Biomarkers In Conjunction Research Articles

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for >5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p<0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for >5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p<0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

Correlating maternal and cord-blood inflammatory markers and BDNF with human fetal brain activity recorded by magnetoencephalography: An exploratory study

BackgroundDuring gestation, the brain development of the fetus is affected by many biological markers, where inflammatory processes and neurotrophic factors have been of particular interest in the past decade. AimThis exploratory study is the first attempt to explore the relationships between biomarker levels in maternal and cord-blood samples and human fetal brain activity measured with non-invasive fetal magnetoencephalography (fMEG). MethodTwenty-three women were enrolled in this study for collection of maternal serum and fMEG tracings immediately prior to their scheduled cesarean delivery. Twelve of these women had a preexisting diabetic condition. At the time of delivery, umbilical cord blood was also collected. Biomarker levels from both maternal and cord blood were measured and subsequently analyzed for correlations with fetal brain activity in four frequency bands extracted from fMEG power spectral densities. ResultsRelative power in the delta, alpha, and beta frequency bands exhibited moderate-sized correlations with maternal BDNF and cord-blood CRP levels before and after adjusting for confounding diabetic status. These correlations were negative for the delta band, and positive for the alpha and beta bands. Maternal CRP and cord-blood BDNF and IL-6 exhibited negligible correlations with relative power in all four bands. Diabetes did not appear to be a strong confounding factor affecting the studied biomarkers. ConclusionsMaternal BDNF levels and cord-blood CRP levels appear to have a direct correlation to fetal brain activity. Our findings indicate the potential use of these biomarkers in conjunction with fetal brain electrophysiology to track fetal neurodevelopment.

Different heart rate variability profile during sleep in mid-later life adults with remitted early-onset versus late-onset depression

BackgroundIn mid-later life adults, early-onset and late-onset (i.e., onset ≥50 years) depression appear to be underpinned by different pathophysiology yet have not been examined in relation to autonomic function. Sleep provides an opportunity to examine the autonomic nervous system as the physiology changes across the night. Hence, we aimed to explore if autonomic profile is altered in mid-later life adults with remitted early-onset, late-onset and no history of lifetime depression. MethodsParticipants aged 50–90 years (n = 188) from a specialised clinic underwent a comprehensive clinical assessment and completed an overnight polysomnography study. General Linear Models were used to examine the heart rate variability differences among the three groups for four distinct sleep stages and the wake after sleep onset. All analyses controlled for potential confounders – age, sex, current depressive symptoms and antidepressant usage. ResultsFor the wake after sleep onset, mid-later life adults with remitted early-onset depression had reduced standard deviation of Normal to Normal intervals (SDNN; p = .014, d = −0.64) and Shannon Entropy (p = .004, d = −0.46,) than those with no history of lifetime depression. Further, the late-onset group showed a reduction in high-frequency heart rate variability (HFn.u.) during non-rapid eye movement sleep stage 2 (N2; p = .005, d = −0.53) and non-rapid eye movement sleep stage 3 (N3; p = .009, d = −0.55) when compared to those with no lifetime history. LimitationsCausality between heart rate variability and depression cannot be derived in this cross-sectional study. Longitudinal studies are needed to examine the effects remitted depressive episodes on autonomic function. ConclusionThe findings suggest differential autonomic profile for remitted early-onset and late-onset mid-later life adults during sleep stages and wake periods. The differences could potentially serve as peripheral biomarkers in conjunction with more disease-specific markers of depression to improve diagnosis and prognosis.

