Search Results (97)

Background: The detection of circulating tumor cells (CTCs) holds significant promise for the diagnosis and monitoring of lung cancer (LC). However, the clinical utility of CTCs is limited by the heterogeneity of their phenotypes and the shortcomings of existing detection methods, which often rely on epithelial markers like EpCAM. DNA aptamers offer a promising alternative due to their high affinity, stability, and ability to recognize diverse cancer-specific biomarkers. Methods: This study utilized DNA aptamers LC-17 and LC-18, previously selected against primary lung tumor tissue, to isolate and detect CTCs in the peripheral blood of 43 non-small cell lung cancer (NSCLC) patients. Mass spectrometry (LC-MS/MS) was employed to identify the target proteins of aptamer LC-17. CTCs from patients’ blood and healthy donors were isolated via filtration after erythrocyte and lymphocyte lysis and stained with FAM-labeled LC-17 and LC-18 aptamers for detection using fluorescence and light microscopy. Results: Mass spectrometry identified neutrophil defensin 1 (DEFA1) and peroxiredoxin-2 (PRDX2) as the primary protein targets of aptamer LC-17 in CTCs, both of which were absent in healthy donor samples. CTC enumeration revealed statistically significant correlations between elevated CTC counts (>3 cells/4 mL blood) and advanced primary tumor size (T4 vs. T1–T3, p = 0.012), extensive regional lymph node metastasis (N3 vs. N1–N2, p = 0.014), and shorter overall survival (median 24 vs. 32 months, p < 0.05). Conclusions: The developed aptamer-based liquid biopsy method effectively captures heterogeneous CTC populations independent of EpCAM expression. The strong correlation of CTC counts with disease progression and survival underscores their clinical relevance as a prognostic biomarker in NSCLC. This approach presents a viable, non-invasive tool for disease monitoring and stratification of NSCLC patients, with potential for integration into clinical practice. Full article

Senescence is a dynamic, multifaceted process implicated in tissue aging, organ dysfunction, and intricately associated with numerous chronic diseases. As senescent cells accumulate, they drive inflammation, fibrosis, and metabolic disruption through the senescence-associated secretory phenotype (SASP). Despite its clinical relevance, senescence remains challenging to detect non-invasively due to its heterogeneous nature and the lack of universal biomarkers. Recent advances in the development of specific imaging probes for positron emission tomography (PET) enable in vivo visualization of senescence-associated pathways across key organs, such as the lung, heart, kidney, and metabolic processes. For instance, [¹⁸F]FPyGal, a β-galactosidase-targeted tracer, has demonstrated selective accumulation in senescent cells in both preclinical and early clinical studies, while FAP-targeted radioligands are emerging as tools for imaging fibrotic remodeling in the lung, liver, kidney, and myocardium. This review examines a new generation of PET radioligands targeting hallmark features of senescence, with the potential to track and measure the process, the ability to be translated into clinical interventions for early diagnosis, and longitudinal monitoring of senescence-driven pathologies. By integrating organ-specific imaging biomarkers with molecular insights, PET probes are poised to transform our ability to manage and treat age-related diseases through personalized approaches. Full article

Background/Objectives: Temporomandibular disorders (TMD) are a heterogeneous group of musculoskeletal conditions affecting the temporomandibular joints and masticatory muscles. In recent years, autogenous injections have been investigated as minimally invasive therapeutic options to alleviate pain and improve function. However, the clinical effectiveness of such therapies across different TMD phenotypes remains uncertain. Methods: Electronic searches were performed in MEDLINE, Embase, and Web of Science for articles published between January 2015 and May 2025. Studies involving intra-articular or intra-muscular autogenous injections in TMD patients were included. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool and the Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: Thirteen studies met the inclusion criteria. Six were randomized controlled trials (RCTs) and seven were non-randomized clinical studies. Ten studies evaluated intra-articular conditions such as disc displacement or Temporomandibular Joint (TMJ) osteoarthritis, while three focused on myofascial pain. Platelet-Rich Plasma (PRP) was the most frequently investigated agent. Most studies reported statistically significant reductions in pain and improvements in mandibular mobility following autogenous injections, with PRP generally outperforming comparators such as hyaluronic acid, corticosteroids, or saline. No serious adverse events were reported. Conclusions: All PRP and Platelet-Rich Fibrin (PRF) injection protocols reviewed were effective in reducing pain and improving mobility in patients with TMD. However, differences in protocols and follow-up times prevented a meta-analysis from being conducted. More standardized RCTs are needed to determine clear clinical guidelines. Full article

