[Management of patients with insomnia and polymorbidity. A draft of the clinical guidelines]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii. Proekt klinicheskikh rekomendatsii. Obshcherossiiskaya obshchestvennaya organizatsiya «Rossiiskoe obshchestvo somnologov¼.

Insomnia is a serious and widespread public health problem, but is often undetected and patients do not receive needed treatment. Insomnia is often comorbid with other diseases and conditions, such as arterial hypertension, type 2 diabetes mellitus, pain syndromes, anxiety and depressive disorders, etc. A separate problem is drug-induced insomnia, when patients develop symptoms due to other diseases treatments. Insomnia has a negative effect on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and decreased quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so clinical guidelines draft for the evaluation and treatment of insomnia in multimorbid patients is proposed. Diagnostic methods are reviewed and recommendations are given for the treatment of acute and chronic insomnia and features of the treatment of insomnia in multimorbid patients. A clinical algorithm has been proposed to determine treatment tactics in multimorbid patients.

Physiological Support of Goal-Directed Activity in Human.

The effectiveness of goal-directed human behavior and the processes underlying organization of such activity are the subjects of various biomedical studies. Here we review both classical and modern evidence on the fundamental principles of goal-directed human activity. Facts are presented about the basic mechanisms that ensure the effectiveness of goal-directed behavior and determine its physiological cost.

Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

[Management of patients with insomnia and polymorbidity: expert consensus]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii: konsensus ekspertov.

Sleep disorders are becoming increasingly important due to the high comorbidity with other diseases and a significant impact on the patient's quality of life. Insomnia is the most common sleep disorder both in the general population and in patients with multimorbid pathology. Its prevalence in the general population is 6-15%, while in patients with somatic diseases it increases up to 20-40% and can reach 90% in patients with comorbid mental disorders. Another problem is the development of drug-induced insomnia. Insomnia has negative impact on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and a worse quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so it is extremely important to identify and correct these disorders in the early stages, therefore recommendations for the diagnosis of insomnia in polymorbid patients are proposed. Modern methods of treating acute and chronic insomnia and features of insomnia treatment in polymorbid patients are also discussed.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

[Molecular Mechanisms to Optimize Gene Translation Elongation Differ Significantly in Bacteria with and without Nonribosomal Peptides].

Nonribosomal peptides play an important role in the vital activity of bacteria and have an extremely broad field of biological activity. In particular, they act as antibiotics, toxins, surfactants, siderophores, and also perform a number of other specific functions. Biosynthesis of these molecules does not occur on ribosomes but by special enzymes that form gene clusters in bacterial genomes. We hypothesized that the presence of nonribosomal peptide synthesis pathways is a specific feature of bacterial metabolism, which may affect other vital processes of the cell, including translational ones. This work was the first to show the relationship between the translation regulation mechanism of protein-coding genes in bacteria, which is largely determined by the efficiency of translation elongation, and the presence of gene clusters in the genomes for the biosynthesis of nonribosomal peptides. Bioinformatic analysis of the translation elongation efficiency of protein-coding genes was performed in 11679 bacterial genomes, some of which contained gene clusters of nonribosomal peptide biosynthesis and some of which did not. The analysis showed that bacteria whose genomes contained clusters of nonribosomal peptide biosynthetic genes and those without such gene clusters differ significantly in the molecular mechanisms that ensure translation efficiency. Thus, among microorganisms whose genomes contain gene clusters of nonribosomal peptide synthetases, a significantly smaller part of them is characterized by optimized regulation of the number of local inverted repeats, while most of them have genomes optimized by the averaged energy of inverted repeats studs in mRNA and additionally by codon composition. Our results suggest that the presence of nonribosomal peptide biosynthetic pathways in bacteria may influence the structure of the overall bacterial metabolism, which is also expressed in the specific mechanisms of ribosomal protein biosynthesis.

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

This corrects the article DOI: 10.1103/PhysRevLett.125.011801.

Pulse shape analysis in Gerda Phase II.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge using isotopically enriched high purity germanium detectors at the Laboratori Nazionali del Gran Sasso of INFN. After Phase I (2011-2013), the experiment benefited from several upgrades, including an additional active veto based on LAr instrumentation and a significant increase of mass by point-contact germanium detectors that improved the half-life sensitivity of Phase II (2015-2019) by an order of magnitude. At the core of the background mitigation strategy, the analysis of the time profile of individual pulses provides a powerful topological discrimination of signal-like and background-like events. Data from regular 228 Th calibrations and physics data were both considered in the evaluation of the pulse shape discrimination performance. In this work, we describe the various methods applied to the data collected in Gerda Phase II corresponding to an exposure of 103.7 kg year. These methods suppress the background by a factor of about 5 in the region of interest around Q ß ß = 2039  keV, while preserving ( 81 ± 3 ) % of the signal. In addition, an exhaustive list of parameters is provided which were used in the final data analysis.

