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Abstract Recent advancements in experimental and computational methods for RNA secondary structure detection have revealed the crucial role of RNA structural elements in diverse molecular processes within living cells. It has been demonstrated that the secondary structure of the entire viral genome is often responsible for performing crucial functions in the viral life cycle and also influences virus evolution. To investigate the role of viral RNA secondary structure, alongside experimental techniques, the use of bioinformatics tools is important for analyzing various secondary structure patterns, including hairpin loops, internal loops, multifurcations, external loops, bulges, stems, and pseudoknots. Here, we have introduced a Python package for analyzing RNA secondary structure elements in viral genomes, which includes the recognition of common secondary structure patterns, the generation of descriptive statistics for these structural elements, and the provision of their basic properties. We applied the developed package to analyze the secondary structures of complete viral genomes collected from the literature, aiming to gain insights into viral function and evolution. Both the package and the collection of secondary structures of viral genomes are available at http://github.com/KazanovLab/RNAsselem .

Abstract A polypyrrole-bismuth tungstate (Ppy-Bi2WO6) core-shell nanocomposite (n-type material) has been developed on a layered Ppy (p-type) base as an efficient light-capturing material exhibiting photodiode behavior. This device demonstrates promising sensitivity for light sensing and captures across a broad spectral range, from near IR to UV. The Bi2WO6/Ppy nanocomposite boasts an optimal bandgap of 2.0 eV, compared to 3.4 eV for Ppy and 2.5 eV for Bi2WO6. The crystalline size of the core-shell composite is approximately 21 nm, emphasizing its photon absorption capabilities. The composite particles, around 100 nm in length, feature a highly porous morphology that effectively traps incident photons. The performance of this optoelectronic device is evaluated using current density (J) measurements under light (Jph) and dark (Jo) conditions. In darkness, the n-p type semiconductor exhibits limited current with a Jo of −0.22 mA cm−2 at 2.0 V. When exposed to white light, the Ppy- Bi2WO6/Ppy device generates hot electrons, achieving a Jph value of 1.1 mA/cm−2 at 2.0 V. It shows a superior responsivity (R) of 6.6 mA/W at 340 nm, gradually decreasing to 6.3 mA/W at 440 nm and 4.2 mA/W at 540 nm, indicating high sensitivity across the UV-Vis spectrum. At 730 nm, the R-value is 2.6 mA/W, highlighting its sensitivity in the near IR region. Additionally, at 340 nm, the device achieves a detectivity (D) value of 0.15 × 10¹⁰ Jones, which decreases with longer wavelengths to 0.14 × 10¹⁰ Jones at 440 nm, 0.9 × 10⁹ Jones at 540 nm, and 0.63 × 10⁹ Jones at 730 nm. With its great stability, low cost, easy fabrication, and potential for mass production, this optoelectronic light sensor and photodiode device holds significant promise for industrial applications as a highly effective optoelectronic device.

BACKGROUND: Distraction arthroplasty of the ankle joint is the treatment method used for the cases of terminal osteoarthritis of the ankle joint that allows for delaying the arthrodesis or the total endoprosthesis replacement. The therapeutic effect is being achieved due to the separation of the articular surfaces (arthrodiastasis) with using the Ilizarov frame (or other devices for external fixation) for a period of 8–12 weeks. Only one research was described with the patients undergoing repeated arthroscopy of the ankle joint after the distraction arthroplasty in a combination with microfracturing of the cartilage defects, or repeated arthroscopy at the moment of removing the external fixation device (after 3 months). АIM: To study the changes in the articular surfaces according to the Outerbridge before and after the distraction arthroplasty of the ankle joint using the repeated arthroscopy of the ankle joint. METHODS: A total of 17 distraction arthroplasty surgical interventions of the ankle joint were performed (7 [41.2%] females and 10 [58.8%] males; the mean age of the patients was 48.5±13.57 years). Repeated arthroscopy of the ankle joint due to the recurrence of anterior impingement-syndrome after the distraction arthroplasty of the ankle joint within up to 12 months from the moment of removing the Ilizarov frame was carried out in 4 patients. For the evaluation of the treatment results, the Foot and Ankle Ability Measure (FAAM) scales were used, with an evaluation of pain, functions, deformity and the alignment of the foot and of the ankle joint (АОFAS Ankle-hindfoot scale), with subjective evaluation of pain (VAS); the status of the cartilage tissue in the ankle joint was evaluated using the modified Outerbridge scale. RESULTS: In all the patients, a statistically significant improvement of the functional result was found in 12 months from the moment of surgery when using the FAAM (р=0.0006) and АОFAS Ankle-hindfoot scales, as well as after removing the Ilizarov frame in 1, 3 and 6 months. The pain intensity according to the VAS scale has decreased from 6.17±1.32 cm before surgery to 2 cm (1.4; 2.1) (p=0.00002) in 12 months. The arthroscopic findings upon the repeated interventions demonstrate the development of the massive arthrofibrosis with its further degradation to the end of 6 months, also showing the restoration of the cartilage defects from Outerbridge grade IV to grade II–III. CONCLUSION: Upon the repeated arthroscopy, including the one performed at the end of 12 months after the distraction arthroplasty of the ankle joint, signs of regeneration were observed in the cartilage tissue defects with further defect coverage with a cartilage-like tissue, which, probably, determines the analgesic effect of the distraction arthroplasty of the ankle joint.

Abstract A nanocomposite with a unique satellite dish-like structure, termed arsenic (III) oxide iodide (AsO2I)/polypyrrole (Ppy) intercalated with iodide ions (AsO2I/Ppy-I), has been meticulously developed via a two-step process. It features natural satellite dish-like nanostructures, potentially serving as nanoresonators for efficient single photon absorption. With a bandgap of 2.8 eV, the AsO2I/Ppy-I nanocomposite efficiently absorbs photons in the UV and visible light regions, making it suitable for single photon detection. Impressive performance is seen in photocurrent sensitivity measurements, recording values of 0.017 mA.cm−2 under white light and 0.009 mA.cm−2 under monochromatic light at 340 nm. Additionally, it exhibits high responsivity and detectivity, with peak values at wavelengths of 340 nm and 440 nm associated with the diameter of the Satellite dish nanostructure. Cost-effectiveness and simple synthesis methods make it attractive for industrial applications, while its unique structural characteristics and enhanced optical properties position it as a valuable asset in optoelectronic technologies. It holds promise as a leading material in advanced quantum technology, marking a significant leap forward in optoelectronic technologies, with potential applications in quantum cryptography, communication, and computing.

Abstract The hippocampus has a crucial role in the formation, consolidation and recall of memories as well as in navigation related processes. These functions are in the focus of neuroscience and different disciplines have contributed to this research field for decades. Two-photon imaging in awake animals is a valuable new aspect for these observations, especially when it is supported by electrophysiology. In this study, we applied high speed two-photon hippocampal imaging through a chronically implanted, soft, transparent microelectrode (STM) device incorporated into a cranial window chamber in awake mice. We monitored the impedance of the recording sites over the course of the experiments to observe long-term changes in recording quality. The large-scale ipsilateral local field potential (LFP) recordings from the dorsal hippocampus provided reliable sharp wave-ripples (SPW-Rs), multi-unit activity (MUA) and single-unit activity (SUA) for up to two months. Calcium imaging of GCaMP6f. labeled cells from the CA1 pyramidal layer under the transparent device was possible even after six months in thy1-GCaMP6f. transgenic mice. We investigated the immune response with GFAP staining after the end of the long-term experiments. Based on our results, this dedicated transparent electrode device proved to be suitable for simultaneous two-photon imaging and large-scale electrophysiological measurements in chronic experiments in mice.

