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Background: Peripheral inflammation is often associated with depressive disorders, and immunological biomarkers of depression remain a focus of investigation. Methods: We performed RNA-seq analysis of RNA transcripts of human peripheral blood mononuclear cells from a case-control study including subjects with self-reported depression in the pre-symptomatic state of major depressive disorder and analyzed differentially expressed genes (DEGs) and the frequency of intron retention (IR) using rMATS. Results: Among the statistically significant DEGs identified, the 651 upregulated DEGs were particularly enriched in the term "bacterial infection and phagocytosis", whereas the 820 downregulated DEGs were enriched in the terms "antigen presentation" and "T-cell proliferation and maturation". We also analyzed 158 genes for which the IR was increased (IncIR) and 211 genes for which the IR was decreased (DecIR) in the depressed subjects. Although the Gene Ontology terms associated with IncIR and DecIR were very similar to those of the up- and downregulated genes, respectively, IR genes appeared to be particularly enriched in genes with sensor functions, with a preponderance of the term "ciliary assembly and function". The observation that IR genes specifically interact with innate immunity genes suggests that immune-related genes, as well as cilia-related genes, may be excellent markers of depression. Re-analysis of previously published RNA-seq data from patients with MDD showed that common IR genes, particularly our predicted immune- and cilia-related genes, are commonly detected in populations with different levels of depression, providing validity for using IR to detect depression. Conclusion: Depression was found to be associated with activation of the innate immune response and relative inactivation of T-cell signaling. The DEGs we identified reflect physiological demands that are controlled at the transcriptional level, whereas the IR results reflect a more direct mechanism for monitoring protein homeostasis. Accordingly, an alteration in IR, namely IncIR or DecIR, is a stress response, and intron-retained transcripts are sensors of the physiological state of the cytoplasm. The results demonstrate the potential of relative IR as a biomarker for the immunological stratification of depressed patients and the utility of IR for the discovery of novel pathways involved in recovery from depression. [ABSTRACT FROM AUTHOR]

Marine invertebrate stem cells (MISCs) represent a distinct category of pluripotent and totipotent cells with remarkable abilities for self-renewal and differentiation into multiple germ layers, akin to their vertebrate counterparts. These unique cells persist throughout an organism's adult life and have been observed in various adult marine invertebrate phyla. MISCs play crucial roles in numerous biological processes, including developmental biology phenomena specific to marine invertebrates, such as senescence, delayed senescence, whole-body regeneration, and asexual reproduction. Furthermore, they serve as valuable models for studying stem cell biology. Despite their significance, information about MISCs remains scarce and scattered in the scientific literature. In this review, we have carefully collected and summarized valuable information about MISC detection by perusing the articles that study and detect MISCs in various marine invertebrate organisms. The review begins by defining MISCs and highlighting their unique features compared to vertebrates. It then discusses the common markers for MISC detection and in vitro techniques employed in invertebrate and vertebrates investigation. This comprehensive review provides researchers and scientists with a cohesive and succinct overview of MISC characteristics, detection methods, and associated biological phenomena in marine invertebrate organisms. We aim to offer a valuable resource to researchers and scientists interested in marine invertebrate stem cells, fostering a better understanding of their broader implications in biology. With ongoing advancements in scientific techniques and the continued exploration of marine invertebrate species, we anticipate that further discoveries will expand our knowledge of MISCs and their broader implications in biology. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Cassava productivity is constrained by low soil nitrogen, which is predominant in most cassava-growing regions in the tropics and subtropical agroecology. Improving the low nitrogen tolerance of cassava has become an important breeding objective. The current study aimed to develop cassava varieties with improved nitrogen use efficiency by identifying genomic regions and candidate genes linked to nitrogen use efficiency in cassava. A genome-wide association study (GWAS) was performed using the Genome Association and Prediction Integrated Tool (GAPIT). A panel of 265 diverse cassava genotypes was phenotyped for 10 physiological and agronomic traits under optimum and low-nitrogen regimes. Whole-genome genotyping of these cassava cloneswas performed using the Diversity Arrays Technology (DArTseq) sequencing platform. A total of 68,814 single nucleotide polymorphisms (SNPs) were identified, which were spread across the entire 18 chromosomes of the cassava genome, of which 52 SNPs at various densities were found to be associated with nitrogen use efficiency in cassava and other yield-related traits. The putative genes identified through GWAS, especially those with significant associated SNP markers for NUE and related traits have the potential, if deployed appropriately, to develop cassava varieties with improved nitrogen use efficiency, which would translate to a reduction in the economic and environmental cost of cassava production. [ABSTRACT FROM AUTHOR]

Annual medic (Medicago spp.) germplasm was collected from the Crimean Peninsula of Ukraine in 2008 to fill gaps in geographic coverage in the United States department of Agriculture, Agricultural Research Service, National Plant Germplasm System (NPGS) temperate-adapted forage legume collection. A total of 102 accessions across 10 Medicago species were collected. To assess genetic diversity, population structure, and to confirm taxonomic identities, the collections were phenotypically and genetically characterized. Phenotyping included the use of 24 descriptor traits while genetic characterization was accomplished using a 3K Diversity Array Technologies (DArTag) panel developed for alfalfa (Medicago sativa L.). For both field and molecular characterizations, a reference set of 92 geographically diverse and speciesrepresentative accessions were obtained from the NPGS collection. Phenotypic descriptors showed consistency among replicated plants within accessions, some variation across accessions within species, and evident distinctions between species. Because the DArTag panel was developed for cultivated alfalfa, the transferability of markers to the species being evaluated was limited, resulting in an average of ~1,500 marker loci detected per species. From these loci, 448 markers were present in 95% of the samples. Principal component and phylogenetic analysis based on a larger set of 2,396 selected markers clustered accessions by species and predicted evolutionary relationships among species. Additionally, the markers aided in the taxonomic identity of a few accessions that were likely mislabeled. The genotyping results also showed that sampling individual plants for these mostly self-pollinating species is sufficient due to high reproducibility between single (n=3) and pooled (n=7) biological replicate leaf samples. The phenotyping and the 2,396 Single Nucleotide Polymorphism (SNP) marker set were useful in estimating population structure in the Crimean and reference accessions, highlighting novel and unique genetic diversity captured in the Crimean accessions. This research not only demonstrated the utility of the DArTag marker panel in evaluating the Crimean germplasm but also highlighted its broader application in assessing genetic resources within the Medicago genus. Furthermore, we anticipate that our findings will underscore the importance of leveraging genetic resources and advanced genotyping tools for sustainable crop improvement and biodiversity conservation in annual medic species. [ABSTRACT FROM AUTHOR]

