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BACKGROUND: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. OBJECTIVES: To investigate the performance of the ESS device in the detection of melanoma. METHODS: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. RESULTS: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. LIMITATIONS: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. CONCLUSION: The ESS devices high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Non-invasively evaluating gene expression products in human pre-implantation embryos remains a significant challenge. Here, we develop a non-invasive method for comprehensive characterization of the extracellular RNAs (exRNAs) in a single droplet of spent media that was used to culture human in vitro fertilization embryos. We generate the temporal extracellular transcriptome atlas (TETA) of human pre-implantation development. TETA consists of 245 exRNA sequencing datasets for five developmental stages. These data reveal approximately 4,000 exRNAs at each stage. The exRNAs of the developmentally arrested embryos are enriched with the genes involved in negative regulation of the cell cycle, revealing an exRNA signature of developmental arrest. Furthermore, a machine-learning model can approximate the morphology-based rating of embryo quality based on the exRNA levels. These data reveal the widespread presence of coding gene-derived exRNAs at every stage of human pre-implantation development, and these exRNAs provide rich information on the physiology of the embryo.

Current malaria diagnostic methods require blood collection, which may be associated with pain and the risk of transmitting blood-borne pathogens, and often create poor compliance when repeated sampling is needed. This study determined the potential use of non-invasive methods (saliva and urine specimens) as alternative sample sources for the diagnosis of malaria infection using real-time polymerase Chain Reaction (qPCR) among children below five years in Nnewi, Anambra State, Nigeria. Biomarkers (18S rRNA) were captured and concentrated from saliva and urine samples using a magnetic bead-based method. DNA recovered from the saliva and urine samples was amplified using qPCR. The results revealed that, out of the 552 participants recruited in this study, the malaria prevalence based on blood microscopy was 55.1%. The prevalence of malaria among children based on the qPCR of saliva specimens was 343 (62.1%), out of which 301 (87.7%) were true positives (TP) and 42 (12.3%) were false positives (FP) when compared with microscopy. Moreover, the prevalence of malaria among children based on qPCR of urine specimens was 269 (48.7%), of which 237 (88.1%) were true positive (TP) and 32 (11.9%) were false positive (FP). When the qPCR method was compared to thick blood film-microscopy as the reference standard, saliva qPCR had a sensitivity of 98.7%, specificity of 80.0%, positive predictive value (PPV) of 87.2%, and negative predictive value (NPV) of 97.8%; urine qPCR had a sensitivity of 88.1%, specificity of 84.3%, PPV of 88.5%, and NPV of 83.8%. Saliva and urine samples are therefore promising non-invasive approaches for malaria diagnosis, and their qPCR has a sensitivity comparable to that of blood microscopy, despite the limitations of cost and turnaround time. [ABSTRACT FROM AUTHOR]

Recent advances in preimplantation genetic testing for aneuploidy (PGT-A) have significantly enhanced its application in ART, providing critical insights into embryo viability, and potentially reducing both the time spent in fertility treatments and the risk of pregnancy loss. With the integration of next-generation sequencing, PGT-A now offers greater diagnostic precision, although challenges related to segmental aneuploidies and mosaicism remain. The emergence of non-invasive PGT-A (niPGT-A), which analyzes DNA in spent embryo culture media, promises a simpler aneuploidy screening method. This mini review assesses the methodological criteria for test validation, the current landscape of PGT-A, and the potential of niPGT-A, while evaluating its advantages and potential pitfalls. It underscores the importance of a robust three-phase validation process to ensure the clinical reliability of PGT-A. Despite initial encouraging data, niPGT-A not only confronts issues of DNA amplification failure and diagnostic inaccuracies but also has yet to meet the three-prong criteria required for appropriate test validation, necessitating further research for its clinical adoption. The review underscores that niPGT-A, like traditional PGT-A, must attain the high standards of precision and reliability expected of any genetic testing platform used in clinical settings before it can be adopted into routine ART protocols. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery. [ABSTRACT FROM AUTHOR]

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High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG. The cross-talk between the systemic biomarkers of four different partakers of tumor microenvironment [ABSTRACT FROM AUTHOR]

