Search

AimsAnecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA).MethodsThe volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit>180) using the CAC scoring CT images acquired in the 5th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam.ResultsA total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm3 [IQR: 1751] vs. 3054 mm3 [3851], p

The utilization of heterosis is of great significance in improving rice yield. To explore the physiological and genetic basis for high yield in indica–japonica hybrid rice, Zheyou18 (z18) and Yongyou12 (y12) were used as materials and compared with indica hybrid rice, Zheyou12 (z12); japonica hybrid rice, Liangyoupeijiu (LYPJ); and the conventional lines zhe04B (04B) and zhehui818 (h818) under seedling growth vigor, functional leaf morphology, chlorophyll content, yield component, panicle trait, and InDel heterosis analysis. Z18 and y12 showed the largest increase in plant height 6 d and 9 d after germination; the root dry weight of z18 was 31.2% and 42.0% higher than its parents on the 12th d. The length of functional leaves ranked in the middle, while the width was the largest, resulting in z18 and y12 having the largest leaf area. Yield components showed that z18 and y12 had the highest number of primary branches, spikelets, and grains, and grain yield, which was 58.1 g in z18, increased by 29.8% and 8.7%, respectively, in comparison with h818 and LYPJ. The InDel genetic distance was significantly positively correlated with single spike weight, with r reaching 0.771, making it the only consistent and most correlated among the seven traits. Therefore, we speculated that as the InDel genetic distance expands, heterosis mainly manifests in the increase in single spike weight. This study comprehensively explored the physiological mechanism of yield improvement in indica–japonica-hybrid rice and used InDel genetic distances to study the genetic basis of heterosis, which will be helpful for future rice yield improvement.

Smoking significantly elevates the risk of lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. This risk is attributed to the harmful chemicals in tobacco smoke that damage lung tissue and impair lung function. Current research on the impact of smoking on gene expression in specific lung cells is limited. This study addresses this gap by analyzing gene expression profiles at the single-cell level from 43,539 lung endothelial cells, 234,349 lung epithelial cells, 189,843 lung immune cells, and 16,031 lung stromal cells using advanced machine learning techniques. The data, categorized by different lung cell types, were classified into three smoking states: active smoker, former smoker, and never smoker. Each cell sample encompassed 28,024 feature genes. Employing an incremental feature selection method within a computational framework, several specific genes have been identified as potential markers of smoking status in different lung cell types. These include B2M, EEF1A1, and TPT1 in lung endothelial cells; FTL and MT-ATP8 in lung epithelial cells; HLA-B and HLA-C in lung immune cells; and HSP90B1 and LCN2 in lung stroma cells. Additionally, this study developed quantitative rules for representing the gene expression patterns related to smoking. This research highlights the potential of machine learning in oncology, enhancing our molecular understanding of smoking’s harm and laying the groundwork for future mechanism-based studies.

Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/β-catenin, Notch, and Sonic Hedgehog. We discuss a wide array of therapeutic modalities ranging from targeted antibodies, small molecule inhibitors, and near-infrared photoimmunotherapy to advanced genetic approaches like RNA interference, CRISPR/Cas9 technology, aptamers, antisense oligonucleotides, chimeric antigen receptor (CAR) T cells, CAR natural killer cells, bispecific T cell engagers, immunotoxins, drug-antibody conjugates, therapeutic peptides, and dendritic cell vaccines. This review spans developments from preclinical investigations to ongoing clinical trials, highlighting the innovative targeting strategies that have been informed by CSC-associated pathways and molecules to overcome therapeutic resistance. We aim to provide insights into the potential of these therapies to revolutionize cancer treatment, underscoring the critical need for a multi-faceted approach in the battle against cancer. This comprehensive analysis demonstrates how advances made in the CSC field have informed significant developments in novel targeted therapeutic approaches, with the ultimate goal of achieving more effective and durable responses in cancer patients.

(1) Background: The number of horses suffering from chronic respiratory diseases, resembling human asthma, is increasing but there is still a lack of reliable and accurate methods to detect these disorders. Numerous studies have found elevated plasma concentrations of one of the myokines, namely, myostatin (MSTN), in people suffering from severe asthma. MSTN normally inhibits myoblast proliferation and differentiation through autocrine or paracrine signals. Therefore, given the pathogenesis of asthma, we hypothesize that MSTN could be a useful biomarker of equine asthma. Thus, this study aimed to compare the concentration of MSTN in the blood plasma of fully healthy and asthmatic horses. (2) Methods: A total of 61 horses were clinically examined to confirm or exclude the occurrence of equine asthma, including bronchoalveolar lavage (BAL) fluid cytology performed on 49 horses. This study included three groups of horses, two of which were clinically healthy, and one of which was asthmatic. (3) Results: The mean circulatory MSTN concentration determined using the ELISA method in asthmatic horses was significantly higher than that in clinically healthy young Thoroughbred racehorses (p < 0.05), but it did not differ as compared to the group of healthy, adult leisure horses. (4) Conclusions: The obtained results did not unambiguously support our original hypothesis that MSTM may be a reliable marker for the early diagnosis of equine asthma. To the best of the authors’ knowledge, this is the first study to analyze the plasma MSTN concentration in equine asthma patients, and therefore further studies are needed to confirm our novel findings.