Abstract Assessments of biodiversity and ecosystem status can benefit from DNA metabarcoding as a means to streamline sample processing and specimen identification. Moreover, processing the fixation medium instead of the precious material introduces straightforward protocols that allow subsequent focus on certain organisms detected among the preserved specimens. In this study, we present a proof of concept via the analysis of freshwater invertebrate samples from the Tatra Mountain lakes (Slovakia). Besides highlighting a match between the lake-specific environmental conditions and the results of our fixative DNA metabarcoding, we observed an option to fine-tune the fixation time: to prefer two weeks over a day or a month. This effect emerged from the presence/absence of individual taxa rather than from coarse per-sample records of taxonomic richness, demonstrating that metabarcoding studies—and efforts to optimize their protocols—can use the robust metrics to explore even subtle trends. We also provide evidence that fixative DNA might better capture large freshwater species than terrestrial or meiofauna.

Abstract Mitochondrial forms account approximately 1–2% of all nonsyndromic cases of hearing loss (HL). One of the most common causative variants of mtDNA is the m.1555A > G variant of the MT-RNR1 gene (OMIM 561000). Currently the detection of the m.1555A > G variant of the MT-RNR1 gene is not included in all research protocols. In this study this variant was screened among 165 patients with HL from the Republic of Buryatia, located in the Baikal Lake region of Russia. In our study, the total contribution of the m.1555A > G variant to the etiology of HL was 12.7% (21/165), while the update global prevalence of this variant is 1.8% (863/47,328). The m.1555A > G variant was notably more prevalent in Buryat (20.2%) than in Russian patients (1.3%). Mitogenome analysis in 14 unrelated Buryat families carrying the m.1555A > G variant revealed a predominant lineage: in 13 families, a cluster affiliated with sub-haplogroup A5b (92.9%) was identified, while one family had the D5a2a1 lineage (7.1%). In a Russian family with the m.1555A > G variant the lineage affiliated with sub-haplogroup F1a1d was found. Considering that more than 90% of Buryat families with the m.1555A > G variant belong to the single maternal lineage cluster we conclude that high prevalence of this variant in patients with HL in the Baikal Lake region can be attributed to a founder effect.

Abstract Coherent beam combination offers a solution to the challenges associated with the power handling capacity of individual fibres, however, the combined intensity profile strongly depends on the relative phase of each fibre. Optimal combination necessitates precise control over the phase of each fibre channel, however, determining the required phase compensations is challenging because phase information is typically not available. Additionally, the presence of continuously varying phase noise in fibre laser systems means that a single-step and high-speed correction process is required. In this work, we use a spatial light modulator to demonstrate coherent combination in a seven-beam system. Deep learning is used to identify the relative phase offsets for each beam directly from the combined intensity pattern, allowing real-time correction. Furthermore, we demonstrate that the deep learning agent can calculate the phase corrections needed to achieve user-specified target intensity profiles thus simultaneously achieving both beam combination and beam shaping.

Background: Accelerated biological ageing is a major underlying mechanism of frailty development. This study aimed to investigate if the biological age measured by a blood biochemistry-based ageing clock is associated with frailty in geriatric rehabilitation inpatients. Methods: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, patients' biological age was measured by an ageing clock based on completed data of 30 routine blood test variables measured at rehabilitation admission. The delta of biological age minus chronological age (years) was calculated. Ordinal logistic regression and multinomial logistic regression were performed to evaluate the association of the delta of ages with frailty assessed by the Clinical Frailty Scale. Effect modification of Cumulative Illness Rating Scale (CIRS) score was tested. Results: A total of 1187 geriatric rehabilitation patients were included (median age: 83.4 years, IQR: 77.7–88.5; 57.4 % female). The biochemistry-based biological age was strongly correlated with chronological age (Spearman r = 0.883). After adjustment for age, sex and primary reasons for acute admission, higher biological age (per 1 year higher in delta of ages) was associated with more severe frailty at admission (OR: 1.053, 95 % CI:1.012–1.096) in patients who had a CIRS score of 12. The delta of ages was not associated with frailty change from admission to discharge. The specific frailty manifestations as cardiac, hematological, respiratory, renal, and endocrine conditions were associated with higher biological age. Conclusion: Higher biological age was associated with severe frailty in geriatric rehabilitation inpatients with less comorbidity burden.

Abstract Predicting wildfire spread behavior is an extremely important task for many countries. On a small scale, it is possible to ensure constant monitoring of the natural landscape through ground means. However, on the scale of large countries, this becomes practically impossible due to remote and vast forest territories. The most promising source of data in this case that can provide global monitoring is remote sensing data. Currently, the main challenge is the development of an effective pipeline that combines geospatial data collection and the application of advanced machine learning algorithms. Most approaches focus on short-term fire spreading prediction and utilize data from unmanned aerial vehicles (UAVs) for this purpose. In this study, we address the challenge of predicting fire spread on a large scale and consider a forecasting horizon ranging from 1 to 5 days. We train a neural network model based on the MA-Net architecture to predict wildfire spread based on environmental and climate data, taking into account spatial distribution features. Estimating the importance of features is another critical issue in fire behavior prediction, so we analyze their contribution to the model’s results. According to the experimental results, the most significant features are wind direction and land cover parameters. The F1-score for the predicted burned area varies from 0.64 to 0.68 depending on the day of prediction (from 1 to 5 days). The study was conducted in northern Russian regions and shows promise for further transfer and adaptation to other regions. This geospatial data-based artificial intelligence (AI) approach can be beneficial for supporting emergency systems and facilitating rapid decision-making.

Abstract Background Huntington’s disease (HD) is a progressive neurodegenerative disease, characterised by motor disturbances and non-motor (i.e., psychiatric) symptoms. Motor symptoms are the hallmark features of HD and take many forms. Their emergence is related to alterations in striatal dopaminergic neurotransmission: dopamine levels increase in the early stages of the disease, while more advanced stages are characterised by reduced dopamine levels. Such a biphasic change potentially explains the alterations in motor symptoms: increased dopamine-production induces hyperkinetic movements early in the disease course, while depleted dopamine storage leads to hypokinetic symptoms in the advanced phase. Dopamine D2-D3 partial agonists could be a promising treatment option in HD, as they have the potential to either elevate or lower the surrounding dopamine levels if the levels are too low or too high, respectively, potentially offering symptom-relief across the illness-course. Therefore, the present study aimed at exploring the effects of cariprazine, a dopamine D2-D3 partial agonist with high affinity to D3 receptors, on motor symptoms associated with HD. Methods This was a single-centre, retrospective study where sixteen patients received off-label cariprazine treatment for 12 weeks (1.5-3 mg/day). Motor symptoms were evaluated using the Motor Assessment of the Unified Huntington’s Disease Rating Scale. Least Square (LS) Mean Changes from Baseline (BL) to Week 8 and Week 12 in the Total Motor Score (TMS) were analysed using the Mixed Model for Repeated Measures method. In addition, improvement from BL to Week 8 and 12 was calculated for all motor items. Results Data of 16 patients were collected, but data of only 15 patients were analysed as one patient dropped out due to non-compliance. Significant changes were observed from BL to Week 8 (LS Mean Change: -9.4, p

Aim to retrospectively evaluate the treatment results in children with diaphyseal forearm fractures operated on using intramedullary metal osteosynthesis with titanium elastic rods according to the Elastic Stable Intramedullary Nailing (ESIN) method. Material and methods. The treatment results of 79 children were included in the retrospective analysis. The patients' mean age was 11.8 years (from 6 to16 years). Results. The results of treatment were evaluated using the classification of Anderson et al. [20] in the early postoperative period, at 2, 4 and 6 months after surgery. Conclusion. The ESIN osteosynthesis for diaphyseal fractures of the forearm bones in children allows for achieving excellent treatment results and early limb functionality in the absolute majority of cases.