Introduction: Lymph node metastasis (LNM) is a critical prognostic factor for colorectal cancer (CRC). Due to the potential influence of immune system on CRC progression, investigation into lymphocyte subsets as clinical markers has gained attention. The objective of this study was to assess the capability of lymphocyte subsets in evaluating the lymph node status and prognosis of CRC. Methods: Lymphocyte subsets, including T cells (CD3+), natural killer cells (NK, CD3- CD56+), natural killer-like T cells (NK-like T, CD3+ CD56+), CD38+ NK cells (CD3- CD56+ CD38+) and CD38+ NK-like T cells (CD3+ CD56+ CD38+), were detected by flow cytometry. Univariate and multivariate analyses were used to assess the risk factors of LNM. The prognostic role of parameters was evaluated by survival analysis. Results: The proportion of CD38+ NK cells within the NK cell population was significantly higher in LNM-positive patients (p <0.0001). However, no significant differences were observed in the proportions of other lymphocyte subsets. Poorer histologic grade (odds ratio [OR] =4.76, p =0.03), lymphovascular invasion (LVI) (OR =22.38, p <0.01), and CD38+ NK cells (high) (OR =4.54, p <0.01) were identified as independent risk factors for LNM. Furthermore, high proportion of CD38+ NK cells was associated with poor prognosis of CRC patients (HR=2.37, p =0.03). Conclusions: It was demonstrated that the proportion of CD38+ NK cells was a marker overexpressed in LNM-positive patients compared with LNM-negative patients. Moreover, an elevated proportion of CD38+ NK cells is a risk factor for LNM and poor prognosis in CRC. [ABSTRACT FROM AUTHOR]

Marine invertebrate stem cells (MISCs) represent a distinct category of pluripotent and totipotent cells with remarkable abilities for self-renewal and differentiation into multiple germ layers, akin to their vertebrate counterparts. These unique cells persist throughout an organism’s adult life and have been observed in various adult marine invertebrate phyla. MISCs play crucial roles in numerous biological processes, including developmental biology phenomena specific to marine invertebrates, such as senescence, delayed senescence, whole-body regeneration, and asexual reproduction. Furthermore, they serve as valuable models for studying stem cell biology. Despite their significance, information about MISCs remains scarce and scattered in the scientific literature. In this review, we have carefully collected and summarized valuable information about MISC detection by perusing the articles that study and detect MISCs in various marine invertebrate organisms. The review begins by defining MISCs and highlighting their unique features compared to vertebrates. It then discusses the common markers for MISC detection and in vitro techniques employed in invertebrate and vertebrates investigation. This comprehensive review provides researchers and scientists with a cohesive and succinct overview of MISC characteristics, detection methods, and associated biological phenomena in marine invertebrate organisms. We aim to offer a valuable resource to researchers and scientists interested in marine invertebrate stem cells, fostering a better understanding of their broader implications in biology. With ongoing advancements in scientific techniques and the continued exploration of marine invertebrate species, we anticipate that further discoveries will expand our knowledge of MISCs and their broader implications in biology.

In the realm of biomedical advancement, extracellular vesicles (EVs) are revolutionizing our capacity to diagnose, monitor, and predict disease progression. However, the comprehensive exploration and clinical application of EVs face significant limitations due to the current isolation techniques. The size exclusion chromatography, commercial precipitation reagents, and ultracentrifugation are frequently employed, necessitating skilled operators and entailing challenges related to consistency, reproducibility, quality, and yields. Notably, the formidable challenge of extracellular vesicle isolation persists when dealing with clinical samples of limited availability. This study addresses these challenges by aiming to devise a rapid, user-friendly, and high-recovery EVs isolation technique tailored for blood samples. The NTI-EXO precipitation method demonstrated a 5-fold increase in the recovery of serum EVs compared to current methodologies. Importantly, we illustrate that a mere two drops of blood (∼100 µL) suffice for the recovery of enriched EVs. The integrity and quality of these isolated EVs were rigorously assessed for the size, purity, and contaminants. This method was validated through the successful isolation of EVs from organ transplant recipients to detect disease-specific exosomal markers, including LKB1, SARS-CoV-2 spike protein, and PD-L1. In conclusion, NTI-EXO method can be used for small clinical samples, thereby advancing discoveries in the EV-centric domain and propelling the frontiers of biomedical research and clinical applications.

Background: The identification of effective tumor markers is of paramount importance for the early diagnosis, treatment, and prognosis of esophageal squamous cell carcinoma (ESCC). The present study endeavors to identify efficacious serological markers that can differentiate patients with early-stage ESCC from those with benign esophageal lesions and healthy controls (HC). Cystatin-SN (CST1), an active cysteine protease inhibitor belonging to the Cystatin (CST) superfamily, is implicated in the pathogenesis of inflammation and tumorigenesis. The objective of this investigation is to assess the diagnostic, therapeutic, and prognostic potential of serum CST1 in ESCC. Methods: In our prior RNA sequencing and screening endeavors, we have identified ten genes that are up-regulated in relation to esophageal cancer. Subsequently, we have verified the gene CST1 from the transcriptome data of the The Cancer Genome Atlas Program (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Following this, we conducted an enzyme-linked immunosorbent assay (ELISA) to ascertain the expression levels of CST1 in serum samples from clinical cohorts. Results: The study revealed a significant elevation in serum CST1 levels among patients with early-stage esophageal squamous cell carcinoma (ESCC) (7.41 ± 4.32 ng/ml) compared to those with esophageal benign lesions (4.67 ± 2.43 ng/ml) (p < 0.0001) and healthy controls (4.87 ± 2.77 ng/ml) (p < 0.0001). The diagnostic sensitivity of CST1 for ESCC was 75.68% (specificity 70.83%, AUC 0.775). Combination of CST1 and SCC-Ag exhibited the AUC up to 0.819. Additionally, serum CST1 levels exhibited a significant decrease at 1-2 weeks post-surgery (4.49 ± 3.31 ng/ml) compared to pre-surgery levels (7.68 ± 3.71 ng/ml) (p<0.0001). Survival analysis demonstrated a strong association between high (844/415-1543 d) or low (1490/645-1710 d) serum CST1 levels at diagnosis and overall survival time (p < 0.001). Furthermore, multivariate regression analysis confirmed CST1 (p=0.024, HR=2.023, 95%CI 1.099-3.725) as an independent prognostic factor. Conclusion: Serum CST1 has the potential to function as a diagnostic indicator for distinguishing early-stage esophageal squamous cell carcinoma (ESCC) from individuals with benign esophageal lesions and healthy individuals. Additionally, it could serve as a prognostic predictor and therapeutic efficacy indicator for patients with ESCC. [ABSTRACT FROM AUTHOR]

Background: The hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT. Methods: Acute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24  h of MT. Clinical outcomes after 3  months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS  >  2) at 3  months, while the secondary outcome was death within 3  months. Results: A total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24  h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24  h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520–0.803, p <  0.001) and death (adjusted OR: 0.615, 95% CI: 0.508–0.744, p <  0.001). Receiver-operating characteristic curve analysis demonstrated the predictive ability of HRR after 24  h, with areas under the curves of 0.790 for poor prognosis and 0.771 for death. Conclusion: Rapidly measurable HRR levels are an independent marker of outcome after MT in AIS patients. This may provide a reliable auxiliary outcome measure for clinical routine and interventional therapy. [ABSTRACT FROM AUTHOR]

Cassava productivity is constrained by low soil nitrogen, which is predominant in most cassava-growing regions in the tropics and subtropical agroecology. Improving the low nitrogen tolerance of cassava has become an important breeding objective. The current study aimed to develop cassava varieties with improved nitrogen use efficiency by identifying genomic regions and candidate genes linked to nitrogen use efficiency in cassava. A genome-wide association study (GWAS) was performed using the Genome Association and Prediction Integrated Tool (GAPIT). A panel of 265 diverse cassava genotypes was phenotyped for 10 physiological and agronomic traits under optimum and low-nitrogen regimes. Whole-genome genotyping of these cassava cloneswas performed using the Diversity Arrays Technology (DArTseq) sequencing platform. A total of 68,814 single nucleotide polymorphisms (SNPs) were identified, which were spread across the entire 18 chromosomes of the cassava genome, of which 52 SNPs at various densities were found to be associated with nitrogen use efficiency in cassava and other yield-related traits. The putative genes identified through GWAS, especially those with significant associated SNP markers for NUE and related traits have the potential, if deployed appropriately, to develop cassava varieties with improved nitrogen use efficiency, which would translate to a reduction in the economic and environmental cost of cassava production.

