Ukraine data on prognostic factors and treatment outcomes in patients with peripheral t-cell lymphomas

Background: Peripheral T-cell lymphomas (PTCLs) is a diverse group of lymphomas (10-15% of all non-Hodgkin’s lymphomas) with aggressive behavior. Despite the standard of 1st line anthracycline-contain ingregimens, clinical outcomes are poor compared to B-cell lymphomas. In addition, there are still debates about specific prognostic factors (PF) in PTCLs. Aims: Primary endpoints -event-free survival (EFS) and over all survival (OS). To evaluate the prognostic significance of five PTCLs scores (International Prognostic Index -IPI, International Peripheral T-cell lymphoma Project Score -IPTCL, Prognostic Index for T-cell lymphoma -PIT, modified Prognostic Index for T-cell lymphoma -mPIT and T-cell score). Patients and methods: From 67 enrolled patients, only 50 were included: PTCL not otherwise specified (22, 44%), anaplastic large cell lymphoma ALK+ (anaplastic lymphoma kinase-positive) (10, 20%) and ALK− (anaplastic lymphoma kinase-negative) (18, 36%). Patients received CHOP-like regimens (CHOP, CHOEP, EPOCH). Results: The over all rate response was observed in 66% of cases (complete response 78%). There were 48% of relapses after the 1st line therapy during follow-up (median 11 months; range 1-85 months). Median age 57 (range 22-80) with male predominance 62%. In total, 40% of patients were > 60 years old, 48% had stage III-IV. Majority of patients were assessed by five prognostic scores. IPI (45 patients): The 3-year EFS and OS were higher for IPI ≤ 1 vs. IPI > 2 (80 vs. 18% and 87 vs. 27%, respectively; p = 0.0002). Receiver operating characteristic analysis confirmed poor clinical outcome to patients with PF > 1 (Se = 88 %; Sp = 68 %; AUC = 0.7; p = 0.0081). IPTCLP (41 patients): The presence of PF = 1-2 showed EFS and OS reduction. A 3-year EFS rate for 1-2 PF was 25 vs. 70% for PF = 0 (p = 0.003). Thus, 3-year OS in patients with PF = 0 vs. PF = 1-2 was 100 vs. 20% (p = 0.0001). PIT (42 patients): Better 3-year EFS and OS in patients with PF = 0 vs. PF = 1-3 (88 vs. 28% and 100 vs. 34%, respectively, p = 0.001). Patients with PF = 1-3 have a higher rate of relapses vs. PF = 0 (p = 0.0005 by Cox-test). mPIT (21 patients): No significant difference between PF and clinical outcomes. T-cell score (18 patients): Higher survival rates with PF ≤ 2. More than 2 PF have an impact on EFS (p = 0.005). The 3-years OS in patients with PF ≤ 2 was 77 vs. 25% in cases with PF ≥ 3 (p = 0.001). Conclusion: IPI, PIT, IPTCLP are still very useful in defining risk stratification. As to mPIT and T-cell score, more patients to evaluate their prognostication possibility are needed

Necrobiosis lipoidica developing within a surgical scar in a non-diabetic patient: Type III Koebner phenomenon (isomorphic response), Wolf's isotopic response or Ruocco's immunocompromised cutaneous district?

Sir, Necrobiosis lipoidica is a chronic granulomatous disease typically associated with diabetes mellitus. We report a case of necrobiosis lipoidica occurring in a surgical scar in a non-diabetic patient. We found only nine previous reports of necrobiosis lipoidica appearing after trauma or in surgical scars, as a manifestation of Type III Koebner phenomenon. Most of these were in diabetic patients..

EXTERNAL ROLLING OF A POLYGON ON CLOSED CURVILINEAR PROFILE

The design of a helical surface tillage tool made of a developable helicoid section has been calculated using the methods of analytical and differential geometry, the theory of surfaces, the systems of computer-generated graphics and mathematics. A helical tool in the form of a skeleton cylinder made of bars, where there is a helical surface made of arranged sheet metal, has been developed. Such a design prevents a helical surface from becoming clogged with soil. The suggested tool operates as a roller and the soil can easily pass through the gaps between the bars. New helical harrow tools have been designed and made for this experiment. An experimental harrow equipped with helical tools has been made and used to conduct a field research. The research was aimed at determining the optimal kinematic parameters and the pattern of field movement, which allow performing the technological process of soil tillage with the performance indices that meet the agricultural requirements

Experimental demonstration of scalable quantum key distribution over a thousand kilometers

