Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

[Predictors of thromboembolic complications in patients with severe SARS-CoV-2 coronavirus infection].

AIM: To identify predictors of the development of thromboembolic complications (TECs) in patients with severe SARS-CoV-2 coronavirus infection. MATERIALS AND METHODS: A single-center observational retrospective study included 1634 patients with a confirmed diagnosis of SARS-CoV-2 coronavirus infection. The patients were divided into 2 groups depending on the availability of the feasibility study. The criterion for inclusion of patients in the main group was the presence of venous feasibility studies in 127 patients (group I), the comparison group consisted of 1507 patients in whom the course of COVID-19 was not complicated by the development of feasibility studies (group II). RESULTS: When performing computed tomography of the chest organs, it was revealed that patients with a feasibility study had a higher percentage of lung tissue damage than patients in the comparison group: 55% [37.5; 67.5] and 37.5% [25.0; 47.5], respectively (p<0.001). The average values of C-reactive protein in I patients group were 129 [60.1; 211] ng/l, which was significantly higher than in II patients group - 41.0 [12.2; 97.6] ng/l (p<0.001), interleukin-6 - 176 [52.9; 471] pg/ml and 39.4 [11.0; 107] pg/ml (p<0.001), respectively. A one-factor regression analysis proved a significant contribution of comorbid pathology to the development of feasibility studies in patients with COVID-19. The presence of three nosologies at the same time: arterial hypertension, coronary heart disease (CHD) and chronic kidney disease increased the probability of a feasibility study by 4.81 times (odds ratio 4.8117, 95% confidence interval 3.2064-7.2207), in patients with arterial hypertension, CHD, chronic kidney disease and type 2 diabetes - by 5.63 times (odds ratio 5.6321, 95% confidence interval 3.1870-9.9531). CONCLUSION: The presence of severe comorbid pathology significantly increased the risk of developing a feasibility study in patients with COVID-19. The most significant predictors of the development of feasibility studies in patients with severe SARS-CoV-2 coronavirus infection. They are: CHD, arterial hypertension and type 2 diabetes.

[SARS-CoV-2 morbidity depending on vitamin D status].

BACKGROUND: The association between vitamin D deficiency and the severity of COVID-19 is currently being actively discussed around the world. AIM: The aim of this study was to assess the prevalence of vitamin D insufficiency and deficiency and compare it with the incidence rates of SARS-CoV-2 in eight Federal Districts of the Russian Federation. MATERIALS AND METHODS: We included 304,564 patients (234,716 women; 77,1%) with serum 25(OH)D levels results performed September 2019 through October 2020. RESULTS: Only 112,877 people (37.1%) had a normal serum 25(OH)D level, others had a deficiency. Vitamin D insufficiency and deficiency was presented with the same frequency in women and men, and no differences were found depending on the geographical location and age in subjects from 18 to 74 years old. However, subjects over 75 years more often had vitamin D deficiency, while subjects under 18 years had normal levels in over 50% cases. In addition, 21,506 patients were tested for SARS-CoV-2 by PCR with further comparison of results with serum 25(OH)D level. The SARS-CoV-2 positivity rate was detected in 3,193 subjects, negative in 18,313. There were no differences in the morbidity in a vitamin D deficiency and a normal level. Thus, 14.8% subjects had positive PCR rates among vitamin D deficiency patients (4,978 tests), 14.9% when 25(OD)D level was from 20 to 30 ng/ml (7,542 tests), 15.0% among those who had 25(OH)D 30- 50 ng/ml (6,622 tests), and 13.9% when vitamin D was more than 50 ng/ml (4,612 tests). CONCLUSION: There was no association between the COVID-19 incidence and vitamin D status in different regions of Russia. Although the nutrient deficiency persists in all regions and is most often diagnosed in people over 75 years old.

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

Revealing the Complex Nature of Bonding in the Binary High-Pressure Compound FeO_{2}.

Extreme pressures and temperatures are known to drastically affect the chemistry of iron oxides, resulting in numerous compounds forming homologous series nFeOmFe_{2}O_{3} and the appearance of FeO_{2}. Here, based on the results of in situ single-crystal x-ray diffraction, Mössbauer spectroscopy, x-ray absorption spectroscopy, and density-functional theory+dynamical mean-field theory calculations, we demonstrate that iron in high-pressure cubic FeO_{2} and isostructural FeO_{2}H_{0.5} is ferric (Fe^{3+}), and oxygen has a formal valence less than 2. Reduction of oxygen valence from 2, common for oxides, down to 1.5 can be explained by a formation of a localized hole at oxygen sites.