Physiological stress in a Hellenistic-early Roman community in Sicily

This paper explores physiological stress patterns in the Hellenistic/early Roman settlement of Menainon, Sicily. A skeletal assemblage dating from the 4th to the 1st c. BCE was examined for cribra orbitalia, porotic hyperostosis, periostitis, and enamel hypoplasia, while the biological index of frailty (BIF), which measures morbidity, was estimated using these biomarkers in conjunction with trauma, mechanical stress, stature and body mass data. The results showed a higher frequency of cribra orbitalia, porotic hyperostosis, and enamel hypoplasia in male individuals, likely supporting greater stress in males earlier in life. In contrast, females were affected mostly by periostitis but the lesions were generally remodeled. BIF values were overall higher in males in all age groups but showed a steady decline throughout adulthood, whereas female morbidity peaked in middle adulthood. Taken together, these patterns suggest a differential exposure of males and females to physiological stress at different points in their lifetime, though this pattern rarely reached statistical significance and it did not affect the mortality patterns in either sex. When compared to other assemblages, cribra orbitalia and periostitis were particularly common in Menainon, porotic hyperostosis showed an average frequency, while enamel hypoplasia was rare. The interpretation of these patterns is complicated by the diverse social and cultural background of the comparative assemblages. Further research, focused on diet, mobility, mechanical stress and other aspects of the life of the Menainon population, could offer a better understanding of the above results. However, the current study highlights the context-specific nature of physiological stress and the necessity to not rely exclusively on textual evidence regarding past gender roles and associated living conditions.

Postnatal epigenome-mediated aging control and global trends

The epigenome can adequately regulate the on/off states of genes in response to external environmental factors and stress. In recent years, it has been observed that the epigenome, which is modulated through DNA methylation, histone modifications, and chromatin remodeling, changes with age. Alterations in the epigenome lead to the loss of cell-specific epigenome/identity, which in turn triggers a decline in tissue function. In mammals, postnatal epigenomic variations are not only caused by metabolic diseases, such as diabetes or DNA damage, but also by social stress and infectious diseases. Unlike Genome-Wide Association Studies (GWAS), dynamically changing epigenomes, along with their cellular roles, need to be established as objective biomarkers in conjunction with various biological signals, such as walking speed, brain waves, and clinical data. The biological age/aging clock, determined by methylated DNA, has attracted attention, and calorie restriction not only slows the progression of aging, but also seems to suppress it. However, as indicated by gene expression analysis in aging mice, aging is not a linear model, but is represented by nonlinear dynamic changes. Consequently, the development of experimental models and analytical methods that enhance temporal resolution through time-series analysis, tailored to spatial resolution, such as cell distribution and organ specificity, is progressing. Moreover, in recent years, in addition to anti-aging efforts targeting epigenomic variations, global attention has increasingly focused on research and development aimed at rejuvenating treatments, thus leading to the birth of many biotech companies. Aging Hallmarks such as inflammation, stem cells, metabolism, genomic instability, and autophagy, interact closely with the epigenome. Various postnatal and reversible epigenomic controls of aging, including Yamanaka factors (OKSM and OSK), are now entering a new phase. In the future, the development of aging control using diverse modalities, such as mRNA, artificial peptides, and genome editing, is expected, along with an improved molecular understanding of aging and identification of useful biomarkers.

Emerging Biomarkers for Early Detection of Cardiovascular Disease

This extensive study explores the field of novel biomarkers for the early detection of cardiovascular disease (CVD), looking at a variety of indicators, including circulating endothelial cells, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein (hs-CRP), microRNAs, and myeloperoxidase (MPO). The review emphasizes how important these indicators are to improving CVD risk assessment, prognosis, and treatment plans. While each biomarker offers distinct insights into particular facets of cardiovascular health, multi-biomarker panel integration is suggested for a more thorough knowledge. The paper also discusses the difficulties with standardization, moral issues, and legal restrictions related to using these biomarkers in therapeutic settings. In addition, the revolutionary potential of these new biomarkers in conjunction with state-of-the-art technologies is emphasized, providing a promising path towards precision cardiovascular care and customized medicine

Voice Biomarkers for Parkinson's Disease Prediction Using Machine Learning Models with Improved Feature Reduction Techniques