Secure communication over long distances is one of the major problems of modern informatics. Classical transmissions are recognized to be vulnerable to quantum computer attacks. Remarkably, the same quantum mechanics that engenders quantum computers offers guaranteed protection against such attacks via quantum key distribution (QKD). Yet, long-distance transmission is problematic since the essential signal decay in optical channels occurs at a distance of about a hundred kilometers. We propose to resolve this problem by a QKD protocol, further referred to as the Terra Quantum QKD protocol (TQ-QKD protocol). In our protocol, we use semiclassical pulses containing enough photons for random bit encoding and exploiting erbium amplifiers to retranslate photon pulses and, at the same time, ensuring that at the chosen pulse intensity only a few photons could go outside the channel even at distances of about a hundred meters. As a result, an eavesdropper will not be able to efficiently utilize the lost part of the signal. The central component of the TQ-QKD protocol is the end-to-end loss control of the fiber-optic communication line since optical losses can in principle be used by the eavesdropper to obtain the transmitted information. However, our control precision is such that if the degree of the leak is below the detectable level, then the leaking states are quantum since they contain only a few photons. Therefore, available to the eavesdropper parts of the bit encoding states representing `0' and `1' are nearly indistinguishable. Our work presents the experimental demonstration of the TQ-QKD protocol allowing quantum key distribution over 1079 kilometers. Further refining the quality of the scheme's components will expand the attainable transmission distances. This paves the way for creating a secure global QKD network in the upcoming years.Comment: 23 pages (main text: 15 pages, supplement: 8 pages), 21 figures (main text: 7 figures, supplement: 14 figures

Visualization of membrane loss during the shrinkage of giant vesicles under electropulsation

We study the effect of permeabilizing electric fields applied to two different types of giant unilamellar vesicles, the first formed from EggPC lipids and the second formed from DOPC lipids. Experiments on vesicles of both lipid types show a decrease in vesicle radius which is interpreted as being due to lipid loss during the permeabilization process. We show that the decrease in size can be qualitatively explained as a loss of lipid area which is proportional to the area of the vesicle which is permeabilized. Three possible mechanisms responsible for lipid loss were directly observed: pore formation, vesicle formation and tubule formation.Comment: Final published versio

Experience in the Design and Production of Recombinant Oral Vaccine «Revax VZT»

Objective of the work was the production of recombinant vaccine «RevaxVZT» in tablet dosage form against hepatitis B and pathogenic for humans orthopoxviruses for further clinical trials. Materials and methods. Recombinant strain b7.5S2-S of vaccinia virus carrying a DNA fragment of hepatitis B virus inserted into thymidinekinase gene was used as an active component of the vaccine. Microbiological, virological, physical, physical and chemical, and biotechnological methods were used for studying the quality of the drug and technological processes. Results and discussion. Results of technological control for semi-finished products and final products of the vaccine “Revax VZT” showed the possibility of using certified hardware-processing line of “TEOVac” for its manufacturing. Same technology can be potentially used with other live tableted embryo smallpox vaccines too. For the development of the vaccine “Revax VZT” with the specific activity of not less than 1.0·107 PFu/tablet, it is necessary to use a dry virus-containing material with activity not less than 2.0·108 PFU/g which is produced by freeze-drying of liquid virus-containing preparation with the activity of not less than 1.0·108 PFU/g, preferentially propagated from chorionic allantoic membranes of chicken embryos as a substrate for viral biomass accumulation

Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state

ABHD4-dependent developmental anoikis safeguards the embryonic brain

During embryonic development, neural progenitor cells undergo numerous cell divisions. Here, the authors show that ABHD4-mediated developmental anoikis distinguishes the physiological delamination and the pathological detachment of progenitor cells with relevance to fetal alcohol-induced apoptosis

A novel single-cell based method for breast cancer prognosis

Breast cancer prognosis is challenging due to the heterogeneity of the disease. Various computational methods using bulk RNA-seq data have been proposed for breast cancer prognosis. However, these methods suffer from limited performances or ambiguous biological relevance, as a result of the neglect of intra-tumor heterogeneity. Recently, single cell RNA-sequencing (scRNA-seq) has emerged for studying tumor heterogeneity at cellular levels. In this paper, we propose a novel method, scPrognosis, to improve breast cancer prognosis with scRNA-seq data. scPrognosis uses the scRNA-seq data of the biological process Epithelial-to-Mesenchymal Transition (EMT). It firstly infers the EMT pseudotime and a dynamic gene co-expression network, then uses an integrative model to select genes important in EMT based on their expression variation and differentiation in different stages of EMT, and their roles in the dynamic gene co-expression network. To validate and apply the selected signatures to breast cancer prognosis, we use them as the features to build a prediction model with bulk RNA-seq data. The experimental results show that scPrognosis outperforms other benchmark breast cancer prognosis methods that use bulk RNA-seq data. Moreover, the dynamic changes in the expression of the selected signature genes in EMT may provide clues to the link between EMT and clinical outcomes of breast cancer. scPrognosis will also be useful when applied to scRNA-seq datasets of different biological processes other than EMT.Xiaomei Li, Lin Liu, Gregory J. Goodall, Andreas Schreiber, Taosheng Xu, Jiuyong Li, Thuc D. L