Fractionation of digesta, as occurs during gastrointestinal transit in chickens, complicates accurate measurements of ileal digestibility using tracers. Dual-tracer methods using separate tracers for solid and fluid digesta phases may improve the accuracy of digestibility measurements when assumptions of the single tracer method are violated. The aim of the present study was to compare the apparent ileal digestibility (AID) of nutrients calculated with single- and dual-tracer methods in chickens fed diets varying in particle size, anticipating digesta phase separation in the proximal gastrointestinal tract. A total of 112 Dekalb White (BW: 1.53 ± 0.107 kg) and 112 Bovans Black (BW: 1.79 ± 0.127 kg) 29-week-old laying hens were distributed over 32 pens (seven birds/pen). Within breed, pens were randomly assigned to one of two experimental diets (coarse vs fine oat hulls; n = 8 replicate pens per diet/breed combination). Diets were supplemented with TiO2 (3 g/kg) and Co-EDTA (2 g/kg). On days 34, 35, or 36, birds were euthanised and digesta from the ileum was collected for tracer and nutrient analyses. Apparent ileal digestibility was subsequently calculated by single- and dual-tracer methods. Although coarse oat hulls were hypothesised to increase the fractionation of solid and fluid digesta phases, no breed or diet × method interactions were found. Using a single tracer method based on TiO2, AID of nitrogen (N) was overestimated by 3%-units (P 0.09) and precision of all AID estimates was improved. In conclusion, these results show that although from a conceptual perspective, dual-tracer methods are presumed to better account for the variation in flow behaviour of different digesta phases, AID estimates obtained by the commonly used single tracer method using solid-phase tracer TiO2 were more precise and only marginally differed from estimates obtained by a dual-tracer method using distinct tracers for solid (TiO2) and liquid (Co-EDTA) digesta phases. Considering technical and economical constraints, the single tracer method may thus be the method of choice in many situations. Only when digestibility of proteins or amino acids is of specific interest, single tracer methods using a solid-phase tracer may not suffice. Nevertheless, for both single- and dual-tracer methods, tracer selection is critical, and the choice of tracers should depend on the nutrient(s) of interest.

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]

Background: Long non-coding RNA (lncRNA) plays a vital role in tumor proliferation, migration, and treatment. Since it is challenging to standardize the gene expression levels detected by different platforms, the signatures composed of many immune-related single lncRNAs are still inaccurate. Utilizing a gene pair formed of two immune-related lncRNAs and strategically assigning values can effectively meet the demand for a higher-accuracy dual biomarker combination. Methods: Co-expression and differential expression analyses were performed on immune genes and lncRNAs data from The Cancer Genome Atlas and the ImmPort database to obtain differentially expressed immune-related lncRNAs for pairwise pairing. The prognostic-related differentially expressed immune-related lncRNAs (PR-DE-irlncRNAs) pairs were then identified by univariate Cox regression and used for lasso regression to construct a prognostic model. Various methods were used to validate the predictive prognostic performance of the model. Additionally, we explored the potential guiding value of the model in immunotherapy and chemotherapy and constructed a nomogram suitable for efficient prognosis prediction. Mechanistic exploration of anti-tumor immunity and mutational perspectives are also included. We also analyzed the correlation between the model and immune checkpoint inhibitors (ICIs)-related, N6-methyadenosine (m6A)-related, and multidrug resistance genes. Results: We used a total of 20 pairs of PR-DE-irlncRNAs to create a prognosis model. Quantitative real-time polymerase chain reaction experiments further verified the abnormal expression of 11 lncRNAs in HNSCC cells. Various methods have confirmed the excellent performance of the model in predicting patient prognosis. We reasoned that lncRNAs/TP53 mutation might play a positive/negative anti-tumor role through the immune system by multi-perspective analyses. Finally, it was found that the prognostic model was closely related to immunotherapy and chemotherapy as well as the expression of ICIs/m6A/multidrug resistance-related genes. Conclusion: The prognostic model performs excellently in predicting the prognosis of patients and provides the potential value of practical guidance for treatment. [ABSTRACT FROM AUTHOR]

Background: Plant genome information is fundamental to plant research and development. Along with the increase in the number of published plant genomes, there is a need for an efficient system to retrieve various kinds of genome-related information from many plant species across plant kingdoms. Various plant databases have been developed, but no public database covers both genomic and genetic resources over a wide range of plant species. Main body: We have developed a plant genome portal site, Plant GARDEN (Genome And Resource Database Entry: https://plantgarden.jp/en/index), to provide diverse information related to plant genomics and genetics in divergent plant species. Elasticsearch is used as a search engine, and cross-keyword search across species is available. Web-based user interfaces (WUI) for PCs and tablet computers were independently developed to make data searches more convenient. Several types of data are stored in Plant GARDEN: reference genomes, gene sequences, PCR-based DNA markers, trait-linked DNA markers identified in genetic studies, SNPs, and in/dels on publicly available sequence read archives (SRAs). The data registered in Plant GARDEN as of March 2023 included 304 assembled genome sequences, 11,331,614 gene sequences, 419,132 DNA markers, 8,225 QTLs, and 5,934 SNP lists (gvcf files). In addition, we have re-annotated all the genes registered in Plant GARDEN by using a functional annotation tool, Hayai-Annotation, to compare the orthologous relationships among genes. Conclusion: The aim of Plant GARDEN is to provide plant genome information for use in the fields of plant science as well as for plant-based industries, education, and other relevant areas. Therefore, we have designed a WUI that allows a diverse range of users to access such information in an easy-to-understand manner. Plant GARDEN will eventually include a wide range of plant species for which genome sequences are assembled, and thus the number of plant species in the database will continue to expand. We anticipate that Plant GARDEN will promote the understanding of genomes and gene diversity by facilitating comparisons of the registered sequences. [ABSTRACT FROM AUTHOR]

