Search Results (46)

The inability of existing super-resolution methods to jointly model short-range and long-range spatial dependencies in remote sensing imagery limits reconstruction efficacy. To address this, we propose LSTMConvSR, a novel framework inspired by top-down neural attention mechanisms. Our approach pioneers an LSTM-first–CNN-next architecture. First, an LSTM-based global modeling stage efficiently captures long-range dependencies via downsampling and spatial attention, achieving 80.3% lower FLOPs and 11× faster speed. Second, a CNN-based local refinement stage, guided by the LSTM’s attention maps, enhances details in critical regions. Third, a top-down fusion stage dynamically integrates global context and local features to generate the output. Extensive experiments on Potsdam, UAVid, and RSSCN7 benchmarks demonstrate state-of-the-art performance, achieving 33.94 dB PSNR on Potsdam with 2.4× faster inference than MambaIRv2. Full article

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

Saffron (Crocus sativus L.) is a vegetatively propagated crop of high economic and cultural value, potentially affected by viral infections that may impact its productivity. Despite Iran’s dominance in global saffron production, knowledge of its virome remains limited. In this study, we conducted the first nationwide virome survey of saffron in Iran employing a high-throughput sequencing (HTS) approach on pooled samples obtained from eleven provinces in Iran and one location in Afghanistan. Members of three virus families were detected—Potyviridae (Potyvirus), Solemoviridae (Polerovirus), and Geminiviridae (Mastrevirus)—as well as one satellite from the family Alphasatellitidae (Clecrusatellite). A novel Potyvirus, tentatively named saffron Iran virus (SaIRV) and detected in three provinces, shares less than 68% nucleotide identity with known Potyvirus species, thus meeting the ICTV criteria for designation as a new species. Genetic diversity analyses revealed substantial intrapopulation SNP variation but no clear geographical clustering. Among the two wild Crocus species sampled, only Crocus speciosus harbored turnip mosaic virus. Virome network and phylogenetic analyses confirmed widespread viral circulation likely driven by corm-mediated propagation. Our findings highlight the need for targeted certification programs and biological characterization of key viruses to mitigate potential impacts on saffron yield and quality. Full article

To compare the clinical characteristics of inherited retinal diseases (IRDs) caused by biallelic versus monoallelic variants in the RP1, BEST1, and PROM1 genes. A total of 52 patients (26 female) with genetically confirmed IRDs were retrospectively selected from the records of the Harkness Eye Institute Clinical Coordinating Center at Columbia University Irving Medical Center. In RP1, 3 individuals with biallelic variants and 22 patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. In BEST1, eight individuals with biallelic variants and nine individuals with monoallelic variants classified as either pathogenic or likely pathogenic were included. In PROM1, four individuals with biallelic variants and six patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. All patients underwent multimodal retinal imaging and, when available, full-field electroretinography (ffERG). In all three genes, individuals with biallelic variants had markedly earlier disease onset and more severe phenotypes. In RP1, on SD-OCT, foveal involvement was observed in all biallelic cases (3/3, 100%) and in 4/22 (18%) monoallelic cases. In BEST1, the average age of onset in the biallelic cohort was 7.12 years, and the average age was 32.7 years in the monoallelic cohort. Four of eight (50%) patients in the biallelic group were additionally found to have widespread serous lesions outside of the central macula. This finding was not observed in the monoallelic group. Three of eight (38%) biallelic BEST1 patients had moderate reductions in their photopic flicker. All monoallelic BEST1 patients had photopic responses within the normal range. PROM1 biallelic cases showed severe functional impairment on ffERG, while most monoallelic cases retained normal responses. In the biallelic cohort, four of four (100%) of patients had severely attenuated or extinguished photopic responses. In the monoallelic PROM1 group, four of five (80%) monoallelic PROM1 patients had normal photopic responses, and P2-2 had mildly attenuated photopic responses. Individuals with biallelic variants exhibited earlier disease onset, more severe retinal degeneration, and significantly reduced retinal function compared with those with monoallelic variants. These observations highlight the role of loss-of-function mechanisms in more aggressive disease courses and underscore the importance of considering zygosity when determining prognosis and planning gene-based therapies. Full article