Mitigating exotic species invasions requires reliable information on abundance and source-sink dynamics to evaluate effectiveness of control efforts. Despite being present in the southeastern United States for centuries, wild pigs (Sus scrofa) continue to invade new areas, including the Sam D. Hamilton Noxubee National Wildlife Refuge (NNWR) in Mississippi, a forested landscape with an emerging wild pig population. Considering the early stage of invasion, we designed and implemented a non-invasive hair sampling technique to estimate abundance and relatedness of wild pigs within the NNWR. Following 8-week sampling periods in 2021 (n = 160 samples) and 2022 (n = 159 samples), we identified 38 and 26 unique individuals, respectively, although recapture rates were too low to yield precise abundance estimates. We also identified low heterozygosity indicating high relatedness among our population which likely reflected lack of barrier features to gene flow and/or a limited number of external source populations. Finally, we observed positive trends in viable samples collected relative to sampling week, suggesting more optimal sampling period(s) may exist (e.g., autumn). We also acknowledge that use of grain in more accessible areas rather than our remote approach using scent-only attractants may increase hair snare attractiveness and wild pig encounters, while permitting increased sampling frequency. Collectively, these modifications (i.e., altered season, bait type, and access) provide viable pathways to increase precision for abundance estimates. When used concomitantly with ongoing monitoring and control efforts, non-invasive hair sampling will contribute to a more holistic understanding of this exotic species and better inform management actions. [ABSTRACT FROM AUTHOR]

Background: Current treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression. Results: Participants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as "very acceptable" or "quite acceptable" by all participants. No participants developed mania or hypomania. Conclusions: In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary. Trial registration: ClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.clinicaltrials.gov/study/NCT05436613. [ABSTRACT FROM AUTHOR]

Featured Application: The methodology and findings can be used as a basis for further research into other predictive models for various diseases, contributing to the advancement of predictive analytics in healthcare. Chronic atrophic gastritis is a serious health issue beyond the stomach health problems that affect normal life. This study aimed to explore the influencing factors related to chronic atrophic gastritis (CAG) using non-invasive indicators and establish an optimal prediction model to aid in the clinical diagnosis of CAG. Electronic medical record data from 20,615 patients with CAG were analyzed, including routine blood tests, liver function tests, and coagulation tests. The logistic regression algorithm revealed that age, hematocrit, and platelet distribution width were significant influences suggesting chronic atrophic gastritis in the Chongqing population (p < 0.05), with an area under the curve (AUC) of 0.879. The predictive model constructed based on the Random Forest algorithm exhibited an accuracy of 83.15%, precision of 97.38%, recall of 77.36%, and an F1-score of 70.86%, outperforming the models constructed using XGBoost, KNN, and SVC algorithms in a comprehensive comparison. The prediction model derived from this study serves as a valuable tool for future studies and can aid in the prediction and screening of chronic atrophic gastritis. [ABSTRACT FROM AUTHOR]

Prostate-Specific Antigen (PSA) based screening of prostate cancer (PCa) needs refinement. The aim of this study was the identification of urinary biomarkers to predict the Prostate Imaging—Reporting and Data System (PI-RADS) score and the presence of PCa prior to prostate biopsy. Urine samples from patients with elevated PSA were collected prior to prostate biopsy (cohort = 99). The re-analysis of mass spectrometry data from 45 samples was performed to identify urinary biomarkers to predict the PI-RADS score and the presence of PCa. The most promising candidates, i.e. SPARC-like protein 1 (SPARCL1), Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), Alpha-1-microglobulin/bikunin precursor (AMBP), keratin 13 (KRT13), cluster of differentiation 99 (CD99) and hornerin (HRNR), were quantified by ELISA and validated in an independent cohort of 54 samples. Various biomarker combinations showed the ability to predict the PI-RADS score (AUC = 0.79). In combination with the PI-RADS score, the biomarkers improve the detection of prostate carcinoma-free men (AUC = 0.89) and of those with clinically significant PCa (AUC = 0.93). We have uncovered the potential of urinary biomarkers for a test that allows a more stringent prioritization of mpMRI use and improves the decision criteria for prostate biopsy, minimizing patient burden by decreasing the number of unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

