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After pediatric liver transplantation (pLT), children undergo life-long immunosuppression since reliable biomarkers for the assessment of rejection probability are scarce. In the multicenter (n = 7) prospective clinical cohort "ChilSFree" study, we aimed to characterize longitudinal dynamics of soluble and cellular immune mediators during the first year after pLT and identify early biomarkers associated with outcome. Using a Luminex-based multiplex technique paired with flow cytometry, we characterized longitudinal dynamics of soluble immune mediators (SIMs, n = 50) and immune cells in the blood of 244 patients at eight visits over 1 year: before, and 7/14/21/28 days and 3/6/12 months after pLT. The unsupervised clustering of patients based on SIM profiles revealed six unique SIM signatures associated with clinical outcome. From three signatures linked to improved outcome, one was associated with 1-year-long rejection-free survival and stable graft function and was characterized by low levels of pro-inflammatory SIMs (CXCL8/9/10/12, CCL7, SCGF-β, sICAM-1), and high levels of regenerative (SCF, TNF-β) and pro-apoptotic (TRAIL) SIMs (all, p <0.001, fold change >100). Of note, this SIM signature appeared 2 weeks after pLT and remained stable over the entire year, pointing towards its potential as a novel early biomarker for minimizing or weaning immunosuppression. In the blood of these patients, a higher frequency of CD56bright natural killer cells (p <0.01), a known hallmark also associated with operationally tolerant pLT patients, was detected. The concordance of the model for prediction of rejection based on identified SIM signatures was 0.715, and 0.795, in combination with living-related transplantation as a covariate, respectively. SIM blood signatures may enable the non-invasive and early assessment of rejection risks in the first year after pLT, paving the way for improved clinical management. ChilSFree represents the largest pediatric liver transplant (pLT) cohort with paired longitudinal data on soluble immune mediators (SIMs) and immune phenotyping in the first year after pLT. SIM signatures allow for the selection of rejection-free patients 2 weeks after pLT independently of patient diagnosis, sex, or age. The SIM signatures may enable the non-invasive and early assessment of rejection risks, paving the way for minimization or withdrawal of immunosuppression after pLT. [Display omitted] • Early long-term predictive biomarkers for rejection-free survival post-pLT are missing. • Longitudinal SIM and immune phenotyping data up to 1-year post-pLT were acquired. • SIM signatures appearing 2 weeks post-pLT identify rejection-free patients. • SIM signatures can rank rejection risks and may facilitate optimization of immunosuppression. • Early intense immunosuppression may prevent development of favorable SIM signatures. [ABSTRACT FROM AUTHOR]

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell‐free DNA (cfDNA) methylomes as a potential source of biomarkers for the non‐invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high‐risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway‐specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate‐rich 1 (ERICH1) methylation discriminated high‐risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non‐invasive detection of colorectal serrated lesions. [ABSTRACT FROM AUTHOR]

Introduction: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers. Objectives: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population. Methods: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy® OMNI® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching. Results: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes. Conclusions: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization. [ABSTRACT FROM AUTHOR]

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell‐free DNA (cfDNA) methylomes as a potential source of biomarkers for the non‐invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high‐risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway‐specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate‐rich 1 (ERICH1) methylation discriminated high‐risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non‐invasive detection of colorectal serrated lesions.

Simple Summary: In recent years, liquid biopsy has been introduced as a new method for the detection and management of cancer, but the studies on oral squamous cell carcinoma (OSCC) are lacking conclusive evidence. The aim of this study was to evaluate the expression of six circulating salivary and plasmatic miRNAs (-21, -31, -138, -145, -184, and -424) as diagnostic biomarkers in patients affected by OSCC and by oral potentially malignant disorders (OPMDs). Our results showed that liquid biopsy from saliva may be a useful tool for the identification of these biomarkers; in particular, miR-138 and miR-424 showed decreased expression levels in saliva samples in OSCC and OPMD patients compared to healthy controls. The introduction of liquid biopsy in daily clinical practice could revolutionize the approach to oral lesions by allowing the mass screening, stratification and monitoring of patients at risk, the monitoring of the response to treatment and the early identification of any recurrences. This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs. [ABSTRACT FROM AUTHOR]

Introduction: Non-invasive hormone assessment is growing in interest as producers and livestock researchers seek new methods to assess animal welfare. Non-invasive wool assessment offers long-term, historic reflections of hormone concentration at the scale of weeks and months - and are not limited by sampling stress - thus making wool an appropriate tissue for long-term hormone analysis. This pilot study quantified cortisol and testosterone concentrations of ram fleece and determined if there is a significant difference between segments of the sample staple, and whether there is a correlation between hormones. Cortisol is a glucocorticoid produced within the adrenal glands and secreted in anticipation of or in response to a stressor. Testosterone is an androgen mainly synthesised within the testes of males and responsible for several critical functions including regulation of muscle growth, libido and spermatogenesis. Methods: In our study, 70 topknot wool samples were collected from rams on a commercial stud property in Dirranbandi, Queensland, Australia. Of these animals, 12 samples were selected at random to undergo cortisol and testosterone quantification. In the laboratory, a single, intact staple was isolated from the total sample, divided into 10 mm segments and prepared for their respective (cortisol or testosterone) immunoassays. Results: No significant difference (p > 0.05) was found between wool segments for either cortisol or testosterone, however, statistical differences (p < 0.05) were found between individuals for both hormones. A strong positive correlation (R2 = 0.9173, p < 0.05) was found between wool cortisol and testosterone concentrations. Discussion: In summary, this study reveals the major future possibilities for noninvasive wool hormone assessment in merino rams. [ABSTRACT FROM AUTHOR]

