Search Results (338)

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder responsible for nearly a quarter of sports-related sudden cardiac deaths. ACM cases caused by mutations in desmosome proteins lead to right ventricular enlargement, the loss of cardiomyocytes, and fibrofatty tissue replacement, disrupting electrical and mechanical stability. It is currently unknown how paracrine factors secreted by infiltrating fatty tissues affect ACM cardiomyocyte electrophysiology. Methods: A normal and a PKP2 mutant (c.971_972InsT) ACM hiPSC line were cultivated and differentiated into cardiomyocytes (CMs). Adipocytes were differentiated from human adipose stem cells, and adipocyte conditioned medium (AdCM) was collected. Optical mapping and phenotypic analyses were conducted on human iPSC-cardiomyocytes (hiPSC-CMs) cultured in cardiac maintenance medium (CMM) and either with AdCM or specific cytokines. Results: Significant differences were observed in voltage parameters such as the action potential duration (APD₈₀, APD₃₀), conduction velocity (CV), and CV heterogeneity. When cultured in AdCM relative to CMM, the APD₈₀ increased and the CV decreased significantly in both groups; however, the magnitudes of changes often differed significantly between 1 and 7 days of cultivation. Cytokine exposure (IL-6, IL-8, MCP-1, CFD) affected the APD and CV in both the normal and PKP2 mutant hiPSC-CMs, with opposite effects. NF-kB signaling was also found to differ between the normal and PKP2 mutant hiPSC-CMs in response to AdCM and IL-6. Conclusions: Our study shows that hiPSC-CMs from normal and mPKP2 ACM lines exhibit distinct molecular and functional responses to paracrine factors, with differences in RNA expression and electrophysiology. These different responses to paracrine factors may contribute to arrhythmogenic propensity. Full article

Background/Objectives: Monogenic primary immunodeficiencies represent a group of disorders with varying levels of severity, many of which remain poorly understood. Activated phosphoinositide-3 kinase delta syndrome (APDS) is a rare genetic condition resulting from dominant point mutations in the phosphoinositide-3 kinase delta (PI3Kδ) gene, which leads to hyperactivation of the PI3Kδ enzyme, primarily expressed in T and B lymphocytes. Children with this mutation often have recurrent sinopulmonary infections and immunodeficiency. Additional complications may include increased susceptibility to herpes virus infections, lymphoid hyperplasia, and autoimmune conditions. In this case, report, we describe the clinical course of a young boy diagnosed with APDS who developed unclassified inflammatory bowel disease (U-IBD) and explore a personalized treatment approach. Methods: We detail the clinical course of a 12-year-old boy with APDS who presented with fever, diarrhea, anemia, and significant weight loss. Diagnostic evaluations, including endoscopy and histological analysis, led to a diagnosis of U-IBD. Genetic testing confirmed a heterozygous PIK3CD mutation (c.G3061A, p.E1021K). Results: Although APDS is characterized by a broad spectrum of immune dysregulation, the occurrence of IBD in this context is rare. We managed the patient’s IBD with exclusively enteral nutrition to induce remission, followed by a maintenance regimen combining the Crohn’s Disease Exclusion Diet (CDED) and mesalamine, achieving sustained long-term clinical remission. Conclusions: This case underscores the importance of personalized treatment approaches in managing the complex manifestations of APDS. Full article

Background/Objectives: Antimicrobial peptides are essential molecules in the innate immunity of various organisms and possess a broad spectrum of antimicrobial, antitumor, and immunomodulatory activities. Due to their multifunctionality, they are seen as an alternative for controlling bacterial infections. Although conventional antibiotics have improved health worldwide, their indiscriminate use has led to the emergence of resistant microorganisms. To discover new molecules with antimicrobial activity that could overcome the limitations of traditional antibiotics, this study aimed to identify antimicrobial peptides in Ambystoma mexicanum. Methods: In this study, hypothetical proteins encoded in the Ambystoma mexicanum transcriptome were predicted. These proteins were aligned with peptides reported in the Antimicrobial Peptide Database (APD3) using the Fasta36 program. After identifying peptide sequences with potential antibacterial activity, their expression was confirmed through conventional polymerase chain reaction (PCR) and then chemically synthesized. The antibacterial activity of the synthesized peptides was evaluated against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. Results: A new antimicrobial peptide named AXOTL-13 was identified. AXOTL-13 is an amphipathic cationic alpha-helical peptide with the ability to inhibit the growth of Escherichia coli without causing hemolysis in red blood cells, with its action likely directed at the membrane, as suggested by morphological changes observed through scanning electron microscopy. Conclusions: This research is pioneering in evaluating the activity of antimicrobial peptides present in Ambystoma mexicanum and in specifically identifying one of these peptides. The findings will serve as a reference for future research in this field. Full article

