Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and PD-1 Inhibitors for Managing Arterioportal Shunt in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Cohort Study.

Purpose: This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Patients and Methods: Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated. Results: APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P<0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred. Conclusion: Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.

Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence.

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.

Photothermal Carbon Dots Chelated Hydroxyapatite Filler: High Photothermal Conversion Efficiency and Enhancing Adhesion of Hydrogel.

The synthesis of photothermal carbon/hydroxyapatite composites poses challenges due to the binding modes and relatively low photothermal conversion efficiency. To address these challenges, the calcium ions chelated by photothermal carbon dots (PTC-CDs) served as the calcium source for the synthesis of photothermal carbon dots chelated hydroxyapatite (PTC-HA) filler via the coprecipitation method. The coordination constant K and chelation sites of PTC-HA were 7.20 × 102 and 1.61, respectively. Compared to PTC-CDs, the coordination constant K and chelation sites of PTC-HA decreased by 88 and 35% due to chelating to hydroxyapatite, respectively. PTC-HA possesses fluorescence and photothermal performance with a 62.4% photothermal conversion efficiency. The incorporation of PTC-HA filler significantly enhances as high as 76% the adhesion performance of the adhesive hydrogel. PTC-HA with high photothermal conversion efficiency and enhancing adhesion performance holds promise for applications in high photothermal conversion efficiency, offering tissue adhesive properties and fluorescence capabilities to the hydrogel.

EGTA-Derived Carbon Dots with Bone-Targeting Ability: Target-Oriented Synthesis and Calcium Affinity.

The bone-targeting mechanism of clinic bisphosphonate-type drugs, such as alendronate, risedronate, and ibandronate, relies on chelated calcium ions on the surface of the bone mineralized matrix for the treatment of osteoporosis. EGTA with aminocarboxyl chelating ligands can specifically chelate calcium ions. Inspired by the bone-targeting mechanism of bisphosphonates, we hypothesize that EGTA-derived carbon dots (EGTA-CDs) hold bone-targeting ability. For the target-oriented synthesis of EGTA-CDs and to endow CDs with bone targeting, we designed calcium ion chelating agents as precursors, including aminocarboxyl chelating agents (EGTA and EDTA) and bisphosphonate agents (ALN and HEDP) for the target-oriented synthesis of aminocarboxyl-derived CDs (EGTA-CDs and EDTA-CDs) and bisphosphonate-derived CDs (ALN-CDs and HEDP-CDs) with high synthetic yield. The synthetic yield of EGTA-CDs reached 87.6%. Aminocarboxyl-derived CDs and bisphosphonate-derived CDs retain the chelation ability of calcium ions and can specifically bind calcium ions. The chemical environment bone-targeting value coordination constant K and chelation sites of EGTA-CDs were 6.48 × 104 M-1 and 4.12, respectively. A novel method was established to demonstrate the bone-targeting capability of chelate-functionalized carbon dots using fluorescence quenching in a simulated bone trauma microenvironment. EGTA-CDs exhibit superior bone-targeting ability compared with other aminocarboxyl-derived CDs and bisphosphonate-derived CDs. EGTA-CDs display exceptional specificity toward calcium ions and better bone affinity than ALN-CDs, suggesting their potential as novel bone-targeting drugs. EGTA-CDs with strong calcium ion chelating ability have calcium ion affinity in simulated body fluid and bone-targeting ability in a simulated bone trauma microenvironment. These findings offer new avenues for the development of advanced bone-targeting strategies.

Dynamic cognitive processes of humor generation: activation and inhibition of information.

Humor is a lubricant of interpersonal relationships and is regarded as an important quality of individual creativity. Previous studies have mainly focused on passive humor appreciation and comprehension but ignored active humor generation, especially the cognitive process of humor generation. Based on the hypothesis that humor generation is similar to creative cognition, this study used humorous two-part allegorical sayings to explore whether humor generation involves the cognitive processes of the activation and inhibition of information. The experiment manipulated the duration (5/10 s) of the presentation of the first part of humorous two-part allegorical sayings, which are called "yinyu," and the type of subthreshold probe words (humorous probe words/usual probe words). The results showed that the interaction between the duration of the presentation of yinyu and the type of subthreshold probe words was significant; the correct number of humorous probe words reported was significantly lower than that of usual probe words when the yinyu was presented for 5 s, which reflected the widespread activation of information. The correct number of humorous probe words reported was significantly higher than that of usual probe words when the yinyu was presented for 10 s, which suggested the inhibition of non-humorous information. This study revealed the dynamic cognitive processes of humor generation and verified possible cognitive similarities between humor generation and creative cognition.

