Definitive Markers Research Articles

West Iranian in historical perspective

Abstract The development of the Persian definitive object marker -rā from Old Persian rādī through Middle Persian benefactive rāy has been established as a model grammaticalization process by Bossong (1985). His explanations on other modern Iranian languages, and their interplay in the historical development, have received far less research attention. This article offers a novel and comprehensive account of the historical development of -rā in West Iranian, from Old Persian up to approximately 20 New Iranian languages. Based on the semantic map model, it demonstrates that concerning -rā, most West Iranian languages can be subdivided into three typological groups, two of which represent more or less clearly defined genetic subgroups within the continuum of West Iranian. The interplay of genetic and typological/functional factors is complex, and open questions remain. The present study aims to provide empirical data, and to raise relevant questions, for future in-depth studies.

Imaging modalities for atraumatic shoulder hypermobility: a scoping review.

Objective measures from imaging studies have the potential to assist in timely diagnosis of atraumatic shoulder hypermobility to better guide management. The aim of this scoping review is to examine imaging modalities and techniques used to characterize atraumatic shoulder hypermobility. MEDLINE, EMBASE, SPORTDiscus, Cochrane Library, and Web of Science were searched up to May 2024 for any primary study investigating imaging findings seen in atraumatic shoulder hypermobility. Patients with unilateral instability were excluded given its frequent association with traumatic origin. Eighteen observational studies met inclusion criteria. Results were divided into outcomes relating to capsular redundancy, glenohumeral anatomy, and muscle activation. Five studies using magnetic resonance arthrography (MRA) demonstrated statistically significant increases in capsular cross-sectional area (CSA), while a significant superior capsular elongation was reported by two studies in patients with multidirectional instability (MDI). Labrocapsular distance, glenocapsular ratio, and the presence of a combined sail and triangle sign on MRA were highly sensitive and specific parameters for identifying MDI. There were inconsistent findings for alterations of glenohumeral anatomy. Ultrasound assessments of acromiohumeral distance (AHD) were significantly increased in patients with MDI, but not in shoulders with hypermobility alone. Similarly, muscle activity measured by electromyography or glenohumeral translations differed significantly in patients with MDI, but not in those with hypermobility alone. Radiographic markers of capsular redundancy (e.g., CSA, labrocapsular distance, glenocapsular ratio), AHD, and muscular activity are useful in the diagnosis of MDI. However, there are no definitive imaging markers for diagnosing atraumatic shoulder hypermobility without MDI.

Prognostic value of Ki67 in phyllodes tumor of the breast: A systematic review and meta‑analysis.

Numerous clinicopathological features have been examined as predictive factors for adverse outcomes in patients with phyllodes tumor (PT) of the breast, but there are still no definitive predictive markers to guide management, despite the persistent risk of recurrence, even in benign disease. Whether Ki67 has prognostic value in PT remains uncertain. Therefore, a systematic review and meta-analysis were performed to examine whether Ki67 is associated with adverse clinical outcomes, particularly recurrence, in patients with PT. The PubMed/MEDLINE, Web of Science, Scopus, Embase and Cochrane Library databases were searched from inception to July 2024. Study characteristics and outcomes (recurrence and overall survival) according to Ki67 status were extracted from each eligible study, and pooled log odds ratios (OR) with 95% CI were derived using a random-effects model. A total of five studies comprising 280 cases were eligible for inclusion. The adverse outcome rate for the Ki67high (Ki67 >10 or >11.2%) population was 28.7% (95% CI, 20.1-38.6%), while the adverse outcome rate for the Ki67low population was 9.4% (95% CI, 5.4-13.5%). Ki67high was associated with an increased odds of an adverse outcome [log OR, 1.26 (95% CI, 0.38-2.15; P=0.005)] compared with a Ki67low status. All five studies scored 8 points on the Newcastle-Ottawa Scale, equivalent to 'good' quality according to Agency for Healthcare Research and Quality standards, and no significant publication bias was noted. This was the first meta-analysis of the predictive value of Ki67 in PT of the breast. A relatively high Ki67 index (>10%) is associated with recurrence. It is timely to re-evaluate the prognostic value of Ki67 in large retrospective cohorts with long follow-up to firmly establish whether it could contribute to identifying patients at risk of recurrence, particularly those with histologically benign disease. Doing so could impact clinical practice by refining follow-up recommendations based on quality evidence.