Since 2012, universal single-dose HAV vaccination in children aged 3 years and older has been implemented in the Tyva Republic, a region of the Russian Federation. The aim of this prospective non-interventional observational single-center study was to determine the immunological and epidemiological effectiveness of single-dose vaccination against hepatitis A 9 to 11 years after its implementation. The anti-HAV IgG antibodies were determined in two independent cohorts of children who were vaccinated with a single dose of monovalent pediatric inactivated vaccine (HAVRIX® 720 EU) in Tyva in 2012 and recruited 9 years (Year 9 Cohort) and 11 years (Year 11 Cohort) after immunization. The seroprotection rates defined as anti-HAV antibody concentrations ≥10 mIU/mL reached 99.4% (95% CI: 98.2–99.9% [501/504]) in the Year 9 Cohort, but decreased significantly to 75.4% (95% CI: 73.0–77.6% [1006/1335]) in the Year 11 Cohort (p < 0.0001). The anti-HAV geometric mean concentrations decreased from 1446.3 mIU/mL (95% CI: 1347.1–1545.4 mIU/mL) in the Year 9 Cohort to 282.6 mIU/mL (95% CI: 203.8–360.8, p < 0.0001) in the Year 11 Cohort. The HAV vaccination program resulted in zero rates of hepatitis A incidence in the Tyva Republic since 2016. However, the limited monitoring of HAV RNA in sewage and environmental samples demonstrated the ongoing circulation of both the regional epidemic strain of HAV genotype IA and another genotype IA strain imported recently from other parts of the Russian Federation, probably due to subclinical infections in non-vaccinated children under 3 years of age. Taken together, these data indicate the effectiveness of the single-dose HAV vaccination strategy but suggest the need to expand the vaccination program to include children aged 12 months and older to achieve maximum effectiveness.

Abstract Three stable microbial consortia, each composed of Bacillus paranthracis and Staphylococcus haemolyticus strains, were isolated from milk of cows diagnosed with mastitis in three geographically remote regions of Russia. The composition of these consortia remained stable following multiple passages on culture media. Apparently, this stability is due to the structure of the microbial biofilms formed by the communities. The virulence of the consortia depended on the B. paranthracis strains. It seems plausible that the ability of the consortia to cause mastitis in cattle was affected by mutations of the cytK gene of B. paranthracis.

Abstract Klebsiella pneumoniae is associated with a variety of infections, such as pneumonia, urogenital infection, liver abscess, and bloodstream infection. It is especially dangerous for patients in medical facilities, where it can cause ventilator-associated pneumonia or intensive care unit-acquired pneumonia. The emergence of multidrug-resistant and hypervirulent strains as well as the ability to form biofilms on various medical devices complicates the treatment of such infections and makes the use of antibiotics ineffective. The application of bacteriophages is a promising alternative for combating Klebsiella pneumoniae biofilms. In the present study a cocktail of 3 bacteriophages with depolymerase activity was used to control antibiotic resistant Klebsiella pneumoniae biofilms in vitro. Biofilms were examined using optical and scanning electron microscopy. The obtained results demonstrate that the studied bacteriophage cocktail can effectively disrupt Klebsiella pneumoniae biofilms.

Abstract To compare mental, cognitive and physical outcomes between COVID-19 and non-COVID-19 patients, 3–6 months after Intensive Care Unit (ICU) treatment during the COVID-19 pandemic and to compare mental outcomes between relatives of these patients. This retrospective cohort study included 209 ICU survivors (141 COVID-19 patients and 68 non-COVID-19 patients) and 168 of their relatives (maximum one per patient) during the COVID-19 pandemic. Primary outcomes were self-reported occurrence of mental, cognitive and/or physical symptoms 3–6 months after ICU discharge. The occurrence of mental symptoms did not differ between former COVID-19 patients (34.7% [43/124]) and non-COVID-19 patients (43.5% [27/62]) (p = 0.309), neither between relatives of COVID-19 patients (37.6% [38/101]) and relatives of non-COVID-19 patients (39.6% [21/53]) (p = 0.946). Depression scores on the Hospital Anxiety and Depression Scale were lower in former COVID-19 patients, compared to non-COVID-19 patients (p = 0.025). We found no differences between COVID-19 and non-COVID-19 patients in cognitive and physical outcomes. Mental, cognitive and physical outcomes in COVID-19 ICU survivors were similar to non-COVID-19 ICU survivors. Mental symptoms in relatives of COVID-19 ICU survivors did not differ from relatives of non-COVID-19 ICU survivors, within the same time frame.

Abstract Background Epigenetic mechanisms are informational cellular processes instructing normal and diseased phenotypes. They are associated with DNA but without altering the DNA sequence. Whereas chemical processes like DNA methylation or histone modifications are well-accepted epigenetic mechanisms, we herein propose the existence of an additional quantum physics layer of epigenetics. Results We base our hypothesis on theoretical and experimental studies showing quantum phenomena to be active in double-stranded DNA, even under ambient conditions. These phenomena include coherent charge transfer along overlapping pi-orbitals of DNA bases and chirality-induced spin selectivity. Charge transfer via quantum tunneling mediated by overlapping orbitals results in charge delocalization along several neighboring bases, which can even be extended by classical (non-quantum) electron hopping. Such charge transfer is interrupted by flipping base(s) out of the double-strand e.g., by DNA modifying enzymes. Charge delocalization can directly alter DNA recognition by proteins or indirectly by DNA structural changes e.g., kinking. Regarding sequence dependency, charge localization, shown to favor guanines, could influence or even direct epigenetic changes, e.g., modification of cytosines in CpG dinucleotides. Chirality-induced spin selectivity filters electrons for their spin along DNA and, thus, is not only an indicator for quantum coherence but can potentially affect DNA binding properties. Conclusions Quantum effects in DNA are prone to triggering and manipulation by external means. By the hypothesis put forward here, we would like to foster research on “Quantum Epigenetics” at the interface of medicine, biology, biochemistry, and physics to investigate the potential epigenetic impact of quantum physical principles on (human) life.

Background: Dislocations of the forearm are rare injuries with the annual incidence of 6.1 cases per 100 000 population. Postero-lateral rotational instability is the most common complication after the conservative treatment of forearm dislocations. To restore the congruency and provide early movements in the elbow joint, the primary repair or reconstruction of the damaged ligaments of the elbow are required. Aim: to evaluate the clinical and functional results after the surgical repair of the elbow joint ligaments in acute postero-lateral rotational instability. Methods: The study was based on a retrospective analysis of a series of clinical cases, including 17 patients with acute postero-lateral rotational instability, among them 5 simple forearm dislocations, 9 fracture-dislocations of the forearm and 3 fractures of the radial head. Refixation of the lateral ulnar ligament was performed with anchor fixation or bone tunnels. The evaluation was performed using the clinical aspects (the lateral pivot shift test, the range of motion), according to the scale for the evaluation of the elbow joint functional condition (MEPS), Oxford scale of the elbow joint evaluation (OEC), the X-ray results were also estimated. Results: In all the cases the elbow joint stability had been achieved, according to the X-ray and clinical aspects. In 4 cases, additional plasty of the medial collateral ligament was needed and performed after the restoration of the lateral ligament complex. According to the MEPS scale, 58% of the achieved results were excellent, 35% were good and 5.8% were satisfactory. Conclusion: The restoration of the lateral ulnar collateral ligament complex is a safe and effective procedure, which restores the elbow joint stability and allows the patients to return to full physical activity and avoid the development of postero-lateral rotational joint instability.

