High Reproducibility Research Articles

Electrochemical Nanomolar Determination of the Anticancer Drug 5-Fluorouracil Using Chitosan Curcumin Schiff Base-Decorated NiO Nanorods Synthesized with Green Method

5-Fluorouracil (5-FU) is widely used in the treatment of various cancers, necessitating accurate and sensitive detection techniques. Hybrid materials, combining organic and inorganic components, offer superior electrochemical characteristics, including enhanced conductivity and stability. Herein, NiO nanorods (NiONRs) were synthesized using Mangifera indica leaves extract and decorated with chitosan curcumin analog Schiff base (Cs-Cur-A). The characterization of the NiONRs and Cs-Cur-A were investigated through different techniques including FT-IR, 1HNMR, XRD, SEM, and EDX. A sensitive and selective electrochemical sensor to determine 5-FU was elucidated using a Cs-Cur-A/NiONRs modified glassy carbon electrode (GCE). The anodic peak current of 5-FU was greatly enhanced at the Cs-Cur-A/NiONRs/GCE with pH 7.0 and a scan rate of 50 mV s−1. According to chronoamperometric measurements, the value of diffusion coefficient (D) was estimated to be 2.96 × 10−6 cm2 s−1. Using differential pulse voltammetry (DPV), the fabricated sensor exhibits a wide linear range (0.1–150.0 μM) with a low limit of detection (21.75 nM). Moreover, the proposed sensor was successfully applied to the detection of 5-FU in blood serum and urine samples with high reproducibility, repeatability, and selectivity.

High-Resolution Melting (HRM) analysis of DNA methylation using semiconductor chip-based digital PCR.

Digital PCR (dPCR) technology allows absolute quantification and detection of disease-associated rare variants, and thus the use of dPCR technology has been increasing in clinical research and diagnostics. The high-resolution melting curve analysis (HRM) of qPCR is widely used to distinguish true positives from false positives and detect rare variants. In particular, qPCR-HRM is commonly used for methylation assessment in research and diagnostics due to its simplicity and high reproducibility. Most dPCR instruments have limited fluorescence channels available and separate heating and imaging systems. Therefore, it is difficult to perform HRM analysis using dPCR instruments. A new digital real-time PCR instrument (LOAA) has been recently developed to integrate partitioning, thermocycling, and imaging in a single dPCR instrument. In addition, a new technique to perform HRM analysis is utilized in LOAA. The aim of the present study is to evaluate the efficiency and accuracy of LOAA dPCR on HRM analysis for the detection of methylation. In this study, comprehensive comparison with Bio-Rad qRT-PCR and droplet-based dPCR equipment was performed to verify the HRM analysis-based methylation detection efficiency of the LOAA digital PCR equipment. Here, sodium bisulfite modification method was applied to detect methylated DNA sequences by each PCR method. Melting curve analysis detected four different Tm values using LOAA and qPCR, and found that LOAA, unlike qPCR, successfully distinguished between different Tm values when the Tm values were very similar. In addition, melting temperatures increased by each methylation were about 0.5℃ for qPCR and about 0.2 ~ 0.6℃ for LOAA. The melting temperature analyses of methylated and unmethylated DNA samples were conducted using LOAA dPCR with TaqMan probes and EvaGreen, and the result found that Tm values of methylated DNA samples are higher than those of unmethylated DNA samples. The present study shows that LOAA dPCR could detect different melting temperatures according to methylation status of target sequences, indicating that LOAA dPCR would be useful for diagnostic applications that require the accurate quantification and assessment of DNA methylation.

Analysis of Three-Dimensional Tooth Movement: A Comparative Study Between Digital Dental Models and Craniofacial Models.

