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OBJECTIVE: Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1 inhibitor combined with transcatheter arterial chemoembolization (TACE), has been widely used in the treatment of HCC. However, there remains a contentious debate regarding the clinical value of the TACE and camrelizumab combination. This study seeks to investigate the efficacy and safety of this combination treatment regimen in patients with HCC. MATERIALS AND METHODS: The related studies were retrieved from four online databases, including PubMed, Cochrane Library, EMBASE, and Web of Science, up to June 1, 2023. The selection of studies was based on screening of titles, abstracts, and full-texts. The primary efficacy outcomes included complete response (CR), objective response rate (ORR), and disease control rate (DCR), while safety outcomes evaluated all treatment-related adverse events (AEs). Additionally, secondary outcomes such as overall (OS) and progression-free survival (PFS) were extracted for further survival analysis. The quality of the included trials was assessed using the MINORS tool. Publication bias was evaluated through funnel plot and Egger"s test. RESULTS: A total of 17 publications involving 1,377 cases were included. The pooled CR rate, ORR, and DCR of the patients treated with TACE plus camrelizumab had a pooled CR rate of 8% (95% CI: 0.01-0.15, p=0.03), ORR of 47% (95% CI: 0.42-0.52, p<0.00001) and DCR of 82% (95% CI: 0.77-0.88, p<0.00001), respectively. Compared with a control group that did not receive TACE or camrelizumab, the pooled RR of CR rate, ORR, and DCR were 1.61 (95% CI: 1.27-2.04, p<0.0001), 1.56 (95% CI: 1.19-2.05, p=0.001) and 1.55 (95% CI: 1.19-2.03, p=0.001), respectively. Besides, the combination regimen can prolong the OS (HR=2.60, 95% CI: 2.25-3.02, p<0.00001) and PFS (HR=4.90, 95% CI: 1.94-12.38, p=0.0008). However, the incidence of treatment-related AEs was relatively high (77%), with 29% for grade 3 AEs. The most common AEs observed were pain (47%), fever (46%), hepatic function abnormalities (44%), hypoalbuminemia (39%), and hypertension (37%). The combination treatment did not increase the incidence of AEs compared to the control group, except for the hand-foot skin reaction (RR=0.85, 0.74-0.97, p=0.01), hepatic encephalopathy (RR=4.29, 2.51-7.35, p<0.00001) and nausea (RR=1.35, 1.13-1.61, p=0.001). CONCLUSIONS: Combination therapy of TACE plus camrelizumab has shown notable clinical benefits, improved survival, and a manageable safety profile in patients with HCC, but it is essential to monitor and manage the specific toxicities, especially for the camrelizumab-related AEs. [ABSTRACT FROM AUTHOR]

We assessed the diagnostic performance of both ultra-high-resolution (UHR) and high-resolution (HR) modes of photon-counting detector (PCD)-CT within the confines of standard pre-TAVI CT scans, as well as the performance of UHR mode adjusted specifically for coronary imaging, using quantitative coronary angiography (QCA) as the reference. We included 60 patients undergoing pre-TAVI planning CT scans. Patients were divided into 3 groups: 20 scanned in HR mode, 20 in UHR mode, and 20 in adjusted UHR mode, on a dual-source PCD-CT. The adjusted UHR mode employed a lower tube voltage (90 kV vs. 120 kV) and a higher image quality level (65 vs. 34) to enhance coronary artery visualization. Patients underwent invasive coronary angiography as part of clinical routine. CCTA and QCA were reviewed to assess CAD presence defined as stenosis ≥ 50% in proximal and middle coronary segments. We included 60 patients (mean age 79 ± 7 years; 39(65%) men). Mean heart rate during scanning was 72 ± 13 bpm. Median coronary calcium score was 973 [379-2007]. QCA identified significant CAD in 24 patients (40%): 9 patients scanned with HR mode, 10 patients with the UHR mode, and 5 patients with the UHR adjusted mode. Per-patient area under the curves were 0.57 for HR, 0.80 for UHR, and 0.80 for adjusted UHR, with no significant differences between the scan modes, and per-vessel the area under the curves were 0.73 for HR, 0.69 for UHR, and 0.87 for adjusted UHR, with significant differences between UHR and adjusted UHR (p = 0.04). UHR and adjusted UHR modes of dual source PCD-CT show potential for improved sensitivity and negative predictive value for detecting CAD in patients undergoing pre-TAVI scans, however, no statistically significant difference from HR mode was observed., (© 2024. The Author(s).)

