Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12 months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35 ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85 mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32 V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

Efficacy and safety of Xileisan combined with mesalazine for ulcerative colitis: A meta-analysis and trial sequential analysis.

BACKGROUND: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear. AIM: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC. METHODS: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively. RESULTS: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema (P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord's test showed no publication bias (P = 0.734). CONCLUSION: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety.

AQUA-GAPS/MONET-Derived Concentrations and Trends of PAHs and Polycyclic Musks across Global Waters.

Polycyclic aromatic hydrocarbons (PAHs), released from petrogenic, pyrogenic or diagenetic sources (degradation of wood materials), are of global concern due to their adverse effects, and potential for long-range transport. While dissolved PAHs have been frequently reported in the literature, there has been no consistent approach of sampling across water bodies. Passive samplers from the AQUA/GAPS-MONET initiative were deployed at 46 sites (28 marine and 18 freshwater), and analyzed for 28 PAHs and six polycyclic musks (PCMs) centrally. Freely dissolved PAH concentrations were dominated by phenanthrene (mean concentration 1500 pg L-1; median 530 pg L-1) and other low molecular weight compounds. Greatest concentrations of phenanthrene, fluoranthene, and pyrene were typically from the same sites, mostly in Europe and North America. Of the PCMs, only galaxolide (72% of samples) and tonalide (61%) were regularly detected, and were significantly cross-correlated. Benchmarking of PAHs relative to penta- and hexachlorobenzene confirmed that the most remote sites (Arctic, Antarctic, and mountain lakes) displayed below average PAH concentrations. Concentrations of 11 of 28 PAHs, galaxolide and tonalide were positively correlated (P < 0.05) with population density within a radius of 5 km of the sampling site. Characteristic PAH ratios gave conflicting results, likely reflecting multiple PAH sources and postemission changes.

Extended nnU-Net for Brain Metastasis Detection and Segmentation in Contrast-Enhanced Magnetic Resonance Imaging With a Large Multi-Institutional Data Set.

PURPOSE: The purpose of this study was to investigate an extended self-adapting nnU-Net framework for detecting and segmenting brain metastases (BM) on magnetic resonance imaging (MRI). METHODS AND MATERIALS: Six different nnU-Net systems with adaptive data sampling, adaptive Dice loss, or different patch/batch sizes were trained and tested for detecting and segmenting intraparenchymal BM with a size ≥2 mm on 3 Dimensional (3D) post-Gd T1-weighted MRI volumes using 2092 patients from 7 institutions (1712, 195, and 185 patients for training, validation, and testing, respectively). Gross tumor volumes of BM delineated by physicians for stereotactic radiosurgery were collected retrospectively and curated at each institute. Additional centralized data curation was carried out to create gross tumor volumes of uncontoured BM by 2 radiologists to improve the accuracy of ground truth. The training data set was augmented with synthetic BMs of 1025 MRI volumes using a 3D generative pipeline. BM detection was evaluated by lesion-level sensitivity and false-positive (FP) rate. BM segmentation was assessed by lesion-level Dice similarity coefficient, 95-percentile Hausdorff distance, and average Hausdorff distance (HD). The performances were assessed across different BM sizes. Additional testing was performed using a second data set of 206 patients. RESULTS: Of the 6 nnU-Net systems, the nnU-Net with adaptive Dice loss achieved the best detection and segmentation performance on the first testing data set. At an FP rate of 0.65 ± 1.17, overall sensitivity was 0.904 for all sizes of BM, 0.966 for BM ≥0.1 cm3, and 0.824 for BM <0.1 cm3. Mean values of Dice similarity coefficient, 95-percentile Hausdorff distance, and average HD of all detected BMs were 0.758, 1.45, and 0.23 mm, respectively. Performances on the second testing data set achieved a sensitivity of 0.907 at an FP rate of 0.57 ± 0.85 for all BM sizes, and an average HD of 0.33 mm for all detected BM. CONCLUSIONS: Our proposed extension of the self-configuring nnU-Net framework substantially improved small BM detection sensitivity while maintaining a controlled FP rate. Clinical utility of the extended nnU-Net model for assisting early BM detection and stereotactic radiosurgery planning will be investigated.

Adaptive Escape of Pseudomonas aeruginosa by Application of Low-Amplitude Electric Pulses.

