Additional Markers Research Articles

Semantico-Pragmatic Approach to the Uses of autem in Plautus

This work aims to study the syntactic and semantico-pragmatic properties of autem in Plautus. The connector has a fundamental binary value expressing the notion of addition and that of opposition. Therefore, autem is used as an addition marker to relate syntactic constituents, a marker ensuring the reorientation of language activity on the level of enunciation, a limitation marker intended to make a thematic selection among elements of a paradigm as well as a marker of contrastive focus with argumentative or non-argumentative scope. Besides, the study of extra-linguistic data has highlighted the functions of autem linking with non-verbal and aspects of the discourse situation.

An immunohistochemical study of diffuse large B-cell lymphoma with molecular subtyping based on Hans algorithm.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma accounting for about 40% of all lymphomas. The international prognostic index (IPI), which relies on clinical and laboratory parameters, is used as a prognostic tool in DLBCL. In this study, we have included cases of DLBCL not otherwise specified (NOS) type to test the usefulness of the biological subclassification of DLBCL by immunohistochemistry (IHC) using the Hans algorithm into the germinal center B-like (GCB) type and nongerminal center (non-GCB) type. We correlated the subtypes with the demographics, site of involvement, IPI scores, and stage. 1. To study the immunohistochemical profile of DLBCL. 2. To classify patients with DLBCL into germinal center and nongerminal center subtypes. 3. To review the clinical presentations, clinical staging, and follow-up data in cases of DLBCL. A total of 152 cases of DLBCL reported from January 2010 to March 2018 were included in this study. Clinical data, treatment details, and follow-up were reviewed. Apart from the routine IHC markers for DLBCL, additional markers CD10, BCL6, and MUM 1 were performed to classify DLBCL into GCB type and non-GCB type using the Hans algorithm. The median age of presentation was 53 years with male-to-female ratio of 2:1. Most of the patients presented with nodal involvement (56.6%); cervical lymph node is the most common site (46.5%). The majority of the patients presented in Ann Arbor stage 1 (44.8%). According to the international prognostic index, 34.8% had a score of 3 (high intermediate). After IHC studies, GCB subtype (51.5%) of DLBCL emerged as more common than non-GCB type (48.5%). The two subtypes differed significantly with regard to sex (i.e. GCB type was more common in males and non-GCB type in females) and showed no significance with regard to any of the other clinical features and prognostic parameters evaluated. Our study showed that IHC was a useful tool to subclassify DLBCL into GCB and non-GCB subtypes and may be easily incorporated in routine clinical practice.

One Journal, Different Practices: A Corpus-Based Study of Interactive Metadiscourse in Applied Linguistics

Abstract Research articles are a primary medium for scholars to communicate with disciplinary community, but there is little evidence suggesting how much writing practices on different research subjects within a discipline diverge in a single journal. This study remedies the oversight by comparing the use of interactive metadiscourse in the papers of Applied Linguistics on language acquisition and discourse analysis. Based on a corpus of 30 research articles on each research subject, results show that writers in language acquisition make a significantly more frequent use of additive and consequential transitional markers, reformulators, and non-integral citations. However, discourse analysts prefer to invest in exemplifiers, linear and non-linear references and topic shifts. All the differences can be attributable to the characteristics of disciplinary research paradigms, which lead to different knowledge-making and interactive patterns in academic writing. The findings offer empirical evidence to the rhetorical function of metadiscourse in constructing disciplinary knowledge, and raise pedagogical implications for EAP instructors to help scholars in applied linguistics increase international publications.

Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis. All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded. A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models). Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

GbyE: an integrated tool for genome widely association study and genome selection based on genetic by environmental interaction.

The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).

SorCS2 is involved in promoting periodontitis-induced depression-like behaviour in mice.

Emerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis-induced depression. An experimental periodontitis model was established using SorCS2 knockout mice and their wild-type littermates, and depression-like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate-associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone-related factors were measured by immunofluorescence, western blotting, and enzyme-linked immunosorbent assays. SorCS2 deficiency alleviated periodontitis-induced depression-like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro-BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered. Our study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis-induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis-associated depression.

