Ferumoxytol-Enhanced 5D Multiphase Steady-State Imaging Using Rotating Cartesian K-Space With Low-Rank Reconstruction for Pediatric Congenital Heart Disease.

BACKGROUND: The rotating Cartesian k-space multiphase steady-state imaging with contrast (ROCK-MUSIC) pulse sequence enables acquisition of whole-heart, cardiac phase-resolved images in pediatric congenital heart disease (CHD) without reliance on the ventilator gating signal. Multidimensional reconstruction with low rank tensor (LRT) has shown promise for resolving complex cardiorespiratory motion. PURPOSE: To enhance ROCK-MUSIC by resolving cardiorespiratory phases using LRT reconstruction and to enable semi-automatic hyperparameter tuning by developing an image quality scoring model. STUDY TYPE: Retrospective. POPULATION: Thirty patients (45% female, age 2 days to 6.7 years) with CHD. FIELD STRENGTH/SEQUENCE: 3-T, four-dimensional (4D) spoiled gradient recalled echo sequence. ASSESSMENT: Eigenvector-based iTerative Self-consistent Parallel Imaging Reconstruction (ESPIRiT) served as the reference comparison for LRT reconstruction. A 4-point Likert scale was used for cardiac and vascular image quality scoring based on cardiac chamber definition, lumen signal uniformity, vascular margin clarity, and motion artifact. Ejection fraction and ventricular volumes were assessed in 16 patients. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and edge sharpness were computed. STATISTICAL TESTS: Intraclass correlation coefficients, Wilcoxon signed-rank test, Bland-Altman. A P-value <0.05 was considered statistically significant. RESULTS: Relative to ESPIRiT, LRT images received significantly higher cardiac (2.81 ± 0.57 vs. 3.19 ± 0.54) and vascular (2.81 ± 0.60 vs. 3.36 ± 0.53) image quality scores. Image quality scoring with semi-automated hyperparameter tuning showed strong correlations (R2 = 0.748) among image quality, SNR, and septal sharpness. Comparison of ejection fraction and volumetry derived from ESPIRiT, and LRT showed no significant systematic difference (P = 0.32). DATA CONCLUSION: Integration of low-rank reconstruction with ROCK-MUSIC acquisition may be feasible, and semi-automatic hyperparameter tuning could be effective for generating cardiorespiratory resolved images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Clinicopathological features and prognosis analysis of proximal colonic mucinous adenocarcinoma.

Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer. Previous studies have confirmed the poor prognosis of rectal or left-sided colon MAC, while the prognosis and response to chemotherapy in proximal colon MAC remains controversial. The aim of this study was to investigate the clinicopathological characteristics, prognosis, response to chemotherapy, and risk prediction factors of proximal colon MAC. Patients with proximal colon MAC and non-mucinous adenocarcinoma (NMAC) were retrospectively analyzed in this study. The analyzed variables included gender, age, smoking, drinking, chemotherapy, metastasis, pathological stage, and tumor size. Overall survival (OS) was the primary outcome. Kaplan-Meier analysis was used to assess the impact of mucinous subtype and chemotherapy on OS. We conducted univariate and multivariate Cox regression analyses to determine prognosis factors for proximal colon MAC and NMAC. A total of 284 cases of proximal colon MAC and 1384 cases of NMAC were included in the study. Compared to NMAC, proximal colon MAC was diagnosed at a younger age. The proportion of synchronous and metachronous metastasis was also higher, as well as the pathological stage and tumor size. Proximal colon MAC had a worse prognosis than NMAC, especially in stage 3. Moreover, the prognosis of proximal colon NMAC improved after chemotherapy, while MAC showed no improvement in prognosis after chemotherapy. Advanced age, N1 and N2 stage were independent prognostic factors for adverse outcomes in MAC. For proximal colon adenocarcinoma, the independent predictors of adverse outcomes included mucinous subtype, order age, N1 and N2 stages, and pathological stage 4. Proximal colon MAC had a worse prognosis compared to NMAC. Chemotherapy did not improve the prognosis of proximal colon mucinous adenocarcinoma.

Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients.