Background: The aim of our current systematic dynamic phantom study was first, to optimize reconstruction parameters of coronary CTA (CCTA) acquired on photon counting CT (PCCT) for coronary artery calcium (CAC) scoring, and second, to assess the feasibility of calculating CAC scores from CCTA, in comparison to reference calcium scoring CT (CSCT) scans., Methods: In this phantom study, an artificial coronary artery was translated at velocities corresponding to 0, < 60, and 60-75 beats per minute (bpm) within an anthropomorphic phantom. The density of calcifications was 100 (very low), 200 (low), 400 (medium), and 800 (high) mgHA/cm 3 , respectively. CCTA was reconstructed with the following parameters: virtual non-iodine (VNI), with and without iterative reconstruction (QIR level 2, QIR off, respectively); kernels Qr36 and Qr44f; slice thickness/increment 3.0/1.5 mm and 0.4/0.2 mm. The agreement in risk group classification between CAC CCTA and CAC CSCT scoring was measured using Cohen weighted linear κ with 95% CI., Results: For CCTA reconstructed with 0.4 mm slice thickness, calcium detectability was perfect (100%). At < 60 bpm, CAC CCTA of low, and medium density calcification was underestimated by 53%, and 15%, respectively. However, CAC CCTA was not significantly different from CAC CSCT of very low, and high-density calcifications. The best risk agreement was achieved when CCTA was reconstructed with QIR off, Qr44f, and 0.4 mm slice thickness (κ = 0.762, 95% CI 0.671-0.853)., Conclusion: In this dynamic phantom study, the detection of calcifications with different densities was excellent with CCTA on PCCT using thin-slice VNI reconstruction. Agatston scores were underestimated compared to CSCT but agreement in risk classification was substantial., Clinical Relevance Statement: Photon counting CT may enable the implementation of coronary artery calcium scoring from coronary CTA in daily clinical practice., Key Points: Photon-counting CTA allows for excellent detectability of low-density calcifications at all heart rates. Coronary artery calcium scoring from coronary CTA acquired on photon counting CT is feasible, although improvement is needed. Adoption of the standard acquisition and reconstruction protocol for calcium scoring is needed for improved quantification of coronary artery calcium to fully employ the potential of photon counting CT., (© 2024. The Author(s).)

Chemotherapy resistance remains a significant obstacle that limits the long-term efficacy of cancer therapy, necessitating further investigations into the underlying mechanisms. Here, we find that DNA fragments induced by chemotherapeutic agents trigger the degradation of cGAS, a potent double-strand DNA (dsDNA) sensor, by lysosomes. Mechanically, the lysosome-localized protein LAMTOR1 is up-regulated, and the interaction between LAMTOR1 and cGAS is enhanced upon exposure to DNA fragments, boosting the accumulation and digestion of cGAS in lysosomes through the receptor protein p62. LAMTOR1 deficiency increases cGAS abundance and promotes activation of the cGAS-STING pathway, leading to subsequent production of type I interferons induced by cytosolic DNA stimulation. Loss of LAMTOR1 synergizes with immunotherapy and chemotherapy to inhibit tumor growth and prolong the survival time of tumor-bearing mice by promoting the infiltration of effective T lymphocytes. Thus, our study reveals a regulation of cGAS abundance and provides a potential strategy to overcome chemotherapy resistance by targeting LAMTOR1., Competing Interests: Competing interests statement:The authors declare no competing interest.

While protein aggregation's association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery., (© 2024. The Author(s).)