Cancer remains a global health challenge, necessitating continuous advancements in diagnostic and treatment strategies. This review focuses on the utility of non-invasive biomarkers in cancer diagnosis and treatment, their role in early detection, disease monitoring, and personalized therapeutic interventions. Through a systematic review of the literature, we identified 45 relevant studies that highlight the potential of these biomarkers across various cancer types, such as breast, prostate, lung, and colorectal cancers. The noninvasive biomarkers discussed include liquid biopsies, epigenetic markers, noncoding RNAs, exosomal cargo, and metabolites. Notably, liquid biopsies, particularly those based on circulating tumour DNA (ctDNA), have emerged as the most promising method for early, non-invasive cancer detection due to their ability to provide comprehensive genetic and epigenetic information from easily accessible blood samples. This review demonstrates how non-invasive biomarkers can facilitate early cancer detection, accurate subtyping, and tailored treatment strategies, thereby improving patient outcomes. It underscores the transformative potential of non-invasive biomarkers in oncology, highlighting their application for enhancing early detection, survival rates, and treatment precision in cancer care. [ABSTRACT FROM AUTHOR]

Background and Aim: Colorectal cancer (CRC) screening programs are most effective at reducing disease incidence and mortality through sustained screening participation. A novel blood test modality is being explored for CRC screening, but it is unclear whether it will provide sustained screening participation. This study aimed to investigate whether a circulating tumor DNA (ctDNA) blood test improved CRC screening re‐participation when compared with a fecal immunochemical test (FIT) and to define the predictors of sustained CRC screening in an Australian population. Methods: South Australians who initially participated in CRC screening using a ctDNA blood test (n = 36) or FIT (n = 547) were offered the same CRC screening test approximately 2 years later through an extended phase of a randomized controlled trial. Surveys collected demographic, psychosocial, and clinical information. Predictors of CRC screening re‐participation were explored using chi‐square, Wilcoxon tests, and logistic regression. Results: Participants offered a second ctDNA blood test were equally likely to re‐participate in CRC screening as those who completed a FIT in the first round and who were offered the same test (61% vs 66% re‐participation respectively, P = 0.6). CRC fatalism, health activation, and self‐efficacy were associated with repeated screening participation. Test awareness was predictive of repeated FIT‐based CRC screening. Conclusions: Targeted interventions to improve CRC screening awareness and increase patient health activation may improve CRC screening adherence. A ctDNA blood test may be a suitable CRC screening option to maintain CRC screening adherence in people who do not participate in screening with FIT. [ABSTRACT FROM AUTHOR]

Globin adducts of various chemicals, persisting in organism over the whole lifetime of erythrocytes, have been used as biomarkers of cumulative exposures to parent compounds. After removal of aged erythrocytes from the bloodstream, cleavage products of these adducts are excreted with urine as alternative, non-invasively accessible biomarkers. In our biomonitoring studies on workers exposed to ethylene oxide, its adduct with globin, N -(2-hydroxyethyl)valine, and the related urinary cleavage product N -(2-hydroxyethyl)-L-valyl-L-leucine have been determined. To describe a toxicokinetic relationship between the above types of biomarkers, a general compartmental model for simulation of formation and removal of globin adducts has been constructed in the form of code in R statistical computing environment. The essential input variables include lifetime of erythrocytes, extent of adduct formation following a single defined exposure, and parameters of exposure scenario, while other possible variables are optional. It was shown that both biomarkers reflect the past exposures differently as the adduct level in globin is a mean value of adduct levels across all compartments (subpopulations of erythrocytes of the same age) while excretion of cleavage products reflects the adduct level in the oldest compartment. Application of the model to various scenarios of continuous exposure demonstrated its usefulness for human biomonitoring data interpretation. • Compartmental model to simulate formation and elimination of adducts with globin. • Toxicokinetics of the adducts in globin and their cleavage products in the urine. • Non-invasive biomonitoring to assess long-term exposures to electrophilic chemicals. [ABSTRACT FROM AUTHOR]

Background: There are currently no laboratory tests that can accurately predict the likelihood of developing acute graft‐versus‐host disease (aGVHD), a patient's response to treatment, or their survival chance. This research aimed to establish circulating miRNAs as diagnostic, prognostic, or predictive biomarkers of aGVHD. Methods: In a prospective cohort, we studied the incidence of cutaneous aGVHD in AML patients undergoing allo‐HSCT at Shariati Hospital in Tehran, Iran during 2020–2023. Patients with cutaneous aGVHD were labeled as the case group, while patients without cutaneous aGVHD were selected as the control group. Accordingly, the expression levels of six significant miRNAs (miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, miR‐548a‐3p) were evaluated by quantitative reverse transcription–polymerase chain reaction (RTqPCR) in three different time‐points: before transplantation, on day 14 and day 21 after transplantation. Results: The levels of plasma miR‐455‐3p, miR‐5787, miR‐638, and miR‐3613‐5p were significantly downregulated, while miR‐548a‐3p, and miR‐6511b‐5p were significantly upregulated in individuals with cutaneous aGVHD in comparison to patients without GVHD. Additionally, the possibility for great diagnostic accuracy for cutaneous aGVHD was revealed by ROC curve analysis of differentially expressed miRNAs (DEMs). Conclusion: The study findings encourage us to hypothesize that the aforementioned miRNAs may contribute to the predominance of aGVHD, particularly low‐grade cutaneous aGVHD. [ABSTRACT FROM AUTHOR]

