Diagnostic and prognostic performance of artificial intelligence-based fully-automated on-site CT-FFR in patients with CAD.

Currently, clinically available coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) is time-consuming and complex. We propose a novel artificial intelligence-based fully-automated, on-site CT-FFR technology, which combines the automated coronary plaque segmentation and luminal extraction model with reduced order 3 dimentional (3D) computational fluid dynamics. A total of 463 consecutive patients with 600 vessels from the updated China CT-FFR study in Cohort 1 undergoing both CCTA and invasive fractional flow reserve (FFR) within 90 d were collected for diagnostic performance evaluation. For Cohort 2, a total of 901 chronic coronary syndromes patients with index CT-FFR and clinical outcomes at 3-year follow-up were retrospectively analyzed. In Cohort 3, the association between index CT-FFR from triple-rule-out CTA and major adverse cardiac events in patients with acute chest pain from the emergency department was further evaluated. The diagnostic accuracy of this CT-FFR in Cohort 1 was 0.82 with an area under the curve of 0.82 on a per-patient level. Compared with the manually dependent CT-FFR techniques, the operation time of this technique was substantially shortened by 3 times and the number of clicks from about 60 to 1. This CT-FFR technique has a highly successful (> 99%) calculation rate and also provides superior prediction value for major adverse cardiac events than CCTA alone both in patients with chronic coronary syndromes and acute chest pain. Thus, the novel artificial intelligence-based fully automated, on-site CT-FFR technique can function as an objective and convenient tool for coronary stenosis functional evaluation in the real-world clinical setting.

Antiaging Effects of Human Fecal Transplants with Different Combinations of Bifidobacterium bifidum LTBB21J1 and Lactobacillus casei LTL1361 in d-Galactose-Induced Mice.

The feces of healthy middle-aged and old people were first transplanted into d-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.

Massage ameliorates lumbar disc herniation-related radicular pain in rats by suppressing TLR4/NLRP3 inflammasome signaling transduction.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease that can cause severe radicular pain. Massage, also known as Tuina in Chinese, has been indicated to exert an analgesic effect in patients with LDH. Nonetheless, the mechanism underlying this effect of massage on LDH remains unclarified. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. A rat LDH model was established by autologous nucleus pulpous (NP) implantation, followed by treatment with or without massage. A toll-like receptor 4 (TLR4) antagonist TAK-242 was administrated to rats for blocking TLR4. Behavioral tests were conducted to examine rat mechanical and thermal sensitivities. Western blotting was employed for determining TLR4 and NLRP3 inflammasome-associated protein levels in the spinal dorsal horn (SDH). Immunofluorescence staining was implemented for estimating the microglial marker Iba-1 expression in rat SDH tissue. RESULTS: NP implantation induced mechanical allodynia and thermal hyperalgesia in rat ipsilateral hindpaws and activated TLR4/NLRP3 inflammasome signaling transduction in the ipsilateral SDH. Massage therapy or TAK-242 administration relieved NP implantation-triggered pain behaviors in rats. Massage or TAK-242 hindered microglia activation and blocked TLR4/NLRP3 inflammasome activation in ipsilateral SDH of LDH rats. CONCLUSION: Massage ameliorates LDH-related radicular pain in rats by suppressing microglia activation and TLR4/NLRP3 inflammasome signaling transduction.

The antibacterial and hemostatic curdlan hydrogel-loading epigallocatechin gallate for facilitating the infected wound healing.

The infected wounds pose one of the major threats to human health today. To address this issue, it is necessary to develop innovative wound dressings with superior antibacterial activity and other properties. Due to its potent antibacterial, antioxidant, and immune-boosting properties, epigallocatechin gallate (EGCG) has been widely utilized. In this study, a multifunctional curdlan hydrogel loading EGCG (Cur-EGCGH3) was designed. Cur-EGCGH3 exhibited excellent physicochemical properties, good biocompatibility, hemostatic, antibacterial, and antioxidant activities. Also, ELISA data showed that Cur-EGCGH3 stimulated macrophages to secrete pro-inflammatory and pro-regenerative cytokines. Cell scratch results indicated that Cur-EGCGH3 promoted the migration of NIH3T3 and HUVECs. In vivo experiments confirmed that Cur-EGCGH3 could inhibit bacterial infection of the infected wounds, accelerate hemostasis, and promote epithelial regeneration and collagen deposition. These results demonstrated that Cur-EGCGH3 holds promise for promoting healing of the infected wounds.