Photographic identification (photo ID) is an established method that is used to count animals and track individuals' movements. This method performs well with some species of elasmobranchs (i.e., sharks, skates, and rays) where individuals have distinctive skin patterns. However, the unique skin patterns used for ID must be stable through time to allow re‐identification of individuals in future sampling events. More recently, artificial intelligence (AI) models have substantially decreased the labor‐intensive process of matching photos in extensive photo ID libraries and increased the reliability of photo ID. Here, photo ID and AI are used for the first time to identify epaulette sharks (Hemiscyllium ocellatum) at different life stages for approximately 2 years. An AI model was developed to assess and compare the reliability of human‐classified ID patterns in juvenile and neonate sharks. The model also tested the persistence of unique patterns in adult sharks. Results indicate that immature life stages are unreliable for pattern identification, using both human and AI approaches, due to the plasticity of these subadult growth forms. Mature sharks maintain their patterns through time and can be identified by AI models with approximately 86% accuracy. The approach outlined in this study has the potential of validating the stability of ID patterns through time; however, testing on wild populations and long‐term datasets is needed. This study's novel deep neural network development strategy offers a streamlined and accessible framework for generating a reliable model from a small data set, without requiring high‐performance computing. Since many photo ID studies commence with limited datasets and resources, this AI model presents practical solutions to such constraints. Overall, this approach has the potential to address challenges associated with long‐term photo ID data sets and the application of AI for shark identification. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a significant global health challenge, ranking among the leading causes of cancer-related mortality worldwide. Despite efforts in prevention and early detection, CRC incidence and mortality rates are expected to rise substantially. Traditional screening methods like gFOBT, FIT, flexible sigmoidoscopy, colonoscopy, CTC, and colon capsule have limitations, including false positives/negatives, limited scope, or invasiveness. Recent developments in CRC screening involve DNA methylation biomarkers, showing promise in detecting early-stage CRC and precancerous lesions. Stool-based DNA testing is emerging as a noninvasive and convenient method for detecting CRC-associated DNA methylation alterations, offering potential for earlier detection compared to traditional methods. Several commercial stool-based DNA methylation tests targeting different genes associated with CRC have demonstrated varying sensitivity and specificity, some surpassing traditional screening methods. Challenges remain in optimizing their performance and accessibility. This review discusses how DNA methylation biomarkers could enhance CRC screening, and stool-based DNA methylation tests could revolutionize CRC screening practices, comparing them to the gold standard. [ABSTRACT FROM AUTHOR]

Background: Captive Indian leopards are exposed to different kind of stresses part of which can be alleviated through supplementation of carotenoids. However, invasive monitoring of antioxidants is often pro-act as a stressor itself. Hence, use of non-invasive monitoring of antioxidants and stress would be desirable. However, before recommendation, such non-invasive procedures must be compared with conventional ones. Hence, this experiment was designed to compare the cortisol and total antioxidants (TAA) status measured either in serum or faecal samples. Methods: Three diets were tested on twelve adult leopards (7 M and 5 F, BW ranging from 45-63 kg) in an experiment based on replicated Latin square design comprising of three treatments, three periods and three sequences and four animals in each sequence. The ratio of buffalo meat: chicken carcass was 100:0, 90:10 and 80:10 in groups CON, GI and GII, respectively. Result: Intake and absolute quantity of carotenoids absorbed increased (P<0.01) with increased level of chicken carcass; however, efficiency of absorption was lower (P<0.05) in GII as compared to other two groups. Faecal concentrations of cortisol decreased (P<0.0001) and TAA increased (P<0.0001) with increased level of carotenoids in the diet. Irrespective of the dietary treatments, concentration of cortisol was lower (P<0.0001) and TAA was higher in faecal as compared to serum samples. Regression analysis revealed positive relationship between serum and faecal sample assay with respect to both TAA and cortisol. Thus, faecal samples could be used to monitor cortisol and antioxidant status in Indian leopards. Assay of faecal samples indicated that replacement of buffalo meat with chicken at 20% in the diet improved the antioxidants and alleviated stress in captive leopards. [ABSTRACT FROM AUTHOR]