Background: Cutaneous aging is a multifactorial process, increasingly understood through the lens of cellular senescence, a state of stable cell cycle arrest accompanied by a pro-inflammatory secretory phenotype that disrupts tissue homeostasis. Recent research has highlighted the accumulation of senescent dermal fibroblasts as a key contributor to age-related skin changes, including loss of elasticity, collagen degradation, and impaired regeneration. Objective: This review explores the emerging hypothesis that energy-based devices (EBDs), particularly lasers, may act as senotherapeutic tools by targeting cellular senescence pathways in aging skin. We examine the molecular and histological effects of laser therapy in relation to known biomarkers of senescence and evaluate their potential role in regenerative dermatology. Methods: We conducted a review of published studies on fractional lasers, red-light therapies, and other EBDs, focusing on their impact on fibroblast activity, extracellular matrix remodeling, and senescence-associated markers such as p16^INK4a, p21^Cip1, telomerase, and SASP-related cytokines. Comparative analysis with pharmacologic senotherapeutics was also performed. Results: Preclinical and clinical data suggest that specific EBDs can modulate dermal aging at the molecular level by enhancing mitochondrial activity, increasing type III collagen synthesis, reducing senescence-related gene expression, and promoting fibroblast turnover. In contrast to systemic senolytics, lasers provide localized and titratable interventions with a favorable safety profile. Conclusions: Energy-based devices, particularly fractional lasers and red-light systems, hold promise as non-invasive senotherapeutic interventions in dermatology. By modulating senescence-associated pathways, EBDs may offer not only cosmetic improvement but also biological rejuvenation. Further mechanistic studies and biomarker-based trials are warranted to validate this paradigm and refine treatment protocols for longevity-oriented skin therapies. Full article

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. Methods: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. Results: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians’ diagnostic confidence when TMS data were incorporated. Conclusions: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability. Full article

The development of scalable, non-invasive tools to assess tumor responsiveness to structurally active immunoformulations remains a critical unmet need in solid tumor immunotherapy. Here, we introduce a real-time, ex vivo functional system to classify tumor cell lines exposed to a phospholipoproteomic platform, without relying on cytotoxicity, co-culture systems, or molecular profiling. Tumor cells were monitored using IncuCyte^® S3 (Sartorius) real-time imaging under ex vivo neutral conditions. No dendritic cell components or immune co-cultures were used in this mode. All results are derived from direct tumor cell responses to structurally active formulations. Using eight human tumor lines, we captured proliferative behavior, cell death rates, and secretomic profiles to assign each case into stimulatory, inhibitory, or neutral categories. A structured decision-tree logic supported the classification, and a Functional Stratification Index (FSI) was computed to quantify the response magnitude. Inhibitory lines showed early divergence and high IFN-γ/IL-10 ratios; stimulatory ones exhibited a proliferative gain under balanced immune signaling. The results were reproducible across independent batches. This system enables quantitative phenotypic screening under standardized, marker-free conditions and offers an adaptable platform for functional evaluation in immuno-oncology pipelines where traditional cytotoxic endpoints are insufficient. This approach has been codified into the STIP (Structured Traceability and Immunophenotypic Platform), supporting reproducible documentation across tumor models. This platform contributes to upstream validation logic in immuno-oncology workflows and supports early-stage regulatory documentation. Full article

The wheat planted at the end of the rainy season in the Cerrado suffers from a strong water deficit. A selection of genetic material with drought tolerance is necessary. In improvement programs that evaluate a large number of materials, efficient, automated, and non-destructive phenotyping is essential, which requires the use of sensors. The experiment was conducted in 2016 using a phenotyping platform, where irrigation gradients ranging from 184 (WR4) to 601 mm (WR1) were created, allowing for the comparison of four genotypes. In addition to productivity, we evaluated plant height, hectoliter weight, the number of spikes per square meter, ear length, photosynthesis, and the indices calculated by the sensors. For most morphophysiological parameters, extreme stress makes it difficult to discriminate materials. WR1 (601 mm) and WR2 (501 mm) showed similar trends in almost all variables. The data validated the phenotyping platform, which creates an irrigation gradient, considering that the results obtained, in general, were proportional to the water levels. The similar trend between sensors (NDVI, PRI, and LIFT) and morphophysiological, plant growth, and crop yield evaluations validated the use of sensors as a tool in selecting drought-tolerant wheat genotypes using a non-invasive methodology. Considering that only four genotypes were used, none showed absolute and unequivocal tolerance to drought; however, each genotype exhibited some desirable characteristics related to drought tolerance mechanisms. Full article