Background: Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients., Methods: The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate., Results: A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74)., Conclusion: This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: To compare coronary artery calcification (CAC) scores measured on virtual non-contrast (VNC) and virtual non-iodine (VNI) reconstructions computed from coronary computed tomography angiography (CCTA) using photon-counting computed tomography (PCCT) to true non-contrast (TNC) images., Methods: We included 88 patients (mean age = 59 years ± 13.5, 69% male) who underwent a TNC coronary calcium scan followed by CCTA on PCCT. VNC images were reconstructed in 87 patients and VNI in 88 patients by virtually removing iodine from the CCTA images. For all reconstructions, CAC scores were determined, and patients were classified into risk categories. The overall agreement of the reconstructions was analyzed by Bland-Altman plots and the level of matching classifications., Results: The median CAC score on TNC was 27.8 [0-360.4] compared to 8.5 [0.2-101.6] (p < 0.001) on VNC and 72.2 [1.3-398.8] (p < 0.001) on VNI. Bland-Altman plots depicted a bias of 148.8 (ICC = 0.82, p < 0.001) and - 57.7 (ICC = 0.95, p < 0.001) for VNC and VNI, respectively. Of all patients with CAC TNC  = 0, VNC reconstructions scored 63% of the patients correctly, while VNI scored 54% correctly. Of the patients with CAC TNC  > 0, VNC and VNI reconstructions detected the presence of coronary calcium in 90% and 92% of the patients. CAC VNC tended to underestimate CAC score, whereas CAC VNI overestimated, especially in the lower risk categories. According to the risk categories, VNC misclassified 55% of the patients, while VNI misclassified only 32%., Conclusion: Compared to TNC images, VNC underestimated and VNI overestimated the actual CAC scores. VNI reconstructions quantify and classify coronary calcification scores more accurately than VNC reconstructions., Clinical Relevance Statement: Photon-counting CT enables spectral imaging, which might obviate the need for non-contrast enhanced coronary calcium scoring, but optimization is necessary for the clinical implementation of the algorithms., Key Points: • Photon-counting computed tomography uses spectral information to virtually remove the signal of contrast agents from contrast-enhanced scans. • Virtual non-contrast reconstructions tend to underestimate coronary artery calcium scores compared to true non-contrast images, while virtual non-iodine reconstructions tend to overestimate the calcium scores. • Virtual non-iodine reconstructions might obviate the need for non-contrast enhanced calcium scoring, but optimization is necessary for the clinical implementation of the algorithms., (© 2023. The Author(s).)

Arterial stiffness has been proved to be an important parameter in the evaluation of cardiovascular diseases, and Pulse Wave Velocity (PWV) is a strong indicator of arterial stiffness. Compared to regional PWV (PWV among different arteries), local PWV (PWV within a single artery) outstands in providing higher precision in indicating arterial properties, as regional PWVs are highly affected by multiple parameters, e.g., variations in blood vessel lengths due to individual differences, and multiple reflection effects on the pulse waveform. However, local PWV is less-developed due to its high dependency on the temporal resolution in synchronized signals with usually low signal-to-noise ratios. This paper presents a method for the noninvasive simultaneous measurement of two local PWVs in both left and right radial arteries based on the Fiber Bragg Grating (FBG) technique via correlation analysis of the pulse pairs at the fossa cubitalis and at the wrist. Based on the measurements of five male volunteers at the ages of 19 to 21 years old, the average left radial PWV ranged from 9.44 m/s to 12.35 m/s and the average right radial PWV ranged from 11.50 m/s to 14.83 m/s. What is worth mentioning is that a stable difference between the left and right radial PWVs was observed for each volunteer, ranging from 2.27 m/s to 3.04 m/s. This method enables the dynamic analysis of local PWVs and analysis of their features among different arteries, which will benefit the diagnosis of early-stage arterial stiffening and may bring more insights into the diagnosis of cardiovascular diseases.

