occurs faster than in precursors obtained under isothermal firing. The elemental composition of α-Na3Fe2(PO4)3 type 2 polycrystals is maintained within the normal range despite the sharp non-equilibrium thermodynamic conditions of synthesis. The microstructure of the type 1 Na3Fe2(PO4)3 polycrystals is dominated by chaotically arranged crystallites of medium (7–10 μm) and large (15–35 μm) sizes, while the polycrystals of type 2 are characterized by the preferential formation of small (3–4 μm) and medium (7–10 μm) crystallites, causing uniaxial deformations in their structure, which contribute to a partial increase in their symmetry. The advantage of type 2 polycrystals is that they have higher density and conductivity and are synthesized faster than type 1 samples by a factor of 4. The article also considers the issues of crystallization in a solid-phase precursor from the classical point of view, i.e., the process of the formation of small solid-phase nuclei in the metastable phase and their growth to large particles due to association with small crystallites using phase transitions. Possible variants and models of crystallite growth in Na3Fe2(PO4)3 polycrystals, as well as distinctive features of crystallization between two types of samples, are discussed.

Neural Network Signal Integration from Thermogas-Dynamic Parameter Sensors for Helicopters Turboshaft Engines at Flight Operation Conditions.

The article's main provisions are the development and application of a neural network method for helicopter turboshaft engine thermogas-dynamic parameter integrating signals. This allows you to effectively correct sensor data in real time, ensuring high accuracy and reliability of readings. A neural network has been developed that integrates closed loops for the helicopter turboshaft engine parameters, which are regulated based on the filtering method. This made achieving almost 100% (0.995 or 99.5%) accuracy possible and reduced the loss function to 0.005 (0.5%) after 280 training epochs. An algorithm has been developed for neural network training based on the errors in backpropagation for closed loops, integrating the helicopter turboshaft engine parameters regulated based on the filtering method. It combines increasing the validation set accuracy and controlling overfitting, considering error dynamics, which preserves the model generalization ability. The adaptive training rate improves adaptation to the data changes and training conditions, improving performance. It has been mathematically proven that the helicopter turboshaft engine parameters regulating neural network closed-loop integration using the filtering method, in comparison with traditional filters (median-recursive, recursive and median), significantly improve efficiency. Moreover, that enables reduction of the errors of the 1st and 2nd types: 2.11 times compared to the median-recursive filter, 2.89 times compared to the recursive filter, and 4.18 times compared to the median filter. The achieved results significantly increase the helicopter turboshaft engine sensor readings accuracy (up to 99.5%) and reliability, ensuring aircraft efficient and safe operations thanks to improved filtering methods and neural network data integration. These advances open up new prospects for the aviation industry, improving operational efficiency and overall helicopter flight safety through advanced data processing technologies.

HPV-driven oropharyngeal cancer burden in Paris and its region (ILE DE FRANCE) from 1981 TO 2021

BackgroundFrance has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France. MethodsOPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data. ResultsSamples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status ConclusionThe proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men.

Комбинированный метод лечения рефрактерного диабетического макулярного отека

Purpose. To determine the effectiveness of the anatomical and functional results of treatment of refractory diabetic macular edema after removal of the inner limiting membrane using the latest generation anti-VEGF drug. Material and methods. We examined 6 patients with 1st type and 2nd type diabetes mellitus. The average age of the subjects was 47.45 ± 27.15 years. Of these, there were 4 women and 2 men. 1st type diabetes mellitus was detected in 2 people, in other patients — 2nd type. 3 patients had previously undergone pan-retinal photocoagulation (from 1st to 2nd stages). All patients received intravitreal injections (anti-VEGF) of Eylea (4–5 injections) during the last year. According to the optical coherence tomogram (OCT), macular edema was recorded, recurring on average after 1.36 ± 0.85 months. All patients underwent surgical treatment. In the presence of lens opacity, surgical treatment was started with phacoemulsification of cataracts. A microinvasive subtotal vitrectomy was performed with the removal of the posterior layers of the vitreous body and proliferative membranes fixed to the retina. The removal of the inner boundary membrane was performed after its staining in the size of two to three diameters of the optic disc without any tamponade. After 2 months, two patients had an increase in retinal thickness in the fovea. These patients received one injection of Vabismo. Results. The compared groups did not differ in morphofunctional characteristics. In the postoperative period, there was a tendency to increase visual acuity and decrease retinal thickness, regression of hard exudates in 4 patients. In 2 patients, an increase in retinal thickness in the fovea was noted after 2 months. After intravitreal injection of the latest generation anti-VEGF drug (Vabismo), these patients also showed an increase in visual acuity, regression of solid exudates and a decrease in retinal thickness. Conclusion. Microinvasive subtotal vitrectomy with removal of the inner limiting membrane in combination with intravitreal injection of the latest generation anti-VEGF drug (Vabismo) is an effective method of treating refractory diabetic macular edema. Keywords: anti-VEGF, Vabismo, diabetic macular edema, intravitreal injections, optical coherence tomogram, subtotal vitrectomy, inner boundary membrane

