Search Results (7,744)

Multimodal knowledge graphs have recently been successfully applied to tasks such as those relating to information retrieval, question and answer, and recommender systems. In this study, we propose a dual-path fine-tuning mechanism technique with a low-rank adapter and an embedded cueing layer, aiming to improve the generalization and accuracy of the model in analogical reasoning tasks. The low-rank fine-tuning (LoRA) technique with rank-stable scaling factor is used to fine-tune the MKGformer model, and a cue-embedding layer is innovatively added to the input layer, which enables the model to better grasp the scale of the relationship between entities according to the dynamic cue vectors during the fine-tuning process and ensures that the model achieves the best results during training. The experimental results show that the R-MKG model improves several evaluation indexes by more than 20%, which is significantly better than the traditional DoRA and FA-LoRA methods. This research provides technical support for multimodal knowledge graph analogical reasoning. We hope that our work will bring benefits and inspire future research. Full article

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Significant progress has been achieved in the treatment of acute aortic dissection over the past 90 years, following the first surgical intervention. This review pays tribute to the dedication of pioneers and innovators who developed advanced medical devices and therapeutic strategies to address this challenging condition. While navigating uncertainties in treatment optimization, the primary focus of the therapeutic strategies has been to save lives by increasing survival rates during the acute phase and to prevent aorta-related lethal events and late-stage thoracoabdominal aortic replacements. From a neutral standpoint, this review traces over 90 years of progress in treating acute aortic dissection. We hope that as many patients as possible will receive treatment rationally, without over- or under-treatment. Full article

Neuroinflammation is the major contributor to the pathology of neonatal hypoxic–ischemic (HI) brain injury. Our previous studies have demonstrated that microRNA210 (miR210) inhibition with antisense locked nucleic acid (LNA) inhibitor mitigates neuroinflammation and provides neuroprotection after neonatal HI insult. However, the underlying mechanisms remain elusive. In the present study, using miR210 knockout (KO) mice and microglial cultures, we tested the hypothesis that miR210 promotes microglial activation and neuroinflammation through suppressing mitochondrial function in microglia after HI. Neonatal HI brain injury was conducted on postnatal day 9 (P9) wild-type (WT) and miR210 knockout (KO) mouse pups. We found that miR210 KO significantly reduced brain infarct size at 48 h and improved long-term locomotor functions assessed by an open field test three weeks after HI. Moreover, miR210 KO mice exhibited reduced IL1β levels, microglia activation and immune cell infiltration after HI. In addition, in vitro studies of microglia exposed to oxygen–glucose deprivation (OGD) revealed that miR210 inhibition with LNA reduced OGD-induced expression of Il1β and rescued OGD-mediated downregulation of mitochondrial iron–sulfur cluster assembly enzyme (ISCU) and mitochondrial oxidative phosphorylation activity. To validate the link between miR210 and microglia activation, isolated primary murine microglia were transfected with miR210 mimic or negative control. The results showed that miR210 mimic downregulated the expression of mitochondrial ISCU protein abundance and induced the expression of proinflammatory cytokines similar to the effect observed with ISCU silencing RNA. In summary, our results suggest that miR210 is a key regulator of microglial proinflammatory activation through reprogramming mitochondrial function in neonatal HI brain injury. Full article

If God cares and is present, can God use pain and suffering in my life? Absolutely. Does this mean that God planned, ordained, or designed the pain (or cancer) to be instrumental in my life for some sort of higher spiritual purpose? If so, why? Why does God allow cancer to invade and interrupt one’s life? There are no theologically sound or definitive answers to these questions. Although asking such questions is basic to our humanity, as we will observe in various passages of Scripture, the answers will always remain elusive. Instead of seeking to answer the question “why?”, I will suggest two areas for theological and pastoral reflection with respect to those facing cancer: humility and hope. Enduring cancer, from diagnosis through treatment, requires humility in mind and body before our Creator and before our caregivers. Cancer also provides an opportunity for Christians to embed themselves in the hope of resurrection and new creation. Resurrection hope is also not reduced to hope beyond death but hope that is manifested now through embodied resurrection “signs” and actions of human sacrificial love, both received and practiced by the patient undergoing illness and by the patient’s caregivers, family, and friends. Full article

