Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Integrin ß3 enhances glycolysis and increases lactate production in endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic disease characterized by endometrial-like tissue present outside of the uterus. Macrophages have been confirmed to participate in the development of EMs. Integrin ß3 (ITGB3), a ß-subunit of the integrin family, is crucial in tumor progression. In this study, we investigated the pivotal role of ITGB3 in endometrial stromal cells (ESCs) and its influence on the development of EMs, particularly focusing on the regulatory impact of macrophages. METHODS: In this study, we used western blot, Real-time qPCR, Immunohistochemistry to detected the high expression of ITGB3 in ESCs. ITGB3-overexpression ESCs (ITGB3-OE) was constructed and detected by RNA-seq with normal ESCs. ATP and lactate expression assay, transwell migration assay, wound healing, cell adhesion assay and other molecular biology techniques were used to explore the potential mechanisms. In vivo, we constructed the EMs mouse model and injected with cilengitite to inhibit ITGB3. RESULTS: Here, we found ITGB3 highly expressed in ectopic lesions in EMs. The increasing ITGB3 resulted in activating the glycolysis, which produced more ATP and lactate in ITGB3-OE. After culturing with lactate, the migration, proliferation and invasion ability of ESCs were enhanced, while the result in 2-DG was reversed. In vivo, the results showed that after antagonizing ITGB3, the number of ectopic lesions was decrease. CONCLUSIONS: Our findings indicate that ITGB3 up-regulated by macrophages are able to regulate the glycolysis to promote the development of EMs and lactate enhances the ability of proliferation, migration, invasion and adhesion of EMs iv vivo and in vitro.

Causality between major depressive disorder and functional dyspepsia: a two-sample Mendelian randomization study.

Background: To investigate the causal relationship between major depression and functional dyspepsia using two-sample Mendelian randomization. Methods: Data for major depression and functional dyspepsia were obtained from genome-wide association studies. We selected Single Nucleotide Polymorphisms (SNPs) strongly associated with severe depression. Mendelian randomization analysis was conducted using methods such as Inverse-Variance Weighted (IVW), MR-Egger, and Weighted Median Estimator (WME). Sensitivity analysis was performed to assess the robustness of the results. Results: A total of 31 eligible SNPs were identified as instrumental variables for major depression. IVW analysis indicated a positive causal relationship between the two conditions (ß = 0.328; SE = 0.137; p = 0.017), suggesting that severe depression increases the risk of functional dyspepsia (OR = 1.389; 95% CI: 1.062-1.816). Sensitivity tests showed no evidence of heterogeneity or horizontal pleiotropy (p > 0.05). Conclusion: MR analysis had shown that major depressive disorder is associated with an increased risk of functional dyspepsia.

Concomitant atypical knee gout and seronegative rheumatoid arthritis: A case report.

BACKGROUND: Gout and seronegative rheumatoid arthritis (SNRA) are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported. Limited information is available regarding the clinical management and prognosis of these combined diseases. CASE SUMMARY: A 57-year-old woman with a 20-year history of joint swelling, tenderness, and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA. The initial regimen of methotrexate, leflunomide, and celecoxib alleviated her symptoms, except for those associated with the knee. After symptom recurrence after medication cessation, her regimen was updated to include iguratimod, methotrexate, methylprednisolone, and folic acid, but her knee issues persisted. Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee, indicating coexistent SNRA and atypical knee gout. After postarthroscopic surgery to remove the synovium and urate crystals, and following a tailored regimen of methotrexate, leflunomide, celecoxib, benzbromarone, and allopurinol, her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year, indicating successful management of both conditions. CONCLUSION: This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

Thyroid Diseases After Total Knee Replacement: A Multi-center, Propensity-score-matched Cohort Study.

BACKGROUND/AIM: Thyroid diseases are prevalent endocrine disorders that significantly affect overall health. Although the impact of pre-existing thyroid dysfunction on total knee replacement (TKR) outcomes has been studied, the potential for TKR to increase the risk of developing thyroid disorders remains unexplored. PATIENTS AND METHODS: We examined electronic medical records from a large U.S. research network in the TriNetX research network. The study focused on patients with osteoarthritis, comparing those who had total knee replacement surgery (TKR) between 2005 and 2018 to a non-TKR group who did not have the surgery. Propensity score matching was employed to control for critical confounders. The hazard ratios (HRs) for the risk of thyroid diseases in TKR patients versus non-TKR controls were assessed. RESULTS: Post-matching, the TKR cohort demonstrated a significantly higher risk of developing thyroid diseases compared to the non-TKR cohort (unadjusted HR=1.218, 95%CI=1.169-1.269). This elevated risk persisted after adjusting for confounders (adjusted HR=1.126, 95%CI=1.061-1.196). Stratification analysis indicated that female TKR patients and those aged ≥65 years were at higher risk of developing thyroid diseases than their respective control groups. CONCLUSION: This study suggests a potential link between TKR and an increased risk of thyroid diseases, particularly among older adults and females. Potential mechanisms include inflammatory processes, surgical stress, autoimmune responses, and pharmacological effects. Healthcare providers should be vigilant in monitoring and managing thyroid dysfunction in TKR patients. Further research is necessary to elucidate the underlying mechanisms and develop preventive strategies.

HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies toward achieving HIV remission without ART.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1[Formula: see text], IL-6, and TNF-[Formula: see text]), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/[Formula: see text]-catenin pathway proteins (Wnt3a, [Formula: see text]-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/[Formula: see text]-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson's Disease Therapy.

Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells can infiltrate continuously, resulting in an overactivated immune microenvironment of Parkinson's disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) to address multiple factors for the management of PD. Specifically, EVN is developed by coating CCR2-enriched mesenchymal stem cell-derived extracellular vesicles (MSCCCR2 EVs) onto a dihydrotanshinone I-loaded nanocarrier (MSeN-DT). The MSCCCR2 EVs (the shell of EVN) can actively show homing to specific chemokines CCL2 in the substantia nigra, which enables them to block the infiltration of peripheral inflammatory cells. Interestingly, MSeN-DT (the core of EVN) can promote the Nrf2-GPX4 pathway for the suppression of the source of inflammation by inhibiting ferroptosis in microglia. In the PD model mice, a satisfactory therapeutic effect is achieved, with inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra, as well as promotion of behavioral improvement and repairing damaged neurons. In this way, the combinatorial code of alleviation of inflammation and modulation of immune homeostasis can reshape the immune microenvironment in PD, which bridges internal anti-inflammatory and external immunity. This finding reveals a comprehensive therapeutic paradigm for PD that breaks the vicious cycle of immune overactivation.

Prospective study of urinary incontinence recovery following endoscopic enucleation of the prostate.

OBJECTIVE: To investigate the clinical trajectories and identify risk factors linked to post-enucleation urinary incontinence (UI). PATIENTS AND METHODS: In this prospective study (April 2020 to March 2022) at a single institution, 316 consecutive patients receiving endoscopic enucleation due to benign prostatic enlargement were included. Patient information and perioperative details were collected. Follow-ups, from 1 to 6 months, assessed postoperative UI using International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and a four-item pad questionnaire, classified per International Continence Society definitions. Logistic regression analysed predictors at 1 week, while generalised estimating equation assessed risk factors from 1 to 3 months postoperatively. RESULTS: Patients with a median prostate volume of 57 mL underwent enucleation, with 22.5% experiencing postoperative UI at 1 week, 5.6% at 3 months, decreasing to 1.9% at 6 months. Multivariable analysis identified age (>80 years), specimen weight (>70 g), en bloc with anteroposterior dissection, and anal tone (Digital Rectal Examination Scoring System score <3) as potential factors influencing UI. Subgroup analysis revealed that specimen weight was associated with both continuous and stress UI. Anal tone was related to both other types and stress UI, while overactive bladder symptoms were associated with urge UI. CONCLUSION: In summary, our study elucidates transient risk factors contributing to temporary post-enucleation UI after prostatectomy. Informed decisions and personalised interventions can effectively alleviate concerns regarding postoperative UI.

Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

Validation of the NULL-EASE Score for Predicting Survival in a Multiethnic Asian Cohort of Out-of-Hospital Cardiac Arrest.

BACKGROUND: NULL-PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out-of-hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL-EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: Using the Singapore OHCA registry, we included consecutive adult patients with out-of-hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In-hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54-75; 67.9% male) included in the study, 2476 (75.6%) had in-hospital mortality. NULL-EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1-4] versus 6 [4-7]; P<0.001) and strongly predictive of mortality (area under receiver operating characteristic, 0.81 [95% CI, 0.79-0.83]). Patients with a score of ≥3 had higher odds of mortality (adjusted odds ratio, 8.11 [95% CI, 6.57-10.00]) when compared with those with lower scores, after adjusting for sex, residential arrest, diabetes, respiratory disease, and stroke. A cutoff value of ≥3 predicted mortality with 92.2% sensitivity, 84.1% positive predictive value, 46.1% specificity, and 65.5% negative predictive value. NULL-EASE score performed better in younger compared with older patients (area under receiver operating characteristic, 0.82 versus 0.77, P=0.008). CONCLUSIONS: The NULL-EASE score has good discriminative performance (sensitivity and accuracy) in our multiethnic Asian cohort, but the cutoff of ≥3 falls short of the desired level of specificity for therapeutic decision-making.

Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Multi-Sensor-Assisted Low-Cost Indoor Non-Visual Semantic Map Construction and Localization for Modern Vehicles.

With the transformation and development of the automotive industry, low-cost and seamless indoor and outdoor positioning has become a research hotspot for modern vehicles equipped with in-vehicle infotainment systems, Internet of Vehicles, or other intelligent systems (such as Telematics Box, Autopilot, etc.). This paper analyzes modern vehicles in different configurations and proposes a low-cost, versatile indoor non-visual semantic mapping and localization solution based on low-cost sensors. Firstly, the sliding window-based semantic landmark detection method is designed to identify non-visual semantic landmarks (e.g., entrance/exit, ramp entrance/exit, road node). Then, we construct an indoor non-visual semantic map that includes the vehicle trajectory waypoints, non-visual semantic landmarks, and Wi-Fi fingerprints of RSS features. Furthermore, to estimate the position of modern vehicles in the constructed semantic maps, we proposed a graph-optimized localization method based on landmark matching that exploits the correlation between non-visual semantic landmarks. Finally, field experiments are conducted in two shopping mall scenes with different underground parking layouts to verify the proposed non-visual semantic mapping and localization method. The results show that the proposed method achieves a high accuracy of 98.1% in non-visual semantic landmark detection and a low localization error of 1.31 m.

Use of fluoroquinolones and the risk of aortic and mitral regurgitation: A nationwide case-crossover study.

BACKGROUND: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals. RESULTS: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48). CONCLUSIONS: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Utilizing Raman spectroscopy for urinalysis to diagnose acute kidney injury stages in cardiac surgery patients.

BACKGROUND: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future. METHODS: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients. RESULTS: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects. CONCLUSIONS: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.

ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

MAS-CL: An End-to-End Multi-Atlas Supervised Contrastive Learning Framework for Brain ROI Segmentation.

Brain region-of-interest (ROI) segmentation with magnetic resonance (MR) images is a basic prerequisite step for brain analysis. The main problem with using deep learning for brain ROI segmentation is the lack of sufficient annotated data. To address this issue, in this paper, we propose a simple multi-atlas supervised contrastive learning framework (MAS-CL) for brain ROI segmentation with MR images in an end-to-end manner. Specifically, our MAS-CL framework mainly consists of two steps, including 1) a multi-atlas supervised contrastive learning method to learn the latent representation using a limited amount of voxel-level labeling brain MR images, and 2) brain ROI segmentation based on the pre-trained backbone using our MSA-CL method. Specifically, different from traditional contrastive learning, in our proposed method, we use multi-atlas supervised information to pre-train the backbone for learning the latent representation of input MR image, i.e., the correlation of each sample pair is defined by using the label maps of input MR image and atlas images. Then, we extend the pre-trained backbone to segment brain ROI with MR images. We perform our proposed MAS-CL framework with five segmentation methods on LONI-LPBA40, IXI, OASIS, ADNI, and CC359 datasets for brain ROI segmentation with MR images. Various experimental results suggested that our proposed MAS-CL framework can significantly improve the segmentation performance on these five datasets.

Inter-reader Agreement for Prostate Cancer Detection Using Micro-ultrasound: A Multi-institutional Study.

Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.

Adaptive spatial-temporal neural network for ADHD identification using functional fMRI.

Computer aided diagnosis methods play an important role in Attention Deficit Hyperactivity Disorder (ADHD) identification. Dynamic functional connectivity (dFC) analysis has been widely used for ADHD diagnosis based on resting-state functional magnetic resonance imaging (rs-fMRI), which can help capture abnormalities of brain activity. However, most existing dFC-based methods only focus on dependencies between two adjacent timestamps, ignoring global dynamic evolution patterns. Furthermore, the majority of these methods fail to adaptively learn dFCs. In this paper, we propose an adaptive spatial-temporal neural network (ASTNet) comprising three modules for ADHD identification based on rs-fMRI time series. Specifically, we first partition rs-fMRI time series into multiple segments using non-overlapping sliding windows. Then, adaptive functional connectivity generation (AFCG) is used to model spatial relationships among regions-of-interest (ROIs) with adaptive dFCs as input. Finally, we employ a temporal dependency mining (TDM) module which combines local and global branches to capture global temporal dependencies from the spatially-dependent pattern sequences. Experimental results on the ADHD-200 dataset demonstrate the superiority of the proposed ASTNet over competing approaches in automated ADHD classification.