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19 pages, 1849 KiB  
Article
A Simultaneous Determination of the B1 and B6 Vitamers Reveals Their Loss During a Single Peritoneal Dialysis Session: Chromatographic and Chemometric Approach
by Paweł Rudnicki-Velasquez, Karol Krzymiński, Magdalena Jankowska, Anna Baraniak and Paulina Czaplewska
Int. J. Mol. Sci. 2025, 26(15), 7177; https://doi.org/10.3390/ijms26157177 - 25 Jul 2025
Viewed by 110
Abstract
This study aimed to assess the extent of vitamin B1 and B6 vitamer loss during a single peritoneal dialysis (PD) session using a combination of chromatographic techniques and chemometric analysis. Dialysis effluent samples were collected from 41 PD patients (22 on [...] Read more.
This study aimed to assess the extent of vitamin B1 and B6 vitamer loss during a single peritoneal dialysis (PD) session using a combination of chromatographic techniques and chemometric analysis. Dialysis effluent samples were collected from 41 PD patients (22 on continuous ambulatory peritoneal dialysis (CAPD) and 19 on automated peritoneal dialysis (APD)) during a standardised peritoneal equilibration test. Concentrations of thiamine monophosphate, thiamine diphosphate (ThDP), pyridoxine, pyridoxal (PL), and pyridoxamine were determined using high-performance liquid chromatography with a fluorescence detector. The analytical method was validated in terms of sensitivity, linearity, accuracy, and recovery. Multiple regression analysis was employed to identify potential clinical and demographic predictors of vitamin washout. All vitamers except pyridoxal 5-phosphate (PLP) were detectable in dialysis effluents. ThDP exhibited the greatest loss among the B1 forms (ca. 0.05–0.57 mg/24 h), while PL exhibited the most significant loss among the B6 forms (ca. 0.01–0.19 mg/24 h). Vitamin losses varied depending on the dialysis modality (continuous ambulatory peritoneal dialysis, or CAPD, versus automated peritoneal dialysis, or APD) and the peritoneal transport category. Regression analysis identified body weight, haemoglobin, and haematocrit as independent predictors of ThDP washout (R2 = 0.58). No statistically robust models were established for the other vitamers. Even short medical procedures (such as single PD) can result in measurable losses of water-soluble vitamins, particularly ThDP and PL. The results emphasise the importance of personalised vitamin supplementation for PD patients and suggest that body composition and haematological parameters significantly influence the loss of thiamine. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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10 pages, 314 KiB  
Communication
Simplifying Antibiotic Management of Peritonitis in APD: Evidence from a Non-Inferiority Randomized Trial
by Jesús Venegas-Ramírez, Benjamín Trujillo-Hernández, Carmen Citlalli Castillón-Flores, Fernanda Janine Landín-Herrera, Erika Herrera-Oliva, Patricia Calvo-Soto, Rosa Tapia-Vargas, Alejandro Figueroa-Gutiérrez, Eder Fernando Ríos-Bracamontes, Karina Esmeralda Espinoza-Mejía, Iris Anecxi Jiménez-Vieyra, Luis Antonio Bermúdez-Aceves, Blanca Judith Ávila-Flores and Efrén Murillo-Zamora
Antibiotics 2025, 14(8), 747; https://doi.org/10.3390/antibiotics14080747 - 24 Jul 2025
Viewed by 211
Abstract
Introduction/Objective: Peritonitis remains a serious complication in patients undergoing automated peritoneal dialysis (APD), requiring prompt and effective antibiotic administration. This study evaluated whether delivering antibiotics directly through APD bags is as effective as administering them via an additional manual daytime exchange. Methods: We [...] Read more.