Liver fibrosis is the result of chronic liver injury of different etiologies produced by an imbalance between the synthesis and degeneration of the extracellular matrix and dysregulation of physiological mechanisms. Liver has a high regenerative capacity in the early stage of chronic diseases so a prompt liver fibrosis detection is important. Consequently, an easy and economic tool that could identify patients with liver fibrosis at the initial stages is needed. To achieve this, many non-invasive serum direct, such as hyaluronic acid or metalloproteases, and indirect biomarkers have been proposed to evaluate liver fibrosis. Also, there have been developed formulas that combine these biomarkers, some of them also introduce clinical and/or demographic parameters, like FIB-4, non-alcoholic fatty liver disease fibrosis score (NFS), enhance liver fibrosis (ELF) or Hepamet fibrosis score (HFS). In this manuscript we critically reviewed different serum biomarkers and formulas for their utility in the diagnosis and progression of liver fibrosis. [ABSTRACT FROM AUTHOR]

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval. [ABSTRACT FROM AUTHOR]

Background of the Study: Mammograms are sometimes met with issues of overdiagnosis and underdiagnosis; therefore, they are less reliable in identifying cancer in women with dense breasts. As a result, it is critical to be aware of other sensitive screening techniques for the early diagnosis of breast cancer. Aim: The ultimate objective of this study was to assess the knowledge of nursing undergraduates regarding non-invasive biomarkers, such as volatile organic compounds in breath, nipple aspirate fluid, sweat, urine, and tears, for the early detection of breast cancer to help improve patient care, determine the risk factors, and encourage practice of breast self-examination. Methods: Cross-sectional research was done in the Department of Nursing at Farasan campus using a self-structured questionnaire as the study tool. A total of 260 students willingly participated. The study tool had evaluation questions focused on the non-invasive biomarkers of breast cancer, risk factors, and breast self-examination practices to collect data. The data were subjected to descriptive and inferential statistics. The statistical significance was calculated at P <.05. Data analyses were done using Microsoft Excel (2013). Results: A s ignificant knowledge gap existed among the study participants about the non-invasive biomarkers of breast cancer. A lesser percentage of students (25%) stated that they do breast self-examination on a monthly basis. The most common reasons for not doing the breast self-examination were "not knowing how to do the breast self-examination" (77.3%), fear of a positive diagnosis (53.9%), thinking that they are not at risk as all were in their teens and hence not required (44.7%), and lack of time (48.7%). Age and frequency of breast self-examination were significantly associated (P <.05) as those few students (22.7%) who were doing breast self-examination practices every 2–4 months belonged to a higher study year. Furthermore, knowledge regarding incidence rates and health care expenditure by the government on breast cancer was also significantly low (P <.05). Conclusions: Outcomes would help prioritize actions to help future nurses better understand breast cancer, allowing them to extend patient care in the best way possible. [ABSTRACT FROM AUTHOR]

IntroductionNon-invasive hormone assessment is growing in interest as producers and livestock researchers seek new methods to assess animal welfare. Non-invasive wool assessment offers long-term, historic reflections of hormone concentration at the scale of weeks and months - and are not limited by sampling stress - thus making wool an appropriate tissue for long-term hormone analysis. This pilot study quantified cortisol and testosterone concentrations of ram fleece and determined if there is a significant difference between segments of the sample staple, and whether there is a correlation between hormones. Cortisol is a glucocorticoid produced within the adrenal glands and secreted in anticipation of or in response to a stressor. Testosterone is an androgen mainly synthesised within the testes of males and responsible for several critical functions including regulation of muscle growth, libido and spermatogenesis.MethodsIn our study, 70 topknot wool samples were collected from rams on a commercial stud property in Dirranbandi, Queensland, Australia. Of these animals, 12 samples were selected at random to undergo cortisol and testosterone quantification. In the laboratory, a single, intact staple was isolated from the total sample, divided into 10 mm segments and prepared for their respective (cortisol or testosterone) immunoassays.ResultsNo significant difference (p > 0.05) was found between wool segments for either cortisol or testosterone, however, statistical differences (p

Cancer remains a global health challenge, necessitating continuous advancements in diagnostic and treatment strategies. This review focuses on the utility of non-invasive biomarkers in cancer diagnosis and treatment, their role in early detection, disease monitoring, and personalized therapeutic interventions. Through a systematic review of the literature, we identified 45 relevant studies that highlight the potential of these biomarkers across various cancer types, such as breast, prostate, lung, and colorectal cancers. The non-invasive biomarkers discussed include liquid biopsies, epigenetic markers, non-coding RNAs, exosomal cargo, and metabolites. Notably, liquid biopsies, particularly those based on circulating tumour DNA (ctDNA), have emerged as the most promising method for early, non-invasive cancer detection due to their ability to provide comprehensive genetic and epigenetic information from easily accessible blood samples. This review demonstrates how non-invasive biomarkers can facilitate early cancer detection, accurate subtyping, and tailored treatment strategies, thereby improving patient outcomes. It underscores the transformative potential of non-invasive biomarkers in oncology, highlighting their application for enhancing early detection, survival rates, and treatment precision in cancer care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023474749 PROSPERO, identifier CRD42023474749.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of exacerbation and remission, making disease monitoring and management challenging. Endoscopy, the gold standard for assessing disease activity and severity, involves invasive procedures and is associated with patient discomfort and risks. Using machine learning (ML) to combine fecal calprotectin with other clinical or biological tests can significantly enhance the non-invasive prediction of endoscopic disease activity (EDA) in UC. Aim: To prove that by fusing fecal calprotectin with other clinical data into an ML model, the performance of the non-invasive prediction of EDA can be significantly improved. Methods: We conducted a prospective, observational, single-center study encompassing 103 patients diagnosed with UC. We employed multilayer perceptron models as the core ML algorithm for predicting EDA. For the constructed models, we utilized the varImp function from the caret library in R to assess the significance of each variable in predicting the outcome. Results: Calprotectin as a sole predictor obtained an accuracy of 70% and an area under the curve (AUC) of 0.68. Combining calprotectin with the list of selected predictors that were fed to the MLP models improved accuracy and the AUC. The accuracy of the algorithm on the test set was 85%. Similarly, the AUC increased to 0.93. This is the first study to propose the use of calprotectin as a predictor in an ML model to estimate UC endoscopic disease activity. Conclusion: The deployment of this ML model can furnish doctors and patients with valuable evaluation of endoscopic disease activity which can be highly beneficial for individuals with UC who need long-term treatment. [ABSTRACT FROM AUTHOR]