As a chronic and life-threatening disease, Parkinson's disease (PD) causes people to become rigid and inactive and have shaky voices. There is an argument that current PD detection techniques are ineffective due to their high latency and low accuracy. To enhance the accuracy of PD identification, voice recordings were used as biomarkers in conjunction with the synthetic minority oversampling technique (SMOTE). Three machine learning (ML) models namely support vector machine (SVM), K-nearest neighbors (KNN), and random forest (RF)were adopted to calculate the prediction accuracy. By applying an unsupervised dimensional reduction method, the generated model eliminates redundant data and speeds up training and testing. Model performance is estimated with three parameters, including accuracy, F1 score, and area under the curve (AUC) values. Experimental outcomes suggested that the RF model outperforms other models with 97.4% of classification accuracy. This type of research aims to analyze patient voice recordings to determine the disease severity.

Abstract 2292: Novel method for the detection and evaluation of disease biomarkers on white blood cells from liquid biopsies

Abstract Purpose: Blood based liquid biopsies of circulating tumor cells (CTCs) are a non-invasive tool with proven effectiveness in the prognosis, treatment selection, and stratification of cancer patients. In this study we demonstrate a novel application of the RareCyte platform, which was developed to find and analyze rare CTCs from blood samples, in evaluating white blood cell (WBC) sub-populations for disease biomarkers. Experimental Procedures: Using AccuCyte®, an unbiased density-based method for collecting nucleated cells from whole blood, we transferred the nucleated cells to slides and stained for CD14, CD66b, and CK/EpCAM to identify monocytes (CD14+/CD66b-), granulocytes (CD14-/CD66b+), and CTCs (CK/EpCAM+), as well as a drug-target biomarker to evaluate its expression across all cells. These slides were then imaged with CyteFinder®, an automated multiparameter immunofluorescent (IF) microscopy system that applies machine learning algorithms for cell identification. Each slide contains millions of cells, so we developed novel scanning and analysis algorithms to quantify WBC sub-populations in addition to rare CTCs. Results: In addition to detection and enumeration of CTCs, the RareCyte system was able to detect individual white blood cells and quantify monocyte and granulocyte subpopulations. Our results correlated very well with standard CBC (Complete Blood Count) readings from multiple donors. Additionally, the monocyte and granulocyte populations were evaluated for expression of a drug-target biomarker. While expression was observed on both granulocytes and monocytes, monocytes had a significantly higher expression of the drug-target biomarker, a critical finding for future implementation of this drug. Conclusions: Our results show that through modifications to the RareCyte platform we can identify rare and non-rare cell populations simultaneously and evaluate expression of biomarkers and drug-targets across multiple cells of interest. This new application combines the benefits of high throughput data analysis of flow cytometry with the specificity and sensitivity of rare cell detection. Additionally, high-resolution multiplexed immunofluorescent imaging provides cell morphology and biomarker localization information. Our ability to add multiple biomarkers in conjunction with CTC and other rare cell detection provides multiple avenues for future research. One possible application is characterizing white blood cells that cluster with CTCs, which are known to portend a worse prognosis for patients. Our modified workflow could be implemented to precisely characterize these WBCs that contribute to the metastatic process. Utilization of the RareCyte platform for both rare and non-rare cell analysis presents an exciting opportunity for a deeper evaluation of patients and their prognosis through liquid biopsies. Citation Format: Erin Bayer, Jon Ladd, Joshua Nordberg, Arturo B. Ramirez, Jessica A. Baker, Thomas Daly. Novel method for the detection and evaluation of disease biomarkers on white blood cells from liquid biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2292.

