Nanomaterials-based aptasensors for rapid detection and early warning of key food contaminants: A review.

The frequent occurrence of food safety incidents has aroused public concern about food safety and key contaminants. Foodborne pathogen contamination, pesticide residues, heavy metal residues, and other food safety problems will significantly impact human health. Therefore, developing efficient and sensitive detection method to ensure food safety early warning is paramount. The aptamer-based sensor (aptasensor) is a novel analytical tool with strong targeting, high sensitivity, low cost, etc. It has been extensively utilized in the pharmaceutical industry, biomedicine, environmental engineering, food safety detection, and in other diverse fields. This work reviewed the latest research progress of aptasensors for food analysis and detection, mainly introducing their application in detecting various key food contaminants. Subsequently, the sensing mechanism and performance of aptasensors are discussed. Finally, the review will examine the challenges and opportunities related to aptasensors for detecting major contaminants in food, and advance implementation of aptasensors in food safety and detection.

Ti3C2 MXene/MoS2@AuNPs ternary nanocomposite for highly sensitive electrochemical detection of phoxim residues in fruits.

Phoxim, extensively utilized in agriculture as an organothiophosphate insecticide, has the potential to cause neurotoxicity and pose human health hazards. In this study, an electrochemical enzyme biosensor based on Ti3C2 MXene/MoS2@AuNPs/AChE was constructed for the sensitive detection of phoxim. The two-dimensional multilayer structure of Ti3C2 MXene provides a robust framework for MoS2, leading to an expansion of the specific surface area and effectively preventing re-stacking of Ti3C2 MXene. Additionally, the synergistic effect of self-reduced grown AuNPs with MoS2 further improves the electrical conductivity of the composites, while the robust framework provides a favorable microenvironment for immobilization of enzyme molecules. Ti3C2 MXene/MoS2@AuNPs electrochemical enzyme sensor showed a significant response to phoxim in the range of 1 × 10-13 M to 1 × 10-7 M with a detection limit of 5.29 × 10-15 M. Moreover, the sensor demonstrated excellent repeatability, reproducibility, and stability, thereby showing its promising potential for real sample detection.

Electrochemical Detection of Nucleic Acids Using Three-Dimensional Graphene Screen-Printed Electrodes.

Electrochemical approaches, along with miniaturization of electrodes, are increasingly being employed to detect and quantify nucleic acid biomarkers. Miniaturization of the electrodes is achieved through the use of screen-printed electrodes (SPEs), which consist of one to a few dozen sets of electrodes, or by utilizing printed circuit boards. Electrode materials used in SPEs include glassy carbon (Chiang H-C, Wang Y, Zhang Q, Levon K, Biosensors (Basel) 9:2-11, 2019), platinum, carbon, and graphene (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). There are numerous modifications to the electrode surfaces as well (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). These approaches offer distinct advantages, primarily due to their demonstrated superior limit of detection without amplification. Using the SPEs and potentiostats, we can detect cells, proteins, DNA, and RNA concentrations in the nanomolar (nM) to attomolar (aM) range. The focus of this chapter is to describe the basic approach adopted for the use of SPEs for nucleic acid measurement.

Epidermal secretion-purified biosensing patch with hydrogel sebum filtering membrane and unidirectional flow microfluidic channels.

The development of biosensing electronics for real-time sweat analysis has attracted increasing research interest due to their promising applications for non-invasive health monitoring. However, one of the critical challenges lies in the sebum interference that largely limits the sensing reliability in practical scenarios. Herein, we report a flexible epidermal secretion-purified biosensing patch with a hydrogel filtering membrane that can effectively eliminate the impact of sebum and sebum-soluble substances. The as-prepared sebum filtering membranes feature a dual-layer sebum-resistant structure based on the poly(hydroxyethyl methacrylate) hydrogel functionalized with nano-brush structured poly(sulfobetaine) to eliminate interferences and provide self-cleaning capability. Furthermore, the unidirectional flow microfluidic channels design based on the Tesla valve was incorporated into the biosensing patch to prevent external sebum contamination and allow effective sweat refreshing for reliable sensing. By seamlessly combining these components, the epidermal secretion-purified biosensing patch enables continuous monitoring of sweat uric acid, pH, and sodium ions with significantly improved accuracy of up to 12 %. The proposed strategy for enhanced sweat sensing reliability without sebum interference shows desirable compatibility for different types of biosensors and would inspire the advances of flexible and wearable devices for non-invasive healthcare.