Predictive Value of the Peripheral Blood Parameters for Preeclampsia.

BACKGROUND: Excessive systemic inflammation plays a vital role in pathophysiology of preeclampsia (PE). The aim is to clarify the predictive value of the peripheral blood parameters including white blood cell (WBC), neutrophils, lymphocyte, monocyte, platelet count, mean platelet volume (MPV), plateletcrit, platelet distribution width (PDW), platelet-large cell ratio (PLCR), and the ratio value for PE. METHODS: This retrospective study enrolled 170 PE patients, 123 healthy control pregnant women, and 122 non-pregnant women. When pregnant women were admitted to the hospital for delivery, peripheral complete blood cell count was detected by an automatic blood cell analyzer. Clinical signs and demographic characteristics were recorded. The receiver operating characteristic (ROC) curve was used to determine the cutoff value and analyze the predictive significances for PE. Furthermore, the risk factors of PE were tested by univariate and stratified analyses. RESULTS: This study showed that WBC, neutrophil count, neutrophil percentage, NLR, NMR, and PLR# were significantly increased in PE patients as compared with pregnant control patients (p < 0.001), whereas lymphocyte percentage, monocyte percentage, and PNR were decreased. In addition, there was no significant difference in the rest of the peripheral blood parameters between women with and without PE. The ROC curve result revealed that WBC and neutrophil count had a higher AUC value than the rest of peripheral blood variables. WBC and neutrophil count are positively correlated MAP. Moreover, the WBC and neutrophil count were indicated as independent risk factors for the development of PE. CONCLUSIONS: This study clarifies that peripheral blood parameters of WBC and neutrophil count have good applied value with high sensitivity and specificity in predicting the development of PE and are also independent risk factors for the development of PE.

An Adaptive Black-Box Defense Against Trojan Attacks (TrojDef).

Trojan backdoor is a poisoning attack against neural network (NN) classifiers in which adversaries try to exploit the (highly desirable) model reuse property to implant Trojans into model parameters for backdoor breaches through a poisoned training process. To misclassify an input to a target class, the attacker activates the backdoor by augmenting the input with a predefined trigger that is only known to her/him. Most of the proposed defenses against Trojan attacks assume a white-box setup, in which the defender either has access to the inner state of NN or is able to run backpropagation through it. In this work, we propose a more practical black-box defense, dubbed TrojDef. In a black-box setup, the defender can only run forward-pass of the NN. TrojDef is motivated by the Trojan poisoned training, in which the model is trained on both benign and Trojan inputs. TrojDef tries to identify and filter out Trojan inputs (i.e., inputs augmented with the Trojan trigger) by monitoring the changes in the prediction confidence when the input is repeatedly perturbed by random noise. We derive a function based on the prediction outputs which is called the prediction confidence bound to decide whether the input example is Trojan or not. The intuition is that Trojan inputs are more stable as the misclassification only depends on the trigger, while benign inputs will suffer when augmented with noise due to the perturbation of the classification features. Through mathematical analysis, we show that if the attacker is perfect in injecting the backdoor, the Trojan infected model will be trained to learn the appropriate prediction confidence bound, which is used to distinguish Trojan and benign inputs under arbitrary perturbations. However, because the attacker might not be perfect in injecting the backdoor, we introduce a nonlinear transform to the prediction confidence bound to improve the detection accuracy in practical settings. Extensive empirical evaluations show that TrojDef significantly outperforms the-state-of-the-art defenses and is highly stable under different settings, even when the classifier architecture, the training process, or the hyperparameters change.

The Role of Creative Publicity in Different Periods of the COVID-19 Outbreak in China: Taking the Creative Publicity of Chinese Poetry as an Example.