Abstract 5474: Combined use of MRI and TAM analysis in GB monitoring

Abstract Glioblastoma (GB) is the most frequent and aggressive primary brain tumor. It is a highly infiltrating tumor. Complete eradication by surgery is difficult. The probability of survival beyond two years is very low. Magnetic resonance imaging (MRI) is a routine procedure for diagnosing gliomas. However, morphological MRI often fails to identify and quantify the presence of infiltration in peritumoral non-enhanced areas, resulting in inaccuracy in the assessment of invasive margins. Up to 50% of the patients show pseudo-progression. Morphological MRI fails to distinguish the marked enhancement in the tumor bed caused by radionecrosis from actual tumor progression. Diagnosis of GB recurrence through MR morphological sequences has a sensitivity and specificity of about 68% and 77%. Such percentages rise thanks to the use of non-morphological sequences (PWI, DWI, MRS), which are used in routine tumor protocols only in large centers and interpreted by expert neuroradiologists. Biomarkers in conjunction with MRI may help improve the classification, prognosis, and treatment choice. GB is highly infiltrated with monocytic cells, tumor-associated macrophages (TAMs), that invade the peripheral blood. Our group has recently identified a splice isoform of FK506-binding protein 51 (FKBP51) as a reliable TAM marker. We found an expansion in circulating CD163/FKBP51s monocytes in a cohort of GB patients. In patients with an MRI diagnosis of complete surgical tumor removal, these monocytes dramatically decreased. In patients with an MRI diagnosis of residual tumor, most of the peripheral CD163 monocytes that in the preoperative stage were FKBP51s- had turned into FKBP51s+. CD163/FKBP51s+ monocytes helped to distinguish between radionecrosis and actual tumor progression. These results suggest that circulating CD163/FKBP51s+ monocytes are associated with GB and can be helpful in monitoring GB patients. Citation Format: Carolina Giordano, Giuseppe Maria Della Pepa, Simona Romano, Laura Marrone, Carlo Maria Donzelli, Maria Fiammetta Romano, Simona Gaudino. Combined use of MRI and TAM analysis in GB monitoring. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5474.

Biological informed graph neural network for tumor mutation burden prediction and immunotherapy-related pathway analysis in gastric cancer

Tumor mutation burden (TMB) has emerged as an essential biomarker for assessing the efficacy of cancer immunotherapy. However, due to the inherent complexity of tumors, TMB is not always correlated with the responsiveness of immune checkpoint inhibitors (ICIs). Thus, refining the interpretation and contextualization of TMB is a requisite for enhancing clinical outcomes. In this study, we conducted a comprehensive investigation of the relationship between TMB and multi-omics data across 33 human cancer types. Our analysis revealed distinct biological changes associated with varying TMB statuses in STAD, COAD, and UCEC. While multi-omics data offer an opportunity to dissect the intricacies of tumors, extracting meaningful biological insights from such massive information remains a formidable challenge. To address this, we developed and implemented the PGLCN, a biologically informed graph neural network based on pathway interaction information. This model facilitates the stratification of patients into subgroups with distinct TMB statuses and enables the evaluation of driver biological processes through enhanced interpretability. By integrating multi-omics data for TMB prediction, our PGLCN model outperformed previous traditional machine learning methodologies, demonstrating superior TMB status prediction accuracy (STAD AUC: 0.976 ± 0.007; COAD AUC: 0.994 ± 0.007; UCEC AUC: 0.947 ± 0.023) and enhanced interpretability (BA-House: 1.0; BA-Community: 0.999; BA-Grid: 0.994; Tree-Cycles: 0.917; Tree-Grids: 0.867). Furthermore, the biological interpretability inherent to PGLCN identified the Toll-like receptor family and DNA repair pathways as potential combined biomarkers in conjunction with TMB status in gastric cancer. This finding suggests a potential synergistic targeting strategy with immunotherapy for gastric cancer, thus advancing the field of precision oncology.