Age-associated deterioration of physiological functions occur at heterogeneous rates across individual organs. A granular evaluation of systemic metabolic mediators of aging in a healthy human cohort (n = 225) identified prominent increases in circulating uremic toxins that were recapitulated in mice, on which we further characterized the aging phenome across five peripheral organs. Our multi-omics analyses connected systemic aging profiles primarily to kidney metabolism, uncovering a metabolic association between localized glucosylceramide (GluCer) accretion and renal functional decline. Elevated GluCers were also associated with higher risk of deaths in an independent cohort of aged individuals (n = 271). We report GluCer-mTOR signaling commencing at late middle-age that disrupts mitophagy and undermines mitochondrial respiration in kidney. Conserved between human and mice, GluCer-mediated renal dysfunction is female-biased and modulated by intracellular purines. Our work provides molecular basis for the sexually disparate effects of mTOR inhibition on mammalian lifespan, possibly ascribed to the evolutionary cost of female reproduction.

A modified open surgical revision technique for malfunctioning peritoneal dialysis catheter.

Backgrounds: The malfunction of peritoneal dialysis (PD) catheter is still an intractable problem. A modified open surgical revision technique with suturing fixation and without catheter removal for malfunctioning catheter was developed to evaluated the efficacy and safety between simultaneous catheter replacement technique.Methods: A total of 167 PD patients with malfunctioning catheter were retrospectively reviewed. For the salvage of PD catheters, patients underwent modified open surgical revision (group A) or simultaneous catheter replacement (group B). The baseline characteristics before operation, perioperative condition, complications and outcomes were compared between both groups.Results: Patients of group A showed significantly shorter operative time (67.4 ± 22.1 versus 82.8 ± 21.1 min, p = 0.009), less postoperative pain score within 24 h (median 0.0 versus 2.0, p < 0.001), quicker start of PD (1.06 ± 0.31 versus 1.89 ± 0.89 days, p < 0.001), shorter length of stay (9.89 ± 5.11 versus 12.55 ± 7.37 days, p = 0.020) than group B. In terms of complications, the incidence of recurred catheter malfunction in group A was significantly lower than those in group B (1/114 versus 12/53, p < 0.001). There were no significant differences in mechanical complications (bloody effluent, dialysate leakage, and hernia) and early peritonitis between the groups. The group A patients had a favorable catheter survival rate compared with group B (log-rank, p = 0.004).Conclusions: Our modified open surgical revision technique is a safe, simple and fast method, and offers a better outcome with minimal risk of recurrence of catheter malfunction without additional cost and equipment. This technique is worthy of clinical application.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.

Anaerobic degradation of pesticide wastewater: Improving sludge characteristics and reducing membrane fouling with combined tandem UASB+membrane system with high velocity settlers.

In this pilot study, a combined tandem UASB+membrane reactor (R2) with high velocity settlers was proposed for the treatment of pesticide wastewater at different hydraulic retention times (HRT) and compared with a control reactor (R1). The average COD removal efficiencies of the R2 at HRTs of 96, 72, and 48 h were 83.7 %, 82.8 %, and 74.2 %, which are 14 %, 17 %, and 21 % higher than those of the R1, respectively. Throughout the operation, the biogas production of R2 was 33 %, 19 % and 28 % higher than that of R1 at the same stage, respectively, and the methane yield of R2 (0.19-0.26 L CH4/gCODremoved) was improved by 10-17 % compared to that of R1. Mean α values (VFA/ALK) of 0.13∼0.22 indicated that R2 did not undergo acidification. R2 reduced the extracellular polymers (EPS) content in the attached sludge by 56-62 % compared to R1. It also successfully delayed membrane fouling rate by 19-22 %. The results demonstrate that the R2 has a high treatment capacity, stability, and methane recovery, while also effectively reducing membrane fouling.

Behind the Curtain: Comparing Predictive Models Performance in 2 Publicly Insured Populations.

INTRODUCTION: Predictive models have proliferated in the health system in recent years and have been used to predict both health services utilization and medical outcomes. Less is known, however, on how these models function and how they might adapt to different contexts. The purpose of the current study is to shed light on the inner workings of a large-scale predictive model deployed in 2 distinct populations, with a particular emphasis on adaptability issues. METHODS: We compared the performance and functioning of a predictive model of avoidable hospitalization in 2 very different populations: Medicaid and Medicare enrollees in Maryland. Specifically, we assessed characteristics of the risk scores from March 2022 for the 2 populations, the predictive ability of the scores, and the driving risk factors behind the scores. In addition, we created and assessed the performance of an "unadapted" model by applying coefficients from the Medicare model to the Medicaid population. RESULTS: The model adapted to, and performed well in, both populations, despite demographic differences in these 2 groups. However, the most salient risk factors and their relative weightings differed, sometimes dramatically, across the 2 populations. The unadapted Medicaid model displayed poor performance relative to the adapted model. CONCLUSIONS: Our findings speak to the need to "peek behind the curtain" of predictive models that may be applied to different populations, and we caution that risk prediction is not "one size fits all": for optimal performance, models should be adapted to, and trained on, the target population.