Non-invasive scores have been proposed to identify patients with fibrotic, metabolic dysfunction-associated steatohepatitis (MASH), who are at the highest risk of progression to complications of cirrhosis and may benefit from pharmacologic treatments. However, data in patients with type 2 diabetes (T2DM) are lacking. The aim of this multicenter prospective study was to perform a head-to-head comparison of FAST (FibroScan-aspartate aminotransferase [AST]), MAST (MRI-AST), MEFIB (magnetic resonance elastography [MRE] plus FIB-4), and FNI (fibrotic NASH index) for detecting fibrotic MASH in patients with T2DM. A total of 330 outpatients with T2DM and biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) from the QUID-NASH study (NCT03634098), who underwent FibroScan, MRI-proton density fat fraction and MRE at the time of liver biopsy were studied. The main outcome was fibrotic MASH, defined as NAS ≥4 (with at least one point for each parameter) and fibrosis stage ≥2 (centrally reviewed). All data for score comparisons were available for 245 patients (median age 59 years, 65% male, median BMI 31 kg/m2; fibrotic MASH in 39%). FAST and MAST had similar accuracy (AUROCs 0.81 vs. 0.79, p = 0.41) but outperformed FNI (0.74; p = 0.01) and MEFIB (0.68; p <0.0001). When using original cut-offs, MAST outperformed FAST, MEFIB and FNI when comparing the percentage of correctly classified patients, in whom liver biopsy would be avoided (69% vs. 48%, 46%, 39%, respectively; p <0.001). When using cut-offs specific to our population, FAST outperformed FNI and MAST (56% vs. 40%, and 38%, respectively; p <0.001). Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. Among patients with type 2 diabetes (T2DM), identifying those with metabolic dysfunction-associated steatohepatitis and significant fibrosis, who are the most at risk of developing clinical liver-related outcomes and who may benefit from pharmacologic treatments, is an unmet need. In this prospective multicenter study, we compared four non-invasive scores, three based on imaging (MRI or ultrasound technologies) and one on laboratory blood tests, for this purpose, using original and study-specific cut-offs. Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. NCT03634098. [Display omitted] • Patients with type 2 diabetes and fibrotic MASH (NAS ≥4, and F≥2) are the most at risk of developing liver-related outcomes. • They may also benefit from pharmacologic treatments when they are available. • We performed a head-to-head comparison of FAST, MAST, MEFIB and FNI scores for identifying fibrotic MASH. • FAST and MAST scores outperformed MEFIB and FNI in patients with type 2 diabetes and MASLD. [ABSTRACT FROM AUTHOR]

Simple Summary: The stress load of cats undergoing lung function diagnostics using barometric whole-body plethysmography has not yet been investigated. In this study, a feline stress score was used to determine the stress level of healthy cats over a 30 min time period during plethysmographic measurement; in addition, the correlation with measured parameters was evaluated. The stress levels of the majority of the 48 cats studied were increased at the beginning of measurements and decreased significantly over time. There was a significant correlation between most measurement parameters and the total stress score. Although the barometric whole-body plethysmography is considered to be a particularly gentle method, most cats initially experienced moderate stress. The stress level must be taken into account when interpreting the measured parameters. Barometric whole-body plethysmography (BWBP) is considered to be a particularly gentle method of assessing lung function in cats. However, there have been no studies to date investigating the stress experienced by cats during measurements. The prospective study included 48 healthy adult cats. Each cat was measured in the plethysmographic chamber for a total of 30 min and stress levels were determined every 10 min using a stress ethogram. At the beginning of measurements, 75% of cats were assessed as tense. Over the three time periods, a significant (p < 0.001) reduction in the total stress score was observed. In addition, all measurement parameters correlated significantly with the stress score, with the exception of enhanced pause and tidal volume. It can therefore be assumed that cats will initially experience stress during examination in the plethysmographic chamber, but stress will decrease significantly over time. As the stress level correlates with many measurement parameters, this should be taken into account when interpreting the results. [ABSTRACT FROM AUTHOR]

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods. [ABSTRACT FROM AUTHOR]

Fontan-associated liver disease (FALD) refers to structural and functional changes of the liver caused by the physiology of the Fontan palliation. Currently, liver biopsy is the gold standard to assess liver fibrosis of FALD. Investigate biomarkers correlating with severity of liver biopsy fibrosis in FALD. A retrospective study of post-Fontan patients ≥ 10 years of age who underwent liver biopsy was conducted. Advanced liver disease (ALD) was defined as bridging fibrosis and/or cirrhosis on liver biopsy. AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) from FibroScan were used as non-invasive fibrosis scores. Sixty-six patients (26/47; 55.3% adults and 13/19 children; 68.4%) had ALD on biopsy. ALD was associated with lower platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32, p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001) in adults. LSM had a high sensitivity at 81.3% with 45.5% specificity at a cut-off 18.5 kPa. APRI and FIB-4 had modest discrimination to identify adults with advanced liver disease, but not children, indicating that these values may be followed as a marker of FALD progression in older patients. [ABSTRACT FROM AUTHOR]