Background: This paper aims to investigate the impact of proprioceptive exercises on postural control in handball players with chronic ankle instability. Methods: The research participants (n = 22) were divided into two groups: the experimental group (n = 11) and the control group (n = 11). Chronic ankle instability was diagnosed using the Identification of Functional Ankle Instability (IdFAI) questionnaire, while postural control was evaluated with the Iso-Shift stabilometric platform. The intervention consisted of a 15-week proprioceptive exercise program, with sessions performed three times a week. The rehabilitation protocol was conducted at the start of each training session, immediately following the warm-up. Results: The data were analyzed using the Wilcoxon and Mann–Whitney U tests. Both groups improved their score on the Identification of Functional Ankle Instability (IdFAI) questionnaire (IdFAI_CG, p < 0.011; IdFAI_EG, p < 0.003) and reduced the number of ankle sprains (NS_EG, p < 0.008). Also, the experimental group had better results for the following tests: ellipse area with open eyes on the left leg (EA_I–OE_L, p < 0.009), ellipse area with closed eyes on the left leg (EA_I–CE_L, p < 0.033), anteroposterior deviation with open eyes on the left leg (APD_I–OE_L, p < 0.023), and the initial and final number of ankle sprains (NS_I, p < 0.01; NS_F, p < 0.024). Conclusions: Athletes who suffer from chronic joint instability are more likely to experience severe postural deviations than those who do not have this condition. Proprioceptive exercises had a positive impact on postural control in both groups, but the experimental group showed a greater improvement. Full article

Background: We have previously reported engineered macrophages (MacTriggers) that can accelerate the release of tumor necrosis factor-α in response to M2 polarization. MacTriggers are characterized by two original characteristics of macrophages: (1) migration to tumors; and (2) polarization to the M2 phenotype in tumors. Intravenously administered MacTriggers efficiently accumulated in the tumors and induced tumor-specific inflammation. This study reports a novel methodology for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Results: In this study, we newly found that the intravenously administered MacTriggers in BALB/c mouse models upregulated the expression levels of immune checkpoint proteins, such as programmed cell death (PD)-1 in CD8⁺ T cells and PD-ligand 1 (PD-L1) in cancer cells and macrophages. Consequently, in two ICI-resistant tumor-inoculated mouse models, the combined administration of MacTrigger and anti-PD-1 antibody (aPD-1) synergistically inhibited tumor growth, whereas monotherapy with aPD-1 did not exhibit anti-tumor effects. This synergistic effect was mainly from aPD-1 enhancing the tumor-attacking ability of CD8⁺ T cells, which could infiltrate into the tumors following MacTrigger treatment. Importantly, no side effects were observed in normal tissues, particularly in the liver and spleen, indicating that the MacTriggers did not enhance the aPD-1 reactivity in normal tissues. This specificity was from the MacTriggers not polarizing to the M2 phenotype in normal tissues, thereby avoiding inflammation and increased PD-1/PD-L1 expression. MacTriggers could enhance aPD-1 reactivity only in tumors following tumor-specific inflammation induction. Conclusions: Our findings suggest that the MacTrigger and aPD-1 combination therapy is a novel approach for potentially overcoming the current low ICI response rates while avoiding side effects. Full article

To achieve higher visible light communication (VLC) traffic capacity, using the wide bandwidth light-emitting diode (LED) and spectral efficiency modulation signal, is currently the most commonly used method. In this demonstration, we apply the orthogonal frequency division multiplexing quadrature amplitude modulation (OFDM-QAM) with bit- and power-loading algorithm on single blue LED to achieve >1 Gbit/s VLC capacity, when a 400 MHz bandwidth avalanche photodiode (APD)-based receiver (Rx) is exploited for decoding. Here, the higher sensitivity APD can be applied to compensate for the wireless VLC link length in the proposed LED VLC system, and due to the lower LED illumination (255 to 40 lux), is used for the indoor access network after passing the wireless link length of 1 to 4 m. As a result, using single blue LED can achieve 0.962 to 1.057 Gbit/s OFDM rate with available 400 MHz bandwidth APD in poorly illuminated condition indoors without applying analogy equalization. Full article