Methylomic signature of lithium response in bipolar disorder

Introduction Bipolar disorder (BD) is a chronic and severe psychiatric disorder, characterized by the alternance of episodes of (hypo)-mania and major depression. Lithium (Li) is the first-line treatment for BD but unfortunately response to Li is highly variable: after at least two consecutive years of treatment, only a fraction of patients receiving Li will display significant improvement in the frequency and/or severity of mood recurrences. This interindividual variability of treatment response is difficult to predict, in the bipolar disorder context. This could be determined by genetic factors still misidentified by available genetic studies. In addition, no clinical or biological markers are available to reliably define eligibility criteria for a lithium treatment in bipolar disorder. A consequence is a long process of therapeutic trials (18-24 months) to phenotype Li response, delaying the stabilization.ObjectivesTo identify objective biomarkers of the prophylactic response to lithium in order to improve patient care and propose therapeutic alternatives to patients who do not respond to lithium.Methods Using a genome-wide methylomic approach, and then logistic regressions incorporating as covariates the different types of treatments, we were able to identify differentially methylated regions (DMRs) whose methylation difference between responders and non-responders was not impacted by co-prescribed treatments. Then, we used Methylation Specific High-Resolution Melting (MS-HRM), a PCR based method than can be implemented in any medical laboratory at low cost and with minimal equipment, to estimate methylation proportion of 9 DMRs in 61 samples of bipolar patients.Results In the sample of 61 individuals with BD, the 9 MS-HRM-measured DMRs combined with clinical variables (age, sex, cigarette smoking status, lifetime number of hospitalizations, age at onset of BD, polarity at onset, psychotic symptoms at onset, family history of BD, lifetime alcohol/cannabis misuse, panic disorders, Li prescribed as the first mood stabilizer (vs 2nd or 3rd choice)) correctly classified 83,6% of individuals as good or non-responders (n=61, prophylactic response phenotype defined using the “Alda” scale). Excluding the partial responders, the percentage of correctly classified individuals is as high as 100% (n=43, 18 non responders and 25 responders). The AUC are respectively AUC=0.913 and AUC=1.0.ConclusionsThe MS-HMR method allow to identify the response status of individuals with BD with 9 DMR. These DMRs discriminate good from non-responders and can be used in combination with clinical variables.Disclosure of InterestNone Declared

Abstract A089: Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII

Abstract Background: Daily aspirin use versus never use is associated with a 10-20% lower risk of developing epithelial ovarian cancer (EOC). Among women with EOC, aspirin use after diagnosis compared with never use is associated with a 30% improvement in ovarian cancer-specific survival. Inhibition of enzymes in prostaglandin synthesis is a key mechanism responsible for the anti-inflammatory and anti-neoplastic effects of aspirin. Prostaglandins influence immune inflammatory cells in the tumor microenvironment therefore our objective was to evaluate how aspirin use may influence the EOC tumor immune microenvironment. Methods: Tissue microarrays (TMAs) representing EOC tumor tissues from participants in the Nurses’ Health Study (NHS) and NHSII were assessed for total T cells, T cell activation and T cell exhaustion markers within the tumor (epithelium) area using multiplex immunofluorescence. Data on aspirin use and information on EOC risk factors and lifestyle variables were collected by questionnaire every two years. Beta-binomial models were used to estimate odds ratios (ORs) and 95% CIs; these models estimate the odds that a cell was positive for the marker(s) of interest comparing recent regular aspirin use (2+ times per week in the questionnaire cycle prior to diagnosis) versus never use, accounting for the total tumor cells in each core. Former users of aspirin were excluded. Multivariable models were adjusted for cohort, histotype (type 1 versus type 2), age and year of cancer diagnosis, number of CD3+ T cells (in tertiles), hysterectomy, tubal ligation, duration of oral contraceptive use, family history of breast or ovarian cancer, parity and body mass index (as fixed effects) and the participant (random effect) to account for multiple tissue cores per case. Results: We compared tumor tissues from 209 participants with recent pre-diagnosis use of aspirin with 88 participants who never used aspirin. Compared with cases who never used aspirin, recent aspirin users had higher odds of having tumors with recently activated cytotoxic T cells (CD3+CD8+CD69+, OR=1.69, 95% CI: 1.10, 2.59) and T cells expressing exhaustion markers (CD3+Lag-3+, OR=1.63, 95% CI: 1.09, 2.43; CD3+Tim-3+, OR= 1.62, 95% CI: 0.96, 2.72). In contrast, there was no association between recent aspirin use versus never use and odds of a tumor being positive for total T cells (CD3+, OR=1.20, 95% CI: 0.80, 1.79). Conclusions: Our data suggest that recent aspirin use before diagnosis was associated with higher odds of having EOC tumors expressing both recently activated cytotoxic T cells and T cell exhaustion markers. By improving our biological understanding of how aspirin use influences the ovarian tumor immune microenvironment, these results will assist to inform the optimal use of aspirin to improve EOC patient outcomes. Future work will focus on additional immune markers, assess non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use and evaluate associations between aspirin/NSAID use with EOC survival considering the context of tumor immune microenvironment biomarkers. Citation Format: Nicola S. Meagher, Cassandra Hathaway, Mary K. Townsend, Mollie E. Barnard, Jose R. Conejo-Garcia, Brooke L. Fridley, Daryoush Saeed-Vafa, Britton Trabert, Shelley S. Tworoger, Melissa A. Merritt. Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A089.