Amphibians, with their unique physiology and habitat requirements, are especially vulnerable to changes in environmental temperatures. While the activation of the physiological stress response can help to mitigate the impact of such habitat alteration, chronic production of elevated glucocorticoid levels can be deleterious in nature. There is no empirical evidence indicating the physiological response of African amphibians to temperature changes, where individuals are unable to emigrate away from potential stressors. To rectify this, we used the edible bullfrog (Pyxicephalus edulis) as a model species to determine the effect of elevated temperature on the adrenocortical response of the species using a recently established matrix. While a control group was kept at a constant temperature (25 °C) throughout the study period, an experimental group was exposed to control (25 °C) and elevated temperatures (30 °C). Mucous swabs were collected throughout the study period to determine dermal glucocorticoid (dGC) concentrations, as a proxy for physiological stress. In addition to this, individual body mass measurements were collected. The results showed that individuals within the experimental group who experienced increased temperatures had significantly elevated dGC levels compared to the control animals. Furthermore, there was a significant difference in the percentage mass change between experimental and control animals. These findings indicate the physiological sensitivity of the edible bullfrog to a thermal stressor in captivity. While this study shows the importance of proper amphibian management within the captive environment, it also highlights the coming danger of global climate change to this and similar amphibian species. [ABSTRACT FROM AUTHOR]

Ankyloglossia, commonly known as Tongue-tie, is a developmental anomaly of the tongue characterized by an abnormally short, thick lingual frenulum resulting in limited tongue movement, feeding and speech problems. It affects quite a large number of infants and children. A careful clinical examination is essential for an early diagnosis of a lingual dysfunction and to choose optimal management, by proper tongue exercises, which leads to satisfactory results in a short time. This report took into consideration a female patient aged 8 years old who was treated with soft tissue diode laser frenectomy and intra and post-surgical bleeding and wound healing were evaluated. A frenectomy can be accomplished either by the routine scalpel technique, electrosurgery or by using lasers. Among various modalities, laser is considered one of the most conservative and simple procedures with good results. They have little absorption in hard tissues, providing selective action and allowing precise cuts, coagulation and vaporization, without causing damage to dental tissues. They reduce the need for anesthesia, control bleeding and do not require sutures. The application of laser resulted in less stress and fear in patients during the procedure, also leading to a more conservative non-invasive method with minimal discomfort and bleeding, therefore making it a boon for Pediartic Dentistry. [ABSTRACT FROM AUTHOR]

Most Pamphagidae species are at risk of being endangered due to their flightlessness, low mobility, and small habitat range. For the same reason, Haplotropis brunneriana (Orthoptera: Pamphagidae) has been designated an endangered species in South Korea. Endangered species with small populations are difficult to observe and investigate because any damage or disturbance to them are prohibited. To address these problems, we first performed non-invasive genomic DNA (gDNA) extraction using exuviae to identify H. brunneriana. Second, we tested the limit of detection of gDNA in the exuviae and how long it could persist when exposed to artificial environmental conditions. Using exuviae, we identified cytochrome b as a species-specific marker of H. brunneriana that could distinguish them from other grasshoppers with sufficient specificity. In the limit of detection test, gDNA could persist and be amplified from exuviae for up to 40 days. Our results demonstrated that fewer than 10 days is recommended for amplifying gDNA from exuviae to obtain reproducible results. In conclusion, this non-invasive identification method using exuviae can be used as an alternative to species identification when it is difficult to find H. brunneriana in the habitat and has the advantage of allowing genetic research to be conducted without harming the endangered species. Implications for insect conservation: Our study used a non-invasive genomic DNA extraction method to conserve endangered grasshoppers. Using exuviae, endangered grasshopper species could be identified, thus confirming their presence or absence in the habitat. This identification method can be an alternative method that can be used when conducting genetic analyses accompanied by physical harm is difficult due to small populations, such as endangered and rare species. [ABSTRACT FROM AUTHOR]

