Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer.

Blood serum of patients with gastric (n = 68) and esophageal (n = 43) cancer was assessed for proteolytic fragments of IgG. Serum samples of 20 healthy donors were used as a control. We analyzed indicators of hemostasis (prothrombin time, fibrinogen, plasminogen activity, a2-antiplasmin activity, protein C activity) in blood plasma and the level of total IgG in the blood serum. The median IgG-LysK of healthy donors was lower than in esophageal cancer and in patients with gastric cancer. ROC-analysis showed high sensitivity (91%) and specificity (85%) in the group with esophageal cancer but 68% and 85%, respectively, in patients with gastric cancer. Analysis of false negatives IgG-LysK in cancer patients showed that most patients had an advanced stage of cancer accompanied by metastases. Total IgG in the plasma of patients with false-negative IgG-LysK values was 30% lower than in samples with positive values, while the level of a2-antiplasmin was increased and the prothrombin time was shorter. These changes in blood homeostasis may be the reason for an increase in the proportion of false-negative values of the IgG-LysK coefficient. Circulatory IgG-LysK levels increase in the early stages of such cancers as gastric and esophageal cancers. Thus, when used in a panel with other more specific markers for these pathologies, this indicator can significantly increase the early detection of cancer.

Resident Microbiome of Kidney Tumors.

Emerging research has uncovered the significance of microbiota in carcinogenesis, with specific bacterial infectious agents linked to around 15% of malignant tumors. This review is focused on the resident kidney microbiome, its composition, and alterations in various diseases. Recent studies have shown that bacteria can infiltrate the kidney, with differences between normal and tumor tissue. These studies have identified distinctive microorganisms unique to both conditions, hinting at their potential clinical relevance. Research into the kidney microbiome diversity reveals differences in tumor tissue, with specific taxa associated with different histological types. Notably, the alpha diversity indices suggest variations in bacterial content between tumor and normal tissue, offering insights into potential diagnostic and prognostic use of these markers. Better studied is the impact of the gut microbiome on therapy efficacy in malignant kidney tumors. Antibiotics, which can alter the gut microbiome, have been linked to survival outcomes in patients receiving targeted therapy and immunotherapy. The findings suggest that the uncontrolled use of antibiotics may not only contribute to bacterial resistance but also disrupt the normal microbiome, potentially influencing the development of oncological diseases. In-depth investigation into the resident kidney microbiome is essential for addressing fundamental and practical aspects of kidney tumor development.

Determination of the Allelic Composition of the sdw1/denso (HvGA20ox2), uzu1 (HvBRI1) and ari-e (HvDep1) Genes in Spring Barley Accessions from the VIR Collection.

The lodging of barley significantly limits its potential yield, leads to the deterioration of grain quality, and complicates mechanized harvesting. More than 30 dwarfness and semi-dwarfness genes and loci are known for barley, and their involvement in breeding can solve the problem of lodging. The most common dwarfing alleles are of the genes sdw1/denso (HvGA20ox2), uzu1 (HvBRI1), and ari-e (HvDep1). The aim of this study was the design of dCAPS markers for the sdw1.c and ari-e.GP alleles and the molecular screening of barley accessions from the VIR collection for identifying these and other dwarfing alleles commonly used in breeding. Two dCAPS markers have been developed to identify the sdw1.c allele of the HvGA20ox2 gene and ari-e.GP of HvDep1. These dCAPS markers and two known from the literature CAPS and dCAPS markers of the alleles sdw1.a/sdw1.e, sdw1.c, sdw1.d, and uzu1.a were used in the molecular screening of 32 height-contrasting barley accessions. This made it possible to identify the accessions with alleles sdw1.a/sdw1.e, sdw1.c, and sdw1.d of the HvGA20ox2 gene, as well as accessions with a combination of sdw1.c and uzu1.a alleles of the genes HvGA20ox2 and HvBRI1. A comparison of the results of genotyping and phenotyping showed that the presence of dwarfing alleles in all genotypes determines high or medium lodging resistance regardless of the influence of weather conditions. Twelve accessions were found to contain the new allele sdw1.ins of the HvGA20ox2 gene, which differs from the known allele sdw1.c by a larger size of PCR products. It is characterized by the Thalos_2 transposon insertion; the subsequent GTTA insertion, common with the sdw1.c allele; and by a single-nucleotide G→A substitution at the 165 position.

Prognostic signature based on mitochondria quality control proteins for the prediction of lung adenocarcinoma patients survival.

