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Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line. Newer targets and newer agents for established targets are being investigated, and this may change the BTC management landscape in the coming years from traditional CT to individualized therapy (TT) or ICI-centered combinations. The latter group may occupy major space in BTC management due to the paucity of targetable mutations and a greater toxicity profile.

Atherosclerosis, the leading cause of death, is a vascular disease of chronic inflammation. We recently showed that angiopoietin-like 4 (ANGPTL4) promotes cardiac repair by suppressing pathological inflammation. Given the fundamental contribution of inflammation to atherosclerosis, we assessed the role of ANGPTL4 in the development of atherosclerosis and determined whether ANGPTL4 regulates atherosclerotic plaque stability. We injected ANGPTL4 protein twice a week into atherosclerotic Apoe−/− mice and analyzed the atherosclerotic lesion size, inflammation, and plaque stability. In atherosclerotic mice, ANGPTL4 reduced atherosclerotic plaque size and vascular inflammation. In the atherosclerotic lesions and fibrous caps, the number of α-SMA(+), SM22α(+), and SM-MHC(+) cells was higher, while the number of CD68(+) and Mac2(+) cells was lower in the ANGPTL4 group. Most importantly, the fibrous cap was significantly thicker in the ANGPTL4 group than in the control group. Smooth muscle cells (SMCs) isolated from atherosclerotic aortas showed significantly increased expression of CD68 and Krüppel-like factor 4 (KLF4), a modulator of the vascular SMC phenotype, along with downregulation of α-SMA, and these changes were attenuated by ANGPTL4 treatment. Furthermore, ANGPTL4 reduced TNFα-induced NADPH oxidase 1 (NOX1), a major source of reactive oxygen species, resulting in the attenuation of KLF4-mediated SMC phenotypic changes. We showed that acute myocardial infarction (AMI) patients with higher levels of ANGPTL4 had fewer vascular events than AMI patients with lower levels of ANGPTL4 ( p  < 0.05). Our results reveal that ANGPTL4 treatment inhibits atherogenesis and suggest that targeting vascular stability and inflammation may serve as a novel therapeutic strategy to prevent and treat atherosclerosis. Even more importantly, ANGPTL4 treatment inhibited the phenotypic changes of SMCs into macrophage-like cells by downregulating NOX1 activation of KLF4, leading to the formation of more stable plaques. Cardiovascular disease: Stopping and stabilizing atherosclerotic plaques Treatment with a protein that stabilizes existing plaques within blood vessels could help reduce the risk of future cardiovascular events in patients with atherosclerosis. These plaques arise in part from a change in the behavior of the muscle cells within the walls of the blood vessels, which leads to the accumulation of lipids and other biomolecules and creates conditions that can ultimately result in a heart attack or stroke. Researchers led by Youngkeun Ahn and Yong Sook Kim at Chonnam National University Hospital, Gwangju, South Korea, have shown that they can counter this process in a mouse model of atherosclerosis by treatment with a protein called ANGPTL4. This molecule keeps vascular muscle cells in a state that prevents further plaque formation, while stabilizing existing plaques and countering the inflammatory processes that can further accelerate the cardiovascular disease.

This study presents the design and implementation of a compact data acquisition system for immersive ultrasonic inspection of small-diameter pipelines, targeting applications where conventional systems are impractical due to size constraints. The system integrates the Eclipse Z7 platform with a customized pulser-receiver module and a rotary pipeline inspection gauge (PIG) equipped with a 5 MHz immersion-type ultrasonic transducer. The PIG module is designed to scan pipelines with an 8.18 mm wall thickness and a 200 mm inner diameter. Before deployment, real-time system calibration is performed via a connected computer interface to ensure optimal performance. Once inside the pipeline, the PIG operates autonomously, with ultrasonic data being acquired and stored locally on a Raspberry Pi. Post-inspection, the recorded data is extracted and analyzed on the computer to assess pipeline integrity. The proposed system offers a compact alternative to commercial solutions, particularly in scenarios involving limited access and small-diameter pipelines.