Cognitive disorders such as major depressive disorder and bipolar disorder severely compromise brain function and neuronal activity. Treatments to restore cognitive abilities can have severe side effects due to their intense and excitatory nature, in addition to the fact that they are expensive and invasive. Low-field magnetic stimulation (LFMS) is a novel non-invasive proposed treatment for cognitive disorders. It repairs issues in the brain by altering deep cortical areas with treatments of low-intensity magnetic stimulation. This paper aims to summarize the current literature on the effects and results of LFMS in cognitive disorders. We developed a search strategy to identify relevant studies utilizing LFMS and systematically searched eight scientific databases. Our review suggests that LFMS could be a viable and effective treatment for multiple cognitive disorders, especially major depressive disorder. Additionally, longer, more frequent, and more personalized LFMS treatments tend to be more efficacious. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion In the present study, we aimed to compare serum CK‐MM levels in patients with and without adenomyosis and to investigate whether CK‐MM level can be a non‐invasive marker for myometrial damage due to adenomyosis.Our study was a prospective case‐control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK‐MM levels of the participants in our study. The samples were analyzed by using the human CK‐MM enzyme‐linked immunosorbent assay (ELISA) kit.In our study, the mean serum CK‐MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK‐MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK‐MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis.In this study, we demonstrated that serum CK‐MM can be used as a non‐invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK‐MM as a diagnostic marker in adenomyosis. [ABSTRACT FROM AUTHOR]

The present study has been designed to establish the thermal profile of complete life cycle of the Antheraea assamensis (muga) silkworms starting from the eggs to the moth. The current study also concurrently addresses the applicability of infrared thermography (IRT) to detect muga larvae infected with pebrine. Because of its non-contact advantage, IRT imaging can be successfully manoeuvred to reduce the risk of spreading infections and ultimately lead to increased silk production. The images and data obtained by the non-invasive IRT technology can be implemented, analysed and translated into deep learning algorithm-based machine learning called 'smart data', which can be fine-tuned to develop an artificial intelligence (AI) and decision support system (DSS) for the management and monitoring of silkworms in their entire life progression. Hence, this will boost their productivity, which will further revolutionize their yearly production and convey attractive revenues in the global silk picturesque. [ABSTRACT FROM AUTHOR]

Conventional screening options for colorectal cancer (CRC) detection are mainly direct visualization and invasive methods including colonoscopy and flexible sigmoidoscopy, which must be performed in a clinical setting and may be linked to adverse effects for some patients. Non-invasive CRC diagnostic tests such as computed tomography colonography and stool tests are either too costly or less reliable than invasive ones. On the other hand, volatile organic compounds (VOCs) are potentially ideal non-invasive biomarkers for CRC detection and monitoring. The present review is a comprehensive presentation of the current state-of-the-art VOC-based CRC diagnostics, with a specific focus on recent advancements in biosensor design and application. Among them, breath-based chromatography pattern analysis and sampling techniques are overviewed, along with nanoparticle-based optical and electrochemical biosensor approaches. Limitations of the currently available technologies are also discussed with an outlook for improvement in combination with big data analytics and advanced instrumentation, as well as expanding the scope and specificity of CRC-related volatile biomarkers. [ABSTRACT FROM AUTHOR]

Background: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation TMS is a non-invasive brain modulation procedure. Magnetic field pulses created in the electromagnetic coil produce electrical activity in the brain. TMS is effective treatment for depression which is the leading cause of disability worldwide and it is a major contributor to the overall global burden of disease. More than 30% of patients treated for depression are resistant to pharmacological treatments. Hereby we present the new insights into transcranial magnetic stimulation (TMS) treatment of depression. Worldwide, the number of centers using TMS to treat depression is increasing. [ABSTRACT FROM AUTHOR]

Simple Summary: This review reports on the current and potential utility of the "koala scat" sample to provide a range of ecological and physiological assessments both at the population and individual animal level and do so in a non-invasive manner. DNA recovered from the scat sample provides useful information on koala distribution, diet, genetics and disease, whereas hormone metabolites can inform physiology. While there are still limitations with respect to the decay of quality DNA (host, microbiome, and pathogen) over time related to climate and sample handling, some of these issues can be overcome with timely sample collection. Other current limitations include an inability to detect and quantify particular hormone metabolites such as oestrogens and/or an appropriate biological interpretation of glucocorticoid metabolite secretion when measured in the faecal sample. The use of samples or scats to provide important ecological, genetic, disease and physiology details on free-range populations is gaining popularity as an alternative non-invasive methodology. Koala populations in SE Queensland and NSW have recently been listed as endangered and continue to face anthropomorphic and stochastic environmental impacts that could potentially lead to their extinction. This scoping review examines the current and potential utility of the koala scat to contribute data relevant to the assessment of koala conservation status and decision making. Although we demonstrate that there is great potential for this methodology in providing details for both individual wild animal and population biology (distribution, abundance, sex ratio, immigration/emigration, genetic diversity, evolutionary significant unit, disease epidemiology, nutrition, reproductive status and stress physiology), the calibre of this information is likely to be a function of the quality of the scat that is sampled. [ABSTRACT FROM AUTHOR]

