Shape analysis has been widely used in digital image processing and computer vision, but they have not been utilized to compare the structural characteristics of the human association pathways. Here ...we used shape analysis to derive length, area, volume, and shape metrics from diffusion MRI tractography and utilized them to study the morphology of human association pathways. The reliability analysis showed that shape descriptors achieved moderate to good test-retest reliability. Further analysis on association pathways showed left dominance in the arcuate fasciculus, cingulum, uncinate fasciculus, frontal aslant tract, and right dominance in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The superior longitudinal fasciculus has a mixed lateralization profile with different metrics showing either left or right dominance. The analysis of between-subject variations shows that the overall layout of the association pathways does not variate a lot across subjects, as shown by low between-subject variation in length, span, diameter, and radius. In contrast, the area of the pathway innervation region has a considerable between-subject variation. A follow-up analysis is warranted to thoroughly investigate the nature of population variations and their structure-function correlation.
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Although immune cell therapy has long been used for treating solid cancer, its efficacy remains limited. Interferon (IFN)-producing killer dendritic cells (IKDCs) exhibit cytotoxicity and present ...antigens to relevant cells; thus, they can selectively induce tumor-associated antigen (TAA)-specific CD8 T cells and may be useful in cancer treatment. Various protocols have been used to amplify human IKDCs from peripheral sources, but the complexity of the process has prevented their widespread clinical application. Additionally, the induction of TAA-specific CD8 T cells through the adoptive transfer of IKDCs to immunocompromised patients with cancer may be insufficient. Therefore, we developed a method for generating an immune cell-based regimen, Phyduxon-T, comprising a human IKDC counterpart (Phyduxon) and expanded TAA-specific CD8 T cells.
Peripheral blood mononuclear cells from ovarian cancer patients were cultured with human interleukin (hIL)-15, hIL-12, and hIL-18 to generate Phyduxon-T. Then, its phenotype, cytotoxicity, and antigen-presenting function were evaluated through flow cytometry using specific monoclonal antibodies.
Phyduxon exhibited the characteristics of both natural killer and dendritic cells. This regimen also exhibited cytotoxicity against primary ovarian cancer cells and presented TAAs, thereby inducing TAA-specific CD8 T cells, as evidenced by the expression of 4-1BB and IFN-γ. Notably, the Phyduxon-T manufacturing protocol effectively expanded IFN-γ-producing 4-1BB
TAA-specific CD8 T cells from peripheral sources; these cells exhibited cytotoxic activities against ovarian cancer cells.
Phyduxon-T, which is a combination of natural killer cells, dendritic cells, and TAA-specific CD8 T cells, may enhance the efficacy of cancer immunotherapy.
Abstract
Connectome maps region-to-region connectivities but does not inform which white matter pathways form the connections. Here we constructed a population-based tract-to-region connectome to ...fill this information gap. The constructed connectome quantifies the population probability of a white matter tract innervating a cortical region. The results show that ~85% of the tract-to-region connectome entries are consistent across individuals, whereas the remaining (~15%) have substantial individual differences requiring individualized mapping. Further hierarchical clustering on cortical regions revealed dorsal, ventral, and limbic networks based on the tract-to-region connective patterns. The clustering results on white matter bundles revealed the categorization of fiber bundle systems in the association pathways. This tract-to-region connectome provides insights into the connective topology between cortical regions and white matter bundles. The derived hierarchical relation further offers a categorization of gray and white matter structures.
A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged ...atlas of the structural connectome derived from diffusion MRI data (N = 842). This was achieved by creating a high-resolution template of diffusion patterns averaged across individual subjects and using tractography to generate 550,000 trajectories of representative white matter fascicles annotated by 80 anatomical labels. The trajectories were subsequently clustered and labeled by a team of experienced neuroanatomists in order to conform to prior neuroanatomical knowledge. A multi-level network topology was then described using whole-brain connectograms, with subdivisions of the association pathways showing small-worldness in intra-hemisphere connections, projection pathways showing hub structures at thalamus, putamen, and brainstem, and commissural pathways showing bridges connecting cerebral hemispheres to provide global efficiency. This atlas of the structural connectome provides representative organization of human brain white matter, complementary to traditional histologically-derived and voxel-based white matter atlases, allowing for better modeling and simulation of brain connectivity for future connectome studies.
Abstract Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic ...malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
Background
Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression‐free survival (PFS) ...and overall survival (OS) merit further investigation.
Purpose
To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer.
Study Type
Prospective cohort study.
Population
In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis.
Field Strength/Sequence
3.0T integrated PET/MRI including diffusion‐weighted echo‐planar imaging (b = 50 and 1000 s/mm2) and 18Ffluorodeoxyglucose PET.
Assessment
Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors.
Statistical Tests
A Mann–Whitney U‐test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival.
Results
In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin, and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio HR = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008).
Data Conclusion
PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively.
