Search Results (80)

Change detection is a crucial field in remote sensing image analysis for tracking environmental dynamics. Although convolutional neural networks (CNNs) have made impressive strides in this field, their grid-based processing structures struggle to capture abundant semantics and complex spatial-temporal correlations of bitemporal features, leading to high uncertainty in distinguishing true changes from pseudo changes. To overcome these limitations, we propose the Attention-guided Graph convolution network for Change Detection (AGCD), a novel framework that integrates a graph convolutional network (GCN) and an attention mechanism to enhance change-detection performance. AGCD introduces three novel modules, including Graph-level Feature Difference Module (GFDM) for enhanced feature interaction, Multi-scale Feature Fusion Module (MFFM) for detailed semantic representation and Spatial-Temporal Attention Module (STAM) for refined spatial-temporal dependency modeling. These modules enable AGCD to reduce pseudo changes triggered by seasonal variations and varying imaging conditions, thereby improving the accuracy and reliability of change-detection results. Extensive experiments on three benchmark datasets demonstrate that AGCD’s superior performance, achieving the best F1-score of 90.34% and IoU of 82.38% on the LEVIR-CD dataset and outperforming existing state-of-the-art methods by a notable margin. Full article

Background: Products of lipid peroxidation include a number of reactive lipid aldehydes including reactive dicarbonyl electrophiles (DEs) and contribute to disease processes. DEs play a significant role in the development and progression of metabolic-associated steatotic liver disease (MASLD) by contributing to oxidative stress, inflammation, protein dysfunction, and mitochondrial impairment. Reducing DE stress may be a potential strategy for managing MASLD. We hypothesized that the DE scavenger 2-hydroxybenzylamine (2-HOBA) would reduce liver injury by reducing liver protein adduct formation by DE in mouse models of MASLD. Methods: Protein adducts were measured in human livers by immunohistochemistry and immunoblot. The effects of 2-HOBA were assessed in two different mouse models of MASLD. Results: Isolevuglandin (IsoLG) protein adducts were increased in MASH-staged human livers relative to histologically normal controls. Diet-Induced Animal Model of Nonalcoholic Fatty Liver Disease (DIAMOND) mice treated with 2-HOBA exhibited significantly lower fibrosis scores (* p = 0.012) and reduced liver transaminases (AST, p = 0.03) and ALT, p = 0.012) by over 40%. In STAM (Stelic Animal Model) mice, 2-HOBA improved NAFLD activity scores (p = 0.03, NAS), hyperglycemia, and inflammatory cytokines and reduced serum F2-isoprostanes (IsoPs) by 30%, p = 0.05. These improvements were absent mRNA changes in hepatic antioxidant enzymes (Cat, Gpx1, or Sod2) or ROS-generating proteins (p22PHOX, p47PHOX, NOX4 or COX1). Conclusions: DE scavenging with 2-HOBA may be a promising therapeutic strategy for managing MASLD. While findings are currently limited to male mice, a nutraceutical that reduces liver fibrosis could significantly improve the management of MASH by offering a non-invasive treatment option to potentially slow or reverse liver scarring, delay progression to cirrhosis, and improve patient outcomes, while also providing a potential treatment option for patients who may not be suitable for other interventions like liver transplantation. Full article

Plants utilize plasma membrane localized receptors like kinases (RLKs) or receptor-like proteins (RLPs) to recognize pathogens and activate pattern-triggered immunity (PTI) responses. A gain-of-function mutation in the Arabidopsis RLP SNC2 (SUPPRESSOR OF NPR1-1, CONSTITUTIVE 2) leads to constitutive activation of defense responses in snc2-1D mutant plants. Transcription factors, SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1) and CALMODULIN-BINDING PROTEIN 60g (CBP60g), define two parallel pathways downstream of SNC2. The autoimmunity of snc2-1D was partially affected by single mutations in SARD1 or CBP60g but completely suppressed by the sard1 cbp60g double mutant. From a suppressor screen using sard1-1 snc2-1D, we identified a deubiquitinating enzyme ASSOCIATED MOLECULE WITH THE SH3 DOMAIN OF STAM 1 (AMSH1) as a key component in SNC2-mediated plant immunity. A loss-of-function mutation in AMSH1 can suppress the autoimmune responses of sard1-1 snc2-1D. In eukaryotes, selective protein degradation often occurs through the ubiquitination/deubiquitination system. The deubiquitinating enzymes that remove ubiquitin from target proteins play essential roles in controlling the level of target protein ubiquitination and degradation. As loss of AMSH1 results in decreased BDA1 abundance and BDA1 is a transmembrane protein required for SNC2-mediated immunity, AMSH1 likely contributes to immunity regulation through controlling BDA1 stability. Full article