An electrochemical sensor based on 2D Zn-MOFs and 2D C-Ti3C2Tx composite materials for rapid and direct detection of various foodborne pathogens.

Rapid screening for foodborne pathogens is crucial for food safety. A rapid and one-step electrochemical sensor has been developed for the detection of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Through the construction of aptamer/two-dimensional carboxylated Ti3C2Tx (2D C-Ti3C2Tx)/two-dimensional Zn-MOF (2D Zn-MOF) composites, the recognition elements, signal tags, and signal amplifiers are integrated on the electrode surface. Pathogens are selectively captured using the aptamer, which increases the impedance of the electrode surface，leads to a decrease in the 2D Zn-MOF current. Bacteria can be rapidly quantified using a one-step detection method and the replacement of aptamers. The detection limits for E. coli, S. aureus, and S. typhimurium are 6, 5, and 5 CFU·mL-1, respectively. The sensor demonstrated reliable detection capabilities in real-sample testing. Therefore, the one-step sensor based on the 2D Zn-MOF and 2D C-Ti3C2Tx has significant application value in the detection of foodborne pathogens.

Smartphone-assisted colorimetric biosensor for the rapid visual detection of natural antioxidants in food samples.

Quantitative monitoring of the concentrations of epigallocatechin gallate (EGCG) and cysteine (Cys) is of great significance for promoting human health. In this study, iron/aluminum bimetallic MOF material MIL-53 (Fe, Al) was rapidly prepared under room temperature using a co-precipitation method, followed by investigating the peroxidase-like (POD-like) activity of MIL-53(Fe, Al) using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate. The results showed that the Michaelis -Menten constants of TMB and H2O2 as substrates were 0.167 mM and 0.108 mM, respectively. A colorimetric sensing platform for detecting EGCG and Cys was developed and successfully applied for analysis and quantitative detection using a smartphone. The linear detection range for EGCG was 15∼80 µM (R2=0.994) and for Cys was 7∼95 µM (R2=0.998). The limits of detection (LOD) were 0.719 µM and 0.363 µM for EGCG and Cys, respectively. This work provides a new and cost-effective approach for the real-time analysis of catechins and amino acids.

Electrochemical biosensors on microfluidic chips as promising tools to study microbial biofilms: a review.

Microbial biofilms play a pivotal role in microbial infections and antibiotic resistance due to their unique properties, driving the urgent need for advanced methodologies to study their behavior comprehensively across varied environmental contexts. While electrochemical biosensors have demonstrated success in understanding the dynamics of biofilms, scientists are now synergistically merging these biosensors with microfluidic technology. This combined approach offers heightened precision, sensitivity, and real-time monitoring capabilities, promising a more comprehensive understanding of biofilm behavior and its implications. Our review delves into recent advancements in electrochemical biosensors on microfluidic chips, specifically tailored for investigating biofilm dynamics, virulence, and properties. Through a critical examination of these advantages, properties and applications of these devices, the review highlights the transformative potential of this technology in advancing our understanding of microbial biofilms in different settings.

A plasmonic biosensor pre-diagnostic tool for Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder, primarily observed in populations around the Mediterranean Sea, linked to MEFV gene mutations. These mutations disrupt inflammatory responses, increasing pyrin-protein production. Traditional diagnosis relies on clinical symptoms, family history, acute phase reactants, and excluding similar syndromes with MEFV testing, which is expensive and often inconclusive due to heterozygous mutations. Here, we present a biosensor platform that detects differences in pyrin-protein levels between healthy and affected individuals, offering a cost-effective alternative to genetic testing. Our platform uses gold nanoparticle-based plasmonic chips enhanced with anti-pyrin antibodies, achieving a detection limit of 0.24 ng/mL with high specificity. The system integrates an optofluidic system and visible light spectroscopy for real-time analysis, with signal stability maintained for up to six months. Our technology will enhance FMF diagnosis accuracy, enabling early treatment initiation and providing a cost-effective alternative to genetic testing, thus improving patient care.

Evaluation of electrodeposition synthesis of gold nanodendrite on screen-printed carbon electrode for nonenzymatic ascorbic acid sensor.

