Non-invasive hemoglobin concentration measurements with multi-wavelength reflectance mode PPG sensor and CNN data processing.

Possibility of non-invasive hemoglobin concentration measurements with wearable devices have been evaluated. The proposed solution is based on the assumption that PPG waveform shape measured at various wavelengths in the reflectance mode carries information about in-depth distribution of optical pathlength in the tissue. Decomposition of temporal and spectral features of PPG signal have been applied to correct estimation of hemoglobin concentration. The dataset including 840 PPG waveforms from 170 volunteers have been collected for the purpose of neural network training and validation. The achieved performance (MAE~13.6 g/l, R~0.62) is confirmed with the invasive blood test.Clinical Relevance - This paper establishes possibility of non-invasive real time hemoglobin concentration measurements by means of low-cost wearable sensor with accuracy comparable to non-invasive clinical instruments.

The Synthesis, Structure, and Luminescent Properties of TmMgB5O10 Crystals.

TmMgB5O10 spontaneous crystals were synthesized via the flux-growth technique from a K2Mo3O10-based solvent. The crystal structure of the compound was solved and refined within the space group P21/n. The first principles calculations of the electronic structure reveal that TmMg-pentaborate with an ideal not defected crystal structure is an insulator with an indirect energy band gap of approximately 6.37 eV. Differential scanning calorimetry measurements and powder X-ray diffraction studies of heat-treated solids show that TmMgB5O10 is an incongruent melting compound. A characteristic band of the Tm3+ cation corresponding to the 3H6 → 1D2 transition is observed in the photoluminescence excitation spectra of TmMg-borate. The as-obtained crystals exhibit intense blue emission with the emission peaks centered at 455, 479, 667, and 753 nm. The most intensive band corresponds to the 1D2 → 3F4 transition. TmMgB5O10 solids demonstrate the thermal stability of photoluminescence.

Multispectral sensor fusion in SmartWatch for in situ continuous monitoring of human skin hydration and body sweat loss.

Post-pandemic health operations have become a near-term reality, discussions around wearables are on the rise. How do wearable health solutions effectively deploy and use this opportunity to fill the gap between wellness and healthcare? In this paper, we will talk about wearable healthcare diagnosis, with a particular focus on monitoring skin hydration using optical multi-wavelength sensor fusion. Continuous monitoring of human skin hydration is a task of paramount importance for maintaining water loss dynamics for fitness lovers as well as for skin beauty, integrity and the health of the entire body. Preserving the appropriate levels of hydration ensures consistency of weight, positively affects psychological state, and proven to result in a decrease in blood pressure as well as the levels of "bad" cholesterol while slowing down the aging processes. Traditional methods for determining the state of water content in the skin do not allow continuous and non-invasive monitoring, which is required for variety of consumer, clinical and cosmetic applications. We present novel sensing technology and a pipeline for capturing, modeling and analysis of the skin hydration phenomena and associated changes therein. By expanding sensing capabilities built into the SmartWatch sensor and combining them with advanced modeling and Machine Learning (ML) algorithms, we identified several important characteristics of photoplethysmography (PPG) signal and spectral sensitivity corresponding to dynamics of skin water content. In a hardware aspect, we newly propose the expansion of SmartWatch capabilities with InfraRed light sources equipped with wavelengths of 970 nm and 1450 nm. Evaluation of the accuracy and characteristics of PPG sensors has been performed with biomedical optics-based simulation framework using Monte Carlo simulations. We performed rigorous validation of the developed technology using experimental and clinical studies. The developed pipeline serves as a tool in the ongoing studies of the next generation of optical sensing technology.

Phase Relations in the Ln2O3-Cr2O3-B2O3 (Ln = Gd-Lu) Ternary Oxide Systems.

In this work, isothermal sections of the Ln2O3-Cr2O3-B2O3 (Ln = Gd-Lu) ternary oxide systems at 900, 1000, and 1100 °C were constructed by determining the phase relations by using a powder X-ray diffraction technique. As a result, these systems were divided into subsidiary subsystems. Two types of double borates, LnCr3(BO3)4 (Ln = Gd-Er) and LnCr(BO3)2 (Ln = Ho-Lu), were observed in the investigated systems. Regions of phase stability for LnCr3(BO3)4 and LnCr(BO3)2 were determined. It was shown that the LnCr3(BO3)4 compounds crystallized in rhombohedral and monoclinic polytype modifications up to 1100 °C; above this temperature and up to the melting points, the monoclinic modification was predominantly formed. The LnCr3(BO3)4 (Ln = Gd-Er) and LnCr(BO3)2 (Ln = Ho-Lu) compounds were characterized by using a powder X-ray diffraction method and thermal analysis.