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic disorder of the liver and affects many people worldwide. Intestinal bacteria are thought to be involved in the pathological progression of NAFLD; therefore, improving the intestinal microbiota may be important in controlling NAFLD. In this study, we assessed the effects of water-soluble cellulose acetate (WSCA) on the intestinal microbiota in a non-alcoholic steatohepatitis (NASH) mouse model. Methods: NASH model (STAM mice) was created by streptozotocin injection and feeding the mice a high-fat diet. The serum biochemical parameters were analyzed. Intestinal bacterial populations were analyzed using paired-end sequencing of 16S rRNA, 18S rRNA, and internal transcribed spacer gene. Results: Our findings indicated that WSCA administration tends to improve the serum alanine aminotransferase and glucose levels in STAM mice and decreased the alpha diversity and altered the beta diversity of their intestinal microbiota. Additionally, WSCA intake resulted in an increase in the abundance of Coriobacteriaceae_UCG-002 and a decrease in the abundance of Enterobacter. Conclusions: WSCA intake can alter specific microbial compositions to improve blood glucose levels and liver functions and may improve the pathogenesis of NAFLD. Full article

This research aims to determine the state of Industry 4.0 readiness and to identify the best practices, challenges, and barriers to implementing Industry 4.0 technology in a medical device manufacturer, thus aiding in improving sustainability. Semi-structured interviews were completed with 12 senior executives representing a wide array of functions in a single large medical device manufacturer. Convenience sampling was used to analyse the interview transcripts to draw out themes that were then discussed and analysed with findings from the literature review. This research determined the state of Industry 4.0 readiness in the case study of medical device manufacturers. This research identified several best practices, challenges, and barriers to implementing Industry 4.0 technology. Currently, there are few case studies in the literature that have a medical device manufacturer as the case study for Industry 4.0 readiness. There are even fewer articles that tackle Industry 4.0 implementation across the entire medical device industry. There is currently no published literature that analyses the best practices for implementing Industry 4.0 in a medical device manufacturer. The best practices for Industry 4.0 implementation identified in this study can be beneficial to stakeholders in the medical device industry and within the healthcare sector, help them plan current and future Industry 4.0 programmes, improve sustainability in their companies, as well as optimise patient treatment and approaches. Full article

Background: Wish-granting interventions are recognized as positive experiences for children with critical illness and their families. While the positive effects have been shown in the immediate and short term, data on their long-term effects are lacking. Objectives: To evaluate the effects of wish-granting interventions on children and parents during and post intervention—both in the weeks after, and up to 5 years after—and to examine any differences between these two groups. Methods: A large-scale international survey was distributed to children (aged 13–17 years old in 2023) and their parents across 24 countries who received a wish-granting intervention in the preceding five years by Make-A-Wish Foundation International. Primary outcomes were positive emotions experienced by children and parents during and after the intervention (short term and long term). The secondary outcomes assessed were negative emotions in wish children, and to what extent children and parents felt the intervention created a sense of normalcy, benefitted other family members, created a happy memory, and gave relief from medical treatment, plus the perceived importance of wish-granting interventions. Results: The responses of 535 children and 1062 parents were analyzed. Both groups reported increases in positive emotions during the early intervention stages, peaking when the wish was granted and persisting in the short and long term. No significant differences were found between children and parents during wish-granting or after the intervention. Negative emotions were reported by a minority of children. Over 80% of children and parents felt the intervention created a happy memory and provided relief from their medical treatments. Nearly all children (96.8%) and parents (95.4%) viewed a wish-granting intervention as important for children with a critical illness. Conclusions: Wish-granting interventions can provide positive emotional benefits to both children and their families in both the short and long term. Full article

The insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). The binding of Ang IV inhibits the enzymatic activity of IRAP and has been proven to enhance learning and memory in animal models. The macrocyclic compound 9 (C9) is a potent synthetic IRAP inhibitor developed from the previously reported inhibitor HA08. In this study, we have examined compound C9 and its effects on cognitive markers drebrin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) in primary hippocampal and cortical cultures. Cells from Sprague Dawley rats were cultured for 14 days before treatment with C9 for 4 consecutive days. The cells were analysed for protein expression of drebrin, MAP2, GFAP, glucose transporter type 4 (GLUT4), vesicular glutamate transporter 1 (vGluT1), and synapsin I using immunocytochemistry. The gene expression of related proteins was determined using qPCR, and viability assays were performed to evaluate toxicity. The results showed that protein expression of drebrin and MAP2 was increased, and the corresponding mRNA levels were decreased after treatment with C9 in the hippocampal cultures. The ratio of MAP2-positive neurons and GFAP-positive astrocytes was altered and there were no toxic effects observed. In conclusion, the IRAP inhibitor compound C9 enhances the expression of the pro-cognitive markers drebrin and MAP2, which further confirms IRAP as a relevant pharmaceutical target and C9 as a promising candidate for further investigation. Full article

Ubiquitin (Ub) signals are recognized and decoded into cellular responses by Ub-receptors, proteins that tether the Ub-binding domain(s) (UBDs) with response elements. Typically, UBDs bind mono-Ub in highly dynamic and weak affinity manners, presenting challenges in identifying and characterizing their binding interfaces. Here, we report the development of a new approach to facilitate the detection of these weak interactions using split-reporter systems where two interacting proteins are proximally co-translated from a single mRNA. This proximity significantly enhances the readout signals of weak protein–protein interactions (PPIs). We harnessed this system to characterize the ultra-weak UBD and ENTH (Epsin N-terminal Homology) and discovered that the yeast Ent1-ENTH domain contains two Ub-binding patches. One is similar to a previously characterized patch on STAM1(signal-transducing adaptor molecule)-VHS (Vps27, Hrs, and STAM), and the other was predicted by AlphaFold. Using a split-CAT selection system that co-translates Ub and ENTH in combination with mutagenesis, we assessed and confirmed the existence of a novel binding patch around residue F53 on ENTH. Co-translation in the split-CAT system provides an effective tool for studying weak PPIs and offers new insights into Ub-receptor interactions. Full article

Background: Stem revisions in revision total hip arthroplasty (THA) with proximal bone stock loss may be dealt with utilizing modular, uncemented conical stems. During stem extraction, surgeons may resort to extended trochanteric osteotomy (ETO). However, ETO is associated with extensive blood loss and infections. This study compared the clinical outcomes, radiographic results and complications in THA revisions utilizing conical modular stem with and without ETO. Methods: Patients who underwent revision THA with or without ETO were assessed retrospectively. The minimal follow-up was 3 years. The functional evaluation included Harris Hip Score (HHS) and Short Form 36 (SF-36) as well as Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Numerical Rating Scale for pain assessment. The radiographic evaluation comprised bone defect assessment, osteotomy healing, stem migration and position, presence of radiolucent lines and stress shielding. Results: In total, 73 patients (80 hips) were included in the final analysis. The ETO group comprised 48 hips, and the no-ETO group comprised 32 hips. In the ETO group, pre-operative WOMAC scores were lower than in the no-ETO group (p = 0.012). No significant differences were found in terms of post-operative HHS, WOMAC, and NRS scores between groups, except worse results were found in the case of claw plate implantation. Patients in the no-ETO group exhibited better results in SF-36 than in the ETO-group. Osteotomy non-union was observed in four hips (9.5%). Stam varus/valgus position was within ±1.5 degrees (85.9%). Conclusions: ETO does not adversely impact outcomes in patients undergoing femoral stem revisions with modular conical stems. The invasive nature of these procedures prompts careful consideration in each case individually. Full article

Current video face-swapping technologies face challenges such as poor facial fitting and the inability to handle obstructions. This paper introduces Amazing FaceSwap (AmazingFS), a novel framework for producing cinematic quality and realistic face swaps. Key innovations include the development of a Source-Target Attention Mechanism (STAM) to improve face-swap quality while preserving target face expressions and poses. We also enhanced the AdaIN style transfer module to better retain the identity features of the source face. To address obstructions like hair and glasses during face-swap synthesis, we created the AmazingSeg network and a small dataset AST. Extensive qualitative and quantitative experiments demonstrate that AmazingFS significantly outperforms other SOTA networks, achieving amazing face swap results. Full article