Level of Evidence
1
Technical Efficacy
3
Emulation of photonic synapses through photo‐recordable devices has aroused tremendous discussion owing to the low energy consumption, high parallel, and fault‐tolerance in artificial neuromorphic ...networks. Nonvolatile flash‐type photomemory with short photo‐programming time, long‐term storage, and linear plasticity becomes the most promising candidate. Nevertheless, the systematic studies of mechanism behind the charge transfer process in photomemory are limited. Herein, the physical properties of APbBr3 perovskite quantum dots (PQDs) on the photoresponsive characteristics of derived poly(3‐hexylthiophene‐2,5‐diyl) (P3HT)/PQDs‐based photomemory through facile A‐site substitution approach are explored. Benefitting from the lowest valance band maximum and longest exciton lifetime of FAPbBr3 quantum dot (FA‐QDs), P3HT/FA‐QDs‐derived photomemory not only exhibits shortest photoresponsive characteristic time compared to FA0.5Cs0.5PbBr3 quantum dots (Mix‐QDs) and CsPbBr3 quantum dots (Cs‐QDs) but also displays excellent ON/OFF current ratio of 2.2 upon an extremely short illumination duration of 1 ms. Moreover, the device not only achieves linear plasticity of synapses by optical potentiation and electric depression, but also successfully emulates the features of photon synaptic such as pair‐pulse facilitation, long‐term plasticity, and multiple spike‐dependent plasticity and exhibits extremely low energy consumption of 3 × 10−17 J per synaptic event.
Engineering of minimum photo‐recording time in poly(3‐hexylthiophene)/APbBr3 perovskite quantum dots‐based photomemory via facile an A‐site substitution approach is demonstrated. poly(3‐hexylthiophene‐2,5‐diyl)/FAPbBr3 quantum dot‐derived photomemory displays an extremely short programming time of 1 ms and enables the extremely low energy consumption of 3 × 10−17 J per synaptic event on the application of photonic synapse.
Organic light‐emitting transistors (OLETs), as novel and attractive kinds of organic electronic devices, have gained extensive attention from both academia and industry. The unique device ...architectures can simultaneously combine the electrical switching functionality of organic field‐effect transistors and the light generation capability of organic light‐emitting diodes in a single device, thereby holding great promise for reducing the complicated processes of next‐generation pixel circuitry. This review involves the design, fabrication, and applications of OLETs with a comprehensive coverage of this field with the aim to give a deep insight into the intrinsic mechanisms of devices. Challenges and future prospects of OLETs are also discussed.
Organic light‐emitting transistors (OLETs) represent a novel class of organic optoelectronic devices that combine the current modulating function of a transistor with light emission. Unipolar OLETs, ambipolar OLETs, and new device structures, most of which intend to elaborate their working principles and the construction of high‐quality optoelectronic devices, are spotlighted in terms of the representative paradigms.
The meta-analysis by Wang et al. (Stem Cell Res Ther 14(1):103, 2023) aims to explore whether mesenchymal stem cells are effective for perianal fistulas. The authors indicated that the difference in ...cell types, cell sources and cell dosages did not influence mesenchymal stem cells' efficacy, which may not be accurate. I think that local treatment with higher dosages of mesenchymal stem cells seems to not result in a higher healing rate. And, future trials should focus on donor characteristics considering past medical history of further autoimmunity, timely and cost-effective treatment to lighten the optimized therapeutic goals. In the future, it will be interesting to assess the safety and feasibility of injection of fibrin glue combined with mesenchymal stem cells in perianal fistulas.
This study presents a novel type of shape memory alloy (SMA) cable‐restrained high damping rubber (SMA‐HDR) bearing, which is particularly suited to near‐fault (NF) regions where the pulsing effect ...potentially exists in the ground motions. The working mechanism of the bearing is first described, followed by an experimental investigation on a full‐scale SMA‐HDR bearing specimen. The test results confirm the efficient restraining effect offered by the SMA cables, which contribute to 65% and 24.4% of the lateral load resistance and total energy dissipation, respectively, prior to the initial fracture of the SMA cables. The failure of the cables is initiated near the end grip where moderate stress concentration exists at this region. Following the experimental study, the numerical modeling strategy for the bearing is discussed, and a case study is then presented, demonstrating the application of the SMA‐HDR bearings in the Datianba #2 highway bridge, a real project that first adopts the proposed bearings in the world. A simplified design process is introduced for the bridge with novel SMA‐HDR bearings to mitigate the potential damage during strong earthquakes especially the NF ones. The system‐level analysis on the prototype bridge shows that the novel SMA‐HDR bearings equipped with ten 7×7×1.2 SMA cables in each bearing could reduce the average maximum bearing displacement (MBD) by nearly 30% compared with the conventional bridge with HDR bearings. The application of the novel SMA‐HDR bearing can significantly alleviate the pounding effect, especially under the NF earthquakes. The presence of the SMA cables tends to increase the maximum force response of the piers, but this effect is minor and under control.
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