Promising Marker Research Articles

Validation of the clinical assessment scale for autoimmune encephalitis in a severe autoimmune encephalitis cohort

ObjectiveThe Clinical Assessment Scale for Autoimmune Encephalitis (CASE) is a novel tool tailored specifically for evaluating the severity of autoimmune encephalitis (AE). However, its application in severe AE patients is limited. This study aimed to evaluate the reliability and validity of the CASE and explore its clinical significance in a severe AE cohort.MethodsThe relevant clinical characteristics, laboratory data, and prognosis of patients diagnosed with severe AE between April 2017 and April 2023 were collected. The CASE and modified Rankin scale (mRS) were performed at admission, discharge, and 1-year follow-up, respectively. The reliability of CASE was validated by calculating the Cronbach’s alpha value. The validity was evaluated by calculating the Spearman’s rank correlation with the corresponding mRS. Univariate and multivariate logistic regression were utilized to identify risk factors for poor prognosis.ResultsA total of 140 patients were recruited for the study. The CASE scale presented great internal consistency, with Cronbach’s α value of 0.768 for the total score. The Spearman’s rank correlation analysis revealed strong criterion validity between CASE and mRS, with coefficients of 0.68, 0.92, and 0.95 at admission, discharge, and 1-year follow-up, respectively (all p < 0.001). ROC analysis identified CASE score at admission served as a promising predictive marker for clinical response to treatment, with an AUC of 0.67 (95% CI: 0.57-0.77, p = 0.003). The optimal cut-off point was 22.5. At 1-year follow-up, 72/140 (51.4%) patients achieved good functional status (mRS, 0-2). Multivariate logistic regression confirmed that higher CASE scores on admission and older age at onset were associated with poor short-term as well as 1-year prognosis, respectively. In addition, no clinical response to treatment (OR = 40.499; 95% CI: 7.077-231.746, p < 0.001) and longer duration of hospitalization (OR = 1.071; 95% CI: 1.017-1.128, p = 0.010) were associated with poor function states at 1-year follow-up.ConclusionThe CASE has proven suitable for evaluating disease severity and prognosis in severe AE patients. Besides, CASE score, age at disease onset, hospital stays, and response to immunotherapy are identified as independent risk factors for unsatisfactory prognosis in severe AE patients.

CylinderTag: An Accurate and Flexible Marker for Cylinder-Shape Objects Pose Estimation Based on Projective Invariants.

High-precision pose estimation based on visual markers has been a thriving research topic in the field of computer vision. However, the suitability of traditional flat markers on curved objects is limited due to the diverse shapes of curved surfaces, which hinders the development of high-precision pose estimation for curved objects. Therefore, this paper proposes a novel visual marker called CylinderTag, which is designed for developable curved surfaces such as cylindrical surfaces. CylinderTag is a cyclic marker that can be firmly attached to objects with a cylindrical shape. Leveraging the manifold assumption, the cross-ratio in projective invariance is utilized for encoding in the direction of zero curvature on the surface. Additionally, to facilitate the usage of CylinderTag, we propose a heuristic search-based marker generator and a high-performance recognizer as well. Moreover, an all-encompassing evaluation of CylinderTag properties is conducted by means of extensive experimentation, covering detection rate, detection speed, dictionary size, localization jitter, and pose estimation accuracy. CylinderTag showcases superior detection performance from varying view angles in comparison to traditional visual markers, accompanied by higher localization accuracy. Furthermore, CylinderTag boasts real-time detection capability and an extensive marker dictionary, offering enhanced versatility and practicality in a wide range of applications. Experimental results demonstrate that the CylinderTag is a highly promising visual marker for use on cylindrical-like surfaces, thus offering important guidance for future research on high-precision visual localization of cylinder-shaped objects.

Serial evaluation of morphological and biophysical placental attributes in women with normal outcome and preeclampsia.