The global population aging poses new challenges in allocating care facilities for the elderly. This demographic trend also influences economic development and the quality of urban life. However, current research focuses on the supply of elderly care facilities and primarily uses administrative divisions as a scale, resulting in low spatiotemporal sensitivity in evaluating the spatial equilibrium of elderly care facilities (SEECF). The relationship between the SEECF and economic development is not clear. In response to these problems, we proposed a spatial equilibrium model of elderly care facilities with high spatiotemporal sensitivity (SEM-HSTS) and explored the spatiotemporal associations between the SEECF and economic development. Considering the spatial accessibility rate of elderly care services (SARecs) and the spatiotemporal supply–demand ratio for elderly care services (STSDRecs), two types of supply–demand relationship factors were constructed. Then, a spatiotemporal accessibility of medical services (STAms) factor was obtained based on a modified two-step floating catchment area (M2SFCA) method. On this basis, the SEM-HSTS was constructed based on the theory of coordinated development. Further, a panel threshold model was employed to evaluate the influence relationships among population aging, SEECF, and gross domestic product (GDP) in different phases. Finally, spatial autocorrelation and Geodetector explored the spatial associations between SEECF and GDP across complex urban land use categories (ULUC). The experimental results at a 100-m grid scale showed that the SEM-HSTS exhibited higher spatiotemporal heterogeneity than the classical accessibility method, with elevated spatiotemporal sensitivity. Effectively identified various spatial imbalances, such as undersupply and resource waste. The panel model captured phased relationship changes, showing that SEECF had inhibitory and promotional effects on GDP in pre- and post-aging societies, with stronger effects as balance approached. Moreover, the combined interaction of ULUC and GDP had a more significant influence on SEECF than any individual factor, with GDP exerting a more significant influence. This study provides an empirical basis for creating resource-efficient elderly care facility systems and optimizing layouts. Full article

Ostrea chilensis (a flat oyster) is native to Chile and New Zealand. In Chile, this oyster has been cultured and harvested for at least 80 years. However, the culture of flat oysters has not developed like other aquaculture activities in Chile, mainly due to the inefficiency of the collectors (made of ribbed mussel shells) and the lack of spats produced. The objective of this study was to determine the capacity of spat collectors for the settlement of O. chilensis. For this purpose, field and laboratory experiments were carried out. Our results indicated that oyster larvae do not have a preference for either side of the shell (periostracum or nacreous) to settle on. However, after one year of growth in the field, juveniles were more abundant on the nacreous side of the shell (spat collector). Also, the oysters that settled on the nacreous side of the valve were larger. This was due to the fact that the periostracum had a greater number of epibionts, and they competed for space and resources with the settled oyster spats, causing a decrease in the abundance of oyster spats on that surface. Our findings raise the possibility that collectors could improve efficiency in the production of spats. Finally, we discuss the implications of these results for the Chilean oyster-farming industry. Full article

The challenges to feed the world in 2050 are becoming more and more apparent. This calls for producing more with fewer inputs (most of them under scarcity), higher resource efficiency, minimum or zero effect on the environment, and higher sustainability. Therefore, increasing the circularity of production systems is highly significant for their sustainability. This study investigates the utilization of waste streams from greenhouse hydroponic drainage nutrient solutions for the cultivation of the microalgae Desmodesmus sp. The cultivation was done in an automatically controlled container-scale closed tubular Photo Bio-Reactor (PBR). The study included lab-scale open-pond system experiments and in situ container-scale experiments in the greenhouse wastewater system to assess biomass growth, optical density, nitrogen consumption, and the influence of enzymatic complexes on microalgae cell breakdown. A batch-harvesting process was followed, and the harvested microalgae biomass was pre-concentrated using FeCl₃ as a flocculant that has demonstrated efficient sedimentation and biomass recovery. Following microalgae sedimentation, the produced biomass was used for biostimulant production by means of a biocatalysis process. The enzymatic complexes, “EnzProt”, “EnzCell”, and “EnzMix” were tested for cell breakdown, with “EnzMix” at a dosage of 10% showing the most promising results. The results demonstrate successful biomass production and nitrogen uptake in the lab-scale open-pond system, with promising upscaling results within container-scale cultivation. The findings contribute to a better assessment of the needs of Desmodesmus sp. culture and highlight the importance in optimizing culture conditions and enzymatic processes for the production of biostimulants. Full article

Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia. Full article

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV. Full article