Marine antibiofouling using low-amplitude electric pulses (EP) is an energy-efficient and eco-friendly approach, but potential mechanisms for preventing biofouling remain unclear. In the present study, the 3D adhesion dynamics of a model microorganism─Pseudomonas aeruginosa (PAO1)─under low-amplitude cathodic EP were examined as a function of applying voltage and its duration (td). The results demonstrated that adhered bacteria escaped from the electrode surface even when EP was removed. The escaped bacteria ratio, induction period of escape, and duration of the detachment were influenced profoundly by EP amplitude but slightly by td when td ≥ 5 min. The acceleration of escaped PAO1 from the surface indicated that their flagellar motor was powered by EP. Particularly, EP enabled swimming bacteria to have adaptive motions that were sustainable and regulated by the gene rsmA. As a result, they had less accumulation near the surface. The propulsion of adhered bacteria and adaptive escape of swimming bacteria were enhanced in response to low-amplitude EP. Hence, low-amplitude and short-duration EP is promising for sustainable antibiofouling applications.

Effects of polymer matrix and temperature on pyrolysis of tetrabromobisphenol A: Product profiles and transformation pathways.

Plastics are crucial constituents in electronic waste (e-waste) and part of the issue in e-waste recycling and environmental protection. However, previous studies have mostly focused on plastic recovery or thermal behavior of flame retardants, but not both simultaneously. The present study simulated the process of e-waste thermal treatment to explore tetrabromobisphenol A (TBBPA) pyrolysis at various temperatures using polystyrene (PS), polyvinyl chloride (PVC), and e-waste plastics as polymer matrices. Pyrolysis of TBBPA produced bromophenol, bromoacetophenone, bromobenzaldehyde, and bromobisphenol A. Co-pyrolysis with the polymer matrices increased emission factors by 1 - 2 orders of magnitude. The pyrolytic products of TBBPA, TBBPA+PS, and TBBPA+PVC were mainly low-brominated bisphenol A, while that of TBBPA in e-waste plastics was consistently bromophenol. Increasing temperature drove up the proportions of gaseous and particulate products, but lowered the relative abundances of inner wall adsorbed and residual products in pyrolysis of pure TBBPA. In co-pyrolysis of TBBPA with polymer matrix, the proportions of products in different phases were no longer governed solely by temperature, but also by polymer matrix. Co-pyrolysis of TBBPA with PS generated various bromophenols, while that with PVC produced chlorophenols and chlorobrominated bisphenol A. Transformation pathways, deduced by ab initio calculations, include hydrogenation-debromination, isopropylphenyl bond cleavage, oxidation, and chlorination.

The role of pericyte in ocular vascular diseases.

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning.

AIMS: Atrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co-existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies. METHODS AND RESULTS: The training set and validation set data of AF and HF patient samples were downloaded from the GEO database, 'limma' was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) identified the modules with the highest positive correlation with AF and HF. Functional enrichment and PPI network construction of key genes were carried out. Biomarkers were screened by machine learning. The infiltration of immune cells in AF and HF groups was evaluated by R-packet 'CIBERSORT'. The miRNA network was constructed and potential therapeutic agents for biomarker genes were predicted through the drugbank database. Through WGCNA analysis, it was found that the modules most positively correlated with AF and HF were MEturquoise (r = 0.21, P value = 0.09) and MEbrown (r = 0.62, P value = 8e-12), respectively. We screened 25 genes that were highly correlated with both AF and HF. Lasso regression analysis results showed 7 and 20 core genes in AF and HF groups, respectively. The top 20 important genes in AF and HF groups were obtained as core genes by RF model analysis. Four biomarkers were obtained after the intersection of core genes in four groups, namely, GLUL, NCF2, S100A12, and SRGN. The diagnostic efficacy of four genes in AF validation sets was good (AUC: GLUL 0.76, NCF2 0.64, S100A12 0.68, and SRGN 0.76), as well as in the HF validation set (AUC: GLUL 0.76, NCF2 0.84, S100A12 0.92, and SRGN 0.68). The highest correlation with neutrophils was observed for GLUL, NCF2, and S100A12, while SRGN exhibited the strongest correlation with T cells CD4 memory resting in the AF group. GLUL, NCF2, S100A12, and SRGN were most associated with neutrophils in the HF group. A total of 101 miRNAs were predicted by four genes, and GLUL, NCF2, and S100A12 predicted a total of 10 potential therapeutic agents. CONCLUSIONS: We identified four biological markers that are highly correlated with AF and HF, namely, GLUL, NCF2, S100A12, and SRGN. Our findings provide theoretical basis for the clinical diagnosis and treatment of AF and HF.