An adaptive harmonic polynomial cell method for three-dimensional fully nonlinear wave-structure interaction with immersed boundaries

To accurately simulate wave-structure interaction based on fully nonlinear potential flow theory, a three-dimensional (3 D) high-order immersed-boundary adaptive harmonic polynomial cell (IB-AHPC) method is proposed. Both the free surface and body surface are immersed in background octree cells that are adaptively refined near the boundaries of interest, thereby dramatically reducing computational costs without loss of accuracy. We also propose an easy-to-implement IB strategy to deal with possible instabilities in the time-domain solution arising from the intersection of Dirichlet–Neumann boundaries. For a linearized problem of wave-wall interaction, a matrix-based stability analysis is performed, providing mathematical support for the robustness of the proposed IB strategy. In contrast to the two-dimensional HPC method, compressed cells are found to offer superior stability compared to stretched cells in the vertical direction, while equal mesh aspect ratio in the horizontal plane is superior. Cubic octree cells are, however, still preferred in practice. The free surface is primarily described by a set of massless background wave markers; however, to address the challenges of IB methods in tracking the free surface evolution near the structure, additional body-fitted wave markers are introduced close to the waterline. The information exchange between these two sets of wave markers is realized by radial basis function (RBF) interpolation. While standard RBF schemes have grid-size-dependent filtering performance, we propose a normalized RBF scheme, which is then optimized in terms of the number of neighboring nodes, a smoothing coefficient and the basis functions. Excellent accuracy properties of the proposed 3 D IB-AHPC method are demonstrated by studying fully nonlinear wave propagation. The method is further applied to study relevant fully nonlinear wave-structure interaction problems, including sloshing in 3 D rectangular tanks and wave diffraction of a bottom-mounted cylinder in regular waves. Satisfactory agreement is demonstrated with existing experimental and numerical results, suggesting that the proposed 3 D IB-AHPC method is a promising potential-flow method in marine hydrodynamics.

Определение соматических мутаций в гене EZH2 и оценка их прогностической значимости при фолликулярной лимфоме 1–3А цитологического типа