Integrated microbiome and metabolome analyses reveal the effects of low pH on intestinal health and homeostasis of crayfish (Procambarus clarkii).

Low pH (LpH) poses a significant challenge to the health, immune response, and growth of aquatic animals worldwide. Crayfish (Procambarus clarkii) is a globally farmed freshwater species with a remarkable adaptability to various environmental stressors. However, the effects of LpH stress on the microbiota and host metabolism in crayfish intestines remain poorly understood. In this study, integrated analyses of antioxidant enzyme activity, histopathological damage, 16S rRNA gene sequencing, and liquid chromatography-mass spectrometry (LC-MS) were performed to investigate the physiology, histopathology, microbiota, and metabolite changes in crayfish intestines exposed to LpH treatment. The results showed that LpH stress induced obvious changes in superoxide dismutase and catalase activities and histopathological alterations in crayfish intestines. Furthermore, 16S rRNA gene sequencing analysis revealed that exposure to LpH caused significant alterations in the diversity and composition of the crayfish intestinal microbiota at the phylum and genus levels. At the genus level, 14 genera including Bacilloplasma, Citrobacter, Shewanella, Vibrio, RsaHf231, Erysipelatoclostridium, Anaerorhabdus, Dysgonomonas, Flavobacterium, Tyzzerella, Brachymonas, Muribaculaceae, Propionivibrio, and Comamonas, exhibited significant differences in their relative abundances. The LC-MS analysis revealed 859 differentially expressed metabolites in crayfish intestines in response to LpH, including 363 and 496 upregulated and downregulated metabolites, respectively. These identified metabolites exhibited significant enrichment in 24 Kyoto Encyclopedia of Genes and Genomes pathways (p < 0.05), including seven and 17 upregulated and downregulated pathways, respectively. These pathways are mainly associated with energy and amino acid metabolism. Correlation analysis revealed a strong correlation between the metabolites and intestinal microbiota of crayfish during LpH treatment. These findings suggest that LpH may induce significant oxidative stress, intestinal tissue damage, disruption of intestinal microbiota homeostasis, and alterations in the metabolism in crayfish. These findings provide valuable insights into how the microbial and metabolic processes of crayfish intestines respond to LpH stress.

The effect of vitamin D2 supplementation on vitamin D levels in humans: A time and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Inconsistencies exist regarding the influence of vitamin D2 (ergocalciferol) supplementation on serum vitamin D levels. These inconsistencies could be attributed to numerous factors, such as dosage, baseline vitamin D levels, and duration of intervention. Hence, this dose-response meta-analysis of randomized controlled trials was conducted to assess the efficacy of vitamin D2 supplementation on vitamin D levels. METHODS: Relevant studies were searched in PubMed/Medline, Web of Science, Embase, and Scopus, from their inception to 3 January 2023. Variable alterations were considered to calculate the pooled weighted mean difference (WMD) with 95% confidence interval (CI) using the random effects model. RESULTS: Pooled results from 33 study arms demonstrated that Vitamin D2 treatment significantly increases total vitamin D concentrations (WMD: 11.47 ng/mL, 95 %CI: 9.29 to 13.64, p < 0.001), 25(OH)D2 concentrations (WMD: 11.40 ng/mL, 95 %CI: 4.72 to 18.09, p = 0.001), and 1,25(OH)D concentrations (WMD: 5.61 ng/mL, 95 %CI: 0.74 to 10.48, p = 0.024), but decreases 25(OH)D3 concentrations (WMD: -4.63 ng/mL, 95 %CI: -6.46 to -2.81, p < 0.001). In subgroup analyses, increase in total vitamin D concentrations was more significant in vitamin D2 doses >2000 IU/day (WMD: 13.82 ng/mL), studies with duration ≤12 weeks (WMD: 12.53 ng/mL), participants aged ≥60 years (WMD: 14.40 ng/mL), and trials with basal 25(OH)D concentrations <20 ng/mL (WMD: 11.47 ng/mL). CONCLUSIONS: This meta-analysis indicates that the supplementation of vitamin D2 significantly increases the serum concentrations of total vitamin D, 25(OH)D2, and 1,25(OH)D, but decreases 25(OH)D3 concentrations. Careful consideration of patient characteristics, dosage, and treatment duration is recommended for vitamin D2 supplementation.