Background: Dementia is a general term for several progressive neurodegenerative disorders including Alzheimer's disease. Timely and accurate detection is crucial for early intervention. Advancements in artificial intelligence present significant potential for using machine learning to aid in early detection. Objective: Summarize the state-of-the-art machine learning-based approaches for dementia prediction, focusing on non-invasive methods, as the burden on the patients is lower. Specifically, the analysis of gait and speech performance can offer insights into cognitive health through clinically cost-effective screening methods. Methods: A systematic literature review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed on three electronic databases (Scopus, Web of Science, and PubMed) to identify the relevant studies published between 2017 to 2022. A total of 40 papers were selected for review. Results: The most common machine learning methods employed were support vector machine followed by deep learning. Studies suggested the use of multimodal approaches as they can provide comprehensive and better prediction performance. Deep learning application in gait studies is still in the early stages as few studies have applied it. Moreover, including features of whole body movement contribute to better classification accuracy. Regarding speech studies, the combination of different parameters (acoustic, linguistic, cognitive testing) produced better results. Conclusions: The review highlights the potential of machine learning, particularly non-invasive approaches, in the early prediction of dementia. The comparable prediction accuracies of manual and automatic speech analysis indicate an imminent fully automated approach for dementia detection. [ABSTRACT FROM AUTHOR]

Background: The rapid development of less invasive and traumatic medical procedures has resulted in a mixture of terms used to describe them, without any agreed definition for each. This is confusing to both medical professionals and patients and can lead to unrealistic patient expectations. The aim of this article is to show the current confused nomenclature and to suggest a new, simple classification based on access and invasiveness (AI) that can be applied to any medical procedure. Methods: We performed an online search for definitions for ‘non-invasive’, ‘non-surgical’, ‘minimally invasive’, ‘minimal access’, ‘pinhole’ and ‘keyhole’. We then searched peer-reviewed medical papers(PRMPs) and patient facing websites (PFWs) for the following index procedures, to see which of the original 6 terms were used to describe them: transvaginal ultrasound, sclerotherapy for leg veins, botulinum toxin injections, dermal fillers, endovenous thermal ablation and laparoscopic gall bladder removal. Results: We found a wide variety of definitions for each of the initial terms. In both PRMPs and PFWs, there were a variety of terms used for each index procedure (i.e.: transvaginal ultrasound, injections of sclerotherapy, botulinum toxin or dermal fillers being both ‘non-invasive’ and ‘minimally invasive’) showing confusion in the classification of procedures. We suggested the ‘AI classification’ based on access (A - none, B - natural orifice or C - penetrating an epithelial surface) and invasiveness (1 - none, 2 - surface damage, 3 ‑ needle = <21G, 4 ‑ cannula >21G but not a surgical trocar, 5 ‑ surgical trocars or small incisions and 6 - incisions). Conclusion: The current confusion of terms used for procedures that are less invasive than the open surgical alternatives leads to confusion and possible false patient expectations. We have proposed an AI classification that can be applied easily to any procedure, giving a uniform classification for medical professionals and patients to understand. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterog-enous populations. Methods: This Swedish multi-centre cohort study included patients (n = 14414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. Results: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM >25kPa, 28.7% developed cirrhosis with portal hypertension within 5years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval =37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. Conclusions: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions. [ABSTRACT FROM AUTHOR]

