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Abstract Background Diabetes is associated with a prothrombotic state that contributes to cardiovascular (CV) events in type 2 diabetes (T2DM). Activated factor VII (FVIIa)– antithrombin (AT) complexes are indicative of tissue factor (TF) exposure and have been associated with thromboembolic risk in coronary artery disease. To our knowledge there have been no reports on FVIIa-AT complexes in T2DM, therefore we assessed factors that determine FVIIa-AT complexes in this disease and the impact of higher complexes on a prothrombotic state. Methods In 108 T2DM patients (mean age 63.8 years, 52.8% men, median HbA1c of 6.9 [interquartile range 6.1–8.2] %) and 83 age- and sex-matched non-diabetic subjects, we measured FVIIa-AT complexes. Metabolic control of T2DM involved fasting glucose, glycated hemoglobin (HbA1c), albumin/creatinine ratio (ACR), and lipid levels. To characterize a prothrombotic state, we determined thrombin generation parameters, fibrinolysis markers, and plasma fibrin clot properties. Results FVII-AT complexes in T2DM patients were similar to controls (73.6 [59.4–91.7] vs. 79.6 [59.2–97.1]pM, respectively, p = 0.30). The T2DM patients with FVIIa-AT in the top vs. the bottom quartile had a larger prevalence of active smoking and insulin use, along with higher fasting glucose (+ 36.4%), HbA1c (+ 27.4%), ACR (+ 72.8%), total cholesterol (+ 34.5%), and LDL-cholesterol (+ 80%). FVIIa-AT complexes showed no associations with in vitro thrombin generation potential, plasma fibrin clot properties, or fibrinolysis variables. On multivariable analysis HbA1c, ACR, and total cholesterol remained independently associated with FVIIa-AT complexes in T2DM. Conclusions This is the first study to show that in T2DM higher FVIIa-AT complexes are associated with markers of dyslipidemia and glycemia control, indicating that TF-induced coagulation activation could be suppressed by achieving treatment targets. Graphical abstract

Artykuł przedstawia postrzeganie ustroju Republiki Weneckiej przez polskich podróżników na przełomie XVIII i XIX w. W relacjach z podróży peregrynanci opisywali poszczególne organy władzy, często porównując je z ich odpowiednikami na ziemiach polskich, bądź wyrażali chęć wprowadzenia podobnych rozwiązań w Rzeczypospolitej Obojga Narodów. Opisywano także zachowania szlachty oraz doszukiwano się przyczyn słabnącej potęgi miasta i upadku Republiki Weneckiej, co także wielokrotnie nawiązywało do sytuacji w ojczyźnie pamiętnikarzy.

Abstract Objectives Emergency department (ED) visits resulting from suicidal thoughts and behaviors have increased at alarming rates among youth in the United States in recent years. Understanding trends among specific racial, ethnic, gender, and/or age subgroups can provide the foundation for tailored solutions for those with the greatest need for support. Methods Using data from the Florida State Emergency Department Database from 2016 to 2021, we calculated annual rates of ED suicide‐related diagnoses per 1000 young people aged 8‒21 years. We explored annual trends by age and intersectional race/ethnicity and sex subgroups. Additionally, we examined subgroup‐specific stratified percent changes from 2016 to 2019 and 2016 to 2021. Results Among 8‒12‐year olds, the highest rates of suicide‐related ED encounters occurred among Black males and females and this trend was steady over time. Among 13‒21‐year‐old patients, Black and White females displayed the highest rates of suicide‐related ED encounters across 2016‒2021, and all subgroups experienced a slight decline in 2020 and 2021. Rates generally increased between 2016 and 2019, with the largest percent increase (10.6%) occurring among Black females aged 18‒21 years, whereas there was a trend of decreased rates among most subgroups between 2019 and 2021. Conclusions Across all years and age groups, Black females showed consistently higher rates of suicide‐related ED encounters than almost any other subgroup, supporting previous research that Black adolescent females may be disproportionately suffering from the mental health crisis faced by young people. Furthermore, preteen Black males need additional mental health support, as do adolescent and young adult White females.

Dissemination of food-borne L. monocytogenes in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-ΔC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-ΔC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes.