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MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than −1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth leading cause of cancer death among men worldwide. Biomarkers are an important tool in the early detection of PCa. Prostate-specific antigen (PSA) is one of the oldest biomarkers for the early detection of PCa. Digital rectal exam (DRE) is another screening test for PCa detection, which is considered as an irritating experience for patients. Biopsy is still the most reliable method for PCa diagnosis; however, patients are prone to complications. Therefore, developing non-invasive and accurate methods for PCa screening seems urgent to avoid unnecessary biopsies. There has been remarkable development in PCa molecular biomarkers discovery, largely through progress in omics technologies. Due to the many benefits of liquid biopsies, a significant set of PCa diagnostic kits have been developed using urine samples. Despite the unique benefits of these kits, there are still many challenges to their widespread use in clinics. Here, we have reviewed the latest developments of PCa biomarkers in liquid biopsies. Methods: Literature on biomarkers for diagnosis of PCa was reviewed during the past two decades. Results: PSA, PHI, PCA3, and 4K score are among the commonly used markers for PCa diagnosis which have been used over a long-moderate length of time with multiple studies on their performance. We performed a review of their performance. Newer markers are among RNA and DNA markers. Multiple non-coding RNAs (mi-RNAs) were reviewed and their performance on Pca diagnosis was reviewed. Long noncoding RNAs (Lnc RNAs) including PlncRNA-1, HOTAIR, SchLAP-1, MALAT1, MEG3, and PRCAT17.3 were summarized. mRNA markers including TMPRSS2:ERG, and HOXC6 were presented. DNA-based markers including PTEN, HOXB13, and BRCA2 were reviewed. Finally, the use of CircRNAs was reviewed for PCa diagnosis. Conclusion: Many reviewed RNA-based biomarkers have promising results in the diagnosis of PCa. [ABSTRACT FROM AUTHOR]

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

Abstract Objective The predictive biomarkers of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) still need to be further explored. This study aims to establish a new immune prognosis biomarker to predict the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors. Methods The subjects of this study were 151 HCC patients receiving ICIs at Harbin Medical University Cancer Hospital from January 2018 to December 2021. This study collected a wide range of blood parameters from patients before treatment and used Cox’s regression analysis to identify independent prognostic factors in blood parameters, as well as their β coefficient. The hepatocellular carcinoma immune prognosis score (HCIPS) was established through Lasso regression analysis and COX multivariate analysis. The cut-off value of HCIPS was calculated from the receiver operating characteristic (ROC) curve. Finally, the prognostic value of HCIPS was validated through survival analysis, stratified analyses, and nomograms. Results HCIPS was composed of albumin (ALB) and thrombin time (TT), with a cut-off value of 0.64. There were 56 patients with HCIPS

Liver fibrosis is the result of chronic liver injury of different etiologies produced by an imbalance between the synthesis and degeneration of the extracellular matrix and dysregulation of physiological mechanisms. Liver has a high regenerative capacity in the early stage of chronic diseases so a prompt liver fibrosis detection is important. Consequently, an easy and economic tool that could identify patients with liver fibrosis at the initial stages is needed. To achieve this, many non-invasive serum direct, such as hyaluronic acid or metalloproteases, and indirect biomarkers have been proposed to evaluate liver fibrosis. Also, there have been developed formulas that combine these biomarkers, some of them also introduce clinical and/or demographic parameters, like FIB-4, non-alcoholic fatty liver disease fibrosis score (NFS), enhance liver fibrosis (ELF) or Hepamet fibrosis score (HFS). In this manuscript we critically reviewed different serum biomarkers and formulas for their utility in the diagnosis and progression of liver fibrosis.