When humans are confronted with an epidemic situation or a continuous natural disaster, success depends largely on how critical information is conveyed to as many people as possible, how individuals' emotional experiences of the crisis are elicited, and how their behaviors are directed going forward. Efficient publicity is key to successful epidemic prevention and control. This study explores the role of creative publicity by comparing the influence of creative publicity and general publicity in different periods of the COVID-19 outbreak in China. The effects of creative and general publicity differed across varying periods of the COVID-19 outbreak. Specifically, compared to general publicity, creative publicity had a significant impact on individuals' emotional arousal in the early period of the COVID-19 outbreak while it significantly promoted individuals' emotional arousal, behavioral regulation, and willingness to actively disseminate information in the middle period. In the stable period of the COVID-19 outbreak, creative publicity performed better than general publicity in regulating individuals' behavior. On the other hand, general publicity was more effective than creative publicity in regulating individuals' behavior and actively disseminating information about the epidemic in the early period of the COVID-19 outbreak. In conclusion, creative and general publicity had differing effects in different periods of the COVID-19 outbreak, which may relate to the characteristics of the publicity format and people's psychological conditions in different periods of the COVID-19 outbreak.

CheXclusion: Fairness gaps in deep chest X-ray classifiers.

Machine learning systems have received much attention recently for their ability to achieve expert-level performance on clinical tasks, particularly in medical imaging. Here, we examine the extent to which state-of-the-art deep learning classifiers trained to yield diagnostic labels from X-ray images are biased with respect to protected attributes. We train convolution neural networks to predict 14 diagnostic labels in 3 prominent public chest X-ray datasets: MIMIC-CXR, Chest-Xray8, CheXpert, as well as a multi-site aggregation of all those datasets. We evaluate the TPR disparity - the difference in true positive rates (TPR) - among different protected attributes such as patient sex, age, race, and insurance type as a proxy for socioeconomic status. We demonstrate that TPR disparities exist in the state-of-the-art classifiers in all datasets, for all clinical tasks, and all subgroups. A multi-source dataset corresponds to the smallest disparities, suggesting one way to reduce bias. We find that TPR disparities are not significantly correlated with a subgroup's proportional disease burden. As clinical models move from papers to products, we encourage clinical decision makers to carefully audit for algorithmic disparities prior to deployment. Our supplementary materials can be found at, http://www.marzyehghassemi.com/chexclusion-supp-3/.

Power-Efficient Wireless Coverage Using Minimum Number of UAVs.

Unmanned aerial vehicles (UAVs) can be deployed as backup aerial base stations due to cellular outage either during or post natural disaster. In this paper, an approach involving multi-UAV three-dimensional (3D) deployment with power-efficient planning was proposed with the objective of minimizing the number of UAVs used to provide wireless coverage to all outdoor and indoor users that minimizes the required UAV transmit power and satisfies users' required data rate. More specifically, the proposed algorithm iteratively invoked a clustering algorithm and an efficient UAV 3D placement algorithm, which aimed for maximum wireless coverage using the minimum number of UAVs while minimizing the required UAV transmit power. Two scenarios where users are uniformly and non-uniformly distributed were considered. The proposed algorithm that employed a Particle Swarm Optimization (PSO)-based clustering algorithm resulted in a lower number of UAVs needed to serve all users compared with that when a K-means clustering algorithm was employed. Furthermore, the proposed algorithm that iteratively invoked a PSO-based clustering algorithm and PSO-based efficient UAV 3D placement algorithms reduced the execution time by a factor of ≈1/17 and ≈1/79, respectively, compared to that when the Genetic Algorithm (GA)-based and Artificial Bees Colony (ABC)-based efficient UAV 3D placement algorithms were employed. For the uniform distribution scenario, it was observed that the proposed algorithm required six UAVs to ensure 100% user coverage, whilst the benchmarker algorithm that utilized Circle Packing Theory (CPT) required five UAVs but at the expense of 67% of coverage density.

Chitosan derived nitrogen-doped carbon dots suppress osteoclastic osteolysis via downregulating ROS.