Recombinant Spidroin Microgel as the Base of Cell-Engineered Constructs Mediates Liver Regeneration in Rats.

Aim: In this study, we seek to check if recombinant spidroin rS1/9 is applicable for cell-engineering construct development. Novel technologies of cell and tissue engineering are relevant for chronic liver failure management. Liver regeneration may represent one of the possible treatment options if a cell-engineered construct (CEC) is used. Nowadays, one can see the continuous study of various matrices to create an appropriate CEC. Materials and Methods: We have adhered allogenic liver cells and multipotent mesenchymal bone marrow stem cells (MMSC BM) to a microgel with recombinant spidroin rS1/9. Then we have studied the developed implantable CEC in a rat model (n = 80) of chronic liver failure achieved by prolonged poisoning with carbon tetrachloride. Results: Our results demonstrate that the CECs change the values of biochemical tests and morphological parameters in chronic liver failure in rats. Conclusion: We consider there to be a positive effect from the microgel-based CECs with recombinant spidroin rS1/9 in the treatment of chronic liver failure.

New Mutations in the 5' Region of the Notch Gene Affect Drosophila melanogaster Oogenesis.

The Notch pathway is an important and evolutionarily conserved signaling system involved in the development of multicellular organisms. Notch signaling plays an important role in the regulation of proliferation and differentiation of many cell types. In this study, we report new aspects of Notch gene participation in oogenesis using our previously generated mutations. The mutations consist of an insertion of an auxiliary element of a transgene construct into the first intron of the gene and a series of directed deletions within the 5' regulatory region of Notch. We showed that some of these mutations affect Drosophila oogenesis. This insertion, either alone or in combination with the deletion of an insulator sequence, led to lower expression of Notch in the ovaries. As a result, the formation of egg chambers was disturbed in middle oogenesis. These abnormalities have not been described previously and imply one more function of Notch in oogenesis. It can be assumed that Notch is associated with not only follicular epithelium morphogenesis but also cellular mechanisms of oocyte growth.

Using the CRISPR/Cas9 System for Dissection of Functional Sites of the Notch Gene in Drosophila melanogaster.

The Notch gene is a key factor in the signaling cascade that allows communication between neighboring cells in many organisms, from worms and insects to humans. The relative simplicity of the Notch pathway in Drosophila, combined with a powerful set of molecular and cytogenetic methods, makes this model attractive for studying the fundamental principles of Notch regulation and functioning. Here, using the CRISPR/Cas9 system in combination with homologous recombination, for the first time at the level of the whole organism, we obtained a directed deletion of the 5'-regulatory region and the first exon of the Notch gene, which were replaced by the attP integration site of the ΦC31 phage. Based on this approach, we obtained and characterized new Notch mutations. Thus, a new powerful tool is provided for studying the genetic regulation of the Notch gene and the organization of chromatin at this locus.

MAPK and Notch-Mediated Effects of Meso-Xanthin F199 Compounds on Proliferative Activity and Apoptosis of Human Melanocytes in Three-Dimensional Culture.