This study aims to validate the efficacy of using a digital dental model (DM) with reference to the palatal region of interest (PROI) for assessing orthodontic tooth movement (TM)by comparing it with the analysis of a computed tomography (CT) model with reference to the cranial region of interest (CROI). Thirty-four patients (mean age: 21 years and 11 months) with jaw deformities underwent DM and CT scans before and after presurgical orthognathic treatment. Linear and angular measurements during TM were conducted in three dimensions using both DM and CT to assess reliability. DM analysis with PROI registration exhibited high levels of reproducibility, with minimal standard errors in X, Y, and Z displacements (<0.15 mm) and 0.43 degrees in angular change. CT analysis with CROI registration demonstrates similarly high reproducibility, with standard errors inferior to DM analysis (<0.20 mm). Bland-Altman analysis indicated agreement in linear changes of each X, Y, and Z displacement between DM and CT measurements, with limits of agreement (LOA) below 0.91 mm. The results of this study suggest that the PROI, focusing on the third palatal rugae and the horizontal part of the palatal vault, serves as a reliable reference region for evaluating three-dimensional (3D) tooth movement. Digital dental models offer distinct advantages including the absence of X-ray exposure, no metal artifacts, and the ability to generate high-resolution 3D models. The methodology demonstrated high precision and reproducibility, supporting its potential clinical utility in orthodontic treatment planning and assessment.

Rapid and robust isolation of microglia and vascular cells from brain subregions for integrative single-cell analyses

Cell isolation protocols from brain tissue include prolonged ex vivo processing durations, rendering them suboptimal for transcriptomic studies. Particularly for microglia and vascular cells, current isolation methods produce lower yields, necessitating addition of an enrichment step, and use of large tissue volumes - in most cases whole brain tissue - to obtain sufficient yields. Here, we developed a simple, rapid, and reproducible cell isolation method for generating single-cell suspensions from micro-dissected brain regions, enriched for microglia and vascular cells, without an enrichment step. Cells isolated using this method are suitable for molecular profiling studies using 10 × Genomics Chromium single-cell RNA sequencing with high reproducibility. Our method is valuable for longitudinal unbiased molecular profiling of microglia and vascular cells within different brain regions, spanning multiple time points across physiological development or disease progression.

Validating the short-version European Health Literacy Survey Questionnaire for community-dwelling older adults in Japan.

The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is available in multiple languages, and shortened versions have also been developed. This study aimed to examine the reliability and validity of the short version of the questionnaire (HLS-Q12) developed for community-dwelling older adults in Japan. The HLS-Q12 was developed using 12 of the 47 items of the Japanese version of the HLS-EU-Q47. In this study, the survey was conducted by distributing self-administered questionnaires to community-dwelling individuals aged 65 years and older who consented to participate; their responses were collected by mail. The correlation between the HLS-Q12 and the HLS-EU-Q47 was tested to assess criterion validity. To test construct validity, nine novel hypotheses were proposed. We also conducted a confirmatory factor analysis of the HLS-Q12. Based on a resurvey after 5-7 days, test-retest reliability was examined using interclass correlation coefficients (ICCs) and Bland-Altman analysis. In total, 118 individuals provided valid responses to the questionnaire. The Spearman rank correlation coefficient between the HLS-Q12 and the HLS-EU-Q47 was r = 0.98 (p < 0.001), and eight of the nine hypotheses were supported. The ICC was 0.96 (p < 0.001), and the 95% limit of agreement was -0.26 ± 5.9, suggesting no systematic error. Thus, the Japanese version of the HLS-Q12 was found to be reliable with high criterion validity and reproducibility. Hence, the HLS-Q12 is a useful scale for measuring health literacy among older adults in Japan.

The establishment of a novel upper cervical complex fracture classification system

BACKGROUND CONTEXTUpper cervical complex fractures are associated with high rates of neurological damage and mortality. The Dickman's classification is widely used in the diagnosis of upper cervical complex fractures. However, it falls short of covering the full spectrum of complex fractures. This limitation hinders effective diagnosis and treatment of these injuries. PURPOSETo address the diagnostic gap in upper cervical complex fractures, the study introduces a novel classification system for these injuries, assessing its reliability and usability. STUDY DESIGNProposal of a new classification system for upper cervical complex fractures. PATIENT SAMPLEThe study comprised the clinical data of 242 patients with upper cervical complex fractures, including 32 patients treated at our hospital, along with an additional 210 cases from the literature. OUTCOME MEASURESThe inter-observer and intra-observer reliability (kappa coefficient, κ) of this classification system were investigated by 3 spine surgeons. The 3 researchers independently re-evaluated the upper cervical complex fracture classification system 3 months later. METHODSThe proposed classification categorizes upper cervical complex fractures into 3 main types: Type I combines odontoid and Hangman's fractures into 2 subtypes; Type II merges C1 with odontoid/Hangman's fractures into 3 subtypes; and Type III encompasses a combination of C1, odontoid, and Hangman's fractures, divided into 2 subtypes. Meanwhile, a questionnaire was administered in 15 assessors to evaluate the system's ease of use and clinical applicability. RESULTSA total of 45 cases (18.6%) unclassifiable by Dickman's classification were successfully categorized using our system. The mean κ value of inter-observer reliability was 0.783, indicating substantial reliability. The mean κ value of intra-observer reliability was 0.862, indicating almost perfect reliability. Meanwhile, thirteen assessors (87.7%) stated that the classification system is easy to remember, easy to apply, and they expressed intentions to apply it in clinical practice in the future. CONCLUSIONSThis system not only offers high confidence and reproducibility but also serves as a precise guide for clinicians in formulating treatment plans. Future prospective applications are warranted to further evaluate this classification system.