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Pseudoinvasion (PI) is a benign lesion in which cancer is mimicked in the colon by misplacement of dysplastic glands in the submucosa. Although there are morphological clues, the discrimination of PI from true invasion can be a challenge during pathological evaluation of colon adenomas. Both overdiagnosis and underdiagnosis can result in inadequate clinical decisions. This calls for novel tools to aid in cases where conventional methods do not suffice. We performed mass spectrometry imaging (MSI)-based spatial glycomics analysis on a cohort of formalin-fixed paraffin-embedded tissue (FFPE) material from 16 patients who underwent polypectomy. We used this spatial glycomic data to reconstruct the molecular histology of the tissue section using spatial segmentation based on uniform manifold approximation and projection for dimension reduction (UMAP). We first showed that the spatial glycomic phenotypes of the different morphological entities separated as distinct clusters in colon tissues, we separated true invasion from the other morphological entities. Then, we found that the glycomic phenotype in areas with suspected PI in the submucosa was strongly correlating with the corresponding glycomic phenotype of the adenomatous colon epithelium from the same tissue section (Pearson correlation distance average = 0.18). These findings suggest that using spatial glycomics, we can distinguish PI as having a molecular phenotype similar to the corresponding surface epithelium and true invasion as having a different phenotype even when compared to high-grade dysplasia. Therefore, when a novel molecular phenotype is found in the deepest submucosal region, this may be used as an argument in favor of true invasion.

IntroductionThe relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated.MethodsThe goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients.ResultsComprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported.ConclusionThe results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Surgical resection can lead to prolonged survival in patients with isolated liver metastases (LM) from various primary cancers. However, there are currently no validated predictive markers to discriminate between these oligo/argometastatic patients, who will benefit from surgery, and those with diffuse metastatic behavior in whom surgery will be futile. To evaluate whether the tumor microenvironment, or histopathological growth pattern (HGP), of LM reflects the type of metastatic progression independently of the origin of the primary cancer, we analyzed a combined series of patients who underwent surgery for colorectal LM (N=263) or non-colorectal LM (N=66). HGPs of LM were scored in each patient to distinguish between desmoplastic HGP (all LM showing a complete encapsulated pattern) and non-desmoplastic HGP (at least one LM with some infiltrating-replacement component). In the entire series, 5-year overall and progression-free survival were, 44.5% and 15.5%, respectively, with no significant differences between colorectal and non-colorectal LM. In patients with desmoplastic HGP, 5-year overall and progression-free survival were 57% and 32%, respectively, as compared to 41% and 12%, respectively, in patients with non-desmoplastic-HGP (p=0.03 and 0.005). Irrespective of cancer origin and compared to traditional risk factors, desmoplastic HGP was the most significant predictor for better post-operative overall survival (adjusted HR: 0.62; 95% CI: [0.49-0.97]; p=0.035) and progression-free survival (adjusted HR: 0.61; 95% CI: [0.42-0.87], p=0.006). This suggests that the HGP of LM may represent an accurate marker that reflects the mode of metastatic behavior, independently of primary cancer type. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). Methods: A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Results: Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). Conclusion: HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19. [ABSTRACT FROM AUTHOR]

Biotic stress is one of the major threats to stable rice production. Climate change affects the shifting of pest outbreaks in time and space. Genetic improvement of biotic stress resistance in rice is a cost-effective and environment-friendly way to control diseases and pests compared to other methods such as chemical spraying. Fast deployment of the available and suitable genes/alleles in local elite varieties through marker-assisted selection (MAS) is crucial for stable high-yield rice production. In this review, we focused on consolidating all the available cloned genes/alleles conferring resistance against rice pathogens (virus, bacteria, and fungus) and insect pests, the corresponding donor materials, and the DNA markers linked to the identified genes. To date, 48 genes (independent loci) have been cloned for only major biotic stresses: seven genes for brown planthopper (BPH), 23 for blast, 13 for bacterial blight, and five for viruses. Physical locations of the 48 genes were graphically mapped on the 12 rice chromosomes so that breeders can easily find the locations of the target genes and distances among all the biotic stress resistance genes and any other target trait genes. For efficient use of the cloned genes, we collected all the publically available DNA markers (~500 markers) linked to the identified genes. In case of no available cloned genes yet for the other biotic stresses, we provided brief information such as donor germplasm, quantitative trait loci (QTLs), and the related papers. All the information described in this review can contribute to the fast genetic improvement of biotic stress resistance in rice for stable high-yield rice production. [ABSTRACT FROM AUTHOR]

Surgical resection can lead to prolonged survival in patients with isolated liver metastases (LM) from various primary cancers. However, there are currently no validated predictive markers to discriminate between these oligo/argometastatic patients, who will benefit from surgery, and those with diffuse metastatic behavior in whom surgery will be futile. To evaluate whether the tumor microenvironment, or histopathological growth pattern (HGP), of LM reflects the type of metastatic progression independently of the origin of the primary cancer, we analyzed a combined series of patients who underwent surgery for colorectal LM (N=263) or non-colorectal LM (N=66). HGPs of LM were scored in each patient to distinguish between desmoplastic HGP (all LM showing a complete encapsulated pattern) and non-desmoplastic HGP (at least one LM with some infiltrating-replacement component). In the entire series, 5-year overall and progression-free survival were, 44.5% and 15.5%, respectively, with no significant differences between colorectal and non-colorectal LM. In patients with desmoplastic HGP, 5-year overall and progression-free survival were 57% and 32%, respectively, as compared to 41% and 12%, respectively, in patients with non-desmoplastic-HGP (p=0.03 and 0.005). Irrespective of cancer origin and compared to traditional risk factors, desmoplastic HGP was the most significant predictor for better post-operative overall survival (adjusted HR: 0.62; 95% CI: [0.49-0.97]; p=0.035) and progression-free survival (adjusted HR: 0.61; 95% CI: [0.42-0.87], p=0.006). This suggests that the HGP of LM may represent an accurate marker that reflects the mode of metastatic behavior, independently of primary cancer type.

Biotic stress is one of the major threats to stable rice production. Climate change affects the shifting of pest outbreaks in time and space. Genetic improvement of biotic stress resistance in rice is a cost-effective and environment-friendly way to control diseases and pests compared to other methods such as chemical spraying. Fast deployment of the available and suitable genes/alleles in local elite varieties through marker-assisted selection (MAS) is crucial for stable high-yield rice production. In this review, we focused on consolidating all the available cloned genes/alleles conferring resistance against rice pathogens (virus, bacteria, and fungus) and insect pests, the corresponding donor materials, and the DNA markers linked to the identified genes. To date, 48 genes (independent loci) have been cloned for only major biotic stresses: seven genes for brown planthopper (BPH), 23 for blast, 13 for bacterial blight, and five for viruses. Physical locations of the 48 genes were graphically mapped on the 12 rice chromosomes so that breeders can easily find the locations of the target genes and distances among all the biotic stress resistance genes and any other target trait genes. For efficient use of the cloned genes, we collected all the publically available DNA markers (~500 markers) linked to the identified genes. In case of no available cloned genes yet for the other biotic stresses, we provided brief information such as donor germplasm, quantitative trait loci (QTLs), and the related papers. All the information described in this review can contribute to the fast genetic improvement of biotic stress resistance in rice for stable high-yield rice production.