Background: Еndoscopic neurolysis of the sciatic nerve has proven itself as a low traumatic and effective technique of treatment for deep gluteal pain syndrome and sciatic nerve neuropathy. Until now, there have been no publications dedicated to the parietal peritoneum damage after endoscopic sciatic nerve decompression. Clinical case description: A 70-year-old female patient with deep gluteal pain syndrome and sciatic nerve neuropathy on the right side and failure of a conservative treatment. According to the VAS scale, the severity of pain syndrome was 10 cm. The severity of the motor dysfunction, according to the BMRC scale, was 4 points. The severity of the sensitive dysfunction, according to the Seddon scale, was 3 points. The functional activity of the lower limb, according to the LEFS scale, was 48 points. The instrumental investigation of the sciatic nerve included MRI, ultrasound, and ENMG. Endoscopic sciatic nerve decompression was performed in the prone position with saline irrigation using the technique published before. After the surgery, an ultrasound study and a CT scan were performed, which determined the presence of a free fluid in the abdominal cavity, and edema of the right retroperitoneal space. The patient underwent laparoscopy, which revealed the area of the parietal peritoneum damage in the lower floor, with a free saline fluid detected in the abdominal cavity, which was evacuated. The patient was discharged from the hospital on the 10th day after the surgery. 6 months after the surgery, the functional activity of the lower extremity, according to the LEFS scale, was 52 points. Pain syndrome, according to the VAS scale, was 8 cm. The severity of the motor dysfunction, according to the BMRC scale, was 4 points. The severity of the sensitive dysfunction, according to the Seddon scale, was 3 points. The performed surgical endoscopic treatment was rendered ineffective. Conclusion: The method of endoscopic sciatic nerve decompression with saline pumping has a risk of the following complication: damaging the parietal peritoneum, saline penetration into the abdominal cavity, edema of the retroperitoneal space. To decrease the risk of this complication, it is necessary to observe the specific surgical conditions such as: controlled hypotension in a patient and a low pressure in the arthroscopic pump, the time of surgery not exceeding 1 hour, and the saline consumption not exceeding 10 liters. It is also crucial not to perform the dissection and neurolysis too proximal to the piriformis area.

Abstract We present a new experimental study of the quantum entanglement of photon pairs produced in positron-electron annihilation at rest. Each annihilation photon has an energy that is five orders of magnitude higher than the energy of photons in optical experiments. It provides a unique opportunity for controlled Compton pre-scattering of initial photons before the polarization measurements. The experimental setup includes a system of Compton polarimeters to measure the angular correlations of annihilation photons in initial and thus prepared pre-scattered states. For the first time, a direct comparison of the polarization correlations of initial and pre-scattered annihilation photons has been carried out. The angular distributions of scattered in polarimeters photons turned out to be the same for both types of events. Moreover, the correlation function in the Bell’s inequality is also the same for both states. We discuss the implications of our results for quantum measurement theory and for the quantum-entangled positron emission tomography.

The audiological features of hearing loss (HL) in patients with autosomal recessive deafness type 1A (DFNB1A) caused by splice site variants of the GJB2 gene are less studied than those of patients with other variants of this gene. In this study, we present the audiological features of DFNB1A in a large cohort of 134 patients with the homozygous splice site variant c.-23+1G>A and 34 patients with other biallelic GJB2 genotypes (n = 168 patients with DFNB1A). We found that the preservation of hearing thresholds in the speech frequency range (PTA0.5,1.0,2.0,4.0 kHz) in patients with the c.[-23+1G>A];[-23+1G>A] genotype is significantly better than in patients with the "severe" c.[35delG];[35delG] genotype (p = 0.005) and significantly worse than in patients with the "mild" c.[109G>A];[109G>A] genotype (p = 0.041). This finding indicates a "medium" pathological effect of this splice site variant on hearing function. A detailed clinical and audiological analysis showed that in patients with the c.[-23+1G>A];[-23+1G>A] genotype, HL is characterized as congenital or early onset (57.5% onset before 12 months), sensorineural (97.8%), bilateral, symmetrical (82.8%), variable in severity (from mild to profound HL, median hearing threshold in PTA0.5,1.0,2.0,4.0 kHz is 86.73±21.98 dB), with an extremely "flat" audioprofile, and with a tendency toward slow progression (a positive correlation of hearing thresholds with age, r = 0.144, p = 0.041). In addition, we found that the hearing thresholds in PTA0.5,1.0,2.0,4.0 kHz were significantly better preserved in females (82.34 dB) than in males (90.62 dB) (p = 0.001). We can conclude that in patients with DFNB1A caused by the c.-23+1G>A variant, male sex is associated with deteriorating auditory function; in contrast, female sex is a protective factor.

Abstract People vary both in their embrace of their society’s traditions, and in their perception of hazards as salient and necessitating a response. Over evolutionary time, traditions have offered avenues for addressing hazards, plausibly resulting in linkages between orientations toward tradition and orientations toward danger. Emerging research documents connections between traditionalism and threat responsivity, including pathogen-avoidance motivations. Additionally, because hazard-mitigating behaviors can conflict with competing priorities, associations between traditionalism and pathogen avoidance may hinge on contextually contingent tradeoffs. The COVID-19 pandemic provides a real-world test of the posited relationship between traditionalism and hazard avoidance. Across 27 societies (N = 7844), we find that, in a majority of countries, individuals’ endorsement of tradition positively correlates with their adherence to costly COVID-19-avoidance behaviors; accounting for some of the conflicts that arise between public health precautions and other objectives further strengthens this evidence that traditionalism is associated with greater attention to hazards.

Abstract Pumilio proteins are RNA-binding proteins that control mRNA translation and stability by binding to the 3’ UTR of target mRNAs. Mammals have two canonical Pumilio proteins, PUM1 and PUM2, which are known to act in many biological processes, including embryonic development, neurogenesis, cell cycle regulation and genomic stability. Here, we characterized a new role of both PUM1 and PUM2 in regulating cell morphology, migration, and adhesion in T-REx-293 cells, in addition to previously known defects in growth rate. Gene ontology analysis of differentially expressed genes in PUM double knockout (PDKO) cells for both cellular component and biological process showed enrichment in categories related to adhesion and migration. PDKO cells had a collective cell migration rate significantly lower than that of WT cells and displayed changes in actin morphology. In addition, during growth, PDKO cells aggregated into clusters (clumps) due to an inability to escape cell–cell contacts. Addition of extracellular matrix (Matrigel) alleviated the clumping phenotype. Collagen IV (ColIV), a major component of Matrigel, was shown to be the driving force in allowing PDKO cells to monolayer appropriately, however, ColIV protein levels remained unperturbed in PDKO cells. This study characterizes a novel cellular phenotype associated with cellular morphology, migration, and adhesion which can aid in developing better models for PUM function in both developmental processes and disease.

Severe congenital neutropenia (SCN) comprises a heterogenous group of disorders characterized by a constantly low absolute neutrophil count (ANC) below 0.5 × 109/l in the peripheral blood and maturation arrest of the myelopoiesis in the bone marrow at the promyelocyte/myelocyte stage that lead to early onset of severe bacterial infections in affected patients. Clinical symptoms of congenital neutropenia include sepsis, recurrent respiratory tract infections, mouth ulceration, chronic gingivitis, bacterial skin infections, and urinary tract infections. Patients with SCN often develop periodontitis despite standard medical and dental care. We present oral symptoms in our patient afflicted with SCN due to homozygous mutations in the JAGN1 gene, based on 16 years of observation and treatment at the Paediatric Dentistry Clinic of Children’s Memorial Health Institute. In our patient, oral cavity changes typical for SCN – in the form of gingivitis and bleeding from periodontal tissues – appeared around the age of 2 and led to the premature loss of primary teeth. The patient also developed an advanced periodontal disease in the permanent dentition, resulting in the loss of 21 teeth at 15 years of age. Dental care of patients with SCN should be carried out in close cooperation with an immunologist, and dental procedures associated with the risk of bacteremia require antibiotic prophylaxis.

Abstract Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.

