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Some adult diseases such as hypertension and kidney disease may have their origins in early life, due to exposure to different adverse stressors. Previously we demonstrated that the administration of a dual endothelin receptor antagonist (ERA) to Sprague-Dawley (SD) rats from day 1-21 of life decreased glomerular number, predisposing adult male rats to salt sensitivity. This new study explores some early molecular mechanisms underlying the alterations observed in the kidneys of ERA-treated rats during the postnatal period, evaluating sex differences. Newborn male and female SD rats were treated with a dual ERA from day 1-6 and then sacrificed on day 7 of life to obtain the kidneys for the preparation of homogenates and mitochondrial fractions to assess: renal cell proliferation and apoptosis, nitric oxide synthases (Nos), neuronal isoform (Nos1) and endothelial isoform (Nos3) mRNA expression, NADPH- diaphorase (NADPH-d) activity, oxidative stress markers and antioxidant enzymes. ERA-treated male rats showed increased thiobarbituric acid-reacting substances (TBARS) and decreased nitric oxide (NO) to superoxide anion (O2-) ratio, with lower NADPH-d activity in the structures that give rise to glomeruli. Sex differences were observed in Nos1 and Nos3 mRNA expression, H2O2 production, and catalase activity, being females more protected than males. The alterations observed in the kidneys of ERA-treated rats during the early postnatal period could be due to a renal imbalance between NO and ROS, with increased oxidative stress, and a misbalance between proliferation and apoptosis. Our current findings show some molecular mechanisms underlying Endothelin inhibition in the early postnatal period, with potential utility for designing reprogramming strategies.

Peritonitis is a serious complication of peritoneal dialysis (PD). Inflammatory indices derived from routine complete blood count (CBC) parameters-including the pan-immune inflammatory value (PIV), systemic immune-inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-monocyte ratio (PMR)-have shown prognostic value in various diseases. However, their comparative utility in predicting PD-associated peritonitis (PDAP) remains unclear. This multicenter cohort study aimed to evaluate and compare these indices to identify the best predictor of PDAP. We retrospectively enrolled 2,036 PD patients from 10 centers. The associations between inflammatory markers (PIV, SII, PLR, NLR, MLR, PMR) and peritonitis risk were analyzed using restricted cubic splines. Optimal cut-offs were determined by ROC analysis. Survival differences were assessed using Kaplan-Meier curves and log-rank tests. Independent predictors were identified via multivariate Cox regression, with model discrimination evaluated by the C-index. Subgroup analyses were conducted by gender, age, body mass index (BMI), diabetes, albumin, PD vintage, and residual renal function. The median age was 51.0 years, 55.01% were male, and median dialysis vintage was 49.47 months. Diabetes prevalence was 21.02%. Over the follow-up, 147 patients (7.22%) developed peritonitis. Among the indices evaluated, PIV, SII, and PLR showed significant nonlinear associations with peritonitis risk (all P&#x2009;<&#x2009;0.05). Adjusted hazard ratios were 2.004 for PIV, 2.144 for SII, and 2.063 for PLR. Adjusted C-indices were 0.67 (PIV), 0.70 (SII), and 0.70 (PLR). No significant interactions were found in subgroup analyses. Elevated PIV, SII, and PLR levels at PD initiation independently predict higher peritonitis risk. Although their discriminative ability is moderate, these routine, cost-effective indices may aid risk stratification and help identify patients needing closer monitoring or preventive interventions.

This study introduces G-I-nonexpansive mapping by combining I-nonexpansive mapping with a directed graph. It also establishes convergence results for a two-step Ishikawa-type iteration. Numerical experiments were conducted on benchmark image deblurring problems, in which images were degraded by motion blur and additive Gaussian noise. The proposed method achieves competitive restoration performance, with peak signal-to-noise ratio values of up to 24.51 dB. It outperforms classical approaches such as Wiener filtering, Lucy-Richardson and the Fast Iterative Shrinkage-Thresholding Algorithm while remaining comparable to Total variation (TV)-based methods. The method reliably enhances signals in 1D, achieving a peak signal-to-noise ratio of 29.73 dB and high structural similarity index measure values. These results suggest that the framework is an effective tool for restoring signals and images degraded by blur and noise.