Development of a 3-dimensional organotypic model with characteristics of peripheral sensory nerves

We developed a rat dorsal root ganglion (DRG)-derived sensory nerve organotypic model by culturing DRG explants on an organoid culture device. With this method, a large number of organotypic cultures can be produced simultaneously with high reproducibility simply by seeding DRG explants derived from rat embryos. Unlike previous DRG explant models, this organotypic model consists of a ganglion and an axon bundle with myelinated A fibers, unmyelinated C fibers, and stereo-myelin-forming nodes of Ranvier. The model also exhibits Ca2+ signaling in cell bodies in response to application of chemical stimuli to nerve terminals. Further, axonal transection increases the activating transcription factor 3 mRNA level in ganglia. Axons and myelin are shown to regenerate 14days following transection. Our sensory organotypic model enables analysis of neuronal excitability in response to pain stimuli and tracking of morphological changes in the axon bundle over weeks.

A Comparison of Tooth Size and Arch Dimensions Among Measurements Taken Intraorally with 3D-Printed and Digital Models Obtained from Intraoral Scans.

To compare measurements of tooth size and arch dimensions among those taken directly intraorally with those made on digital and 3D printed models produced by intraoral scanning. Sixty-six participants were recruited. Intraoral tooth size and arch measurements were taken intraorally with a digital caliper. Digital impressions were taken with an iTero® intraoral scanner. The three-dimensional digital models were measured using a 3D diagnostics tool (OrthoCAD software). The same digital models were used to fabricate physical models using a resin 3D printer (Elegoo Saturn). The measurements were repeated on 3D printed models by using the digital caliper. The recorded parameters included mesiodistal tooth widths, transverse, and antero-posterior dimensions. All measurements were repeated to assess intra- and inter- examiner reliability. The validity of each measurement method was assessed by repeated measures ANOVA with post-hoc pairwise comparisons (p<0.5). The mean differences among three methods for all parameters were statistically significant (p<.05) but were considered to be clinically insignificant, except for the upper intercanine width. Direct intraoral measurements tend to be smaller than the digital and 3D printed models. The ICCs values indicated excellent intra- and inter-examiner reliability which demonstrates high reproducibility for all measurements on all model types. Direct intraoral measurements tend to be smaller than the digital and 3D printed models. However, the accuracy of measurements made directly intraorally, and on digital and 3D models from intraoral scans is clinically acceptable, except for the upper intercanine width. Key words:Tooth measurements, Accuracy, Dental models, 3D printing, Digital model.

Quantification of Glycyrrhizic Acid in FLEGMEN-SIP Capsules Using High-Performance Liquid Chromatography for CNS Disorders

Background: Neurological diseases affect over one billion people globally, presenting a significant health burden, especially for vulnerable populations. The FLEGMEN-SIP capsule was developed as a treatment option for central nervous system disorders, containing glycyrrhizic acid as its primary active ingredient. This study aims to quantify the glycyrrhizic acid content in FLEGMEN-SIP capsules using high-performance liquid chromatography (HPLC) to ensure compliance with therapeutic standards. Methods: The study utilized HPLC to quantify glycyrrhizic acid in FLEGMEN-SIP capsules. The capsules contain a dry extract derived from Phlomis regelii, Leonurus turkestanicus, Mentha piperita, and Glycyrrhiza glabra, with glycyrrhizic acid comprising 1.39% of the dry extract. Samples were prepared by dissolving 0.050 g of the drug in the mobile phase and filtered using a 0.45 µm membrane filter. The HPLC system included a Zorbax column and UV detection at 254 nm. The analysis was repeated five times for accuracy. Results: The glycyrrhizic acid content in FLEGMEN-SIP capsules was determined to be 0.55%, surpassing the minimum regulatory requirement of 0.4%. The chromatographic method demonstrated high reproducibility and reliability, confirming the quality and therapeutic efficacy of the capsules. Conclusion: The study validated the use of HPLC as an effective method for quantifying glycyrrhizic acid in FLEGMEN-SIP capsules. The results confirm the capsules meet regulatory standards, ensuring their suitability for treating central nervous system disorders.