Introduction/Objective: Peritonitis remains a serious complication in patients undergoing automated peritoneal dialysis (APD), requiring prompt and effective antibiotic administration. This study evaluated whether delivering antibiotics directly through APD bags is as effective as administering them via an additional manual daytime exchange. Methods: We conducted a randomized, single-blind, non-inferiority clinical trial involving patients diagnosed with peritonitis. Participants were randomly assigned to receive Ceftazidime and Vancomycin, either via APD bags or through a combined approach of continuous ambulatory peritoneal dialysis (CAPD) plus APD. A total of 64 patients (32 per group) were enrolled, with comparable baseline demographic and clinical profiles, including laboratory markers of infection severity and dialysis history. Results: Peritonitis resolved in 90.6% of the patients treated via APD bags and in 81.3% of those receiving antibiotics through manual exchange plus APD. Although this difference did not reach statistical significance (p = 0.281), the observed absolute difference of 9.3% was well within the predefined non-inferiority margin of 30%, supporting the clinical non-inferiority of the APD-only method. The mean time to resolution was similar between groups (p = 0.593). Post hoc power analyses indicated limited statistical power (18.5% for the resolution rate and 9.2% for time to resolution), suggesting that modest differences may not have been detectable given the sample size. Nevertheless, the high resolution rates observed in both groups reflect valid and encouraging clinical outcomes. Conclusion: Antibiotic administration via APD bags demonstrated comparable clinical effectiveness to the combined manual exchange plus APD method for treating peritonitis. Given its operational simplicity and favorable results, the APD-only strategy may offer a pragmatic alternative in routine care. Further studies with larger sample sizes are recommended to confirm these findings and optimize treatment protocols. Trial registration: NCT04077996. Funding source: None to declare. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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20 pages, 7123 KiB  
Article
Ionic and Electrotonic Contributions to Short-Term Ventricular Action Potential Memory: An In Silico Study
by Massimiliano Zaniboni
Computation 2025, 13(7), 175; https://doi.org/10.3390/computation13070175 - 20 Jul 2025
Viewed by 226
Abstract
Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates—the so-called dynamic restitution (ERdyn) curve—or as APD changes after pre- or post-mature stimulations—the so-called standard restitution [...] Read more.
Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates—the so-called dynamic restitution (ERdyn) curve—or as APD changes after pre- or post-mature stimulations—the so-called standard restitution (ERs1s2) curve. Short-term AP memory (Ms) has been described as the slope difference between the ERdyn and ERs1s2 curves, and represents the information stored in repolarization dynamics due to previous pacing conditions. Although previous studies have shown its dependence on ion currents and calcium cycling, a systematic picture of these features is lacking. By means of simulations with a human ventricular AP model, I show that APD restitution can be described under randomly changing pacing conditions (ERrand) and Ms derived as the slope difference between ERdyn and ERrand. Thus measured, Ms values correlate with those measured using ERs1s2. I investigate the effect on Ms of modulating the conductance of ion channels involved in AP repolarization, and of abolishing intracellular calcium transient. I show that Ms is chiefly determined by ERdyn rather than ERrand, and that interventions that shorten/prolong APD tend to decrease/increase Ms. Full article
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14 pages, 1583 KiB  
Article
Impact of Anthropomorphic Shape and Skin Stratification on Absorbed Power Density in mmWaves Exposure Scenarios
by Silvia Gallucci, Martina Benini, Marta Bonato, Valentina Galletta, Emma Chiaramello, Serena Fiocchi, Gabriella Tognola and Marta Parazzini
Sensors 2025, 25(14), 4461; https://doi.org/10.3390/s25144461 - 17 Jul 2025
Viewed by 169
Abstract
As data exchange demands increase also in widespread wearable technologies, transitioning to higher bandwidths and mmWave frequencies (30–300 GHz) is essential. This shift raises concerns about RF exposure. At such high frequencies, the most crucial human tissue for RF power absorption is the [...] Read more.
As data exchange demands increase also in widespread wearable technologies, transitioning to higher bandwidths and mmWave frequencies (30–300 GHz) is essential. This shift raises concerns about RF exposure. At such high frequencies, the most crucial human tissue for RF power absorption is the skin, since EMF penetration is superficial. It becomes thus very important to assess how the model used to represent the skin in numerical dosimetry studies affects the estimated level of absorbed power. The present study, for the first time, assesses the absorbed power density (APD) using FDTD simulations on two realistic human models in which: (i) the skin has a two-layer structure made of the stratum corneum and the viable epidermis and dermis layers, and (ii) the skin is modelled as a homogeneous dermis stratum. These results were compared with ones using flat phantom models, with and without the stratified skin. The exposure assessment study was performed with two sources (a wearable patch antenna and a plane wave) tuned to 28 GHz. For the wearable antenna, the results evidence that the exposure levels obtained when using the homogeneous version of the models are always lower than the levels in the stratified skin version with percentage differences from 16% to 30%. This trend is more noticeable with the female model. In the case of plane wave exposure, these differences were less pronounced and lower than 11%. Full article
(This article belongs to the Special Issue Design and Measurement of Millimeter-Wave Antennas)
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24 pages, 6608 KiB  
Article
The Link Between Left Atrial Longitudinal Reservoir Strain and Mitral Annulus Geometry in Patients with Dilated Cardiomyopathy
by Despina-Manuela Toader, Alina Paraschiv, Diana Ruxandra Hădăreanu, Maria Iovănescu, Oana Mirea, Andreea Vasile and Alina-Craciun Mirescu
Biomedicines 2025, 13(7), 1753; https://doi.org/10.3390/biomedicines13071753 - 17 Jul 2025
Viewed by 188
Abstract
Background/Objectives: Anatomical and functional damage of the mitral valve (MV) apparatus in patients with dilated cardiomyopathy (DCM) is secondary to left ventricular (LV) injury, leading to functional mitral regurgitation (FMR). Real-time four-dimensional echocardiography (RT 4DE) is a useful imaging technique in different [...] Read more.