Aim. To determine the incidence and prognostic value of mutations in exon 16 of EZH2 as well as those of polymorphism с.1582-21А&gt;G (rs2072407) in EZH2 in patients with follicular lymphoma (FL) grades 1–3А in relation to morphologic and cytogenetic tumor characteristics.&#x0D; Materials &amp; Methods. The prospective cohort study conducted by the National Research Center for Hematology from January 2017 to April 2021 enrolled 80 patients with newly diagnosed FL grades 1/2 and 3А. The median follow-up was 53 months. Molecular and cytogenetic analyses were based on biopsy samples of lymph nodes obtained before chemotherapy. The mutation status of exon 16 in EZH2 and the presence of intronic polymorphism rs2072407 in EZH2 were examined by Sanger sequencing method. Translocation t(14;18)(q32;q21) was detected by karyotyping or FISH.&#x0D; Results. Mutations in exon 16 of EZH2 (mutEZH2) were identified in 10/80 (13 %) patients. All patients showed missense mutation in codon 646 of EZH2. Translocation t(14;18) was detected in 45/80 (56 %) cases. Poor outcome in the cohort with no t(14;18) was observed 3 times more often than in the group of patients with t(14;18) (p = 0.0001). The presence of t(14;18) was associated with favorable prognosis irrespective of either the mutation status of exon 16 in EZH2 or the FL grade. The analysis of the polymorphism rs2072407 status yielded the following genotypes: AA in 24 % (n = 19), AG in 42 % (n = 34), and GG in 34 % (n = 27) of cases. The variants АА and AG were associated with higher risk of death (hazard ratio 2.9; 95% confidence interval 1.2–10.6; p = 0.01), whereas the genotype GG was associated with wtEZH2 (10 % vs. 37 %) and favorable prognosis (p = 0.065).&#x0D; Conclusion. Significant biological markers for favorable prognosis in FL appeared to be the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407 in EZH2. The previously identified prognostic factors (grade 3А, bulky tumor lesions &gt; 6 cm, Ki-67 &gt; 35 %, and a short interval between symptom onset and chemotherapy start) were incorporated into a new unified personalized predictive (index PPI) FL model by supplementing it with two additional biological markers: the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407. This approach may increase the prognostic value of the new personalized design which will provide the basis for risk-adapted algorithms for FL treatment.

Development of a novel five dye insertion/deletion (INDEL) panel for ancestry determination.

The use of genetic markers, specifically Short Tandem Repeats (STRs), has been a valuable tool for identifying persons of interest. However, the ability to analyze additional markers including Single Nucleotide Polymorphisms (SNPs) and Insertion/Deletion (INDELs) polymorphisms allows laboratories to explore other investigative leads. INDELs were chosen in this study because large panels can be differentiated by size, allowing them to be genotyped by capillary electrophoresis. Moreover, these markers do not produce stutter and are smaller in size than STRs, facilitating the recovery of genetic information from degraded samples. The INDEL Ancestry Informative Markers (AIMs) in this study were selected from the 1000 Genomes Project based on a fixation index (FST) greater than 0.50, high allele frequency divergence, and genetic distance. A total of 25 INDEL-AIMs were optimized and validated according to SWGDAM guidelines in a five-dye multiplex. To validate the panel, genotyping was performed on 155 unrelated individuals from four ancestral groups (Caucasian, African, Hispanic, and East Asian). Bayesian clustering and principal component analysis (PCA) were performed revealing clear separation among three groups, with some observed overlap within the Hispanic group. Additionally, the PCA results were compared against a training set of 793 samples from the 1000 Genomes Project, demonstrating consistent results. Validation studies showed the assay to be reproducible, tolerant to common inhibitors, robust with challenging casework type samples, and sensitive down to 125 pg. In conclusion, our results demonstrated the robustness and effectiveness of a 25 loci INDEL system for ancestry inference of four ancestries commonly found in the United States.

Population genetic structure in the critically endangered Crocodylus intermedius (Crocodilia: Crocodylidae): a shift in perspective for conservation actions in Colombia

Abstract Conservation actions for threatened species and populations aim to preserve their genetic diversity and prevent issues such as inbreeding or outbreeding depressions. This perspective has been incorporated into the management plans proposed for the critically endangered Orinoco crocodile (Crocodylus intermedius) in Colombia. A previous study, which used mitochondrial cytochrome b and cytochrome c oxidase subunit I, suggested that the in situ population management of the Orinoco crocodile in Colombia does not face genetic restrictions. In this research, we re-evaluated this proposal by using an expanded sampling and additional molecular markers (microsatellite nuclear DNA and the mitochondrial D-loop) that have successfully identified crucial information at the population level in other crocodilians. Our findings reveal, for the first time, a pattern of population structure consisting of three genetic clusters with geographical correspondence, matching three ecoregions in the Colombian Orinoco basin. This pattern might be a historical and current consequence of the ecological, bioclimatic, and/or geographical features of the ecoregion. Additionally, we examined the correspondence with the genetic clusters of the confiscated individuals that formed part of the initial population (F0) of the Colombian ex situ species population and successfully assigned most of them to one of these clusters. The genetically distinct clusters should be regarded as independent management units for conserving and managing the species in Colombia.