Non-invasive Assessment and Management of Folliculitis Decalvans by Trichoscopy and Reflectance Confocal Microscopy.

Folliculitis decalvans (FD) is a rare scarring alopecia mainly affecting middle-aged men, characterized by recurring episodes of follicular pustules, crusts, erythema, tufted hairs, and scars. This study investigates the effectiveness of reflectance confocal microscopy (RCM) compared to trichoscopy for diagnosing and monitoring FD. The study involved 24 Caucasian patients diagnosed with FD. Patients were examined using trichoscopy and RCM, with a focus on specific features like erythema and inflammatory cell distribution. A subgroup of 16 patients was followed up after 3 months of therapy. The reproducibility of RCM and trichoscopy was assessed using Cohen Kappa Test. RCM and trichoscopy consistently detected features such as tufted hairs, pustules, and perifollicular fibrosis. However, RCM provided more detailed insights into inflammatory activity and types of fibrosis, often overlooked by trichoscopy. It showed a reduction in vessels and inflammatory cells, which trichoscopy failed to detect. The concordance between RCM evaluations was excellent, indicating high reproducibility. RCM is effective in diagnosing and monitoring FD, offering detailed insights into inflammation and fibrosis. It complements trichoscopy, especially in aspects where trichoscopy is limited, such as precise measurement of inflammation. The study suggests that combining RCM with trichoscopy could enhance the accuracy of diagnosis and monitoring of FD, leading to tailored therapeutic approaches. Further studies with larger sample sizes and longitudinal designs are recommended to confirm these findings.

Towards novel classification of infants’ movement patterns supported by computerized video analysis

BackgroundPositional preferences, asymmetry of body position and movements potentially indicate abnormal clinical conditions in infants. However, a lack of standardized nomenclature hinders accurate assessment and documentation of these preferences over time. Video tools offer a safe and reproducible method to analyze and describe infant movement patterns, aiding in physiotherapy management and goal planning. The study aimed to develop an objective classification system for infant movement patterns with particular emphasis on the specific distribution of muscle tension, using methods of computer analysis of video recordings to enhance accuracy and reproducibility in assessments.MethodsThe study involved the recording of videos of 51 infants between 6 and 15 weeks of age, born at term, with an Apgar score of at least 8 points. Based on observations of a recording of infant spontaneous movements in the supine position, experts identified postural-motor patterns: symmetry and typical asymmetry linked to the asymmetrical tonic neck reflex. Deviations from the typical postural-motor system were indicated, and subcategories of atypical patterns were distinguished. A computer-based inference system was developed to automatically classify individual patterns.ResultsThe following division of motor patterns was used: (1) normal patterns, including (a) typical (symmetrical, asymmetrical: variants 1 and 2); and (b) atypical (variants: 1 to 4), (2) positional preference, and (3) abnormal patterns. The proposed automatic classification method achieved an expert decision mapping accuracy of 84%. For atypical patterns, the high reproducibility of the system’s results was confirmed. Lower reproducibility, not exceeding 70%, was achieved with typical patterns.ConclusionsBased on the observation of infant spontaneous movements, it is possible to identify movement patterns divided into typical and atypical patterns. Computer-based analysis of infant movement patterns makes it possible to objectify and satisfactorily reproduce diagnostic decisions.

Development and psychometric properties of the Functional Assessment of Cancer Therapy-Cutaneous T-Cell Lymphoma (FACT-CTCL).