Objective: No previous studies investigated the association between decrement of low-frequency repetitive nerve stimulation (LF-RNS) and amyotrophic lateral sclerosis (ALS) survival. We aim to study the relationship between decrement and survival in ALS. Methods: Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, Chinese PLA General Hospital from January 2018 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. A decremental response of 10% or greater at least in one muscle was considered positive. According to the decrement, the participants were divided into LF-RNS (+) and LF-RNS (-) groups. Results: One hundred and eighty-one sporadic ALS patients were recruited in our study, including 100 males and 81 females. Among them, 10 cases (5.5%) were lost to follow-up, 99 cases (54.7%) died, and 72 patients (39.8%) were still alive at the last follow-up. The median survival time of all ALS patients in this study was 42.0 months. There was no significant difference of median survival in LF-RNS(+) group and LF-RNS(-) group (p = 0.159, Kaplan-Meier method). In multivariate Cox regression analysis, age of onset, diagnostic delay, and ALS Functional Rating Scale-Revised (ALSFRS-R) score were associated with ALS survival, but the decrement was not correlated with ALS survival (p = 0.238). Conclusion: The decrement in accessory and ulnar nerves was not associated with the survival of ALS. The decrement of LF-RNS could not be an electrophysiological marker to predict ALS survival. [ABSTRACT FROM AUTHOR]

Aflatoxin (AF) contamination, caused by Aspergillus flavus, compromises the food safety and marketability of commodities, such as maize, cotton, peanuts, and tree nuts. Multigenic inheritance of AF resistance impedes conventional introgression of resistance traits into high-yielding commercial maize varieties. Several AF resistance-associated quantitative trait loci (QTLs) and markers have been reported from multiple biparental mapping and genome-wide association studies (GWAS) in maize. However, QTLs with large confidence intervals (CI) explaining inconsistent phenotypic variance limit their use in marker-assisted selection. Meta-analysis of published QTLs can identify significant meta-QTLs (MQTLs) with a narrower CI for reliable identification of genes and linked markers for AF resistance. Using 276 out of 356 reported QTLs controlling resistance to A. flavus infection and AF contamination in maize, we identified 58 MQTLs on all 10 chromosomes with a 66.5% reduction in the average CI. Similarly, a metaanalysis of maize genes differentially expressed in response to (a)biotic stresses from the to-date published literature identified 591 genes putatively responding to only A. flavus infection, of which 14 were significantly differentially expressed (-1.0 ≤ Log2Fc ≥ 1.0; p ≤ 0.05). Eight MQTLs were validated by their colocalization with 14 A. flavus resistance-associated SNPs identified from GWAS in maize. A total of 15 genes were physically close between the MQTL intervals and SNPs. Assessment of 12 MQTL-linked SSR markers identified three markers that could discriminate 14 and eight cultivars with resistance and susceptible responses, respectively. A comprehensive meta-analysis of QTLs and differentially expressed genes led to the identification of genes and makers for their potential application in marker-assisted breeding of A. flavus-resistant maize varieties. [ABSTRACT FROM AUTHOR]

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) play an important role in the inflammatory response in various diseases, but the role in the course of spontaneous intracerebral hemorrhage (ICH) is unclear. Methods: This study retrospectively collected baseline characteristics and laboratory findings, including NLR and PLR at different time points, from spontaneous ICH patients undergoing surgery between January 2016 and June 2021. Patients were scored using the modified Rankin Scale (mRS) to evaluate their functional status at 30 days post-operation. Patients with mRS score ≥3 were defined as poor functional status, and mRS score <3 was defined as good functional status. The NLR and PLR were calculated at admission, 48 h after surgery and 3-7 days after surgery, respectively, and their trends were observed by connecting the NLR and PLR at different time points. Multivariate logistic regression analysis was used to identify independent risk factors affecting the prognosis of ICH patients at 30 days after surgery. Results: A total of 101 patients were included in this study, and 59 patients had a poor outcome at 30 days after surgery. NLR and PLR gradually increased and then decreased, peaking at 48 h after surgery. Univariate analysis demonstrated that admission Glasgow Coma Scale (GCS) score, interval from onset to admission, hematoma location, NLR within 48 h after surgery and PLR within 48 h after surgery were associated with poor 30-day prognosis. In multivariate logistic regression analysis, NLR within 48 h after surgery (OR, 1.147; 95% CI, 1.005, 1.308; P, 0.042) was an independent risk factor for 30-day after surgery prognosis in spontaneous ICH patients. Conclusion: In the course of spontaneous intracerebral hemorrhage, NLR and PLR initially increased and subsequently decreased, reaching their peak values at 48 h after surgery. High NLR within 48 h after surgery was an independent risk factor for poor prognosis 30 days after surgery in spontaneous ICH patients. [ABSTRACT FROM AUTHOR]

Extra-axial brain tumors are extra-cerebral tumors and are usually benign. The choice of treatment for extra-axial tumors is often dependent on the growth of the tumor, and imaging plays a significant role in monitoring growth and clinical decision-making. This motivates the investigation of imaging biomarkers for these tumors that may be incorporated into clinical workflows to inform treatment decisions. The databases from Pubmed, Web of Science, Embase, and Medline were searched from 1 January 2000 to 7 March 2022, to systematically identify relevant publications in this area. All studies that used an imaging tool and found an association with a growth-related factor, including molecular markers, grade, survival, growth/progression, recurrence, and treatment outcomes, were included in this review. We included 42 studies, comprising 22 studies (50%) of patients with meningioma; 17 studies (38.6%) of patients with pituitary tumors; three studies (6.8%) of patients with vestibular schwannomas; and two studies (4.5%) of patients with solitary fibrous tumors. The included studies were explicitly and narratively analyzed according to tumor type and imaging tool. The risk of bias and concerns regarding applicabilitywere assessed using QUADAS-2.Most studies (41/44) used statistics-based analysis methods, and a small number of studies (3/44) usedmachine learning. Our review highlights an opportunity for future work to focus on machine learning-based deep feature identification as biomarkers, combining various feature classes such as size, shape, and intensity. [ABSTRACT FROM AUTHOR]

Aflatoxin (AF) contamination, caused by Aspergillus flavus, compromises the food safety and marketability of commodities, such as maize, cotton, peanuts, and tree nuts. Multigenic inheritance of AF resistance impedes conventional introgression of resistance traits into high-yielding commercial maize varieties. Several AF resistance-associated quantitative trait loci (QTLs) and markers have been reported from multiple biparental mapping and genome-wide association studies (GWAS) in maize. However, QTLs with large confidence intervals (CI) explaining inconsistent phenotypic variance limit their use in marker-assisted selection. Meta-analysis of published QTLs can identify significant meta-QTLs (MQTLs) with a narrower CI for reliable identification of genes and linked markers for AF resistance. Using 276 out of 356 reported QTLs controlling resistance to A. flavus infection and AF contamination in maize, we identified 58 MQTLs on all 10 chromosomes with a 66.5% reduction in the average CI. Similarly, a meta-analysis of maize genes differentially expressed in response to (a)biotic stresses from the to-date published literature identified 591 genes putatively responding to only A. flavus infection, of which 14 were significantly differentially expressed (−1.0 ≤ Log2Fc ≥ 1.0; p ≤ 0.05). Eight MQTLs were validated by their colocalization with 14 A. flavus resistance-associated SNPs identified from GWAS in maize. A total of 15 genes were physically close between the MQTL intervals and SNPs. Assessment of 12 MQTL-linked SSR markers identified three markers that could discriminate 14 and eight cultivars with resistance and susceptible responses, respectively. A comprehensive meta-analysis of QTLs and differentially expressed genes led to the identification of genes and makers for their potential application in marker-assisted breeding of A. flavus-resistant maize varieties.

