Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) Study: Linking Claims Data to Phase 3 GRADUATE Study of Gantenerumab.

BACKGROUND: Linking data from clinical trials and real-world claims may improve the robustness of trial data and provide information on the health, economic, and societal impacts of a disease. OBJECTIVE: To report on the feasibility of linking trial data to Medicare claims data in early symptomatic Alzheimer's disease (AD) in the US. DESIGN AND SETTING: Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) was a noninterventional cohort study that included participants recruited from the GRADUATE program whose trial data were linked to their Medicare claims. PARTICIPANTS: AD-LINE participants were 66 years and older with early symptomatic AD (ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) and were enrolled in the GRADUATE program and a Medicare fee-for-service or Medicare Advantage plan. MEASUREMENTS: The Centers for Medicare and Medicaid Services linked participants' clinical trial identifiers to their Medicare beneficiary identifiers using a deterministic, exact matching process. Demographics and clinical characteristics of the AD-LINE cohort at baseline were collected. Outcomes measured in this study included healthcare resource utilization derived from Medicare claims data. RESULTS: In total, 147 participants across 21 US sites were invited to participate and 111 provided informed consent. Of those, 61 patients had linkable data (ie, Medicare beneficiary identifier), Medicare Parts A/B enrollment, and no health maintenance organization (HMO) enrollment in the year before trial entry. Of the 61 participants whose data were analyzed in this study, 30 had MCI due to AD and 31 had mild AD dementia. Participants in the MCI due to AD group had more healthcare resource utilization on average in the baseline period than those in the mild AD dementia group (29.9 [SD, 20.9] vs 24.5 claims [SD, 12.3]). In an ad hoc analysis, a relatively high concordance (85.3%) was seen between the rates of clinically confirmed AD diagnosis and evidence of AD diagnosis in claims data. CONCLUSION: This linkage process may serve as a proof of concept for researchers interested in linking clinical trial and real-world claims data. The lessons learned from AD-LINE and innovation of data linkage approaches may encourage key stakeholders to link data in the future.

[The Expression of TP53TG1, LINC00342, MALAT1, H19, and MEG3 Long Noncoding RNAs in Type 2 diabetes mellitus].

Type 2 diabetes is a complex and multifactorial metabolic disorder. The frequency of type 2 diabetes has dramatically increased worldwide. Long noncoding RNAs play a regulatory role in pathological processes of type 2 diabetes. The aim of the study was to analyze TP53TG1, LINC00342, MALAT1, H19, and MEG3 lncRNAs in patients with type 2 diabetes and metabolic parameters, as well as the risk of diabetic retinopathy. Participants included 51 patients with diabetes and 70 healthy individuals. The expression of the TP53TG1 and LINC00342 genes was significantly decreased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was higher in diabetes patients. H19 gene expression was increased in the patients with diabetic retinopathy compared patients without retinopathy. TP53TG1, LINC00342, and MEG3 expression was decreased in patients with diabetic retinopathy and MALAT1 expression was increased. H19 is positively correlated with triglyceride levels; TP53TG1 and LINC00342 are positively correlated with HbA1c levels and fasting glucose levels. MALAT1 is negatively correlated with HDL levels and positively correlated with LDL levels. A decrease in the expression level of TP53TG1 and LINC00342 and an increase in the level of MALAT1 in diabetes, as well as an association with glycemic control, indicate the role of the studied noncoding RNAs in the development of type 2 diabetes mellitus and retinopathy and can be considered as candidates for early diagnosis of type 2 diabetes.

Unusual BA222-like strains of Rotavirus A (Sedoreoviridae: Rotavirus: Rotavirus A): molecular and genetic analysis based on all genome segments.