The dynamics of the state of done tissue of the alveolar process of the upper jaw when using a complete removable plate prosthesis

Objective. Improving the assessment of the state of the bone tissue of the alveolar process of the toothless upper jaw, by calculating the level of its atrophy according to the diagnostic model of the jaw. Material and methods. The study of patients was carried out: anamnesis of the disease, examination of the oral cavity, analysis of diagnostic plaster models of the upper jaw according to the method we proposed. In accordance with the classification of the Shreder, groups were formed: the first is the 1st type of Shreder (n=24); the second is the 2nd type of Shreder (n=23); the third is the 3rd type of Shreder (n=19). Results. In some areas of the alveolar process of the toothless upper jaw, atrophy reaches vertical values at points A1-D: 0.71±0.20 mm (group 1), 0.57±0.19 mm (group 2), 0.19±0.26 mm (group 3), sagitally A1-A2: 4.72±0.28 mm (group 1), 4.48± 0.30 mm (group 2), 3.85±0.32 mm (group 3); transversal – K1-K2: 3.22±0.29 mm (group 1), 3.67±0.32 mm (group 2), 3.37±0.47 mm (group 3) and more intensive in the first year of operation the prosthesis. Conclusion. Thus, the proposed diagnostic method makes it possible to determine the uneven level of bone loss in various areas of the alveolar process of the upper jaw. The data obtained are taken into account to minimize the negative consequences of the transfer of masticatory pressure from the basis of the prosthesis when planning orthopedic treatment of patients with this pathology.

TOUCHARD POLYNOMIALS APPROACH FOR SOLVING NON- LINEAR FREDHOLM INTEGRO- DIFFERENTIAL EQUATION OF SECOND TYPE

A numerical approach to solve Non- linear Fredholm integro- differential (NLFID) equation of the 1st order and 2nd type has been proposed. The approach was based upon Touchard polynomials. The non-linear Fredholm integro- differential equation was changed into a system of non- linear algebraic equations and solved using Newton repeating approach. The proposed approach was evaluated by displaying three numerical problems, and the approximate numerical solutions were compared with exact solution and four methods in the literature. MATLAB R2018b was used to perform all calculations and graphs.

Types of the nasal septum deviations and their influence on the state of mucociliary clearance of the nasal cavity in patients with postnasal obstruction syndrome

The flow of nasal secretions into the pharynx and larynx manifests itself differently throughout the day. At night, this mucus flows into the larynx, irritates reflexogenic zones and causes coughing, and during the day these complaints are less noticeable, due to involuntary swallowing of secretions. We hypothesized that different types of nasal septum deviations may affect mucociliary clearance and, as a result, lead to postnasal drip syndrome. However, we did not find any studies in the literature that examined the effect of types of nasal septum deviation (NSD) on mucociliary clearance (MCC). Therefore, in our study, we evaluated the effect of the types of nasal septum deviations on MCC. The aim of the study. To investigate the activity of mucociliary clearance of the mucous membrane of the nasal cavity in patients with different types of NSD. Materials and methods. 100 patients were investigated. All patients underwent an endoscopic examination of the nasal cavity, a ST scan of the nasal cavity, and a saccharin test. The results. The analysis made it possible to reveal that in most patients with type 2 deviation of the nasal septum with the presence of a unilateral caudal ridge, which cuts into the middle turbinate, there is PNDS. At the same time, while the average ST time of the concave side of the nasal mucosa in patients with type 1 was almost unchanged, it was significantly longer in patients with type 2 (P=0,02). Therefore, in this study, the ST indicator in min. was longer on the concave side of the nasal cavity than on the convex side. Conclusions. Our research has shown that nasal septum deviation reduces nasal mucociliary activity, and this effect can be easily assessed using the saccharin test. According to our observations and research results, it was the 2nd and 3rd types of deviation that significantly disturbed the architecture of the nasal cavity, due to the presence of contralateral vertical deviation of the nasal septum, contralateral hyperplasia of the nasal turbinates, and contralateral conchobulosis. And, as a result, led to a decrease in mucociliary clearance