Evidence suggests that diets with high pro-inflammatory potential may play a substantial role in the origin of gastric inflammation. This study aimed to examine the association between the energy-adjusted dietary inflammatory index (E-DIITM) and gastric diseases at baseline and after a mean follow-up of 7.4 years in a Korean population. A total of 144,196 participants from the Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort were included. E-DII scores were computed using a validated semi-quantitative food frequency questionnaire. Multivariate logistic regression and Cox proportional hazards regression were used to assess the association between the E-DII and gastric disease risk. In the prospective analysis, the risk of developing gastric disease was significantly increased among individuals in the highest quartile of E-DII compared to those in the lowest quartile (HRquartile4vs1 = 1.22; 95% CI = 1.08–1.38). Prospective analysis also showed an increased risk in the incidence of gastritis (HRquartile4vs1 = 1.19; 95% CI = 1.04–1.37), gastric ulcers (HRquartile4vs1 = 1.47; 95% CI = 1.16–1.85), and gastric and duodenal ulcers (HRquartile4vs1 = 1.46; 95% CI = 1.17–1.81) in the highest E-DII quartile compared to the lowest quartile. In the cross-sectional analysis, the E-DII score was not associated with the risk of gastric disease. Our results suggest that a pro-inflammatory diet, indicated by high E-DII scores, is prospectively associated with an increased risk of gastric diseases. These results highlight the significance of an anti-inflammatory diet in lowering the risk of gastric disease risk in the general population.

PurposeThe purpose of this paper is to thoroughly investigate the interplay between institutions, foreign direct investment (FDI) and entrepreneurship in the context of emerging markets (EMs).Design/methodology/approachThe authors argue that the impact of FDI on entrepreneurial activity depends on different natures of capital flow and entrepreneurial motivation and relates to the quality of institutional environment. First, the roles of inward and outward FDI are examined in connection with the new firm creation by opportunity- and necessity-motivated entrepreneurs. Second, the integrated influences of (inward/outward) FDI and governance quality (GQ) on (opportunity/necessity) entrepreneurship are tested. This nexus of relationships is analyzed through segmented regressions using the GEM data of 39 EMs over the 2004–2015 period.FindingsIt is evidenced that the quality of governance infrastructure affects the relationship between FDI and entrepreneurship: in emerging countries with low GQ, opportunity entrepreneurship is stimulated by inward FDI and diminished by outward FDI; and in emerging countries with high GQ, necessity entrepreneurship is discouraged by inward FDI and promoted by outward FDI.Practical implicationsThis research has implications for the institutional context-based execution of public policy in emerging economies. As the entrepreneurial effects of inward and outward FDI are pronounced differently under the two types of entrepreneurship and the two extremes of GQ, public policy makers who recognize the catalytic role of FDI in domestic business development should take the distinct institutional context of their country into consideration.Originality/valueThe paper contributes to the extant literature on international entrepreneurship in emerging economies by making a breakdown on the roles played by different types of FDI in the entrepreneurial activity, analyzing the mediating effects of GQ on the relationship between inward/outward FDI and entrepreneurship, and interpreting the capital and institutional determinants of entrepreneurship in terms of entrepreneurial motivations by opportunity and necessity.

Water management is an important criterion in the operation of proton-exchange membrane fuel cells to maintain the high performance and reliability of the system. The water content in the cathode air that is supplied to the cathode channel contributes to the membrane humidification and the transport of protons inside the membrane structure. In automotive applications, the supply air is typically driven through an external membrane humidifier to absorb more moisture from the recirculated cathode exhaust. In the literature, humidifiers and fuel cell stacks have been separately investigated without considering whole-system configurations for water management. This study investigates changes in the cathode air characteristics through a membrane humidifier and compares two configurations using a humidifier bypass of the supply flow and exhaust flow to adjust the cathode inlet air relative humidity. Each component in the system was modeled using mathematical relations and converted into blocks of inputs and outputs in MATLAB/Simulink for simulation. The bypass valve was demonstrated to effectively reduce the relative humidity of the supply air from the saturation rate to above 60%, with a bypass fraction of up to 0.6 in both configurations. These adjustments provide system flexibility to accommodate load changes and prevent flooding in the stack channels. Bypassing the supply air through the humidifier effectively maintained consistent cathode inlet humidity across a wide operational range. A 0.4 bypass fraction on the supply side sustained a relative humidity of around 80% for the whole range of operating flow rates. In contrast, the exhaust-side bypass had a smaller impact, and the relative humidity of the cathode air was reduced when the flow rate and bypass fraction increased. This study further supports the control system design to regulate the bypass fraction according to load transients.