INTRODUCTION: Rotavirus infection is the major cause of severe dehydrating diarrhea requiring hospitalization in young children worldwide. Due to their segmented genome, rotaviruses are capable of gene reassortment, which makes the emergence and spread of genetically novel strains possible. The purpose of this study was to search for unusual rotaviruses circulating in Nizhny Novgorod in 2021‒2023 and their molecular genetic characterization based on all genome segments. MATERIALS AND METHODS: Rotavirus-positive stool samples of children were examined by PCR genotyping and electrophoresis in PAAG. cDNA fragments of each of the 11 genes (VP1‒VP4, VP6, VP7, NSP1‒NSP5), 570 to 850 nucleotide pairs in length were sequenced for the selected strains. The phylogenetic analysis was performed in the MEGA X program. RESULTS: In the study period 2021‒2023, 11 G[P] combinations with a predominance of G3P[8] (59.5%) were identified. Six atypical Rotavirus А (RVA) strains were identified: 2 strains of the G2P[4] genotype (G2-P[4]-I2-R2-C2-M2-A3-N2-T3-E2-H3, G2-P[4]-I2-R2-C2-M2-A3-N2-T3-E3-H2) and 4 G3P[9] strains (all strains had the genotype G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3). Phylogenetic analysis based on all genes showed an evolutionary relationship between rotaviruses similar to rotaviruses of cats and dogs (BA222-like) and unusual strains of the G2P[4] genotype, for which a mixed combination of genotypes was identified and characterized for the first time. DISCUSSION: The results obtained expand the understanding of the diversity of reassortant RVAs, as well as complement the data on the genotypic structure of the rotavirus population in Nizhny Novgorod. CONCLUSION: The wide genetic diversity of reassortant RVA can help rotaviruses overcome the immunological pressure provided by natural and vaccine-induced immunity. In this regard, to control the emergence of new variants and assess changes in the virulence of rotaviruses after reassortment processes, continuous molecular monitoring for circulating RVA is necessary.

First detection of influenza A virus subtypes H1N1 and H3N8 in the Antarctic region: King George Island, 2023.

RELEVANCE: Influenza A virus is characterized by a segmented single-stranded RNA genome. Such organization of the virus genome determines the possibility of reassortment, which can lead to the emergence of new virus variants. The main natural reservoir of most influenza A virus subtypes are wild waterfowl. Seasonal migrations gather waterfowl from all major migration routes to nesting areas near the northern and southern polar circles. This makes intercontinental spread of influenza A viruses possible. Objective ‒ to conduct molecular genetic monitoring and study the phylogenetic relationships of influenza A virus variants circulating in Antarctica in 2023. MATERIALS AND METHODS: We studied 84 samples of biological material obtained from birds and marine mammals in April‒May 2023 in coastal areas of Antarctica. For 3 samples, sequencing was performed on the Miseq, Illumina platform and phylogenetic analysis of the obtained nucleotide sequences of the influenza A virus genomes was performed. RESULTS: The circulation of avian influenza virus in the Antarctic region was confirmed. Heterogeneity of the pool of circulating variants of the influenza A virus (H3N8, H1N1) was revealed. Full-length genomes of the avian influenza virus were sequenced and posted in the GISAID database (EPI_ISL_19032103, 19174530, 19174467). CONCLUSION: The study of the genetic diversity of influenza A viruses circulating in the polar regions of the Earth and the identification of the conditions for the emergence of new genetic variants is a relevant task for the development of measures to prevent biological threats.

Detection of Tissue Macrophages in Different Organs Using Antibodies to the Microglial Marker Iba-1.

Resident macrophages of different organs have structural and functional features, which can complicate their identification and analysis. A promising candidate for the role of a universal immunohistochemical marker of resident macrophages is the calcium-binding protein Iba-1, a well-known marker of brain microglia. The purpose of this work was to study the possibility of using one variant of antibodies to the Iba-1 protein for the immunohistochemical detection of resident macrophages in the liver, myocardium, lung, and choroid plexus of the rat brain. The study was performed on male Wistar rats (n = 15). It was shown that the use of rabbit monoclonal antibodies against Iba-1 allows highly effective detection of Kupffer cells in the liver, resident macrophages in the myocardium, alveolar and interstitial macrophages in the lung, and Kolmer cells in the choroid plexus of the rat brain. In all cases, the reaction is characterized by a high specificity and the absence of background staining. In contrast to the classical marker of macrophages, the CD68 molecule, the Iba-1 protein is evenly distributed in the cytoplasm of cell bodies and processes. This makes it possible to more fully identify cells using immunostaining for Iba-1, carry out their three-dimensional reconstructions, and study their structural and functional organization. Immunohistochemical reaction against Iba-1 can be successfully used as a universal alternative to other common methods for identifying resident macrophages.