The study's aim was to perform serial placental biometry and Doppler assessments in antenatal women and compare the characteristics of preeclampsia (PE) and normal outcome. This prospective cohort study was carried out after ethical clearance. Placental length (PL), thickness, and plavental volume (PV), along with the uterine artery (Ut), middle cerebral artery (MCA), and umbilical artery (UA) blood flow were evaluated serially at 11-14, 20-24, and 28-32 weeks of gestation. The women were followed until delivery, those with PE were considered cases, and those with no other adverse outcome were controls. The placental attributes between cases and controls were compared. A total of 135/1008 (13.4%) had hypertensive disorders of pregnancy (HDP) and 44/1008 (4.4%) had PE, and no maternal or fetal adverse outcomes were seen in 600 (59.5%) women. The PL and PV were significantly less in those with PE (P = 0.005) than in controls. The ratios of PL/Ut A PI and PV/Ut A PI were significantly lower in cases than in controls in all trimesters (P <0.001). In the first trimester, the area under the curve (AUC), sensitivity, and specificity of PV/Ut A PI for PE prediction were 0.801, 81.8%, and 70.5%, respectively. The sensitivity and specificity of the PL/Ut PI ratio was 81.8% and 70.5%, whereas that at 28-32 weeks was 73.3% & 70.7%. Placental parameters were significantly lower in PE than in normal outcome, and the ratios of PL/Ut A PI and PV/Ut A PI proved to be promising markers.

Digital Outcomes as Biomarkers of Disease Progression in Early Parkinson's Disease: A Systematic Review.

Outcomes derived from digital health technologies (DHTs) are promising candidate markers for monitoring Parkinson's disease (PD) progression. They have the potential to represent a significant shift in clinical research and therapeutic development in PD. However, their ability to track disease progression is yet to be established. This systematic review aimed to identify digital biomarkers capable of tracking early PD progression (disease duration <5 years) by reviewing longitudinal studies (minimum follow-up of 6 months). We evaluated study design and quality, population features, reported DHTs and their performance to track progression. Of 1507 records screened, 15 studies were selected, published between 2009 and 2023, with the majority coming from the last 5 years. Of the 15, 11 were observational and four were interventional trials (follow-up range: 6-60 months). Twelve different DHTs were used (8 required active tests, 8 in-hospital use), capturing features related to motor function and daily activities, including five DHTs focused on gait/posture. Rating scales were used as comparators in all but one study. Three DHTs detected longitudinal changes when scales did not, with one study showing larger effect sizes for change over time of selected DHT features compared to rating scales. Four studies showed longitudinal correlations among DHT features and rating scales. Preliminary promising data suggest that DHT-derived outcomes may help reduce sample sizes in disease-modifying trials. There is a need to standardize study methodologies and facilitate data sharing to confirm these results and further validate the sensitivity of DHTs to track disease progression in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dual RNA-seq study of the dynamics of coding and non-coding RNA expression during Clostridioides difficile infection in a mouse model.

Clostridioides difficile is the leading cause of healthcare-associated diarrhea in industrialized countries. Many questions remain to be answered about the mechanisms governing its interaction with the host during infection. Non-coding RNAs (ncRNAs) contribute to shape virulence in many pathogens and modulate host responses; however, their role in C. difficile infection (CDI) has not been explored. To better understand the dynamics of ncRNA expression contributing to C. difficile infectious cycle and host response, we used a dual RNA-seq approach in a conventional murine model. From the pathogen side, this transcriptomic analysis revealed the upregulation of virulence factors, metabolism, and sporulation genes, as well as the identification of 61 ncRNAs differentially expressed during infection that correlated with the analysis of available raw RNA-seq data sets from two independent studies. From these data, we identified 118 potential new transcripts in C. difficile, including 106 new ncRNA genes. From the host side, we observed the induction of several pro-inflammatory pathways, and among the 185 differentially expressed ncRNAs, the overexpression of microRNAs (miRNAs) previously associated to inflammatory responses or unknown long ncRNAs and miRNAs. A particular host gene expression profile could be associated to the symptomatic infection. In accordance, the metatranscriptomic analysis revealed specific microbiota changes accompanying CDI and specific species associated with symptomatic infection in mice. This first adaptation of in vivo dual RNA-seq to C. difficile contributes to unravelling the regulatory networks involved in C. difficile infectious cycle and host response and provides valuable resources for further studies of RNA-based mechanisms during CDI.IMPORTANCEClostridioides difficile is a major cause of nosocomial infections associated with antibiotic therapy classified as an urgent antibiotic resistance threat. This pathogen interacts with host and gut microbial communities during infection, but the mechanisms of these interactions remain largely to be uncovered. Noncoding RNAs contribute to bacterial virulence and host responses, but their expression has not been explored during C. difficile infection. We took advantage of the conventional mouse model of C. difficile infection to look simultaneously to the dynamics of gene expression in pathogen, its host, and gut microbiota composition, providing valuable resources for future studies. We identified a number of ncRNAs that could mediate the adaptation of C. difficile inside the host and the crosstalk with the host immune response. Promising inflammation markers and potential therapeutic targets emerged from this work open new directions for RNA-based and microbiota-modulatory strategies to improve the efficiency of C. difficile infection treatments.

