Clinical Research Directory

Biomarkers in Apical Periodontitis

Aim: To evaluate the effects of three different irrigation activation techniques-conventional syringe irrigation (CSI), ultrasonic irrigation (UI), and SWEEPS (Shock Wave Enhanced Emission Photoacoustic Streaming)-on the levels of proinflammatory cytokines (Tumor Necrosis Factor Alpha (TNF-α), interleukin-1beta (IL-1β)) and proteolytic enzymes matrix metalloproteinase-9 (MMP-9) in teeth with chronic apical periodontitis. Methodology: Sixty-six male patients (aged 18-35) with single-rooted teeth, previous root canal treatment (at least 4 years ago), and periapical lesions (\<1 cm, PAI score 3 or 4) were included. Sample size was determined by G\*Power (Power=0.90, α=0.05). Following local anesthesia and rubber dam isolation, endodontic access was performed under a dental operating microscope. After removing old filling material and completing root canal preparation with Reciproc R25/R50 files, patients were randomly assigned into three groups (n=22 each): (1) CSI (30G needle), (2) UI (EMS miniPiezon), and (3) SWEEPS (Er:YAG laser, 2940 nm). Periapical exudate samples were collected using sterile paper points (2 mm beyond the apex for 60s) at the first visit (pre-treatment) and the second visit (one week post-medication with calcium hydroxide). Samples were analyzed via ELISA for TNF-α, IL-1β, and MMP-9 levels. Statistical Analysis: Data were analyzed using IBM SPSS 20. Percent changes in biomarker levels were evaluated using the Kruskal-Wallis test for inter-group comparisons and the Wilcoxon test for intra-group (pre- vs. post-treatment) comparisons. Linear regression was used to identify effective factors (group, age, gender, tooth type). Significance was set at (p \< 0.05). Keywords: Apical periodontitis, SWEEPS, Ultrasonic activation, Cytokines, MMP-9, Endodontics.

Pleural Effusion Biomarkers in Lung Adenocarcinoma Patients

This project aims to assess the expression levels of novel molecular markers identified through screening in clinical samples of malignant pleural effusion, to evaluate the feasibility and clinical utility of these markers as potential diagnostic genes for lung adenocarcinoma.

Molecular Assessment and Profiling of Liver Transplant Recipients

The objective of this protocol is to conduct longitudinal and prospective studies of liver transplant recipients, using a multimodality approach, akin to that used in kidney transplantation. The primary aim will compare the clinical outcomes of LiverCare post-transplant surveillance in liver transplant with standard of care consisting of liver function tests, DSA measurements, drug level monitoring, and 'for cause' biopsy. The protocol will assess the correlation between clinical events (e.g. rejection, recurrent disease, biliary obstruction), dd-cfDNA levels, gene expression profiling, ability to assess microchimerism, develop predictive analytics, infectious disease diagnoses and finally examine graft histology.

Liquid Biopsy in Early Colorectal Lesions

Early colorectal cancer screening increasingly detects small superficial colonic lesions, but current diagnostic tools still struggle to distinguish benign from malignant lesions and to assess lymph node risk. As histology after resection has limited accuracy, many patients undergo unnecessary surgery. Liquid biopsy, analyzing circulating biomarkers such as tumor DNA, extracellular vesicles, and nucleosomes, offers a non-invasive way to better classify these lesions. Emerging evidence suggests it may outperform current criteria for predicting lymph node involvement in T1 colorectal cancer. This study will establish a biobank of 1,000 patients to identify blood-based signatures that predict tumor stage and lymph node status. The hypothesis of the study is that circulating biomarkers can accurately differentiate benign from malignant lesions and identify patients with or without lymph node metastasis.