TRIAD multi‐dimensional biobank for biomarker discovery

AbstractBackgroundThe Translational Biomarkers in Aging and Dementia (TRIAD) is a longitudinal, biomarker‐based cohort designed to study interactions between the pathophysiological processes driving to dementia. Currently, 50 million people worldwide have dementia [1]. PET and MRI imaging have been widely used to assess disease stage, though expensive and not readily accessible [2]. More recently though, breakthroughs in blood‐based biomarkers have proven a useful, available, and more cost‐effective way of evaluating amyloid and tau positivity. The TRIAD Biobank provides a unique framework to study disease stage using blood‐based biomarkers in conjunction with PET and CSF studies. Our cohort allows for validation of novel biomarkers as we simultaneously acquire gold standard second generation imaging acquisitions with full spectrum fluid biomarkers (CSF, saliva, plasma, urine). Importantly, the data acquired is integrated in a database compliant to multi‐dimensional biomarker analysis.MethodFigure 1 depicts the cohort's banked fluids by diagnostic group. Figure 2 depicts the cohort's banked fluids by sex grouping.ResultThe TRIAD Biobank stores 1,034 blood samples from 655 participants, 658 of these being follow‐up collections. Additionally, cerebrospinal fluid has been collected from 381 individuals accounting for 520 collections in the bank, 812 urine collections from 662 individuals and 591 saliva samples from 432 individuals.Additionally, the cohort has collected 761 tau PET scans using [18F]MK6240, 644 amyloid PET scans using [18F]AZD4694 and 804 MRI using 3 Tesla.ConclusionWith dementia being one of the leading, most costly causes of death, the need for early detection, more affordable, less invasive, and more readily available ways to determine disease stage is apparent [2]. The TRIAD multi‐dimensional biobank provides a wealth of resources to discover affordable biomarkers needed for early diagnosis and Alzheimer’s disease prevention.[1] Patterson, C. 2018. World Alzheimer Report 2018: The state of the art of dementia research, new frontiers. London, England: Alzheimer's Disease International.[2] Gauthier S, Rosa‐Neto P, Morais JA, & Webster C. 2021. World Alzheimer Report 2021: Journey through the diagnosis of dementia. London, England: Alzheimer’s Disease International.

TRIAD multi‐dimensional biobank for biomarker discovery

AbstractBackgroundThe Translational Biomarkers in Aging and Dementia (TRIAD) is a longitudinal, biomarker‐based cohort designed to study interactions between the pathophysiological processes driving to dementia. Currently, 50 million people worldwide have dementia [1]. PET and MRI imaging have been widely used to assess disease stage, though expensive and not readily accessible [2]. More recently though, breakthroughs in blood‐based biomarkers have proven a useful, available, and more cost‐effective way of evaluating amyloid and tau positivity. The TRIAD Biobank provides a unique framework to study disease stage using blood‐based biomarkers in conjunction with PET and CSF studies. Our cohort allows for validation of novel biomarkers as we simultaneously acquire gold standard second generation imaging acquisitions with full spectrum fluid biomarkers (CSF, saliva, plasma, urine). Importantly, the data acquired is integrated in a database compliant to multi‐dimensional biomarker analysis.MethodFigure 1 depicts the cohort's banked fluids by diagnostic group. Figure 2 depicts the cohort's banked fluids by sex grouping.ResultThe TRIAD Biobank stores 1,034 blood samples from 655 participants, 658 of these being follow‐up collections. Additionally, cerebrospinal fluid has been collected from 381 individuals accounting for 520 collections in the bank, 812 urine collections from 662 individuals and 591 saliva samples from 432 individuals.Additionally, the cohort has collected 761 tau PET scans using [18F]MK6240, 644 amyloid PET scans using [18F]AZD4694 and 804 MRI using 3 Tesla.ConclusionWith dementia being one of the leading, most costly causes of death, the need for early detection, more affordable, less invasive, and more readily available ways to determine disease stage is apparent [2]. The TRIAD multi‐dimensional biobank provides a wealth of resources to discover affordable biomarkers needed for early diagnosis and Alzheimer’s disease prevention.[1] Patterson, C. 2018. World Alzheimer Report 2018: The state of the art of dementia research, new frontiers. London, England: Alzheimer's Disease International[2] Gauthier S, Rosa‐Neto P, Morais JA, & Webster C. 2021. World Alzheimer Report 2021: Journey through the diagnosis of dementia. London, England: Alzheimer’s Disease International.