Previous studies have observed alterations in excitation–contraction (EC) coupling during end-stage heart failure that include action potential and calcium (Ca²⁺) transient prolongation and a reduction of the Ca²⁺ transient amplitude. Underlying these phenomena are the downregulation of potassium (K⁺) currents, downregulation of the sarcoplasmic reticulum Ca²⁺ ATPase (SERCA), increase Ca²⁺ sensitivity of the ryanodine receptor, and the upregulation of the sodium–calcium (Na⁼-Ca²⁺) exchanger. However, in human heart failure (HF), debate continues about the relative contributions of the changes in calcium handling vs. the changes in the membrane currents. To understand the consequences of the above changes, they are incorporated into a computational human ventricular myocyte HF model that can explore the contributions of the spontaneous Ca²⁺ release from the sarcoplasmic reticulum (SR). The reduction of transient outward K⁺ current (I_to) is the main membrane current contributor to the decrease in RyR2 open probability and L-type calcium channel (LCC) density which emphasizes its importance to phase 1 of the action potential (AP) shape and duration (APD). During current-clamp conditions, RyR2 hyperphosphorylation exhibits the least amount of Ca²⁺ release from the SR into the cytosol and SR Ca²⁺ fractional release during a dynamic slow–rapid–slow (0.5–2.5–0.5 Hz) pacing, but it displays the most abundant and more lasting Ca²⁺ sparks two-fold longer than a normal cell. On the other hand, under voltage-clamp conditions, HF by decreased SERCA and upregulated I_NCX show the least SR Ca²⁺ uptake and EC coupling gain, as compared to HF by hyperphosphorylated RyR2s. Overall, this study demonstrates that the (a) combined effect of SERCA and NCX, and the (b) RyR2 dysfunction, along with the downregulation of the cardiomyocyte’s potassium currents, could substantially contribute to Ca²⁺ mishandling at the spark level that leads to heart failure. Full article

This paper investigates the applicability of deep learning models for predicting the severity of forest wildfires, utilizing an innovative benchmark dataset called EO4WildFires. EO4WildFires integrates multispectral imagery from Sentinel-2, SAR data from Sentinel-1, and meteorological data from NASA Power annotated with EFFIS data for forest fire detection and size estimation. These data cover 45 countries with a total of 31,730 wildfire events from 2018 to 2022. All of these various sources of data are archived into data cubes, with the intention of assessing wildfire severity by considering both current and historical forest conditions, utilizing a broad range of data including temperature, precipitation, and soil moisture. The experimental setup has been arranged to test the effectiveness of different deep learning architectures in predicting the size and shape of wildfire-burned areas. This study incorporates both image segmentation networks and visual transformers, employing a consistent experimental design across various models to ensure the comparability of the results. Adjustments were made to the training data, such as the exclusion of empty labels and very small events, to refine the focus on more significant wildfire events and potentially improve prediction accuracy. The models’ performance was evaluated using metrics like F1 score, IoU score, and Average Percentage Difference (aPD). These metrics offer a multi-faceted view of model performance, assessing aspects such as precision, sensitivity, and the accuracy of the burned area estimation. Through extensive testing the final model utilizing LinkNet and ResNet-34 as backbones, we obtained the following metric results on the test set: 0.86 F1 score, 0.75 IoU, and 70% aPD. These results were obtained when all of the available samples were used. When the empty labels were absent during the training and testing, the model increased its performance significantly: 0.87 F1 score, 0.77 IoU, and 44.8% aPD. This indicates that the number of samples, as well as their respectively size (area), tend to have an impact on the model’s robustness. This restriction is well known in the remote sensing domain, as accessible, accurately labeled data may be limited. Visual transformers like TeleViT showed potential but underperformed compared to segmentation networks in terms of F1 and IoU scores. Full article

This paper presents a novel optoelectronic transimpedance amplifier (OTA) for short-range LiDAR sensors used in 180 nm CMOS technology, which consists of a main transimpedance amplifier (m-TIA) with an on-chip P⁺/N-well/Deep N-well avalanche photodiode (P⁺/NW/DNW APD) and a replica TIA with another on-chip APD, not only to acquire circuit symmetry but to also obtain concurrent automatic gain control (AGC) function within a narrow single pulse-width duration. In particular, for concurrent AGC operations, 3-bit PMOS switches with series resistors are added in parallel with the passive feedback resistor in the m-TIA. Then, the PMOS switches can be turned on or off in accordance with the DC output voltage amplitudes of the replica TIA. The post-layout simulations reveal that the OTA extends the dynamic range up to 74.8 dB (i.e., 1 µA_pp~5.5 mA_pp) and achieves a 67 dBΩ transimpedance gain, an 830 MHz bandwidth, a 16 pA/√Hz noise current spectral density, a −31 dBm optical sensitivity for a 10⁻¹² bit error rate, and a 6 mW power dissipation from a single 1.8 V supply. The chip occupies a core area of 200 × 120 µm². Full article