Background/Objectives: A preventative vaccine against human cytomegalovirus (HCMV) infection and disease remains an unmet medical need. Several attenuated virus and antigen-based HCMV vaccine candidates have been proposed; however, development challenges have limited their progression through the clinical pipeline. Method: A high-throughput and robust relative potency assay, Imaging of Relative Viral Expression (IRVE), was developed and applied to measure the infection of a live-attenuated HCMV vaccine candidate in ARPE-19 epithelial cells. The IRVE assay measures HCMV infection by immunostaining Immediate Early 1 (IE1) protein and enumeration of IE1-positive, infected cells against total cells. Increased throughput was accomplished using 384-well plate automation on a custom-designed integrated robotic system. Results: The IRVE assay effectively measures relative potency changes in an HCMV vaccine candidate under different upstream processes, downstream processes, and formulation conditions. Key assay parameters including microplate format, cell density, serum concentration, infection time and influence of cell age were evaluated and optimized. The IRVE assay was correlated to historical, lower throughput HCMV potency assays, including plaque and Infectivity of Early Gene Expression (IEE), validating its application as a potency screening tool. Conclusions: The IRVE assay has been successfully implemented to support HCMV vaccine development over several years of clinical development. Full article

Background/Objectives: Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. Methods: This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. Results: Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher postvaccination hemagglutination inhibition assay geometric mean titers and fold rises and seroconversion rates observed with qIRV versus QIV for A strains, with no consistent pattern for B strains. Cell-mediated immune responses to qIRV by Day 7 showed overall higher T-cell responses against all strains versus QIV. Antibody and cell-mediated immune responses showed comparable trends across qIRV doses in 18- through 85-year-olds; a dose-related pattern was observed in 65- through 85-year-olds (60 μg > 30 μg). Conclusions: Phase 3 investigations of qIRV 60 µg in older adults and qIRV 30 µg in younger adults are warranted (ClinicalTrials.gov Identifier: NCT05052697). Full article

Background/Objectives: Managing ventilatory strategies in patients with obesity under general anesthesia presents significant challenges due to obesity-related pathophysiological changes. Inverse ratio ventilation (IRV) has emerged as a potential strategy to optimize respiratory mechanics during laparoscopic surgery in this population. The primary outcomes were changes in respiratory mechanics, including peak inspiratory pressure (P_Peak), plateau pressure (P_Plat), mean airway pressure (P_Mean), and dynamic compliance (C_Dyn). Secondary outcomes included gas exchange parameters, hemodynamic measures, inflammatory cytokines, and postoperative complications. Methods: A systematic review and meta-analysis were conducted, searching PubMed, Scopus, EMBASE, and PMC Central. Only English-language randomized controlled trials (RCTs) evaluating the impact of IRV in adult surgical patients with obesity were included. The quality and certainty of evidence were assessed using the Risk of Bias 2 (RoB 2) tool and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework, respectively. Results: Three RCTs including 172 patients met the inclusion criteria. Compared to conventional ventilation without prolonged inspiratory time or IRV, IRV significantly reduced P_Peak (MD [95%CI]: −3.15 [−3.88; −2.42] cmH₂O, p < 0.001) and P_Plat (MD [95%CI]: −3.13 [−3.80; −2.47] cmH₂O, p < 0.001) while increasing P_Mean (MD [95%CI]: 4.17 [3.11; 5.24] cmH₂O, p < 0.001) and C_Dyn (MD [95%CI]: 2.64 [0.95; 4.22] mL/cmH₂O, p = 0.002) during laparoscopy, without significantly affecting gas exchange. IRV significantly reduced mean arterial pressure (MD [95%CI]: −2.93 [−3.95; −1.91] mmHg, p < 0.001) and TNF-α levels (MD [95%CI]: −9.65 [−17.89; −1.40] pg/mL, p = 0.021). Conclusions: IRV optimizes intraoperative respiratory mechanics but has no significant impact on postoperative outcomes, necessitating further research to determine its clinical role. Full article

Drought presents significant challenges in arid regions, influencing local climate and environmental dynamics. While the large-scale climatic phenomena in Xinjiang, northwest China, are well-documented, the finer-scale climatic variability in subregions such as the Ili River Valley (IRV) remains insufficiently studied. This knowledge gap impedes effective regional planning and environmental management in this ecologically sensitive area. In this study, we analyze the spatiotemporal evolution of drought in the IRV from 1961 to 2023, using data from ten meteorological stations. The SPEI drought index, along with Sen’s trend analysis, the Mann–Kendall test, the cumulative departure method, and wavelet analysis, were employed to assess drought patterns. Results show a significant drying trend in the IRV, starting in 1995, with frequent drought events from 2018 onwards, and no notable transition year observed from wet to dry conditions. The overall drought rate was −0.09 per decade, indicating milder drought severity in the IRV compared to broader Xinjiang. Seasonally, the IRV experiences drier summers and wetter winters compared to regional averages, with negligible changes in autumn and milder drought conditions in spring. Abrupt changes in the drying seasons occurred later in the IRV than in Xinjiang, with delays of 21 years for summer, and over 17 and 35 years for spring and autumn, respectively, indicating a lagged response. Spatially, the western plains are more prone to aridification than the central and eastern mountainous regions. The study also reveals significant differences in drought cycles, which are longer than those in Xinjiang, with distinct wet–dry phases observed across multiple time scales and seasons, emphasizing the complexity of drought variability in the IRV. In conclusion, the valley exhibits unique drought characteristics, including milder intensity, pronounced seasonal variation, spatial heterogeneity, and notable resilience to climate change. These findings underscore the need for region-specific drought management strategies, as broader approaches may not be effective at the subregional scale. Full article