Characterization of inverted coaxial 76 Ge detectors in GERDA for future double- ß decay experiments.

Neutrinoless double- ß decay of 76 Ge is searched for with germanium detectors where source and detector of the decay are identical. For the success of future experiments it is important to increase the mass of the detectors. We report here on the characterization and testing of five prototype detectors manufactured in inverted coaxial (IC) geometry from material enriched to 88% in 76 Ge. IC detectors combine the large mass of the traditional semi-coaxial Ge detectors with the superior resolution and pulse shape discrimination power of point contact detectors which exhibited so far much lower mass. Their performance has been found to be satisfactory both when operated in vacuum cryostat and bare in liquid argon within the Gerda setup. The measured resolutions at the Q-value for double- ß decay of 76 Ge ( Q ß ß  = 2039 keV) are about 2.1 keV full width at half maximum in vacuum cryostat. After 18 months of operation within the ultra-low background environment of the GERmanium Detector Array (Gerda) experiment and an accumulated exposure of 8.5 kg · year, the background index after analysis cuts is measured to be 4 . 9 - 3.4 + 7.3 × 10 - 4 counts / ( keV · kg · year ) around Q ß ß . This work confirms the feasibility of IC detectors for the next-generation experiment Legend.

Calibration of the Gerda experiment.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge with an array of about 40 high-purity isotopically-enriched germanium detectors. The experimental signature of the decay is a monoenergetic signal at Q ß ß = 2039.061 ( 7 )  keV in the measured summed energy spectrum of the two emitted electrons. Both the energy reconstruction and resolution of the germanium detectors are crucial to separate a potential signal from various backgrounds, such as neutrino-accompanied double- ß decays allowed by the Standard Model. The energy resolution and stability were determined and monitored as a function of time using data from regular 228 Th calibrations. In this work, we describe the calibration process and associated data analysis of the full Gerda dataset, tailored to preserve the excellent resolution of the individual germanium detectors when combining data over several years.

[Evaluation of the effectiveness of surgical treatment of recurrent urethral stricture].

INTRODUCTION: The recurrent course of the disease stricture is a complex problem for both the patient and the operating surgeon and requires an integrated approach to treatment only in expert centers. PURPOSE OF THE STUDY: To assess the effectiveness of methods of surgical treatment of recurrent urethral strictures. MATERIALS AND METHODS: At the University Clinic of Urology, Russian National Research Medical University named after N.I. Pirogov, an analysis of the results of surgical treatment of patients with recurrent urethral stricture from 2012 to 2020 was carried out. This work included patients who underwent surgical treatment for recurrent urethral stricture. A total of 120 men were involved in the work. The median length of the stricture was (min-max) - 2 (0.5-16 cm). In 95 (79.1%) patients, stricture of the bulbous urethra, in 15 (12.5%) - in the penile urethra, in 2 (1.7%) patients had panurethral stricture, in 6 (5.0%) - membranous urethra and in 2 (1.7%) - meatus. All patients were divided into two groups: with recurrent urethral stricture after primary DVIU (group I, n=77) and recurrent urethral stricture after primary urethroplasty (group II, n=43). Depending on the method of surgical treatment of recurrent urethral stricture, patients in group I were divided into 4 subgroups. Repeated DVIU + 3 months Autocatheterization - 16 (20.8%) patients; End-to-end urethroplasty - 37 (48.1%) patients; one-stage urethroplasty with a buccal graft or skin graft - 22 (28.6%) patients; multistage urethroplasty or perineostomy - 2 (2.5%) patients. Group II was also divided into 4 subgroups. DVIU - 17 (39.5%) patients; end-to-end urethroplasty - 6 (13.9%) patients; one-stage urethroplasty with a buccal graft or skin graft - 9 (20.9%) patients; multistage urethroplasty - 11 (16.7%) patients. Median Qmax - 4.68 ml/sec. Preoperative cystostomy was observed in 31 (25.8%) patients. RESULTS: The median follow-up was 24 months (range 12 to 76 months). Depending on the method of surgical treatment of recurrent urethral stricture, the effectiveness of DVIU according to strict indications was 75.7%. End-to-end urethroplasty showed an efficiency of -88,4%. One-stage augmentation urethroplasty had an efficiency of -77,4%, and multi-stage urethroplasty showed an efficiency of 84.6%. The IPSS value for the observation period 2 years was 2.6+/-0.9 points. The average value of Qmax at the time of observation was 19.4+/-7.1 ml/sec. The effectiveness of the treatment was 82%. During the follow-up period, a relapse was noted in 22 (18%) patients. The overall effectiveness of the treatment of recurrent urethral stricture, taking into account the treatment of recurrent cases of disease recurrence, was 97.5%. CONCLUSIONS: Urethroplasty is the treatment of choice for recurrent urethral strictures, which has been shown to be more effective than DVIU. However, the results of urethroplasty for recurrent strictures are worse than for primary strictures.