Fatty acid biomarkers as indicators of organic matter origin and processes in recent turbidites: The case of the terminal lobe complex of the Congo deep-sea fan

The Congo River is connected to its submarine canyon and supplies large quantities of terrestrial organic carbon via powerful turbiditic currents down to the Congo deep-sea fan. We investigated sediment cores from the terminal lobe complex of the Congo deep-sea fan (∼750 km offshore, ∼5000 m water depth), in order to assess the value of fatty acid biomarkers as indicators of organic matter (OM) origin and processes affecting its distribution and preservation in recent turbidites. Sediments from the Congo deep-sea fan are enriched in fatty acids compared to the surrounding abyssal plains and their composition closely resembles that of sediments recovered in the Congo River. Long chain fatty acid (LCFA) biomarkers in conjunction with the branched vs isoprenoid tetraether index (BIT) show that OM mostly originates from soil erosion and continental higher plants. This material has undergone limited reprocessing during transit certainly due to tight interactions with mineral particles and rapid transfer. The presence of phytoplankton biomarkers at the entrance of the terminal lobe area highlights that inputs of fresh OM, albeit limited, can reach the lobe complex. By combining fatty acid profiles and geochemical proxies in a multivariate analysis, we highlight that OM degradation is mostly limited to the oxic layer, and that fine soil-derived particles and the coarser higher plant detritus display distinct depositional dynamics. Finally, LCFA are remarkably well preserved under anoxic conditions at different time scales, in recent turbidites deposited during the last century and those deposited several thousand years ago.

Impact of CT screening in lung cancer: Scientific evidence and literature review

The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.

Improving the ACS Triage-Using High Sensitivity TroponinI and Copeptin for Early 'Rule-Out' of AMI.

Rule-out of acute myocardial infarction (AMI) in patients presenting with acute chest pain at the emergency department (ED) is a major challenge across the globe. Patients presenting very early with chest pain may provide a diagnostic challenge even when using a cardiac necrosis specific biomarker, high sensitivity troponin (hs-Tn) as they are elevated at 3-6h after the symptom onset. Copeptin is a marker of acute hemodynamic stress which is released within few minutes of the occurrence of MI and is elevated immediately at the presentation of patients with AMI. This indicates a complementary pathophysiology and kinetics of these two biomarkers. Hence, we evaluated whether or not a protocol with combined testing of copeptin and hs-TnI at admission in patients presenting with chest pain within 6h in low to intermediate risk and suspected ACS leads to an earlier diagnosis of AMI and thereby, aids to prevent a higher proportion of major adverse cardiac events than the current standard protocol followed in ED. A total of 148 patients as per the inclusion criterion were recruited for the study. The dual biomarker copeptin and hs-TnI allows a rule-out of AMI at presentation with a sensitivity of 100% and NPV of 99.8%. Hence, the use of dual biomarker in conjunction with clinical assessment may obviate the need for a prolonged stay in the ED and retesting hs-TnI after 2h (for delta check) in more than two-thirds of the patients. The inclusion of these tests could have an impact on the economic burden of the ED without jeopardizing the outcome for the patient.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. • Maximum standardiseduptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

Biomarkers and Tools for Predicting Alzheimer's Disease in the Preclinical Stage.