[Tactics of antihypertensive therapy during COVID-19 pandemic].

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

[Provision of vitamin D in the adult population of Western Siberia: a population-based study].

The results of research in recent years indicate a widespread low intake of vitamin D, its deficiency or lack among the population of many countries around the world. It is of interest to study vitamin D status of the population living at different geographic latitudes and depending on socio-demographic characteristics. The aim of the research is to analyze vitamin D status of the adult population living in the Omsk Region over the age of 18 in different seasons of the year. Material and methods. Evaluation of vitamin D status has been carried out in 818 adult residents (325 men and 493 women) aged 18 to 92 years, the median of age - 49 (35; 63) years. Vitamin D status was determined by the level of [25 (OH) D] in serum by the method of immuno-chemiluminescent or electrochemiluminescent analysis. Design: cross-section (simultaneous) uncontrolled epidemiological study. Research period: 2017, from January to December. Results and discussion. 25.8±1.5% showed optimal vitamin D provision, insufficient vitamin content was found in 32.5±1.6% of studied participants, and deficit in 41.4±1.7%. The median level of 25(OH)D for all subjects was in the suboptimal sufficiency range and amounted to 22.17 (16.5; 30.3) ng/ml. The lowest level of the metabolite has been registered in patients over the age of 80 years - 16.5 (13.2-22.6) ng/ml, at the age of 70-79 years - 19.1 (12.9-26.9) ng/ml. In persons aged 18-60 years, the median concentrations were higher (22.2-24.8 ng/ml) and did not differ in the age groups. Deficiencies of varying degrees were most prevalent in age groups over 80, 70-79, and 50-59 years. Slightly better sufficiency of men compared with women has been revealed (p=0.052). Seasonal differences were found in the nature of vitamin D supply characterized by a deficit state from January to June [median 18.7 (13.9; 23.5) ng/ml] and a state of insufficiency from July to December [median 24.8 (17.8; 32.04) ng/ml]. The dependence of the level of vitamin D status on the number of sunshine days during the periods of 15-90 days preceding blood collection hasn't been established. Conclusion. The problem of insufficiency of vitamin D applies to all age groups of the adult population of the region of Western Siberia, especially those over 70 years of age. For the first half of the year, predominantly deficient states are characteristic, and for the period from July to December - the state of vitamin D insufficiency in the residents.

Metastable silica high pressure polymorphs as structural proxies of deep Earth silicate melts.

Modelling of processes involving deep Earth liquids requires information on their structures and compression mechanisms. However, knowledge of the local structures of silicates and silica (SiO2) melts at deep mantle conditions and of their densification mechanisms is still limited. Here we report the synthesis and characterization of metastable high-pressure silica phases, coesite-IV and coesite-V, using in situ single-crystal X-ray diffraction and ab initio simulations. Their crystal structures are drastically different from any previously considered models, but explain well features of pair-distribution functions of highly densified silica glass and molten basalt at high pressure. Built of four, five-, and six-coordinated silicon, coesite-IV and coesite-V contain SiO6 octahedra, which, at odds with 3rd Pauling's rule, are connected through common faces. Our results suggest that possible silicate liquids in Earth's lower mantle may have complex structures making them more compressible than previously supposed.

Fe-N system at high pressure reveals a compound featuring polymeric nitrogen chains.

Poly-nitrogen compounds have been considered as potential high energy density materials for a long time due to the large number of energetic N-N or N=N bonds. In most cases high nitrogen content and stability at ambient conditions are mutually exclusive, thereby making the synthesis of such materials challenging. One way to stabilize such compounds is the application of high pressure. Here, through a direct reaction between Fe and N2 in a laser-heated diamond anvil cell, we synthesize three ironnitrogen compounds Fe3N2, FeN2 and FeN4. Their crystal structures are revealed by single-crystal synchrotron X-ray diffraction. Fe3N2, synthesized at 50 GPa, is isostructural to chromium carbide Cr3C2. FeN2 has a marcasite structure type and features covalently bonded dinitrogen units in its crystal structure. FeN4, synthesized at 106 GPa, features polymeric nitrogen chains of [N42-]n units. Based on results of structural studies and theoretical analysis, [N42-]n units in this compound reveal catena-poly[tetraz-1-ene-1,4-diyl] anions.