CD27 is not an ideal marker for human memory B cells and can be modulated by IL-21 upon stimulated by Anti-CD40

B cells play a key role in humoral immune responses by producing antibodies. Although there are numerous research on memory B cells definition markers and cytokines on B cell development, different studies have yielded contradictory conclusions due to species studied, the different cells and stimulating agents used. In the current study, we conducted a detailed characterization of B cells in human CBMCs, PBMCs and tonsil, including expression of Igs, activation and memory markers. Furthermore, we found that considerable amounts of IgA and IgG were expressed by CD27− B cells. These “Atypical” memory B cells corresponded to approximately 50% of IgG+ and IgA+B cells in blood, this proportion even reached 90% in tonsil. In addition, we investigated the effect of IL-21 and TGF-β1 on the membrane-bound form and secreted form of Igs using PBMCs and purified blood B cells. There were actual differences between the effect of cytokines on Igs secretion and surface expression. Our study will be helpful to advance the knowledge and understanding of humoral memory.

Order Effects in Second Language Learning

AbstractWe explore how general principles of learning apply to and combine with usage‐based approaches to language learning and teaching, with a focus on the effects of order of exposure to new information in second language (L2) instruction. Although the effects of input spacing and timing on memory and learning have been previously explored (see Rogers, 2020; Shintani, 2017, for an overview), the effects of order of exposure to the input remain understudied. In this study, we tested whether order of exposure to information in the L2 plays a role in L2 learning and whether an optimal order where the most reliable cues are introduced first ensures that foreign language learners are better equipped to form representations that allow flexible, yet accurate generalisations. We analysed data collected through a training study that teaches the English article system to first language (L1) speakers whose language does not have markers of definiteness.

Unraveling the chemosensory characteristics on different types of spirits based on sensory contours and quantitative targeted flavoromics analysis

Due to differences in raw materials and production processes, different spirits exhibit various flavor even if undergo distillation operation. In this study, sensory analysis could clearly distinguish 5 types spirits, and had been validated through quantitative targeted flavoromics analysis. Consequently, 44 potential differential markers between 5 types spirits were screened. Among, 34 definite differential markers were further confirmed to be highly correlated with target sensory attributes and could effectively distinguish types of spirits. Ultimately, 14 key differential markers (including 2-methylbutane, linalool, acetaldehyde, d-limonene, β-myrcene, phenylethyl alcohol, phenethyl acetate, heptyl formate, ethyl octanoate, ethyl decanoate, ethyl pentanoate, ethyl hexanoate, hexanoic acid, and ethyl hexadecanoate) could reveal the chemical sources of spirit sensory and serve as targets for identifying different types of spirits. Overall, the results of flavoromic characterization of 5 types spirits provided a significant step forwards in understanding of differentiation of spirits by sensory coupled with quantitative, and statistical analysis

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48months; 19 demonstrated typical development, mean age: 61.16 ± 8.11months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.

Severity and Prevalence in Non-Specific Interstitial Pneumonia and COVID-19 Associated Pneumonia