Lung cancer is the leading cause of cancer mortality worldwide. In recent years, the incidence of lung cancer subtype lung adenocarcinoma (LUAD) has steadily increased. Mitochondria, as a pivotal site of cell bioenergetics, metabolism, cell signaling, and cell death, are often dysregulated in lung cancer cells. Mitochondria maintenance and integrity depend on mitochondrial quality control proteins (MQCPs). During lung cancer progression, the levels of MQCPs could change and promote cancer cell adaptation to the microenvironment and stresses. Here, univariate and multivariate proportional Cox regression analyses were applied to develop a signature based on the level of MQCPs (dimeric form of BNIP3, DRP1, and SIRT3) in tumorous and non-tumorous samples of 80 patients with LUAD. The MQCP signature could be used to separate the patients with LUAD into high- and low-risk groups. Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with the low-risk patients. Moreover, a nomogram combining clinicopathologic features and the MQCP signature was constructed and validated to predict 1-, 3-, and 5-year overall survival of the patients. Thus, this study presents a novel signature based on MQCPs as a reliable prognostic tool to predict overall survival for patients with LUAD.

Tourette syndrome and obsessive-compulsive disorder: A comprehensive review of structural alterations and neurological mechanisms.

Currently, it is possible to study the pathogenesis of Tourette's syndrome (TS) in more detail, due to more advanced methods of neuroimaging. However, medical and surgical treatment options are limited by a lack of understanding of the nature of the disorder and its relationship to some psychiatric disorders, the most common of which is obsessive-compulsive disorder (OCD). It is believed that the origin of chronic tic disorders is based on an imbalance of excitatory and inhibitory influences in the Cortico-Striato-Thalamo-Cortical circuits (CSTC). The main CSTCs involved in the pathological process have been identified by studying structural and neurotransmitter disturbances in the interaction between the cortex and the basal ganglia. A neurotransmitter deficiency in CSTC has been demonstrated by immunohistochemical and genetic methods, but it is still not known whether it arises as a consequence of genetically determined disturbances of neuronal migration during ontogenesis or as a consequence of altered production of proteins involved in neurotransmitter production. The aim of this review is to describe current ideas about the comorbidity of TS with OCD, the involvement of CSTC in the pathogenesis of both disorders and the background of structural and neurotransmitter changes in CSTC that may serve as targets for drug and neuromodulatory treatments.

Macrophage - tumor cell interaction beyond cytokines.

Tumor cells communication with tumor associated macrophages is a highly important factor of tumor malignant potential development. For a long time, studies of this interaction were focused on a cytokine- and other soluble factors -mediated processes. Discovery of exosomes and regulatory RNAs as their cargo opened a broad field of research. Non-coding RNAs (ncRNAs) were demonstrated to contribute significantly to the development of macrophage phenotype, not only by regulating expression of certain genes, but also by providing for feedback loops of macrophage activation. Being a usual cargo of macrophage- or tumor cell-derived exosomes ncRNAs provide an important mechanism of tumor-stromal cell interaction that contributes significantly to the pathogenesis of various types of tumors. Despite the volume of ongoing research there are still many gaps that must be filled before the practical use of ncRNAs will be possible. In this review we discuss the role of regulatory RNAs in the development of macrophage phenotype. Further we review recent studies supporting the hypothesis that macrophages may affect the properties of tumor cells and vice versa tumor cells influence macrophage phenotype by miRNA and lncRNA transported between these cells by exosomes. We suggest that this mechanism of tumor cell - macrophage interaction is highly promising for the development of novel diagnostic and therapeutic strategies, though many problems are still to be solved.

Role of macrophages in progression of colorectal cancer: a contrast with the traditional paradigm.

The phenotype of tumor-associated macrophages may be critical for tumor immunity, angiogenesis, and clinical disease outcome. Here, we elucidated the prognostic significance of the neovasculature and macrophages in colorectal cancer. We analyzed the effect of M2 macrophage density on the clinical behavior of 151 primary colorectal carcinomas using CD206 as a marker for type 2 macrophages. Triple immunohistochemical staining (ERG, SMA, and podoplanin) was used for microvessel evaluation. We found that M2 macrophages in colorectal cancer did not have a direct association with metastatic behavior. However, high numbers of CD206 tumor-associated macrophages correlated positively with recurrence-free interval duration (P=0.005). Fewer macrophages in the tumor microenvironment resulted in insufficient coverage of newly formed vessels by pericytes (P=0.011), and a high number of pericyte-impaired microvessels correlated with metastatic behavior (P<0.001). These results suggested that type 2 macrophages had a role in limiting the metastatic process by affecting vascular maturity and normalization. These findings contribute to understanding complex interactions in the tumor microenvironment and the clinical behavior of colorectal cancer.