Measuring and classifying IP usage scenarios: a continuous neural trees approach.

Understanding user behavior via IP addresses is a crucial measure towards numerous pragmatic IP-based applications, including online content delivery, fraud prevention, marketing intelligence, and others. While profiling IP addresses through methods like IP geolocation and anomaly detection has been thoroughly studied, the function of an IP address-e.g., whether it pertains to a private enterprise network or a home broadband-remains underexplored. In this work, we initiate the first attempt to address the IP usage scenario classification problem. We collect data consisting of IP addresses from four large-scale regions. A novel continuous neural tree-based ensemble model is proposed to learn IP assignment rules and complex feature interactions. We conduct extensive experiments to evaluate our model in terms of classification accuracy and generalizability. Our results demonstrate that the proposed model is capable of efficiently uncovering significant higher-order feature interactions that enhance IP usage scenario classification, while also possessing the ability to generalize from the source region to the target one.

Lightweight Meter Pointer Recognition Method Based on Improved YOLOv5.

In substation lightning rod meter reading data taking, the classical object detection model is not suitable for deployment in substation monitoring hardware devices due to its large size, large number of parameters, and slow detection speed, while is difficult to balance detection accuracy and real-time requirements with the existing lightweight object detection model. To address this problem, this paper constructs a lightweight object detection algorithm, YOLOv5-Meter Reading Lighting (YOLOv5-MRL), based on the improved YOLOv5 model's speed while maintaining accuracy. Then, the YOLOv5s are pruned based on the convolutional kernel channel soft pruning algorithm, which greatly reduces the number of parameters in the YOLOv5-MRL model while maintaining a certain accuracy loss. Finally, in order to facilitate the dial reading, the dial external circle fitting method is proposed to calculate the dial reading using the circular angle algorithm. The experimental results on the self-built dataset show that the YOLOv5-MRL object detection model achieves a mean average precision of 96.9%, a detection speed of 5 ms/frame, and a model weight size of 5.5 MB, making it better than other advanced dial reading models.

Corrigendum: LncRNA-AC02278.4 is a novel prognostic biomarker that promotes tumor growth and metastasis in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.860961.].

Analgesia efficacy of lidocaine transfused by a novel disposable injectable cervical dilator during intrauterine device removal procedure: A randomized clinical trial.

OBJECTIVE: The majority of intrauterine devices (IUDs) inserted in China are tailless, requiring intrauterine manipulations for removal and causing pain. This study aimed to investigate the analgesic efficacy of lidocaine injection into a novel disposable injectable cervical dilator for IUD removal procedures. STUDY DESIGN: A double-blinded, placebo-controlled, randomized clinical trial was conducted with women aged 18-65 years old requesting outpatient IUD removal. The study randomly assigned participants to either lidocaine (injecting 5 ml of 2% lidocaine into the injectable cervical dilator) or placebo (injecting 5 ml of normal saline into the device) group. All participants received a standardized paracervical block. The primary outcome was pain reported during IUD removal on a 100 mm Visual Analog Scale (VAS). Intention-to-treat were conducted to evaluate the analgesic effectiveness of injecting lidocaine into the injectable cervical dilators. RESULTS: We enrolled seventy-four eligible participants (37 in lidocaine group and 37 in placebo group). The results showed that the median intraoperative VAS score in the lidocaine group was lower than the placebo group (30.0 mm [IQR 20.0-46.0, n = 37] vs 46.0 mm [IQR 30.0-55.0, n = 37], p = 0.01. In subgroup analyses, among participants with IUD removal and without uterine manipulation and additional procedures, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (15.0 mm [IQR 10.0-27.5, n = 8] vs 20.0 mm [IQR 20.0-40.0, n = 6]), p = 0.28). Among participants with an IUD removal necessitating intrauterine manipulations and without additional procedures, showing lower intraoperative VAS scores in lidocaine group (25.0 mm [IQR 15.0-40.5, n = 17]) compared to placebo group (46.0 mm [IQR 38.5-50.0, n = 23]), p < 0.01. Among participants with additional procedures in addition to IUD removal, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (41.0 mm [IQR 32.5-57.5, n = 12] vs 45.0 mm [IQR 22.5-69.0, n = 8]), p = 0.97). CONCLUSIONS: Injecting lidocaine into the novel disposable injectable cervical dilator for cervix dilation can significantly reduce pain during an IUD removal, particularly in patients necessitating intrauterine manipulations during IUD removal. IMPLICATIONS: When we have to perform intrauterine manipulations to remove an IUD, surgical pain and narrow cervical canal undoubtedly affect the implementation of the procedure. Injecting lidocaine into the injectable cervical dilator can achieve local anesthesia while dilating the cervix, and might reduce the choice of general anesthesia for IUD removal.