Background: The non-specific clinical presentation and absence of definitive diagnostic markers further complicate the diagnosis of nterstitial lung diseases (ILD), particularly idiopathic interstitial pneumonia (IIP). This study aimed to investigate the clinical and epidemiological characteristics, along with imaging diagnostics, of patients with non-specific interstitial pneumonia (NsIP) in the Samarkand region from 2020 to 2023. Methods: A retrospective analysis of medical records was conducted for 262 patients diagnosed with ILD and hospitalized at the Samarkand State Medical Association (SamSMA). Using a multidisciplinary approach and adhering to the international classification of diseases (ICD-10) criteria, patients were categorized into two groups: those diagnosed with NsIP and a comparison group of patients with COVID-19-associated pneumonia (COVID-19 AP). The patients were further subdivided based on disease severity: moderate (IA) and severe (IB) for the NsIP group, and moderate (IIA) and severe (IIB) for the COVID-19 AP group. Results: The study found that 72.5% of ILD patients had NsIP, predominantly older males. Moderate disease severity was more common in NsIP patients, while severe cases were more prevalent in the COVID-19 AP group. The age groups 45-59 and 60-74 years represented 78% of the NsIP cases. Conclusion: The study found a higher prevalence of NsIP among men, with the majority of cases occurring in older age groups. Moderate disease severity was more common in NsIP patients, contrasting with COVID-19 AP patients, where severe cases were more prevalent.

Roles of cerebrospinal fluid-contacting neurons as potential neural stem cells in the repair and regeneration of spinal cord injuries.

Cerebrospinal fluid-contacting neurons (CSF-cNs) represent a distinct group of interneurons characterized by their prominent apical globular protrusions penetrating the spinal cord's central canal and their basal axons extending towards adjacent cells. Identified nearly a century back, the specific roles and attributes of CSF-cNs have just started to emerge due to the historical lack of definitive markers. Recent findings have confirmed that CSF-cNs expressing PKD2L1 possess attributes of neural stem cells, suggesting a critical function in the regeneration processes following spinal cord injuries. This review aims to elucidate the molecular markers of CSF-cNs as potential neural stem cells during spinal cord development and assess their roles post-spinal cord injury, with an emphasis on their potential therapeutic implications for spinal cord repair.

The Contrastive and Referential Function of Specific Classifiers in Xiamen Southern Min—Evidence from a Cognitive Experimental Study

Southern Min is generally known for not using classifiers [CL] for expressing definiteness/indefiniteness as it is associated with the bare classifier construction [CL N]. This paper offers evidence from Xiamen Southern Min (XSM) that the use of a specific classifier vs. the general classifier é contributes to referentiality in an alternative way by supporting object identification as it is due to the semantic specificity present in specific classifiers and absent in the general classifier. In a dialogic cognitive experiment adapted from the “Hidden color-chips” task (Enfield and Bohnemeyer 2001), 18 participants had to manipulate their addressees’ attention toward various objects situated in their immediate physical space through language as well as deictic gestures. The objects were associated with different specific classifiers or with the general classifier, and they were arranged according to the factors of (a) distance from speaker, (b) visibility for speaker, and (c) uniqueness (adjacency of similar items). The results show, among other things, that there is a higher tendency to use the specific CL in the [demonstrative CL N] construction if adjacent similar objects [−unique] are too far away from the speaker for clear identification by a demonstrative or a pointing gesture. This is seen as a last-resort strategy for creating contrast. Further corroboration comes from the use of specific classifiers in later mentions after the general CL failed to achieve clear identification. These findings can be situated in the broader context of other languages with classifiers in contrastive function (Thai, Vietnamese, and Ponapean) and they show the relevance of using dialogic texts for modeling classifier selection in contrast to narrative texts. Finally, dialogic contexts may serve as bridging contexts for grammaticalization from numeral classifiers to definiteness markers.

Linguistic Contact and Tracing Persian Construction onto Khuzestani Arabic Structures

Unlike other dialects of Arabic, Khuzestani vernacular Arabic seems to have attracted little attention within the linguistic community. In this vein, the present study aims to present some evidence to show that matter replication of Persian material is mostly found in Khuzestani vernacular Arabic and thus linguistic contact and grammatical borrowing is most often mapped from Persian onto Khuzestani Arabic. Replication of Persian material primarily occurs in the domain of lexical vocabulary, and partly in grammatical vocabulary. Also, pattern replication is notable in the emerging change of constraints on word order, the favoring of analytic constructions and emergence of a new analytic past tense, and the reduction of overt marking of definiteness. In addition, the most remarkable contact-induced change in the dialect is the identification of Khuzestani Arabic grammatical morphemes in attributive constructions – the Construct State marker and the definite article that appears between head and attribute – with the Persian attributive particle, and the consequent merger of two historically distinct attributive constructions – adjectival and nominal – into a single type, which replicates the state of affairs in Persian.