Gold nanodendrite (AuND) is a type of gold nanoparticles with dendritic or branching structures that offers advantages such as large surface area and high conductivity to improve electrocatalytic performance of electrochemical sensors. AuND structures can be synthesized using electrodeposition method utilizing cysteine as growth directing agent. This method can simultaneously synthesize and integrate the gold nanostructures on the surface of the electrode. We conducted a comprehensive study on the synthesis of AuND on screen-printed carbon electrode (SPCE)-based working electrode, focusing on the optimization of electrodeposition parameters, such as applied potential, precursor solution concentration, and deposition time. The measured surface oxide reduction peak current and electrochemical surface area from cyclic voltammogram were used as the optimization indicators. We confirmed the growth of dendritic gold nanostructures across the carbon electrode surface based on FESEM, EDS, and XRD characterizations. We applied the SPCE/AuND electrode as a nonenzymatic sensor on ascorbic acid (AA) and obtained detection limit of 16.8 µM, quantification limit of 51.0 µM, sensitivity of 0.0629 µA µM-1, and linear range of 180-2700 µM (R2 value = 0.9909). Selectivity test of this electrode against several interferences, such as uric acid, dopamine, glucose, and urea, also shows good response in AA detection.

A reconfigurable and conformal liquid sensor for ambulatory cardiac monitoring.

The severe mismatch between solid bioelectronics and dynamic biological tissues has posed enduring challenges in the biomonitoring community. Here, we developed a reconfigurable liquid cardiac sensor capable of adapting to dynamic biological tissues, facilitating ambulatory cardiac monitoring unhindered by motion artifacts or interference from other biological activities. We employed an ultrahigh-resolution 3D scanning technique to capture tomographic images of the skin on the wrist. Then, we established a theoretical model to gain a deep understanding of the intricate interaction between our reconfigurable sensor and dynamic biological tissues. To properly elucidate the advantages of this sensor, we conducted cardiac monitoring alongside benchmarks such as the electrocardiogram. The liquid cardiac sensor was demonstrated to produce stable signals of high quality (23.1 dB) in ambulatory settings.

Double-layer optical fiber interferometer with bio-layer-modified reflector for label-free biosensing of inflammatory proteins.

This work discusses label-free biosensing application of a double-layer optical fiber interferometer where the second layer tailors the reflection conditions at the external plain and supports changes in reflected optical spectrum when a bio-layer binds to it. The double-layer nanostructure consists of precisely tailored thin films, i.e., titanium (TiO2) and hafnium oxides (HfO2) deposited on single-mode fiber end-face by magnetron sputtering. It has been shown numerically and experimentally that the approach besides well spectrally defined interference pattern distinguishes refractive index (RI) changes taking place in a volume and on the sensor surface. These are of interest when label-free biosensing applications are considered. The case of myeloperoxidase (MPO) detection-a protein, which concentration rises during inflammation-is reported as an example of application. The response of the sensor to MPO in a concentration range of 1 × 10-11-5 × 10-6 g/mL was tested. An increase in the MPO concentration was followed by a redshift of the interference pattern and a decrease in reflected power. The negative control performed using ferritin proved specificity of the sensor. The results reported in this work indicate capability of the approach for diagnostic label-free biosensing, possibly also at in vivo conditions.

Using Biosensor Devices and Ecological Momentary Assessment to Measure Emotion Regulation Processes: Pilot Observational Study With Dialectical Behavior Therapy.

Background: Novel technologies, such as ecological momentary assessment (EMA) and wearable biosensor wristwatches, are increasingly being used to assess outcomes and mechanisms of change in psychological treatments. However, there is still a dearth of information on the feasibility and acceptability of these technologies and whether they can be reliably used to measure variables of interest. Objective: Our objectives were to assess the feasibility and acceptability of incorporating these technologies into dialectical behavior therapy and conduct a pilot evaluation of whether these technologies can be used to assess emotion regulation processes and associated problems over the course of treatment. Methods: A total of 20 adults with borderline personality disorder were enrolled in a 6-month course of dialectical behavior therapy. For 1 week out of every treatment month, participants were asked to complete EMA 6 times a day and to wear a biosensor watch. Each EMA assessment included measures of several negative affect and suicidal thinking, among other items. We used multilevel correlations to assess the contemporaneous association between electrodermal activity and 11 negative emotional states reported via EMA. A multilevel regression was conducted in which changes in composite ratings of suicidal thinking were regressed onto changes in negative affect. Results: On average, participants completed 54.39% (SD 33.1%) of all EMA (range 4.7%-92.4%). They also wore the device for an average of 9.52 (SD 6.47) hours per day and for 92.6% of all days. Importantly, no associations were found between emotional state and electrodermal activity, whether examining a composite of all high-arousal negative emotions or individual emotional states (within-person r ranged from -0.026 to -0.109). Smaller changes in negative affect composite scores were associated with greater suicidal thinking ratings at the subsequent timepoint, beyond the effect of suicidal thinking at the initial timepoint. Conclusions: Results indicated moderate overall compliance with EMA and wearing the watch; however, there was no concurrence between EMA and wristwatch data on emotions. This pilot study raises questions about the reliability and validity of these technologies incorporated into treatment studies to evaluate emotion regulation mechanisms.

