View-guided Cost Volume for Light Field Arbitrary-view Disparity Estimation.

Per-view disparity estimation for light field (LF) is critical for various applications such as light field editing, but previous work mostly focuses on estimating disparity for the center view. In this paper, we propose a view-guided cost volume (VGCV), which successfully generates high-quality disparity maps for LF arbitrary view. Unlike previous methods that construct a static cost for center view only, VGCV is designed with view information and can be applicable to arbitrary-view estimation. In particular, since the key to achieving it is to condition cost on view, we extend previous static cost to a conditional one by introducing the spatial and angular information of target view into cost construction and aggregation, experiments show that this way can effectively adapt VGCV to arbitrary-view task. For construction, previous stereo-matching methods usually adopt correlation (e.g., variance) for dynamic estimation, but just using correlation can lose image structure information, which is essential for scene detail recovery, therefore we design an image-guided construction module and use cross-view attention to adapt cost for conditional construction while keeping its spatial information. Then for aggregation, we present a coordinate-guided aggregation module for VGCV regularization, which is specially designed to solve the problem of LF view deviation. Finally, we implement a Light Field Arbitrary-View Disparity Estimation Network (LFAVNet), then perform it on both synthetic and real LFs. Experiments demonstrate that LFAVNet can generate a higher-quality disparity map for arbitrary view in LF. We also extend our method to center-view estimation and light field editing tasks, which all achieve advanced performance.

Cholesterol suppresses AMFR-mediated PDL1 ubiquitination and degradation in HCC.

The degradation of proteasomes or lysosomes is emerging as a principal determinant of programmed death ligand 1 (PDL1) expression, which affects the efficacy of immunotherapy in various malignancies. Intracellular cholesterol plays a central role in maintaining the expression of membrane receptors; however, the specific effect of cholesterol on PDL1 expression in cancer cells remains poorly understood. Cholesterol starvation and stimulation were used to modulate the cellular cholesterol levels. Immunohistochemistry and western blotting were used to analyze the protein levels in the samples and cells. Quantitative real-time PCR, co-immunoprecipitation, and confocal co-localization assays were used for mechanistic investigation. A xenograft tumor model was constructed to verify these results in vivo. Our results showed that cholesterol suppressed the ubiquitination and degradation of PDL1 in hepatocellular carcinoma (HCC) cells. Further mechanistic studies revealed that the autocrine motility factor receptor (AMFR) is an E3 ligase that mediated the ubiquitination and degradation of PDL1, which was regulated by the cholesterol/p38 mitogenic activated protein kinase axis. Moreover, lowering cholesterol levels using statins improved the efficacy of programmed death 1 (PD1) inhibition in vivo. Our findings indicate that cholesterol serves as a signal to inhibit AMFR-mediated ubiquitination and degradation of PDL1 and suggest that lowering cholesterol by statins may be a promising combination strategy to improve the efficiency of PD1 inhibition in HCC.

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

Deep learning for detecting and characterizing oil and gas well pads in satellite imagery.

Methane emissions from the oil and gas sector are a large contributor to climate change. Robust emission quantification and source attribution are needed for mitigating methane emissions, requiring a transparent, comprehensive, and accurate geospatial database of oil and gas infrastructure. Realizing such a database is hindered by data gaps nationally and globally. To fill these gaps, we present a deep learning approach on freely available, high-resolution satellite imagery for automatically mapping well pads and storage tanks. We validate the results in the Permian and Denver-Julesburg basins, two high-producing basins in the United States. Our approach achieves high performance on expert-curated datasets of well pads (Precision = 0.955, Recall = 0.904) and storage tanks (Precision = 0.962, Recall = 0.968). When deployed across the entire basins, the approach captures a majority of well pads in existing datasets (79.5%) and detects a substantial number (>70,000) of well pads not present in those datasets. Furthermore, we detect storage tanks (>169,000) on well pads, which were not mapped in existing datasets. We identify remaining challenges with the approach, which, when solved, should enable a globally scalable and public framework for mapping well pads, storage tanks, and other oil and gas infrastructure.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Brain implantation of tissue-level-soft bioelectronics via embryonic development.

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

Orchestration of Macrophage Polarization Dynamics by Fibroblast-Secreted Exosomes during Skin Wound Healing.

Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early proinflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to proresolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. In this study, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast-derived exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet they also accelerated timely switching from M1 to M2 phenotypes. Exosome inhibition dysregulated macrophage responses, resulting in aberrant inflammation and impaired healing, whereas provision of exogenous fibroblast-derived exosomes corrected defects. Topical application of fibroblast-derived exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.

A tricalcium phosphate (TCP) and hydroxyapatite (HA) based light-cured biomaterial for vital pulp therapy.