Clinical significance of urinary inflammatory biomarkers in patients with IgA nephropathy

BackgroundIgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN.MethodsFrom 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression.ResultsThe IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C–X–C motif chemokine 10, C–X–C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein–creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17–0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01–5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05–8.64, P = 0.04) were associated with progression in IgAN.ConclusionsUrinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

The chronic pancreatitis (CP) Type Cambridge 2 as a cause of unclear upper abdominal pain: a radiologically underestimated diagnosis

AbstractThe time interval from symptom onset to the diagnosis of chronic pancreatitis (CP) remains disproportionately long today due to nonspecific symptoms and the absence of a definitive laboratory marker. Nevertheless, mortality is increased by 3.6 times compared to the general population. Additionally, the risk of developing pancreatic carcinoma is 16 times higher in the presence of CP. According to the current S3 guideline, the morphological staging of CP should be based on the Cambridge Classification for CT/MRCP. Most radiologists morphologically associate CP with Cambridge Stage 4, which is characterized by classic calcifications. The subtle morphologies of earlier Cambridge Stages are often unrecognized, leading to delayed diagnosis. The aim of this study was to diagnose CP at Cambridge Stage 2 as the cause of unexplained upper abdominal discomfort.A retrospective analysis was conducted on 266 patients with unexplained upper abdominal pain who underwent outpatient MRI with MRCP between January 1, 2021, and October 1, 2023. The criteria for Cambridge Stage 2 were evaluated: pancreatic duct in the corpus measuring between 2 and 4 mm, pancreatic hypertrophy, cystic changes < 10 mm, irregularities in the duct, or > 3 pathological side branches. Patients with known tumors or other leading diagnoses, which explained the discomfort, were excluded.25 patients (15 female, 10 male) met the criteria for CP Stage 2 (9%). Ductal dilation between 2 and 4 mm was visible in 21 cases. Pancreatic hypertrophy was observed in six cases. Cystic changes < 10 mm were identified in three cases. Irregularities in the duct (“wavy duct”) were diagnosed in 19 patients. Dilation of > 3 side branches was recognized in 17 cases. Lipase levels were additionally determined, with 13 patients showing pathologically elevated levels (> 60 U/l).CP at Cambridge Stage 2 is an important and underestimated diagnosis in patients with unexplained upper abdominal pain in the outpatient setting. Radiologists should pay attention not only to common signs like calcifications, large cysts, or duct strictures but also to subtle changes such as duct irregularities (“wavy duct configuration”) and pathologically dilated side branches, which could lead to a significantly earlier diagnosis of CP. Lipase determination may be an additional indication of chronic pancreatitis in this context.

Exploring the Labyrinth: Imaging in Systemic Vasculitis.

Systemic vasculitis is an immune-mediated group of disorders broadly classified based on the involved vessel type. It has myriad clinical presentations, adding to the challenge of timely diagnosis and management. Thus, imaging has taken center stage in the diagnosis of these disorders as there is a lack of definitive clinical diagnostic markers. Various available imaging modalities can be used for diagnosis and follow-up on these patients. The coronavirus disease 2019 (COVID-19) has added a new dimension to the already existing problem of vasculitis. The virus has shown great affinity for the vascular endothelium, leading to multisystem organ vasculitis. There has been a spike in vasculitis cases in the COVID-19 pandemic era, thus necessitating more research and studies in this field for a better understanding of the disease. In this review, we wish to summarize the various imaging spectrums of classical systemic vasculitis along with the new addition of COVID-19-related vasculitis to the already long list.