Reproductive efficiency is a critical determinant of productivity and profitability in sheep farming. Traditional selection methods have largely relied on phenotypic traits and historical reproductive records, which are often limited by subjectivity and delayed feedback. Recent advancements in artificial intelligence (AI), including video tracking, wearable sensors, and machine learning (ML) algorithms, offer new opportunities to identify behavior-based indicators linked to key reproductive traits such as estrus, lambing, and maternal behavior. This review synthesizes the current research on AI-powered behavioral monitoring tools and proposes a conceptual model, ReproBehaviorNet, that maps age- and sex-specific behaviors to biological processes and AI applications, supporting real-time decision-making in both intensive and semi-intensive systems. The integration of accelerometers, GPS systems, and computer vision models enables continuous, non-invasive monitoring, leading to earlier detection of reproductive events and greater breeding precision. However, the implementation of such technologies also presents challenges, including the need for high-quality data, a costly infrastructure, and technical expertise that may limit access for small-scale producers. Despite these barriers, AI-assisted behavioral phenotyping has the potential to improve genetic progress, animal welfare, and sustainability. Interdisciplinary collaboration and responsible innovation are essential to ensure the equitable and effective adoption of these technologies in diverse farming contexts. Full article

Renal cell carcinoma (RCC) is a major global health issue with an increasing incidence and mortality rate. Current diagnostic methods are either invasive or limited in their ability to accurately differentiate between benign and malignant tumours and to predict early treatment response. This can lead to incorrect diagnosis, delayed treatment, patient anxiety, and suboptimal outcomes. RCC subtypes are known to exhibit distinct metabolic alterations, for example in glucose metabolism. These metabolic phenotypes offer potential targets for non-invasive imaging techniques to improve diagnosis and treatment, but current clinically available metabolic imaging tools such as ¹⁸F-FDG-PET and ^99mTc-sestamibi SPECT have limitations. Therefore, new approaches are required to assess this metabolism, and novel metabolic MRI techniques including hyperpolarised [1-¹³C]pyruvate MRI and deuterium metabolic imaging offer promising alternatives. These techniques are non-radioactive, demonstrate spatial metabolic heterogeneity, and can probe metabolic flux beyond tracer uptake. This review aims to explore the potential of metabolic MRI in the clinical management of RCC by (1) summarising current clinical guidelines; (2) reviewing metabolic heterogeneity across RCC subtypes; (3) discussing the potential of metabolic MRI to advance the understanding of in vivo metabolism; (4) and finally suggesting future directions for research in this field. Full article

Platelets, traditionally recognized for their role in hemostasis, have emerged as pivotal players in cancer biology. They actively contribute to tumor proliferation, angiogenesis, immune evasion, and metastasis and thus play a significant role in cancer progression. Tumor-educated platelets (TEPs) acquire protumorigenic phenotypes through RNA, protein, and receptor profile alterations driven by interactions with tumors and their microenvironment. These modifications enable TEPs to enhance tumor growth and dissemination and to play a critical role throughout the metastatic process. Moreover, TEPs are promising biomarkers that can easily be analyzed in liquid biopsies. Since they dynamically mirror tumor activity through transcriptomic and proteomic changes, their analysis offers a non-invasive method for determining cancer detection and diagnosis, patient prognosis, therapy monitoring, and personalization of treatment. Their demonstrated accuracy in identifying cancer types and predicting treatment responses underscores their ability to provide real-time insights into tumor biology, including in urological malignancies. Their diagnostic potential and their accessibility as blood-sourced biomarkers position TEPs as transformative tools in advancing personalized oncology. Here, we focus on the role of TEPs in urological tumors, exploring their applications in early cancer detection, disease monitoring, and the design of tailored therapeutic strategies. Full article

Background: Glioblastoma (GB) is a particularly malignant brain tumour which carries a poor prognosis and presents limited treatment options. MRI is standard practice for differential diagnosis at initial presentation of GB and can assist in both treatment planning and response assessment. MRI radiomics allows for discerning GB features of clinical importance that are not evident by visual analysis, augmenting the morphological and functional tumour characterisation beyond traditional imaging techniques. Given that radiotherapy is part of the standard of care for GB patients, establishing a platform for phenotyping radiation treatment responses using non-invasive methods is of high relevance. Methods: In this study, we modelled the responses to ionising radiation across four orthotopic mouse models of GB using diffusion and perfusion radiomics. We have identified the optimal set of radiomic features that reflect tumour cellularity, microvascularity, and blood flow changes brought about by radiation treatment in these murine orthotopic models of GB, and directly compared them with endpoint histopathological analysis. Results: We showed that the selected radiomic features can quantify textural information and pixel interrelationships of tumour response to radiation therapy, revealing subtle image patterns that may reflect intra-tumoural spatial heterogeneity. When compared to GB patients, similarities in selected radiomic features were noted between orthotopic murine tumours and non-enhancing central tumour areas in patients, along with several discrepancies in tumour cellularity and vascularization, denoted by distinct grey level intensities and nonuniformity metrics. Conclusion: As the field evolves, radiomic profiling of GB may enhance the evaluation of targeted therapeutic strategies, accelerate the development of new therapies, and act as a potential virtual biopsy tool. Full article