Currently, in dairy farming, there is growing concern for the welfare of calves during the critical period between the separation from their dams and weaning. During weaning, rationed feeding is a practice used to improve feed efficiency and control the calves’ growth, but it could also have negative consequences associated with hunger and feed restriction behavior. One such consequence could be the performance by calves of stereotyped behaviors indicative of poor welfare, such as non-nutritive oral behaviors. We hypothesized that making a Total Mixed Ration (TMR) available to calves, in addition to the standard pelleted starter diet, thanks to its structural and nutritional characteristics, could help to focus the oral behavior of the subjects towards nutritional activities and therefore limit the development of stereotyped behaviors, even when the amount of starter is restricted. To test this hypothesis, 30 female Holstein calves (equipped with an accelerometer based on an ear tag), were randomly assigned to one of three treatments: a control diet (CTR) with an ad libitum calf starter but without TMR; Treatment 1 (TRT1) with both ad libitum calf starter and ad libitum TMR; Treatment 2 (TRT2) with ad libitum TMR and a restricted amount of a calf starter (50% of the intake starter of the control group day by day). All animals were kept in individual cages equipped with a slow-flow teat bucket apparatus for milk feeding and with access to separated buckets (one for drinking water, one for the starter, and one for the TMR) placed on the outside of the front gate of each cage. Sucking behavior, as well as resting, ruminating and activity behavior, was recorded individually from 7 days of life to weaning (63 d of age) by an automated monitoring system based on ear-tag accelerometers (SCR eSense, Allflex, Irving, TX, USA). The results showed that in the CTR group, there was a greater sucking activity compared to the TRT1 group (26.25 min/head/day vs. 16.83 min/head/day, p = 0.0181), while the TRT2 group showed intermediate values (20.41 min/head/day). We hypothesized that this increased sucking activity may be explained by the oral activity directed at sucking the Milk Bar tube observed only in CTR calves after complete consumption of available milk and could indicate a higher stress level than in the TRT1 group. The time spent resting was significantly lower for the CTR group compared to the TRT1 group (9.20 h/day vs. 11.15 h/day, p = 0.0049) while the TRT2 group was in an intermediate situation (10.65 h/day). Furthermore, the increase in time dedicated to rest observed in TRT1, in light of the good vitality of the calves shown by the daily patterns of resting behavior and daily activity, also seems to suggest an improvement in welfare conditions compared to calves receiving pelleted starter alone. Based on these results, we can deduce that providing TMR ad libitum in the diet of weaning calves could be an effective strategy to improve calf welfare due to the reduction in stereotyped oral activity. However, further studies are needed to establish threshold values useful for distinguishing physiological from pathological resting times in weaning calves raised in individual cages. Full article

This study aims to characterize graphene epoxy nanocomposite properties using multiscale modeling. Molecular dynamics was used to study the nanocomposite at the nanoscale and finite element analysis at the macroscale to complete the multiscale modeling. The coupling of these two scales was carried out using the Irving–Kirkwood averaging method. First, the functionalization of graphene was carried and 6% grafted graphene was selected based on Young’s modulus and the tensile strength of the grafted graphene sheet. Functionalized graphene with weight fractions of 1.8, 3.7, and 5.6 wt.% were reinforced with epoxy polymer to form a graphene epoxy nanocomposite. The results showed that the graphene with 3.7 wt.% achieved the highest modulus. Subsequently, a functionalized graphene sheet with an epoxy matrix was developed to obtain the interphase properties using the MD modeling technique. The normal and shear forces at the interphase region of the graphene epoxy nanocomposite were investigated using a traction-separation test to analyze the mechanical properties including Young’s modulus and traction forces. The mean stiffness of numerically tested samples with 1.8, 3.7, and 5.6 wt.% graphene and the stiffness obtained from experimental results from the literature were compared. The experimental results are lower than the multiscale model results because the experiments cannot replicate the molecular-scale behavior. However, a similar trend could be observed for the addition of up to 3.7 wt.% graphene. This demonstrated that the graphene with 3.7 wt.% shows improved interphase properties. The macroscale properties of the graphene epoxy nanocomposite models with 1.8 and 3.7 wt.% were comparatively higher. Full article