Tiller number is an important trait associated with yield in rice. Tiller number in Korean japonica rice was analyzed under greenhouse conditions in 160 recombinant inbred lines (RILs) derived from a cross between the temperate japonica varieties Odae and Unbong40 to identify quantitative trait loci (QTLs). A genetic map comprising 239 kompetitive allele-specific PCR (KASP) and 57 cleaved amplified polymorphic sequence markers was constructed. qTN3, a major QTL for tiller number, was identified at 132.4 cm on chromosome 3. This QTL was also detected under field conditions in a backcross population; thus, qTN3 was stable across generations and environments. qTN3 co-located with QTLs associated with panicle number per plant and culm diameter, indicating it had pleiotropic effects. The qTN3 regions of Odae and Unbong40 differed in a known functional variant (4 bp TGTG insertion/deletion) in the 5ʹ UTR of OsTB1, a gene underlying variation in tiller number and culm strength. Investigation of variation in genotype and tiller number revealed that varieties with the insertion genotype had lower tiller numbers than those with the reference genotype. A high-resolution melting marker was developed to enable efficient marker-assisted selection. The QTL qTN3 will therefore be useful in breeding programs developing japonica varieties with optimal tiller numbers for increased yield. [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: Rheumatoid arthritis (RA) is a systemic autoimmune disease that chronically affects patients with episodes of inflammation. New inflammatory hematological markers were investigated for follow‐up, such as the neutrophil–monocyte ratio (NMR), lymphocyte monocyte ratio (LMR), and neutrophil–lymphocyte ratio (NLR). This study was conducted to determine the most useful marker based on studies of association with RA disease activity and correlation with the classical markers C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). Methods: This case‐control study included 62 chronic RA patients who had previously been diagnosed and experienced episodes of symptoms while attending a variety of public and private rheumatology clinics in Ibb City, Republic of Yemen, for the period of September 1 to November 30, 2021. Twenty healthy volunteers were included in this study. Complete blood count, CRP, ESR, and RF levels were measured in all participants. Results: The total leukocyte count, neutrophil count, platelet count, NMR, LMR, and NLR were positively correlated with CRP and ESR, but the monocyte count was reversed. The area under the curve (AUC = 0.861, 95% confidence interval [CI] = 0.769–0.948) for the NMR cutoff value of 4.7 was equal to that of CRP and close to that of ESR. This NMR cutoff value had 87% sensitivity and 80% specificity. LMR and NLR cutoff values of 4.35 and 1.35, respectively, resulted in AUCs of (AUC = 0.807, 95% CI, 0.708–0.905) and (AUC = 0.699, 95% CI, 0.571–0.819); their sensitivity and specificity were 62.3%, 90%, 57.4%, and 80%, respectively. Conclusions: As a convenient and low‐cost inflammatory marker of RA activity, NMR outperformed LMR and NLR. [ABSTRACT FROM AUTHOR]

This study explores using the speech of Najdi social media influencers in Snapchat and TikTok as a source of sociolinguistic production data. Saudis in general, Najdis in particular, post their daily life vlogs on these apps building a huge volume of recorded speech in the local dialects. This type of content has been examined to introduce the possibility of using it as a source of production data alongside/instead of the sociolinguistic interview. The speech of 18 social media influencers, representing three sub-dialects of Najd, has been transcribed and analyzed to test whether it is natural and not mostly formal. The variables have been ranked according to Labov's (1972) classification of speakers' awareness: stereotype, marker and indicator. It was found in this study that, similar to data elicited from the interview, social media influencers tend to use their local variants which are classified as markers and/or indicators, and they avoid using stereotypes. In some social settings, the social media influencers were even more spontaneous than they would be in an interview. The study suggests that the speech of social media influencers in Najd is an easily accessible, larger, and better-quality source of sociolinguistic production data. [ABSTRACT FROM AUTHOR]

Wheat dwarf virus (WDV) causes an important vector transmitted virus disease, which leads to significant yield losses in barley production. Due to the fact that, at the moment, no plant protection products are approved to combat the vector Psammotettix alienus, and this disease cannot be controlled by chemical means, the use of WDV-resistant or -tolerant genotypes is the most efficient method to control and reduce the negative effects of WDV on barley growth and production. In this study, a set of 480 barley genotypes were screened to identify genotypic differences in response to WDV, and five traits were assessed under infected and noninfected conditions. In total, 32 genotypes showed resistance or tolerance to WDV. Subsequently, phenotypic data of 191 out of 480 genotypes combined with 34,408 single-nucleotide polymorphisms (SNPs) were used for a genome-wide association study to identify quantitative trait loci (QTLs) and markers linked to resistance/tolerance to WDV. Genomic regions significantly associated with WDV resistance/tolerance in barley were identified on chromosomes 3H, 4H, 5H, and 7H for traits such as relative virus titer, relative performance of total grain weight, plant height, number of ears per plant, and thousand grain weight. [ABSTRACT FROM AUTHOR]