Background: Photon-counting CT (PCCT) is the next-generation CT scanner that enables improved spatial resolution and spectral imaging. For full spectral processing, higher tube voltages compared to conventional CT are necessary to achieve the required spectral separation. This generated interest in the potential influence of thin slice high tube voltage PCCT on overall image quality and consequently on radiation dose., Purpose: This study first evaluated tube voltages and radiation doses applied in patients who underwent coronary CT angiography with PCCT and energy-integrating detector CT (EID-CT). Next, image quality of PCCT and EID-CT was objectively evaluated in a phantom study simulating different patient sizes at these tube voltages and radiation doses., Methods: We conducted a retrospective analysis of clinical doses of patients scanned on a conventional and PCCT system. Average patient water equivalent diameters for different tube voltages were extracted from the dose reports for both EID-CT and PCCT. A conical phantom made of polyethylene with multiple diameters (26/31/36 cm) representing different patient sizes and containing an iodine insert was scanned with a EID-CT scanner using tube voltages and phantom diameters that match the patient scans and characteristics. Next, phantom scans were made with PCCT at a fixed tube voltage of 120 kV and with CTDI VOL values and phantom diameters identical to the EID-CT scans. Clinical image reconstructions at 0.6 mm slice thickness for conventional CT were compared to PCCT images with 0.4 mm slice thickness. Image quality was quantified using the detectability index (d'), which estimated the visibility of a 3 mm diameter contrast-enhanced coronary artery by considering noise, contrast, resolution, and human visual perception. Alongside d', noise, contrast and resolution were also individually assessed. In addition, the influence of various kernels (Bv40/Bv44/Bv48/Bv56), quantum iterative reconstruction strengths (QIR, 3/4) and monoenergetic levels (40/45/50/55 keV) for PCCT on d' was investigated., Results: In this study, 143 patients were included: 47 were scanned on PCCT (120 kV) and the remaining on EID-CT (74 small-sized at 70 kV, 18 medium-sized at 80 kV and four large-sized at 90 kV). EID-CT showed 7%-17% higher d' than PCCT with Bv40 kernel and strength four for small/medium patients. Lower monoenergetic images (40 keV) helped mitigate the difference to 1%-6%. For large patients, PCCT's detectability was up to 31% higher than EID-CT. PCCT has thinner slices but similar noise levels for similar reconstruction parameters. The noise increased with lower keV levels in PCCT (≈30% increase), but higher QIR strengths reduced noise. PCCT's iodine contrast was stable across patient sizes, while EID-CT had 33% less contrast in large patients than in small-sized patients., Conclusion: At 120 kV, thin slice PCCT enables CCTA in phantom scans representing large patients without raising radiation dose or affecting vessel detectability. However, higher doses are needed for small and medium-sized patients to obtain a similar image quality as in EID-CT. The alternative of using lower mono-energetic levels requires further evaluation in clinical practice., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Antiferroelectric materials with an electrocaloric effect (ECE) have been developed as promising candidates for solid-state refrigeration. Despite the great advances in positive ECE, reports on negative ECE remain quite scarce because of its elusive physical mechanism. Here, a giant negative ECE (maximum Δ S ∼ -33.3 J kg -1 K -1 with Δ T ∼ -11.7 K) is demonstrated near room temperature in organometallic perovskite, i BA 2 EA 2 Pb 3 I 10 ( 1 , where i BA = isobutylammonium and EA = ethylammonium), which is comparable to the greatest ECE effects reported so far. Moreover, the ECE efficiency Δ S /Δ E (∼1.85 J cm kg -1 K -1 kV -1 ) and Δ T /Δ E (∼0.65 K cm kV -1 ) are almost 2 orders of magnitude higher than those of classical inorganic ceramic ferroelectrics and organic polymers, such as BaTiO 3 , SrBi 2 Ta 2 O 9 , Hf 1/2 Zr 1/2 O 2 , and P(VDF-TrFE). As far as we know, this is the first report on negative ECE in organometallic hybrid perovskite ferroelectric. Our experimental measurement combined with the first-principles calculations reveals that electric field-induced antipolar to polar structural transformation results in a large change in dipolar ordering (from 6.5 to 45 μC/cm 2 under the Δ E of 18 kV/cm) that is closely related to the entropy change, which plays a key role in generating such giant negative ECE. This discovery of field-induced negative ECE is unprecedented in organometallic perovskite, which sheds light on the exploration of next-generation refrigeration devices with high cooling efficiency.