This paper presents an 8 × 8 channel optoelectronic readout array (ORA) realized in the TSMC 180 nm 1P6M RF CMOS process for the applications of short-range light detection and ranging (LiDAR) sensors. We propose several circuit techniques in this work, including an amplitude-to-voltage (A2V) converter that reduces the notorious walk errors by intensity compensation and a time-to-voltage (T2V) converter that acquires the linear slope of the output signals by exploiting a charging circuit, thus extending the input dynamic range significantly from 5 μA_pp to 1.1 mA_pp, i.e., 46.8 dB. These results correspond to the maximum detection range of 8.2 m via the action of the A2V converter and the minimum detection range of 56 cm with the aid of the proposed T2V converter. Optical measurements utilizing an 850 nm laser diode confirm that the proposed 8 × 8 ORA with 64 on-chip avalanche photodiodes (APDs) can successfully recover the narrow 5 ns light pulses even at the shortest distance of 56 cm. Hence, this work provides a potential CMOS solution for low-cost, low-power, short-range LiDAR sensors. Full article

Gels, specifically hydrogels and aerogels, have emerged as versatile materials with profound implications in pharmaceutical sciences. This comprehensive review looks into detail at hydrogels and aerogels, providing a general introduction to gels as a foundation. The paper is then divided into distinct sections for hydrogels and aerogels, each delving into their unique formulations, advantages, disadvantages, and applications. In the realm of hydrogels, we scrutinize the intricacies of formulation, highlighting the versatile advantages they offer. Conversely, potential limitations are explored, paving the way for a detailed discussion on their applications, with a specific focus on their role in antimicrobial applications. Shifting focus to aerogels, a thorough overview is presented, followed by a detailed explanation of the complex formulation process involving sol–gel chemistry; aging; solvent exchange; and drying techniques, including freeze drying, supercritical drying, and ambient-pressure drying (APD). The intricacies of drug loading and release from aerogels are addressed, providing insights into their pharmaceutical potential. The advantages and disadvantages of aerogels are examined, accompanied by an exploration of their applications, with a specific emphasis on antimicrobial uses. The review culminates in a comparative analysis, juxtaposing the advantages and disadvantages of hydrogels and aerogels. Furthermore, the current research and development trends in the applications of these gels in pharmaceutical sciences are discussed, providing a holistic view of their potential and impact. This review serves as a comprehensive guide for researchers, practitioners, and enthusiasts, seeking a deeper understanding of the distinctive attributes and applications of hydrogels and aerogels in the ever-evolving research concerning pharmaceutical sciences. Full article

Objectives: This study aims to measure, at two time points, the relationship between self-perceived global stress and the personality traits of the mothers of children who have central auditory processing disorder (APD) and compare it with the results from mothers of typically developing (TD) children. The comparisons were made before the COVID-19 pandemic, as well as late in the pandemic. Methods: The level of stress was assessed using the Perceived Stress Scale (PSS-10), while the Short Big Five Markers (IPIP-BFM-20) were used to assess Big Five personality traits. The study used two independent samples: one evaluated before the COVID-19 pandemic and the other late in the pandemic. Each sample consisted of 108 mothers of children with APD and 79 mothers whose children did not have APD (TD children) as controls. Results: The average global stress levels were similar in mothers of children with APD and in mothers of TD children, both before and in the late stage of the COVID-19 pandemic. During the late stage, both sets of mothers scored similarly on all personality dimensions, but significantly, mothers of TD children exhibited lower emotional stability compared to during the pre-pandemic period. In both groups, emotional stability predicted global stress level at both time points; however, during the pandemic, conscientiousness also became a predictor of global stress level but only in the group of mothers of TD children. Conclusions: Mothers of APD children might be more resistant to additional stressors. It would be prudent to watch mothers of APD and TD children for signs of needing psychological intervention. Full article