The link between plasma D-dimer levels and underlying malignancy has been established. How this translates in clinical practice as a marker of detection and prognosis of cervical cancer (CC) is still unknown. This study compared the plasma D-dimer levels in women with and without CC and assessed the associations between plasma D-dimer levels and the stage and grade of CC. It was a comparative cross-sectional study of 65 women with histological diagnosis of CC and an equal number of age-matched cancer-free women enrolled at the University Teaching Hospital in Lagos, Nigeria. Participants' sociodemographic and clinical data as well as venous blood samples for estimation of plasma D-dimer were collected for statistical analyses. A receiver operating characteristic (ROC) analysis is performed to select the cut-off value of plasma D-dimer for differentiating CC from non-cancer. There was a statistically significant difference in the median levels of plasma D-dimer of women with CC and their cancer-free comparison groups (3,120 (1,189-4,515) versus 210 (125-350) ng/mL; p = 0.001). A plasma D-dimer value of 543 ng/mL was chosen in a ROC analysis as the discriminatory cut-off to differentiate CC from non-cancer. There were significant associations between plasma D-dimer levels and the International Federation of Gynaecology and Obstetrics stage (p = 0.001) or grade (p = 0.001) of CC. The study, therefore, demonstrated the potential clinical usefulness of plasma D-dimer as a diagnostic and prognostic marker of CC. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic Encephalopathy (HE) is a term used to describe a reversible syndrome of impaired brain function involving a complex spectrum of non specific neurological and psychiatric manifestations occurring in patients of severe acute or Chronic Liver Disease (CLD). The current clinical standard employed is psychometric analysis by computing Psychometric Hepatic Encephalopathy Score (PHES), which is cumbersome to perform. Hence, this necessitates the requirement of a serum biomarker which could correlate with the grades of HE. Following a metabolic injury, the earliest response involving the glial response and astrocyte activation results in the secretion of S100 Beta. Hence, estimation of serum S100 beta levels is considered as a strong marker of Central Nervous System (CNS) injury. Aim: To verify S100 Beta as a marker of HE. Materials and Methods: This was a case-control study conducted from 1st April 2021 to 31st July 2022. All diagnosed cases of cirrhosis of liver in the Medicine Department of a tertiary care hospital of North India. A total of 40 age and sex matched healthy controls were recruited after due consent and application of exclusion criteria. They were subjected to psychometric analysis (Five pen and paper tests) and on basis of PHES were divided into four groups on the basis of grades of encephalopathy. Serum samples of patients were run for all routine biochemical parameters in line with Child Turcotte Pugh (CTP) score and S100 Beta levels estimation. Statistical analysis was done to find correlation between S100 Beta levels, PHES and CTP score. Results: A total of 150 patients and 40 controls were recruited in the study. A progressive deterioration of PHES score was found in the various groups of the study population with worsening of grade of HE. S100 Beta levels correlated with the PHES and also Receiver Operating Characteristic (ROC) curve analysis showed that the sensitivity of the marker stood at 92.7% and specificity at 84.8%. S100 Beta levels could fairly differentiate between patients with and without HE. Hence, S100 Beta levels correlated more with grades of HE than with hepatic functional status (CTP Score). At higher grades of HE when it becomes more clinically apparent, S100 Beta levels would help, when other causes of behaviour changes like psychiatric illness coexist or cannot be ruled out. In the diagnosis of low-grade HE whenever neuro psychometric tests are suboptimal, or when competing psychiatric differential diagnoses are in place, S100 beta levels would have a role over and above the PHES score. Conclusion: Currently, psychometric analysis holds to be the best clinical standard for diagnosis of HE. S100 Beta holds promising results as a marker for establishing a liquid diagnosis of HE. [ABSTRACT FROM AUTHOR]

Cancer is considered as one of the main causes of human deaths and a global health challenge. Despite the therapeutic and diagnostic progresses, there is a high rate of mortality among cancer patients. Late diagnosis is one of the most important reasons of high mortality rate, which is mainly due to the lack of efficient and non-invasive diagnostic methods to monitor cancer patients. Therefore, the introduction of non-invasive markers can play an effective role in the early diagnosis and better therapeutic management in these patients. MicroRNAs (miRNAs) have critical functions in regulation of various physiological and pathophysiological cellular processes. Deregulation of miRNAs has been frequently reported in different tumor types. On the other hand, due to the high stability of these factors in body fluids, these factors can be used as the non-invasive tumor markers. In this study, for the first time, we discussed the role of miR-185 during tumor progression. It has been reported that miR-185 mainly functions as a tumor suppressor through the regulation of PI3K/AKT, JAK/STAT, TGF-β, Hippo, and WNT signaling pathways as well as the transcription factors and cell cycle components. PI3K/AKT was reported as the main oncogenic signaling pathway that can be inhibited by miR-185 during tumor progression. Therefore, miR-185/PI3K/AKT axis can be suggested as a probable target in tumor therapy that requires further animal studies. The present review can be an effective step towards introducing the miR-185 as a non-invasive diagnostic marker and a therapeutic target in cancer patients. • Late diagnosis is one of the most important reasons of high cancer mortality rate. • MiRNAs can be used as non-invasive markers for the early tumor detection. • MiR-185 can be suggested as a novel non-invasive diagnostic tumor marker. [ABSTRACT FROM AUTHOR]