Suboptimal reporting of randomized controlled trials on non-pharmacological therapies in Chinese medicine.

With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.

Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series.

Rationale & Objective: Membranous nephropathy (MN), recognized as an autoimmune kidney disease, responds well to anti-CD20 monoclonal antibodies. Obinutuzumab, a type Ⅱ humanized anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody, when compared with rituximab, has demonstrated superior efficacy in B-cell leukemia and lymphoma, especially in rituximab-resistant cases. However, the efficacy and safety of obinutuzumab in MN remain unclear. Study Design: A case series study. Setting & Participants: A total of 18 patients were diagnosed with MN and had received obinutuzumab at our center without secondary MN, undergoing dialysis, having a history of kidney transplantation, or infections requiring treatment. Exposure: Obinutuzumab treatment. Outcomes: Primary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period. Analytical Approach: Survival analysis was performed with Cox proportional hazards models, log-rank test, and Kaplan-Meier survival analysis. Results: Patients with MN (median age of 52.5 years, 83.3% males) received an average dose of 2.1 ± 0.8 g of obinutuzumab during a median follow-up period of 13.6 months. During the follow-up, 17 patients (94.4%) achieved remission, with 12 patients (66.7%) achieving partial remission, and 5 patients (27.8%) achieving complete remission. The median time to first remission and first relapse-free survival time was 2.7 (1.0-6.1) months and 9.8 (2.6-11.2) months, respectively. Of 12 patients with previous rituximab treatment, all achieved remission successfully, with 8 (66.7%) achieving partial remission and 4 (33.3%) achieving complete remission. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Limitations: Limited or missing data; risks of selection bias; or recall bias; underestimated first relapse-free survival time because of a limited follow-up period; unmonitored counts of CD19+ B-cells and other lymphocyte subsets. Conclusions: Obinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.

Membranous nephropathy (MN), an autoimmune kidney disease, usually responds favorably to rituximab, a chimeric anti-CD20 monoclonal antibody. Nevertheless, certain patients exhibit inadequate responses to rituximab. Obinutuzumab, a novel humanized anti-CD20 monoclonal antibody, has shown enhanced efficacy in cases where rituximab fails to address B-cell leukemias and lymphomas. However, its efficacy and safety in MN treatment remain uncertain. A case series involving 18 patients treated with obinutuzumab at our center demonstrated promising results, suggesting favorable efficacy and safety in inducing and maintaining remission, particularly among patients who did not respond well to rituximab previously. These findings signify a potential alternative for MN treatment, though further research is needed to confirm them.

Effect of different sedatives on the prognosis of patients with mechanical ventilation: a retrospective cohort study based on MIMIC-IV database.

Aim: To compare the effects of midazolam, propofol, and dexmedetomidine monotherapy and combination therapy on the prognosis of intensive care unit (ICU) patients receiving continuous mechanical ventilation (MV). Methods: 11,491 participants from the Medical Information Mart for Intensive Care (MIMIC)-IV database 2008-2019 was included in this retrospective cohort study. The primary outcome was defined as incidence of ventilator-associated pneumonia (VAP), in-hospital mortality, and duration of MV. Univariate and multivariate logistic regression analyses were utilized to evaluate the association between sedation and the incidence of VAP. Univariate and multivariate Cox analyses were performed to investigate the correlation between sedative therapy and in-hospital mortality. Additionally, univariate and multivariate linear analyses were conducted to explore the relationship between sedation and duration of MV. Results: Compared to patients not receiving these medications, propofol alone, dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine were all association with an increased risk of VAP; dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine may be protective factor for in-hospital mortality, while propofol alone was risk factor. There was a positive correlation between all types of tranquilizers and the duration of MV. Taking dexmedetomidine alone as the reference, all other drug groups were found to be associated with an increased risk of in-hospital mortality. The administration of propofol alone, in combination with midazolam and dexmedetomidine, in combination with propofol and dexmedetomidine, in combination with midazolam, propofol and dexmedetomidine were associated with an increased risk of VAP compared to the use of dexmedetomidine alone. Conclusion: Dexmedetomidine alone may present as a favorable prognostic option for ICU patients with mechanical ventilation MV.