Abstract We present a novel problem, called MetaEC, which aims to infer gene-species assignments in a collection of partially leaf-labeled gene trees labels by minimizing the size of duplication episode clustering (EC). This problem is particularly relevant in metagenomics, where incomplete data often poses a challenge in the accurate reconstruction of gene histories. To solve MetaEC, we propose a polynomial time dynamic programming (DP) formulation that verifies the existence of a set of duplication episodes from a predefined set of episode candidates. In addition, we design a method to infer distributions of gene-species mappings. We then demonstrate how to use DP to design an algorithm that solves MetaEC. Although the algorithm is exponential in the worst case, we introduce a heuristic modification of the algorithm that provides a solution with the knowledge that it is exact. To evaluate our method, we perform two computational experiments on simulated and empirical data containing whole genome duplication events, showing that our algorithm is able to accurately infer the corresponding events.

This article analyses and evaluates the model used by the Jastrzebie Coal Company in Poland to forecast the values of continuous deformations of land surfaces caused by underground mining. Particular attention is paid to the values of terrain inclinations, which cause significant deflections of buildings located in mining areas affected by exploitation. The inclination forecasts were made using Bialek’s model, with the values of its parameters determined in situ and after completion of the exploitation of a longwall. The obtained results were compared with the values of the terrain inclinations calculated from the results of geodetic measurements carried out at observation points located near the buildings and discontinuous linear deformations (i.e., the ground steps). The conducted research shows that the correlations between the absolute values of the practical inclinations and the values of the theoretical inclinations were rather weak, as the values of their correlation coefficients did not exceed 0.24. The tested model underestimated 45.5% of the values of the inclinations observed in situ by an average of −53.5%. The model values of the inclinations for the remaining observed inclinations (54.5%) were overestimated by an average of 461.9%. The largest anomalies were obtained in the case of inclination values from points located near the ground steps. The effectiveness of predicting inclination values with a commonly used model is strongly reduced when discontinuous linear deformations appear. Nonetheless, it reflects well the mining area categories.

MicroRNAs (miRNA) are involved in the process of carcinogenesis, including the development of endometrial cancer (EC). This study aimed to investigate the association between the expression of three miRNAs (miR-21-5p, miR-205-5p, and miR-222-3p) in endometrial cancer tissues. In addition, the stability of expression of SNORD48 and U6, which were initially planned to be used as reference miRNAs for normalization, was investigated. Endometrial tissue was obtained from 111 patients with EC during hysterectomy and from 19 patients undergoing surgery for uterine fibroids or pelvic organ prolapse as a control group without neoplastic changes. Our study was based on calculations made with a digital PCR method (Qiagen, Hilden, Germany) to measure the absolute expression. In the endometrial cancer tissue, miR-205-5p was upregulated, while miR-222-3p and SNORD48 were downregulated compared to the control group. We detected statistically significant correlation of miR-205-5p, U6, and SNORD48 expression with different histological grades; the expression of miR-205-5p increases with the histopathological grade advancement (intraepithelial neoplasia- EIN = 1590, G1 = 3367.2, G2 = 8067 and G3 = 20,360), while U6 and SNORD expression decreases from EIN to G2 and increases again in the G3 grade (U6: EIN = 19,032, G1 = 16,482.4, G2 = 13,642.4, G3 = 133,008; SNORD48: EIN = 97,088, G1 = 59,520, G2 = 43,544, G3 = 227,200). Our study suggests that upregulation of miR-205-5p and downregulation of miR-222-3p and SNORD48 may influence development of endometrial cancer. Moreover, miR-205-5p, U6, and SNORD48 expression changes may be associated with progression of endometrial cancer. The results also indicate that SNORD48 and U6, commonly used as internal references, may influence endometrial cancer development and progression; therefore, they should not be used as references. However, it is important to note that further research is required to understand their role in endometrial cancer.

During the more than 3 years of the “Quality” program at JSW S.A., a geological database has been built from scratch, collecting data from all exploratory boreholes, roadway profiling and the results of chemical analyses in one place – placing particular emphasis on parameters affecting the quality of coke. Working with digital databases requires new competencies for geologists – the ability to efficiently obtain information ready for further processing. As intended, the geological model became the basis for forecasting the quantity and quality of mined coal used in coke production. In the course of the work, a discrepancy became apparent between the geological interpretation of the structure of the deposit – as understood by the assumptions of the geological documentation, and the technological conditions of mining. The article presents resulting changes in the approach to modeling lithology and quality parameters. In addition, examples of the application of the geological database and the geological model in the daily work of the geological department are presented.