Patients with Mycosis Fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy - General (FACT-G), in patients with MF/SS. Qualitative interviews were conducted with expert clinicians and MF/SS patients. Thematic analysis identified the most common concerns, and 19 items were selected.MF/SS patients were recruited from a single center. FACT-G, CTCL-S (collectively "FACT-CTCL"), Skindex29, and Visual Analogue Scale-Pruritis (VAS itch) were administered. A subset repeated FACT-CTCL and VAS itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical record.Psychometric properties were assessed. Internal consistency was estimated using Cronbach's alpha (α). Convergent and discriminant validity were assessed by comparing CTCL-S to disease stage, age, VAS itch, FACT-G, and SkinDex29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and within-subject coefficient of variation. Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS itch after ≈2 weeks. Two-thirds were male, most were white (78%). The majority (85%) had MF, 15% SS, and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high (α: 0.95 [95% CI: 0.93-0.96]). There was no significant change in CTCL-S average test-retest scores (ICC of 0.93 (p = 0.63)). CTCL-S was significantly lower in advanced vs early stage disease (median[IQR]: 34[26, 48] vs. 59[44, 68], p < 0.001) and strongly correlated with VAS itch (Spearman's r (rs): -0.70, 95% CI: -0.81, -0.55), FACT-G (rs: 0.77, 95% CI: 0.65, 0.85), and Skindex29 (rs: -0.90, 95% CI: -0.94, -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs: 0.19, 95% CI: -0.05, 0.41, p = 0.12), supporting discriminant validity. The FACT-CTCL is a disease specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.

Clinical application potential of large language model: a study based on thyroid nodules.

Limited data indicated the performance of large language model (LLM) taking on the role of doctors. We aimed to investigate the potential for ChatGPT-3.5 and New Bing Chat acting as doctors using thyroid nodules as an example. A total of 145 patients with thyroid nodules were included for generating questions. Each question was entered into chatbot of ChatGPT-3.5 and New Bing Chat five times and five responses were acquired respectively. These responses were compared with answers given by five junior doctors. Responses from five senior doctors were regarded as gold standard. Accuracy and reproducibility of responses from ChatGPT-3.5 and New Bing Chat were evaluated. The accuracy of ChatGPT-3.5 and New Bing Chat in answering Q2, Q3, Q5 were lower than that of junior doctors (all P < 0.05), while both LLMs were comparable to junior doctors when answering Q4 and Q6. In terms of "high reproducibility and accuracy", ChatGPT-3.5 outperformed New Bing Chat in Q1 and Q5 (P < 0.001 and P = 0.008, respectively), but showed no significant difference in Q2, Q3, Q4, and Q6 (P > 0.05 for all). New Bing Chat generated higher accuracy than ChatGPT-3.5 (72.41% vs 58.62%) (P = 0.003) in decision making of thyroid nodules, and both were less accurate than junior doctors (89.66%, P < 0.001 for both). The exploration of ChatGPT-3.5 and New Bing Chat in the diagnosis and management of thyroid nodules illustrates that LLMs currently demonstrate the potential for medical applications, but do not yet reach the clinical decision-making capacity of doctors.

Facile fabrication of THz metasurfaces by a spatially shaped femtosecond laser printing system

Terahertz (THz) metasurfaces provide unprecedented abilities to realize versatile THz wavefronts manipulations. Nevertheless, these high degree of freedom, non-periodic, densely arranged subwavelength unit cells pose numerous extreme parameter requirements for the fabrication of metasurfaces, presenting significant challenges to their practical application. Herein, a spatial shaping femtosecond laser printing system, based on spatial light modulation (SLM), is proposed for the creation of THz metasurfaces. Through programming the SLM with a sequence of computer-generated holograms (CGH) corresponding to C-shaped Bessel beams with varying opening angles and orientation angles, the C-shaped slit resonant rings with different geometric parameters—fundamental units of the metasurface—were precisely printed onto a gold film. To validate this technique, a THz metalens based on a phased gradient design and a THz holographic plate employing simultaneous phase and amplitude modulation were meticulously fabricated, displaying outstanding performance. Owing to the simple processing flow, high reproducibility, and wide applicability of materials, this technique stands out as a versatile and efficient approach for fabricating THz metasurfaces, with the potential to promote the commercialization of terahertz metasurfaces.