Background/Objectives: Strengthening antimicrobial stewardship (AMS) programs is an invaluable intervention in the ongoing efforts to contain the threat of antimicrobial resistance (AMR), particularly in low-resource settings. This study evaluates the impact of the Telementoring, Education, and Advocacy Collaboration initiative for Health through Antimicrobial Stewardship (TEACH AMS), which uses the virtual Extension for Community Healthcare Outcomes (ECHO) learning model to enhance AMS capacity in Kenya, Ghana, and Malawi. Methods: A mixed-methods approach was used, which included attendance data collection, facility-level assessments, post-session and follow-up surveys, as well as focus group discussions. Results: Between September 2023 and February 2025, 77 virtual learning sessions were conducted, engaging 2445 unique participants from hospital-based AMS committees and health professionals across the three countries. Participants reported significant knowledge gain, and data showed facility improvements in two core AMS areas, including the implementation of multidisciplinary ward-based interventions/communications and enhanced monitoring of antibiotic resistance patterns. Along those lines, participants reported that the program assisted them in improving prescribing and culture-based treatments, and also evidence-informed antibiotic selection. The evidence of implementing ward-based interventions was further stressed in focus group discussions, as well as other strengthened practices like point-prevalence surveys, and development or revision of stewardship policies. Substantial improvements in microbiology services were also shared by participants, particularly in Malawi. Other practices mentioned were strengthened multidisciplinary communication, infection prevention efforts, and education of patients and the community. Conclusion: Our findings suggest that a virtual case-based learning educational intervention, providing structured and tailored AMS capacity building, can drive behavior change and strengthen healthcare systems in low resource settings. Future efforts should aim to scale up the engagements and sustain improvements to further strengthen AMS capacity. Full article

Schizophrenia (SZ) is a complex neuropsychiatric disorder characterized by heterogeneous symptoms, relatively poor clinical outcome, and widespread disruptions in neural connectivity and oscillatory dynamics. This article attempts to review current evidence linking genomic and proteomic alterations with aberrant neural oscillations observed in SZ, including aberrations in all oscillatory frequency bands obtained via human EEG. The numerous genes discussed are mainly involved in modulating synaptic transmission, synaptic function, interneuron excitability, and excitation/inhibition balance, thereby influencing the generation and synchronization of neural oscillations at specific frequency bands (e.g., gamma frequency band) critical for different cognitive, emotional, and perceptual processes in humans. The review highlights how polygenic influences and gene–circuit interactions underlie the neural oscillatory and connectivity abnormalities central to SZ pathophysiology, providing a framework for future research on common genetic-neural function interactions and on potential therapeutic interventions targeting local and global network-level neural dysfunction in SZ patients. As will be discussed, many of these genes affecting neural oscillations in SZ also affect other neurological disorders, ranging from autism to epilepsy. In time, it is hoped that future research will show why the same genetic anomaly leads to one illness in one person and to another illness in a different person. Full article

For mineral exploration, an increasing number of geophysical instruments have adopted unmanned aerial vehicles (UAVs) as their carrier platforms. The effective fusion of multi-modal geophysical information will be conducive to further enhancing the reliability of exploration results. However, the integration degree of UAVs and geophysical equipment is still low, and the advantages of UAVs as robots have not been fully exploited. In addition, the existing fusion methods are still difficult to use to establish the spatial distribution model of ore-bearing rock. Therefore, we reviewed the development status of UAVs and the geophysical instruments. We believe that only by integrating the system, designing the observation plan in accordance with the requirements of the fusion method, and treating the hardware part as an external extension of the algorithm, can high-matching data be provided for fusion. Subsequently, we analyzed the progress of the fusion methods, leading us to believe that the cross-dimensional and cross-abstract-level issues are major challenges in the algorithm aspect. Meanwhile, the fusion should be carried out simultaneously with the generation of the ore-bearing rock model, that is, to establish an integrated system of fusion and generation. It is hoped that this research can promote the development of UAV-borne multi-modal observation technology. Full article

Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more complex models incorporating biomarkers (e.g., NT-proBNP, sST2), imaging, and artificial intelligence techniques. In acute HF, models like EHMRG and STRATIFY aid early triage, while in chronic HF, tools like SHFM and BCN Bio-HF support long-term management decisions. Despite their utility, most models are limited by poor generalizability, reliance on static inputs, lack of integration into electronic health records, and underuse in clinical practice. Novel approaches involving machine learning, multi-omics profiling, and remote monitoring hold promise for dynamic and individualized risk assessment. However, these innovations face challenges regarding interpretability, validation, and ethical implementation. For prognostic models to transition from theoretical promise to practical impact, they must be continuously updated, externally validated, and seamlessly embedded into clinical workflows. This review emphasizes the potential of prognostic models to transform HF care but cautions against uncritical adoption without robust evidence and practical integration. In the evolving landscape of HF management, prognostic models represent a hopeful avenue, provided their limitations are acknowledged and addressed through interdisciplinary collaboration and patient-centered innovation. Full article