[Influence of cardiorespiratory training program on the intercellular adhesion molecule level in patients with postmastectomy syndrome]. / Vliyanie programmy kardiorespiratornykh trenirovok na uroven' molekul mezhkletochnoi adgezii u patsientok s postmastektomicheskim sindromom.

Postmastectomy syndrome (PMS) is a complex neurovascular set of symptoms that develops in most patients after breast cancer (BC) treatment and significantly reduces the quality of life. One of the potential mechanisms of its occurrence is considered to be an endothelial dysfunction. The possible method of reducing manifestation of endothelial dysfunction is systematic aerobic dynamic training. OBJECTIVE: To evaluate the influence of 12-week aerobic dynamic training program of moderate intensity on the endothelial dysfunction laboratory markers and life quality in patients with PMS. MATERIAL AND METHODS: Single-center prospective randomized trial included 40 patients with PMS divided into study (20 patients) and comparative (20 patients) groups, as well as 20 healthy female volunteers. The expression level of soluble intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were evaluated in all participants at baseline by enzyme-linked immunosorbent assay method, and additionally psychological and physical component of health by SF-36 questionnaire were assessed in patients with PMS.Patients of study group received a course of 12-week partially controlled aerobic dynamic training of moderate intensity lasting 45 minutes with frequency equal 5 times per week. Patients with PMS were re-evaluated for ICAM-1 and PECAM-1, as well as for life quality. RESULTS: The group of patients with PMS after BC treatment had increased level of ICAM-1 in long-term period, that may indicate endothelial dysfunction. Statistically significant decrease of endothelial dysfunction laboratory markers was revealed in patients with PMS, who underwent the course of cardiorespiratory training. In the same time, the dynamics of changes in ICAM-1 was higher in the study group than in comparative group. Further, improvement of physical and psychological components of health by SF-36 questionnaire was found. CONCLUSIONS: The program of cardiorespiratory trainings of moderate intensity in patients, who had BC treatment a year ago, decreases intercellular adhesion molecules level that may show an improvement of endothelial dysfunction.

Random telegraph processes with nonlocal memory.

We study two-state (dichotomous, telegraph) random ergodic continuous-time processes with dynamics depending on their past. We take into account the history of the process in an explicit form by introducing integral nonlocal memory term into conditional probability function. We start from an expression for the conditional transition probability function describing additive multistep binary random chain and show that the telegraph processes can be considered as continuous-time interpolations of discrete-time dichotomous random sequences. An equation involving the memory function and the two-point correlation function of the telegraph process is analytically obtained. This integral equation defines the correlation properties of the processes with given memory functions. It also serves as a tool for solving the inverse problem, namely for generation of a telegraph process with a prescribed pair correlation function. We obtain analytically the correlation functions of the telegraph processes with two exactly solvable examples of memory functions and support these results by numerical simulations of the corresponding telegraph processes.

Fano-resonant mechanism of terajet formation using graphene-covered high-index mesoscale spheres.

Photonic jet in terahertz (THz) frequency range (terajet) plays an important role in modern THz scanning systems to achieve a superresolution beyond the diffraction limit. Based on analytical simulations, we introduce a synergetic effect of a mesoscale dielectric sphere and graphene to improve the focusing properties of a particle. We show that a graphene-covered dielectric sphere is able to enhance the field behind it if the refractive index is high. This conflicts with a generally accepted statement that a jet is generated only for low-index dielectrics with n < 2. We demonstrate the tunability of the terajet characteristics with respect to the graphene Fermi energy and discover a Fano resonance causing the field increase. This design leverages the tuning properties of the graphene allowing dynamic control over the power and size of the generated terajet in real time. With high-index materials, we get the opportunity for integration of terajet-assisted imaging with semiconductor technology.

[Highly selective sodium-glucose co-transporter type 2 inhibitor empagliflozin as means of brain protection in conditions of chronic brain dyscirculation].