Occurrence, Spatial Distribution, and Bioaccumulation of Dissolved Synthetic Musks in Freshwaters across China.

Commercial chemicals, such as synthetic musks, are of global concern, but data on their occurrence and spatial distribution in aquatic environments of large scale are scarce. Two sampling campaigns were conducted in the present study to measure freely dissolved synthetic musks in freshwaters across China using passive samplers, along with biological coexposure at selected sites. Polycyclic musks (PCMs) dominated synthetic musks, with a detection frequency of 95%. Higher concentrations of PCMs were observed in densely populated Mid, East, and South China compared to less populated regions, indicating the significance of anthropogenic activities for synthetic musks in water. The concentration ratios of galaxolide (HHCB)/tonalide (AHTN) were significantly higher in low-latitude areas than in high-latitude areas from June to September, suggesting that solar radiation played an important role in the degradation of HHCB/AHTN. Significant correlations were found between dissolved concentrations of HHCB and AHTN and their lipid-normalized concentrations in coexposed fish and clam. The estimated hazard quotients for HHCB and AHTN in freshwater fish consumed by humans were less than 0.01 at all sampling sites except the Yangtze River Basin. These results help to understand the environmental fate and ecological risks of synthetic musks on a large geographical scale.

Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Use of machine learning to identify key factors regulating volatilization of semi-volatile organic chemicals from soil to air.

Volatilization from soil to air is a key process driving the distribution and fate of semi-volatile organic contaminants. However, quantifying this process and the key environmental governing factors remains difficult. To address this issue, the volatilization fluxes of polybrominated diphenyl ethers (PBDEs) and organophosphate esters (OPEs) from soil were determined in 16 batch experiments orthogonally with six variables (chemical property, soil concentration, air velocity, ambient temperature, soil porosity, and soil moisture) and analyzed with machine learning methods. The results showed that gradient-boosting regression tree models satisfactorily predicted the volatilization fluxes of PBDEs (r2 = 0.82 ± 0.07) and OPEs (r2 = 0.62 ± 0.13). Permutation importance analysis showed that partitioning potential of chemicals between soil and air was the most important factor regulating the volatilization of the target compounds from soil. Temperature and soil porosity played a secondary role in controlling the migration of PBDEs and OPEs, respectively, due to higher volatilization enthalpies of PBDEs than those of OPEs and dominant adsorption of OPEs on mineral surface. The effect of soil moisture was negative and positive for the volatilization fluxes of PBDEs and OPEs, respectively. These results suggested different responses in the soil-air diffusive transport of PBDEs and OPEs to high temperature and rainstorm induced by climate change.

Thromboembolic phenomena in patients with nephrotic syndrome: pathophysiology, risk factors, prophylaxis and treatment.

Thromboembolic events resulting from disturbances in the body's balance of thrombotic and antithrombotic abilities are among the most life-threatening complications of nephrotic syndrome. Certain causes of nephrotic syndrome leave the patient particularly susceptible to thromboembolism. The severity of proteinuria and degree of hypoalbuminaemia are other common predictors of risk. Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with this complication in patients with nephrotic syndrome. The duration of treatment and choice of therapeutic agent depends on several factors, including the degree of hypoalbuminaemia, risk factors for thrombosis and risk of bleeding. This article reviews current understanding of the pathophysiology and risk factors for thromboembolism associated with nephrotic syndrome, and summarises recommendations and strategies for preventing and treating thromboembolic events in patients with nephrotic syndrome.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

BACKGROUND: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. METHODS: qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. RESULTS: The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. CONCLUSIONS: The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence.

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Long duration of atrial high-rate episode is more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score.

OBJECTIVE: This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation. METHODS: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA2 DS2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted. RESULTS: A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA2 DS2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927). CONCLUSION: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score (≥2).

Conduction system pacing for ventricular pacing requirement is feasible and effective on patients with hypertrophic cardiomyopathy and cardiac dysfunction.