"Quality of Life of Patients with 2nd Type Diabetes Mellitus and Chronic Heart Failure"

"Quality of Life of Patients with 2nd Type Diabetes Mellitus and Chronic Heart Failure"

Fundamental theorems of quasi-geodesic mappings of generalized-recurrent-parabolic spaces

In previous papers we studied mappings of pseudo-Riemannian spaces being mutually quasi-geodesic and almost geodesic of the 2nd type. As a result, we arrived at the quasi-geodesic mapping f: (Vn, gij, Fih) → (Vn, gij, Fih) of spaces with an affine structure, which was called generalized-recurrent. Quasi-geodesic mappings are divided into two types: general and canonical. In this article, the fundamental issues of the theory of quasi-geodesic mappings of generalized-recurrent-parabolic spaces are considered. First, the fundamental equations of quasi-geodesic mappings are reduced to a form that allows effective investigation. Then, using a new form of the fundamental equations, we prove theorems that allow for any generalized-recurrent-parabolic space (Vn, gij, Fih) or to find all spaces (Vn, gij, Fih) onto which Vn admits a quasi-geodesic mapping of the general form, or prove that there are no such spaces.

A large, real-world cohort analysis of arrhythmia detections with insertable cardiac monitors

Abstract Background Insertable cardiac monitors (ICMs) provide long-term continuous monitoring for arrhythmia diagnosis and management for various clinical indications. However, little data exists on the real-world diagnostic yield of ICMs across indicated patient populations, including both expected and incidental arrhythmic findings. Validated artificial intelligence (AI) algorithms have been developed to identify true arrhythmia episodes while significantly reducing false positives, enabling the adjudication of ICM episodes for larger cohorts of patients. Purpose To characterize comprehensive true arrhythmia detection rates in a large real-world population with long-term ICM monitoring. Methods De-identified patients ≥18 years receiving a Reveal LINQ ICM between Oct 1, 2016 – Sept 30, 2020 with no prior cardiac implantable electronic devices and ≥1 year of follow-up in the CareLink monitoring database were identified (N=12,013). Patients were stratified by reason for ICM placement: N=9,841 who received ICM for diagnosis of suspected arrhythmias (40.8% unexplained syncope, 38.3% cryptogenic stroke, 9.7% palpitations, 9.7% suspected atrial fibrillation (AF), 1.6% ventricular tachycardia), and N=2,172 who received ICM for management of known AF. Device-detected ECGs during long-term follow-up were identified and processed through previously validated arrhythmia-specific AI algorithms designed to reduce false positive arrhythmia detections (each trained using ICM data from ≥25,000 adjudicated ECG episodes and validated on an independent set of ≥5,000 adjudicated ECGs). Results Mean (SD) and median follow-up were 24.6(12.7) and 24.5 months, respectively. In patients receiving ICM for Suspected Arrhythmia, 5,492 patients (55.8%) had ≥1 AI-adjudicated arrhythmia detected during follow-up, with 2,472 (45.0%) of these patients having ≥2 arrhythmia types detected (Table). Mean (SD) time to 1st arrhythmia detection was 7.7(9.1) months; time to 2nd arrhythmia type detected was 12.3(10.4) months. Among the 6,958 patients with longer-term ICM follow-up ≥2 years, 2,931 (42.1%) had no arrhythmias detected (i.e., arrhythmia rule-out occurred). In patients receiving ICM for AF Management, 1,737 patients (80.0%) had ≥1 arrhythmia detected, and notably 1,074 (61.8%) of these patients had ≥1 arrhythmia detected during follow-up that was not AF. Mean (SD) time to 1st arrhythmia detection was 5.3 (7.7) months; time to 2nd arrhythmia type detected was 10.4(9.9) months. Conclusions In a large real-world ICM population, >50% of patients had AI-adjudicated arrhythmia detections during long-term follow-up, with a significant proportion receiving additional arrhythmia diagnoses beyond the initial type diagnosed or suspected. These results suggest that in indicated patients, long-term continuous monitoring with ICMs can enable diagnosis of a variety of cardiac arrhythmias that may have otherwise remained undetected.