Meso-Xanthin (Meso-Xanthin F199™) is a highly active antiaging injection drug of the latest generation. The main acting compound is fucoxanthin, supplemented with several growth factors, vitamins, and hyaluronic acid. Previous examination of fucoxanthin on melanocytes showed its ability to inhibit skin pigmentation through different signaling pathways focused on suppression of melanogenic-stimulating receptors. In turn, the anticancer property of fucoxanthin is realized through MAPK and PI3K pathways. We aimed to evaluate the effect of fucoxanthin and supplemented growth factors on melanocyte growth and transformation at a proteomic level. The effect of fucoxanthin on melanocytes cultivated in three-dimensional (3D) condition was examined using high-throughput proteomic and system biology approaches to disclose key molecular events of the targeted action. Our results demonstrated significant inhibition of cell differentiation and ubiquitination processes. We found that the negative regulation of PSME1 and PTGIS largely determines the inhibition of NF-κB and MAPK2. Besides, fucoxanthin selectively inhibits cell differentiation via negative regulation of Raf signaling and the upstream activation of IL-1 signaling. It is assumed that inhibition of Raf influences the Notch-4 signaling and switches off the MAPK/MAPK2 cascade. Blockage of MAPK/MAPK2 is feasible due to suppression of Ras and NF-κB by the addressed action of IKKB, IKK2, and TRAF6. Suggestively, Meso-Xanthin F199™ can manage processes of proliferative activity and inhibition of apoptosis due to composition of fucoxanthin and growth-stimulating factors, which may increase the risk of skin cancer development under certain condition.

Crystal Chemistry of High-Temperature Borates.

In recent years borate-based crystals has attracted substantial interest among the research community. The overall importance of this family of materials is reflected in miscellaneous articles and several reviews that have been published over the years. Crystalline borate materials exhibit numerous interesting physical properties, which make them promising for further practical applications. Diversity of functional characteristics results from their high structural flexibility caused in the linkage of planar/non-planar BO3 groups and BO4 tetrahedra, which can occur as isolated or condensed structural units. This report is a brief review on crystal chemistry and structure features of anhydrous/high-temperature borates. Polymorphism of boron-oxygen radicals has been considered basing on cations' nature and synthesis conditions. Analysis of the laws governing borates structures and general principles of their systematics was discussed. As a result, an alternative classification of anhydrous compounds has been considered. It is based on four orders of their subdivision: (1) by the variety of anion formers, (2) by the cation charge, (3) by the N = NM:NB, i.e., ratio of metal atoms number to the ratio of boron atoms number (N-factor) value indicating the borate structural type (if it is known), (4) by the cation type and size.

Establishing reference intervals for major biochemical analytes for the Russian population: a research conducted as a part of the IFCC global study on reference values.

OBJECTIVES: Because reference intervals (RIs) for biochemistry analytes matched to the Russian population are not well defined, we joined the global study on reference values (RVs) coordinated by the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: According to the C-RIDL harmonized protocol, 793 healthy volunteers were recruited in Saint-Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for 34 biochemistry analytes. Sources of variation of RVs were explored using multiple regression analysis. The need for partitioning RVs by sex and age were judged using standard deviation ratio based on ANOVA. Latent abnormal values exclusion (LAVE) method was applied to reduce the influence of individuals with metabolic syndrome and/or inappropriate sampling conditions. RIs were computed by the parametric method. RESULTS: No appreciable between-city differences were observed. Partition of RVs by sex was required for 17 analytes. Age-related changes in RVs were observed in many analytes, especially in females. The trend was exaggerated in nutritional and inflammatory markers that were closely associated with body mass index (BMI), because BMI increases prominently with age. Therefore, for those analytes, volunteers with BMI > 28 kg/m2 were excluded in determining RIs for age-specific RIs. The LAVE method was effective in lowering the upper limits of the RIs for nutritional and inflammatory markers. CONCLUSION: RIs matched to the Russian population were established for 34 biochemical analytes using up-to-date methods in detailed consideration of sources of variation of RVs. The majority of Russian RIs are similar to those of Caucasian populations among the participating countries.

Structural and Functional Dissection of the 5' Region of the Notch Gene in Drosophila melanogaster.

Notch is a key factor of a signaling cascade which regulates cell differentiation in all multicellular organisms. Numerous investigations have been directed mainly at studying the mechanism of Notch protein action; however, very little is known about the regulation of activity of the gene itself. Here, we provide the results of targeted 5'-end editing of the Drosophila Notch gene in its native environment and genetic and cytological effects of these changes. Using the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) system in combination with homologous recombination, we obtained a founder fly stock in which a 4-kb fragment, including the 5' nontranscribed region, the first exon, and a part of the first intron of Notch, was replaced by an attachment Phage (attP) site. Then, fly lines carrying a set of six deletions within the 5'untranscribed region of the gene were obtained by ΦC31-mediated integration of transgenic constructs. Part of these deletions does not affect gene activity, but their combinations with transgenic construct in the first intron of the gene cause defects in the Notch target tissues. At the polytene chromosome level we defined a DNA segment (~250 bp) in the Notch5'-nontranscribed region which when deleted leads to disappearance of the 3C6/C7 interband and elimination of CTC-Factor (CTCF) and Chromator (CHRIZ) insulator proteins in this region.