Nanozymes, as a new generation of artificial enzymes, have attracted increasing attention in the field of biomedicine due to their multiple enzymatic characteristics, multi-functionality, low cost, and high stability. Among them, carbon dot nanozymes (CDzymes) possess excellent enzymatic-like catalytic activity and biocompatibility and have been developed for various diagnostic and therapeutic studies of diseases. Here, we briefly review the representative research on CDzymes in recent years, including their synthesis, modification, and applications, especially in orthopedic diseases, including osteoarthritis, osteoporosis, osteomyelitis, intervertebral disc degenerative diseases, bone tumors, and bone injury repair and periodontitis. Additionally, we briefly discuss the potential future applications and opportunities and challenges of CDzymes. We hope this review can provide some reference opinions for CDzymes and offer insights for promoting their application strategies in the treatment of orthopedic disease. Full article

Person-centered navigation (PCN) in healthcare refers to a proactive collaboration among professionals, researchers, patients, and their families to guide individuals toward timely access to screening, treatment, follow-up, and psychosocial support. PCN—which includes professional, peer, and virtual guidance, is particularly crucial for rare cancers, where affected individuals face uncertainty, limited support, financial strain, and difficulties accessing relevant information, testing, and other services. The Canadian Cholangiocarcinoma Collaborative (C3) prioritizes PCN implementation to address these challenges in the context of Biliary Tract Cancers (BTCs). C3 uses a virtual PCN model and staffs a “C3 Research Navigator” who provides clinical and research navigation such as personalized guidance and support, facilitating access to molecular testing, clinical trials, and case reviews through national multidisciplinary rounds. C3 also supports a national network of BTC experts, a patient research registry, and advocacy activities. C3’s implementation strategies include co-design, timely delivery of support, and optimal outcomes across its many initiatives. Future priorities include expanding the C3 network, enhancing user engagement, and further integrating its innovative approach into routine care. Full article

The heterogeneous automatic guided vehicle (AGV) system, composed of several AGVs with different load capability and handling function, has good flexibility and agility to operational requirements. Accurate task travel time prediction (T3P) is vital for the efficient operation of heterogeneous AGV systems. However, T3P remains a challenging problem due to individual task correlations and dynamic changes in model input/output dimensions. To address these challenges, a biomimetics-inspired learning framework based on a radial basis function (RBF) neural network with an improved mayfly algorithm and a selective update strategy (IMA-SURBF) is proposed. Firstly, a T3P model is constructed by using travel-influencing factors as input and task travel time as output of the RBF neural network, where the input/output dimension is determined dynamically. Secondly, the improved mayfly algorithm (IMA), a biomimetic metaheuristic method, is adopted to optimize the initial parameters of the RBF neural network, while a selective update strategy is designed for parameter updates. Finally, simulation experiments on model design, parameter initialization, and comparison with deep learning-based models are conducted in a complex assembly line scenario to validate the accuracy and efficiency of the proposed method. Full article

This paper presents an ethnographically informed analysis of research in Cairo and Sharm El-Sheikh (Egypt) surrounding the 2022 United Nations Framework Convention on Climate Change (UNFCCC) Conference of Parties (COP27) summit. I discuss the geopolitics and geopolitical disruptions of researching activism and activist lives in politically sensitive environments. As shown here, developing new methodological interventions plays a crucial role in understanding contextual methodological limitations, dealing with logistical challenges, and building authentic relationships with research participants. Here, I introduce counter-interviews as a methodological strategy to build trust and invest in researcher–participant relationships. This article draws on participant observation, conversations with environmental and climate activists and non-activists in Cairo prior to and after COP27 and in Sharm El-Sheikh during the second week of the summit, reflective field notes, and 20 semi-structured interviews conducted online between February and August 2023. Here, I use the term “environmental non-activism” to draw attention to the sensitivity, complexity, and fragility of political or apolitical environmental and climate action in an authoritarian context where any form of collective action is highly monitored, regulated, and sometimes criminalized by the state. The main argument of this paper is that examining interlocking power dynamics that shape and reshape the activist space in relation to the state is a requirement for understanding and researching the complexities and specificities of climate activism and non-activism in authoritarian contexts. Along with this argument, this paper invites climate education researchers to reevaluate what non-movements and non-activists in the Global South offer to their analyses of possible alternatives, socio-political change, and politics of hope (and to the broader field of activism in educational research, where commitment to disruption, refusal, and subversion play a key role. Full article