Extra-axial brain tumors are extra-cerebral tumors and are usually benign. The choice of treatment for extra-axial tumors is often dependent on the growth of the tumor, and imaging plays a significant role in monitoring growth and clinical decision-making. This motivates the investigation of imaging biomarkers for these tumors that may be incorporated into clinical workflows to inform treatment decisions. The databases from Pubmed, Web of Science, Embase, and Medline were searched from 1 January 2000 to 7 March 2022, to systematically identify relevant publications in this area. All studies that used an imaging tool and found an association with a growth-related factor, including molecular markers, grade, survival, growth/progression, recurrence, and treatment outcomes, were included in this review. We included 42 studies, comprising 22 studies (50%) of patients with meningioma; 17 studies (38.6%) of patients with pituitary tumors; three studies (6.8%) of patients with vestibular schwannomas; and two studies (4.5%) of patients with solitary fibrous tumors. The included studies were explicitly and narratively analyzed according to tumor type and imaging tool. The risk of bias and concerns regarding applicability were assessed using QUADAS-2. Most studies (41/44) used statistics-based analysis methods, and a small number of studies (3/44) used machine learning. Our review highlights an opportunity for future work to focus on machine learning-based deep feature identification as biomarkers, combining various feature classes such as size, shape, and intensity.Systematic Review Registration: PROSPERO, CRD42022306922

BackgroundColorectal cancer (CRC) is one of the most prevalent gastrointestinal cancers. Evidence for the importance of inflammation and immunology in the development and progression of CRC is growing steadily. The purpose of this study was to determine the clinical importance of Lactic Dehydrogenase (LDH) to Albumin (ALB) Ratio (LAR) and immune-inflammation biomarkers (IIBs) in patients with CRC.MethodsThis study enrolled 382 CRC patients. The LAR was determined as the serum LDH(U/l) to ALB(g/l) ratio. We compared the levels of LAR and IIBs in different TNM stages and tumor differentiation. The relationship between LAR and IIBs and overall survival (OS) of CRC was determined by Cox regression models. A prognostic nomogram was created using the results of the multivariate analysis and the effectiveness of the nomogram was assessed using the ROC, calibration, and decision curves. We evaluated the relationship between LAR and IIBs and clinical features of CRC.ResultsThe levels of LAR, SII, NLR and PLR in TNM IV stage group (LAR:5.92 (5.23–8.24); SII: 1040.02 (499.51–1683.54); NLR: 2.87 (2.07–5.3); PLR:187.08 (125.31–276.63)) were significantly higher than those in other groups. LAR and NLR showed no significant difference in different tumor differentiation groups, while SII and PLR in undifferentiated groups (SII:543.72 (372.63–1110.20); PLR: 147.06 (106.04–203.92)) were significantly higher than those in well and moderate groups (SII: 474.29 (323.75–716.01); PLR: 126.28 (104.31–167.88)). LAR (HR = 1.317, 95% CI = 1.019–1.454), TNM stage (HR = 2.895, 95% CI = 1.838–4.559), age (HR = 1.766, 95% CI = 1.069–2.922) and lymphocytes (HR = 0.663, 95% CI = 0.456–0.963) were predictors of OS. IIBs, including SII, NLR, and PLR are independent of OS. The LAR-based nomogram AUCs of 1-year, 3-year and 5-year survival probabilities in the training cohort were 0.86, 0.72, and 0.71, respectively, and the AUCs of the validation cohort were 0.85, 0.71, and 0.69 respectively. The LAR-based nomogram's ROC curves and calibration curves demonstrated higher OS discriminative performance. The decision curves demonstrated greater net benefit in the survival prediction.ConclusionPreoperative LAR is a potential prognostic marker in CRC patients, while SII, NLR, and PLR are independent of OS. LAR was associated with tumor stage in CRC patients, but not with tumor differentiation.

Astrocytes play diverse roles in the central nervous system (CNS) in both physiological and pathological conditions. Previous studies have identified many markers of astrocytes to analyze their complicated roles. Recently, closure of the critical period by mature astrocytes has been revealed, and the need for finding mature astrocyte-specific markers has been growing. We previously found that Ethanolamine phosphate phospholyase (Etnppl) was almost not expressed in the developing neonatal spinal cord, and its expression level slightly decreased after pyramidotomy in adult mice, which showed weak axonal sprouting, suggesting that its expression level negatively correlates with axonal elongation. Although the expression of Etnppl in astrocytes in adult is known, its utility as an astrocytic marker has not yet been investigated in detail. Here, we showed that Etnppl was selectively expressed in astrocytes in adult. Re-analyses using published RNA-sequencing datasets revealed changes in Etnppl expression in spinal cord injury, stroke, or systemic inflammation models. We produced high-quality monoclonal antibodies against ETNPPL and characterized ETNPPL localization in neonatal and adult mice. Expression of ETNPPL was very weak in neonatal mice, except in the ventricular and subventricular zones, and it was heterogeneously expressed in adult mice, with the highest expression in the cerebellum, olfactory bulb, and hypothalamus and the lowest in white matter. Subcellular localization of ETNPPL was dominant in the nuclei with weak expression in the cytosol in the minor population. Using the antibody, astrocytes in adult were selectively labeled in the cerebral cortex or spinal cord, and changes in astrocytes were detected in the spinal cord after pyramidotomy. ETNPPL is expressed in a subset of Gjb6C astrocytes in the spinal cord. The monoclonal antibodies we created, as well as fundamental knowledge characterized in this study, will be valuable resources in the scientific community and will expand our understanding of astrocytes and their complicated responses in many pathological conditions in future analyses. [ABSTRACT FROM AUTHOR]

Hemorrhage is the leading cause of death in severe trauma injuries. When organs or tissues are subjected to prolonged hypoxia, danger signals—known as damage-associated molecular patterns (DAMPs)—are released into the intercellular environment. The endothelium is both the target and a major provider of damage-associated molecular patterns, which are directly involved in immuno-inflammatory dysregulation and the associated tissue suffering. Although damage-associated molecular patterns release begins very early after trauma, this release and its consequences continue beyond the initial treatment. Here we review a few examples of damage-associated molecular patterns to illustrate their pathophysiological roles, with emphasis on emerging therapeutic interventions in the context of severe trauma. Therapeutic intervention administered at precise points during damage-associated molecular patterns release may have beneficial effects by calming the inflammatory storm triggered by traumatic hemorrhagic shock. [ABSTRACT FROM AUTHOR]

IntroductionAs one of the most common malignant tumors in clinical practice, hepatocellular carcinoma (HCC) is a major threat to human health, where alpha-fetoprotein (AFP) is widely used for early screening and diagnoses. However, the level of AFP would not elevate in about 30-40% of HCC patients, which is clinically referred to as AFP-negative HCC, with small tumors at an early stage and atypical imaging features, making it difficult to distinguish benign from malignant by imaging alone.MethodsA total of 798 patients, with the majority being HBV-positive, were enrolled in the study and were randomized 2:1 to the training and validation groups. Univariate and multivariate binary logistic regression analyses were used to determine the ability of each parameter to predict HCC. A nomogram model was constructed based on the independent predictors. ResultsA unordered multicategorical logistic regression analyses showed that the age, TBIL, ALT, ALB, PT, GGT and GPR help identify non-hepatic disease, hepatitis, cirrhosis, and hepatocellular carcinoma. A multivariate logistic regression analyses showed that the gender, age, TBIL, GAR, and GPR were independent predictors for the diagnosis of AFP-negative HCC. And an efficient and reliable nomogram model (AUC=0.837) was constructed based on independent predictors.DiscussionSerum parameters help reveal intrinsic differences between non-hepatic disease, hepatitis, cirrhosis, and HCC. The nomogram based on clinical and serum parameters could be used as a marker for the diagnosis of AFP-negative HCC, providing an objective basis for the early diagnosis and individualized treatment of hepatocellular carcinoma patients.