Polyarteritis Nodosa Confined to the Kidneys in a Patient with Proteinuria and Mild Renal Impairment

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis predominantly involving medium- or small-sized arteries, typically of the kidneys and other internal organs. Given the rarity of PAN and the variable clinical presentation, diagnosis is challenging and, to date, no definitive diagnostic marker has been identified. A patient diagnosed with immunoglobulin A nephropathy was observed to exhibit deterioration in renal function. To determine whether new structural abnormalities had developed, computed tomography scans of the kidneys, ureters, and bladder were obtained. Both kidneys exhibited multiple cortical defects, and a renal angiogram was performed to determine the cause. Angiography revealed partial obliteration of the left distal renal artery branches and multifocal extensive infarctions in both kidneys, and the patient was diagnosed with renal-limited PAN. Following steroid monotherapy, an improvement in renal function was observed. We believe that this case report may be helpful to physicians who assess and treat patients with suspected renal-limited PAN.

Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans.

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.

Abstract 1043: Identification of the novel immune synapse-localized proteome for immuno-oncology using Microscoop-induced targeted photo-biotinylation

Abstract Although tens of immune synapse (IS) protein species are known, there remain many unknown IS-localized protein species. Understanding the proteome of the IS between a target cell and a lymphocyte is crucial for advancing immuno-oncology. The low abundance of ISs and the lack of a definitive enrichment marker have limited efficient proteomic profiling. Here, we used Microscoop™, an innovative system that integrates microscopy, machine learning, and targeted photo-biotinylation to enable precise and spatially specific enrichment of IS proteins, thereby facilitating proteomic discovery of the IS. We utilized Raji B cells as antigen-presenting cells (APCs) and induced IS formation with Jurkat T cells. The system first employed immunofluorescence imaging of CD3, a common IS marker in Jurkat T cells, and used a convolutional neural network-based deep learning algorithm to train the recognition of ISs from CMTPX-stained Raji B cells. Our automated system then successfully achieved spatially-targeted biotin-tagging of proteins at ISs through thousands of fields of view of imaging, deep learning-driven pattern generation, and photochemical labeling. Subsequent streptavidin pull-down and mass spectrometry analysis enabled the identification of IS-specific proteins. Remarkably, our spatial proteomic approach led to the isolation and identification of hundreds of different species at the IS interface, including proteins associated with key components of T-cell receptor (TCR) signaling pathways such as the TCR/CD3 complex, Src and Tec family tyrosine kinases, and pivotal NF-kB signaling proteins. Beyond these, we also identified a significant enrichment of proteins not previously associated with the IS. Our study not only illuminates previously unknown aspects of immune regulation at the IS interface, but also shedded light on proteins potentially important for immuno-oncology. These insights have significant implications for cancer research, particularly in understanding and manipulating immune responses for therapeutic purposes. Citation Format: Weng-Man Chong, Cecile Li, Chun-Kai Huang, Chantal Hoi Yin Cheung, Hsiao-Jen Chang, Chia-Wen Chung, Jung-Chi Liao. Identification of the novel immune synapse-localized proteome for immuno-oncology using Microscoop-induced targeted photo-biotinylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1043.

Abstract 5355: A novel subset of Treg-like MDSCs expressing LAG-3 found in advanced gastric cancer