Socioeconomic inequality in adults undertaking HIV testing over time in Ethiopia based on data from demographic and health surveys.

HIV testing is the entry point to HIV prevention, care and treatment and needs continuous evaluation to understand whether all social groups have accessed services equally. Addressing disparities in HIV testing between social groups results in effective and efficient response against HIV prevention. Despite these benefits, there was no previous study on inequality and determinants over time in Ethiopia. Thus, the objective of this research was to examine socioeconomic inequality in individuals undertaking HIV testing over time, allowing for the identification of persistent and emerging determinants. Data sources for the current study were the 2011 and 2016 Ethiopian Demographic Health Surveys. The 2016 population health survey is the one that Ethiopia used to set national AIDS response strategies; there was no other recent survey with HIV/AIDS-related indicators in Ethiopia. The final sample size for the current study was 28,478 for the year 2011 and 25,542 for the year 2016. The concentration curve and Erreygers' concentration index were used to estimate socioeconomic inequality in HIV testing. Subsequently, decomposition analysis was performed to identify persistent and emerging contributors of socioeconomic inequality. Generalized linear regression model with the logit link function was employed to estimate the marginal effect, elasticity, Erreygers' concentration index (ECI), and absolute and percentage contributions of each covariate. The concentration curve was below the line of equality over time, revealing the pro-rich inequality in HIV testing. The inequality was observed in both 2011 (ECI = 0.200) and 2016 (ECI = 0.213). A household wealth rank had the highest percentage contribution (49.2%) for inequality in HIV testing in 2011, which increased to 61.1% in 2016. Additional markers include listening to the radio (13.4% in 2011 and 12.1% in 2016), education status (8.1% in 2011 and 6.8% in 2016), and resident (-2.0% in 2011 and 6.3% in 2016). Persistent determinants of individuals undertaking HIV testing were age 20-34 years, geographic region, education status, marital status, religion, income, media exposure (listening to the radio, reading newspaper, watching television), knowledge about HIV/AIDS, and attitudes towards people living with HIV. Age between 35 and 44 years and urban residence emerged as new associated factors in 2016. The higher HIV testing coverage was among individuals with higher socioeconomic status in Ethiopia. Socioeconomic inequality amongst individuals undertaking HIV testing was diverging over time. Household wealth rank, mass media exposure, education status, and resident took the largest share in explaining the disparity in individuals undertaking HIV testing between the lower and higher income groups. Therefore, interventions to equalise HIV testing coverage should take account of these determinants.

Thyroid Stimulating Hormone as a Possible Additional COVID-19 Outcome Marker.

Background and Objectives: The interaction between thyroid and SARS-CoV-2 is complex and not yet fully understood. This study aimed to identify a predictive value of serum TSH levels on the short-term and middle-term outcomes of patients hospitalized for COVID-19. Materials and Methods: We retrospectively analyzed electronic records (ERs) data for hospitalized COVID-19 patients between March 2020 and June 2021 and their ERs during outpatient visits, 6-8 weeks post-discharge, in cases of known serum TSH levels and no previous thyroid disorder. The short-term (length of hospital stay, MSCT findings of lung involvement, required level of oxygen supplementation, admission to the ICU, and death) and middle-term outcomes after 6 to 8 weeks post-discharge (MSCT findings of lung involvement) were analyzed. Results: There were 580 patients included: 302 males and 278 females, average age of 66.39 ± 13.31 years, with no known thyroid disease (TSH mean 1.16 ± 1.8; median 0.80; no value higher than 6.0 mIU/L were included). Higher TSH was observed in patients with less severe outcomes and was associated with significantly higher SpO2 during hospitalization. Patients who required overall more oxygen supplementation or HFOT, mechanical ventilation, and patients who were more frequently admitted to the ICU or were more often treated with corticosteroids had lower TSH than those who did not show these indicators of disease severity. Lower TSH was also present in non-survivors when compared to survivors (all p < 0.01). Patients with low TSH during hospitalization more often had persistent lung involvement during the post-COVID-19 period (p = 0.028). In the post-COVID-19 period, there was an overall, statistically significant increase in the TSH levels when compared to TSH during hospitalization (p < 0.001). Conclusions: Low/suppressed serum TSH levels during acute COVID-19 may be an additional laboratory test that should be included in the prediction of unfavorable short- and middle-term outcomes.