The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review

Human papillomavirus (HPV) infection is a major etiologic factor in cervical cancer, a major cause of cancer-related morbidity and mortality among women worldwide. The role of microRNA (miRNA) dysregulation in cervical carcinogenesis is still largely unknown, but epigenetic changes, including DNA methylation and miRNA regulation, are crucial factors. The integration of HPV DNA into the host genome can lead to alterations in DNA methylation patterns and miRNA expression, contributing to the progression from normal epithelium to cervical intraepithelial neoplasia and, ultimately, to cervical cancer. This review aimed to examine the relationship between epigenetic changes in the development and progression of HPV associated with cervical cancer. A systematic literature search was conducted in major databases using predefined inclusion and exclusion criteria. Studies that investigated the expression, function, and clinical significance of miRNAs, DNA methylation, and the expression of oncoproteins in HPV-related cervical cancer were included. Data extraction, quality assessment, and synthesis were performed to provide a comprehensive overview of the current state of knowledge. We provide an overview of the studies investigating miRNA expression in relation to cervical cancer progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched the Pubmed database for all articles published between January 2018 and December 2023. Our systematic review revealed a substantial body of evidence supporting the pivotal role of miRNA dysregulation in the pathogenesis of HPV-related cervical cancer and related oncoproteins. From the 28 studies retrieved, miR-124, FAM194/miR-124-2, and DNA methylation are the most frequently down- or up-regulated in CC progression. Notably, FAM194/miR-124-2 and DNA methylation emerged as a promising molecular marker for distinguishing between cases requiring immediate surgical intervention and those amenable to a more conservative wait-and-see approach. This systematic review underscores the critical involvement of microRNA in the context of HPV-related cervical cancer and sheds light on the potential clinical utility of FAM194/miR-124-2 and DNA methylation as a discriminatory tool for guiding treatment decisions. The identification of patients who may benefit from early surgical intervention versus those suitable for observation has important implications for personalized and targeted management strategies in the era of precision medicine.

B7-H3 in glioblastoma and beyond: significance and therapeutic strategies

Cancer has emerged as the second most prevalent disease and the leading cause of death, claiming the lives of 10 million individuals each year. The predominant varieties of cancer encompass breast, lung, colon, rectal, and prostate cancers. Among the more aggressive malignancies is glioblastoma, categorized as WHO stage 4 brain cancer. Following diagnosis, the typical life expectancy ranges from 12 to 15 months, as current established treatments like surgical intervention, radiotherapy, and chemotherapy using temozolomide exhibit limited effectiveness. Beyond conventional approaches, the exploration of immunotherapy for glioblastoma treatment is underway. A methodology involves CAR-T cells, monoclonal antibodies, ADCC and nanobodies sourced from camelids. Immunotherapy’s recent focal point is the cellular ligand B7-H3, notably abundant in tumor cells while either scarce or absent in normal ones. Its expression elevates with cancer progression and serves as a promising prognostic marker. In this article, we delve into the essence of B7-H3, elucidating its function and involvement in signaling pathways. We delineate the receptors it binds to and its significance in glioblastoma and other cancer types. Lastly, we examine its role in immunotherapy and the utilization of nanobodies in this domain.