Background: Posttraumatic axillary nerve neuropathy is a widely spread pathology, more often seen after a shoulder joint trauma. It can also appear as a complication after orthopedic surgeries, for example, after the Latarjet procedure for shoulder stabilization. The technique of open axillary nerve decompression is very popular but has a number of disadvantages: a large trauma of soft tissue, severe bleeding, a high rate of complications, and also a poor cosmetic effect. The endoscopic surgical technique of decompression is an effective and less traumatic alternative to open procedures. Clinical case description: We present the results of endoscopic transcapsular axillary nerve decompression in 5 patients with a clinical picture of neuropathic pain syndrome, hypoesthesia in the deltoid area, hypotrophy of the deltoid muscle, who were operated from 2018 to 2021. The mean age of patients was 44.414.9. An original surgical technique of decompression was developed and applied to all the patients which included arthroscopy of the shoulder joint with diagnostic and treatment components and transcapsular endoscopic axillary nerve decompression in the beach-chair position. The statistical analysis was performed using the MannWhitney U test. According to the VAS-scale, the severity of pain syndrome before the surgery was 64.6 points, while 6 months after the surgery it decreased to 1.40.5 points (p 0.05). According to the DASH scale, the function of the shoulder joint before the surgery was 77.66.9 points, and 6 months after surgery it increased to 125.2 points (p 0.05). According to the BMRC scale (M0M5), the strength of the deltoid muscle before the surgery was 20.4 points, and after the surgery it increased to 4.40.5 points (p 0.05). The range of motion in the shoulder joint was as follows: before the surgery flexion 10745.6, extension 10249, external rotation 2213.6; 6 months after the surgery flexion 15425.6, extension 15622.4, external rotation 508 (p 0.05). The thickness of the middle portion of the deltoid muscle according to the US was 7.21.04 mm before the surgery, 11.81.44 mm after the surgery (p 0.05). All the patients (100%) at a long-term follow-up noticed complete relief of pain and regression of the neurological symptoms. Conclusion: The achieved results allow us to characterize the method of endoscopic transcapsular decompression as a reproducible, minimally invasive and highly effective technique, providing pain relief to patients, curing neurological and intraarticular pathology, thus promoting early restoration of the upper limb function in the treated group of patients.

Background: Distal femoral fractures are a widely spread problem in traumatology, which can be caused by both a high-energy trauma and a low-energy trauma in senile patients with osteoporosis. The conservative treatment shows little promise. The surgical treatment of patients is still a challenge for orthopedic surgeons regarding both the technical aspect and a high risk of complications. There are several surgical methods with the use of plates and nails, but there is still no universal conception of the surgical treatment. Aim: comparative analysis of methods of intramedullary retrograde osteosynthesis and bone osteosynthesis in the treatment of fractures of the distal femur. Methods: In this study, we evaluated the treatment results of 46 patients who underwent osteosynthesis for intraarticular fractures of the distal femur using an intramedullary retrograde nail. The evaluation was carried out based on such parameters as the duration of the operation and the time from the moment of injury to the operation, the intraoperative blood loss and the function of the knee joint. On average, the operation time using a retrograde femoral nail was 45 minutes. Reducing the duration of the operation improved the functional results of the treatment. Reducing the operation time when installing a retrograde intramedullary nail was achieved with a relatively simple technique for installing this type of a fixator and the use of minimally invasive approaches. Results: On average, the operation time using a retrograde femoral nail was 45 minutes. Reducing the duration of the operation improved the functional results of treatment. Reducing the operation time when installing a retrograde intramedullary nail was due to a relatively simple technique for installing this type of fixator and the use of minimally invasive approaches. One year after the surgery, the following mean values were achieved: 78 (6485) points according to the KSS knee score, 85 (6889) points according to the KSS function score, 3.1 (1.34.2) cm for the severity of pain syndrome according to the VAS scale, 105 (88120) degrees for the flexion in the knee joint. However, a number of post-op complications were observed: deep vein thrombosis of lower extremities was found in 6 (13.1%) patients, formation of a false-joint was seen in 3 (6.5%) patients, 1st grade arthritis of the knee joint was detected in 36 patients (78.2%), 2nd grade arthritis was observed in 10 patients (21.8%). 3rd grade arthritis was not detected. 3.5 years after the operation, none of the patients needed a knee joint replacement. Conclusion: Retrograde intramedullary osteosynthesis in type C distal femoral fractures promotes early rehabilitation, a complete recovery of the knee joint function and healing of the fracture, and represents an effective method of treatment.

Abstract Background Many patients who recovered from COVID are still suffering from pulmonary dysfunction that can be persistent even for months after infection. Therefore, treatment to prevent irreversible impairment of lung function is needed. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory and antifibrotic effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae. Methods The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history (with the first symptoms of COVID appear no earlier than 2 months before screening) and having fibrotic changes in the lungs, decreased lung function (percentage of predicted FVC and/or DLCO

Background: Thoracic outlet syndrome compression of the brachial plexus in the area between the clavicle and the first rib is a commonly spread and important pathology. It occurs, as usual, after a trauma or due to an anatomical malformation of this area. Thoracic outlet syndrome can be combined with a shoulder joint pathology. In the case of a conservative treatment's failure, the standard surgical procedure is decompression of the brachial plexus in the thoracic aperture. This procedure is usually done via an open approach. The development of the endoscopic surgical technique of decompression allows reducing the risk of complications and recurrences, improving the cosmetic result and relieving the rehabilitation period. Clinical case description: A 73-year-old female patient with a clinical picture of posttraumatic brachial plexopathy and a massive shoulder rotator cuff tear. The patient underwent a conservative treatment for 6 months after the trauma without a significant improvement. To confirm the diagnosis, ENMG and an ultrasound investigation of the brachial plexus, as well as MRI of the shoulder joint were performed. Simultaneous shoulder joint arthroscopy with subacromial spacer implantation and brachial plexus decompression in the thoracic aperture were performed to the patient. According to the VAS-scale (Visual Analogue Scale), the severity of pain syndrome before the surgery was 10 cm, while 6 months after the surgery, it decreased to 1 cm. According to the DASH scale (Disabilities of the Arm, Shoulder, and Hand), the dysfunction of the of shoulder joint before the surgery was 76 points, while 6 months after the surgery, it decreased to 12 points. The range of motion in the shoulder joint before the surgery was as follows: flexion 105, abduction 95, external rotation 15, which increased to 160, 165, and 45, respectively, 6 months after the surgery. Conclusion: The results allow us to characterize the method of simultaneous shoulder joint arthroscopy and endoscopic decompression of the brachial plexus in the thoracic aperture as a low-traumatic and effective technique. The technique provides complete brachial plexus decompression in the thoracic aperture which promotes restoration of the function of the upper extremity and shoulder joint, and elimination of pain syndrome from the upper extremity area.

Abstract Small and medium-sized reservoirs play an important role in water systems that need to cope with climate variability and various other man-made and natural challenges. Although reservoirs and dams are criticized for their negative social and environmental impacts by reducing natural flow variability and obstructing river connections, they are also recognized as important for social and economic development and climate change adaptation. Multiple studies map large dams and analyze the dynamics of water stored in the reservoirs behind these dams, but very few studies focus on small and medium-sized reservoirs on a global scale. In this research, we use multi-annual multi-sensor satellite data, combined with cloud analytics, to monitor the state of small (10–100 ha) to medium-sized (> 100 ha, excluding 479 large ones) artificial water reservoirs globally for the first time. These reservoirs are of crucial importance to the well-being of many societies, but regular monitoring records of their water dynamics are mostly missing. We combine the results of multiple studies to identify 71,208 small to medium-sized reservoirs, followed by reconstructing surface water area changes from satellite data using a novel method introduced in this study. The dataset is validated using 768 daily in-situ water level and storage measurements (r2 > 0.7 for 67% of the reservoirs used for the validation) demonstrating that the surface water area dynamics can be used as a proxy for water storage dynamics in many cases. Our analysis shows that for small reservoirs, the inter-annual and intra-annual variability is much higher than for medium-sized reservoirs worldwide. This implies that the communities reliant on small reservoirs are more vulnerable to climate extremes, both short-term (within seasons) and longer-term (across seasons). Our findings show that the long-term inter-annual and intra-annual changes in these reservoirs are not equally distributed geographically. Through several cases, we demonstrate that this technology can help monitor water scarcity conditions and emerging food insecurity, and facilitate transboundary cooperation. It has the potential to provide operational information on conditions in ungauged or upstream riparian countries that do not share such data with neighboring countries. This may help to create a more level playing field in water resource information globally.