Marker and readout genes for defense priming in Pseudomonas cannabina pv. alisalensis interaction aid understanding systemic immunity in Arabidopsis

Following localized infection, the entire plant foliage becomes primed for enhanced defense. However, specific genes induced during defense priming (priming-marker genes) and those showing increased expression in defense-primed plants upon rechallenge (priming-readout genes) remain largely unknown. In our Arabidopsis thaliana study, genes AT1G76960 (function unknown), CAX3 (encoding a vacuolar Ca2+/H+ antiporter), and CRK4 (encoding a cysteine-rich receptor-like protein kinase) were strongly expressed during Pseudomonas cannabina pv. alisalensis-induced defense priming, uniquely marking the primed state for enhanced defense. Conversely, PR1 (encoding a pathogenesis-related protein), RLP23 and RLP41 (both encoding receptor-like proteins) were similarly activated in defense-primed plants before and after rechallenge, suggesting they are additional marker genes for defense priming. In contrast, CASPL4D1 (encoding Casparian strip domain-like protein 4D1), FRK1 (encoding flg22-induced receptor-like kinase), and AT3G28510 (encoding a P loop-containing nucleoside triphosphate hydrolases superfamily protein) showed minimal activation in uninfected, defense-primed, or rechallenged plants, but intensified in defense-primed plants after rechallenge. Notably, mutation in only priming-readout gene NHL25 (encoding NDR1/HIN1-like protein 25) impaired both defense priming and systemic acquired resistance, highlighting its previously undiscovered pivotal role in systemic plant immunity.

Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development

BackgroundThe common house spider Parasteatoda tepidariorum represents an emerging new model organism of arthropod evolutionary and developmental (EvoDevo) studies. Recent technical advances have resulted in the first single-cell sequencing (SCS) data on this species allowing deeper insights to be gained into its early development, but mid-to-late stage embryos were not included in these pioneering studies.ResultsTherefore, we performed SCS on mid-to-late stage embryos of Parasteatoda and characterized resulting cell clusters by means of in-silico analysis (comparison of key markers of each cluster with previously published information on these genes). In-silico prediction of the nature of each cluster was then tested/verified by means of additional in-situ hybridization experiments with additional markers of each cluster.ConclusionsOur data show that SCS data reliably group cells with similar genetic fingerprints into more or less distinct clusters, and thus allows identification of developing cell types on a broader level, such as the distinction of ectodermal, mesodermal and endodermal cell lineages, as well as the identification of distinct developing tissues such as subtypes of nervous tissue cells, the developing heart, or the ventral sulcus (VS). In comparison with recent other SCS studies on the same species, our data represent later developmental stages, and thus provide insights into different stages of developing cell types and tissues such as differentiating neurons and the VS that are only present at these later stages.

Assessment of Platelet Indices as Biomarker for Neonatal Sepsis

Introduction: There is a need to increase the diagnostic capability of the traditional septic screen by adding additional markers. Platelet indices are one such marker that is readily available in routine hemogram reports. Materials and Methods: In this cross-sectional study, all newborn babies were recruited who had signs or symptoms of sepsis or had high-risk factors. Those who had clinical sepsis with positive cultures and/or a positive sepsis screen were classified under group “cases” ( n = 174), whereas all neonates suspected to have sepsis but who had a negative blood culture and a negative sepsis screen were classified under group “control” ( n = 126). Blood culture, sepsis screen, and platelet indices [platelet count, mean platelet volume (MPV), and platelet distribution width (PDW)] were performed on all babies. Babies with congenital or acquired causes of platelet abnormalities (including medication use by mothers with antiplatelet activity) were excluded from this study. Results: In this study, a total of 300 newborn babies were recruited for final analyses. Overall culture positivity was 38%. The mean platelet count was lower in the cases group ( P &lt; 0.001). MPV and PDW were higher in septic babies with statistically significant differences ( P &lt; 0.0001 and P = 0.012, respectively). Thrombocytopenia was the most sensitive marker (85.60%). However, it had low specificity (28.2%). On combining all three platelet markers, specificity increased to 48.4% (with a sensitivity of 64.5%) in detecting babies with neonatal sepsis. The sensitivity of the septic screen alone was 58% (with a specificity of 32.62%). When combining the sepsis screen and platelet indices, the specificity for the diagnosis of neonatal sepsis increased to 62.6%. On receiver operator curve analyses, thrombocytopenia had the highest area under the curve (0.692), followed by MPV (0.644). Conclusion: Platelet indices may be used as sensitive markers in combination with traditional sepsis screening to make an early diagnosis of neonatal sepsis.

Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis.

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients' clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

Определение диагностической значимости маркеров наследственных болезней обмена с применением метода хромато-масс-спектрометрии

Thorough investigation of metabolome by mass spectrometry is of great importance for personalized and preventive medicine. It is only timely laboratory diagnosis involving the use of high-tech chromatographic analysis methods that can help identify the patients with disorders of amino acid and acylcarnitine metabolism. The study was aimed to determine the efficacy of conventional and additional markers of metabolic disorders of amino acids and acylcarnitines detected by chromatography–mass spectrometry for the diagnosis of congenital metabolic disorders in children, as well as to create specific panels of the most effective indicators and determine the potential diagnostic efficacy of indentification of the relationships between the levels of amino acids and acylcarnitines in pediatric patients with congenital metabolic disorders. We assessed amino acid and acylcarnitine profiles in blood spots by high-performance liquid chromatography–tandem mass spectrometry in patients aged 6 months to 16 years (48 boys and 32 girls) with suspected aminoacidopathy and organic aciduria/acidemia. The comparison group consisted of 35 children with suspected peroxisomal metabolic disorders, the control group included 40 generally healthy children of various age groups. The data obtained were used to conduct the analysis of correlations between the groups of markers. Strong correlation was revealed for the levels of metabolically most closely related compounds (r &lt; 0.8, р &lt; 0.001). However, a similar relationship between metabolically not closely related compounds (correlation coefficient 0.45–0.73 (р &lt; 0.001)) was revealed for some groups of compounds. Thus, the acylcarnitine profile can be proposed as an additional potential marker to be used in cases of borderline phenylalanine levels, and the sum of normalized acylcarnitine levels (С12+С16) can be a potential secondary marker of phenylketonuria.

Canine soft tissue sarcomas: the expression of RUNX2 and karyopherin alpha-2 in extraskeletal (soft tissues) and skeletal osteosarcomas.

Extraskeletal osteosarcoma (EOS) is a malignant tumor producing bone matrix and/or chondroid material, without direct attachment to bone or periosteum. In humans and dogs, EOS is highly infiltrating, rapidly growing, often characterized by osteoid deposition and variable ossification, similar to primary skeletal osteosarcoma (SOS). In dogs, EOS arises from visceral and soft tissue locations, occasionally in trauma or foreign body sites, or in granulomas. Few data are currently available on the phenotype of these tumors. The present study aims to assess the expression RUNX2 and Karyopherin alpha-2 in EOS, comparing it with SOS and the data available from the human counterpart. Seventeen cases of canine osteosarcoma (13 EOS and 4 SOS) were retrospectively selected and submitted to immunohistochemistry for RUNX2 and Karyopherin alpha-2. Our results showed that, in EOS, RUNX2 is expressed in a mean of 73.07 ± 5.36 neoplastic cell nuclei, in face of a mean 36.15 ± 6.25 of Karyopherin alpha-2 positive nuclei. Osteoclasts, when present, were negative for both markers. No correlation was observed among the two markers (p > 0.05), nor statistically significant difference in quantitative expression was assessed comparing EOS and SOS groups. RUNX2 is expressed in canine EOS similarly to SOS and could be used as a diagnostic marker in a larger panel. Karyopherin alpha-2 is expressed in canine EOS and SOS similarly to human SOS and could be validated in future studies as an additional diagnostic marker. Further studies should be planned to evaluate the expression of these proteins as prognostic predictive parameters.