Osteoclasts are the main cells involved in normal bone remodeling and pathological bone destruction in vivo. Overactivation of osteoclasts can lead to osteolytic diseases, including breast cancer, bone tumors, arthritis, the aseptic loosening of orthopedic implants, and Paget's disease. Excessive reactive oxygen species are the main cause of osteoclast overactivation. We have synthesized chitosan derived nitrogen-doped carbon dots (N-CDs) with a high synthetic yield and the ability to scavenge reactive oxygen species (ROS). N-CDs effectively abrogated RANKL-induced elevation in ROS generation and therefore impaired the activation of NF-κB and MAPK pathways. Osteoclastogenesis and bone resorption was effectively attenuated in vitro. Furthermore, the in vivo administration of N-CDs in mice protected them against lipopolysaccharide (LPS)-induced calvarial bone destruction and breast cancer cell-induced tibial bone loss. Based on the good biocompatibility of N-CDs and the ability to efficiently remove ROS, a nanomaterial treatment scheme was provided for the first time for the clinical treatment of osteolytic diseases.

Analysis of bisphosphonate using ultraviolet-visible spectroscopy based on modified phosphorus determination reagent.

An improved phosphorous determination was developed using ethanol, phosphorus determination reagent (PDR) and Ultraviolet-visible spectroscopy (UV-Vis) for analyzing the bisphosphonates (BPs). The method was carried out under mild conditions without digestion, high temperature, high pressure, and other extreme conditions. Alcohols played an important role in this method. Without alcohol, this reaction system did not have a color reaction. Alendronate (ALN) and risedronate (RIS) were used to demonstrate the reliability of the improved phosphorous determination under different reaction conditions. The absorbance had an equal ratio of increase as well as a good trend line when the content of BPs increased. The improved phosphorous determination could be a new method to measure the drug content of BPs.

Low-Frequency Current Fluctuations and Sliding of the Charge Density Waves in Two-Dimensional Materials.

We investigated low-frequency noise in two-dimensional (2D) charge density wave (CDW) systems, 1 T-TaS2 thin films, as they were driven from the nearly commensurate (NC) to incommensurate (IC) CDW phases by voltage and temperature stimuli. This study revealed that noise in 1 T-TaS2 has two pronounced maxima at the bias voltages, which correspond to the onset of CDW sliding and the NC-to-IC phase transition. We observed unusual Lorentzian features and exceptionally strong noise dependence on electric bias and temperature, leading to the conclusion that electronic noise in 2D CDW systems has a unique physical origin different from known fundamental noise types. We argue that noise spectroscopy can serve as a useful tool for understanding electronic transport phenomena in 2D CDW materials characterized by coexistence of different phases and strong pinning.

Bone-targeted methotrexate-alendronate conjugate inhibits osteoclastogenesis in vitro and prevents bone loss and inflammation of collagen-induced arthritis in vivo.

Rheumatoid arthritis (RA), a disease that causes joint destruction and bone erosion, is related to osteoclast activity. RA is generally treated with methotrexate (MTX). In this study, a MTX-Alendronate (ALN) conjugate was synthesized and characterized. The conjugate dramatically inhibited osteoclast formation and bone resorption compared with MTX and ALN used alone or in combination. Due to the characteristics of ALN, the MTX-ALN conjugate can adhere to the exposed bone surface and enhance drug accumulation in the pathological region for targeted therapy against osteoclastogenesis. Additionally, MTX was rapidly released in the presence of lysozyme under mildly acidic conditions, similar to inflammatory tissue and osteoclast-surviving conditions, which contributes to inflammatory inhibition; this was confirmed by the presence of pro-inflammatory cytokines. Our study highlights the use of the MTX-ALN conjugate as a potential therapeutic approach for RA by targeting osteoclastogenesis.

Removal of Carmine from Aqueous Solution by Carbonated Hydroxyapatite Nanorods.

In this study, carbonated hydroxyapatite (CHA) nanorods were prepared by a novel hydrothermal method. The crystallinity and chemical structure of synthesized CHA nanorods was characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS), respectively. Carmine was selected as representative organic dyes to study the adsorption capacities of CHA nanorods. Mechanistic studies of carmine adsorption by CHA nanorods show that the adsorption processes both follow the pseudo-second-order kinetic model and fit the Langmuir isotherm model well. The CHA nanorods exhibited a high adsorption capacity of 85.51 mg/g for carmine at room-temperature. The experimental results prove that CHA nanorods can be promising absorbents for removing organic dye pollutants in wastewater from paper and textile plants.