The virulence of Mycobacterium tuberculosis (M. tuberculosis) is related to many factors, including intracellular survival, cell wall permeability, and cell envelope proteins. However, the biological function of the M. tuberculosis membrane protein Rv1476 remains unclear. To investigate the potential role played by Rv1476, we constructed an Rv1476 overexpression strain and found that overexpression of Rv1476 enhanced the intracellular survival of M. tuberculosis, while having no impact on the growth rate in vitro. Stress experiments demonstrated that the Rv1476 overexpression strain displayed increased susceptibility to different stresses compared to the wild-type strain. Transcriptome analysis showed that Rv1476 overexpression causes changes in the transcriptome of THP-1 cells, and differential genes are mainly enriched in cell proliferation, fatty acid degradation, cytokine–cytokine receptor interaction, and immune response pathways. Rv1476 overexpression inhibited the expression of some anti-tuberculosis-related genes, such as CCL1, IL15, IL16, ISG15, GBP5, IL23, ATG2A, IFNβ, and CSF3. Altogether, we conclude that Rv1476 may play a critical role for M. tuberculosis in macrophage survival. Full article

The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment. Full article

When the icebreaker sails in the polar region, it adopts continuous and ramming icebreaking operations. When the ice condition exceeds the design working condition, it uses the ramming icebreaking method to advance. The nonlinear icebreaking process and complex ice conditions make it difficult to accurately predict the ice-strengthened ships’ ramming performance. This paper develops a scale-ratio brittle model of ice to simulate thick, level ice and predicts the ice penetration distance and bow load of an icebreaking research vessel (IRV) model at different speeds. The test results show that the penetration distance of the scoop-shaped bow IRV increases with the ramming speed and the average and extreme values of the contact load increase with the increase in the speed. The experimental results are a valid complement to the ice tank tests and do not cover all aspects of ship design. The main purpose is to develop a test program and performance prediction scheme for studying penetration distance and ice load during ram icebreaking. Full article

Colorectal polyps in the colon or rectum are precancerous growths that can lead to a more severe disease called colorectal cancer. Accurate segmentation of polyps using medical imaging data is essential for effective diagnosis. However, manual segmentation by endoscopists can be time-consuming, error-prone, and expensive, leading to a high rate of missed anomalies. To solve this problem, an automated diagnostic system based on deep learning algorithms is proposed to find polyps. The proposed IRv2-Net model is developed using the UNet architecture with a pre-trained InceptionResNetV2 encoder to extract most features from the input samples. The Test Time Augmentation (TTA) technique, which utilizes the characteristics of the original, horizontal, and vertical flips, is used to gain precise boundary information and multi-scale image features. The performance of numerous state-of-the-art (SOTA) models is compared using several metrics such as accuracy, Dice Similarity Coefficients (DSC), Intersection Over Union (IoU), precision, and recall. The proposed model is tested on the Kvasir-SEG and CVC-ClinicDB datasets, demonstrating superior performance in handling unseen real-time data. It achieves the highest area coverage in the area under the Receiver Operating Characteristic (ROC-AUC) and area under Precision-Recall (AUC-PR) curves. The model exhibits excellent qualitative testing outcomes across different types of polyps, including more oversized, smaller, over-saturated, sessile, or flat polyps, within the same dataset and across different datasets. Our approach can significantly minimize the number of missed rating difficulties. Lastly, a graphical interface is developed for producing the mask in real-time. The findings of this study have potential applications in clinical colonoscopy procedures and can serve based on further research and development. Full article

Neck disorders have a significant impact on people because of their high incidence. The head-mounted display (HMD) systems, such as Meta Quest 2, grant access to immersive virtual reality (iRV) experiences. This study aims to validate the Meta Quest 2 HMD system as an alternative for screening neck movement in healthy people. The device provides data about the position and orientation of the head and, thus, the neck mobility around the three anatomical axes. The authors develop a VR application that solicits participants to perform six neck movements (rotation, flexion, and lateralization on both sides), which allows the collection of corresponding angles. An InertiaCube3 inertial measurement unit (IMU) is also attached to the HMD to compare the criterion to a standard. The mean absolute error (MAE), the percentage of error (%MAE), and the criterion validity and agreement are calculated. The study shows that the average absolute errors do not exceed 1° (average = 0.48 ± 0.09°). The rotational movement’s average %MAE is 1.61 ± 0.82%. The head orientations obtain a correlation between 0.70 and 0.96. The Bland–Altman study reveals good agreement between the HMD and IMU systems. Overall, the study shows that the angles provided by the Meta Quest 2 HMD system are valid to calculate the rotational angles of the neck in each of the three axes. The obtained results demonstrate an acceptable error percentage and a very minimal absolute error when measuring the degrees of neck rotation; therefore, the sensor can be used for screening neck disorders in healthy people. Full article