Circular RNAs (circRNAs) are a class of closed circular non-coding RNAs widely exist in eukaryotes, with high stability and species conservation. A large number of studies have shown that circRNAs are abnormally expressed in various tumor tissues, and are abundant in plasma with long half-life and high specificity, which may be served as potential tumor biomarkers for early diagnosis, treatment and prognosis of malignant tumors. However, the role of circRNAs is still poorly understood in gastric cancer. This article reviews the research progress of circRNAs in gastric cancer in recent years so as to explore the relationship between circRNAs and the occurrence and the development of gastric cancer, and provide new ideas for the diagnosis and treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the predictive role of inflammation-related parameters in prognosis of esophageal squamous cell carcinoma (ESCC). Methods: A total of 370 ESCC patients subjected to curative surgery were enrolled. All patients had complete medical records and did not receive preoperative adjuvant therapy. Preoperative systemic immune-inflammation index (SII) was calculated as platelet count × neutrophil count/lymphocyte count, prognostic nutrition index (PNI) as albumin concentration (g/L) + 5 × total lymphocyte count (109/L), and systemic inflammation response index (SIRI) as neutrophil count × monocyte count/lymphocyte count. The optimal cut-off values of preoperative SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), PNI, and SIRI were determined via receiver operating characteristic (ROC) analysis, and their correlations with clinical parameters and survival analyzed. Results: NLRwas associated with gender (P = 0.022), and PLR (P=0.037), PNI (P = 0.017) was associated with survival status, LMR was related with gender (P=0.034) and survival status (P = 0.01), SIRI was correlated with gender (P = 0.000), smoking history (P = 0.000) and drinking history (P = 0.004). Survival analysis indicated that high PLR (P = 0.042), low LMR (P=0.001), and lowPNI (P=0.007)were predictive of poor prognosis of ESCC. Stratified analysis revealed the prognostic predictor roles of distinct markers in different ESCC subgroups. SII and SIRI were predominantly correlated with the clinical outcome in the lymphatic metastasis subgroup. Further univariate analysis disclosed that T stage, smoking history, lymphatic metastasis, TNM staging, PLR, LMR, and PNI potentially serve as influencing factors(P < 0.05). Multivariate analysis identified T stage (HR = 1.781, P = 0.002), TNM staging (HR = 8.617, P = 0.001) and LMR (HR = 0.504, P = 0.001) as independent predictors for outcomes of ESCC. Conclusions: Low LMR could serve as an independent marker of poor prognosis in patients with ESCC. Inflammation-related markers have distinct predictive roles in ESCC subgroups with different features. [ABSTRACT FROM AUTHOR]

Individuals with high risk of internet gaming disorder (HIGD) showed abnormal psychological performances in response inhibition, impulse control, and emotion regulation, and are considered the high-risk stage of internet gaming disorder (IGD). The identification of this population mainly relies on clinical scales, which are less accurate. This study aimed to explore whether these performances have highly accurate for discriminating HIGD from low-risk ones. Eye tracking based anti-saccade task, Barratt impulsiveness scale (BIS), and Wong and Law emotional intelligence scale (WLEIS) were used to evaluate psychological performances in 57 individuals with HIGD and 52 matched low risk of internet gaming disorder (LIGD). HIGD group showed significantly increased BIS total (t = -2.875, p = 0.005), attention (t = -2.139, p = 0.035), motor (t = -2.017, p = 0.046), and non-planning (t = -2.171, p = 0.032) scores, but significantly decreased WLEIS emotion regulation score (t = 2.636, p = 0.010) and correct rate of eye tracking anti-saccade task (t = 2.294, p = 0.024) compared with LIGD group. BIS total score was negatively correlated with the WLEIS total (r = -0.473, p < 0.001) and WLEIS emotion regulation (r = -0.366, p < 0.001) scores. A combination of the WLEIS emotion regulation score and the correct rate of anti-saccade task could discriminate HIGD from LIGD with 91.23% sensitivity, 82.69% specificity, and 87.16% accuracy. Participants with higher gaming hours daily were 40 times more likely to be high risk than their counterparts (p < 0.001). Hence, psychological performances were worse in HIGD. A combination of abnormal emotion regulation and response inhibition might be a potential marker to identify HIGD individuals. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a class of closed circular non-coding RNAs widely exist in eukaryotes, with high stability and species conservation. A large number of studies have shown that circRNAs are abnormally expressed in various tumor tissues, and are abundant in plasma with long half-life and high specificity, which may be served as potential tumor biomarkers for early diagnosis, treatment and prognosis of malignant tumors. However, the role of circRNAs is still poorly understood in gastric cancer. This article reviews the research progress of circRNAs in gastric cancer in recent years so as to explore the relationship between circRNAs and the occurrence and the development of gastric cancer, and provide new ideas for the diagnosis and treatment of gastric cancer.