Sensitivity of unconstrained quantitative magnetization transfer MRI to amyloid burden in preclinical Alzheimer’s disease

Abstract Magnetization transfer MRI is sensitive to semisolid macromolecules, including amyloid beta, and has previously been used to discriminate Alzheimer’s disease (AD) patients from controls. Here, we fit an unconstrained 2-pool quantitative MT (qMT) model, that is, without constraints on the longitudinal relaxation rate R1s of semisolids, and investigate the sensitivity of the estimated parameters to amyloid accumulation in preclinical participants. We scanned 15 cognitively normal volunteers, of which 9 were amyloid positive by [18F]florbetaben PET. A 12 min hybrid-state qMT scan with an effective resolution of 1.24 mm isotropic and whole-brain coverage was acquired to estimate the unconstrained 2-pool qMT parameters. Group comparisons and correlations with florbetaben PET standardized uptake value ratios were analyzed at the lobar level. We find that the exchange rate and semisolid pool’s R1s were sensitive to the amyloid concentration, while morphometric measures of cortical thickness derived from structural MRI were not. Changes in the exchange rate are consistent with previous reports in clinical AD, while changes in R1s have not been reported previously as its value is typically constrained in the literature. Our results demonstrate that qMT MRI may be a promising surrogate marker of amyloid beta without the need for contrast agents or radiotracers.

Could SLC26A7 Be a Promising Marker for Preoperative Diagnosis of High-Grade Papillary Thyroid Carcinoma?

Background/Objectives: A modern classification distinguishes between two nosological entities posing an intermediate risk between differentiated and anaplastic carcinoma: poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. There are currently few studies searching for the preoperative molecular genetic markers of high-grade papillary thyroid carcinoma (PTC HG), primarily because of a recent WHO reclassification and singling out of a separate entity: high-grade follicular cell-derived nonanaplastic thyroid carcinoma. Therefore, this work was aimed at identifying PTC HG-specific microRNAs and mRNAs that reliably distinguish them from differentiated papillary thyroid carcinoma in preoperative cytology specimens (fine-needle aspiration biopsies). Methods: A molecular genetic profile (expression levels of 14 genes and eight microRNAs) was studied in 110 cytology specimens from patients with PTC: 13 PTCs HG and 97 PTCs without features of HG. Results: Of the examined eight microRNAs and 14 genes, significant differences in the expression levels between the PTC and PTC HG groups were revealed for genes SLC26A7, TFF3, and TPO. Only one gene (SLC26A7) proved to be crucial for detecting PTC HG. It showed the largest area under the ROC curve (0.816) in differentiation between the PTC and PTC HG groups and was the key element of the decision tree by ensuring 54% sensitivity and 87.6% specificity. Conclusions: Early preoperative diagnosis of PTC HG in patients with early stages of this cancer type will allow clinicians to modify a treatment strategy toward a larger surgery volume and lymph node dissection and may provide indications for subsequent radioactive iodine therapy.

Clinically assessed mycosis fungoides tumor burden index as a prognostic marker in tumor-stage mycosis fungoides: a retrospective cohort study.

Prognostic markers are needed for tumor-stage mycosis fungoides (MF) because of their variable prognosis. The objectives of this study were to explore prognostic markers for tumor-stage MF and assess the prognostic significance of clinically assessed MF tumor burden index (MTBI). MTBI was devised to consider the tumor size ≥ 2cm, number ≥ 5, ulcers, and body surface area ≥ 50%. The prognostic value of MTBI and other potential markers derived from blood tests and skin biopsy were evaluated retrospectively using a tertiary medical center database. We included 38 cases of tumor-stage MF. The mean age was 52.1 years, and the male-to-female ratio was 2.5:1. In multivariable analysis, MTBI ≥ 3 (adjusted hazard ratio, 9.41; 95% confidence interval, 1.13-78.15) was significantly associated with worse disease-specific survival. Ulcers were the only MTBI constituent significantly associated with survival. Among other markers, elevated lactate dehydrogenase level was associated with a worse disease-specific survival. Neutrophil-lymphocyte-ratio, pan-inflammation-value, CD30 positivity, Ki-67 index, large cell transformation, and monoclonal T-cell receptor gene rearrangement were not associated with prognosis. In conclusion, MTBI is useful and promising prognostic marker for tumor-stage MF.