Acoustic-resolution photoacoustic microscopy (AR-PAM) enables visualization of biological tissues at depths of several millimeters with superior optical absorption contrast. However, the lateral resolution and sensitivity of AR-PAM are generally lower than those of optical-resolution PAM (OR-PAM) owing to the intrinsic physical acoustic focusing mechanism. Here, we demonstrate a computational strategy with two generative adversarial networks (GANs) to perform semi/unsupervised reconstruction with high resolution and sensitivity in AR-PAM by maintaining its imaging capability at enhanced depths. The b-scan PAM images were prepared as paired (for semi-supervised conditional GAN) and unpaired (for unsupervised CycleGAN) groups for label-free reconstructed AR-PAM b-scan image generation and training. The semi/unsupervised GANs successfully improved resolution and sensitivity in a phantom and i n vivo mouse ear test with ground truth. We also confirmed that GANs could enhance resolution and sensitivity of deep tissues without the ground truth.

Soil phosphorus is heavily restricted by soil acidification and salinization. There is a need to determine a biological solution for this issue to replace the overuse of chemical phosphorus fertilizer that aggravates adverse conditions, such as salinity, acidity, and metallic toxicity. Therefore, this study aimed at determining the phosphorus dynamics in terms of the soil, growth, and yield of rice under the supplementation of phosphate (P)-solubilizing purple nonsulfur bacteria (PNSB), Cereibacter sphaeroides ST16 and ST26, in salinized soil collected from An Bien district, Kien Giang province, Vietnam, under greenhouse conditions. The experiment followed a completely randomized block design with two factors and four replications. In particular, the reduced percentages of P fertilizer (A) were 0%, 25%, 50%, 75%, and 100% P. The supplementations of C. sphaeroides strains (B) were the negative control, ST16, ST26, and a mixture of both ST16 and ST26. The results showed that supplying the C. sphaeroides ST16 and ST26 reduced the insoluble P content by 10.1–10.6% Fe-P, 10.3–12.2% Ca-P, and 12.7–43.1% Al-P and increased available P by 8.33–27.8%, leading to total P uptake in plants increasing by 29.4–56.1%. The C. sphaeroides strains also reduced soil Na+. Therefore, supplying the C. sphaeroides strains increased the rice growth and yield components of rice, leading to a greater yield of 26.5–51.0%. Supplying each strain of ST16 and ST26 reduced 50–100% P fertilizer as recommended. Ultimately, inoculation of the bacterial mixture allowed a reduction by 100% P fertilizer percentage as recommended but the yield remained the still.

In this paper, the results of making a reduced graphene oxide cathode electrode with Cu2S nanoparticles are shown so that it can be used as a counter electrode in quantum dot solar cells to replace other counter electrodes. An rGO-Cu2S paste obtained by hydrolysis was scanned onto the surface of the fluorine-doped tin oxide (FTO) conductive substrate when bound to Cu2S nano by a screen-printing process, then calcined at 350 °C to crystallize the film. Following calcination, the film was examined for structure using energy-dispersive X-ray (EDX) and X-ray diffraction (XRD) spectroscopy, as well as for type and particle size using scanning and transmission electron microscopy and transmission electron microscopy, respectively. Mott-schottky measurement is used to determine the semiconductor and carrier concentrations in the film, and an electrochemical device is used to assess the electrodes redox capacity in a polysulfide electrolyte solution. The operability of the rGO-Cu2S cathode at the peak of the current density in the C-V curve was 24 mA/cm2, a 30-fold increase compared to that of the Cu2S electrode. This result shows that the efficiency, Voc, FF, Jsc are 4.92%, 0.525 V, 0.418, and 22.4 mA/cm2, respectively.

BackgroundNeoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy.ObjectiveThe objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer.Patients and MethodsA retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery.ResultsA total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (> 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity < 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity.ConclusionThe TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.