This article analyses and evaluates the model used by the Jastrzebie Coal Company in Poland to forecast the values of continuous deformations of land surfaces caused by underground mining. Particular attention is paid to the values of terrain inclinations, which cause significant deflections of buildings located in mining areas affected by exploitation. The inclination forecasts were made using Bialek's model, with the values of its parameters determined in situ and after completion of the exploitation of a longwall. The obtained results were compared with the values of the terrain inclinations calculated from the results of geodetic measurements carried out at observation points located near the buildings and discontinuous linear deformations (i.e., the ground steps). The conducted research shows that the correlations between the absolute values of the practical inclinations and the values of the theoretical inclinations were rather weak, as the values of their correlation coefficients did not exceed 0.24. The tested model underestimated 45.5% of the values of the inclinations observed in situ by an average of −53.5%. The model values of the inclinations for the remaining observed inclinations (54.5%) were overestimated by an average of 461.9%. The largest anomalies were obtained in the case of inclination values from points located near the ground steps. The effectiveness of predicting inclination values with a commonly used model is strongly reduced when discontinuous linear deformations appear. Nonetheless, it reflects well the mining area categories. [ABSTRACT FROM AUTHOR]

Dissemination of food-borne L. monocytogenes in the host relies on internalinmediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-DC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-DC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes. [ABSTRACT FROM AUTHOR]

Mutagenesis is responsive to many environmental factors. Evolution therefore depends on the environment not only for selection but also in determining the variation available in a population. One such environmental dependency is the inverse relationship between mutation rates and population density in many microbial species. Here, we determine the mechanism responsible for this mutation rate plasticity. Using dynamical computational modelling and in culture mutation rate estimation, we show that the negative relationship between mutation rate and population density arises from the collective ability of microbial populations to control concentrations of hydrogen peroxide. We demonstrate a loss of this density-associated mutation rate plasticity (DAMP) when Escherichia coli populations are deficient in the degradation of hydrogen peroxide. We further show that the reduction in mutation rate in denser populations is restored in peroxide degradation-deficient cells by the presence of wild-type cells in a mixed population. Together, these model-guided experiments provide a mechanistic explanation for DAMP, applicable across all domains of life, and frames mutation rate as a dynamic trait shaped by microbial community composition. In some bacteria, mutation rates depend on environmental factors such as population density. This study uses simulation-guided experiments to show that denser microbial populations detoxify their environment more efficiently, resulting in a reduced rate of mutation. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer has emerged as the main gynecological malignant tumour in developed countries. The development of molecular techniques allows the precise profiling of each case. This affects the selection of a therapy and the patient's prognosis. Long non-coding RNAs, which influence tumour development, are a novelty in endometrial cancer. They can both stimulate and inhibit the progression of the disease. Their number is constantly growing, and the mechanisms of action are not fully discovered. Some of them may become targets for new molecular therapies in the future. Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer are long non-coding RNAs (lncRNAs). LncRNA-coding genes occupy a large fraction of the human genome. LncRNAs regulate many aspects of cell development, metabolism, and other physiological processes. Diverse types of lncRNA can function as a tumour suppressor or an oncogene that can alter migration, invasion, cell proliferation, apoptosis, and immune system response. Recent studies suggest that selected lncRNAs are important in an endometrial cancer course. Our article describes over 70 lncRNAs involved in the development of endometrial cancer, which were studied via in vivo and in vitro research. It was proved that lncRNAs could both promote and inhibit the development of endometrial cancer. In the future, lncRNAs may become an important therapeutic target. The aim of this study is to review the role of lncRNAs in the development of carcinoma of uterine body. [ABSTRACT FROM AUTHOR]

The article presents Leo Lipski’s Wybór listów do Ireny Lewulis (Selected Letters to Irena Lewulis) as a heterological document on the creative process. Alongside the traditional intimate semantic fabric typical of love epistolography, Wybór listów embodies a significant self-reflexive and self-thematizing discourse on writing as a form of life and raison d’être. The article employs post-deconstructive practices of micrological readings and re-readings to conceptualize Lipski’s texts as plastic forms of writing. In line with theorists such as Morin and Malabou, these forms engage the intertwined dimensions of the personal, the global, the organic, and the discursive. Moreover, the article argues that the letters’ rough drafts comprising the above selection prove to be textual battlegrounds where real writerly toil thoroughly intensifies the present, the corporeal, the linguistic, and the graphic. Ultimately, the presented approach to Lipski’s specific autography provides one of many keys to understanding his oeuvre. Furthermore, such an approach forms a basis for diagnosing new ontologies of subjectivity, works, and the text–life relationship in a more general way. [ABSTRACT FROM AUTHOR]

Background: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. Methods: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. Results: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 μg/L vs. 1176.42 μg/L, p < 0.001; Zn: 707.05 μg/L vs. 901.67 μg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). Conclusion: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels. [ABSTRACT FROM AUTHOR]

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The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose‐dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full‐length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose‐dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations. [ABSTRACT FROM AUTHOR]