WWR-K reactor LEU core design optimization for improving the experimental characteristics

The increase in demand for irradiation activities in the WWR-K reactor dictates the need to increase the number of irradiation positions in the core. Several core designs were considered by simulation with using MCNP6 code. As a result, core consisting of 22 FAs of the 1st type and 4 FAs of the 2nd type was chosen. An analysis of the calculation results showed that the new design of the core improves the experimental characteristics of the reactor and, at the same time, ensures nuclear safety. In particular, the number of irradiation positions in the fuel area increases from 3 to 5, in the new core design. The maximum thermal neutron flux increases to 2.1x1014 cm-2s−1. This paper presents the results of neutron analysis of the new WWR-K reactor core design in comparison with the existing.

Does achieving clinically important thresholds after first shoulder arthroplasty predict similar outcomes of the contralateral shoulder?

Patients are increasingly undergoing bilateral total shoulder arthroplasty (TSA). At present, it is unknown whether success after the 1st TSA is predictive of success after contralateral TSA. We aimed to determine whether exceeding clinically important thresholds of success after primary TSA predicts similar outcomes for subsequent contralateral TSA. We performed a retrospective review of a prospectively-collected shoulder arthroplasty database for patients undergoing bilateral primary anatomic (aTSA) or reverse (rTSA) total shoulder arthroplasty since January 2000 with preoperative and 2- or 3-year clinical follow-up. Our primary outcome was whether exceeding clinically important thresholds in the American Shoulder and Elbow Surgeons (ASES) score for the 1st TSA was predictive of similar success of the contralateral TSA; thresholds for the ASES score were adopted from prior literature and included the minimal clinically important difference (MCID), the substantial clinical benefit (SCB), 30% of maximal possible improvement (30%MPI), and the patient acceptable symptomatic state (PASS). The PASS is defined as the highest level of symptom beyond which patients consider themselves well, which may be a better indicator of a patient's quality of life. To determine whether exceeding clinically important thresholds was independently predictive of similar success after 2nd contralateral TSA, we performed multivariable logistic regression adjusted for age at 2nd surgery, sex, BMI, and type of 1st and 2nd TSA. Of the 134 patients identified that underwent bilateral shoulder arthroplasty, 65 (49%) had bilateral rTSAs, 45 (34%) had bilateral aTSAs, 21 (16%) underwent aTSA/rTSA, and 3 (2%) underwent rTSA/aTSA. On multivariable logistic regression, exceeding clinically important thresholds after 1st TSA was not associated with greater odds of achieving thresholds after 2nd TSA when success was evaluated by the MCID, SCB, and 30%MPI. In contrast, exceeding the PASS after 1st TSA was associated with 5.9-times greater odds (95% CI = 2.5-14.4, P<0.001) of exceeding the PASS after 2nd TSA. Overall, patients that exceeded the PASS after 1st TSA exceeded the PASS after 2nd TSA at a higher rate (71% vs. 29%, P<0.001); this difference persisted when stratified by type of prosthesis for 1st and 2nd TSA. Patients that achieve the ASES score PASS after 1st TSA have greater odds of achieving the PASS for the contralateral shoulder regardless of prostheses type.

Microstructure, magnetoresistivity and carrier mobility of HTSC-YBCO tape with pinning centers generated by electron irradiation

Artificial pinning center lattice formed in HTSC both chemically and by irradiation is believed to increase critical current and field although Abrikosov vortex core is in the normal state. The paper presents SEM-EDS, XRD and Hall effect (80-300 K at magnetic field 0.55 Tesla) data in YBCO microfilm on 276-steel tape with metal coating exposed to 5 MeV electrons (1014 cm-2 at 400 nA) in air. No long-living radioisotope was generated. This irradiation resulted in structure modification of microinterfaces YBCO-AgCu, ten times decrease in the magneto-resistance >T c, increase in the 2nd type phase transition steep. The charge carrier mobility μ decreased by a few orders of value, especially at T <100 K and 280 K, where Cooper pairs and magnons condensate, respectively. Within 80-300 K the tape is in mixed magnetic states of YBCO and steel substrate, thereby providing effective flux pinning by highly correlated non-superconducting state.