BackgroundVitamin D plays an invaluable role in reproductive health, but vitamin D insufficiency and deficiency are generally common among couples of childbearing age and pregnant women. This study aimed to evaluate the evolution, development trend, and research hotspot of publications on vitamin D and reproductive health.MethodsThe literature on vitamin D and reproductive health between 2012 and 2021 was retrieved from the Web of Science Core Collection (WoSCC). We used VOSviewer and CiteSpace to analyze publication years, countries, institutions, journals, highly cited authors and publications, and co-occurrence and citation bursts of keywords.ResultsA total of 1,828 articles and reviews on vitamin D and reproductive health published between 2012 and 2021 were identified. The annual publication outputs showed steady growth, with the most publications (272) and citations (7,097) in 2021. The United States contributed the most publications (458) and had the highest h-index (58). In terms of the number of publications and h-index, the journal named Nutrients ranked first. Nutrition dietetics, obstetrics gynecology, and endocrinology metabolism were three well-represented disciplines in research on vitamin D and reproductive health. Hollis BW, Wagner CL, and Litonjua AA were the top three most productive authors in this field during the last decade. Apart from vitamin D, the five keywords with the most frequent occurrence were vitamin D deficiency, pregnancy, risk, vitamin D supplementation, and 25-hydroxyvitamin D. Keyword citation burst analysis revealed that low birth weight, adipose tissue, marker, and embryo had a citation burst lasting until 2021.ConclusionIn conclusion, vitamin D has received continuous attention in the field of reproductive health, and there appears to have a higher level of research in North America. Multidisciplinary intersection contributed to the in-depth exploration in this field. And the effect of maternal vitamin D levels on fetal lipid metabolism and the prediction of fertility by vitamin D-related markers might be hotspots for the research.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm with rising incidence worldwide. Gremlin 1 (GREM1), a regulator of bone morphogenetic protein (BMP) signaling, fine-tunes extensive biological processes, including organ morphology, cellular metabolism, and multiple pathological developments. The roles of GREM1 in PDAC remain unknown. Methods: Varieties of public databases and online software were employed to analyze the expressions at transcription and protein levels of GREM1 in multiple malignant neoplasms including PDAC, and in addition, its potential pro-tumoral functions in PDAC were further evaluated. A total of 340 serum samples of pancreatic disease, including PDAC, low-grade malignant pancreatic neoplasm, benign pancreatic neoplasm, pancreatitis, and 132 healthy controls, were collected to detect GREM1. The roles of serum GREM1 in the diagnosis and prediction of survival of PDAC after radical resection were also analyzed. Results: Bioinformatics analyses revealed that GREM1 was overexpressed in PDAC and predicted a poorer survival in PDAC. A higher protein level of GREM1 in PDAC correlated with stroma formation and immunosuppression by recruiting varieties of immunosuppressive cells, including T regulatory cells (Tregs), M2 macrophages, myeloid-derived suppressor cells (MDSCs), and exhaustion T cells into the tumor microenvironment. A higher level of serum GREM1 was observed in PDAC patients, compared to healthy control (p < 0.001). Serum GREM1 had a good diagnostic value (area under the curve (AUC) = 0.718, p < 0.001), and its combination with carbohydrate antigen 199 (CA199) achieved a better diagnostic efficacy (AUC = 0.914, p < 0.001), compared to CA199 alone. The cutoff value was calculated by receiver operating characteristic (ROC) analysis, and PDAC patients were divided into two groups of low and high GREM1. Logistic analyses showed serum GREM1 positively correlated with tumor size (hazard ratio (HR) = 7.097, p = 0.032) and histopathological grades (HR = 2.898, p = 0.014). High-level serum GREM1 (1,117.8 pg/ml) showed a shorter postoperative survival (p = 0.0394). Conclusion: Higher intra-tumoral expression of GREM1 in PDAC contributes to tumor stroma and immunosuppressive tumor microenvironment, presenting its therapeutic potential. High-level serum GREM1 predicts poorer survival after resection. A combination of serum CA199 and GREM1 shows a stronger diagnostic efficacy in PDAC. [ABSTRACT FROM AUTHOR]

Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell-cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immunerelated pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is the interstitial lung disease with the highest incidence and mortality. The lack of specific markers results in limited treatment methods for IPF patients. Numerous prognostic signatures represented effective indexes in predicting the survival of patients in various diseases; however, little is investigated on their application in IPF. Methods: This study attempted to explore the clinical markers suitable for IPF by constructing a prognostic signature from the perspective of 7-methylguanosine (m7G). An m7G-related prognostic signature (m7GPS) was established based on the discovery cohort with the LASSO algorithm and was verified by internal and external validation cohorts. The area under the curve (AUC) values were utilized to assess the accuracy of m7GPS in predicting the prognosis of IPF patients and the ability of m7GPS in screening IPF patients. Kaplan-Meier curves and Cox regression analyses were used to identify the relationship of m7GPS with the prognosis of IPF individuals. Enrichment analyses, CIBERSORT algorithm, and weighted gene co-expression network analysis were applied to explore the underlying mechanisms and correlation of m7GPS in IPF. Results: The two m7G regulatory genes can divide IPF into subtypes 1 and 2, and subtype 2 demonstrated a poor prognosis for IPF patients (p < 0.05). For the first time in this field, the m7GPS was constructed. m7GPS made it feasible to predict the 1–5 years survival status of IPF patients (AUC = 0.730–0.971), and it was an independent prognostic risk factor for IPF patients (hazard ratio > 1, p < 0.05). The conspicuous ability of m7GPS to screen IPF patients from the healthy was also revealed by an AUC value of 0.960. The roles of m7GPS in IPF may link to inflammation, immune response, and immune cell levels. Seven genes (CYR61 , etc.) were identified as hub genes of m7GPS in IPF. Three drugs (ZM447439-1050, AZD1332-1463, and Ribociclib-1632) were considered sensitive to patients with high m7GPS risk scores. Conclusion: This study developed a novel m7GPS, which is a reliable indicator for predicting the survival status of IPF patients and is identified as an effective marker for prognosis and screening of IPF patients. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) refers to a heterogeneous group of cardiomyopathies characterized by ventricular dilatation and myocardial systolic dysfunction, which can lead to serious consequences such as malign arrhythmia, sudden death, heart failure, and thromboembolism. With its economical, non-invasive, simple and reproducible advantages, electrocardiogram (ECG) has become an important indicator for assessing the prognosis of cardiovascular diseases. In recent years, more and more studies of electrocardiography on DCM have been carried out, but there is still a lack of a comprehensive summary of its prognostic value. This article reviews the prognostic value of electrocardiographic markers in children with DCM.

BackgroundSarcopenia is associated with poor clinical outcomes in patients with locally advanced gastric cancer (LAGC). Currently, the diagnostic criteria for sarcopenia are complex and laborious. Increased evidence suggests the inflammatory state of the body is closely associated with the development of sarcopenia. The systemic immune-inflammatory index (SII) and the prognostic nutritional index (PNI) are representative blood indicators of the status of the systemic inflammatory response, but the clinical significance of the combined testing of these two indicators remains unclear. We aimed to develop a simple and practical risk score (SII-PNI score) to screen patients with LAGC for sarcopenia on admission for early diagnosis.MethodsWe registered a prospective clinical study from January 2011 to May 2016 involving 134 patients with LAGC undergoing radical surgical resection. All patients followed the definition of sarcopenia in the Asian Working Group on Sarcopenia (AWGS) guidelines and were divided into sarcopenia and non-sarcopenia groups. SII-PNI score 0–2 was scored as 2 for high SII (≥432.9) and low PNI ( ≤ 49.5); score 1, either high SII or low PNI; score 0, no high SII or low PNI.ResultsAll patients underwent radical surgery, including 31 patients (23.13%) with sarcopenia according to AWGS criteria. The SII-PNI score was significantly lower in the non-sarcopenic patients than in the sarcopenic patients (p < 0.001). Logistic multivariate analysis showed that the SII-PNI score predicted an independent prognostic factor for sarcopenia (p < 0.001). Patients with high SII-PNI scores had significantly worse prognosis than those with low SII-PNI scores (p < 0.001). The SII-PNI score was an independent prognostic factor for predicting overall survival and disease-free survival (p = 0.016, 0.023).ConclusionPeripheral blood parameters SII-PNI scores accurately identify sarcopenia in patients with LAGC and could be used as potential systemic markers.