Background/Objectives: Anatomical and functional damage of the mitral valve (MV) apparatus in patients with dilated cardiomyopathy (DCM) is secondary to left ventricular (LV) injury, leading to functional mitral regurgitation (FMR). Real-time four-dimensional echocardiography (RT 4DE) is a useful imaging technique in different pathologies, including DCM. Left atrial (LA) strain, as measured by left atrium quantification software, is an accurate technique for evaluating increased filling pressure. The MV has a complex three-dimensional morphology and motion. Four-dimensional echocardiography (4DE) has revolutionized clinical imaging of the mitral valve apparatus. This study aims (1) to characterize the mitral annulus (MA) parameters in patients with DCM and advanced-stage heart failure (HF) according to etiology and (2) to find correlations between left atrial function and MA remodeling in this group of patients, using 4DE quantification software. Methods: A total of 82 patients with DCM and an LV ejection fraction ≤ 40% were recruited. Conventional 2DE and RT 4DE were conducted in DCM patients with a compensated phase of HF before discharge. The measured parameters were left atrial reservoir strain (LASr), annular area (AA), annular perimeter (AP), anteroposterior diameter (A-Pd), posteromedial to anterolateral diameter (PM-ALd), commissural distance (CD), interregional distance (ITD), annular height (AH), nonplanar angle (NPA), tenting height (TH), tenting area (TA), and tenting volume (TV). Results: Measured parameters revealed more advanced damage of LA and MA parameters in ischemic compared to nonischemic etiology. Univariate analysis identified AA, AP, A-Pd, PM-ALd, CD, ITD, TH, TA, and TV (p < 0.0001) as determinants of LASr. Including these parameters in a stepwise multivariate logistic regression, PM-ALd (p = 0.03), TH (p = 0.043), and TV (p = 0.0001) were the best predictors of LAsr in these patients. Conclusions: The results of this study revealed the correlation between LA function depression and MA remodeling in patients with DCM. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 4958 KiB  
Article
Sensor-Reduced Active Power Decoupling Method for Single-Phase Rectifiers
by Ming Chen, Shui Liu, Qinglong Cao and Hui Wang
Energies 2025, 18(14), 3711; https://doi.org/10.3390/en18143711 - 14 Jul 2025
Viewed by 199
Abstract
Active power decoupling (APD) technology demonstrates significant advantages in addressing the mismatched second-order ripple power issue in single-phase rectifiers. However, conventional methods typically require additional voltage or current sensors to achieve precise decoupling control, thereby increasing the cost of the decoupling circuit. To [...] Read more.