Background/Objectives: The coronavirus disease (COVID-19) pandemic was associated with an intense impact on health worldwide. Among the sequelae, it became necessary to clarify respiratory impairment related to lung function and aerobic capacity, as well as the treatment of curative and preventive measures of pulmonary involvement. In this context, this study aimed to compare vital signs, the sensation of dyspnea (Borg scale), lung function, and exercise tolerance before and after the use of non-invasive mechanical ventilation (NIV) in adults of both sexes after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A cross-sectional analytical clinical study was performed with the inclusion of individuals who had been diagnosed with COVID-19 at least three months before data collection. Individuals were evaluated for vital signs (heart rate and peripheral oxygen saturation), Borg scale, spirometry, and submaximal exercise protocol of two minutes of the step test before and after receiving NIV in ventilation mode by continuous positive airway pressure of 6 cm H₂O for 30 min. Results: A total of 50 participants were enrolled and grouped as a mild (N = 25) or severe (N = 25) clinical phenotype during SARS-CoV-2 infection according to the criteria of the World Health Organization. In our data, the forced vital capacity (p < 0.001), the ratio between the forced expiratory volume in the first one second to the forced vital capacity and the forced vital capacity (p = 0.020), and the two-minute submaximal step exercise protocol (number of steps—p = 0.001) showed a statistical improvement in the severe clinical phenotype group after NIV. In addition, forced expiratory volume in the first one second to the forced vital capacity (p = 0.032) and the two-minute submaximal step exercise protocol (number of steps—p < 0.001) showed a statistical improvement in the mild clinical phenotype group after NIV. No changes were described for vital signs and the Borg scale. Conclusions: This study allowed us to identify that NIV is a tool that promotes better exercise capacity by increasing the number of steps achieved in both clinical phenotype groups and improving lung function observed in the spirometry markers. Full article

Acute respiratory distress syndrome (ARDS) is a heterogeneous group of disease entities that are associated with acute hypoxic respiratory failure and significant morbidity and mortality. With a better understanding and phenotyping of lung injury, novel pathophysiologic mechanisms demonstrate the impact of a patient’s excessive spontaneous breathing effort on perpetuating lung injury. Patient self-inflicted lung injury (P-SILI) is a recently identified phenomenon that delves into the impact of spontaneous breathing on respiratory mechanics in patients with lung injury. While the studies are hypothesis-generating and have been demonstrated in animal and human studies, further clinical trials are needed to identify its impact on ARDS management. The purpose of this review article is to highlight the physiologic mechanisms of P-SILI, novel tools and methods to detect P-SILI, and to review the current literature on non-invasive and invasive respiratory management in patients with ARDS. Full article

(1) Background: Autism, as an important global problem that affects many phenotypically different individuals, is associated with electroencephalographic (EEG) abnormalities and adaptability impairment. (2) Materials and Methods: In this retrospective study of a group of 101 autistic children, we aimed to evaluate the presence of EEG abnormalities, adaptive features, and clinical phenotypes via EEG, the Adaptive Behavior Assessment System II (ABAS II) scale, and neurological examination. (3) Results: Our results showed statistically significant associations between the level of adaptability obtained through the ABAS II scale and neurological deficit, specifically in terms of coordination impairment. There were also statistically significant differences between the level of adaptability and clinical phenotypes between autism type groups. (4) Conclusions: This study shows that children with autism are likely to exhibit neurological and adaptive abnormalities. Non-invasive assessment tools, such as EEG recordings, the ABAS II scale, and neurological examination offer valuable support for improved diagnosis and management. Full article

Monitoring and assessing the progression of symptoms in neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are critical for improving patient outcomes. Traditional biomarkers, such as cerebrospinal fluid analysis and brain imaging, are widely used to investigate the underlying mechanisms of disease and enable early diagnosis. In contrast, digital biomarkers derived from phenotypic changes—such as EEG, eye movement, gait, and speech analysis—offer a noninvasive and accessible alternative. Leveraging portable and widely available devices, such as smartphones and wearable sensors, digital biomarkers are emerging as a promising tool for ND diagnosis and monitoring. This review highlights the comprehensive developments in digital biomarkers, emphasizing their unique advantages and integration potential alongside traditional biomarkers. Full article