Thrombus Composition in Ischemic Stroke: Analysis of the Correlation With Plasma Biomarkers, Efficacy of Treatment, Etiology and Prognosis

The recent validation of thrombectomy in addition to thrombolysis with intravenous administration of alteplase suggests a major revolution in the management of acute strokes. This treatment option also opens up a new field of research, making possible the analysis of the clot responsible for intracranial occlusion. Indeed, in about 30% of the cases, the thrombectomy procedure makes it possible to retrieve either partially or completely the clot. Previous studies have analyzed the correlation between the composition of the thrombus and the etiology of stroke. Their discordant results do not yet make it possible to distinguish a particular profile of thrombus according to etiology. Other studies have shown a correlation between the proportion of red blood cells in a thrombus and the likelihood that it is visible in MRI or cerebral scanning. More recently, one study has demonstrated a correlation between the presence of lymphocytes in the thrombus and an atheromatous etiology. The main limitations of these studies are the small number of patients included, the high variability of conservation protocols and the absence of plasma data, which does not allow for research on the correlation between clot composition and plasma biomarkers.

Evaluation of a Plasma Marker (p-Tau217) for the Biological Diagnosis of Alzheimer's Disease, and Comparison With CSF Markers

The biological diagnosis of AD is actually performed by analysing Aβ1-40 and Aβ1-42 peptides, total tau and tau phosphorylated at Thr181 (p-Tau181) from cerebrospinal fluid (CSF) samples obtained by lumbar puncture (LP). Phospho-Tau 217 (p-Tau217) is a new biomarker that could be measured in plasma. The aim of this study is to compare the performances of plasma p-Tau217 with those of the reference CSF biomarkers in 150 patients recruited in the memory center of CHU Amiens (France). The study will be conducted during 18 months. The inclusion will be proposed to all patients for whom an indication of lumbar puncture / CSF is raised in a context of clinical suspicion of AD. During the daily hospitalization during which CSF will be collected for the "classical" biomarkers testing, a single tube of blood will be collected (anticoagulant EDTA, collected for p-Tau 217 analysis). The performances of CSF and plasma pTau 217 will be compared with the clinical diagnosis of AD (+, -, or indeterminate).

Clinical Aspects, Management and Surveillance of Febrile Illnesses in DRC

The epidemiology and outcome of febrile illnesses in the Democratic Republic of Congo (DRC) is poorly documented. The FIKI² study, a prospective observational study of community-acquired febrile illnesses coordinated by ITM and INRB and conducted at 2 clinical sites from 2021 to 2023, has deepened the knowledge of clinical presentation, etiology, outcome and profile of inflammatory/infectious biomarkers (white blood cells and C-reactive protein, or CRP). The management of febrile illnesses remains fraught with clinical challenges. Overuse of antibiotics in primary care remains a reality in the field, and has been observed in several studies, including FIKI². A number of initiatives are underway to address this problem, such as the use of biomarkers, the development of treatment guidelines and electronic decision support systems. The FIKI² study highlighted the potential role of CRP in rationalizing antibiotic use. In parallel, the 'AWARE antibiotic book' was published at the end of 2022 by the WHO, providing recommendations on the choice (or otherwise) of antibiotic therapy for over 30 common clinical infections, in both primary care and hospital settings. Based on the results of the FIKI² study, the main aim of the FI-CARE study is to investigate the impact of these new tools (CRP biomarker, AWARE antibiotic book, and electronic decision support systems) on first-line antibiotic use. Secondly, the study will consolidate previous results from FIKI² sites in terms of monitoring the etiologies of community-acquired febrile illnesses (particularly arboviruses); and reinforce this monitoring at new sites (depending on opportunities). This complementary study will also pursue FIKI²'s strategic objectives of strengthening clinical research capacity and consolidating biobanks in the DRC. FI-CARE is a prospective, observational, multicenter cohort study of adults and children presenting to the emergency department or outpatient clinic with community-acquired febrile illness. A laboratory component with sample storage in a biobank is added in a modular fashion according to laboratory and research capacities, epidemiological interest and available funds.