Active power decoupling (APD) technology demonstrates significant advantages in addressing the mismatched second-order ripple power issue in single-phase rectifiers. However, conventional methods typically require additional voltage or current sensors to achieve precise decoupling control, thereby increasing the cost of the decoupling circuit. To reduce costs and simplify the control system, a sensor-reduced decoupling control method is proposed, with its key advantages highlighted in three aspects: First, the proposed method operates by replacing actual sampled variables with designed reference values, reducing the number of sensors—only the DC bus voltage information is required for operation. Second, the sensor-reduced control scheme is designed based on Lyapunov stability conditions and ensures system stability. Third, virtual impedance produces the reference current of the decoupling circuit, which eliminates grid signal interaction and simplifies control. Simulation and experimental results validate the effectiveness and feasibility of the proposed method. Full article
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14 pages, 743 KiB  
Article
The Discovery, Characterization, and Quantification of Bioactive Peptides Contained in Palbio Porcine Intestinal Mucosa Hydrolysate Products
by Sergi Segarra, Carolina de la Torre, Joan Josep Bech-Serra, Bernat Cucurull, Anna Marazuela-Duque, Alejandro Vaquero, Daniel Martínez-Puig and Javier Velasco-Alvarez
Int. J. Mol. Sci. 2025, 26(14), 6656; https://doi.org/10.3390/ijms26146656 - 11 Jul 2025
Viewed by 220
Abstract
Porcine intestinal mucosa hydrolysates (PIMHs) are by-products of heparin production obtained through a specific enzymatic hydrolysis process, which can theoretically generate bioactive peptides (BAPs). This study aimed to identify, characterize, and quantify BAPs in two Palbio products manufactured by Bioiberica S.A.U. (Palafolls, Spain), [...] Read more.
Porcine intestinal mucosa hydrolysates (PIMHs) are by-products of heparin production obtained through a specific enzymatic hydrolysis process, which can theoretically generate bioactive peptides (BAPs). This study aimed to identify, characterize, and quantify BAPs in two Palbio products manufactured by Bioiberica S.A.U. (Palafolls, Spain), which are PIMH protein sources used for animal feed: Palbio® HP (PHP) and Palbio® 62 SP® (P62). Using mass spectrometry (MS)-based peptidomics, we analyzed three samples from each product, fractionated based on molecular weight (<3 kDa, 3 to 10 kDa, and >10 kDa). The <3 kDa fraction was analyzed directly, while the other two fractions were enzymatically digested before MS analysis. The workflow identified 961 peptides in PHP and 1134 in P62. Subsequent bioinformatic analysis using public databases (APD2, StraPep, AHTPDB, and BIOPEP-UWM) led to the identification of six significant BAPs in both PHP and P62, with respective quantified amounts (pg peptide/μg sample): DAVEDLESVGK (0.1626, 0.1939), EGIPPDQQRLIFAGK (0.2637, 0.1852), TITLEVEPSDTIENVK (0.3594, 0.4327), TNVPRASVPDGFLS (1.4596, 0.1898), TNVPRASVPDGFLSEL (8.0500, 0.9224), and VHVVPDQLMAF (0.0310, 0.0054). The first three BAPs are related to antimicrobial activity, while the latter three are associated with cytokine/growth factor-like, antioxidant, and immunomodulatory activities. These bioactivities align with previously reported in vivo benefits observed in animal nutrition using Palbio products. Our findings demonstrate that PHP and P62 are valuable sources of BAPs, supporting their potential role in improving animal health and performance. Full article
(This article belongs to the Section Molecular Pharmacology)
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20 pages, 3689 KiB  
Article
Active Colitis-Induced Atrial Electrophysiological Remodeling
by Hiroki Kittaka, Edward J. Ouille V, Carlos H. Pereira, Andrès F. Pélaez, Ali Keshavarzian and Kathrin Banach
Biomolecules 2025, 15(7), 982; https://doi.org/10.3390/biom15070982 - 10 Jul 2025
Viewed by 346
Abstract
Patients with ulcerative colitis exhibit an increased risk for supraventricular arrhythmia during the active disease phase of the disease and show signs of atrial electrophysiological remodeling in remission. The goal of this study was to determine the basis for colitis-induced changes in atrial [...] Read more.