Abstract The development and progression of cancers are frequently promoted by immunosuppressive cells, such as Treg and myeloid-derived suppressor cells (MDSCs) mediated by various immune checkpoint molecules. Therefore, MDSCs are potential diagnostic and therapeutic targets in cancer. However, the definitive cell surface markers for defining MDSC and the subset that correlates with cancer progression are not clear. In our previous studies, there was no difference in the amount of total granulocyte MDSCs (G-MDSCs) between early and advanced gastric cancer. We inferred that there is a novel subset of G-MDSCs involved in cancer progression rather than the previous marker-based classification. The purpose of this study is to analyze MDSCs in gastric cancer patients at different stages of progression and to identify subsets of G-MDSCs that are involved in cancer progression. As a result, we identified a subset of novel G-MDSCs that correlate with cancer progression by expressing LAG-3. LAG-3 is a molecule that is expressed in Tregs and causes strong immunosuppression, suggesting that it is involved in the immunosuppressive potential of MDSCs. Citation Format: Takumi Iwasawa, Suguru Yamauchi, Tetsu Fukunaga, Hajime Orita, Tomoaki Ito, Kato Kazunori. A novel subset of Treg-like MDSCs expressing LAG-3 found in advanced gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5355.

High Fibroblast Growth Factor 23, Sialic Acids, and Albumin Modulation in Alzheimer’s Patients

Background: Alzheimer’s disease (AD) is a prevalent form of dementia, posing significant health and societal burdens. Pathologically characterized by neurofibrillary tangles and senile plaques, it lacks definitive diagnostic markers. Fibroblast growth factor (FGF)23 and Sialic Acids (Sias) are implicated in cell signaling and antioxidative defense, while lipid peroxidation (LPO) is linked to neurodegeneration. The aim of this study was to assess serum levels of Fibroblast Growth Factor 23 (FGF23), Malondialdehyde (MDA) as a marker of lipid peroxidation, Sialic Acids (Sias), and albumin in Alzheimer's disease (AD) patients compared to age-matched healthy controls. Method: A case-control study involving 17 AD patients and 17 healthy controls investigated serum levels of FGF23, Sias, malondialdehyde (MDA), and albumin. Biochemical assays and statistical analyses were conducted. Results: Biochemical analyses revealed a significant increase in serum FGF23 and MDA levels in AD patients compared to controls (p < 0.05). Additionally, AD patients exhibited lower levels of serum Sias and albumin. Furthermore, in the patient group, serum MDA levels were inversely correlated with normalized global gray matter volume (GMV), adjusted for age, sex, and Child-Pugh class. Conclusion: This study underscores the potential of FGF23, MDA, Sias, and albumin as biomarkers for AD. Further research elucidating their roles in AD pathogenesis is warranted. Decreased FGF23 in AD may involve disrupted phosphate regulation and neuroprotection mechanisms. Elevated MDA suggests increased lipid peroxidation, contributing to neuronal damage. Reduced Sias may impair antioxidative defense, exacerbating oxidative stress. Low albumin levels correlate with cognitive decline and oxidative damage in AD.

MRNA expression profiling of leptin and adiponectin and its receptors in colorectal carcinoma – Biomarker development

BackgroundMetastatic colorectal carcinoma (CRC) is one of the leading causes of mortality of colorectal CRC. Very few prognostic markers and factors affecting progression are studied between metastatic CRC and early CRC. Adipokines are speculated to be associated with this area of interest. In the current study leptin, leptin receptor (Ob-R), adiponectin, adiponectin R1, and adiponectin R2 expression were measured at gene levels to determine a possible association between adipokines and early/metastatic cancer to ultimately identifying a definitive diagnostic marker. Materials and methodsTissue samples were obtained from 62 patients with radical specimens of CRC. Genes expression was determined by Quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR). The association between the clinicopathological parameters and gene expression levels were analyzed by statistical analysis. ResultsOverexpression of leptin mRNA is observed in small tumors (size< 5 cms) (P<0.05).b. Leptin receptor were overexpressed in advanced tumors (1.013 ± 0.152) than early tumors (0.453 ± 0.131). c.Adiponectin expression was higher in early tumors (1.535 ± 0.406) than in advanced tumors (0.48 ± 0.148). d. Distant organ metastasis shows under-expression of adipoR1. e.Overexpression of adipoR2 is seen in small (size<5 cms) (P<0.05) tumors. ConclusionLEPR is better indicator of advancement of tumor than Leptin. ADIPOR1 is a better indicator in advanced CRC than ADIPOR2 and ADIPOQ.