Multilayer patch functionalized microfibrillated cellulosic paper sensor for sweat glucose monitoring.

Electrochemical analysis of glucose monitoring without painful blood collection provides a new noninvasive route for monitoring glucose levels. Thus, in this study, biobased cellulosic papers (methylated and phosphorylated one) based glucose monitoring sensor is developed. To achieve high hydrophilicity, microfibrillated cellulose (MFC) were functionalized using hexokinase mediated phosphorylation (-OH to -[Formula: see text]). The instinctive increased surface charge density from 36.2 ± 3.4 to 118.4 ± 1.2 µmol/g and decrease contact angle (45°-22°) confirms the increased hydrophilicity of paper. Furthermore, functionalized phos-MFC paper increase the capillary flow of sweat, required low quantity (1 µl) of sweat for accurate analysis of glucose level. Additionally, chemically induced methyl groups (-CH3) make the sensor more barrier to other chemicals. In addition, a multilayer patch design combined with sensor miniaturization was used to lead to an increase in the efficiency of the sweat collection and sensing processes. Besides, this paper sensor integrated with artificial transdermal drug delivery unit (agarose gel as skin) for monitoring glucose levels in sweat. The patch monitoring system increase the accuracy of sensing with fluctuation in sweat vol. (1-4 µl), temperature (20-70 °C), and pH (4.0-7.0). In addition, temperature dependency artificial transdermal delivery (within agarose gel) of drug metformin agrees the measurement accuracy of sensor, called "switch system" without any error. As a result, the reported MFC paper based multi-patch disposable sensing system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

Rapid tear screening of diabetic retinopathy by a detachable surface acoustic wave enabled immunosensor.

BACKGROUND: Diabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples. RESULTS: The device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip. SIGNIFICANCE: This comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition.

Label-Free Biosensor Based on Particle Plasmon Resonance Coupled with Diffraction Grating Waveguide.

Particle plasmon resonance (PPR), or localized surface plasmon resonance (LSPR), utilizes intrinsic resonance in metal nanoparticles for sensor fabrication. While diffraction grating waveguides monitor bioaffinity adsorption with out-of-plane illumination, integrating them with PPR for biomolecular detection schemes remains underexplored. This study introduces a label-free biosensing platform integrating PPR with a diffraction grating waveguide. Gold nanoparticles are immobilized on a glass slide in contact with a sample, while a UV-assisted embossed diffraction grating is positioned opposite. The setup utilizes diffraction in reflection to detect changes in the environment's refractive index, indicating biomolecular binding at the gold nanoparticle surface. The positional shift of the diffracted beam, measured with varying refractive indices of sucrose solutions, shows a sensitivity of 0.97 mm/RIU at 8 cm from a position-sensitive detector, highlighting enhanced sensitivity due to PPR-diffraction coupling near the gold nanoparticle surface. Furthermore, the sensor achieved a resolution of 3.1 × 10-4 refractive index unit and a detection limit of 4.4 pM for detection of anti-DNP. The sensitivity of the diffracted spot was confirmed using finite element method (FEM) simulations in COMSOL Multiphysics. This study presents a significant advancement in biosensing technology, offering practical solutions for sensitive, rapid, and label-free biomolecule detection.

Wearable Sensor-Based Assessments for Remotely Screening Early-Stage Parkinson's Disease.

Prevalence estimates of Parkinson's disease (PD)-the fastest-growing neurodegenerative disease-are generally underestimated due to issues surrounding diagnostic accuracy, symptomatic undiagnosed cases, suboptimal prodromal monitoring, and limited screening access. Remotely monitored wearable devices and sensors provide precise, objective, and frequent measures of motor and non-motor symptoms. Here, we used consumer-grade wearable device and sensor data from the WATCH-PD study to develop a PD screening tool aimed at eliminating the gap between patient symptoms and diagnosis. Early-stage PD patients (n = 82) and age-matched comparison participants (n = 50) completed a multidomain assessment battery during a one-year longitudinal multicenter study. Using disease- and behavior-relevant feature engineering and multivariate machine learning modeling of early-stage PD status, we developed a highly accurate (92.3%), sensitive (90.0%), and specific (100%) random forest classification model (AUC = 0.92) that performed well across environmental and platform contexts. These findings provide robust support for further exploration of consumer-grade wearable devices and sensors for global population-wide PD screening and surveillance.