Patients with ulcerative colitis exhibit an increased risk for supraventricular arrhythmia during the active disease phase of the disease and show signs of atrial electrophysiological remodeling in remission. The goal of this study was to determine the basis for colitis-induced changes in atrial excitability. In a mouse model (C57BL/6; 3 months) of dextran sulfate sodium (DSS)-induced active colitis (3.5% weight/volume, 7 days), electrocardiograms (ECG) revealed altered atrial electrophysiological properties with a prolonged P-wave duration and PR interval. ECG changes coincided with a decreased atrial conduction velocity in Langendorff perfused hearts. Action potentials (AP) recorded from isolated atrial myocytes displayed an attenuated maximal upstroke velocity and amplitude during active colitis, as well as a prolonged AP duration (APD). Voltage clamp analysis revealed a colitis-induced shift in the voltage-dependent activation of the Na-current (INa) to more depolarizing voltages. In addition, protein levels of Nav1.5 protein and connexin isoform Cx43 were reduced. APD prolongation depended on a reduction in the transient outward K-current (Ito) mostly generated by Kv4.2 channels. The changes in ECG, atrial conductance, and APD were reversible upon remission. The change in conduction velocity predominantly depended on the reversibility of the reduced Cx43 and Nav1.5 expression. Treatment of mice with inhibitors of Angiotensin-converting enzyme (ACE) or Angiotensin II (AngII) receptor type 1 (AT1R) prevented the colitis-induced atrial electrophysiological remodeling. Our data support a colitis-induced increase in AngII signaling that promotes atrial electrophysiological remodeling and puts colitis patients at an increased risk for atrial arrhythmia. Full article
(This article belongs to the Special Issue Molecular Advances in Inflammatory Bowel Disease)
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17 pages, 1027 KiB  
Review
Photon Detector Technology for Laser Ranging: A Review of Recent Developments
by Zhihui Li, Xin Jin, Changfu Yuan and Kai Wang
Coatings 2025, 15(7), 798; https://doi.org/10.3390/coatings15070798 - 8 Jul 2025
Viewed by 474
Abstract
Laser ranging technology holds a key position in the military, aerospace, and industrial fields due to its high precision and non-contact measurement characteristics. As a core component, the performance of the photon detector directly determines the ranging accuracy and range. This paper systematically [...] Read more.
Laser ranging technology holds a key position in the military, aerospace, and industrial fields due to its high precision and non-contact measurement characteristics. As a core component, the performance of the photon detector directly determines the ranging accuracy and range. This paper systematically reviews the technological development of photonic detectors for laser ranging, with a focus on analyzing the working principles and performance differences of traditional photodiodes [PN (P-N junction photodiode), PIN (P-intrinsic-N photodiode), and APD (avalanche photodiode)] (such as the high-frequency response characteristics of PIN and the internal gain mechanism of APD), as well as their applications in short- and medium-range scenarios. Additionally, this paper discusses the unique advantages of special structures such as transmitting junction-type and Schottky-type detectors in applications like ultraviolet light detection. This article focuses on photon counting technology, reviewing the technological evolution of photomultiplier tubes (PMTs), single-photon avalanche diodes (SPADs), and superconducting nanowire single-photon detectors (SNSPDs). PMT achieves single-photon detection based on the external photoelectric effect but is limited by volume and anti-interference capability. SPAD achieves sub-decimeter accuracy in 100 km lidars through Geiger mode avalanche doubling, but it faces challenges in dark counting and temperature control. SNSPD, relying on the characteristics of superconducting materials, achieves a detection efficiency of 95% and a dark count rate of less than 1 cps in the 1550 nm band. It has been successfully applied in cutting-edge fields such as 3000 km satellite ranging (with an accuracy of 8 mm) and has broken through the near-infrared bottleneck. This study compares the differences among various detectors in core indicators such as ranging error and spectral response, and looks forward to the future technical paths aimed at improving the resolution of photon numbers and expanding the full-spectrum detection capabilities. It points out that the new generation of detectors represented by SNSPD, through material and process innovations, is promoting laser ranging to leap towards longer distances, higher precision, and wider spectral bands. It has significant application potential in fields such as space debris monitoring. Full article
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13 pages, 1142 KiB  
Article
Flash 3D Imaging of Far-Field Dynamic Objects: An EMCCD-Based Polarization Modulation System
by Shengjie Wang, Xiaojia Yang, Donglin Su, Weiqi Cao and Xianhao Zhang
Sensors 2025, 25(13), 3852; https://doi.org/10.3390/s25133852 - 20 Jun 2025
Viewed by 284
Abstract
High-resolution 3D visualization of dynamic environments is critical for applications such as remote sensing. Traditional 3D imaging systems, such as lidar, rely on avalanche photodiode (APD) arrays to determine the flight time of light for each scene pixel. In this context, we introduce [...] Read more.