Comparing two unitisation manipulations: effects on familiarity, recollection-based recognition, and semantic interference.

The recognition of associative memory can be significantly influenced by the use of an encoding strategy known as unitisation, which has been implemented through various manipulations. However, [Shao, H., Opitz, B., Yang, J., & Weng, X. (2016). Recollection reduces unitised familiarity effect. Memory (Hove, England), 24(4), 535-547. https://doi.org/10.1080/09658211.2015.1021258] found intriguing distinctions between two common manipulations, the compound task and the imagery task, leading to a dispute. We propose that differences in levels of processing in the imagery task may account for these discrepancies. This study tested our hypothesis using two approaches. The first two experiments utilised the R/K paradigm to investigate the effects of these methods on familiarity-based and recollection-based recognition. The results demonstrated that familiarity was increased in the compound task, while recollection was increased in the imagery task. In the subsequent two experiments, an interference paradigm was employed to examine differences in semantic processing within the two tasks. The results showed that the compound task did not impact participants' inclination towards lures, while the imagery task led to a bias towards semantic lures over episodic lures, suggesting that the two encodings in the imagery task involve different levels of semantic processing. These results support our hypothesis and underscore the importance of carefully choosing comparisons that account for other variables in the study of unitisation.

Preimplantation genetic testing for X-linked chronic granulomatous disease induced by a CYBB gene variant: A case report.

INTRODUCTION: X-linked recessive chronic granulomatous disease (XR-CGD) is a severe primary immunodeficiency principally caused by a CYBB (OMIM: 300481) gene variant. Recurrent fatal bacterial or fungal infections are the main clinical manifestations of XR-CGD. PATIENT CONCERNS: In the current case, in vitro fertilization (IVF) associated with preimplantation genetic testing for monogenic disorder (PGT-M) was applied for a Chinese couple who had given birth to a boy with XR-CGD. DIAGNOSIS: Next-generation sequencing-based SNP haplotyping and Sanger-sequencing were used to detect the CYBB gene variant (c.804 + 2T>C, splicing) in this family. INTERVENTIONS: The patient was treated with IVF and PGT-M successively. OUTCOMES: In this IVF cycle, 7 embryos were obtained, and 2 of them were euploid and lacked the CYBB gene variant (c.804 + 2T>C). The PGT results were verified by prenatal diagnosis after successful pregnancy, and a healthy girl was eventually born. CONCLUSION: PGT-M is an effective method for helping families with these fatal and rare inherited diseases to have healthy offspring. It can availably block the transmission of disease-causing loci to descendant.

Barriers and facilitators to older adult participation in intergenerational physical activity program: a systematic review.

BACKGROUND: The intergenerational physical activity program aims to promote the health, social engagement, and well-being of older adults. It is essential to comprehend the barriers and facilitators that affect their involvement to develop successful intervention strategies. This systematic review critically examines available research to identify the factors that impact the participation of older adults in intergenerational physical activity programs. METHODS: This study retrieved 13 electronic databases (from January 2000 to March 2023) and used a social-ecological model to classify and analyze the identified facilitators and barriers. RESULTS: A total of 12 articles were included, which identified 73 facilitators and 37 barriers. These factors were condensed into 7 primary themes and 14 sub-themes in total. CONCLUSIONS: The factors influencing the participation of older adults in intergenerational physical activities are multifaceted. These factors guide project developers, policymakers, and practitioners in developing and implementing intergenerational physical activity programs to help address global aging issues and promote intergenerational connections. TRIAL REGISTRY: PROSPERO ID: CRD42023420758.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

Feasibility and Tolerability of Anlotinib Plus PD-1 Blockades for Patients with Treatment-Refractory Metastatic Colorectal Cancer: A Retrospective Exploratory Study.