Abstract Background Eosinophilic esophagitis (EoE) is a chronic progressive inflammatory disease of the esophagus, characterized by extracellular matrix remodeling and fibrotic stricture formation. Disease monitoring requires multiple re-endoscopies with esophageal biopsies. Hence non-invasive methods for determining tissue fibrosis and treatment efficacy are warranted. Aims To investigate the ability of extracellular matrix proteins in serum as potential biomarkers of tissue remodeling and clinical, endoscopic, and histological disease outcomes in adult EoE patients. Methods Protein-fingerprint assays were used to measure neo-epitope specific fragments of collagen remodeling, human-neutrophil elastase degraded calprotectin, and citrullinated or non-citrullinated vimentin in the serum of an adult EoE-cohort. Biomarker analysis, symptoms, endoscopic features and histological disease activity (eosinophils(eos) per high-power-field(hpf)) were evaluated at baseline and after six weeks of dietary intervention. Results Patients with a baseline (Endoscopic Reference score) EREFS fibrosis subscore ≥ 2 presented with increased fibrolysis of cross-linked type III collagen (CTX-III) (p

Recent advances in diffusion imaging have given it the potential to non-invasively detect explicit neurobiological properties, beyond what was previously possible with conventional structural imaging. However, there is very little known about what cytoarchitectural properties these metrics, especially those derived from newer multi-shell models like Neurite Orientation Dispersion and Density Imaging (NODDI) correspond to. While these diffusion metrics do not promise any inherent cell type specificity, different brain cells have varying morphologies, which could influence the diffusion signal in distinct ways. This relationship is currently not well-characterized. Understanding the possible cytoarchitectural signatures of diffusion measures could allow them to estimate important neurobiological properties like cell counts, potentially resulting in a powerful clinical diagnostic tool. Here, using advanced diffusion imaging (NODDI) in the mouse brain, we demonstrate that different regions have unique relationships between cell counts and diffusion metrics. We take advantage of this exclusivity to introduce a framework to predict cell counts of different types of cells from the diffusion metrics alone, in a region-specific manner. We also outline the challenges of reliably developing such a model and discuss the precautions the field must take when trying to tie together medical imaging modalities and histology.

We aimed to conduct a state-of-the-art review of the current literature and offer further insights into the methodological aspects concerning induced sputum. The increasing popularity of sputum induction as a non-invasive and cost-effective method for obtaining lower airway secretions from patients who cannot produce sputum naturally has led to extensive research and applications in respiratory conditions like asthma and COPD. This technique allows for analysis of the cellular and biochemical components of the sputum to take place, providing insights into airway inflammation, immune cells, and help in predicting treatment response. Furthermore, induced sputum enables various analyses, including microRNA and gene expression studies and immunophenotyping. The procedure is generally safe and well tolerated, even in patients with airflow limitations; however, monitoring lung function is essential, especially in those with airway hyperresponsiveness. Optimal saline solution concentration and inhalation duration have been investigated, recommending a 15–20 min induction with hypertonic saline. Expectoration involves coughing at the end of each inhalation time. Careful handling during sputum processing is necessary for obtaining accurate results in cell cytology, immunocytochemistry, and in situ hybridization. Overall, induced sputum offers significant advantages as a preferred alternative for large-scale and repeated airway sampling, despite some technical demands and limitations.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2–3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

Objective: The predictive biomarkers of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) still need to be further explored. This study aims to establish a new immune prognosis biomarker to predict the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors. Methods: The subjects of this study were 151 HCC patients receiving ICIs at Harbin Medical University Cancer Hospital from January 2018 to December 2021. This study collected a wide range of blood parameters from patients before treatment and used Cox's regression analysis to identify independent prognostic factors in blood parameters, as well as their β coefficient. The hepatocellular carcinoma immune prognosis score (HCIPS) was established through Lasso regression analysis and COX multivariate analysis. The cut-off value of HCIPS was calculated from the receiver operating characteristic (ROC) curve. Finally, the prognostic value of HCIPS was validated through survival analysis, stratified analyses, and nomograms. Results: HCIPS was composed of albumin (ALB) and thrombin time (TT), with a cut-off value of 0.64. There were 56 patients with HCIPS < 0.64 and 95 patients with HCIPS ≥ 0.64, patients with low HCIPS were significantly related to shorter progression-free survival (PFS) (13.10 months vs. 1.63 months, P < 0.001) and overall survival (OS) (14.83 months vs. 25.43 months, P < 0.001). HCIPS has also been found to be an independent prognostic factor in this study. In addition, the stratified analysis found a significant correlation between low HCIPS and shorter OS in patients with tumor size ≥ 5 cm (P of interaction = 0.032). The C-index and 95% CI of the nomograms for PFS and OS were 0.730 (0.680–0.779) and 0.758 (0.711–0.804), respectively. Conclusions: As a new score established based on HCC patients receiving ICIs, HCIPS was significantly correlated with clinical outcomes in patients with ICIs and might serve as a new biomarker to predict HCC patients who cloud benefit from ICIs. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a chronic progressive inflammatory disease of the esophagus, characterized by extracellular matrix remodeling and fibrotic stricture formation. Disease monitoring requires multiple re-endoscopies with esophageal biopsies. Hence non-invasive methods for determining tissue fibrosis and treatment efficacy are warranted. Aims: To investigate the ability of extracellular matrix proteins in serum as potential biomarkers of tissue remodeling and clinical, endoscopic, and histological disease outcomes in adult EoE patients. Methods: Protein-fingerprint assays were used to measure neo-epitope specific fragments of collagen remodeling, human-neutrophil elastase degraded calprotectin, and citrullinated or non-citrullinated vimentin in the serum of an adult EoE-cohort. Biomarker analysis, symptoms, endoscopic features and histological disease activity (eosinophils(eos) per high-power-field(hpf)) were evaluated at baseline and after six weeks of dietary intervention. Results: Patients with a baseline (Endoscopic Reference score) EREFS fibrosis subscore ≥ 2 presented with increased fibrolysis of cross-linked type III collagen (CTX-III) (p < 0.01), whereas low CTX-III levels were observed in patients achieving histological remission (< 15 eos/hpf) (vs. no histological remission (p < 0.05). Progression of endoscopic fibrosis after intervention was associated with increased levels of type-III (PRO-C3) and -VI collagen (PRO-C6) formation (all; p < 0.05). A baseline EREFS inflammatory subscore ≥ 2 correlated with higher neutrophilic activity (Cpa9-HNE) at week 6 (p < 0.05). Moreover, increased degradation of type-III (C3M) and -IV (C4M/PRO-C4) collagens were associated with remission of food impaction after intervention (all; p < 0.05). Conclusion: Serum extracellular matrix remodeling proteins demonstrated potential as surrogate biomarkers for assessing histological disease remission, endoscopic fibrosis, and remission of symptoms of food impaction after diet intervention in adult EoE patients. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD. [ABSTRACT FROM AUTHOR]