Smoking and alcohol use among women in Russia: Dual risk for prenatal exposure.

Alcohol consumption during pregnancy can produce adverse outcomes; maternal smoking compounds this risk. We examined prevalence of smoking and associations between smoking and alcohol use in Russian women of childbearing age (N = 648). Smoking was reported by 35% of nonpregnant and 14% of pregnant women. Smoking prevalence was higher (45%) among at-risk drinkers and those at risk for an alcohol-exposed pregnancy (AEP). In a multivariate model, smoking status and city of residence significantly predicted AEP risk. Pregnant women in urban locations were more likely to smoke. Smoking and alcohol misuse often co-occur among Russian women, presenting risk for dual prenatal exposure.

SERS detection of ceftriaxone and sulfadimethoxine using copper nanoparticles temporally protected by porous calcium carbonate.

The authors describe a new composite based on SERS-active copper nanoparticles (CuNPs; 10 ± 2 nm) incorporated into calcium carbonate microspheres (CaCO3-CuNPs; 3.4 ± 0.3 µm). The CaCO3 coating acts as a temporal protector of CuNPs against oxidation. Incorporated CuNPs have significantly improved stability during storage and a month-long shelf lifetime. The composite was used for SERS detection of rhodamine 6G and two antibacterial drugs (ceftriaxone and sulfadimethoxine). Two analytical formats, one with and one without solid phase extraction, are introduced to demonstrate the flexibility of the method. Both formats imply the dissolution of CaCO3 matrix before SERS analysis to release CuNP used as SERS substrate. The study of the influence of pH value and acid nature on the SERS signal demonstrated that HCl is the most efficient candidate to release the CuNPs. Sensitivity (expressed as LOD) is shown to be improved by more than one order when solid phase extraction is used. The average SERS enhancement factor is 10^7 which makes the material efficiency comparable to the one of silver nanoparticles. The LOD (<5 µM), precision (RSDs between 20 and 24% at LOD levels), and trueness (apparent recoveries 84-113%) for the two antibiotics (ceftriaxone and sulfadimethoxine) make the method quite useful for quantitative analysis and therapeutic drug monitoring at physiologically relevant concentrations. Graphical abstract A composite with temporally stable copper nanoparticles was synthesized, studied, and used for SERS detection of two antibacterial drugs. The analytical efficiency of the composite was found appropriate for quantitative analysis due to Raman enhancement comparable with silver nanostructures.

Anticoagulation and the risk of complications in ventricular tachycardia and premature ventricular complex ablation.

BACKGROUND: Many patients undergoing ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation receive antithrombotic medications.  Their uninterrupted use has the potential to affect complication rates. We assessed the incidence of complications in a large cohort of patients undergoing these procedures, according to antithrombotic medication use. METHODS: From June 2014 to June 2016, 201 VT and PVC ablations were performed at a single center. We allocated patients to three groups: (A) anticoagulation group (international normalized ratio ≥ 1.5 or non-vitamin K anticoagulant or full-dose low-molecular-weight (LMW) heparin on day of procedure); (B) antithrombotic group (antiplatelet therapy and/or prophylactic LMW heparin on day of procedure); and (C) no antithrombotics group.  We assessed periprocedural complication rates in each group.  Multivariable analysis was performed. RESULTS: Group A (47 patients) had 8.5% procedural complication rate: one stroke, one pseudoaneurysm, one femoral artery occlusion, and one access site hematoma. In this group, 37 patients had femoral arterial and 18 had epicardial access. In Group B (46 patients), the complication rate was 6.5%: two cardiac tamponades and one pericardial effusion without compromise. Group C (108 patients) had a 5.6% complication rate: three cardiac tamponades (with one periprocedural death and one concomitant gastric vessel injury), one pericardial effusion without compromise, one stomach perforation, and two access site hematomas. Multivariable analysis did not show any significant predictors of complications, though age approached significance. CONCLUSIONS: Complication rates were not significantly different between groups. These findings suggest that VT and PVC ablation can be performed safely in patients with uninterrupted antithrombotic medications.