BACKGROUND: Chronic brain dyscirculation is one of the frequent type 2 diabetes mellitus (DM) complications and leads to patients' disability. Sodium-glucose co-transporter type 2 inhibitors (SGLT-2i) have been proven to have advantages for cardiovascular system, but their effect on the central nervous system (CNS) has not been studied enough. AIM: To study empagliflozin effect on CNS damage functional and laboratory parameters in patients with type 2 DM and, under experimental conditions, to investigate the mechanisms of the drug neurotropic effect. MATERIALS AND METHODS: The clinical part of the study included patients with type 2 DM on metformin monotherapy (n=39). Patients with a target glycated hemoglobin level formed the "MET" group (n=19), in patients with a non-target glycated hemoglobin level empagliflozin was co-administered for the following 6 months (the "MET+EMPA" group, n=20). Healthy volunteers comprised the control group (n=16). The cognitive status and neuron-specific enolase (NSE) and neurofilament light chains (NLC) concentration were studied. DM was modeled in rats, thereafter the rats were treated with empagliflozin for 8 weeks. Microglia activation was assessed using anti-Iba-1 antibodies and morphological changes in neurons when stained by the Nissl method. RESULTS: Both in the "MET+EMPA" and the "MET" groups cognitive deficits were observed, according to the Montreal Cognitive Assessment (MOCA) (24.0 (23.0; 27.0) and 25.0 (21.0; 27.0) points) and the Mini-Mental State Examination (MMSE) (23.75 (23.0; 27.0) and 25.0 (21.0; 27.0) points). Empagliflozin therapy led to the cognitive status normalization after 6 months (26.5 (24.0; 27.0) points according to the MOCA scale and 27.5 (24.0; 28.0) points according to the MMSE). Initially, all patients had a significant increase of NSE (3.60 (2.66; 3.76) ng/ml in the "MET" group, 3.22 (2.94; 3.54) ng/ml in the "MET+EMPA¼ group, 2.72 (2.13; 2.72) ng/ml in the «Control¼ group) and NLC (4.50 (3.31; 5.56) ng/ml in the «MET¼ group, 5, 25 (3.75; 6.25) ng/ml in the «MET+EMPA¼ group comparing with 3.50 (2.25; 3.50) ng/ml in the «Control¼ group). Empagliflozin therapy led to a significant decrease in NLC already after 3 months (3.80 (3.25; 3.87) ng/ml), without significant influence on the NSE level. In the experiment, DM was characterized by an increased number of activated microgliocytes and destructured neurons and a decreased number of neurons with a normal structure. Empagliflozin therapy was accompanied by a decrease in the number of immunopositive microgliocytes in the CA1 zone of the hippocampus and an increase in the number of structured neurons. CONCLUSION: Type 2 diabetes mellitus is characterized by functional and biochemical changes in the central nervous system even under satisfactory glycemic control. Therapy with empagliflozin has a neuroprotective effect, manifested in an improvement in cognitive status and a decrease in NLC level. Empagliflozin reduces neuronal damage and abnormal microglial activation.

[Repeated liver resections for recurrent intrahepatic cholangiocarcinoma]. / Povtornye rezektsii pecheni pri retsidive vnutripechenochnoi kholangiokartsinomy.

OBJECTIVE: To evaluate the safety and advisability of repeated liver resection (RLR) for recurrent intrahepatic cholangiocarcinoma (ICC). MATERIAL AND METHODS: The results of RLR for ICC recurrence (n=10) were retrospectively analyzed between 1999 and 2023. The control group consisted of patients undergoing primary liver resection for ICC (n=195). RESULTS: Surgery time (p=0.001) and blood loss (p=0.038) were lower in the RLR group. There were no blood transfusions (0 vs. 31.8%, p=0.034) and 90-day mortality (0 vs. 3.2%, p=1.0) in the same group. The risk of complications (30.0% vs.45.6%, p=0.517) and adverse events grade ≥ III (20.0% vs. 17.9%, p=1.0) was similar in both groups. Multifocal intrahepatic nodes were more common in the RLR group (60% vs. 37.9%, p=0.193), while there were no negative factors such as lymph nodes involvement (0 vs. 34.4%, p=0.032) and invasion of surrounding structures (0 vs. 38.5%, p=0.015). Dimensions of the largest node were smaller in repeated resection (2 vs. 8 cm, p<0.0001). Incidence of R0 resections (80.0% vs. 82.1%, p=1.0) was comparable. Long-term results were similar: five-year overall survival 17.2% and 34.7% (p=0.912), three-year disease-free survival 20.0% and 26.5% (p=0.421). CONCLUSION: Similar results of repeated and primary liver resections confirm advisability of RLR for intrahepatic recurrence of ICC.