Abstract The Mezmaiskaya cave is located on the North Caucasus near the border that divides Europe and Asia. Previously, fossil remains for two Neanderthals were reported from Mezmaiskaya Cave. A tooth from the third archaic hominin specimen (Mezmaiskaya 3) was retrieved from layer 3 in Mezmaiskaya Cave. We performed genome sequencing of Mezmaiskaya 3. Analysis of partial nuclear genome sequence revealed that it belongs to a Homo sapiens neanderthalensis female. Based on a high-coverage mitochondrial genome sequence, we demonstrated that the relationships of Mezmaiskaya 3 to Mezmaiskaya 1 and Stajnia S5000 individuals were closer than those to other Neanderthals. Our data demonstrate the close genetic connections between the early Middle Palaeolithic Neanderthals that were replaced by genetically distant later group in the same geographic areas. Based on mitochondrial DNA (mtDNA) data, we suggest that Mezmaiskaya 3 was the latest Neanderthal individual from the early Neanderthal’s branches. We proposed a hierarchical nomenclature for the mtDNA haplogroups of Neanderthals. In addition, we retrieved ancestral mtDNA mutations in presumably functional sites fixed in the Neanderthal clades, and also provided the first data showing mtDNA heteroplasmy in Neanderthal specimen.

Abstract Background More than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress-induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise). Results We identified 44,680 CAGE TSS clusters (including 3764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of “classic” transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors. Conclusions Transcriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.

Background: Suprascapular nerve neuropathy is a commonly spread pathology, caused by a traction force trauma or compression in the scapular notch area. In the case of a conservative treatment failure, a standard surgical procedure is neurolysis (decompression) of the suprascapular nerve in the scapular notch. This procedure can be done in an open manner or endoscopically. Aims: to evaluate the results of endoscopic decompression of the suprascapular nerve in the scapular notch area at a 6 months follow-up. Methods: We operated 10 patients with the clinical picture of posttraumatic suprascapular nerve neuropathy in the period from 2015 to 2021. The mean age of patients was 52.311.8. All the patients underwent the shoulder joint and subacromial space arthroscopy, and decompression of the suprascapular nerve in the scapular notch area. Results: According to the VAS-scale, the severity of pain syndrome before the surgery was 6 cm, while in 6 months after the surgery it decreased to 2 cm. According to the DASH scale, the dysfunction of the of shoulder joint before the surgery was 70 points, in 6 months after the surgery it decreased to 10 points. The range of motion in the shoulder joint before the surgery was: flexion 15514,4, abduction 14042, external rotation 125,6; 6 months after the surgery we observed: flexion 17415,6, abduction 17514,4, external rotation 489. Conclusion: The obtained results let us characterize the method of endoscopic decompression of the suprascapular nerve as a low-traumatic and effective technique, which promotes restoration of the function of the suprascapular nerve and shoulder joint, and elimination of pain syndrome from the shoulder area.

Abstract Being the second most abundant element on earth after oxygen, silicon remains the working horse for key technologies for the years. Novel photonics platform for high-speed data transfer and optical memory demands higher flexibility of the silicon modification, including on-chip and in-bulk inscription regimes. These are deepness, three-dimensionality, controllability of sizes and morphology of created modifications. Mid-IR (beyond 4 µm) ultrafast lasers provide the required control for all these parameters not only on the surface (as in the case of the lithographic techniques), but also inside the bulk of the semiconductor, paving the way to an unprecedented variety of properties that can be encoded via such an excitation. We estimated the deposited energy density as 6 kJ cm−3 inside silicon under tight focusing of mid-IR femtosecond laser radiation, which exceeds the threshold value determined by the specific heat of fusion (~ 4 kJ cm−3). In such a regime, we successfully performed single-pulse silicon microstructuring. Using third-harmonic and near-IR microscopy, and molecular dynamics, we demonstrated that there is a low-density region in the center of a micromodification, surrounded by a “ring” with higher density, that could be an evidence of its micro-void structure. The formation of created micromodification could be controlled in situ using third-harmonic generation microscopy. The numerical simulation indicates that single-shot damage becomes possible due to electrons heating in the conduction band up to 8 eV (mean thermal energy) and the subsequent generation of microplasma with an overcritical density of 8.5 × 1021 cm−3. These results promise to be the foundation of a new approach of deep three-dimensional single-shot bulk micromachining of silicon.

Breast and other estrogen receptor α-positive cancers tend to develop resistance to existing drugs. Chalcone derivatives possess anticancer activity based on their ability to form covalent bonds with targets acting as Michael acceptors. This study aimed to evaluate the anticancer properties of a series of chalcones (7a–l) with a sulfonamide group attached to the vinyl ketone moiety. Chalconesulfonamides showed a potent antiproliferative effect at low micromolar concentrations against several cancer cell lines, including ERα-positive 4-hydroxytamoxifen-resistant MCF7/HT2. Immunoblotting of samples treated with the lead compound 7e revealed its potent antiestrogenic activity (ERα/GREB1 axis) and induction of PARP cleavage (an apoptosis marker) in breast cancer cells. The obtained compounds represent a promising basis for further development of targeted drugs blocking hormone pathways in cancer cells.

Abstract The advent of free-electron lasers opens new routes for experimental high-pressure physics, which allows studying dynamics of condensed matter with femtosecond resolution. A rapid compression, that can be caused by laser-induced shock impact, leads to the cascade of high-pressure phase transitions. Despite many decades of study, a complete understanding of the lattice response to such a compression remains elusive. Moreover, in the dynamical case (in contrast to quasi-static loading) the thresholds of phase transitions can change significantly. Using the third harmonic pump–probe technique combined with molecular dynamics to simulate the terahertz (THz) spectrum, we revealed the dynamics of ultrafast laser-induced phase transitions in MgF2 in all-optical experiment. Tight focusing of femtosecond laser pulse into the transparent medium leads to the generation of sub-TPa shock waves and THz coherent phonons. The laser-induced shock wave propagation drastically displaces atoms in the lattice, which leads to phase transitions. We registered a cascade of ultrafast laser-induced phase transitions (P42/mnm ⇒ Pa-3 ⇒ Pnam) in magnesium fluoride as a change in the spectrum of coherent phonons. The phase transition has the characteristic time of 5–10 ps, and the lifetime of each phase is on the order of 40–60 ps. In addition, phonon density of states, simulated by molecular dynamics, together with third-harmonic time-resolved spectra prove that laser-excited phonons in a bulk of dielectrics are generated by displacive excitation (DECP) mechanism in plasma mediated conditions.

Background: Iron has dual properties: it may promote both tumor growth and cell apoptosis. Compared to healthy cells, cancer cells are more dependent on the iron levels. Ferroptosis can be triggered directly in cancer cells, which would result in their self-destruction. Identification of iron balance abnormalities and their correction could impact the effects of specific treatments in cancer patients. Aim: To assess the prevalence of iron deficiency in patients with metastatic colorectal cancer (mCRC) and to identify an association of low serum iron levels with clinical and morphological characteristics of the disease. Materials and methods: The study included 69 treatment-nave patients with mCRC. Iron deficiency was defined as low serum iron levels before the initiation of any specific therapy: serum iron concentration 10.7 mcmol/L in men and 9.0 mcmol/L in women. Results: The mean age of the mCRC patients was 61.1 years (range, 28 to 83 years), 35/69 (50.7%) were men. The bigger proportion of the tumors was left-sided (62.3%). In 48.3% of the patients, the disease was diagnosed at the metastatic stage. The most frequent locations of metastasis were liver (41.3%) and lungs (32.1%). 55.1% (38/69) of the patients had undergone a non-radical resection or primary curative surgery. KRAS mutations were found in 37.7% of the patients. Low serum iron levels were found in 53.6% (37/69) of the total sample of the mCRC patients and in 72.4% (19/38) of the patients with a non-resected primary tumor (p = 0.05). Conclusion: Irrespective on the clinical and morphological characteristics, the majority of patients with metastatic colorectal cancer have iron deficiency anemia before the initiation of specific anti-tumor therapy.