The oral bacteriome, gut bacteriome, and gut mycobiome are associated with coronavirus disease 2019 (COVID‐19). However, the oral fungal microbiota in COVID‐19 remains unclear. This article aims to characterize the oral mycobiome in COVID‐19 and recovered patients. Tongue coating specimens of 71 COVID‐19 patients, 36 suspected cases (SCs), 22 recovered COVID‐19 patients, 36 SCs who recovered, and 132 controls from Henan are collected and analyzed using internal transcribed spacer sequencing. The richness of oral fungi is increased in COVID‐19 versus controls, and beta diversity analysis reveals separate fungal communities for COVID‐19 and control. The ratio of Ascomycota and Basidiomycota is higher in COVID‐19, and the opportunistic pathogens, including the genera Candida, Saccharomyces, and Simplicillium, are increased in COVID‐19. The classifier based on two fungal biomarkers is constructed and can distinguish COVID‐19 patients from controls in the training, testing, and independent cohorts. Importantly, the classifier successfully diagnoses SCs with positive specific severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies as COVID‐19 patients. The correlation between distinct fungi and bacteria in COVID‐19 and control groups is depicted. These data suggest that the oral mycobiome may play a role in COVID‐19. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, a global health issue, claim the lives of many every year. Lifestyle changes and genetic predisposition are the key drivers for the development of CVDs. In many of the patients, the disease is detected at the end stage making heart transplantation the only treatment option. Hence every attempt should be made to identify the risk at an early stage and initiate preventive measures to improve the quality of their life. Biomarkers are one of the critical factors that aid in the early diagnosis of CVDs. More specific and highly sensitive biomarkers have been discovered lately and have been employed for prognosis and diagnosis of CVDs. The present review briefs about the various categories of cardiovascular biomarkers with emphasis on novel biomarkers and discusses the biomarkers employed for different purposes in CVDs. The biomarkers have also helped in identifying COVID-19 patients with increased risk for developing cardiovascular complications. Being non-invasive makes biomarkers advantageous over other methods for evaluating the pathophysiological status of CVDs.

A suitable, non-invasive biomarker for assessing endoscopic disease activity (EDA) in ulcerative colitis (UC) has yet to be identified. Our study aimed to develop a cost-effective and non-invasive machine learning (ML) method that utilizes the cost-free Inflammatory Bowel Disease Questionnaire (IBDQ) score and low-cost biological predictors to estimate EDA. Four random forest (RF) and four multilayer perceptron (MLP) classifiers were proposed. The results show that the inclusion of IBDQ in the list of predictors that were fed to the models improved accuracy and the AUC for both the RF and the MLP algorithms. Moreover, the RF technique performed noticeably better than the MLP method on unseen data (the independent patient cohort). This is the first study to propose the use of IBDQ as a predictor in an ML model to estimate UC EDA. The deployment of this ML model can furnish doctors and patients with valuable insights into EDA, a highly beneficial resource for individuals with UC who need long-term treatment. [ABSTRACT FROM AUTHOR]

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, misroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is now classified as a silent pandemic due to concerning current statistics and future predictions. Despite this, no effective treatment or accurate diagnosis currently exists. The negative impacts of invasive techniques and the failure of clinical trials have prompted a shift in research towards non-invasive treatments. In light of this, there is a growing need for early detection of AD through non-invasive approaches. The abundance of data generated by non-invasive techniques such as blood component monitoring, imaging, wearable sensors, and bio-sensors not only offers a platform for more accurate and reliable bio-marker developments but also significantly reduces patient pain, psychological impact, risk of complications, and cost. Nevertheless, there are challenges concerning the computational analysis of the large quantities of data generated, which can provide crucial information for the early diagnosis of AD. Hence, the integration of artificial intelligence and deep learning is critical to addressing these challenges. This work attempts to examine some of the facts and the current situation of these approaches to AD diagnosis by leveraging the potential of these tools and utilizing the vast amount of non-invasive data in order to revolutionize the early detection of AD according to the principles of a new non-invasive medicine era. [ABSTRACT FROM AUTHOR]