A sensitive, expandable AQC-based LC-MS/MS method to measure amino metabolites and sphingolipids in cell and serum samples

Sphingolipids are a major lipid species found in all eukaryotes. Among structurally complex and diversified lipids, sphingoid bases have been heavily linked to various metabolic diseases. However, most current LC-MS-based methods lack the sensitivity to detect low-abundant sphingoid bases. The 6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization reagent, which efficiently forms covalent bonds with amino groups, has been widely used for amino acid detection. Nevertheless, the commonly used reverse-phase HPLC method for amino acid analysis is not suitable for amphipathic sphingolipids. To address this issue, we report a robust reverse-phase HPLC-MS/MS method capable of separating and detecting hydrophilic amino acids and sphingoid bases in a single run with high sensitivity. This method is also inclusive of other amino metabolites with an expandable target list. We tested this method under various conditions and samples, demonstrating its high reproducibility and sensitivity. Using this approach, we systematically analyzed human serum samples from healthy individuals, dyslipidemia, and type II diabetes mellitus (T2DM) patients, respectively. Two sphingolipids and five amino acids were identified with significant differences between the control and T2DM groups, highlighting the potential of this method in clinical studies.

TEG® 6s coagulation testing with a novel heparin neutralization cartridge: Technical validation and determination of normal reference ranges.

We sought to establish normal reference ranges (NRRs) for a novel TEG 6s cartridge (TEG 6s Citrated: K, KH, RTH, FFH [Global Hemostasis]) (Haemonetics Corporation, Boston, MA, US). Healthy volunteers (≥18 years of age) included in this single-arm study provided single samples of whole blood. Primary end points included TEG parameters in the citrated kaolin (CK), CK with heparinase (CKH), RapidTEG with heparinase (CRTH), and functional fibrinogen with heparinase (CFFH) assays. Evaluable data were contributed by 164 volunteers (48.8% female; 62% White/Caucasian). The following NRRs were established: CK maximum amplitude (MA), 51.0 to 67.6mm; CKH-MA, 51.8 to 67.9mm; CRTH-MA, 53.0 to 68.9mm; CFFH-MA, 15.3 to 34.4mm; CK reaction time, 5.0 to 9.1 minutes; CKH reaction time, 4.9 to 9.4 minutes; CKH lysis 30 minutes after MA, 0% to 3.2%. Duplicate measurements demonstrated high reproducibility. CFFH-MA correlated with Clauss fibrinogen concentration (Pearson correlation coefficient, 0.74). Laboratory-based studies demonstrated maintenance of the relationship between CFFH-MA and fibrinogen up to 1344mg/dL (hyperfibrinogenemic samples) and acceptability of heparin neutralization up to concentrations of low molecular weight and unfractionated heparin of 1.3 IU/mL and 5 IU/mL, respectively. This study established NRRs for the Global Hemostasis cartridge and serves as a proof of concept for the validity of results obtained using this cartridge.

High-Performance Gate-Controlled Superconducting Switches: Large Output Voltage and Reproducibility.

Logic circuits consist of devices that can be controlled between two distinct states. The recent demonstration that a superconducting current flowing in a constriction can be controlled via a gate voltage (VG)─gate-controlled supercurrent (GCS)─can lead to superconducting logic with better performance than existing logics. However, before such logic is developed, high reproducibility in the functioning of GCS devices and optimization of their performance must be achieved. Here, we report an investigation of gated Nb devices showing GCS with very high reproducibility. Based on the investigation of a statistically significant number of devices, we demonstrate that the GCS is independent of the constriction width, in contrast with previous reports, and confirm a strong correlation between the GCS and the leakage current (Ileak) induced by VG. We also achieve a voltage output in our devices larger than the typical values reported to date by at least 1 order of magnitude, which is relevant for the future interconnection of devices, and show that Ileak can be used as a tool to modulate the operational VG of devices on a SiO2 substrates. These results altogether represent an important step forward toward the optimization of reproducibility and performance of GCS devices, and the future development of a GCS-based logic.