Catheter ablation for atrial fibrillation on uninterrupted direct oral anticoagulants: A safe approach.

BACKGROUND: Current consensus guidelines suggest direct oral anticoagulants (DOACs) are interrupted periprocedurally for catheter ablation (CA) of atrial fibrillation (AF). However, this may predispose patients to thromboembolic complications. This study investigates the safety of CA for AF on uninterrupted DOACs compared to uninterrupted warfarin. METHODS: This was a single-center, retrospective study of consecutive patients undergoing CA for AF. All patients were heparinized prior to transseptal puncture with a target-activated clotting time (ACT) of 300-350 seconds. Patients who had procedures performed on continuous DOAC were compared to those on continuous warfarin. Clinical, procedural data, and complications occurring up to 3 months were analyzed from a prospective registry with additional review of electronic health records. RESULTS: A total of 1,884 procedures were performed over 28 months: 761 (609 patients) on uninterrupted warfarin and 1,123 (900 patients) on uninterrupted DOAC (rivaroxaban 64%, apixaban 32%, and dabigatran 4%). There was no difference in the composite endpoint of death, thromboembolism, or major bleeding complication (2.2% vs 1.4%, P = 0.20). There was no difference in the complications comprising this, including tamponade, hematoma, pseudoaneurysm, and transfusion (P-values 0.28, 0.13, 0.45, and 0.36). There were no strokes, transient ischemic attacks, or other thromboembolic complications. There was no difference between groups in the proportion of tamponades requiring reversal of oral anticoagulation, the volume of blood lost, the proportion transfused, or the proportion drained percutaneously (P-values 0.50, 0.51, 0.36, and 0.38). CONCLUSION: Catheter ablation for AF can be performed safely and effectively in patients anticoagulated with DOACs and heparinized with a therapeutic ACT. There is no increased risk of periprocedural bleeding when compared to uninterrupted warfarin.

Tethering of CHROMATOR and dCTCF proteins results in decompaction of condensed bands in the Drosophila melanogaster polytene chromosomes but does not affect their transcription and replication timing.

Instulator proteins are central to domain organization and gene regulation in the genome. We used ectopic tethering of CHROMATOR (CHRIZ/CHRO) and dCTCF to pre-defined regions of the genome to dissect the influence of these proteins on local chromatin organization, to analyze their interaction with other key chromatin proteins and to evaluate the effects on transcription and replication. Specifically, using UAS-GAL4DBD system, CHRO and dCTCF were artificially recruited into highly compacted polytene chromosome bands that share the features of silent chromatin type known as intercalary heterochromatin (IH). This led to local chromatin decondensation, formation of novel DHSes and recruitment of several "open chromatin" proteins. CHRO tethering resulted in the recruitment of CP190 and Z4 (PZG), whereas dCTCF tethering attracted CHRO, CP190, and Z4. Importantly, formation of a local stretch of open chromatin did not result in the reactivation of silent marker genes yellow and mini-white immediately adjacent to the targeting region (UAS), nor did RNA polII become recruited into this chromatin. The decompacted region retained late replicated, similarly to the wild-type untargeted region.

Delivery and reveal of localization of upconversion luminescent microparticles and quantum dots in the skin in vivo by fractional laser microablation, multimodal imaging, and optical clearing.

Delivery and spatial localization of upconversion luminescent microparticles [Y2O3:Yb, Er] (mean size ∼1.6 µm) and quantum dots (QDs) (CuInS2/ZnS nanoparticles coated with polyethylene glycol-based amphiphilic polymer, mean size ∼20 nm) inside rat skin was studied in vivo using a multimodal optical imaging approach. The particles were embedded into the skin dermis to the depth from 300 to 500 µm through microchannels performed by fractional laser microablation. Low-frequency ultrasound was applied to enhance penetration of the particles into the skin. Visualization of the particles was revealed using a combination of luminescent spectroscopy, optical coherence tomography, confocal microscopy, and histochemical analysis. Optical clearing was used to enhance the image contrast of the luminescent signal from the particles. It was demonstrated that the penetration depth of particles depends on their size, resulting in a different detection time interval (days) of the luminescent signal from microparticles and QDs inside the rat skin in vivo. We show that luminescent signal from the upconversion microparticles and QDs was detected after the particle delivery into the rat skin in vivo during eighth and fourth days, respectively. We hypothesize that the upconversion microparticles have created a long-time depot localized in the laser-created channels, as the QDs spread over the surrounding tissues.