Introduction: Production of high-quality seeds to stabilize crop yield is an important challenge for breeders. One of the most important answers to this challenge is to clarify the molecular mechanisms associated with seed vigor characteristics. Functional proteins of Cupin superfamily are among the molecules in signaling pathway. Previous research has shown that in maize, a storage protein similar to the functional Cupin superfamily protein called ZmGLP is effective in seed germination. However, in the previous experiments, suitable indicators were not used to assess seed vigor and its relationship with field establishment. So, it is needed to study the performance of ZmGLP in predicting field emergence to complete the previous research. Materials and Methods: An experiment was performed on 14 samples of commercial inbred maize lines. In this experiment, in addition to the laboratory evaluation of seed germination, field indices of physiological seed quality including the percentage of seedling emergence in the field, time to 50% seedling emergence, time to 90% seedling emergence, seedling dry weight, seedling height and coefficient of variation of seedling height was also assessed. In the polymerase chain reaction, two pairs of primers (CF / CR primers and IDF / IDR primers) were used to identify the DNA sequence of the Cupin. Results: The results show that the seeds were different in terms of physiological quality. The lowest percentage of germination in laboratory was related to K1264/1, while the lowest physiological quality of seeds in field indices was observed in K1263/17. The molecular test confirmed the presence of the desired allele at the InDel9 site of vigor-related genes in the three samples of B73, K1264/1, and K1264/5-1, but no amplification band of the InDel9 site was observed in all K1263/17 seed samples. Due to the fact that line K1264/1, which had the lowest germination percentage in the laboratory, had an amplification band at this related site to vigor, it is not enough to rely on the results of the laboratory germination test to investigate the relationship between this gene and seed vigor. The field emergence test and seed vigor test that have a good prediction of field emergence must be used in these studies. Conclusions: According to the results of this experiment, molecular tests with functional markers based on Indel9 can be used to accelerate the evaluation of vigor, especially when the breeder is breeding a new line or hybrid. It is a useful, rapid, and effective molecular method to predict seed emergence in the field and screen the lines to ensure the genetic strength of the germination of the lines, especially in the temperate germplasms of corn. Finally, it is necessary to determine the threshold of low vigor during seed quality investigation in different cultivars, and relationship between the presence or absence InDel9 site should be considered in future research. [ABSTRACT FROM AUTHOR]

Background: SOX17 (SRY‐box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens. In this study, validation of the utility of SOX17 immunohistochemistry (IHC) in diagnosing metastatic gynecologic carcinomas in cytology specimens was sought. Methods: The study cohort included 84 cases of metastatic carcinomas that included 29 metastatic gynecologic carcinomas (24 ovarian high‐grade serous carcinomas, two endometrial serous carcinomas, one low‐grade serous carcinoma, one ovarian clear cell carcinoma, and one endometrial endometrioid carcinoma) and 55 cases of metastatic nongynecologic carcinomas (10 clear cell renal cell carcinomas, 10 papillary thyroid carcinomas, 11 gastrointestinal adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, and four urothelial carcinomas). Cytology specimen types included peritoneal fluid (n = 44), pleural fluid (n = 25), and fine‐needle aspiration (n = 15). SOX17 IHC was performed on the cell block sections. The intensity of staining and percent positivity of the tumor cells were evaluated. Results: SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse and strong nuclear expression (29 of 29; 100%). SOX17 was negative in other metastatic nongynecologic carcinomas (54 of 55; 98.18%) except for one papillary thyroid carcinoma that showed low positivity (<10%). Conclusions: SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. Therefore, SOX17 IHC should be included in the workup of differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. The results of this study showed that SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse (100%) and strong nuclear expression (29 of 29) and was negative in 54 of 55 metastatic nongynecologic carcinomas. SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the diagnosis of metastatic gynecologic carcinomas in cytology specimens. [ABSTRACT FROM AUTHOR]

In-hospital cardiac arrest (IHCA) is associated with high mortality and poor neurological outcomes. Our objective was to assess whether the lactate-to-albumin ratio (LAR) can predict the outcomes in patients after IHCA. We retrospectively screened 75,987 hospitalised patients at a university hospital between 2015 and 2019. The primary endpoint was survival at 30-days. Neurological outcomes were assessed at 30 days using the cerebral performance category scale. 244 patients with IHCA and return of spontaneous circulation (ROSC) were included in this study and divided into quartiles of LAR. Overall, there were no differences in key baseline characteristics or rates of pre-existing comorbidities among the LAR quartiles. Patients with higher LAR had poorer survival after IHCA compared to patients with lower LAR: Q1, 70.4% of the patients; Q2, 50.8% of the patients; Q3, 26.2% of the patients; Q4, 6.6% of the patients (p = 0.001). Across increasing quartiles, the probability of a favourable neurological outcome in patients with ROSC after IHCA decreased: Q1: 49.2% of the patients; Q2: 32.8% of the patients; Q3: 14.7% of the patients; Q4: 3.2% of the patients (p = 0.001). The AUCs for predicting 30-days survival using the LAR were higher as compared to using a single measurement of lactate or albumin. The prognostic performance of LAR was superior to that of a single measurement of lactate or albumin for predicting survival after IHCA. [ABSTRACT FROM AUTHOR]