Non-Invasive Disposable 2D Ti3C2Tx based Enzyme Free Electrochemical Sweat Glucose Biosensor

Modern analytical chemistry, enhanced by advancements in materials science, is crucial for cost-effectively improving measurement techniques, and making analyses more accessible and user-friendly. Disposable screen-printed electrodes have emerged as promising tools, offering miniaturization, high reproducibility, high sensitivity, rapid detection, and inherent selectivity. This study highlights the development of advanced 2D Ti3C2Tx MXene-modified disposable screen-printed gold electrodes for non-invasive, enzyme-free glucose sensing. Ti3C2Tx was synthesized using direct and in-situ etchants to achieve controlled surface chemistry. Techniques such as XRD, UV–visible spectroscopy, SEM, and TEM were employed to characterize Ti3C2Tx synthesized with different etchants. The synthesized materials were then used as working electrodes to investigate their electrocatalytic performance, tailored for continuous glucose monitoring. Upon optimization, in-situ LiF and HCl etched Li-Ti3C2Tx@SPGE exhibited a high sensitivity of 569.70 µA mM−1cm−2, followed by HF-Ti3C2Tx@SPGE and N-Ti3C2Tx@SPGE with sensitivities of 249.62 and 297.78 µA mM−1cm−2, respectively. These sensors demonstrated low limits of detection (LOD) of 5 nM, 28 nM, and 19 nM within a linear range of 5 to 350 µM. Additionally, real sweat analysis was conducted by collecting natural sweat through fast walking and evaluating sensor performance after beverage consumption. Overall, Li-Ti3C2Tx@SPGE, without any additional composition or doping, shows potential as a superior commercial sweat sensor for routine glucose monitoring. This study underscores the innovative use of 2D materials in developing highly sensitive, non-invasive sweat glucose sensors that are both effective and accessible.

Unenhanced computed tomography as a diagnostic tool in suspected pulmonary hypertension: a retrospective cross-sectional pilot study.

Computed tomography pulmonary angiography (CTPA) has been proposed to be diagnostic for pulmonary hypertension (PH) in multiple studies. However, the utility of the unenhanced CT measurements diagnosing PH has not been fully assessed. This study aimed to assess the diagnostic utility and reproducibility of cardiac and great vessel parameters on unenhanced computed tomography (CT) in suspected pulmonary hypertension (PH). In total, 42 patients with suspected PH who underwent unenhanced CT thorax and right heart catheterization (RHC) were included in the study. Three observers (a consultant radiologist, a specialist registrar in radiology, and a medical student) measured the parameters by using unenhanced CT. Diagnostic accuracy of the parameters was assessed by area under the receiver operating characteristic curve (AUC). Inter-observer variability between the consultant radiologist (primary observer) and the two secondary observers was determined by intra-class correlation analysis (ICC). Overall, 35 patients were diagnosed with PH by RHC while 7 patients were not. Main pulmonary arterial (MPA) diameter was the strongest (AUC 0.79 to 0.87) and the most reproducible great vessel parameter. ICC comparing the MPA diameter measurement of the consultant radiologist to the specialist registrar's and the medical student's were 0.96 and 0.92, respectively. Right atrial area was the cardiac measurement with highest accuracy and reproducibility (AUC 0.76 to 0.79; ICC 0.980, 0.950) followed by tricuspid annulus diameter (AUC 0.76 to 0.79; ICC 0.790, 0.800). MPA diameter and right atrial areas showed high reproducibility. Diagnostic accuracies of these were within the range of acceptable to excellent, and might have clinical value. Tricuspid annular diameter was less reliable and less diagnostic and was therefore not a recommended diagnostic measurement.

Direct ink writing of biomimetic hydroxyapatite scaffolds with tailored concave porosity

Direct ink writing is a promising technology for the fabrication of personalized bone grafts, as it enables the customization of their geometrical conformation with high reproducibility and is compatible with the use of self-setting calcium deficient hydroxyapatite inks. However, the scaffolds obtained by DIW consist mostly of convex filaments, which is a limitation since concave surfaces have been shown to promote bone regeneration in vivo. In this work, we explore the use of triply periodic minimal surface (TPMS) designs in DIW of calcium phosphate self-hardening inks as a strategy to obtain scaffolds with controlled concave macropores. The limitations of the printing parameters with high ceramic loaded inks used in DIW enabled achieving only 20% nominal porosities of Gyroid-, Diamond- and Schwarz-based structures. The inherent layered pores from TPMS geometries allowed obtaining concavities typically unattainable via DIW, bearing substantial implications for subsequent osteoinductive capabilities. Although the mechanical properties were lower in the TPMS-based scaffolds than in the orthogonal patterned ones, the blood permeability of the TPMS-based structures was higher. The concave pore architecture enhanced the osteogenic potential of the biomimetic ceramic, increasing SaOs-2 cell adhesion, proliferation, differentiation and mineralisation.&amp;nbsp;&amp;nbsp;