Breakdown of Magnetic Order in the Pressurized Kitaev Iridate ß-Li_{2}IrO_{3}.

Temperature-pressure phase diagram of the Kitaev hyperhoneycomb iridate ß-Li_{2}IrO_{3} is explored using magnetization, thermal expansion, magnetostriction, and muon spin rotation measurements, as well as single-crystal x-ray diffraction under pressure and ab initio calculations. The Néel temperature of ß-Li_{2}IrO_{3} increases with the slope of 0.9 K/GPa upon initial compression, but the reduction in the polarization field H_{c} reflects a growing instability of the incommensurate order. At 1.4 GPa, the ordered state breaks down upon a first-order transition, giving way to a new ground state marked by the coexistence of dynamically correlated and frozen spins. This partial freezing in the absence of any conspicuous structural defects may indicate the classical nature of the resulting pressure-induced spin liquid, an observation paralleled to the increase in the nearest-neighbor off-diagonal exchange Γ under pressure.

High-pressure single-crystal synchrotron diffraction study of MnGe and related compounds.

Single crystal synchrotron diffraction for pressures up to 50 GPa has revealed an essential difference in structural properties and compressibility of MnGe compared with Mn1-x Co x Ge and Mn1-x Fe x Ge solid solutions. A negative thermal expansion has been observed for MnGe at low-temperatures and high-pressures. The single crystal refinement has shown a discontinuous change of the atomic coordinates and Mn-Ge interatomic distances of MnGe in contrast to Mn0.1Co0.9Ge. These peculiarities of MnGe are likely to be associated with high-spin-low-spin transition. The relation between anisotropy of the coordination of Mn-atom and its magnetic moment is discussed.

Thermal expansion of monogermanides of 3d-metals.

Temperature dependent powder and single-crystal synchrotron diffraction, specific heat, magnetic susceptibility and small-angle neutron scattering experiments have revealed an anomalous response of MnGe. The anomaly becomes smeared out with decreasing Mn content in Mn1-x Co x Ge and Mn1-x Fe x Ge solid solutions. Mn spin state instability is discussed as a possible candidate for the observed effects.

Structural complexity of simple Fe2O3 at high pressures and temperatures.

Although chemically very simple, Fe2O3 is known to undergo a series of enigmatic structural, electronic and magnetic transformations at high pressures and high temperatures. So far, these transformations have neither been correctly described nor understood because of the lack of structural data. Here we report a systematic investigation of the behaviour of Fe2O3 at pressures over 100 GPa and temperatures above 2,500 K employing single crystal X-ray diffraction and synchrotron Mössbauer source spectroscopy. Crystal chemical analysis of structures presented here and known Fe(II, III) oxides shows their fundamental relationships and that they can be described by the homologous series nFeO·mFe2O3. Decomposition of Fe2O3 and Fe3O4 observed at pressures above 60 GPa and temperatures of 2,000 K leads to crystallization of unusual Fe5O7 and Fe25O32 phases with release of oxygen. Our findings suggest that mixed-valence iron oxides may play a significant role in oxygen cycling between earth reservoirs.

[Effect of the auxin polar transport inhibitor on the morphogenesis of leaves and generative structures during fasciation in Arabidopsis thaliana (L.) Heynh].

An increase in the proliferative activity of a shoot apical meristem (SAM) and the further accumulation of a pool of undifferentiated cells (fasciation) results in phyllotaxis changes. In the case of Arabidopsis thaliana, a typical spiral leaf arrangement is replaced by an opposite or verticillate one (depending on the level of a fasciation manifestation). Pistil development in mutant plants is accompanied by the appearance of a group of undifferentiated meristematic cells in its central part. The addition of N-1-naphthylphthalamic acid (NPA) causes an increase in the meristem volume and number of stipules in both mutant and control plants. The NPA effect on the floral morphogenesis results in a significant growth of meristemic cell pool. The interaction of different mechanisms of a meristem volume control is discussed.

[Morphological Changes in the Structure of Blastozones during Fasciation of Pisum sativum L. and Arabidopsis thaliana (L.) Heynh].