[Display omitted] Skin tension plays a pivotal role in clinical settings, it affects scarring, wound healing and skin necrosis. Despite its importance, there is no widely accepted method for assessing in vivo skin tension or its natural pre-stretch. This study aims to utilise modern machine learning (ML) methods to develop a model that uses non-invasive measurements of surface wave speed to predict clinically useful skin properties such as stress and natural pre-stretch. A large dataset consisting of simulated wave propagation experiments was created using a simplified two-dimensional finite element (FE) model. Using this dataset, a sensitivity analysis was performed, highlighting the effect of the material parameters and material model on the Rayleigh and supersonic shear wave speeds. Then, a Gaussian process regression model was trained to solve the ill-posed inverse problem of predicting stress and pre-stretch of skin using measurements of surface wave speed. This model had good predictive performance (R 2 = 0.9570) and it was possible to interpolate simplified parametric equations to calculate the stress and pre-stretch. To demonstrate that wave speed measurements could be obtained cheaply and easily, a simple experiment was devised to obtain wave speed measurements from synthetic skin at different values of pre-stretch. These experimental wave speeds agree well with the FE simulations, and a model trained solely on the FE data provided accurate predictions of synthetic skin stiffness. Both the simulated and experimental results provide further evidence that elastic wave measurements coupled with ML models are a viable non-invasive method to determine in vivo skin tension. To prevent unfavourable patient outcomes from reconstructive surgery, it is necessary to determine relevant subject-specific skin properties. For example, during a skin graft, it is necessary to estimate the pre-stretch of the skin to account for shrinkage upon excision. Existing methods are invasive or rely on the experience of the clinician. Our work aims to present an innovative framework to non-invasively determine in vivo material properties using the speed of a surface wave travelling through the skin. Our findings have implications for the planning of surgical procedures and provides further motivation for the use of elastic wave measurements to determine in vivo material properties. [ABSTRACT FROM AUTHOR]

Background: Non-invasive deep brain modulation (DBM) stands as a promising therapeutic avenue to treat brain diseases. Acoustic DBM represents an innovative and targeted approach to modulate the deep brain, employing techniques such as focused ultrasound and shock waves. Despite its potential, the optimal mechanistic parameters, the effect in the brain and behavioral outcomes of acoustic DBM remains poorly understood. Objective: To establish a robust protocol for the shock wave DBM by optimizing its mechanistic profile of external stimulation, and to assess its efficacy in preclinical settings. Methods: We used shockwaves due to their capacity to leverage a broader spectrum of peak intensity (10–127 W/mm2) in contrast to ultrasound (0.1–5.0 W/mm2), thereby enabling a more extensive range of neuromodulation effects. We established various types of shockwave pressure profiles of DBM and compared neural and behavioral responses. To ascertain the anticipated cause of the heightened neural activity response, numerical analysis was employed to examine the mechanical dynamics within the brain. Results: An optimized profile led to an enhancement in neuronal activity within the hypothalamus of mouse models. The optimized profile in the hippocampus elicited a marked increase in neurogenesis without neuronal damage. Behavioral analyses uncovered a noteworthy reduction in locomotion without significant effects on spatial memory function. Conclusions: The present study provides an optimized shock wave stimulation protocol for non-invasive DBM. Our optimized stimulation profile selectively triggers neural functions in the deep brain. Our protocol paves the way for new non-invasive DBM devices to treat brain diseases.

Chloé Rauzier,1,2 Dominic J Chartrand,1,3 Natalie Alméras,1,3 Isabelle Lemieux,1 Eric Larose,1,4 Patrick Mathieu,1,5 Philippe Pibarot,1,4 Benoît Lamarche,6,7 Caroline Rhéaume,1,8,9 Paul Poirier,1,2 Jean-Pierre Després,1,3,9 Frédéric Picard1,2 1Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) – Université Laval, Québec, QC, Canada; 2Faculté de pharmacie, Université Laval, Québec, QC, Canada; 3Département de kinésiologie, Faculté de médecine, Université Laval, Québec, QC, Canada; 4Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada; 5Département de chirurgie, Faculté de médecine, Université Laval, Québec, QC, Canada; 6Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada; 7École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation, Université Laval, Québec, QC, Canada; 8Département de médecine familiale et de médecine d’urgence, Faculté de médecine, Université Laval, Québec, QC, Canada; 9VITAM – Centre de recherche en santé durable, Québec, QC, CanadaCorrespondence: Frédéric Picard; Jean-Pierre Després, Email Frederic.Picard@criucpq.ulaval.ca; jean-pierre.despres.ciussscn@ssss.gouv.qc.caAbstract: Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat > 5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.Keywords: humans, insulin-like growth factor-binding protein 2, waist circumference, hepatic fat, metabolic dysfunction-associated steatotic liver disease, biomarker, plasma, non-invasive

Abstract Background Current treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression. Results Participants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as “very acceptable” or “quite acceptable” by all participants. No participants developed mania or hypomania. Conclusions In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary. Trial registration ClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.clinicaltrials.gov/study/NCT05436613.

Abstract Background Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.