Abstract The oral bacteriome, gut bacteriome, and gut mycobiome are associated with coronavirus disease 2019 (COVID‐19). However, the oral fungal microbiota in COVID‐19 remains unclear. This article aims to characterize the oral mycobiome in COVID‐19 and recovered patients. Tongue coating specimens of 71 COVID‐19 patients, 36 suspected cases (SCs), 22 recovered COVID‐19 patients, 36 SCs who recovered, and 132 controls from Henan are collected and analyzed using internal transcribed spacer sequencing. The richness of oral fungi is increased in COVID‐19 versus controls, and beta diversity analysis reveals separate fungal communities for COVID‐19 and control. The ratio of Ascomycota and Basidiomycota is higher in COVID‐19, and the opportunistic pathogens, including the genera Candida, Saccharomyces, and Simplicillium, are increased in COVID‐19. The classifier based on two fungal biomarkers is constructed and can distinguish COVID‐19 patients from controls in the training, testing, and independent cohorts. Importantly, the classifier successfully diagnoses SCs with positive specific severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies as COVID‐19 patients. The correlation between distinct fungi and bacteria in COVID‐19 and control groups is depicted. These data suggest that the oral mycobiome may play a role in COVID‐19.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of exacerbation and remission, making disease monitoring and management challenging. Endoscopy, the gold standard for assessing disease activity and severity, involves invasive procedures and is associated with patient discomfort and risks. Using machine learning (ML) to combine fecal calprotectin with other clinical or biological tests can significantly enhance the non-invasive prediction of endoscopic disease activity (EDA) in UC. Aim: To prove that by fusing fecal calprotectin with other clinical data into an ML model, the performance of the non-invasive prediction of EDA can be significantly improved. Methods: We conducted a prospective, observational, single-center study encompassing 103 patients diagnosed with UC. We employed multilayer perceptron models as the core ML algorithm for predicting EDA. For the constructed models, we utilized the varImp function from the caret library in R to assess the significance of each variable in predicting the outcome. Results: Calprotectin as a sole predictor obtained an accuracy of 70% and an area under the curve (AUC) of 0.68. Combining calprotectin with the list of selected predictors that were fed to the MLP models improved accuracy and the AUC. The accuracy of the algorithm on the test set was 85%. Similarly, the AUC increased to 0.93. This is the first study to propose the use of calprotectin as a predictor in an ML model to estimate UC endoscopic disease activity. Conclusion: The deployment of this ML model can furnish doctors and patients with valuable evaluation of endoscopic disease activity which can be highly beneficial for individuals with UC who need long-term treatment.

Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.

Objective: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Early identification of renal disease in SLE is important. Renal biopsy is currently recognized as the gold standard for diagnosing LN, however, it is invasive and inconvenient for dynamic monitoring. Urine has been considered more promising and valuable than blood in identifying inflamed kidney tissue. Here, we determine whether the signatures of tRNA-derived small noncoding RNA (tsRNA) in urinary exosomes can serve as novel biomarkers for the diagnosis of LN. Methods: tsRNA sequencing was performed in exosome extracted from pooled urine of 20 LN patients and 20 SLE without LN, and the top 10 upregulated tsRNAs were screened as candidate markers of LN. The candidate urinary exosomal tsRNAs were primarily elected by TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) in 40 samples (20 LN and 20 SLE without LN) in the training phase. In the validation phase, selected tsRNAs from the training phase were further confirmed in a larger cohort (54 LN patients and 39 SLE without LN). Receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic efficacy. Results: Upregulated levels of tRF3-Ile-AAT-1 and tiRNA5-Lys-CTT-1 in the urinary exosomes were observed in LN compared with SLE without LN (P < 0.0001 and P < 0.001) and healthy controls (P < 0.01 and P < 0.01), with the area under the curve (AUC) of 0.777 (95% CI: 0.681-0.874, sensitivity 79.63%, specificity 66.69%) and 0.715 (95% CI: 0.610-0.820, sensitivity 66.96%, specificity 76.92%) for discriminating LN from SLE without LN patients. SLE patients with mild activity and moderate to severe activity had higher levels of urinary exosome derived tRF3-Ile AAT-1 (P = 0.035 and P < 0.001) and tiRNA5-Lys-CTT-1 (P = 0.021 and P < 0.001) compared with patients with no activity. Moreover, bioinformatics analysis revealed that both of the tsRNAs regulate the immune process by modulating metabolism and signal pathway. Conclusion: In this study, we demonstrated that urinary exosome tsRNAs can be served as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is a condition that affects 25% of the population. Non-alcoholic steatohepatitis (NASH) is a progressive form of the disease that can lead to severe complications such as cirrhosis and hepatocellular carcinoma. Despite its high prevalence, no drugs are currently approved for the treatment of NASH. The drug development pipeline in NASH is very active, yet most assets do not progress to phase III trials and those that do reach phase III often fail to achieve the endpoints necessary for approval by regulatory agencies. Amongst other reasons, the methodological and operational features of traditional clinical trials in NASH might impede optimal drug development. In this regard, platform trials might be an attractive complement or alternative to conventional clinical trials. Platform trials use a master protocol which enables evaluation of multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. Through Bayesian interim analyses, these trials allow for early exit of drugs from the trial based on success or futility, while providing participants better chances of receiving active compounds through adaptive randomisation. Overall, platform trials represent an alternative for patients, pharmaceutical companies, and clinicians in the quest to accelerate the approval of pharmacologic treatments for NASH. [ABSTRACT FROM AUTHOR]

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes. [ABSTRACT FROM AUTHOR]

