Heart rate time series are widely used to characterize physiological states and athletic performance. Among the main indicators of metabolic and physiological states, the detection of metabolic thresholds is an important tool in establishing training protocols in both sport and clinical fields. This paper reviews the most common methods, applied to heart rate (HR) time series, aiming to detect metabolic thresholds. These methodologies have been largely used to assess energy metabolism and to identify the appropriate intensity of physical exercise which can reduce body weight and improve physical fitness. Specifically, we focused on the main nonlinear signal evaluation methods using HR to identify metabolic thresholds with the purpose of identifying a method which can represent a useful tool for the real-time settings of wearable devices in sport activities. While the advantages and disadvantages of each method, and the possible applications, are presented, this review confirms that the nonlinear analysis of HR time series represents a solid, robust and noninvasive approach to assess metabolic thresholds.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with cirrhosis being a major risk factor. Traditional blood markers like alpha-fetoprotein (AFP) demonstrate limited efficacy in distinguishing between HCC and cirrhosis, underscoring the need for more effective diagnostic methodologies. In this context, extracellular vesicles (EVs) have emerged as promising candidates; however, their practical diagnostic application is restricted by the current lack of label-free methods to accurately profile their molecular content. To address this gap, our study explores the potential of mid-infrared (mid-IR) spectroscopy, both alone and in combination with plasmonic nanostructures, to detect and characterize circulating EVs. EVs were extracted from HCC and cirrhotic patients. Mid-IR spectroscopy in the Attenuated Total Reflection (ATR) mode was utilized to identify potential signatures for patient classification, highlighting significant changes in the Amide I-II region (1475-1700 cm^-1). This signature demonstrated diagnostic performance comparable to AFP and surpassed it when the two markers were combined. Further investigations utilized a plasmonic metasurface suitable for ultrasensitive spectroscopy within this spectral range. This device consists of two sets of parallel rod-shaped gold nanoantennas (NAs); the longer NAs produced an intense near-field amplification in the Amide I-II bands, while the shorter NAs were utilized to provide a sharp reflectivity edge at 1800-2200 cm^-1 for EV mass-sensing. A clinically relevant subpopulation of EVs was targeted by conjugating NAs with an antibody specific to Epithelial Cell Adhesion Molecule (EpCAM). This methodology enabled the detection of variations in the quantity of EpCAM-presenting EVs and revealed changes in the Amide I-II lineshape. The presented results can positively impact the development of novel laboratory methods for the label-free characterization of EVs, based on the combination between mid-IR spectroscopy and plasmonics. Additionally, data obtained by using HCC and cirrhotic subjects as a model system, suggest that this approach could be adapted for monitoring these conditions.

During exercise with increasing intensity, the human body transforms energy with mechanisms dependent upon actual requirements. Three phases of the body’s energy utilization are recognized, characterized by different metabolic processes, and separated by two threshold points, called aerobic (AerT) and anaerobic threshold (AnT). These thresholds occur at determined values of exercise intensity(workload) and can change among individuals. They are considered indicators of exercise capacities and are useful in the personalization of physical activity plans. They are usually detected by ventilatory or metabolic variables and require expensive equipment and invasive measurements. Recently, particular attention has focused on AerT, which is a parameter especially useful in the overweight and obese population to determine the best amount of exercise intensity for weight loss and increasing physical fitness. The aim of study is to propose a new procedure to automatically identify AerT using the analysis of recurrences (RQA) relying only on Heart rate time series, acquired from a cohort of young athletes during a sub-maximal incremental exercise test (Cardiopulmonary Exercise Test, CPET) on a cycle ergometer. We found that the minima of determinism, an RQA feature calculated from the Recurrence Quantification by Epochs (RQE) approach, identify the time points where generic metabolic transitions occur. Among these transitions, a criterion based on the maximum convexity of the determinism minima allows to detect the first metabolic threshold. The ordinary least products regression analysis shows that values of the oxygen consumption VO₂, heart rate (HR), and Workload correspondent to the AerT estimated by RQA are strongly correlated with the one estimated by CPET (r > 0.64). Mean percentage differences are <2% for both HR and VO₂ and <11% for Workload. The Technical Error for HR at AerT is <8%; intraclass correlation coefficients values are moderate (≥0.66) for all variables at AerT. This system thus represents a useful method to detect AerT relying only on heart rate time series, and once validated for different activities, in future, can be easily implemented in applications acquiring data from portable heart rate monitors.