The Level of Markers Stimulating Growth Factor 2 (ST2), N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP), and D-Dimer in Healthy Volunteer Testers in 21-Day Head-Down -6° Tilt Bed Rest as a Model of Hypodynamia.

The paper presents an analysis of the proteomic composition in relation to both the risk of thrombosis and changes in the state of cardiomyocytes associated with the risk of cardiac fibrosis and heart failure. We examined 12 practically healthy male volunteers exposed to head-down -6° tilt bed rest (HDBR) for 21 days. The revealed decrease in the level of stimulating growth factor 2 (ST2) on days 10 and 21 relative to the initial values (background; 5 days before HDBR) indicated a decrease in the myocardial load and cardiomyocyte extensibility. The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increased on day 2, decreased on days 10 and 21 of HDBR relative to the background levels, and returned to baseline values after the recovery period (5 days after HDBR). The revealed changes in the level of NT-proBNP reflected the increase in circulating blood volume corresponding to HDBR duration and the role of the gravity component in increasing the functional load on the myocardium. Unchanged blood level of D-dimer at all points of the study indicates that there is no risk of thrombosis under the conditions of this study.

Transduced Olfactory Mucosa Cells Expressing Nerve Growth Factor for the Therapy of Experimental Spinal Cord Cysts.

A new gene-cell construct expressing nerve growth factor (NGF) has been developed. After obtaining engineered adenovectors Ad5-RGD-CAG-NGF and Ad5-RGD-CAG-EGFP, transduction efficiency and transgene expression were studied and multiplicity of infection was determined. The efficacy of transduced human olfactory ensheathing cells expressing NGF in restoring motor activity in rats has been shown in a limited period of time. Improved rat hindlimb mobility and cyst size reduction after gene-cell construct transplantation were more likely due to the cellular component of the construct.

Spontaneous and Stimulated Production of Cytokines by Blood Cells Ex Vivo as a Biomarker of Initially High or Low Hypoxia Resistance in Rats.

Spontaneous and stimulated production of cytokines by peripheral blood cells obtained from the caudal vein of male Wistar rats was assessed before testing their resistance to oxygen deficiency in a decompression chamber. To study the spontaneous production of cytokines, heparinized blood cells were incubated in a culture medium (24 h, 5% CO2, 37°C) and the content of proinflammatory cytokines IL-6 and TNFα and anti-inflammatory IL-10 in the culture medium was assessed by ELISA. To stimulate cytokine production, blood cells were incubated for 24 h with LPS, phytohemagglutinin, and concanavalin A at final concentrations of 2, 4, and 4 µg, respectively. Two weeks after blood sampling, individual resistance of the animals to hypoxia in a decompression chamber was determined. In animals with low resistance to hypoxia, the levels of spontaneous production of all three cytokines were significantly higher, while after stimulation, the level of IL-1ß increased by more than 2 times. The animals with spontaneous production of IL-10>50 pg/ml, IL-6>10 pg/ml, and TNFα>10 pg/ml, as well as with the increase in IL-1ß production by more than 2 times upon stimulation were classified as low-resistant. At IL-10<15 pg/ml, IL-6<9 pg/ml, and TNFα<7 pg/ml, as well as the absence of the increase in IL-1ß production upon stimulation, they were classified as high-resistant. The identified features of spontaneous and stimulated production of cytokines can be used as non-invasive biomarkers to determine the resistance to hypoxia without exposure to sublethal hypoxia in a decompression chamber.