OBJECTIVES: Evaluate a new light-cured material with better properties for vital pulp therapy. METHODS: Light-cured resin materials consisted of polyethylene glycol (600) diacrylate mixed with different ratios of TCP to HA. In addition to the temperature change (n = 5 for each subgroup) were tested, cell viability and Alizarin Red Staining (ARS) assay were also tested in vitro on human dental pulp cells (n = 6 for each subgroup). Lastly, the material was then compared with Biodentine and control groups in the molars of Wistar rats in vivo for histology assessment. RESULTS: The temperature change for the new materials were under 5 degrees Celsius. For the in vitro assessments, there was no significant difference on day 3 and day 7 for cell viability test. ARS assay showed significantly higher mineralized nodule formation when treated without induction medium for Group D and Biodentine on day 10 compared to Group C and control. On the contrary, Biodentine and control groups treated with induction medium showed significant higher mineralization than the new materials. Histology assessments demonstrated higher mineralized content in Group D and Biodentine on week 3 and week 6. The inflammatory cells in the dental pulp complex of the Biodentine group resolved on week 6 while the inflammation resolved in Group D on week 3. SIGNIFICANCE: The new material exhibits low heat production, low cytotoxicity, and good calcium ion release capability. Compared to traditional materials, it has shorter setting time and better aesthetic outcomes, making it highly suitable for use in vital pulp therapy.

Impulse oscillometry in patients with persistent post-COVID-19 symptoms: A retrospective study.

Introduction: Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms. Material and Method: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date. Result: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways. Conclusion: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Spatiotemporal orchestration of macrophage activation trajectories by Vγ4 T cells during skin wound healing.

Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vγ4+ γδ T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-γ (IFN-γ) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vγ4+ γδ T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vγ4+ γδ T cells expand populations of IFN-γ-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vγ4+γδ T cells flushed into bone marrow stimulate increased IFN-γ production, which elevates the output of pro-inflammatory Ly6C+monocytes. Mobilization of these monocytes continually replenishes the M1 macrophage pool in wounds, preventing phenotypic conversion to M2 activation. Thus, multi-axis coordination of macrophage activation trajectories by trafficking Vγ4+ γδ T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair.

Interactions of neural-like cells with 3D-printed polycaprolactone with different inner diameters for neural regeneration.

Background/purpose: Peripheral neural regeneration is an interesting and challenging field. The aim of this study was to investigate the interactions of neural-like PC12 cells and Poly-D-Lysine (PDL)-coated 3D-printed polycaprolactone (PCL) scaffolds with different inner diameters of half tubular array (HTA) (0, 200, 300, and 400 µm), respectively. Materials and methods: This study used the fused deposition modeling (FDM) technique with 3D-printing to fabricate the thermoplastic polymer. Scaffold properties were measured by mechanical testing, and coating quality was observed under a scanning electron microscope (SEM). PC12 cell biocompatibility was examined by an MTT assay. Cell differentiation was evaluated by immunofluorescence staining. Results: The cell viability of PC12 cells on PDL-coated PCL scaffolds with a 200-µm inner diameter of HTA was shown with significant differences (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001) than other PCL groups at all experimental dates. The SEM observation showed that PDL-coated PCL scaffolds with 200-µm inner diameters of HTA promoted cell adhesion. An immunofluorescence staining of PC12 cells on the PDL-coated PCL scaffold with a 200-µm inner diameter of the HTA group showed that it stimulated PC12 cells for neurite formation much better than the other groups.A PDL-coated PCL scaffold with a 200-µm inner diameter of HTA can promote the growth and differentiation of PC12 cells better than other groups. It indicated that PDL-coated PCL scaffolds with a 200-µm inner diameter HTA can be used for further neural regeneration application.

The Prognostic Value of Positron Emission Tomography/Computed Tomography in Clinical Stage I Lung Cancer Patients: A Propensity-Match Analysis.

Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

An automatic system for recognizing fly courtship patterns via an image processing method.

Fruit fly courtship behaviors composed of a series of actions have always been an important model for behavioral research. While most related studies have focused only on total courtship behaviors, specific courtship elements have often been underestimated. Identifying these courtship element details is extremely labor intensive and would largely benefit from an automatic recognition system. To address this issue, in this study, we established a vision-based fly courtship behavior recognition system. The system based on the proposed image processing methods can precisely distinguish body parts such as the head, thorax, and abdomen and automatically recognize specific courtship elements, including orientation, singing, attempted copulation, copulation and tapping, which was not detectable in previous studies. This system, which has high identity tracking accuracy (99.99%) and high behavioral element recognition rates (> 97.35%), can ensure correct identification even when flies completely overlap. Using this newly developed system, we investigated the total courtship time, and proportion, and transition of courtship elements in flies across different ages and found that male flies adjusted their courtship strategy in response to their physical condition. We also identified differences in courtship patterns between males with and without successful copulation. Our study therefore demonstrated how image processing methods can be applied to automatically recognize complex animal behaviors. The newly developed system will largely help us investigate the details of fly courtship in future research.