Different effects of fasciation on the structure of blastozones and ultimately on the morphology of the plants of the two families investigated was detected. The results of this study demonstrate that in Arabidopsis thaliana phyllotaxis changes, leading to the formation of whorled leaf aestivation (two or four leaf in the whorl). We also demonstrated that in Pisum sativum the number of folioles of a compound leaf increased, the number of stipules also increased, and stipules can grow together and form a structure similar to the sheath of Gramineae. Our results demonstrated that a common manifestation of fasciations in Arabidopsis and Pisum is the formation of a flattened meristem, which extended along the same line (axes of fasciation).

The most incompressible metal osmium at static pressures above 750 gigapascals.

Metallic osmium (Os) is one of the most exceptional elemental materials, having, at ambient pressure, the highest known density and one of the highest cohesive energies and melting temperatures. It is also very incompressible, but its high-pressure behaviour is not well understood because it has been studied so far only at pressures below 75 gigapascals. Here we report powder X-ray diffraction measurements on Os at multi-megabar pressures using both conventional and double-stage diamond anvil cells, with accurate pressure determination ensured by first obtaining self-consistent equations of state of gold, platinum, and tungsten in static experiments up to 500 gigapascals. These measurements allow us to show that Os retains its hexagonal close-packed structure upon compression to over 770 gigapascals. But although its molar volume monotonically decreases with pressure, the unit cell parameter ratio of Os exhibits anomalies at approximately 150 gigapascals and 440 gigapascals. Dynamical mean-field theory calculations suggest that the former anomaly is a signature of the topological change of the Fermi surface for valence electrons. However, the anomaly at 440 gigapascals might be related to an electronic transition associated with pressure-induced interactions between core electrons. The ability to affect the core electrons under static high-pressure experimental conditions, even for incompressible metals such as Os, opens up opportunities to search for new states of matter under extreme compression.

[Description of the phylogenetic structure of hydrolytic prokaryotic complex in the soils].

With the help of the molecular-biological method of cell hybridization in situ (FISH), the abundance of a physiologically active hydrolytic prokaryotic complex in chernozem and gley-podzolic soils is determined. The total proportion of metabolically active cells, which were detected by hybridization with universal probes as representatives of the domains Bacteria and Archaea, in samples of the studied soil, was from 38% for chernozem up to 78% for gley-podzolic soil of the total number of cells. The differences in the structure of chitinolytic and pectinolytic prokaryotic soil complexes are detected. Along with the high abundance of Actinobacteria and Firmicutes in the soils with chitin, an increase in phylogenetic groups such as Alphaproteobacteria and Bacteroidetes is observed.

Portable double-sided laser-heating system for Mössbauer spectroscopy and X-ray diffraction experiments at synchrotron facilities with diamond anvil cells.

The diamond anvil cell (DAC) technique coupled with laser heating is a major method for studying materials statically at multimegabar pressures and at high temperatures. Recent progress in experimental techniques, especially in high-pressure single crystal X-ray diffraction, requires portable laser heating systems which are able to heat and move the DAC during data collection. We have developed a double-sided laser heating system for DACs which can be mounted within a rather small (~0.1 m(2)) area and has a weight of ~12 kg. The system is easily transferable between different in-house or synchrotron facilities and can be assembled and set up within a few hours. The system was successfully tested at the High Pressure Station of White Beam (ID09a) and Nuclear Resonance (ID18) beamlines of the European Synchrotron Radiation Facility. We demonstrate examples of application of the system to a single crystal X-ray diffraction investigation of (Mg(0.87),Fe(3+) (0.09),Fe(2+) (0.04))(Si(0.89),Al(0.11))O(3) perovskite (ID09a) and a Synchrotron Mössbauer Source (SMS) study of (Mg(0.8)Fe(0.2))O ferropericlase (ID18).

[Prognostic value of diastolic dysfunction for sudden cardiac death of patients after myocardial infarction].

We studied prognostic value of left ventricular (LV) diastolic dysfunction (DD) in relation to sudden cardiac death (SCD) after myocardial infarction (MI). We examined 603 patients in acute period of MI (including 551 with preserved LV systolic function and DD). Duration of follow-up was 1-7 years. According to data of Cox multifactorial regression analysis LVDD was not an independent prognostic factor. ut it increased SCD risk at the account of interrelationship with such predictors as ventricular rhythm disturbances, lowering of heart rate variability, and sensitivity of cardiochronotropic component of arterial baroreflex.