Biocenosis of the vaginal tract in patients with fertility on the background of chronic endometritis

The objective: to determine the microbiota profile of vagina, cervical canal and endometrium by chronic endometritis (CE) in patients with a history of infertility.Materials and methods. A prospective study and clinical-laboratory analysis of the microbiocenosis of the vagina, cervical canal and uterine cavity in women with CE and infertility in history was conducted. The 1st group included 100 women of reproductive age with CE and infertility, the 2nd group – 40 women of reproductive age without impaired fertility.The scope of research is pH-metry of vaginal secretions, assessment of vaginal microbiocenosis based on Gram-stained smear microscopy, polymerase chain reaction method, cultural research of vaginal secretions, study of the microflora of the cervical canal and the uterine body.Results. In women with CE and a history of infertility, normobiocenosis of the vagina was found in only 32 patients (32.0±3.1%). In other cases, bacterial vaginosis, vulvovaginal candidiasis, and bacterial vulvovaginitis were detected. Microscopy and PCR-diagnostics of secretions from the cervical canal and uterine cavity in women with CE determined Streptococcus agalactiae, Enterococcus faecalis, Chlamidia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, HPV, Gardnerella, HSV 1st or 2nd types and CMV.Conclusions. A characteristic feature of the vaginal flora in chronic endometritis is a high level of dysbiotic changes combined with high rates of insemination by opportunistic flora. The microbiota of the cervical canal and endometrium during inflammatory processes of the endometrium is characterized by the predominance of obligate anaerobic microorganisms in the form of associations with viral infection, which are significantly more often (more than 2 times) detected in the endocervix compared to the endometrium.

Evaluation of the treatment options for COVID-19 patients using generalized hesitant fuzzy- multi criteria decision making techniques

The breakout of the pandemic COVID-19 has affected numerous countries and territories worldwide. As COVID-19 specific medicines yet to be invented, at present the treatment is case specific, hence identification and evaluation of different prevalent treatment options based on various criteria and attributes are very important not only from the point of view of present pandemic but also for futuristic pandemic preparedness. The present study focuses on identifying, evaluation and ranking of treatment options using Multi Criteria Decision Making (MCDM). In this regard, the existing literature, doctors and scientist were interviewed to know the current treatment options in vogue and the scale of their importance with respect to the criteria. The criteria taken are side effect, regime cost, treatment duration, plasma stability, plasma turnover, time of suppression, ease of application, drug-drug interaction, compliance, fever, pneumonia, intensive care, organ failure, macrophage activation syndrome, hemophagocytic syndrome, pregnancy, kidney problem, age. This study extended Hesitant Fuzzy Set (HFS) to Generalized Hesitant Fuzzy Sets (GHFS). Generalized Hesitant Pentagonal Fuzzy Number (GHPFN) is developed. The properties of GHPFN are demonstrated. Two types of GHPFN has been described. The GHPFN (2nd type) along with MCDM tool Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) has been applied to rank the treatment options. The result of the study ranked ‘Hydroxychloroquine’ as the first alternative followed by, ‘Plasma Exchange’, ‘Tocilizumab’, ‘Remdesivir’ and ‘Favipravir’. To check the robustness and steadiness of the proposed methodology, comparative analysis and sensitivity analysis has been conducted.

Efficacy and safety study of a novel alpha-fetoprotein (AFP)-maytansine conjugate in an ovarian xenograft model.