Rationale: Non-small cell lung cancer (NSCLC) is an aggressive disease with median survival of 1214 months in inoperable patients in the pre-immunotherapy era. Nowadays, under treatment with checkpoint inhibitors median survival is 1922 months. However, only a proportion of patients are sensitive to immune therapy. In this regard, inclusion into clinical trials remains a priority option for patients from medical perspective. Aim: To compare the results in NSCLC patients treated in accordance with the current clinical guidelines and in international clinical trials using the propensity score matching. Materials and methods: The study included data from 344 patients with histologically verified unresectable advanced NSCLC without activating mutations, who received the 1st line systemic medical therapy at various combinations (single agent chemotherapy, platinum doublet-based therapy, chemoimmunotherapy, single agent immunotherapy) within the compulsory health insurance (CHI), and from 90 patients, who received therapy in clinical trials. A direct comparison of long-term treatment results was carried out with the log-rank method. To exclude any influence of individual factors on survival rates, an univariate regression analysis and pseudorandomization accounting for these factors were carried out. Results: The direct comparison of the treatment results showed a higher progression-free survival rate in the patients treated according to clinical trial protocols, than in those treated under CHI (13.3 [95% confidence interval (CI) 8.118.5] months vs 6.4 [95% CI 5.96.9] months). Pseudorandomization of patients based on a combination of statistically significant parameters from the CHI and clinical trial groups showed a significantly longer time to progression in the trial group (13.3 [95% CI 8.318.3] vs 6.3 [95% CI 4.87.7] months). Conclusion: Participation in clinical trials is per se a factor that can significantly impact the longer duration of the treatment effect. This indicates the necessity of the most active use of this tool in clinical practice.

Background: Currently, there is a tendency to increasing the proportion of knee joint organ-preserving surgeries. High tibial osteotomy (HTO) has proven itself a good method for the treatment of the knee joint varus deformity in extra-articular deformity cases. The question of the perfect angle of correction, which will not significantly impair the biomechanics of the knee and adjacent joints, remains controversial, as well as the issue of preventing excessive hypercorrection as an osteotomy complication. Clinical case description: A clinical case of a 59-year-old patient who underwent primary and revision HTOs is analyzed in this article. The patient had a varus deformity of the left lower limb with isolated medial knee osteoarthritis. The patients body mass index (BMI) was 28 kg/m2. The patient complained only of pain and a limited range of motion in the knee joint. According to the arthroscopy and magnetic resonance imaging (MRI) data, there was a cartilage damage classified as Outerbridge 4 stage of the medial compartment. There were no signs of a lateral compartment cartilage damage and patellofemoral joint arthritis. The varus deformity of the knee joint was 10. The patient underwent a medial high tibial open wedge osteotomy. During the preoperative planning, topograms of the lower limb with weight bearing were used. The clinical status before the operation, according to the used scales, was as follows: Knee injury and Osteoarthritis Outcome Score (KOOS) 46 points, Visual Analogue Scale (VAS) 7 cm, American Orthopaedic Foot and Ankle Society (AOFAS) 92 points. 6 months after the initial surgery, the clinical status was as follows: knee joint VAS 1 cm, ankle joint VAS 5 cm, KOOS 88 points, AOFAS 63 points. During the clinical examination and according to the instrumental studies, excessive valgus hypercorrection of 11.2 was noted. Also, the tibial plafond inclination (TPI) and the talar inclination (TI) were significantly increased. 1.5 years after the primary osteotomy, a revision closed wedge osteotomy was performed. The valgus deformity of the knee joint became 3, the axis of the ankle joint changed to the normal values. The clinical and functional results 6 months after the revision osteotomy were the following: KOOS 92 points, AOFAS 99 points, pain in the knee and ankle joint 1 cm by the VAS scale. Conclusions: The case showed that the careful preoperative planning and the use of additional methods for monitoring the intraoperative correction were important. Excessive valgus hypercorrection promotes good regeneration of the medial compartment cartilage; however, it overloads a lateral compartment and adversely affects the ankle joint and foot.

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate.

Abstract The region of the Western Carpathians is, among other aspects, very important for survival and diversity of European freshwater fauna due to the presence of a large number of (sub)mountain springs and streams. However, these ecologically and faunistically diversified habitats are still understudied in the context of genetic diversity and population structure of their inhabitants. This study focuses on genetic diversity and distribution patterns of the caddisfly Rhyacophila tristis, common and widespread representative of mountain freshwater fauna. Analysis of the COI mitochondrial marker revealed presence of the western and eastern lineages, with samples from both lineages being grouped in BOLD (Barcode of Life Data System) into separate BINs (Barcode Index Numbers). Our data indicates that eastern lineage (BIN_E) is more closely related to the Balkan populations than to co-occurring western lineage (BIN_W), and that the contact zone of the lineages passes through the W Carpathians. The study revealed phylogeographic and demographic differences between lineages, supporting hypothesis of their evolutionary independence and specific ecological preferences. The obtained genetic data of the R. tristis population from W Carpathians improved our knowledge about population genetics of this aquatic species and can contribute to understanding the state and evolution of biodiversity of freshwater ecosystems in Europe.

Background: The technique of regional isolated perfusion makes it possible to increase local levels of an anti-tumor agent, to perform the treatment procedure under hypothermia or hyperthermia, to reduce or even eliminate any systemic effect of a cytostatic on the patient. In this context, the use of isolated perfusion to modify the pH milieu of the tumor seems to be a promising strategy that could potentially ensure the anti-tumor effect. Aim: To evaluate the efficacy of a rat limb perfusion with 4% NaHCO3 solution in vivo in the Pliss' lymphosarcoma rat graft model. Materials and methods: The experiment was carried out in Wistar rats with Pliss' lymphosarcoma graft. The isolated limb was perfused with an isotonic sodium chloride solution (the control group) or a 4% sodium bicarbonate solution (the treatment group). The following parameters were assessed: tumor node growth over time, survival rate, hematology analysis at various time points of the experiment, and histological examination of autopsy samples from the tumor. Results: Median survival in the group perfused with 4% NaHCO3 (N = 6) was 17.2 days, whereas in the non-perfused group (the pathogenesis group) (N = 4) and in the group perfused with isotonic saline (N = 5) they were 13.2 and 13.6 days, respectively. The risk of death in the treatment group was lower compared to that in the control group (Cox regression model, hazard ratio 0.129; 95% confidence interval 0.0280.583; p = 0.0079). There were no significant differences in the tumor growth rate over time in the perfused groups. Conclusion: A single exposure of the tumor micro-milieu in the model with isolated perfusion of the limb with Pliss' lymphosarcoma graft does not lead to any changes in the tumor growth kinetics, but is associated with a change in the animal survival.

Abstract In this paper we describe the properties of the crystal of guanylurea hydrogen phosphate (NH $$_2$$ 2 ) $$_2$$ 2 CNHCO(NH $$_2$$ 2 )H $$_2$$ 2 PO $$_3$$ 3 (GUHP) and propose its application in terahertz photonics and optoelectronics. GUHP crystal has a wide window of transparency and a high optical threshold in the visible and NIR spectral regions and narrow absorption bands in the terahertz frequency range. The spectral characteristics of absorption and refraction in the THz range were found to be strongly dependent on crystal temperature and orientation. Computer simulations made it possible to link the nature of the resonant response of the medium at THz frequencies with the molecular structure of the crystal, in particular, with intermolecular hydrogen bonds and the layered structure of the lattice. The possibility of application of the crystal under study for the conversion of femtosecond laser radiation from visible an NIR to terahertz range was demonstrated. It was shown that dispersion properties of the crystal allow the generation of narrow band terahertz radiation, whose spectral properties are determined by conditions close to phase matching. The properties of the generated terahertz radiation under various temperatures suggest the possibility of phonon mechanism of enhancement for nonlinear susceptibility of the second order.