High-resolution 3D visualization of dynamic environments is critical for applications such as remote sensing. Traditional 3D imaging systems, such as lidar, rely on avalanche photodiode (APD) arrays to determine the flight time of light for each scene pixel. In this context, we introduce and demonstrate a high-resolution 3D imaging approach leveraging an Electron Multiplying Charge Coupled Device (EMCCD). This sensor’s low bandwidth properties allow for the use of electro-optic modulators to achieve both temporal resolution and rapid shuttering at sub-nanosecond speeds. This enables range-gated 3D imaging, which significantly enhances the signal-to-noise ratio (SNR) within our proposed framework. By employing a dual EMCCD setup, it is possible to reconstruct both a depth image and a grayscale image from a single raw data frame, thereby improving dynamic imaging capabilities, irrespective of object or platform movement. Additionally, the adaptive gate-opening range technology can further refine the range resolution of specific scene objects to as low as 10 cm. Full article
(This article belongs to the Section Sensing and Imaging)
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13 pages, 3937 KiB  
Article
A 5 Gb/s Optoelectronic Receiver IC in 180 nm CMOS for Short-Distance Optical Interconnects
by Yunji Song and Sung-Min Park
Photonics 2025, 12(6), 624; https://doi.org/10.3390/photonics12060624 - 19 Jun 2025
Viewed by 309
Abstract
This paper presents a CMOS-based optoelectronic receiver integrated circuit (CORIC) realized in a standard 180 nm CMOS technology for the applications of short-distance optical interconnects. The CORIC comprises a spatially modulated P+/N-well on-chip avalanche photodiode (P+/NW APD) for optical-to-electrical [...] Read more.
This paper presents a CMOS-based optoelectronic receiver integrated circuit (CORIC) realized in a standard 180 nm CMOS technology for the applications of short-distance optical interconnects. The CORIC comprises a spatially modulated P+/N-well on-chip avalanche photodiode (P+/NW APD) for optical-to-electrical conversion, a dummy APD at the differential input for enhanced common-mode noise rejection, a cross-coupled differential transimpedance amplifier (CCD-TIA) for current-to-voltage conversion, a 3-bit continuous-time linear equalizer (CTLE) for adaptive equalization by using NMOS registers, and a fT-doubler output buffer (OB). The CTLE and fT-doubler OB combination not only compensates the frequency-dependent signal loss, but also provides symmetric differential output signals. Post-layout simulations of the proposed CORIC reveal a transimpedance gain of 53.2 dBΩ, a bandwidth of 4.83 GHz even with a 490 fF parasitic capacitance from the on-chip P+/NW APD, a dynamic range of 60 dB that handles the input photocurrents from 1 μApp to 1 mApp, and a DC power consumption of 33.7 mW from a 1.8 V supply. The CORIC chip core occupies an area of 260 × 101 μm2. Full article
(This article belongs to the Special Issue New Insights in Low-Dimensional Optoelectronic Materials and Devices)
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18 pages, 2608 KiB  
Article
Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted
by Lukas Kraehenbuehl, Nicola Winkelbeiner, Patrick Turko, Ramon Staeger, Adhideb Ghosh, Vivienn Kaiser, Pia-Charlotte Stadler, Thierry M. Nordmann, Marie-Charlotte Brüggen, Mitchell P. Levesque, Emmanuel Contassot, Lars E. French, Reinhard Dummer and Barbara Meier-Schiesser
Cancers 2025, 17(12), 1992; https://doi.org/10.3390/cancers17121992 - 14 Jun 2025
Viewed by 613
Abstract
Background/Objectives: Immune-related cutaneous adverse events (ircAEs) are common complications of cancer immunotherapy and provide insight into immune-related adverse events (irAEs) more broadly. To enhance our molecular understanding, we characterized ircAEs resulting from single-agent (PD1) and combined immunotherapy regimens (P+C). Clinically, maculopapular rash [...] Read more.