e14570 Background: AFP receptor is an oncofetal antigen and a novel target for cancer therapeutics. It is highly expressed on the surfaces of many cancers and Myeloid Derived Suppressor Cells (MDSCs) but absent on normal tissues. By conjugating maytansine toxin to a recombinant human AFP, we selectively deliver toxin to cancer cells and MDSCs while sparing normal cells, enabling a combination of targeted and immune activating approaches. We previously reported high efficacy of AFP-maytansine conjugate in a xenograft model of colorectal cancer. Here we report the effect of this conjugate in an ovarian xenograft model and in 2 independent patient-derived 3D ovarian organoids, supporting the wider utility of this approach. Methods: Four dose regimens of AFP-maytansine conjugate were compared to control in a mouse A2780 ovarian xenograft model. The conjugate was administered IV 10 days after implantation, when tumor volumes reached ≈150 mm3. Mice were randomized into 4 treatment and 1 control group (10 mice/group, table below). Tumor growth, survival and clinical observations were assessed for 62 days post implantation. In addition, organoids were cultured from primary reprogrammed tumor cells from 2 separate patients with high-grade serous ovarian carcinoma. Conjugate, staurosporine, thapsigargin or DMSO (control) were added to the media. Cytotoxicity was assessed by staining for AnnexinV and TMRE. Results: A statistically significant dose-dependent reduction in tumor volume (p&lt;0.001) and increase in survival (p&lt;0.002) were seen in all treatment groups relative to control. All animals in Groups 1,3 and 4 survived to the end of the study and 6 of 10 mice survived in the lowest dose group. 100% of mice in Group 1, highest dose group had complete tumor regression with no regrowth seen by day 62. In the other treatment groups majority of animals had complete tumor regression with no regrowth. All control animals were dead by day 38 due to excessive tumor burden. No signs of toxicity, such as ocular toxicity or vascular scarring of the tail were seen. All mice gained weight during the study. Gross pathology at the time of sacrifice was unremarkable. In addition, in the 2 ovarian organoids the AFP-maytansine conjugate demonstrated a cytotoxic effect over 72 hours exposure similar to that of thapsigargin and staurosporine given at known effective concentrations. Conclusions: This ovarian xenograft study confirms high activity without obvious toxicity of the novel AFP-maytansine conjugate in a 2nd tumor type. The targeted cytotoxic activity is further confirmed by the effect of the conjugate in 2 different ovarian cancer organoids. These results support advancing this novel conjugate toward clinical use with a dose-dense regimen. [Table: see text]

STRUCTURE OF BICARPELLATE GYNOECIUM IN &lt;i&gt;SYMPHYTUM&lt;/i&gt; &lt;i&gt;ASPERUM&lt;/i&gt; (BORAGINACEAE) IN RELATION TO EREM FORMATION

The genesis of the bicarpellate syncarpous gynoecium was analysed in Symphytum asperum in relation to the septa formation in it, which determines the structure of erems (a dispersal unit of schizogenetic fruits forming as a result of dividing each carpel of syncarpous gynoecium into two independent parts) and the coenobium as a whole. In the gynoecium, at early stages of development, a short fertile synascidiate zone arises due to the formation of a basal septum (septum of 1st type) at the fusing of the involute carpel edges. A symplicate zone is formed above. A double U-shaped synplacenta appears at the gynoecium base. The structure of the basal septum is characterized by some features. The sutures that form the septum are obsagittate, with their wide part directed towards the center, and their narrow part directed outward. The septum of the 1st type is characterized by a 4-rayed structure, resembling an elongated rhombus or 2 tetrahedral pyramids facing each other: short rays are located between the walls of emerging erems of the same carpel, and long rays are between the walls of the erems of adjacent carpels. The central part of the septum subsequently stops developing, and the rays are transformed into branches of syncarpous sutures (2 in each carpel), to form 4 septa of the 2nd type. The length of the septa of the 2nd type increases longitudinally. In the wall of the ovary on the dorsal side in the area of the vascular bundle, 4 strands of small thin-walled cells are formed. Then, a splitting of these strands and the dorsal vascular bundle in half takes place. The septa of the 2nd type, like curtains or inserts, connect open ventral margins with dorsal halves of the ovary wall in each carpel, later becoming part of the pericarp of single-celled erems. At the same time, the symplicate zone is divided into 4 independent compartments. In S. asperum, septa of the 2nd type do not divide the loculi of carpels into 2 compartments and are not united into single partitions. They remain autonomous, growing between open edges of the halves in each carpel. The resulting diaspores (erems) are surrounded by a fruit coat on all sides. The outgrowths are not detected between the erems. This growth of the septa of the 2nd type is unique and correlates with the growth of the gynobasic style, while the shape of the growing septa ideally coincides with the shape of its faces.

T-lymphocytes of the 2nd type of the immune response and their role in enhancing inflammation during the professional activities of firefighters