Screen-Printed Electrodes as Low-Cost Sensors for Breast Cancer Biomarker Detection.

This review explores the emerging role of screen-printed electrodes (SPEs) in the detection of breast cancer biomarkers. We discuss the fundamental principles and fabrication techniques of SPEs, highlighting their adaptability and cost-effectiveness. The review examines various modification strategies, including nanomaterial incorporation, polymer coatings, and biomolecule immobilization, which enhance sensor performance. We analyze the application of SPEs in detecting protein, genetic, and metabolite biomarkers associated with breast cancer, presenting recent advancements and innovative approaches. The integration of SPEs with microfluidic systems and their potential in wearable devices for continuous monitoring are explored. While emphasizing the promising aspects of SPE-based biosensors, we also address current challenges in sensitivity, specificity, and real-world applicability. The review concludes by discussing future perspectives, including the potential for early screening and therapy monitoring, and the steps required for clinical implementation. This comprehensive overview aims to stimulate further research and development in SPE-based biosensors for improved breast cancer management.

Photonic Dipstick Immunosensor to Detect Adulteration of Ewe, Goat, and Donkey Milk with Cow Milk through Bovine κ-Casein Detection.

The quality and authenticity of milk are of paramount importance. Cow milk is more allergenic and less nutritious than ewe, goat, or donkey milk, which are often adulterated with cow milk due to their seasonal availability and higher prices. In this work, a silicon photonic dipstick sensor accommodating two U-shaped Mach-Zehnder Interferometers (MZIs) was employed for the label-free detection of the adulteration of ewe, goat, and donkey milk with cow milk. One of the two MZIs of the chip was modified with bovine κ-casein, while the other was modified with bovine serum albumin to serve as a blank. All assay steps were performed by immersion of the chip side where the MZIs are positioned into the reagent solutions, leading to a photonic dipstick immunosensor. Thus, the chip was first immersed in a mixture of milk with anti-bovine κ-casein antibody and then in a secondary antibody solution for signal enhancement. A limit of detection of 0.05% v/v cow milk in ewe, goat, or donkey milk was achieved in 12 min using a 50-times diluted sample. This fast, sensitive, and simple assay, without the need for sample pre-processing, microfluidics, or pumps, makes the developed sensor ideal for the detection of milk adulteration at the point of need.

Preliminary Evaluation of New Wearable Sensors to Study Incongruous Postures Held by Employees in Viticulture.

Musculoskeletal Disorders (MSDs) stand as a prominent cause of injuries in modern agriculture. Scientific research has highlighted a causal link between MSDs and awkward working postures. Several methods for the evaluation of working postures, and related risks, have been developed such as the Rapid Upper Limb Assessment (RULA). Nevertheless, these methods are generally applied with manual measurements on pictures or videos. As a consequence, their applicability could be scarce, and their effectiveness could be limited. The use of wearable sensors to collect kinetic data could facilitate the use of these methods for risk assessment. Nevertheless, the existing system may not be usable in the agricultural and vine sectors because of its cost, robustness and versatility to the various anthropometric characteristics of workers. The aim of this study was to develop a technology capable of collecting accurate data about uncomfortable postures and repetitive movements typical of vine workers. Specific objectives of the project were the development of a low-cost, robust, and wearable device, which could measure data about wrist angles and workers' hand positions during possible viticultural operations. Furthermore, the project was meant to test its use to evaluate incongruous postures and repetitive movements of workers' hand positions during pruning operations in vineyard. The developed sensor had 3-axis accelerometers and a gyroscope, and it could monitor the positions of the hand-wrist-forearm musculoskeletal system when moving. When such a sensor was applied to the study of a real case, such as the pruning of a vines, it permitted the evaluation of a simulated sequence of pruning and the quantification of the levels of risk induced by this type of agricultural activity.

Analytical Performance of the FreeStyle Libre 2 Glucose Sensor in Healthy Male Adults.

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.