Background/Objectives: Immune-related cutaneous adverse events (ircAEs) are common complications of cancer immunotherapy and provide insight into immune-related adverse events (irAEs) more broadly. To enhance our molecular understanding, we characterized ircAEs resulting from single-agent (PD1) and combined immunotherapy regimens (P+C). Clinically, maculopapular rash (MPR) and toxic epidermal necrolysis (TEN) resemble ircAEs, providing a valuable basis for investigations. Methods: To investigate the transcriptome and immune infiltrates in ircAEs, we conducted transcriptomic analyses and multiplexed immunohistochemistry on skin biopsies from patients receiving PD1 and P+C, as well as those with MPR, TEN, and healthy controls. Results: Principal component analysis revealed distinct transcriptomic clustering between ircAEs, MPR, and TEN. Specifically, PD1 ircAEs exhibited a gene expression profile similar to TEN, with upregulation of Type-I-response-related genes (e.g., CXCL9 Log2FC 5.34, p < 0.0001, CXCL10 Log2FC 6.03, p < 0.0001), while P+C ircAEs more closely resembled MPR. Immune infiltrates differed significantly between all groups (p = 0.002 by PERMANOVA for all groups). CD4 T-cells were abundant in the dermis of ircAEs from any type of immunotherapy. However, PD1 stained positive in 1.07% of CD4 cells with PD1 monotherapy, compared to 0.3%, 0.4%, and 0.08% in P+C, MPR, and TEN, respectively. Conclusions: This study identified distinct molecular and cellular signatures in ircAEs depending on the type of immune checkpoint blockade. aPD1-associated ircAEs share similarities with the cytotoxic profile of TEN, while P+C more closely mirrored MPR. These findings support the need for tailored management strategies for ircAEs, emphasizing personalized therapeutic approaches to minimize treatment interruptions while preserving the efficacy of cancer immunotherapy. Full article
(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)
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17 pages, 270 KiB  
Review
Digital Health in Parkinson’s Disease and Atypical Parkinsonism—New Frontiers in Motor Function and Physical Activity Assessment: Review
by Manuela Violeta Bacanoiu, Ligia Rusu, Mihnea Ion Marin, Denisa Piele, Mihai Robert Rusu, Raluca Danoiu and Mircea Danoiu
J. Clin. Med. 2025, 14(12), 4140; https://doi.org/10.3390/jcm14124140 - 11 Jun 2025
Viewed by 684
Abstract
In addition to axial motor complications such as abnormal posture, instability, falls, and gait variability, neurodegenerative diseases like Parkinsonian syndromes include executive dysfunction, Parkinson’s disease dementia, and neuropsychiatric symptoms. These motor disorders significantly affect mobility, quality of life, and well-being. Recently, physical activity [...] Read more.
In addition to axial motor complications such as abnormal posture, instability, falls, and gait variability, neurodegenerative diseases like Parkinsonian syndromes include executive dysfunction, Parkinson’s disease dementia, and neuropsychiatric symptoms. These motor disorders significantly affect mobility, quality of life, and well-being. Recently, physical activity of various intensities monitored both remotely and face-to-face via digital health technologies, mobile platforms, or sensory cues has gained relevance in managing idiopathic and atypical Parkinson’s disease (PD and APD). Remote monitoring solutions, including home-based digital health assessments using semi-structured activities, offer unique advantages. Real-world gait parameters like walking speed can now be continuously assessed with body-worn sensors. Developing effective strategies to slow pathological aging and mitigate neurodegenerative progression is essential. This study presents outcomes of using digital health technologies (DHTs) for remote assessment of motor function, physical activity, and daily living tasks, aiming to reduce disease progression in PD and APD. In addition to wearable inertial sensors, clinical rating scales and digital biomarkers enhance the ability to characterize and monitor motor symptoms. By reviewing recent literature, we identified emerging trends in quantifying and intervening in neurodegeneration using tools that evaluate both remote and face-to-face physical activity. Our findings confirm that DHTs offer accurate detection of motor fluctuations and support clinical evaluations. In conclusion, DHTs represent a scalable, effective strategy for improving the clinical management of PD and APD. Their integration into healthcare systems may enhance patient outcomes, support early intervention, and help delay the progression of both motor and cognitive symptoms in aging individuals. Full article
34 pages, 2554 KiB  
Article
An Improved Whale Optimization Algorithm via Angle Penalized Distance for Automatic Train Operation
by Longda Wang, Yanjie Ju, Long Guo, Gang Liu, Chunlin Li and Yan Chen
Biomimetics 2025, 10(6), 384; https://doi.org/10.3390/biomimetics10060384 - 9 Jun 2025
Viewed by 373
Abstract
This study proposes a novel effective improved whale optimization algorithm via angle penalized distance (IWOA-APD) for automatic train operation (ATO) to effectively improve the ATO quality. Specifically, aiming at the high-quality target speed curve of urban rail trains, a target speed curve multi-objective [...] Read more.