Background: Giant tumors of the abdominal cavity, as a rule, occur in elderly patients with characteristic features and represent a serious problem in terms of choosing a radical method of therapy. Of particular difficulty are cases of giant serous endometrial cancer, requiring a differential diagnosis with ovarian cancer. Clinical case description: A clinical case of giant serous endometrial cancer mimicking ovarian cancer in a 55-year-old woman is presented. The patient came to the oncology department with complaints of abdominal enlargement, difficulty breathing and bloody discharge from the genital tract. The examination revealed the following: a giant formation (4065 cm), occupying the entire pelvic and the entire abdominal cavities, ascites, lesions of the retroperitoneal lymph nodes, and the greater omentum, an umbilical hernia. A chest CT showed multiple contrast-accumulating circular shadows of 313 mm (metastases). By the decision of the council, after the preliminary chemoembolization of both the uterine and ovarian arteries, a supravaginal amputation of the uterus with appendages was performed, along with the resection of the greater omentum, removal of the umbilical hernia with positioning a plastic mesh implant and excision of an excess skin flap. The histological examination of the intraoperative material made it possible to verify the diagnosis of a serous endometrial carcinoma with subtotal tumor necrosis, the myometrium invasion of more than a half of its thickness, with the egress to the perimetrium, metastatic lesions of both ovaries, the greater omentum, anterior abdominal wall. Stage T3b (FIGO IIIB). In the postoperative period, 6 courses of Paclitaxel / Carboplatin (AUC4-5) chemotherapy were carried out with a pronounced clinical effect. The patient was discharged in a satisfactory condition. The control PET-CT scan after the 6th chemotherapy course showed no pathology in the thoracic cavity, and no process progress in the abdominal cavity. Currently, the remission of the disease is 9 months. Conclusion: An algorithm for the diagnostic measures aimed at making the correct diagnosis is presented, and the tactics of treating a patient with giant serous endometrial cancer is described.

Abstract The Carpathians are one of the key biodiversity hotspots in Europe. The mountain chain uplifted during Alpine orogenesis and is characterised by a complex geological history. Its current biodiversity was highly influenced by Pleistocene glaciations. The goal of the current study was to examine the phylogenetic and demographic history of Gammarus balcanicus species complex in the Carpathians using multiple markers as well as to delimit, using an integrative approach, and describe new species hidden so far under the name G. balcanicus. Results showed that divergence of the studied lineages reaches back to the Miocene, which supports the hypothesis of their survival in multiple micro refugia. Moreover, the increase of their diversification rate in the Pleistocene suggests that glaciation was the driving force of their speciation. The climatic changes during and after the Pleistocene also played a major role in the demography of the local Carpathian lineages. Comparison of diversity patterns and phylogenetic relationships of both, the mitochondrial and nuclear markers, provide evidence of putative hybridisation and retention of ancient polymorphism (i.e., incomplete lineage sorting). The morphological examination supported the existence of two morphological types; one we describe as a G. stasiuki sp. nov. and another we redescribe as a G. tatrensis (S. Karaman, 1931).

In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules. In this study, we compared the features of the HLA-I genotype in symptomatic patients with COVID-19 in the first and third waves of the pandemic. As a result, we could identify the diminishing of carriers of the HLA-A*01:01 allele in the third wave and demonstrate the unique properties of this allele. Thus, HLA-A*01:01-binding immunoprevalent epitopes are mostly derived from ORF1ab. A set of epitopes from ORF1ab was tested, and their high immunogenicity was confirmed. Moreover, analysis of the results of single-cell phenotyping of T-cells in recovered patients showed that the predominant phenotype in HLA-A*01:01 carriers is central memory T-cells. The predominance of T-lymphocytes of this phenotype may contribute to forming long-term T-cell immunity in carriers of this allele. Our results can be the basis for highly effective vaccines based on ORF1ab peptides.

Background. Despite on the general trend towards decreasing the incidence of newly diagnosed active forms of tuberculosis, the situation with spreading of this disease in Russian Federation remains extremely tense. At the same time, the diagnosis is carried out according to the standard scheme, which takes about a month; another month takes test formulation for drug sensitivity. Thus, the development of new methods for diagnostics and typing of mycobacteria, as well as practice implementation of these developments is an urgent direction. Modern developments in the field of microfluidic technologies open up great opportunities in this direction. Aim. Development of a method for identification and typing of Mycobacterium tuberculosis using a label-free biosensor on surface waves in a one-dimensional photonic crystal (PC SM biosensor). Methods. Oligonucleotide probes were selected and synthesized as DNA targets for M. tuberculosis typing. The photonic crystal surface was modified with aqueous solutions of (3-aminopropyl)triethoxysilane, Leuconostoc mesenteroides dextrans and bovine serum albumin. Experiments were carried out using a PC SM biosensor. Results. Sequences of detecting oligonucleotide probes were selected for spoligotyping of M. tuberculosis on the PC SM biosensor. Modification of their 3'-ends was carried out in order to create extended single-stranded regions that are not subject to the formation of secondary structures and facilitate hybridization with a single-stranded DNA target. Several series of experimental modifications of the PC surface were carried out by using L. mesenteroides dextrans with different functional groups (including detection of the modification results real time) with simultaneous registration of the increment layer size and volume refractive index of the mixture, which excludes the use of a reference cell. Other experiments were carried out to detect the specific binding of biotinylated oligonucleotide probes to the modified PC surface. Conclusions. A technique for the design of probes was developed and a model system of oligonucleotides for the detection of single-stranded DNA using a PC biosensor was proposed. The developed technique of modification of the PC surface with dextrans from L. mesenteroides, which allows to increase the sensitivity of detection of oligonucleotides using the PC SM biosensor. This approach will further expand the panel of diagnostic probes, including identification of resistance markers.

Abstract Real-time seizure detection is a resource intensive process as it requires continuous monitoring of patients on stereoelectroencephalography. This study improves real-time seizure detection in drug resistant epilepsy (DRE) patients by developing patient-specific deep learning models that utilize a novel self-supervised dynamic thresholding approach. Deep neural networks were constructed on over 2000 h of high-resolution, multichannel SEEG and video recordings from 14 DRE patients. Consensus labels from a panel of epileptologists were used to evaluate model efficacy. Self-supervised dynamic thresholding exhibited improvements in positive predictive value (PPV; difference: 39.0%; 95% CI 4.5–73.5%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.03) with similar sensitivity (difference: 14.3%; 95% CI − 21.7 to 50.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.42) compared to static thresholds. In some models, training on as little as 10 min of SEEG data yielded robust detection. Cross-testing experiments reduced PPV (difference: 56.5%; 95% CI 25.8–87.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.002), while multimodal detection significantly improved sensitivity (difference: 25.0%; 95% CI 0.2–49.9%; Wilcoxon–Mann–Whitney test; N = 14; p

ABSTRACT Introduction and objectives: Between 10% and 25% of patients hospitalized due to an acute coronary syndrome develop acute kidney injury, a condition associated with higher morbidity and mortality rates. Scores have been developed to predict the occurrence of post-coronary angiography contrast-induced nephropathy (CIN) in patients with acute coronary syndrome. The objective of this study was to assess the association between microalbuminuria and post-coronary angiography CIN in patients with acute coronary syndrome. Methods: Patients admitted with acute coronary syndrome in whom a coronary angiography was performed during their hospitalization and with urinary albumin-to-creatinine ratio (ACR) assessment within the first 24 hours were analyzed. The best ACR cutoff value for coronary angiography-induced CIN was determined using the C-statistic measure. The receiver operating characteristic (ROC) curves were built to compare between the predictive ability of the Mehran score alone and also in combination with the ACR. Results: A total of 148 patients were analyzed. Median age was 64 years (56-73), 35% were women, mean creatinine clearance rate at admission was 86 mL/min (66-107) and the ACR was 5 mg/g (0-14). The analysis showed that 9.6% of the patients developed post-coronary angiography CIN with ACR levels ≥ 20 mg/g compared to 1.6% when these levels were < 20 mg/g. The area under the ROC curve of the Mehran score to predict the development of post-coronary angiography CIN was 0.75 (95%CI, 0.68-0.81) and when the ACR was added it went up to 0.82 (95%CI, 0.76-0.87). Conclusions: The ACR levels at admission were associated with the development of post-coronary angiography CIN and bring added value to an already validated predictive score. Therefore, the ACR should be used as a simple and accessible tool to detect and prevent this severe complication in patients with acute coronary syndrome.