Comparison of Aquaporin -4, -5, -9 and IL-8 Levels in GCF, Dentin Fluid and Pulp Samples

This study aimed to compare the changes in AQP -4, -5, -9, and IL-8 levels in pulp tissue, GCF, and dentin fluid samples routinely obtained during the treatment of healthy and symptomatic teeth diagnosed with irreversible pulpitis and investigate whether there is a correlation between them. A total of 70 patients aged 18-64 years with healthy (Group 1) and symptomatic irreversible pulpitis (Group 2) diagnosed at Kırıkkale University, Faculty of Dentistry, Department of Endodontics who will undergo routine root canal treatment will be included in the study, with a minimum of 35 participants for each group. Before starting treatment, DOS samples will be taken from healthy, symptomatic, irreversible pulpitis-diagnosed teeth and teeth contralateral to these teeth. A dentin fluid sample will be taken by holding the membrane on the dentin surface, and the pulp tissue will be removed and transferred to Eppendorf tubes. The treatment process will be completed by applying routine root canal procedures to the teeth. The samples' Aquaporin -4, -5, -9, and IL-8 levels will be analyzed by specific enzyme-linked immunosorbent assay (ELISA).

Influence of Timing of Implant Placement on Early Healing Molecular Events

Dental implants have been on the market for several years and they are routinely used to replace single/multiple missing teeth with a high success rate. However, there is still a limited number of studies comparing the influence of timing of implant placement on wound healing. In addition, there is no data available on the signaling pathways and the expression of healing biomarkers involved in the early stages of osseointegration after immediate implant placement (IP) or delayed implant placement (DP). The primary objective of this study is to describe changes in the expression of inflammatory, angiogenesis and osseous biomarkers of saliva at 1, 3, 7, 15 and 30 days and of PICF at 3, 7, 15 and 30 days after immediate implant placement (IP) compared with delayed placement (DP).

Combining Biomarkers and Electronic Risk Scores to Predict AKI in Hospitalized Patients

The study's objective is to evaluate the additive value of renal biomarkers (from blood and urine) for identifying individuals at high risk for severe acute kidney injury (AKI) above that of a novel natural language processing (NLP)-based AKI risk algorithm. The risk algorithm is based on electronic health records (EHR) data (labs, vitals, clinical notes, and test reports). Patients will enroll at the University of Chicago Medical Center and the University of Wisconsin Hospital, where the risk score will run in real time. The risk score will identify those patients with the highest risk for the future development of Stage 2 AKI and collect blood and urine for biomarker measurement over the subsequent 3 days.

Detection of Disease Marker Factors in Cyst Fluid

The purpose of this observational study is to examine the cyst fluid obtained after a puncture procedure performed for cyst diagnosis in participants with cystic lesions on clinical and radiological examination.The main question it aims to answer is: \- What is the exact mechanism of formation of odontogenic cysts? Biomarkers in the cyst fluid obtained after a puncture procedure performed as part of the diagnosis and treatment process of odontogenic cysts will be examined. The aim of this study is to gain insight into cyst pathology by examining the levels of biomarkers in odontogenic cyst fluid.

The Relation of Albumin/Globulin Ratio and Platelet/Albumin Ratio to Lupus Nephritis

Albumin/globulin ratio and platelet/albumin ratio as a predictive non-invasive biomarker for lupus nephritis (LN) presence and severity

Vanderbilt Memory and Aging Project

This study will use an observational cohort to cross-sectionally and longitudinally relate vascular health to clinical, imaging, and biological markers of early Alzheimer's disease and cerebrovascular disease among aging adults. Adjusting for relevant clinical covariates, we will test the hypothesis that vascular health is associated with clinical, brain magnetic resonance imaging (MRI), neuropsychological, and cerebrospinal fluid markers of early cerebrovascular and Alzheimer's disease changes (i.e., prior to the onset of significant cognitive decline or dementia). Secondarily, we will examine medical and genetic factors that might mediate associations between vascular health and brain aging, such as inflammatory processes, insulin resistance, and genetic factors (e.g., APOE, a susceptibility risk factor for dementia). Findings will advance knowledge regarding the role that vascular health plays in brain aging.

Effect of Bio-C Temp Versus Calcium Ydroxide as Intracanal Dressings on Postoperative Pain Intensity and Periapical MMP-9 Level in Patients With Necrotic Pulp

To compare the effect of Bio-C Temp Bioceramic intracanal dressing versus calcium hydroxide as intracanal medicaments on: * Intensity of postoperative pain * levels of MMP -9 in Periapical Fluids.