Clinical Significance of the Expression of Long Non-Coding RNA LINC01508 in Non-Small Cell Lung Cancer.

The expression of long non-coding RNA (lncRNA) LINC01508 was studied in tumor samples from patients with non-small cell lung cancer (NSCLC), and its clinical significance was evaluated. The expression of LINC01508 lncRNA was measured in 16 pairs of NSCLC samples and its association with clinical and morphological features of the disease and prognosis analyzed. A comparative analysis showed a significant decrease in the expression of LINC01508 in tumor lung tissue in comparison with the surrounding normal lung tissue. The informativity of the diagnostic method was tested using ROC curve analysis and calculation of the area under the curve (AUC) for LINC01508 in NSCLC patients, which showed an AUC of 0.875 (p=0.001). No significant associations of LINC01508 expression level with clinical and morphological characteristics of the disease were found. The analysis of prognostic significance showed that high expression of LINC01508 in NSCLC samples was a favorable prognostic factor. Despite the fact that the results did not reach statistical significance (p=0.107), the median survival rate for patients with low LINC01508 expression was 16 months, while for patients with high expression, it was not reached during the follow-up period. We believe that LINC01508 can be a promising independent prognostic marker for NSCLC.

Morphometric Characteristics of Postmortem Changes in the Brain of Newborns Depending on the Duration of the Postmortem Period.

The morphometric characteristics of brain tissue were studied based on autopsy material from 49 deceased newborns divided into 7 groups based on the time after death. Samples were taken from the upper (frontal lobe) and lower (occipital lobe) regions relative to the supine position of the body. Paraffin sections were prepared from these samples and stained with hematoxylin and eosin. Histological preparations were analyzed using an image analysis system to determine the area of gliocyte nuclei, cross-cut blood vessels, and expanded area around them in the white matter of the brain. Based on these data, severity indices were calculated for both cellular (pericellular) and vascular (perivascular) expansion. The dynamics of changes in morphometric parameters within the range of cellular and vascular alterations on brain tissue specimens, which reflect the development of postmortem hypostasis and autolysis in this organ, can be used to estimate the duration of the postmortem interval. At the same time, these changes, when combined with other non-specific postmortem findings, should be distinguished from long-term pathological processes and diseases that may have occurred during life.

The Use of Neurotrophic Factors as a Promising Strategy for the Treatment of Neurodegenerative Diseases (Review).

The review considers the use of exogenous neurotrophic factors in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and others. This group of diseases is associated with the death of neurons and dysfunction of the nervous tissue. Currently, there is no effective therapy for neurodegenerative diseases, and their treatment remains a serious problem of modern medicine. A promising strategy is the use of exogenous neurotrophic factors. Targeted delivery of these factors to the nervous tissue can improve survival of neurons during the development of neurodegenerative processes and ensure neuroplasticity. There are methods of direct injection of neurotrophic factors into the nervous tissue, delivery using viral vectors, as well as the use of gene cell products. The effectiveness of these approaches has been studied in numerous experimental works and in a number of clinical trials. Further research in this area could provide the basis for the creation of an alternative treatment for neurodegenerative diseases.

Comparative Study of the Anxiolytic Activity of Songorine in Elevated Plus Maze Test and by Recording Ultrasonic Vocalizations.

It was found that the diterpene alkaloid songorine administered per os to mice at a dose of 25 µg/kg provides a pronounced anxiolytic effect during elevated plus maze testing comparable to the effect of the benzodiazepine anxiolytic phenazepam. Recording of ultrasonic vocalizations of animals revealed an increase in the number of short high-frequency (50 kHz) signals under the action of songorine and the reference drug, which confirms their anti-anxiety properties.

Proteome of plasma extracellular vesicles as a source of colorectal cancer biomarkers.