Purpose: The study is intended to assess the image quality of ultra-high resolution (UHR) coronary computed tomography angiography (CCTA) performed on dual source photon-counting detector CT (PCD-CT)., Method: Consecutive patients, who underwent clinically indicated CCTA on PCD-CT (UHR 120x 0.2 mm collimation), were included. CCTA images were reconstructed at 0.2 mm slice thickness with Bv40, Bv44, Bv48 and Bv56 kernels and quantum iterative reconstruction level 4. Contrast-to-noise (CNR) and signal-to-noise ratios (SNR) were quantified from contrast-enhanced blood and subcutaneous adipose tissue. All reconstructions were scored per coronary segment (18-segment model) for presence, image quality, motion artefacts, stack artefacts, plaque presence and composition, and stenosis degree. Image quality was scored by two independent observers., Results: Sixty patients were included (median age 62 [25th - 75th percentile: 53-67] years, 45% male, median calcium score 62 [0-217]). The mean heart rate during scanning was 71 ± 11 bpm. Median CTDIvol was 19 [16-22]mGy and median DLP 243 [198-327]mGy.cm. The SNR was 9.3 ± 2.3 and the CNR was 11.7 ± 2.6. Of the potential 1080 coronary segments (60 patients x 18 segments), 255/256 (reader1/reader2) segments could not be assessed for being absent or non-evaluable due to size. Both readers scored 85% of the segments as excellent or very good (Intraclass Correlation Coefficient: 0.88 (95% CI: 0.87-0.90). Motion artefacts were present in 45(5%) segments, stack artefacts in 60(7%) segments and metal artefacts in 9(1%) segments., Conclusion: UHR dual-source PCD-CT CCTA provides excellent or very good image quality in 85% of coronary segments at relatively high heart rates at moderate radiation dose with only limited stack artefacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The bursa of Fabricius (BF) is pivotal for B lymphocyte ontogenesis. In the present investigation, a novel bursal peptide, designated BP7, was extracted from BF and was found to stimulate colony-forming unit pre-B (CFU pre-B) formation at various concentrations (1 μg/mL, P < 0.05; 5 μg/mL, P < 0.05; 25 μg/mL, P < 0.05). Moreover, BP7 modulated B cell differentiation pathways. The immunoregulatory potential of BP7 was further assessed in avian and murine models subjected to immunization with inactivated avian influenza virus (AIV, H9N2 subtype). BP7 significantly augmented AIV-specific antibody levels (Prime immunization: 5 mg/kg, P < 0.05; Boost immunization: 0.4, 1, and 5 mg/kg, P < 0.05) and cytokine secretion in the avian model (IL-4 and IFN-γ: 0.4, 1, and 5 mg/kg, P < 0.05). Similarly, in the murine model, AIV-specific antibody levels (Prime and Boost immunization: 0.4, 1, and 5 mg/kg, P < 0.05) and cytokine production (IL-4 and IFN-γ: 0.4, 1, and 5 mg/kg, P < 0.05) were notably enhanced. This study offers novel insights into the mechanisms underlying B cell maturation and holds implications for future immunopharmacological interventions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A facile Z-scheme AgCl/BiOCl heterojunction photocatalyst with oxygen vacancies was fabricated by a water-bath method. The structural, morphological, optical and electronic properties of as-synthesized samples were systematically characterized. The oxygen vacancies were confirmed by EPR, which could optimize the band-gap of the AgCl/BiOCl heterojunction and improve the photo-induced electron transfer. The optimized AgCl/BiOCl heterojunction showed excellent photocatalytic degradation efficiency (82%) for tetracycline (TC). Simultaneously, E. coli was completely inactivated within 60 min due to the AgCl/BiOCl heterojunction. The elevated catalytic activity of the optimal AgCl/BiOCl heterojunction was ascribed to the synergistic effect of the enhanced light absorption and effective photoinduced charge carrier separation and transfer. Moreover, the degradation efficiency of the AgCl/BiOCl heterojunction towards ofloxacin, norfloxacin and Lanasol Red 5B was 73%, 74% and 96%, respectively. The experimental factors for the degradation efficiency of TC were also studied. Furthermore, active species trapping experiments indicated that superoxide radicals (˙O 2 - ) were the main reactive species, and the Z-scheme charge transfer mechanism helped to improve the photocatalytic activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)