T lymphocytes of the 2nd type of immune response contribute to the development and exacerbation of inflammation, mainly allergic. Increased inflammation with prolonged exposure to adverse factors during the work of firefighters can lead to the development of various diseases. Evaluation of the immunity of firefighters is important for the appointment of adequate treatment and prevention of infectious and allergic diseases. This paper aimed to analyze the indicators of immunity in employees of the state fire service of EMERCOM of Russia, depending on the age and intensity of the professional workload. The surveyed were men (n = 79), mean age 31 years, work experience from 1 to 22 years, with different workload intensity. In peripheral blood, flow cytometry (Navios, FC 500, Beckman Coulter) was used to evaluate subpopulations of monocytes, the relative number of T lymphocytes of the 2nd type of immune response CD3+CD294+. The concentration of total immunoglobulin E (Immulite) was determined. From nasal secretions, the content of secretory immunoglobulin A (Vector Best) was evaluated (n = 30). Statistical processing of the results was performed using the Statistica 12.0 package (StatSoft). An increase in the number of CD3+CD294+ cells was observed in 16.5%. A direct correlation was found between the number of T lymphocytes 2 and the age of the examined persons (р &lt; 0.05). In the group of firefighters with a more intense workload, an increase in the number of CD3+CD294+ cells were 5 times higher (р &lt; 0.05). Among patients who had any disease of the respiratory tract, an increase in this population was observed statistically significantly more often – in 26% of cases versus 11.5%. A strong direct correlation was found between the number of T lymphocytes 2 and the duration of smoking experience (р &lt; 0.05). A direct correlation was established between the number of T lymphocytes 2 and the concentration of total IgE (р &lt; 0.05). A decrease in secretory IgA in the secret from the nasal passages was observed in 23% of firefighters, in 13% of the examined, the indicator went beyond the upper limit of the reference interval. Significantly more often revealed the deviation of this indicator from the reference values in firefighters with a high workload. An increase in the subpopulation of classical monocytes was established in the group of those examined with a high number of CD3+CD294+ cells (p &lt; 0.05). Thus, with an increase in the professional workload of firefighters in unfavorable conditions of service, inhibition of protection to infection and aggravation of damage to the respiratory tract with an increase in the 2nd type of immune response are noted. Evaluation of the number of type 2 T lymphocytes in peripheral blood will reveal a predisposition to the T2 profile of immune inflammation, which will contribute to a personalized approach to patient management.

P326 FALSE POSITIVE BONE–SCINTIGRAPHY IN ELDERLY HYPERTROPHIC CARDIOMYOPATHY

Abstract Differential diagnosis of cardiomyopathies with hypertrophic phenotype is crucial because some secondary forms of cardiac hypertrophy can be susceptible of specific treatment aimed to revert and/or stabilize the increase in wall thickness.A positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc–HPD)is believed to have high sensitivity and specificity for the diagnosis of transthyretin (TTR) amyloid cardiomyopathy. An 85–year–old man with systemic arterial hypertension was admitted because of pre–syncope associated to evidence at Holter monitoring of both bradiarrhythmias(1st degree AV block with PR interval of 300 ms and several episodes of 2nd degree Mobitz type 1 AV block with electrical pause &amp;gt;3 s) and tachyarrhythmias.He suffered from a bilateral carpal tunnel syndrome that underwent surgery 2 years earlier.Routine laboratory tests were normal except for elevated cardiac troponin HS(0.295 mcg/L,nv &amp;lt; 0.014 mcg/L) and N–terminal pro–BNP (384.3 pg/mL,nv = 0–254 pg/mL).Because of clinical suspicion of senile amyloidosis,nuclear scintigraphy with hydroxy bisphosphonate bone tracer(99mTc–HPD)was performed,that revealed a grade 3 myocardial uptake.Serum–urine immunofixation and immunoglobulin free light–chain was negative for monoclonal gammopathy.Neurological examination was unremarkable Genetic test did not show TTR mutation.Thus,a diagnosis of wild–type TTR cardiac amyloidosis was suggested.The patient,in view of Tafamidis treatment,underwent a LV endomyocardial biopsy.Six specimens were drawn from the LV,cut and processed for histology,immunohistochemistry,and transmission electron microscopy. Unexpectedly,histology failed to confirm amyloid deposition but revealed the presence of severely hypertrophied disarrayed cardiomyocytes fragmented in short runs by interstitial and replacement fibrosis,denoting a sarcomeric hypertrophic cardiomyopathy.Congo red staining at polarized light scored negative for areas of apple–green florescence.Immunohistochemistry form transthyretin,kappa/lambda light chain and SAA was negative.Transmission electron microscopy failed to demonstrate the presence of rigid unbranched amyloid fibrils.Thus,a final diagnosis of hypertrophic cardiomyopathy was reached. Coclusion:A positive cardiac signal of bone scintigraphy can occur in other pathologic settings.Future studies are needed to investigate the incidence of false–positive TTR cardiac amyloidosis to bone scintigraphy compared with endomyocardial biopsy.