Diagnostic and prognostic potential of the resident non-small cell lung cancer microbiome.

The data of a comprehensive comparative study of the taxonomic composition of the resident microbiome of tumors from 26 patients with non-small cell lung cancer are presented. Analysis of taxonomic diversity revealed 10 types, 280 genera and 788 species of microorganisms. The analysis of the relative content and prognostic significance was carried out for 62 dominant genera. Differences in the relative abundance of bacteria of the genera Acinetobacter, Halomonas, and Chryseobacterium between tumor and conditionally normal lung tissue were found, but their diagnostic potential was not confirmed. The correlation analysis did not reveal any relationship between the content of various genera of bacteria and the histological type of the tumor, its localization, and the age of the patients. Differences were found in the content of the studied bacteria depending on the stage of the disease, the presence of regional metastases and tumor differentiation. The prognostic significance of bacteria of the genera Variovorax and Pseudoclavibacter in non-small cell lung cancer was established. The results obtained can be used in the development of new effective methods for the diagnosis and prognosis of non-small cell lung cancer.

Risk modeling of femoral neck fracture based on geometric parameters of the proximal epiphysis.

BACKGROUND: Fractures of the proximal femur epiphysis are problematic for state health care because they are associated with severe medical and social problems and high morbidity and mortality rates. AIM: To model the potential risk of hip fracture via femur geometric parameters. METHODS: Seventy educational cadaveric femurs from people aged 14 to 80 years, 10 X-ray images from the records of the Human Anatomy Department and 10 X-ray images from the Department of Traumatology, Orthopedics and Disaster Surgery of Sechenov University, were evaluated. The parameters of the fractured bone were measured using images captured with a Canon d60 camera. The projection values of the proximal epiphysis of the cadaveric femurs and geometric parameters of the bones shown in the X-ray images were measured with Autodesk software (AutoCAD 2018). Analysis of the video frames showing bone rotation reveal that the greater trochanter can be inscribed in a parallelepiped, where one of the faces is parallel to the plane of view in the frontal standard projection and is rectangular. The angle of bone rotation obtained by turning the cube corresponded to the angle measured with the second technique. This reliable method of calculating the rotation of the bone relative to the anterior projection was employed in subsequent calculations. The geometric parameters of the femur were measured using X-ray images according to the proposed method. RESULTS: The geometric parameters of 70 femurs were analyzed, and correlation coefficients were calculated. Our measurement results were compared with those reported by other authors. The potential influence of femur geometry on force distribution in the proximal epiphysis of the femur was described, and a 2-dimensional model of the femur epiphysis associated with minimal neck fracture risk was provided. The assessment of the geometric parameters of the femoral epiphysis indicated the greatest risk of a varus fracture of the neck if the angle of the minimal resistance zone (AMRZ) index > 24° and the neck-shaft angle (NSA) < 127.5°. In contrast, the minimum risk was observed at AMRZ < 14° and NSA > 128.87°. CONCLUSION: The proposed method provides the potential femur neck fracture risk based on geometric parameters.

Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients' Survival: A Pilot Study.

The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC and 24 chromophobe RCC). The microbiome was analyzed in tumor and normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was performed using immunohistochemistry. A significant difference in alpha diversity was demonstrated between normal kidney tissue and all types of RCC. Further, we demonstrated that the bacterial burden was higher in adjacent normal tissue than in a tumor. For the first time, we demonstrated a significant correlation between bacterial burden and the content of PU.1+ macrophages and CD66b+ neutrophils in kidney tumors. Tumors with high content of PU.1+ cells and CD66b+ cells in the stroma were characterized by a lower bacterial burden. In the tumors with high bacterial burden, the number of PU.1+ cells and CD66b+ was associated with a poor prognosis. The identified associations indicate the great prognostic potential of a combined tumor microbiome and stromal cell analysis.

Clinical and prognostic significance of the soluble form of the VISTA immunity control point in patients with primary bone tumors.