Environment-induced overheating phenomena in Au-nanowire based Josephson junctions.

Unlike conventional planar Josephson junctions, nanowire-based devices have a bridge geometry with a peculiar coupling to environment that can favor non-equilibrium electronic phenomena. Here we measure the influence of the electron bath overheating on critical current of several bridge-like junctions built on a single Au-nanowire. Using the Usadel theory and applying the two-fluid description for the normal and superconducting components of the flowing currents, we reveal and explain the mutual influence of the neighbouring junctions on their characteristics through various processes of the electron gas overheating. Our results provide additional ways to control nanowire-based superconducting devices.

[The place of riociguat in the treatment of patients with pulmonary arterial hypertension associated with systemic connective tissue diseases].

Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.

First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-ß decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}<3×10^{-12} and α^{'}/α<6.5×10^{-24} at 90% credible interval, respectively, were obtained.

Final Results of GERDA on the Search for Neutrinoless Double-ß Decay.

The GERmanium Detector Array (GERDA) experiment searched for the lepton-number-violating neutrinoless double-ß (0νßß) decay of ^{76}Ge, whose discovery would have far-reaching implications in cosmology and particle physics. By operating bare germanium diodes, enriched in ^{76}Ge, in an active liquid argon shield, GERDA achieved an unprecedently low background index of 5.2×10^{-4} counts/(keV kg yr) in the signal region and met the design goal to collect an exposure of 100 kg yr in a background-free regime. When combined with the result of Phase I, no signal is observed after 127.2 kg yr of total exposure. A limit on the half-life of 0νßß decay in ^{76}Ge is set at T_{1/2}>1.8×10^{26} yr at 90% C.L., which coincides with the sensitivity assuming no signal.

Correlation Connections between Individual-and-Typological Features, Indices of Performance of Goal-Directed Activity, and Heart Rate Variability Parameters.

Correlation analysis of the performance of goal-directed activity and heart rate variability parameters in people with different individually-typological features was conducted on the model of endosurgical training. It was found that people with low level of intro-extroversion and neuroticism, but high index of situational anxiety were more successful during goal-directed behavior. The subjects with low level of neuroticism finished the tasks more quickly, both at the beginning and at the end of the observations. It was established that the number of mistakes in subjects with low personal anxiety on the 10th day of training was lower than in high-anxious individuals. It is shown that people with high rate of intro-extroversion are characterized by more pronounced increase in parasympathetic influences during basic endosurgical training. Hence, the achievement of the result in extroverts in these experimental conditions is provided by lower physiological penalty than in introverts. The definition of psychophysiological indices could be recommended for inclusion in the complex of measures for the assessment of proficiency in the training of endosurgeons.

Anomalous magneto-resistance of Ni-nanowire/Nb hybrid system.

We examine the influence of superconductivity on the magneto-transport properties of a ferromagnetic Ni nanowire connected to Nb electrodes. We show experimentally and confirm theoretically that the Nb/Ni interface plays an essential role in the electron transport through the device. Just below the superconducting transition, a strong inverse proximity effect from the nanowire suppresses superconducting correlations at Nb/Ni interfaces, resulting in a conventional anisotropic magneto-resistive response. At lower temperatures however, the Nb electrodes operate as superconducting shunts. As the result, the magneto-resistance exhibits a strongly growing hysteretic behavior accompanied by a series of saw-like jumps. The latter are associated with the penetration/escape of individual Abrikosov vortices that influence non-equilibrium processes at the Nb/Ni interface. These effects should be taken into account when designing superconducting quantum nano-hybrids involving ferromagnetic nanowires.

Probing Majorana neutrinos with double-ß decay.

A discovery that neutrinos are Majorana fermions would have profound implications for particle physics and cosmology. The Majorana character of neutrinos would make possible the neutrinoless double-ß (0νßß) decay, a matter-creating process without the balancing emission of antimatter. The GERDA Collaboration searches for the 0νßß decay of 76Ge by operating bare germanium detectors in an active liquid argon shield. With a total exposure of 82.4 kg⋅year, we observe no signal and derive a lower half-life limit of T 1/2 > 0.9 × 1026 years (90% C.L.). Our T 1/2 sensitivity, assuming no signal, is 1.1 × 1026 years. Combining the latter with those from other 0νßß decay searches yields a sensitivity to the effective Majorana neutrino mass of 0.07 to 0.16 electron volts.