Interventional radiotherapy (brachytherapy) has become the new therapeutic standard in the management of early stages nasal vestibule tumors; in fact it allows for high local control rates and low toxicity profiles. However, since more and more patients will receive interventional radiotherapy (brachytherapy) as primary treatment, it is desirable to implement novel strategies to reduce the dose to organs at risk with the future aim to result in further lowering long-term side effects. Materials and methods: We were able to identify two different strategies to reduce dose to the treatment volume, including the implantation technique (the implant can be interstitial, endocavitary or mixed and the catheters may be placed either using the Paris system rules or the anatomical approach) and the dose distribution within the implant (the most commonly used parameter to consider is the dose non-uniformity ratio). We subsequently propose two novel strategies to reduce dose to organs at risk, including the use of metal shields for fixed organs as in the case of the eyes and the use of a mouth swab to push away mobile organs, such in the case of the mandible. We used two different algorithms to verify the values namely the TG-43 and the TG-186. Results: We provided an accurate literature review regarding strategies to reduce toxicity to the treatment volume, underlining the pros and cons of all implantation techniques and about the use dose non-uniformity ratio. Regarding the innovative strategies to reduce the dose to organs at risk, we investigated the use of eye shielding and the use of swabs to push away the mandible by performing an innovative calculation using two different algorithms in a series of three consecutive patients. Our results show that the dose reduction, both in the case of the mandible and in the case of eye shielding, was statistically significant. Conclusion: Proper knowledge of the best implantation technique and dose non-uniformity ratio as highlighted by existing literature is mandatory in order to reduce toxicity within the treatment volume. With regard to the dose reduction to the organs at risk we have demonstrated that the use of eye shielding and mouth swab could play a pivotal role in clinical practice; in fact, they are effective at lowering the doses to the surrounding organs and do not require any change to the current clinical workflow.

A new method based on the Recurrence Quantification Analysis (RQA) of the heart rate (HR) offers an objective, efficient alternative to traditional methods for Aerobic Threshold (AerT) identification that have practical limitations due to the complexity of equipment and interpretation. This study aims to validate the RQA-based method’s applicability across varied demographics, exercise protocols, and health status. Data from 123 cardiopulmonary exercise tests were analyzed, and participants were categorized into four groups: athletes, young athletes, obese individuals, and cardiac patients. Each participant’s AerT was assessed using both traditional ventilatory equivalent methods and the automatic RQA-based method. Ordinary Least Products (OLP) regression analysis revealed strong correlations (r > 0.77) between the RQA-based and traditional methods in both oxygen consumption (VO₂) and HR at the AerT. Mean percentage differences in HR were below 2.5%, and the Technical Error for HR at AerT was under 8%. The study validates the RQA-based method, directly applied to HR time series, as a reliable tool for the automatic detection of the AerT, demonstrating its accuracy across diverse age groups and fitness levels. These findings suggest a versatile, cost-effective, non-invasive, and objective tool for personalized exercise prescription and health risk stratification, thereby fulfilling the study’s goal of broadening the method’s applicability.

This study compares dosimetric outcomes of high-dose-rate (HDR) interventional radiotherapy (IRT) using Iridium-192, Volumetric Modulated Arc Therapy (VMAT), and electron beam therapy for non-melanoma skin cancer (NMSC). A retrospective analysis of 25 patients showed that IRT provided a significantly higher mean dose to the clinical target volume (CTV) compared to VMAT and electron beam therapy. IRT and VMAT had comparable V95%CTV coverage, whilst electron therapy was less feasible for large CTVs. IRT delivered higher surface doses while minimizing deep tissue exposure compared to partial arc VMAT. Our findings support IRT for personalized and effective NMSC treatment.