Comparison of the Effects of Aerobic-Anaerobic Exercises on Hormonal and Immune Biomarkers

This study aims to compare the effects of aerobic and anaerobic exercise on hormonal, immunological, and metabolic biomarkers in young individuals using blood and saliva samples. It will also assess participants' physical activity levels, depression levels, and general lifestyle habits to explore their relationship with biomarker profiles. Biomarkers such as testosterone, progesterone, cortisol, IgA, alpha-amylase, insulin, lactate, and various inflammatory cytokines will be measured using ELISA. The study seeks to evaluate the physiological and psychosocial effects of different types of exercise in a holistic manner.

Exploring the Predicting Biomarkers From Mild Cognitive Impairment to Dementia (EBMID)

Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects more than 15% of the population over the age of 60 in China. About 15% patients with MCI could progress into dementia after two years and about one-third develop into dementia within five years, which will lead to suffering, as well as staggering economic and care burden. So, exploring the predicting biomarkers from MCI to dementia to identify and delay progression to dementia at an early stage is of great social and clinical significance. Some reports based on a single neural biomarker suggest that risk models can predict the conversion of MCI to dementia, but no widely recognized prediction models basing on multiple complex markers have been used in clinical practice. The objectives of this study are to outline the spectrum of MCI transforming into dementia through a 5-year prospective longitudinal cohort study; Secondly, screening biomarkers for MCI transmit to dementia are based on clinical symptoms, neuropsychology, neuroimaging, neuroelectrophysiology, and humoral markers tests data.

Fruit and Vegetable Biomarker Discovery

The purpose of this research is to find a set of markers in the blood and/or urine that can be linked to consumption of specific fruits and vegetables. This will allow for better understanding of the link between diet and health-related outcomes. Furthermore, the results of this study will lead to the development of new methods to evaluate the nutritional status of individuals in both community and clinical settings. Food frequency questionnaires and diaries/recalls can be affected by intentional or unintentional misreporting, and thus can create errors in determining nutritional status. This study will lead to the development of an objective way to assess the consumption of specific fruits and vegetables by the general population.

The Exploration of OX40 (CD134) Expression Levels in Sarcoma Specimens and Its Clinical Application in Prognosis Determination

This study aims to investigate the expression of OX40 (CD134) in sarcomas and its impact on prognosis, with the goal of identifying novel biomarkers for early resistance detection and optimizing treatment strategies for sarcoma patients. Sarcomas are a highly heterogeneous group of malignant tumors, for which current treatment options are often suboptimal in certain patients, and effective biomarkers to guide therapy are lacking. As a T-cell costimulatory receptor, OX40 plays a significant role in immune regulation across various solid tumors and holds promise as a potential therapeutic target. The researcher's team has previously identified high OX40 expression in sarcomas through database analysis and validated the therapeutic efficacy of antibody-drug conjugates targeting OX40 in in vivo experiments using sarcoma cell lines in murine models. This study will evaluate the mRNA expression levels of OX40 in tumor tissues from sarcoma patients and assess OX40 protein expression using immunohistochemical staining. By integrating these findings with clinical and pathological data, the study will explore the potential of OX40 expression levels in tumor tissues as biomarkers for predicting treatment response and prognosis in primary bone tumors. The results aim to provide scientific evidence for the clinical application of OX40-targeted therapies and to propose novel therapeutic strategies to improve survival outcomes in sarcoma patients.

Map of Tumor Genetic Actionability in Argentina

The study of the human genome laid the foundations for the search for a large number of molecular alterations related to different diseases. The Precision medicine allows us to know molecular alterations that can be detected and targeted for therapeutic purposes. There is little data in Argentina about the incidence and frequencies of alterations molecules associated with the most frequent tumors. Through the selection of a gene panel, analysis of the genetic information obtained analysis allows classifying tumors from a point of view therapeutic. On the other hand, through the same panel, markers of resistance to drugs that allow the incorporation of retreatment therapies. Together with the proposed panel, the ancestry of the patients will be evaluated to determine whether the frequencies of molecular alterations vary between the different ethnic origins of the country.