Objective: Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively. Methods: A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions. Results: A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%-27.1%) and a disease control rate of 76.5% (95% CI: 64.6%-85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01-7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40-15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89-10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome. Conclusion: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.

Coronary chronic total occlusion on coronary CT angiography: what radiologists should know?

Coronary chronic total occlusion (CTO) often occurs in patients with obstructive coronary artery disease, which remains one of the greatest challenges for interventional cardiologists. Coronary computed tomography angiography (CCTA) with its emerging post-processing techniques can provide a detailed assessment of CTO lesions before percutaneous coronary intervention (PCI), playing an important role in the clinical management of CTO PCI, from early diagnosis, pre-procedural outcome prediction, the crossing algorithm planning, intraprocedural guidance, and finally post-procedural assessment and follow-up. In addition, the feasibility of CT perfusion (CTP) in patients with CTO has been validated. Combined CCTA and CTP have the great potential to be the one-stop-shop imaging modality for assessing both anatomy and function of CTO lesions. This review aims to make radiologists understand the role of CCTA in the diagnosis and assessment of CTO lesions, thus assisting interventionalists in optimizing CTO PCI crossing strategies with the expertise of radiologists.Critical relevance statement The anatomical features of CTO on CCTA can reveal the complexity of CTO lesions and are associated with CTO PCI outcome, thus helping interventionalists optimize CTO PCI crossing strategies.Key points • CTO is the common lesion in invasive coronary angiography, and CTO PCI is technically difficult and its success rate is relatively low.• Length, collaterals, and attenuation-related signs can help distinguish CTO from subtotal occlusion.• The anatomical features of CTO lesions can help grade the difficulty of CTO PCI and predict procedural outcomes and long-term outcomes of CTO PCI.• The real-time fusion of CCTA with fluoroscopic angiography can be applied in highly complicated CTO lesions.• After CTO PCI, CCTA can help guide a second CTO PCI re-entry or follow up stent patency.

Impact of ageing on homologous and human-coronavirus-reactive antibodies after SARS-CoV-2 vaccination or infection.

The endemic human coronaviruses (HCoVs) circulate worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses and the boosting of HCoV-reactive antibodies after SARS-CoV-2 vaccination or infection in individuals up to 98 years old. All the vaccinees were home-dwelling with no documented SARS-CoV-2 infection before receiving the COVID-19 mRNA vaccine (BNT162b2). The first two vaccine doses elicited potent SARS-CoV-2 spike binding antibodies in individuals up to 80 years. The third dose largely boosted the previously low S2 domain binding and neutralizing antibodies in elderly 80-90 years old, but less so in those above 90 years. The endemic betacoronavirus (HKU1 and OC43) reactive antibodies were boosted in all vaccinees, although to a lesser extent in those above 80 years old. COVID-19 patients had potent elevation of alpha- and betacoronavirus (229E, NL63, HKU1 and OC43) reactive antibodies. In both patients and vaccinees, S2 domain specific antibody increases correlated with SARS-CoV-2 neutralizing and HCoV-reactive antibody responses in all ages, indicating S2 domain as a candidate for future universal coronavirus vaccine design.

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS.

Quorum sensing (QS) is considered an appealing target for interference with bacterial infections. ß-Adrenergic blockers are promising anti-QS agents but do not have antibacterial activity. We assessed the potential ability of adrenergic receptor inhibitors to enhance the antibacterial activity of polymyxin B (PB) against Klebsiella pneumoniae and determined that dronedarone has the most potent activity both in vitro and in vivo. We found that dronedarone increases the thermal stability of LuxS, decreases the production of AI-2, and affects the biofilm formation of K. pneumoniae. We also identified the direct binding of dronedarone to LuxS. However, the mechanism by which dronedarone enhances the antibacterial activity of PB has not been elucidated and is worthy of further exploration. Our study provides a basis for the future development of drug combination regimens.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

OBJECTIVES: The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). MATERIALS AND METHODS: Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. RESULTS: Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6 years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). CONCLUSIONS: In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. CLINICAL RELEVANCE STATEMENT: In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. KEY POINTS: • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.