Evaluating alcohol use among Russian women at risk for an alcohol-exposed pregnancy: A comparison of three measures of alcohol use.

The Quick Drinking Screen (QDS) and Timeline Followback (TLFB), measures of alcohol use, have yielded similar reports of drinking with English speakers. The present study, a secondary data analysis, compared three measures of alcohol use (i.e., QDS, TLFB, and AUDIT) among Russian-speaking women. This is the first study to compare all three measures. This study replicated the findings of studies with English speakers and demonstrated that brief screening measures (QDS, AUDIT) provide reliable summary measures of alcohol use when compared to a detailed drinking measure (TLFB). The use of brief screening measures is recommended for use with Russian women.

Latent Class Analysis of HIV Risk Behaviors Among Russian Women at Risk for Alcohol-Exposed Pregnancies.

The number of HIV cases attributed to heterosexual contact and the proportion of women among HIV positive individuals has increased worldwide. Russia is a country with the highest rates of newly diagnosed HIV infections in the region, and the infection spreads beyond traditional risk groups. While young women are affected disproportionately, knowledge of HIV risk behaviors in women in the general population remains limited. The objectives of this study were to identify patterns of behaviors that place women of childbearing age at high risk for HIV transmission and determine whether socio-demographic characteristics and alcohol use are predictive of the risk pattern. A total of 708 non-pregnant women, aged between 18 and 44 years, who were at risk for an alcohol-exposed pregnancy were enrolled in two regions in Russia. Participants completed a structured interview focused on HIV risk behaviors, including risky sexual behavior and alcohol and drug use. Latent class analysis was utilized to examine associations between HIV risk and other demographic and alcohol use characteristics and to identify patterns of risk among women. Three classes were identified. 34.93% of participants were at high risk, combining their risk behaviors, e.g., having multiple sexual partners, with high partner's risk associated with partner's drug use (class I). Despite reporting self-perceived risk for HIV/STI, this class of participants was unlikely to utilize adequate protection (i.e., condom use). The second high risk class included 13.19% of participants who combined their risky sexual behaviors, i.e., multiple sexual partners and having STDs, with partner's risk that included partner's imprisonment and partner's sex with other women (class II). Participants in this class were likely to utilize protection/condoms. Finally, 51.88% of participants were at lower risk, which was associated primarily with their partners' risk, and these participants utilized protection (class III). The odds of being in class I compared with class III were 3.3 (95% CI [1.06, 10.38]) times higher for those women who had Alcohol Use Disorders Identification Test scores ≥ 8 than those who had lower scores, and were 3.9 (95% CI [1.69, 8.97]) times higher for those who used alcohol before sex than those who did not. In addition, women who drank more days per week were 1.36 times more likely to be in class II than in class III. The study informs prevention by identifying specific population groups and targets for interventions. Alcohol use is a significant predictor and an overarching factor of HIV risk in women. Since at-risk drinking is common among young Russian women, alcohol risk reduction should be an essential component of HIV prevention efforts.

Alcohol and HIV Risk Among Russian Women of Childbearing Age.

Russia has one of the fastest rising rates of HIV among women in the world. This study sought to identify key factors in HIV transmission among women in Russia. Data were collected as part of a larger clinical trial to prevent alcohol-exposed pregnancies (AEP). Women at risk for an AEP were recruited at women's clinics; 708 women, aged 18-44 (M = 29.04 years), completed HIV risk surveys. Structural Equation Modeling was used to test the relationships between alcohol use and sex behavior constructs with HIV/STI risk. While the model indicated that multiple factors are involved in women's HIV/STI risk, the independent alcohol use variable explains 20 % of the variance in women's HIV/STI risk. The findings suggest that alcohol use directly and indirectly predicts HIV/STI risk among women, and its effect is mediated by alcohol use before sex.