IL-40 and IL-41 Levels in Sepsis, Septic Shock, and Healthy Individuals

This study aims to investigate the blood levels of two recently identified immune-related proteins, Interleukin-40 (IL-40) and Interleukin-41 (IL-41), in patients with sepsis and its more severe form, septic shock. Sepsis is a serious condition caused by an abnormal immune response to infection, which can lead to organ dysfunction. Septic shock represents an advanced stage of sepsis, characterized by significantly higher mortality risk. IL-40 and IL-41 are newly discovered molecules that are thought to play important roles in the immune system. In this study, the blood concentrations of IL-40 and IL-41 in patients diagnosed with sepsis or septic shock will be measured and compared with those in healthy individuals. The findings may contribute to understanding whether these proteins can be used as biomarkers in the diagnosis or monitoring of treatment in sepsis-related conditions.

Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of MPD-1 in Patients With Advanced Solid Tumor

A Phase I, Open-label, Single-center, Dose-escalation and Dose-finding Clinical trial to evaluate the safety, tolerability and pharmacokinetics of MPD-1 in patients with advanced solid tumor

Application of Salivary Biomarkers in Risk Assessment for Oral Diseases in Children With Type 1 Diabetes

This research contributes to a deeper understanding of the etiopathogenesis of periodontal and other oral diseases in children with T1D. By analyzing the composition of the salivary microbiome and detecting pathogenic and opportunistic microorganisms, the study aims to develop targeted preventive strategies. The findings could lead to personalized preventive programs, improving early diagnosis and oral health management in this vulnerable population.This study hypothesizes that children with Type 1 Diabetes (T1D) will exhibit significantly different oral health parameters compared to healthy peers. Specifically: 1. Higher KEP and KEPS index values (Klein-Palmer system) indicating increased caries incidence. 2. Higher Silness and Loe plaque index and Loe and Silness gingival index, suggesting greater plaque accumulation and gingival inflammation. 3. Lower salivary buffering capacity and pH, potentially contributing to an increased risk of oral diseases. 4. A distinct microbial profile, with a greater presence of pathogenic and opportunistic bacteria. 5. A significantly higher Candida albicans count in the saliva. These findings could provide insights into the oral health challenges faced by children with T1D and guide preventive strategies. This study explores how saliva can help assess the risk of dental and gum problems in children with Type 1 Diabetes (T1D). Researchers will analyze saliva samples to identify specific markers that may indicate a higher chance of cavities, gum disease, and oral infections. The goal is to develop early detection and prevention methods to improve oral health care for children with T1D. The study will include 112 children aged 6 to 18. Half of them have Type 1 Diabetes, while the other half are healthy children of the same age and gender for comparison. All participants will be selected from the Clinic for Dentistry of Vojvodina, ensuring they are not currently sick and have not taken antibiotics in the past month. Children with other serious health conditions, fixed braces, or difficulty cooperating will not be included. Researchers will examine different factors that could affect oral health in children with T1D, including saliva acidity (pH), its ability to neutralize acids, the presence of bacteria and fungi, and the condition of teeth and gums. They expect that children with T1D will have: 1. More cavities compared to healthy children. 2. More plaque buildup on teeth and greater gum inflammation. 3. Lower saliva protection against acids, increasing the risk of dental problems. 4. A different mix of bacteria in the mouth, with more potentially harmful microbes. 5. Higher levels of the fungus Candida albicans in saliva. The findings from this study may help better understand oral health challenges in children with T1D and lead to improved prevention and treatment strategies.