A multi-class support vector machine classification model based on 14 microRNAs for forensic body fluid identification

MicroRNAs (miRNAs) are promising biomarkers for forensic body fluid identification owing to their small size, stability against degradation, and differential expression patterns. However, the expression of most body fluid-miRNAs is relative (differentially expressed in certain body fluids) rather than absolute (exclusively expressed in a specific body fluid). Moreover, different body fluids contain heterogeneous cell types, complicating their identification. Therefore, appropriate normalization strategies to eliminate non-biological variations and robust models to interpret expression levels accurately are necessary prerequisites for applying miRNAs in body fluid identification. In this study, the expression stability of six candidate reference genes (RGs) across five body fluids was validated using geNorm, NormFinder, BestKeeper and RankAggreg, and the most suitable combination of RGs (hsa-miR-484 and hsa-miR-191–5p) was identified under our experimental conditions. Subsequently, we systematically evaluated the expression patterns of the 28 most promising body fluid-specific miRNA markers using TaqMan RT-qPCR and selected the optimal combination of markers (12 miRNAs) to establish a multi-class support vector machine (MSVM) classification model. An independent test set (60 samples) was used to validate the accuracy of the proposed classification model, while an additional 30 casework samples were used to assess its robustness. The MSVM model accurately predicted the body fluid origin for almost all (59/60) single-source samples. Moreover, this model demonstrated the capability to identify aged forensic samples and to predict the primary components of mixed stains to a certain extent. In summary, this study presented a miRNA-based MSVM classification model for forensic body fluid identification using the qPCR platform. However, extensive validation, especially inter-laboratory collaborative exercises, is necessary before miRNA can be routinely applied in forensic identification practice.

The Potential Utility of (2S,4R)-4-[18F]fluoroglutamine as a Novel Metabolic Imaging Marker for Inflammation Explored by Rat Models of Arthritis and Paw Edema.

(2S,4R)-4-[18F]fluoroglutamine ([18F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [18F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA). The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [18F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90min under anesthesia with isoflurane. The standard uptake value of [18F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET. The CIPE models showed a trend toward higher uptake in the injected paw compared to the non-injected paw (P = 0.068). In CIA models, uptake in the paws with severe inflammation was significantly higher than the controls (P = 0.011), while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [18F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (r = 0.88, P = 0.009). The pathological findings confirmed profound inflammation in CIA. [18F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.

Comprehensive analysis identifies endocrine fibroblast growth factors as promising prognostic markers for colorectal carcinoma

Endocrine fibroblast growth factors (eFGFs) play essential roles in cellular signaling processes, including development and differentiation, and are implicated in various cancers. However, their precise involvement in colon neoplasia and colon adenocarcinoma (COAD) remains incompletely understood. Here, we conducted a comprehensive investigation utilizing multiple databases to explore the multifaceted characteristics of eFGFs. Through integrated analyses of diverse databases, including TIMER2.0, UALCAN, OncoDB, cBioPortal, LinkedOmics, STRING, htfTarget, mirTarBase, circBank, and DGIdb, we explored eFGFs’ gene expression, DNA methylation, prognostic significance, genetic alterations, gene regulatory networks, functional analysis, and drug interactions in COAD patients. Our findings revealed elevated expression levels of eFGFs in COAD, with aberrant gene expression potentially linked to promoter methylation. Importantly, hypermethylation of FGF21 and FGF23 and downregulation of FGF23 correlated with poor survival outcomes in COAD patients. Functional analyses highlighted the involvement of eFGF genes in Ras signaling, PI3K-Akt signaling, and cancer pathways. Furthermore, we validated our findings through a cross-sectional study by quantitative real-time polymerase chain reaction (qRT-PCR), confirming significant overexpression of FGF21 in colon polyps compared to normal mucosa. Additionally, we observed elevated RNA expression of FGF21 and FGF23 in adenomatous polyps compared to hyperplastic polyps. This study sheds new light on the critical roles of eFGFs in COAD tumorigenesis and underscores their potential as promising prognostic markers for COAD, as well as discriminative markers for distinguishing high-risk from low-risk polyps. These findings provide valuable insights into the complex molecular mechanisms underlying colorectal neoplasia and offer potential avenues for targeted therapeutic strategies.