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it the leading etiology of chronic liver diseases and a prime cause of liver-related mortality. MASLD can progress into steatohepatitis (termed MASH), fibrosis, cirrhosis, and ultimately cancer. MASLD is associated with increased risks of hepatocellular carcinoma (HCC) and also extrahepatic malignancies, which can develop in both cirrhotic and non-cirrhotic patients, emphasizing the importance of identifying patients with MASLD at risk of developing MASLD-associated malignancies. However, the optimal screening, diagnostic, and risk stratification strategies for patients with MASLD at risk of cancer are still under debate. Individuals with MASH-associated cirrhosis are recommended to undergo surveillance for HCC (e.g. by ultrasound and biomarkers) every six months. No specific screening approaches for MASLD-related malignancies in non-cirrhotic cases are established to date. The rapidly developing omics technologies, including genetics, metabolomics, and proteomics, show great potential for discovering non-invasive markers to fulfill this unmet need. This review provides an overview on the incidence and mortality of MASLD-associated malignancies, current strategies for HCC screening, surveillance and diagnosis in patients with MASLD, and the evolving role of omics technologies in the discovery of non-invasive markers for the prediction and risk stratification of MASLD-associated HCC. Red circles indicate extrahepatic cancer sites. Created with BioRender.com. [Display omitted] • MASLD is associated with increased risks of hepatic and extrahepatic cancer. • Optimal screening and diagnostic tactics for MASLD at risk of cancer are missing. • MASLD-cirrhosis should undergo HCC surveillance by ultrasound every six months. • Surveillance measures for non-cirrhotic cases "at-risk" are yet to be defined. • Omics technologies can discover potential non-invasive markers for MASLD-HCC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo−/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited.In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and “omic” approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all “well-known” and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers’ use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

Background: Gastric cancer (GC) remains the fifth most common incident cancer with the highest incidence in East Asian countries and the third leading cause of cancer death worldwide. The causal association between non-cardia GC and Helicobacter pylori (H. pylori) has been firmly documented by clinical and epidemiological studies. According to the guidelines for diagnosis and treatment of H. pylori infection, eradication therapy is strongly recommended. Early detection of GC is critical and can save lives through rapid technological advancement. At present, endoscopy remains the most efficient technique. However, it is invasive and costs highly. Methods: An extensive bibliographic search was performed via PubMed/Medline, Web of Science, and EBSCO host databases to select studies conducted within the past 8 years. Forty-six relevant analyses were encompassed in this review. Results: Several non-invasive candidate biomarkers associated with H. pylori, divided into virulence markers, transcriptome markers, genomic markers, and inflammatory markers, have been shown to be potential predictors of GC at an early stage. Conclusion: The discovery of non-invasive biomarkers offers new perspectives for screening, early detection, and monitoring of individuals at risk. [ABSTRACT FROM AUTHOR]

Objective: The microRNA-200 family plays a key role in inflammatory and vascular processes, making it a relevant target for Kawasaki disease, a vasculitis with coronary complications. This study aimed to evaluate the diagnostic potential of urinary exosomal microRNA-200 family members in Kawasaki disease patients., Methods: Urine samples from 15 Kawasaki disease patients and 15 healthy controls underwent total exosome isolation and high-throughput sequencing. Differential expression of microRNA-200 family members was validated using quantitative real-time polymerase chain reaction. Diagnostic potential was assessed via receiver operating characteristic analysis, and correlations with clinical parameters were evaluated using Spearman correlation., Results: High-throughput sequencing identified upregulation of microRNA-429, microRNA-200b-3p/5p, microRNA-141-3p, microRNA-200a-3p/5p, and microRNA-200c-3p in Kawasaki disease patients. We confirmed significant upregulation of microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, with receiver operating characteristic analysis showing high diagnostic potential for these microRNAs (area under the curves of 0.844, 0.791, 0.942, 0.842, and 0.898, respectively) and a combined analysis yielding a perfect area under the curve of 1.000. MicroRNA-141 and microRNA-200c-3p/5p, however, showed no significant diagnostic value. MicroRNA-200a-3p and microRNA-200a-5p were positively correlated with white blood cells, platelet counts, and C-reactive protein, while microRNA-200b-3p and microRNA-429 were positively correlated with white blood cells, platelet counts, erythrocyte sedimentation rate, and C-reactive protein. microRNA-200b-5p showed moderate correlations with platelet counts and erythrocyte sedimentation rate., Conclusion: Urinary exosomal microRNA-200 family members, especially microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, demonstrate strong diagnostic potential for Kawasaki disease, correlating with key inflammatory markers. MicroRNA-141 and microRNA-200c did not demonstrate significant diagnostic utility.

Background & Aims: There is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis. The paper presents the secondary analysis of a clinical trial of the effect of probiotic supplementation on the levels of non-invasive markers of liver steatosis and fibrosis in adult patients with depressive disorders., Methods: The research had a two-arm, parallel-group, prospective, randomized, double-blind, controlled design on probiotics in depression. 116 participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. Here, data from 92 subjects was analyzed. The following were assessed: alanine aminotransferase (ALT), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, Hepatic Steatosis Index, Framingham Steatosis Index, as well as non-invasive biomarkers of liver fibrosis (AST to Platelet Ratio Index, Fibosis-4 Index), or baseline socio-demographic, clinical, and laboratory parameters., Results: The probiotics did not influence liver steatosis and fibrosis parameters compared with placebo (p = 0.940 for HSI). However, the subgroup analysis revealed significant differences in liver-related parameters when stratified by the main diagnosis group (better improvement in steatosis indices after probiotics in depressive episode than mixed depression and anxiety disorder patients) or psychotropic medications use (better improvement in ALT-based indices after probiotics in antidepressant-treated subjects than those non-antidepressant-treated). The interplay between probiotics, medications, clinical and metabolic profiles of depression, and the changes in liver-related parameters has been discussed., Conclusions: Multiple factors may modulate the postulated hepatoprotective properties of probiotics efficacy in patients with depression. Further studies with larger sample sizes, different probiotic strains, and longer intervention period are necessary to assess the real significance of probiotics for liver health in this population., Gov Identifier: NCT04756544., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)