The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the CARTPT gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of CART protein in the development of neoplasms remains unclear. This systematic review includes articles retrieved from the Scopus, PubMed, Web of Science and Medline Complete databases. Nineteen publications that met the inclusion criteria and describe the association of CART and cancer were analyzed. CART is expressed in various types of cancer, e.g., in breast cancer and neuroendocrine tumors (NETs). The role of CART as a potential biomarker in breast cancer, stomach adenocarcinoma, glioma and some types of NETs was suggested. In various cancer cell lines, CARTPT acts an oncogene, enhancing cellular survival by the activation of the ERK pathway, the stimulation of other pro-survival molecules, the inhibition of apoptosis or the increase in cyclin D1 levels. In breast cancer, CART was reported to protect tumor cells from tamoxifen-mediated death. Taken together, these data support the role of CART activity in the pathogenesis of cancer, thus opening new diagnostic and therapeutic approaches in neoplastic disorders. [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]

Doubled haploid (DH) technology is an efficient strategy for producing completely homozygous lines for breeding programs. Mutations in the MATRILINEAL (MTL) phospholipase trigger intraspecific haploid induction in cereals. Although an in vivo haploid induction system based on OsMTL-edited plants has been established in rice (Oryza sativa), DH technology is still limited by other factors, such as haploid identification, which is one of the essential steps required for DH technology. In the study, we addressed this technical challenge by integrating specific molecular and phenotypic markers into rice haploid inducers. We first generated large fragment insertion or deletion mutations within the OsMTL gene and designed a pair of primers flanking the mutational sites to be used as the specific and universal molecular markers between wild-type and Osmtl plants. Next, we screened for hairy leaf as a single dominant trait and integrated it into specific molecular marker-based haploid inducers using the cross and self-cross method. When crossing cytoplasmic male sterile lines with these haploid inducers, we utilized the specific InDel marker and hairy leaf phenotypic marker to identify putative haploids (or double haploids). These putative haploids were further confirmed through ploidy and phenotypic analysis, demonstrating the high efficiency of haploid identification using these markers. The haploid induction rate (HIR) of the developed specific molecular and phenotypic marker-based haploid inducers ranged from 3.7% to 12.5%. We have achieved successful integration of distinct molecular and phenotypic markers into rice haploid inducers. Our advanced marker-based system has significantly enhanced the accuracy of haploid identification, thereby expediting the adoption of DH technology in rice breeding. [ABSTRACT FROM AUTHOR]

Computer vision is an emerging area with a huge number of applications. Identification of fingertip is one of the major parts in those areas. Augmented reality and virtual reality are the most recent technological advancements that use fingertip identification. The interaction between computer and human can be performed easily by this technique. Virtual reality, robotics, smart gaming are the main application domains of this fingertip detection techniques. Gesture recognition is one of the most fascinating fields of fingertip detection. Gestures provide an easy and simple way of communication between computer and human. This review article thoroughly examines different studies done in the field of fingertip identification. A comparison study is also included based on various fingertip detection methods and measures. Based on this study some important observations and difficulties in the fingertip detection fields are identified. This study helps for effectively utilizing the features of fingertip recognition in a wide range of applications from person identification to intelligent home. A correlation chart of various experts is an additional result mentioned in this paper. [ABSTRACT FROM AUTHOR]

Nowadays, the mixing of low-quality species in canned products, especially in fishery products, is considered as one of the most important problems of monitoring some food industry production units. Among the new methods of detecting counterfeits, genetic methods such as DNA barcoding have high accuracy and precision. Therefore, the purpose of this research is to investigate the fraud in canned Iranian tuna fish produced using DNA barcoding, by cytochrome oxidase 1 detector. In this research, canned tuna stuffed with one piece of meat and canned tuna stuffed with chopped meat from different brands available in the market were collected from different regions of the country. The samples after DNA extraction and optimizing its process, were subjected to PCR by cytochrome oxidase 1 gene and then sequenced. The results of the sequencing showed that out of 100 canned samples examined, 80 samples have 97% genetic similarity to the fish listed on the can label, 18 samples have 90% genetic similarity to short fish. (Sillaginidae), and 3 samples belonged to 3 different fish species. Among these, only 3 samples were related to canned tuna prepared from one piece of meat. The results showed that this method is very useful due to its high speed and accuracy, for canned fish, where DNA parts may be lost during the canning process and it can be used to check the amounts of fraud in processed foods are recommended. [ABSTRACT FROM AUTHOR]

Introductıon: Systemic immune-inflammation index (SII) is an indicator of the inflammatory process. In this study we aimed to determine whether there is a relationship between the level of hearing loss and SII in patients diagnosed with idiopathic sudden sensorineural hearing loss (ISSHL), and to reveal whether SII has an indicator in the rate of improvement in hearing loss after treatment. Methods: Patients with ISSHL were included in the study. According to the audiometry performed before the initial treatment, the patients were divided into 3 groups (250, 500, 1000, 2000, 4000, 8000 Hz pure tone averages) below 40 dB defined as mild, between 40 and 80 dB defined as moderate and above 80 dB defined as severe. Results: In total 201 patients, 64 were in the mild hearing loss group, 115 in the moderate hearing loss group, and 22 in the severe hearing loss group. Multivariable logistic regression analysis revealed that higher SII [OR=1.002, 95% CI (1.001-1.003); p<0.001] associated with the severity of hearing loss. A statistically significant difference was found between the mean SII of the three groups (p<0.001). A negative correlation was found between improvement in hearing loss after treatment and SII levels. (R=-0.195, p<0.001). In addition, a negative correlation was found between the improvement in hearing loss and SII (R=-0.195, p<0.001). Conclusıon: SII is an easily available and relatively cheap marker, was associated with the severity of hearing loss. In addition, it was also associated with the recovery of hearing loss. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) is a rare yet devastating complication following total joint arthroplasty (TJA). Early and accurate diagnosis of PJI is paramount in order to maximize the chances of successful treatment. However, we are yet to identify a single "gold standard" test for the diagnosis of PJI. As a result, the diagnosis of PJI is often challenging. Currently, the 2018 ICM definition of PJI is the only validated diagnostic criteria available. This article will review the importance of serum and synovial biomarkers in the diagnosis of PJI. In addition, it will provide a brief overview of the emerging modalities for the identification of infections in this setting. [ABSTRACT FROM AUTHOR]