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications.

Objective: This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications. Methods: Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators. Results: Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-ß exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15). Conclusion: The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.

Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

Corrigendum: Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

[This corrects the article DOI: 10.3389/fimmu.2024.1302903.].

SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury.

Acute kidney injury (AKI) signifies a sudden and prolonged decline in kidney function characterized by tubular cell death and interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles in oxidative stress and inflammation, and may play an important role in the AKI process, which remains elusive. an elevated expression of Snord3a is revealed in renal tubules in response to AKI and demonstrates that Snord3a deficiency alleviates renal injury in AKI mouse models. Notably, the deficiency of Snord3a exhibits a mitigating effect on the stimulator of interferon genes (STING)-associated ferroptosis phenotypes and the progression of tubular injury. Mechanistically, Snord3a is shown to regulate the STING signaling axis via promoting STING gene transcription; administration of Snord3a antisense oligonucleotides establishes a significant therapeutic advantage in AKI mouse models. Together, the findings elucidate the transcription regulation mechanism of STING and the crucial roles of the Snord3a-STING axis in ferroptosis during AKI, underscoring Snord3a as a potential prognostic and therapeutic target for AKI.

Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

GAS6-AS1 drives bladder cancer progression by increasing MMP7 expression in a ceRNA- and RBP-dependent manner.

Numerous recent studies have underscored the indispensable roles of long non-coding RNAs (lncRNAs) in various diseases. However, their precise mechanisms in urinary bladder cancer (UBC) remain to be further elucidated. To delve into this inquiry, online databases were analyzed to identify differentially expressed lncRNAs in UBC, followed by the functional experiments in vivo and in vitro functional experiments. GAS6-AS1 exhibited high expression levels in UBC tissues and was shown to regulate the proliferation, migration, invasion, and cell cycle progression of UBC cells in vitro and in vivo. Then, a series of molecular biology experiments, including RNA pull-down, dual-luciferase reporter gene assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH), and the triplex-capture assay demonstrated its interaction with miR-367-3p and PRC1. Mechanistically, GAS6-AS1 was found to enhance MMP7 expression by sequestering miR-367-3p. Moreover, GAS6-AS1 inhibited APC transcription by binding with PRC1, thereby activating several oncogenes downstream of the WNT pathway. To sum up, GAS6-AS1 promotes UBC progression through two distinct axes: the GAS6-AS1/miR-367-3p/MMP7 axis and the GAS6-AS1/PRC1/APC/Wnt/MMP7 axis, respectively. As a potential biomarker for UBC, GAS6-AS1 holds promising prospects for the diagnosis, treatment, and prognosis of UBC.

Plastic debris mediates bacterial community coalescence by breaking dispersal limitation in the sediments of a large river.

Plastic debris has recently been proposed as a novel habitat for bacterial colonization, which can raise perturbations in bacterial ecology after burial in riverine sediments. However, community coalescence, as a prevalent process involving the interrelationships of multiple communities and their surrounding environments, has been rarely discussed to reveal the impact of the plastisphere on sedimentary bacterial community. This study analyzed the bacterial community in plastic debris and sediment along the Nujiang River, elucidating the role of the plastisphere in mediating community coalescence in sediments. Our results demonstrated that the plastisphere and sedimentary bacterial communities exhibited distinct biogeography along the river (r = 0.694, p < 0.01). Based on overlapped taxa and SourceTracker, the extent of coalescence between adjacent communities was in following orders: plastic-plastic (0.589) > plastic-sediment (0.561) > sediment-sediment (0.496), indicating the plastisphere promoted bacterial community coalescence along the river. Flow velocity and geographic distance were the major factors driving the plastisphere changes, suggesting that the plastisphere were vulnerable to dispersal. The null model and the neutral model provided additional support for the higher immigration ability of the plastisphere to overcome dispersal limitation, highlighting the potential importance of the plastisphere in community coalescence. Network analysis indicated the critical role of keystone species (Proteobacteria, Bacteroidetes, and Gemmatimonadetes) in mediating the coalescence between sedimentary bacterial community and the plastisphere. In summary, the plastisphere could mediate the coalescence of bacterial communities by overcoming dispersal limitation, which provides new perspectives on the plastisphere altering bacterial ecology in riverine sediments.