Alzheimer's disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Over the past decade, a string of disappointing clinical trial results has forced us to shift our focus to the preclinical stage of AD, which represents the most promising therapeutic window. However, the accurate diagnosis of preclinical AD requires the presence of brain β- amyloid deposition determined by cerebrospinal fluid or amyloid-positron emission tomography, significantly limiting routine screening and diagnosis in non-tertiary hospital settings. Thus, an easily accessible marker or tool with high sensitivity and specificity is highly needed. Recently, it has been discovered that individuals in the late stage of preclinical AD may not be truly "asymptomatic" in that they may have already developed subtle or subjective cognitive decline. In addition, advances in bloodderived biomarker studies have also allowed the detection of pathologic changes in preclinical AD. Exosomes, as cell-to-cell communication messengers, can reflect the functional changes of their source cell. Methodological advances have made it possible to extract brain-derived exosomes from peripheral blood, making exosomes an emerging biomarker carrier and liquid biopsy tool for preclinical AD. The eye and its associated structures have rich sensory-motor innervation. In this regard, studies have indicated that they may also provide reliable markers. Here, our report covers the current state of knowledge of neuropsychological and eye tests as screening tools for preclinical AD and assesses the value of blood and brain-derived exosomes as carriers of biomarkers in conjunction with the current diagnostic paradigm.

Prognostic Value of 18F-FDG PET in Neuroendocrine Neoplasm: A Systematic Review and Meta-analysis.

Accurate assessment of the prognosis is critical for the rational treatment of neuroendocrine neoplasms (NENs). We performed a systematic review and meta-analysis of the prognostic value of 18F-FDG PET for NENs. PubMed and Embase databases were searched up to September 2020 for studies that evaluated 18F-FDG PET as prognostic factors in patients with NENs with overall survival (OS) and event-free survival (EFS) as outcomes. Hazards ratios (HRs) comparing high and low FDG uptakes were pooled using the DerSimonian-Laird method. Publication bias was assessed and adjusted for using the trim-and-fill method. Metaregression and subgroup analyses were performed to explore the cause of heterogeneity. Twenty-three studies (1799 patients) were included. The overall pooled HRs of high FDG uptake on EFS and OS were 2.84 (95% confidence interval [CI], 2.21-3.64) and 3.50 (95% CI, 2.42-4.12), respectively. Publication biases were present regarding both EFS and OS (P = 0.0342 and 0.0009, respectively). After adjustment, effect sizes remained significant for EFS and OS (adjusted HR, 2.26 [95% CI, 1.76-2.89]; 3.16 [95% CI, 2.42-4.12]). In metaregression analyses, the proportion of grade 3 tumors positively correlated with the HR of OS (adjusted P = 0.0422). 18F-FDG PET is a significant prognostic factor in patients with NENs. 18F-FDG PET might be a useful prognostic biomarker in conjunction with the histologic grade and can help select the optimal treatment.

New GOLD COPD Guideline 2019: How We Deal with It? (Inhaled Corticosteroid Use and Blood Eosinophil Count)

Background: Blood eosinophils may predict response to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), where ICS is recommended in patients at high risk of exacerbations by the Global Initiative for COPD (GOLD) strategy. It can help clinicians to estimate the likelihood of beneficial preventive responses to the addition ICS to regular bronchodilator treatment, and thus can be used as a biomarker in conjunction with clinical assessment when making decisions regarding ICS use. This study aims to compare therapeutic data with blood eosinophil count in COPD patients.&#x0D; Methods: Data were collected from consecutive COPD outpatients in Bukit Asam Medika Hospital starting from March 1st, 2019 until June 30th, 2019 and dr. H. Mohamad Rabain Hospital starting from Oct 1st, 2019 until Dec 27th, 2019. We collected demographics, anthropometrics, smoking history, therapy, dynamic lung volumes, the Medical Research Council scale (MRC), CAT score, and blood eosinophil count.&#x0D; Results: From 57 data collected, 24 (42,1%) patients were having blood eosinophil count ≥300. Patients who have more exacerbation in COPD Group C were 33,3% and 63,2% in COPD Group D. The proportions of ICS-treated COPD Group D patients and blood eosinophil count of &lt;300 and ≥300 was 63,9% and 36,1%, respectively.&#x0D; Conclusion: This study may provide information and characteristic of COPD patient in Indonesia rural area and showed who may have benefit to ICS therapy based on recommendation GOLD COPD 2019. Blood eosinophils counts is a low-cost biomarker and may help clinicians to made decision therapy.