Predictive Value of Neurovascular Coupling in Infants With COngenital Heart Disease

Infants with congenital heart disease (CHD) are at increased risk for delayed neurodevelopment. Multiple etiological explanations have been proposed, as there seems to be a multifactorial interplay of both prenatal and perioperative factors. The main goal of this research project is to focus on peri-operative physiological risk factors in infants with CHD which impair functional brain maturation or elicit brain injury, and subsequently creating a risk model and guidelines for standardized developmental follow-up in this population. PART 1: investigation of cerebral autoregulation and neurovascular coupling The homeostasis in cerebral blood supply regardless of perfusion pressure, is called Cerebral autoregulation (CAR). Neurovascular coupling (NVC) is the phenomenon in which blood supply increases as a result of increased brain activity in a specific area. At different times in the perioperative phase, these regulatory mechanisms will be estimated based on Electroencephalography (EEG) and Near Infrared Spectroscopy (NIRS), in addition to hemodynamic parameters. PART 2: cell-free DNA (cfDNA) extraction. Non-invasive monitoring of neuronal degeneration can be performed using cfDNA extraction techniques. Serial measurements of neuronal cfDNA will be used to determine whether and when this neuronal damage has occurred. PART 3: Prognosis and outcome. These risk factors, supplemented with demographic factors and medications administered, will be combined in an Artificial Intelligence-driven model, thus establishing a risk model for neurodevelopmental outcome. This model will be compared to the current standard-of-care, both structural imaging (ultrasound and MRI) and a clinical developmental assessment at 9 and 24 months of age (Bayley Scales of Infant Development-III).

Genomic and Methylation Markers in SCLC and LCNEC for Chemo-Immunotherapy Resistance Prediction (STRATUS)

The goal of this observational study is to understand how genomic and epigenetic factors contribute to resistance against chemo-immunotherapy in adults diagnosed with extensive-stage small cell lung cancer (ES-SCLC) or metastatic large cell neuroendocrine carcinoma (LCNEC). Both ES-SCLC and LCNEC are aggressive forms of lung cancer with limited treatment options and poor prognosis. While initial responses to chemo-immunotherapy are often promising, most patients develop resistance within a few months, resulting in disease progression and limited survival. This study seeks to explore the molecular and cellular changes that drive resistance, providing insights that could guide more personalized and effective treatment strategies in the future. The study focuses on identifying genomic and methylation signatures, as well as analyzing circulating tumor cells (CTCs) and tumor DNA (ctDNA), to better understand the mechanisms of resistance. By collecting and analyzing these biomarkers over time, researchers aim to identify patterns that distinguish patients who benefit long-term from therapy from those who experience early resistance. These findings may pave the way for new diagnostic tools and therapies to predict and overcome resistance to chemo-immunotherapy. The main questions this study seeks to answer are: Are there specific genomic or methylation patterns that predict resistance to chemo-immunotherapy in ES-SCLC and LCNEC? How are circulating tumor cells (CTCs) and tumor DNA (ctDNA) associated with disease progression, treatment response, and survival? What molecular differences exist between patients who respond long-term and those who develop resistance early in their treatment? Participants will: Provide blood and tumor tissue samples before treatment to establish baseline molecular profiles. Undergo follow-up visits every 9 weeks during treatment, where additional blood samples and imaging tests will be collected to monitor disease progression and treatment response. Optionally provide tissue samples through re-biopsy if the disease progresses, enabling researchers to compare changes in tumor biology over time. All blood and tissue samples will be de-identified and securely stored for genomic and epigenetic analyses. Blood samples will be examined for circulating tumor cells and tumor DNA, while tumor tissue samples will undergo in-depth genomic and methylation profiling. Researchers will use advanced molecular and bioinformatics techniques to uncover specific patterns associated with resistance, aiming to improve current treatment strategies and develop more precise therapies. The study will analyze data from patients over three years, encompassing various stages of treatment and disease progression. By examining longitudinal samples, the study aims to capture the dynamic changes that occur in the tumor microenvironment and how these relate to treatment outcomes. This research is particularly important because current treatment options for ES-SCLC and LCNEC are limited, and there are no established methods to predict which patients will respond to chemo-immunotherapy. Identifying biomarkers of resistance could transform clinical care, allowing oncologists to tailor treatments to individual patients' molecular profiles and improve survival outcomes. Ultimately, the findings from this study could lead to the development of new biomarkers for resistance, improve early detection of treatment failure, and provide the foundation for novel therapies targeting resistant cancer cells. By addressing a critical gap in the understanding of resistance mechanisms, the STRATUS trial has the potential to significantly advance the field of personalized oncology.