The data of a comparative enzyme-linked immunosorbent assay of the content of the soluble form of the immunity checkpoint VISTA in the blood serum of 30 healthy donors (control group), 79 patients with primary malignant (osteosarcoma - 30, chondrosarcoma - 31, chordoma - 14) and 14 borderline (giant cell tumor) bone neoplasms are presented. In the general group of patients with malignant neoplasms of bones, the median sVISTA content in blood serum is statistically significant lower than in the control (p = 0.040). In patients with bone tumors and healthy donors over 18 years of age, there was a decrease with age in serum sVISTA levels. There were no significant differences in sVISTA concentration between patients with osteosarcoma, chondrosarcoma and healthy donors. Only in patients with chordoma were sVISTA levels statistically significant lower than in controls (p = 0.013). In the groups of patients with chondrosarcoma and osteosarcoma of the bone, there were no significant associations between the serum sVISTA content and the main clinical and morphological characteristics of the disease. In patients with osteosarcoma, no relationship was found between sVISTA levels and overall survival rates, while in patients with bone chondrosarcoma, there was a tendency towards a favorable prognosis with a high content of the marker in the blood serum.

Prognostic Significance of the Microbiome and Stromal Cells Phenotype in Esophagus Squamous Cell Carcinoma.

Esophageal cancer is one of the most aggressive malignant neoplasms, with low survival rates and limited treatment options. In this study we analyzed the microbiome composition and the phenotype of inflammatory tumor infiltrate in squamous cell carcinoma of esophagus (ESCC) and examined possible relationships between them and their prognostic significance. We found that the predominant phyla of microorganisms found in both tumors and adjacent normal tissues were Firmicutes, Proteobacteria, Actinobacteria, Gemmatimonadetes and Bacteroidetes. We established that only bacteria of the genus Staphylococcus differ between tumors and normal tissues. We found a significant correlation between bacterial burden and the phenotype of the tumor stroma. Namely, a group of tumors characterized by a high expression of CD206 (r = -0.3976, p = 0.0056) in the stroma and iNOS (r = -0.2953, p = 0.0439) in tumor cells is characterized by a higher bacterial burden. Further, we established that in the group with a high content of CD206+ macrophages, there is also a predominance of gram-positive bacteria over gram-negative ones. We found that gram-positive bacterial burden is associated with disease prognosis in ESCC showing high content of CD206+ macrophages. In conclusion we established that the tumor microbiome, can be prognostically significant for ESCC when combined with other stromal markers.

Bioactive Components in Oat and Barley Grain as a Promising Breeding Trend for Functional Food Production.

Cereal crops, such as oats and barley, possess a number of valuable properties that meet the requirements for functional diet components. This review summarized the available information about bioactive compounds of oat and barley grain. The results of studying the structure and physicochemical properties of the cell wall polysaccharides of barley and oat are presented. The main components of the flavonoids formation pathway are shown and data, concerning anthocyanins biosynthesis in various barley tissues, are discussed. Moreover, we analyzed the available information about structural and regulatory genes of anthocyanin biosynthesis in Hordeum vulgare L. genome, including ß-glucan biosynthesis genes in Avena sativa L species. However, there is not enough knowledge about the genes responsible for biosynthesis of ß-glucans and corresponding enzymes and plant polyphenols. The review also covers contemporary studies about collections of oat and barley genetic resources held by the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR). This review intended to provide information on the processes of biosynthesis of biologically active compounds in cereals that will promote further researches devoted to transcription factors controlling expression of structural genes and their role in other physiological processes in higher plants. Found achievements will allow breeders to create new highly productive varieties with the desirable properties.

Hard for humans, hard for machines: predicting readmission after psychiatric hospitalization using narrative notes.

Machine learning has been suggested as a means of identifying individuals at greatest risk for hospital readmission, including psychiatric readmission. We sought to compare the performance of predictive models that use interpretable representations derived via topic modeling to the performance of human experts and nonexperts. We examined all 5076 admissions to a general psychiatry inpatient unit between 2009 and 2016 using electronic health records. We developed multiple models to predict 180-day readmission for these admissions based on features derived from narrative discharge summaries, augmented by baseline sociodemographic and clinical features. We developed models using a training set comprising 70% of the cohort and evaluated on the remaining 30%. Baseline models using demographic features for prediction achieved an area under the curve (AUC) of 0.675 [95% CI 0.674-0.676] on an independent testing set, while language-based models also incorporating bag-of-words features, discharge summaries topics identified by Latent Dirichlet allocation (LDA), and prior psychiatric admissions achieved AUC of 0.726 [95% CI 0.725-0.727]. To characterize the difficulty of the task, we also compared the performance of these classifiers to both expert and nonexpert human raters, with and without feedback, on a subset of 75 test cases. These models outperformed humans on average, including predictions by experienced psychiatrists. Typical note tokens or topics associated with readmission risk were related to pregnancy/postpartum state, family relationships, and psychosis.