Gal-3 plays an important role in cell survival, mRNA splicing, and cell–cell and cell–matrix interactions. Depending on its cellular localization and cancer type, Gal-3 may have tumour-suppressive or tumour-promoting activities. Given the promising diagnostic role of Gal-3 in the urine of PCa patients found in our previous study, its concordant gene and protein expression levels, and its involvement in PCa-related biological processes (e.g., morphogenesis of the prostate gland epithelium), we aimed to investigate this protein immunohistochemically in tumour and normal prostate tissues. Gal-3 protein expression was evaluated in 48 tumour prostate tissues, eight normal prostate tissues and 14 adjacent-normal prostate tissues. Decreased Gal-3 staining was detected in tumour tissues compared with normal tissues. Although Gal-3 staining was decreased in tumour tissues with GS 5-8 and pT2 and pT3 stages compared with normal prostate tissue, no correlation was found between Gal-3 expression and PCa progression. In the present study, the pattern of cellular localization differed between groups, as Gal-3 was predominantly excluded from the nucleus in tumour tissues. Furthermore, Gal-3 had no significant effect on survival and relapse in these PCa patients. This work confirms Gal-3 as a promising marker for PCa diagnosis.

Abstract MicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.

Abstract The diagnosis of internal neoplasia in horses is challenging. Increased production of hormones physiologic for adult animals (e.g., adrenocorticotropin, norepinephrine, and erythropoietin) or typical for the foetal phase (alpha‐fetoprotein, anti‐Müllerian hormone, and parathyroid‐hormone‐related protein) might aid in tumour diagnostics. Thymidine kinase‐1 and alkaline phosphatase are examples of intracellular enzymes, whose activity in the blood may increase in some neoplasia cases. Furthermore, inappropriate production of abnormal monoclonal or autologous antibodies can accompany lymphoma and multiple myeloma. Many of those tumour markers lead to clinical or laboratory changes, called paraneoplastic syndromes, such as hypercalcaemia and erythrocytosis. The interpretation of the results of the tumour marker measurements in horses is complicated due to many factors affecting the markers’ concentration or activity (e.g., young age, pregnancy, and inflammation) and other diseases triggering the same changes. Moreover, the presence of paraneoplastic syndromes is inconsistent, which leads to low sensitivity of those substances as tumour markers. In conclusion, screening for neoplasia in horses is not recommended. The measurement of tumour markers should be performed only in risk groups with suspicious clinical or laboratory findings, and the results should be interpreted with caution. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements.

The image-symbol of mountain, a key image-symbol in Skovoroda’s poetical and philosophical discourse never was an object of special attention, thus making the article relevant.It aims at an attempt to ascertain the semantic and emotional function of this image in H. Skovoroda’s spiritual space, conditioned by the correlation of the Christian written tradition with the signs of its author’s interpretation determined by the advancement towards God as an advancement towards yourself, urging to rise above ordinariness and to relinquish the world’s temptations.And at the same time, the symbol of spiritual summit matches the images of earthly mountains, with spatiality of feelings enabling the emphasis on the commensurability of the visible and the invisible, of the immanent and the transcendental.This correlation makes Skovoroda’s spiritual journey both intensely dramatic and lyrical, earthly and heavenly, and the sign of Christ’s visible Crucifixion coexists with His invisible Resurrection.The image of mountain holds an important position in Skovoroda’s world.Even the affinity or the identity the images of mountain and rock have reveals this characteristic to be the foundation and the summit at the same time, the aim and the way to that aim, to watch the earth and the heaven, the man’s and the God’s.H. Skovoroda perceives the heavenly mountain as the Wisdom of God, the place of revelation, meeting with God, announcement of His will, and the earthly mountain as the visible trace of God.The image of mountain connects the visible to the invisible, becomes an equivalent of the measure of human life. One author’s text opens another one, and all of them together path the way to the Holy Scripture because they grow from it.Along these lines, Skovoroda continues the tradition which united different authors preceding him and touched the summits of Ukrainian literature. Along these lines, Skovoroda continues the tradition which united different authors preceding him and touched the summits of Ukrainian literature. We make a conclusion that talking about mountains in Skovoroda’s sense brings about a certain reverse perspective projected on the general experience of man and the experience of reading in particular.