BackgroundThe WHO emphasized the importance of knowing the risk factors for the severity of the disease in the COVID-19 pandemic. Our aim in this study was to determine the relationship between serum Butyrylcholinesterase (BChE) level, which is rapidly affected by inflammation, and the severity of COVID-19 pneumonia and mortality.MethodsPatients diagnosed with COVID-19 pneumonia between March and May 2021 were included in the study. The patients were divided into two groups as severe and mild to moderate pneumonia according to the WHO's guidelines. Serum BChE levels were studied by ELISA method from the blood samples taken from the patients on the day of hospitalization. The severity of the disease and other factors affecting hospital mortality were also evaluated.Results147 patients with COVID-19 pneumonia were included in this study. Of these patients, 58% had severe pneumonia and 42% had mild to moderate pneumonia. The BChE level was median 13 (IQR: 11.2–21.5)ng/ml in patients with severe COVID-19 pneumonia and median 20 (IQR: 10–35.7)ng/ml in patients with mild to moderate pneumonia (p: 0.001). Hospital with mortality rate was higher in patients with low BChE levels. However, statistically, BChE hasn't associated mortality in COVID-19 pneumonia [OR 1.002 (0.957–1.049) p: 0.490]. CRP, procalcitonin, lactate, and D-dimer levels were associated mortality in COVID-19 pneumonia.ConclusionBeing not statistically significant, the mortality rate was higher in patients with low BChE levels. BChE level is an important marker in determining the severity of COVID-19 pneumonia. Early prediction of the severity of COVID-19 pneumonia will enable early planning of the treatment process.

Introduction and objectivesIn patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease.Materials and methodsThe study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR.ResultsA total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91–10.46) and 4.00 (2.33–6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay (p < 0.001), death (p < 0.001), and invasive ventilation (p < 0.001) while that of dNLR with ICU stay (p = 0.002), death (p < 0.001), and invasive ventilation (p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT).ConclusionBoth markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients.

Background: Idiopathic pulmonary fibrosis (IPF) is the interstitial lung disease with the highest incidence and mortality. The lack of specific markers results in limited treatment methods for IPF patients. Numerous prognostic signatures represented effective indexes in predicting the survival of patients in various diseases; however, little is investigated on their application in IPF.Methods: This study attempted to explore the clinical markers suitable for IPF by constructing a prognostic signature from the perspective of 7-methylguanosine (m7G). An m7G-related prognostic signature (m7GPS) was established based on the discovery cohort with the LASSO algorithm and was verified by internal and external validation cohorts. The area under the curve (AUC) values were utilized to assess the accuracy of m7GPS in predicting the prognosis of IPF patients and the ability of m7GPS in screening IPF patients. Kaplan-Meier curves and Cox regression analyses were used to identify the relationship of m7GPS with the prognosis of IPF individuals. Enrichment analyses, CIBERSORT algorithm, and weighted gene co-expression network analysis were applied to explore the underlying mechanisms and correlation of m7GPS in IPF.Results: The two m7G regulatory genes can divide IPF into subtypes 1 and 2, and subtype 2 demonstrated a poor prognosis for IPF patients (p < 0.05). For the first time in this field, the m7GPS was constructed. m7GPS made it feasible to predict the 1–5 years survival status of IPF patients (AUC = 0.730–0.971), and it was an independent prognostic risk factor for IPF patients (hazard ratio > 1, p < 0.05). The conspicuous ability of m7GPS to screen IPF patients from the healthy was also revealed by an AUC value of 0.960. The roles of m7GPS in IPF may link to inflammation, immune response, and immune cell levels. Seven genes (CYR61, etc.) were identified as hub genes of m7GPS in IPF. Three drugs (ZM447439-1050, AZD1332-1463, and Ribociclib-1632) were considered sensitive to patients with high m7GPS risk scores.Conclusion: This study developed a novel m7GPS, which is a reliable indicator for predicting the survival status of IPF patients and is identified as an effective marker for prognosis and screening of IPF patients.

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker.

Background: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies. Materials and Methods: Serum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA). Results: The data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log10 IL-8, log10 MCP-1, and log10 tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA. Conclusions: The novel combination of serum markers identified in this study could be employed to help triage patients into "low-" and "high-risk" categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence has revealed that epithelial–mesenchymal transition (EMT) and immunity play key roles in idiopathic pulmonary fibrosis (IPF). However, correlation between EMT and immune response and the prognostic significance of EMT in IPF remains unclear. Methods: Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database. EMT- and immune-related genes were identified by gene set variation analysis (GSVA) and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the functions of these EMT- and immune-related genes. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen prognostic genes and establish a gene signature. Gene Set Enrichment Analysis (GSEA) and Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) were used to investigate the function of the EMT- and immune-related signatures and correlation between the EMT- and immune-related signatures and immune cell infiltration. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the mRNA expression of genes in the EMT- and immune-related signatures. Results: Functional enrichment analysis suggested that these genes were mainly involved in immune response. Moreover, the EMT- and immune-related signatures were constructed based on three EMT- and immune-related genes (IL1R2, S100A12, and CCL8), and the K–M and ROC curves presented that the signature could affect the prognosis of IPF patients and could predict the 1-, 2-, and 3-year survival well. Furthermore, a nomogram was developed based on the expression of IL1R2, S100A12, and CCL8, and the calibration curve showed that the nomogram could visually and accurately predict the 1-, 2-, 3-year survival of IPF patients. Finally, we further found that immune-related pathways were activated in the high-risk group of patients, and the EMT- and immune-related signatures were associated with NK cells activated, macrophages M0, dendritic cells resting, mast cells resting, and mast cells activated. qRT-PCR suggested that the mRNA expression of IL1R2, S100A12, and CCL8 was upregulated in whole blood of IPF patients compared with normal samples. Conclusion: IL1R2, S100A12, and CCL8 might play key roles in IPF by regulating immune response and could be used as prognostic biomarkers of IPF. [ABSTRACT FROM AUTHOR]

Meat color is the primary criterion by which consumers evaluate meat quality. However, there are a few candidate genes and molecular markers of meat color that were reported for pig molecular breeding. The purpose of the present study is to identify the candidate genes affecting meat color and provide the theoretical basis for meat color molecular breeding. A total of 306 Suhuai pigs were slaughtered, and meat color was evaluated at 45 min and 24 h after slaughter by CIELAB color space. All individuals were genotyped using GeneSeek GGP-Porcine 80K SNP BeadChip. The genomic estimated breeding values (GEBVs), heritability, and genetic correlation of meat color were calculated by DMU software. The genome-wide association studies (GWASs) and the fixation index (FST) tests were performed to identify SNPs related to meat color, and the candidate genes within 1 Mb upstream and downstream of significant SNPs were screened by functional enrichment analysis. The heritability of L* 45 min, L* 24 h, a* 45 min, a* 24 h, b* 45 min, and b* 24 h was 0.20, 0.16, 0.30, 0.13, 0.29, and 0.22, respectively. The genetic correlation between a* (a* 45 min and a* 24 h) and L* (L* 45 min and L* 24 h) is strong, whereas the genetic correlation between b* 45 min and b* 24 h is weak. Forty-nine significant SNPs associated with meat color were identified through GWAS and FST tests. Among these SNPs, 34 SNPs were associated with L* 45 min within a 5-Mb region on Sus scrofa chromosome 11 (SSC11); 22 SNPs were associated with a* 45 min within a 14.72-Mb region on SSC16; six SNPs were associated with b* 45 min within a 4.22-Mb region on SSC13; 11 SNPs were associated with b* 24 h within a 2.12-Mb region on SSC3. These regions did not overlap with meat color–associated QTLs reported previously. Moreover, six candidate genes (HOMER1 , PIK3CG , PIK3CA , VCAN , FABP3 , and FKBP1B), functionally related to muscle development, phosphatidylinositol phosphorylation, and lipid binding, were detected around these significant SNPs. Taken together, our results provide a set of potential molecular markers for the genetic improvement of meat color in pigs. [ABSTRACT FROM AUTHOR]