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer.

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.

Thermogemmata fonticola gen. nov., sp. nov., the first thermophilic planctomycete of the order Gemmatales from a Kamchatka hot spring.

A novel aerobic moderately thermophilic bacterium, designated strain 2918T, was isolated from a terrestrial hot spring of Kamchatka, Russian Federation. Gram-negative, motile, spherical cells were present singly, in pairs, or aggregates, and reproduced by budding. The strain grew at 25-60°C and within a pH range of 5.0-8.0 with an optimum at 54-60°C and pH 7.5. Strain 2918T did not require sodium chloride or yeast extract for growth. It was a chemoorganoheterotroph, growing on mono-, di- and polysaccharides (starch, lichenan, galactan, arabinan, xanthan gum, beta-glucan). No growth was observed under anaerobic conditions neither in the presence of sulfur, nitrate, or thiosulfate nor without adding any electron acceptor. Major cellular fatty acids were C18:0 and C20:0. The respiratory quinone was MK-6. The size of the genome of strain 2918T was 4.81 Mb. Genomic DNA G+C content was 60.4mol%. According to the 16S rRNA gene sequence and conserved protein sequences phylogenies, strain 2918T represented a distinct lineage of the order Gemmatales within Planctomycetes. Based on phylogenetic analysis and phenotypic features, the novel isolate was assigned to a novel genus in the Gemmatales for which the name Thermogemmata gen. nov. is proposed. Strain 2918T (=KCTC 72012T =VKM B-3161T) represents its first species Thermogemmata fonticola sp. nov.

Cold Conditioned: Discovery of Novel Alleles for Low-Temperature Tolerance in the Vavilov Barley Collection.

Climate changes leading to higher summer temperatures can adversely affect cool season crops like spring barley. In the Upper Midwest region of the United States, one option for escaping this stress factor is to plant winter or facultative type cultivars in the autumn and then harvest in early summer before the onset of high-temperature stress. However, the major challenge in breeding such cultivars is incorporating sufficient winter hardiness to survive the extremely low temperatures that commonly occur in this production region. To broaden the genetic base for winter hardiness in the University of Minnesota breeding program, 2,214 accessions from the N. I. Vavilov Institute of Plant Industry (VIR) were evaluated for winter survival (WS) in St. Paul, Minnesota. From this field trial, 267 (>12%) accessions survived [designated as the VIR-low-temperature tolerant (LTT) panel] and were subsequently evaluated for WS across six northern and central Great Plains states. The VIR-LTT panel was genotyped with the Illumina 9K SNP chip, and then a genome-wide association study was performed on seven WS datasets. Twelve significant associations for WS were identified, including the previously reported frost resistance gene FR-H2 as well as several novel ones. Multi-allelic haplotype analysis revealed the most favorable alleles for WS in the VIR-LTT panel as well as another recently studied panel (CAP-LTT). Seventy-eight accessions from the VIR-LTT panel exhibited a high and consistent level of WS and select ones are being used in winter barley breeding programs in the United States and in a multiparent population.

Bak and Bcl-xL Participate in Regulating Sensitivity of Solid Tumor Derived Cell Lines to Mcl-1 Inhibitors.

BH3 mimetics represent a promising tool in cancer treatment. Recently, the drugs targeting the Mcl-1 protein progressed into clinical trials, and numerous studies are focused on the investigation of their activity in various preclinical models. We investigated two BH3 mimetics to Mcl-1, A1210477 and S63845, and found their different efficacies in on-target doses, despite the fact that both agents interacted with the target. Thus, S63845 induced apoptosis more effectively through a Bak-dependent mechanism. There was an increase in the level of Bcl-xL protein in cells with acquired resistance to Mcl-1 inhibition. Cell lines sensitive to S63845 demonstrated low expression of Bcl-xL. Tumor tissues from patients with lung adenocarcinoma were characterized by decreased Bcl-xL and increased Bak levels of both mRNA and proteins. Concomitant inhibition of Bcl-xL and Mcl-1 demonstrated dramatic cytotoxicity in six of seven studied cell lines. We proposed that co-targeting Bcl-xL and Mcl-1 might lead to a release of Bak, which cannot be neutralized by other anti-apoptotic proteins. Surprisingly, in Bak-knockout cells, inhibition of Mcl-1 and Bcl-xL still resulted in pronounced cell death, arguing against a sole role of Bak in the studied phenomenon. We demonstrate that Bak and Bcl-xL are co-factors for, respectively, sensitivity and resistance to Mcl-1 inhibition.