The search for minimally invasive methods for diagnostics of colorectal cancer (CRC) is the most important task for early diagnostics of the disease and subsequent successful treatment. Human plasma represents the main type of biological material used in the clinical practice; however, the complex dynamic range of substances circulating in it complicates determination of CRC protein markers by the mass spectrometric (MS) method. Studying the proteome of extracellular vesicles (EVs) isolated from human plasma represents an attractive approach for the discovery of tissue-secreted CRC markers. We performed shotgun mass spectrometry analysis of EV samples obtained from plasma of CRC patients and healthy volunteers. This MS analysis resulted in identification of 370 proteins (which were registered by at least two peptides). Stable isotope-free relative quantitation identified 55 proteins with altered abundance in EV samples obtained from plasma samples of CRC patients as compared to healthy controls. Among the EV proteins isolated from blood plasma we found components involved in cell adhesion and the VEGFA-VEGFR2 signaling pathway (TLN1, HSPA8, VCL, MYH9, and others), as well as proteins expressed predominantly by gastrointestinal tissues (polymeric immunoglobulin receptor, PIGR). The data obtained using the shotgun proteomic profiling may be added to the panel for targeted MS analysis of EV-associated protein markers, previously developed using CRC cell models.

Integration of an electronic hand hygiene auditing system with electronic health records using machine learning to predict hospital-acquired infection in a healthcare setting.

BACKGROUND: Hospital-acquired infections (HAIs) increase morbidity, mortality, and healthcare costs. Effective hand hygiene (HH) is crucial for prevention, but achieving high compliance remains challenge. This study explores using machine learning to integrate an electronic HH auditing system with electronic health records to predict HAIs. METHODS: A retrospective cohort study was conducted at a Brazilian hospital during 2017-2020. HH compliance was recorded electronically, and patient data were collected from electronic health records. The primary outcomes were HAIs per CDC/NHSN surveillance definitions. Machine learning algorithms, balanced with Random Over Sampling Examples (ROSE), were utilized for predictive modeling, including generalized linear models (GLM); generalized additive models for location, scale, and shape (GAMLSS); random forest; support vector machine; and extreme gradient boosting (XGboost). RESULTS: 125 of 6,253 patients (2%) developed HAIs and 920,489 HH opportunities (49.3% compliance) were analyzed. A direct correlation between HH compliance and HAIs was observed. The GLM algorithm with ROSE demonstrated superior performance, with 84.2% sensitivity, 82.9% specificity, and a 93% AUC. CONCLUSIONS: Integrating electronic HH auditing systems with electronic health records and using machine learning models can enhance infection control surveillance and predict patient outcomes. Further research is needed to validate these findings and integrate them into clinical practice.

Original Moxonidine and Generics: Where is the Edge of Difference?

AIM: To compare the efficacy of adding original moxonidine and its generics to previous ineffective antihypertensive therapy in patients with poorly controlled arterial hypertension (AH). MATERIAL AND METHODS: This observational prospective non-randomized study included 120 patients with poorly controlled blood pressure on the previous antihypertensive therapy. All patients underwent clinical evaluation, including anthropometric and laboratory indexes, and 24-hour blood pressure monitoring (24-h BPM) at baseline and after 12 weeks of observation. Office systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) were recorded after 4 and 12 weeks of treatment. During the observation period, 4 equal groups were formed: group 1, Physiotens was added to the treatment; group 2, Moxonitex; group 3, Moxonidine SZ; and group 4, Moxonidine Canon. Statistical analysis was performed with the StatTech v.4.2.7 software (© OOO StatTech, Russia). RESULTS: After 4 weeks of therapy, the BP target was achieved significantly more frequently in group 1 (63% of patients) compared to groups 2 (36.7% of patients), 3 (16.7% of patients), and 4 (16.7% of patients) (p<0.05). At 12 weeks, office SBP, DBP, and HR were significantly decreased in all groups, but the decrease was significantly greater in group 1. The therapy was associated with a more pronounced decrease in all studied 24-h BPM parameters in the Physiotens group than in other groups, as well as with a significantly more frequent normalization of the 24-h BP profile, in 66.7% of patients vs. 46.7%, 33.4%, and 23.2% of patients in groups 2, 3, and 4, respectively. CONCLUSION: The treatment with original moxonidine demonstrated advantages over generic drugs in terms of achieving the BP goal, reducing office BP and HR, and improving 24-h BPM parameters.