Elevated cerebral oxygen extraction in patients with post-COVID conditions

Abstract Objectives Dysfunction of cerebral microcirculation due to SARS-CoV-2 infection has been postulated to be a plausible mechanism for the neurological symptoms of post-COVID-19 conditions (neuro-PCC), affecting oxygen homeostasis in the brain. In this study, we aimed to investigate the balance between cerebral oxygen delivery and consumption, measured by oxygen extraction fraction (OEF), in patients with neuro-PCC. Methods 25 participants with neuro-PCC (8 previously hospitalized and 17 not hospitalized) and 59 age-matched healthy controls were studied. Global OEF was quantified using TRUST MRI and compared across the three groups. Associations between OEF and neurobehavioral measures were also evaluated in participants with neuro-PCC. Results OEF was significantly different (one-way ANCOVA-p=0.046) among the three groups, after accounting for age and sex. On post-hoc analyses, previously hospitalized neuro-PCC participants had significantly higher OEF (42.40 ± 5.40 %) than both uninfected controls (37.70 ± 5.09 %, p=0.032) and neuro-PCC participants without hospitalization (37.02 ± 5.05 %, p=0.015). Within the participants with neuro-PCC, OEF was significantly associated with locomotor function assessed with the 4-m walk gait speed score (β=−0.03, r=0.34, p=0.003). Conclusions Participants with neuro-PCC had altered cerebral OEF, which is also associated with slower locomotion. OEF is a promising marker for studying neuro-PCC.

BN SO19 - Evaluating Wrap Pressure Augmentation Ratio and Physiological Transit Time for Post-Fundoplication Dysphagia

Abstract Background Post-fundoplication dysphagia affects many patients that can often lead to significant weight loss and reduced quality of life, and prompt some to seek surgical reversal. Current diagnostic methods may not fully explain the dysphagia which may necessitate repeat oesophageal physiology testing. This study retrospectively evaluates two novel markers, Wrap Pressure Augmentation Ratio (WPAR) and Physiological Transit Time (PTT), to better understand and manage the post-fundoplication dysphagia. Method The study retrospectively reviewed 54 post-Nissen’s fundoplication patients from January 2020 to May 2024. WPAR was calculated as the ratio of the augmented wrap basal pressure to the median integrated relaxation pressure found during high-resolution manometry following the Chicago Classification guideline [1]. PTT was measured from controlled measurements of antegrade bolus movement [2] during multichannel impedance-pH studies [3]. Patients completed HODQ forms to assess dysphagia [4]. Optimal WPAR and PTT thresholds were determined using Youden’s J index from receiver operating characteristic curves. This study was ethically approved (REC 18/NW/0120, IRAS 333800). Results Out of 54 cases (female=28:26, mean age 50.6), 75.9% reported clinical dysphagia post-fundoplication. Significant correlations were found with WPAR (&amp;lt;1.49, p=0.017) and PTT (&amp;gt;0.83 minutes, p=0.028)(see Table 1). These findings suggest WPAR and PTT as effective markers for post-fundoplication dysphagia. The analysis revealed a moderate correlation between WPAR and PTT (r =-0.45, p&amp;lt;0.05), suggesting that lower WPAR values tend to be associated with longer PTT. SensitivityPositive Predictive Valueχ2p-valueWPAR &amp;lt;1.490.610.895.680.017PTT &amp;gt;0.83 minutes0.780.844.820.028 Table 1 showing predictive DR and PTT values for clinical dysphasia post fundoplication. Conclusion This pilot study identifies PAR and PTT as promising physiological markers for diagnosing post-fundoplication dysphagia. The moderate correlation between PAR and PTT suggests a potential link, indicating that lower pressure augmentation might be associated with slower oesophageal transit times. These markers could enhance management strategies for affected patients. However, the study's small sample size and lack of a control group limit generalizability. Larger, controlled studies are necessary to validate these findings and further explore the relationship between PAR and PTT.