This research was carried out with the aim of revealing the genetic differences of 30 cotton varieties from 14 countries using the iPBS-retrotransposon marker method. Genetic differences were determined by using iPBS marker method in PCR for 30 cotton varieties. According to the genetic distance matrix obtained in the NTSYS-pc 2.10e program, the closest genotypes were determined to be AzGR-11468 (Azerbaijan) and Maydos Yerlisi (India), and the similarity value between them was found to be 0.0318. The most distant genotypes were determined to be Hill Cotton 3 (Bangladesh) and Shazbaz (Pakistan), and the similarity value between them was found to be 0.7572. When the dendrogram generated based on the UPGMA method was examined.30 cotton varieties were divided into 2 clades. According to the PCA made in the JMP program, the graphic results and eigen values obtained on the two-dimensional plane also supported these results. The first 3 eigen values explained 85% of the total variance in the population. Overall results suggest that Hill Cotton 3 (Bangladesh) (Gossypium arboreum) and Shazbaz (Pakistan) (Gossypium hirsutum) cultivars, which are the most distant relatives among 30 cotton genotypes, can be used as breeding cultivars in future cotton breeding studies.

The measurement of vitamin D metabolites aids in assessing vitamin D status and in diagnosing disorders of calcium homeostasis. Most laboratories measure total 25-hydroxyvitamin D (25(OH)D), while others have taken the extra effort to measure 25(OH)D2 and 25(OH)D3 separately and additional metabolites such as 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D. The aim of this review is to provide an updated overview of the main markers of vitamin D metabolism, define the intended measurands, and discuss the advantages and disadvantages of the two most widely used assays, automated assays and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Whether using the easy and fast automated assays or the more complex LC-MS/MS, one should know the pitfalls of the used technique in order to interpret the measurements. In conclusion, automated assays are unable to accurately measure 25(OH)D in all patient groups, including persons using D2. In these cases, an LC-MS/MS method, when appropriately developed and standardized, produces a more reliable measurement.

Recognizing entities and extracting their relations are significant tasks for information extraction. Many recent works focus on leveraging entity markers for better span (pair) representations, which have achieved promising performance. Nevertheless, existing works have two shortcomings: (1) previous markers are randomly embedded into distributed representations, which ignores semantic information relevant to the targeted tokens that we want to highlight. (2) most works simply implant markers into a sentence, which is weak to encode the interrelation between multiple tokens. In this work, we propose a marker collaborating model for entity and relation extraction, which is composed of two modules. The first module is semantic marker module, where two kinds of semantic markers are proposed to leverage semantic features from the PLMs. The second module is collaborative marker attention module, where a marker-oriented directional attention is proposed to model the interaction between multiple tokens. Our model yields SOTA performance on three standard benchmarks (ACE04, ACE05 and SciERC).

Abstract Background Immune checkpoint inhibitors (ICIs) represent an approved treatment for various cancers; however, only a small proportion of the population is responsive to such treatment. We aimed to develop and validate a plain CT-based tool for predicting the response to ICI treatment among cancer patients. Methods Data for patients with solid cancers treated with ICIs at two centers from October 2019 to October 2021 were randomly divided into training and validation sets. Radiomic features were extracted from pretreatment CT images of the tumor of interest. After feature selection, a radiomics signature was constructed based on the least absolute shrinkage and selection operator regression model, and the signature and clinical factors were incorporated into a radiomics nomogram. Model performance was evaluated using the training and validation sets. The Kaplan–Meier method was used to visualize associations with survival. Results Data for 122 and 30 patients were included in the training and validation sets, respectively. Both the radiomics signature (radscore) and nomogram exhibited good discrimination of response status, with areas under the curve (AUC) of 0.790 and 0.814 for the training set and 0.831 and 0.847 for the validation set, respectively. The calibration evaluation indicated goodness-of-fit for both models, while the decision curves indicated that clinical application was favorable. Both models were associated with the overall survival of patients in the validation set. Conclusions We developed a radiomics model for early prediction of the response to ICI treatment. This model may aid in identifying the patients most likely to benefit from immunotherapy.

The incidence of diabetes mellitus (DM) is steadily growing and today the World Health Organization (WHO) describes this situation as an epidemic. Diabetic retinopathy (DR) is one of the most common complications of DM, as well as one of the main causes of acquired irreversible vision loss. Nowadays the pathogenesis of proliferative DR remains completely unexplored, but many authors think about the important role of biologically significant mediators of this process cytokines and growth factors. Cytokines and growth factors are protein mediators that regulate various functions, both locally and systemically. They carry out the cells’ life cycle, the processes of proliferation, participate in the regulation of the protective inflammatory response of the body, control angiogenesis and other mechanisms. It is proved that the main links in the pathogenesis of DR are oxidative stress, thickening of the endothelial basement membrane in capillaries, loss of pericytes, end products of glycation and inflammation. Chorioretinal hypoxia and ischemia play a major role in the formation of newly formed vessels. Newly formed vessels are defective (with a thin wall devoid of pericytes), often lead to hemorrhages, hypoxia, which in turn closes the pathological circle and causes the production of cytokines and vasoproliferative factors. Frequent complications of DR are intraocular hemorrhages, retinal fibrosis and pathological changes in the posterior hyaloid membrane, traction retinal detachment, etc. This review examines some types of cytokines and growth factors and their role in the light in the pathogenesis of proliferative DR. Modern technologies make it possible to conduct effective studies of intraocular fluids to study the content of biologically active substances both in the moisture of the anterior chamber of the eye and in the vitreous body. To narrow the scope of the review on the subject attention is focused on the works that examined various markers locally in the intraocular fluids in patients with DM. It is worth noting that there are few such studies and their results often differ significantly from each other. This fact is a subject for discussion and encourages further study of this topic.