Photodetectors play a critical role in space lidars designed for scientific investigations from orbit around planetary bodies. The detectors must be highly sensitive due to the long range of measurements and tight constraints on the size, weight, and power of the instrument. The detectors must also be space radiation tolerant over multi-year mission lifetimes with no significant performance degradation. Early space lidars used diode-pumped Nd:YAG lasers with a single beam for range and atmospheric backscattering measurements at 1064 nm or its frequency harmonics. The photodetectors used were single-element photomultiplier tubes and infrared performance-enhanced silicon avalanche photodiodes. Space lidars have advanced to multiple beams for surface topographic mapping and active infrared spectroscopic measurements of atmospheric species and surface composition, which demand increased performance and new capabilities for lidar detectors. Higher sensitivity detectors are required so that multi-beam and multi-wavelength measurements can be performed without increasing the laser and instrument power. Pixelated photodetectors are needed so that a single detector assembly can be used for simultaneous multi-channel measurements. Photon-counting photodetectors are needed for active spectroscopy measurements from short-wave infrared to mid-wave infrared. HgCdTe avalanche photodiode arrays have emerged recently as a promising technology to fill these needs. This paper gives a review of the photodetectors used in past and present lidars and the development and outlook of HgCdTe APD arrays for future space lidars. Full article

The diversity and complexity of the agricultural environment pose significant challenges for the collection of pest and disease data. Additionally, pest and disease datasets often suffer from uneven distribution in quantity and inconsistent annotation standards. Enhancing the accuracy of pest and disease recognition remains a challenge for existing models. We constructed a representative agricultural pest and disease dataset, FIP6Set, through a combination of field photography and web scraping. This dataset encapsulates key issues encountered in existing agricultural pest and disease datasets. Referencing existing bounding box regression (BBR) loss functions, we reconsidered their geometric features and proposed a novel bounding box similarity comparison metric, DDRIoU, suited to the characteristics of agricultural pest and disease datasets. By integrating the focal loss concept with the DDRIoU loss, we derived a new loss function, namely Focal-DDRIoU loss. Furthermore, we modified the network structure of YOLOV7 by embedding the MobileViTv3 module. Consequently, we introduced a model specifically designed for agricultural pest and disease detection in precision agriculture. We conducted performance evaluations on the FIP6Set dataset using mAP75 as the evaluation metric. Experimental results demonstrate that the Focal-DDRIoU loss achieves improvements of 1.12%, 1.24%, 1.04%, and 1.50% compared to the GIoU, DIoU, CIoU, and EIoU losses, respectively. When employing the GIoU, DIoU, CIoU, EIoU, and Focal-DDRIoU loss functions, the adjusted network structure showed enhancements of 0.68%, 0.68%, 0.78%, 0.60%, and 0.56%, respectively, compared to the original YOLOv7. Furthermore, the proposed model outperformed the mainstream YOLOv7 and YOLOv5 models by 1.86% and 1.60%, respectively. The superior performance of the proposed model in detecting agricultural pests and diseases directly contributes to reducing pesticide misuse, preventing large-scale pest and disease outbreaks, and ultimately enhancing crop yields. These outcomes strongly support the promotion of sustainable agricultural development. Full article

This paper presents the theory, design, and application of a dual-branch series-diode analog pre-distortion (APD) linearizer to improve the linearity and efficiency of a K-band high-power amplifier (HPA). A first-of-its-kind, frequency-dependent large-signal APD model is presented. This model is used to evaluate different phase relationships between the linear and nonlinear branches, suggesting independent gain and phase expansion characteristics with this topology. This model is used to assess the impact of diode resistance, capacitance, and ideality factors on the APD characteristics. This feature is showcased with two similar GaAs diodes to find the best fit for the considered HPA. The selected diode is characterized and modeled between 1 and 26.5 GHz. A comprehensive APD design and simulation workflow is reported. Before fabrication, the simulated APD is evaluated with the measured HPA to verify linearity improvements. The APD prototype achieves a large-signal bandwidth of 6 GHz with 3 dB gain expansion and 8° phase rotation. This linearizer is demonstrated with a 17–21 GHz GaN HPA with 41 dBm output power and 35% efficiency. Using a wideband 750 MHz signal, this APD improves the noise–power ratio (NPR) by 6.5–8.2 dB over the whole HPA bandwidth. Next, the HPA output power is swept to compare APD vs. power backoff for the same NPR. APD improves the HPA output power by 1–2 W and efficiency by approximately 5–9% at 19 GHz. This efficiency improvement decreases by only 1–2% when including the APD post-amplifier consumption, thus suggesting overall efficiency and output power improvements with APD at K-band frequencies. Full article