The Role of Osteocalcin in Patients with Osteoporosis: A Systematic Review.

Osteoporosis is the most common systemic skeletal disease worldwide. We aimed to review the latest studies related to osteocalcin and osteoporosis to clarify this relationship more precisely. A systematic literature search was performed to review studies on the effects of osteocalcin on osteoporosis, on studied published between January 2013 and January 2023. We systematically reviewed Web of Science, PubMed, ProQuest, Scopus, and Google Scholar. The search yielded 4903 records, including 1063 from PubMed, 2307 from Scopus, 1084 from Web of Science, 408 from ProQuest, and 41 from Google Scholar, and twelve articles were included for data extraction and quality assessment. A significant increase in the serum level of osteocalcin was observed in postmenopausal women with osteoporosis (P<0.05), and there was a negative correlation between bone mineral density and the serum level of osteocalcin. Osteocalcin could be a promising marker for the diagnosis and screening of patients with osteoporosis.

Abstract 4137309: Superior Ventricular Longitudinal Strain Is Linked To Metabolic Adaptations, Protective Ventricular Remodeling Among Older Women And Clinical Outcomes.

Background: Superior left ventricular (LV) systolic function among older women over men has been linked to differences in aging-related ventricular remodeling. Global longitudinal strain (LVGLS) is particularly susceptible to early aging perturbations and may precede systolic failure. Combining cardiovascular magnetic resonance (CMR) with metabolomics, we investigated LVGLS in parallel with markers of myocardial biosynthesis and metabolism pathways to explore the mechanisms and sex dimorphisms of cardiac aging. Methods: Community adults without cardiovascular disease (CVD) underwent serum metabolomics profiling and simultaneous CMR. Prospective clinical outcomes were tracked from 2014 to 2021. Multiple logistic regression adjusted for significant baseline variables. Results: Among 202 participants (46% women, 70.2±8.8 years), participants with better LVGLS were characterized by smaller LV chambers (LVESVi 30.0±14.2 vs 22.0±5.6ml/m 2 , adj. p &lt;0.001; LVEDVi 70.9±19.9 vs 64.0±10.2ml/m 2 , p=0.001 adj. p=0.054) and mass (LVMi 51.5±14.5 vs 43.9±8.8g/m 2 , adj. p=0.008) accompanied by lower levels of several long-chain acylcarnitines species (C12:2-OH/C10:2-DC, C12:1-OH, C12-OH/C10-DC, C14, C16:3-OH/C14:3-DC) independent of sex, diastolic blood pressure, smoking history, and body habitus. Compared to men of similar age, women had superior LVGLS (-21.9±2.6 vs -20.1±2.8%, adj. p=0.024) in tandem with smaller ventricles and less hypertrophy despite similar adjusted LVEF. Higher anaplerotic (methionine, arginine) and proteogenic (phenylalanine, tyrosine) amino acids (AA), together with lower acylcarnitines, distinguished women with better over poorer LVGLS while no AA differences were observed among men. During follow-up, poorer baseline LVGLS was associated with incident composite mortality and hospitalizations (OR=1.12 95%CI 1.01-1.24, p=0.026 adj. p=0.049). Conclusion: Preserved ventricular systolic function among older women was linked to superior LVGLS and favorable remodeling than men. Better LVGLS was accompanied by biomarkers of better mitochondrial oxidation, anaplerosis, and proteogenesis, suggesting enhanced myocardial fuel energetics and biosynthesis with better strain. LVGLS represents a promising quantifiable marker of early systolic aging among older adults without CVD linked to prospective clinical outcomes. Biological insights into the aging-adaptive mechanisms of strain conservation may reveal targets in preventing aging susceptibilities to myocardial dysfunction.