Objective: We aimed to evaluate the feasibility and safety of his-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with hypertrophic cardiomyopathy (HCM) and heart failure (HF). Methods: Patients with HF and interventricular septal thickness (IVST) ≥ 13 mm resulted from HCM, who accepted conduction system pacing (CSP) with a percentage of ventricular pacing > 40% from May 2018 to April 2022 were consecutively enrolled in our center. LBBP was preferred and HBP was the alternative therapy unless IVST ≥ 16 mm or LBBP failed, whereas LBBP would be the alternative therapy if HBP failed in patients with IVST ≥ 16 mm. All patients were followed up for at least one year. Data including clinical, echocardiographic parameters and electrocardiogram measurements, were collected and evaluated in patients with and without left ventricular ejection fraction (LVEF) < 50%. Results: A total of 27 patients (65.93 ± 9.09 years old) were enrolled and only 3 patients failed in CSP (11.11%) via LBBP (6/13) and HBP (18/21) procedures. LVEF (P = 0.521), left ventricular end-diastolic diameter (LVEDD) (P = 0.816), and QRS duration (P = 0.928) did not worsen after CSP, and left atrial diameter (LAD) (49.58 ± 8.99 mm vs.47.04 ± 9.82 mm, P = 0.045) tended to improve slightly after 19.19 ± 7.71 months follow-up. Of note, LVEF (39.22%±7.51% vs. 45.22%±9.59%, P = 0.015), LVEDD (52.11 ± 10.10 mm vs. 48.33 ± 9.07 mm, P = 0.037), LAD (50.33 ± 8.93 mm vs. 46.11 ± 5.97 mm, P = 0.013) and New York Heart Association (NYHA) grade (2.67 ± 0.5 vs. 1.38 ± 1.02, P = 0.029) improved in 9 patients with LVEF < 50%, whereas LVEF (P = 0.372), LVEDD (P = 0.665), LAD (P = 0.093) and NYHA grade (P = 0.452) did not deteriorate in patients with preserved ejection fraction. Conclusion: CSP was safe and feasible in patients with HCM and cardiac dysfunction, and did not worsen cardiac performance especially in patients with LVEF < 50%. HBP might be an effective alternative to LBBP in patients with significantly thickened interventricular septum.

Fluorescent Visualization of Chemical Profiles across the Air-Water Interface.

Chemical transfer across the air-water interface is one of the most important geochemical processes of global significance. Quantifying such a process has remained extremely challenging due to the lack of suitable technologies to measure chemical diffusion across the air-water microlayer. Herein, we present a fluorescence optical system capable of visualizing the formation of the air-water microlayer with a spatial resolution of 10 µm and quantifying air-water diffusion fluxes using pyrene as a target chemical. We show for the first time that the air-water microlayer is composed of the surface microlayer in water (∼290 ± 40 µm) and a diffusion layer in air (∼350 ± 40 µm) with 1 µg L-1 of pyrene. The diffusion flux of pyrene across the air-water interface is derived from its high-resolution concentration profile without any pre-emptive assumption, which is 2 orders of magnitude lower than those from the conventional method. This system can be expanded to visualize diffusion dynamics of other fluorescent chemicals across the air-water interface and provides a powerful tool for furthering our understanding of air-water mass transfer of organic chemicals related to their global cycling.

Organ-aware CBCT enhancement via dual path learning for prostate cancer treatment.

BACKGROUND: Cone-beam computed tomography (CBCT) plays a crucial role in the intensity modulated radiotherapy (IMRT) of prostate cancer. However, poor image contrast and fuzzy organ boundaries pose challenges to precise targeting for dose delivery and plan reoptimization for adaptive therapy. PURPOSE: In this work, we aim to enhance pelvic CBCT images by translating them to high-quality CT images with a particular focus on the anatomical structures important for radiotherapy. METHODS: We develop a novel dual-path learning framework, covering both global and local information, for organ-aware enhancement of the prostate, bladder and rectum. The global path learns coarse inter-modality translation at the image level. The local path learns organ-aware translation at the regional level. This dual-path learning architecture can serve as a plug-and-play module adaptable to other medical image-to-image translation frameworks. RESULTS: We evaluated the performance of the proposed method both quantitatively and qualitatively. The training dataset consists of unpaired 40 CBCT and 40 CT scans, the validation dataset consists of 5 paired CBCT-CT scans, and the testing dataset consists of 10 paired CBCT-CT scans. The peak signal-to-noise ratio (PSNR) between enhanced CBCT and reference CT images is 27.22 ± 1.79, and the structural similarity (SSIM) between enhanced CBCT and the reference CT images is 0.71 ± 0.03. We also compared our method with state-of-the-art image-to-image translation methods, where our method achieves the best performance. Moreover, the statistical analysis confirms that the improvements achieved by our method are statistically significant. CONCLUSIONS: The proposed method demonstrates its superiority in enhancing pelvic CBCT images, especially at the organ level, compared to relevant methods.