Low-Frequency Electronic Noise in Quasi-1D TaSe3 van der Waals Nanowires.

We report results of investigation of the low-frequency electronic excess noise in quasi-1D nanowires of TaSe3 capped with quasi-2D h-BN layers. Semimetallic TaSe3 is a quasi-1D van der Waals material with exceptionally high breakdown current density. It was found that TaSe3 nanowires have lower levels of the normalized noise spectral density, SI/I2, compared to carbon nanotubes and graphene (I is the current). The temperature-dependent measurements revealed that the low-frequency electronic 1/f noise becomes the 1/f2 type as temperature increases to ∼400 K, suggesting the onset of electromigration (f is the frequency). Using the Dutta-Horn random fluctuation model of the electronic noise in metals, we determined that the noise activation energy for quasi-1D TaSe3 nanowires is approximately EP ≈ 1.0 eV. In the framework of the empirical noise model for metallic interconnects, the extracted activation energy, related to electromigration is EA = 0.88 eV, consistent with that for Cu and Al interconnects. Our results shed light on the physical mechanism of low-frequency 1/f noise in quasi-1D van der Waals semimetals and suggest that such material systems have potential for ultimately downscaled local interconnect applications.

Breakdown current density in h-BN-capped quasi-1D TaSe3 metallic nanowires: prospects of interconnect applications.

We report on the current-carrying capacity of the nanowires made from the quasi-1D van der Waals metal tantalum triselenide capped with quasi-2D boron nitride. The chemical vapor transport method followed by chemical and mechanical exfoliation were used to fabricate the mm-long TaSe3 wires with the lateral dimensions in the 20 to 70 nm range. Electrical measurements establish that the TaSe3/h-BN nanowire heterostructures have a breakdown current density exceeding 10 MA cm(-2)-an order-of-magnitude higher than that for copper. Some devices exhibited an intriguing step-like breakdown, which can be explained by the atomic thread bundle structure of the nanowires. The quasi-1D single crystal nature of TaSe3 results in a low surface roughness and in the absence of the grain boundaries. These features can potentially enable the downscaling of the nanowires to lateral dimensions in a few-nm range. Our results suggest that quasi-1D van der Waals metals have potential for applications in the ultimately downscaled local interconnects.

A charge-density-wave oscillator based on an integrated tantalum disulfide-boron nitride-graphene device operating at room temperature.

The charge-density-wave (CDW) phase is a macroscopic quantum state consisting of a periodic modulation of the electronic charge density accompanied by a periodic distortion of the atomic lattice in quasi-1D or layered 2D metallic crystals. Several layered transition metal dichalcogenides, including 1T-TaSe2, 1T-TaS2 and 1T-TiSe2 exhibit unusually high transition temperatures to different CDW symmetry-reducing phases. These transitions can be affected by the environmental conditions, film thickness and applied electric bias. However, device applications of these intriguing systems at room temperature or their integration with other 2D materials have not been explored. Here, we demonstrate room-temperature current switching driven by a voltage-controlled phase transition between CDW states in films of 1T-TaS2 less than 10 nm thick. We exploit the transition between the nearly commensurate and the incommensurate CDW phases, which has a transition temperature of 350 K and gives an abrupt change in current accompanied by hysteresis. An integrated graphene transistor provides a voltage-tunable, matched, low-resistance load enabling precise voltage control of the circuit. The 1T-TaS2 film is capped with hexagonal boron nitride to provide protection from oxidation. The integration of these three disparate 2D materials in a way that exploits the unique properties of each yields a simple, miniaturized, voltage-controlled oscillator suitable for a variety of practical applications.

Synthesis of Biocompatible Hydroxyapatite Using Chitosan Oligosaccharide as a Template.

In this study, a novel biocompatible hydroxyapatite (HA) was synthesized by using chitosan oligosaccharide (COS) as a template. These HA samples were studied by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). The biocompatibility of HA samples was evaluated via cell viability, cell morphology and alkaline phosphatase staining of MG-63 cell lines. The results show that HA synthesized in the presence of COS was favorable to proliferation and osteogenic differentiation of MG-63 cells. These hydroxyapatites are potentially attractive biomaterials for bone tissue engineering applications.