Anion and Substituents Effect on Spectral-Kinetic and Biological Characteristics of Spiropyran Salts.

Spiropyran salts containing a cationic vinyl-3H-indolium moiety are characterized by NIR absorption and fluorescence of their merocyanine forms. This feature makes them promising fluorescent probes and markers for bioimaging. The article focuses on the synthesis and study of the spectral, kinetic and toxic characteristics of such compounds with respect to various substituents in different moieties and the type of anion. A detailed analysis of the acquired data made it possible to draw some important conclusions regarding the influence of structural factors, which will be very useful for the further rational design of such derivatives. In particular, it was shown that the counterion has minimal effect on the spectral and kinetic characteristics of the dyes but dramatically affects the toxicity of the compounds. Following selection of the most appropriate compounds, bioimaging experiments were carried out to visualize planktonic bacteria and bacterial biofilms of E. coli and A. calcoaceticus. The ability to visualize biofilms is critical for the diagnosis of chronic diseases. By the results of molecular docking a theoretical interaction pattern between spiropyran molecules and DNA was proposed.

Exploring Haptoglobin as a Promising Marker for Severe Liver Diseases: A Comprehensive Review

Liver damage is a common symptom of many diseases, including metabolic disorders and cancers. Such patient condition requires effective examinations aimed at prompt diagnosis and implementation of the most appropriate treatment for a specific disease. Haptoglobin, the subject of many studies, has proven to be a protein that can be used as a biomarker of liver damage, thereby aiding not only in the diagnosis but also in the treatment, resulting in more favorable prognoses regarding patient longevity and quality of life.The aim of this study is to elucidate the role of haptoglobin as a diagnostic and prognostic biomarker in cases of liver damage.This is a review of scientific literature and analysis of clinical data regarding haptoglobin levels in liver damage were conducted to assess the reliability of haptoglobin as a biomarker.This paper primarily utilized the latest publications produced after 2015. PubMed and Google Scholar were used to find relevant publications. All cited works provided useful information to achieve the aim of our article.Analysis of the literature suggests that haptoglobin levels may be significantly associated with the development and severity of liver damage. It may serve as a suitable biomarker for diagnosing diseases that coincide with hepatocyte damage, thus improving the diagnosis of these diseases and increasing the chance of appropriate treatment, which may contribute to prolonging and improving the patient's quality of life.Haptoglobin appears to be a promising biomarker in liver damage; however, further research is necessary to confirm its diagnostic and prognostic accuracy. Haptoglobin exists in various genotypic forms, each characteristic of different disease entities. Understanding the mechanisms regulating haptoglobin levels may lead to a better understanding of liver damage pathogenesis and the development of more effective therapies, increasing the chance of patient recovery and improving their quality of life.

BIOM-26. ROLE OF EXTRA-DOMAIN B FIBRONECTIN IN MODULATING GLIOBLASTOMA CELL INVASIVE PROPERTIES

Abstract Glioblastoma (GBM) is a highly malignant tumor characterized by its resistance to current treatment modalities and high recurrence rates. Extra-domain B Fibronectin (EDB-FN), a glycoprotein not found in normal tissues but selectively expressed in the tumor microenvironment, was previously identified by our team as a promising molecular marker for brain tumors, offering potential for both prognostic prediction and therapeutic targeting. However, the specific role and mechanism of action of EDB-FN in GBM cells remain unclear. In this study, we sought to elucidate the potential role of EDB-FN and the underlying mechanisms contributing to GBM malignancy through in vitro investigations. Our findings reveal that silencing EDB-FN in GBM cells leads to a decrease in cell migration, invasiveness, extracellular matrix adhesion ability, and stem cell-like properties. Furthermore, we discovered that FAK and ERK signaling pathways play a crucial role in GBM cell progression in response to EDB-FN. This study underscores the potential of EDB-FN as a specific biomarker for GBM treatment, paving the way for future research in this area.