This study proposes a novel effective improved whale optimization algorithm via angle penalized distance (IWOA-APD) for automatic train operation (ATO) to effectively improve the ATO quality. Specifically, aiming at the high-quality target speed curve of urban rail trains, a target speed curve multi-objective optimization model for ATO is established with energy saving, punctuality, accurate stopping, and comfort as the indexes; and the comprehensive evaluation strategy utilizing angle-penalized distance as the evaluation index is proposed to enhance the assessment’s rationality and applicability. On this basis, the IWOA-APD is proposed using strategies of non-linear decreasing convergence factor, solutions of out-of-bounds eliminating via combination of reflection and refraction, mechanisms of genetic evolution with variable probability, and elite maintenance based on fusion distance and crowding degree distance. In addition, the detailed design scheme of IWOA-APD is given. The test results show that the proposed IWOA-APD achieves significant performance improvements compared to traditional MOWOA. In the optimization scenario from Lvshun New Port Station to Tieshan Town Station of Dalian urban rail transit line No.12, the IGD value shows a remarkable 69.1% reduction, while energy consumption decreases by 12.5%. The system achieves a 64.6% improvement in punctuality and a 76.5% enhancement in parking accuracy. Additionally, comfort level improves by 15.9%. Full article
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14 pages, 241 KiB  
Article
The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis
by Mbakise P. Matebele, Kanthi R. Vemuri, John F. Sedgwick, Lachlan Marshall, Robert Horvath, Nchafatso G. Obonyo and Mahesh Ramanan
Hearts 2025, 6(2), 15; https://doi.org/10.3390/hearts6020015 - 6 Jun 2025
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Abstract
Background: This study aims to evaluate the impact of critical illness, defined as the need for preoperative intensive care unit (ICU) admission for invasive monitoring or organ support, on cardiac surgery outcomes for patients with acute infective endocarditis (IE). Methods: A [...] Read more.
Background: This study aims to evaluate the impact of critical illness, defined as the need for preoperative intensive care unit (ICU) admission for invasive monitoring or organ support, on cardiac surgery outcomes for patients with acute infective endocarditis (IE). Methods: A retrospective analysis of prospectively collected data from patients treated between 1 January 2017 and 30 May 2024 at a single Australian tertiary cardiothoracic centre was performed. Data were collected from the Australian and New Zealand Cardiothoracic Society (ANZCTS) database and the Australian and New Zealand Intensive Care Adult Patients Database (ANZICS-APD). Results: Among 342 patients who underwent cardiac surgery for IE, 32 (9.4%) were critically ill. The critically ill patients were admitted to the ICU before surgery with a diagnosis of septic or cardiogenic shock, with 86% (n = 30) requiring mechanical ventilation. Compared to the non-critically ill cohort, critically ill patients were more likely to have a history of intravenous drug use (IVDU) (41% vs. 14%, p = 0.03) and a younger age (median age 49 years [42–56] vs. 61 years [44–70], p = 0.03), and although methicillin-sensitive Staphylococcus aureus (MSSA) was the most common causative organism in both groups, it was found significantly more often in the critically ill cohort (66% and 27%, p = 0.001). The median EuroSCORE II was comparable between the groups (2.1 [1.3–10] vs. 2.8 [1.3–5.7], p = 0.69); however, the APACHE III (57 [49–78] vs. 52 [39–67], p = 0.03) and ANZROD scores (0.04 [0.02–0.09] vs. 0.013 [0.004–0.038], p = 0.00002) were significantly higher in the critically ill patients. The overall 30-day mortality rates were similar between the groups (13% vs. 5%, p = 0.60). The median ICU length of stay (LOS) was significantly longer for the critically ill patients (5 days [IQR 2–10 days] vs. 2 days [1–4 days], p = 0.0004), with a similar hospital LOS (23 days [IQR 14–36] vs. 21 days [12–34], p = 0.46). Renal replacement therapy was three times higher in the critically ill (34% vs. 11%, p = 0.0001). Reoperations for bleeding were similar between the groups (16% vs. 11%, p = 0.74). Conclusions: Despite being associated with higher ANZROD and APACHE III scores, a longer ICU length of stay, and higher use of renal replacement therapy, critical illness did not have an impact on the EuroSCORE II, hospital length of stay, or reoperation rates for bleeding or 30-day mortality among patients with IE undergoing cardiac surgery. The lessons from this study will guide and inform the development of better infective endocarditis databases and registries. Full article
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