Some drinking water contaminants, including disinfection byproducts, are known or suspected carcinogens with endocrine-disrupting properties. Few epidemiologic studies have evaluated associations with uterine cancer. To investigate prospective associations between multiple regulated contaminants in drinking water and the risk of uterine cancer. The California Teachers Study is a prospective cohort of female California educators. Participants who were cancer-free and had not undergone hysterectomy at enrollment (1995-1996) were followed up through December 31, 2020. Data were analyzed from November 2024 to October 2025. The 15-year mean concentrations (1990-2005) of individual and total trihalomethanes (THMs) and haloacetic acids (HAAs), nitrate, arsenic, and uranium were calculated. The mixture effects of individual THMs, arsenic, uranium, and nitrate were also evaluated using quantile-based g-computation. Associations with incident uterine cancer overall, endometrioid tumors, and nonendometrioid tumors were analyzed categorically by tertile and continuously per log2 increase in water contaminant exposures, using Cox models adjusted for age, body mass index, and smoking status. This study included 53&#x202f;100 women (median [IQR] age, 50 [43-60] years) with enrollment addresses linked to a community water supply among women with residential duration at enrollment of 10 years or more. Higher levels of total THMs were associated with a higher risk of uterine cancer (hazard ratio [HR], 1.18 [95% CI, 1.02-1.38]; P for trend&#x2009;=&#x2009;.06) and endometrioid tumors specifically (HR, 1.23 [95% CI, 1.05-1.46]; P for trend&#x2009;=&#x2009;.01). Positive associations were found for the individual THM chloroform. Higher levels of the sum of 5 HAAs were associated with nonendometrioid tumors (HR, 1.86 [95% CI, 1.06-3.25]; P for trend&#x2009;=&#x2009;.01), with similar associations for the HAA monochloroacetic acid. No associations were observed with nitrate, arsenic, or uranium levels. Associations per IQR increase in the drinking water contaminant mixture composed of individual THMs, nitrate, arsenic, and uranium were 1.21 (95% CI, 0.96-1.53) and 1.34 (95% CI, 1.04-1.74) for uterine and endometrioid histotypes, respectively. The THMs chloroform and dibromochloromethane were the major contributors. In this cohort study of female California educators, associations between drinking water THMs and uterine cancer overall and with endometrioid tumors specifically were consistent with findings from the only prior study, conducted in the midwestern US. Further investigation of drinking water contaminants as modifiable risk factors for this common gynecologic cancer is warranted.

The metabolic consequences of extreme temperature exposure in nondiabetic populations remain poorly understood. This study aimed to examine associations between heatwave and coldwave exposure and incident diabetes mellitus (DM) and impaired glucose tolerance (IGT) in middle-aged and older Chinese adults. A total of 1803 China Health and Retirement Longitudinal Study participants aged &#x2265;45 years with normoglycemia at baseline were followed from Wave 1 (2011) to Wave 3 (2015). Eighteen extreme-temperature indicators were derived from city-level fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis data. Outcomes were classified according to American Diabetes Association criteria. Generalized linear mixed-effects models (GLMMs) were pooled across five imputed datasets, with Bonferroni correction for multiple comparisons (&#x3b1; = 0.0028) and sensitivity analysis adjusting for individual follow-up duration. All nine heatwave indicators showed odds ratios (ORs) < 1.0 for DM and IGT. HT9 (&#x2265;97.5th percentile, &#x2265;4 consecutive days) was the sole Bonferroni-significant result: OR = 0.845 (95% confidence interval [CI]: 0.802-0.890). Coldwave indicators showed no consistent associations. Age significantly modified the HT9 effect (P-interaction = 0.004): adults aged 65-84 showed a stronger inverse association (OR = 0.616) than those aged < 65 (OR = 0.921). Prolonged heatwave exposure was consistently associated with reduced diabetes risk, with pronounced age heterogeneity. Replication in larger prospective studies is warranted.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have become the standard of care for stage IV non-small cell lung cancer (NSCLC). In 2021, Lebanon experienced a severe economic collapse that resulted in major shortages of immunotherapy and treatment interruptions. The aim of this study was to explore the potential impact of immunotherapy shortage on progression-free survival (PFS). This retrospective multicenter study included patients with newly diagnosed stage IV NSCLC treated between January 2019 and December 2020 (control group) and between October 2021 and December 2022 (crisis group). The primary end point was PFS, defined from treatment initiation to progression according to RECIST 1.1 criteria or death. Kaplan-Meier survival curves were generated, and differences were assessed using log-rank test. A total of 500 medical records were reviewed; 158 eligible patients were included (73 control, 85 crisis). The total cohort included 60.8% men with a mean age of 69.7 years. Among immunotherapy recipients, 44.0% received full-dose therapy (dose density ratio = 1.0), 41.4% received 50%-99% of standard dose (dose density ratio = 0.50-0.99), and 14.7% received <50% (dose density ratio = <0.50). The median PFS was 6.33, 12.86, and 10.23 months, respectively; no statistically significant difference was observed (P = .132). Despite a statistically significant reduction in immunotherapy dose density during the economic crisis, no statistically significant difference in PFS was detected between the precrisis and crisis groups. These findings suggest that reduced immunotherapy dosing may not be associated with inferior short-term survival outcomes in stage IV NSCLC, although the study was not designed or powered to establish equivalence.

In many real-time measurement and monitoring systems, the quality of acquired signals is often severely degraded by complex environmental noise sources with non-stationary properties, rendering analysis, important feature extraction, and decision-making unreliable. This study proposes a multi-stage adaptive denoising architecture based on the least mean square (LMS) algorithm, in which the number of filter stages and the step size are automatically adjusted according to error statistics, the remaining correlation between the residual and the reference signal, and the real-time signal-to-noise ratio (SNR) of the signal. The stopping mechanism is determined by a two-tailed Fisher-z correlation test, with effective sample size correction in the presence of autocorrelation and modulation based on SNR, to ensure the stability of the adaptive system against non-stationary noise. The filter is evaluated on simulated signal datasets and real-world measured data. Compared with the conventional LMS filter configuration under the tested simulated conditions, the proposed architecture reduces mean squared error (MSE) by 38-82% and mean absolute error (MAE) by 15-45%, while improving both SNR and peak signal-to-noise ratio (PSNR). The execution time of the proposed method is approximately 3.5-4 times lower than that of the fixed-threshold method under the tested settings. These results indicate that the proposed method can improve the trade-off between denoising performance and computational efficiency, showing potential for low-latency implementation on resource-constrained devices.

Emerging evidence indicates that inflammation plays a crucial role in cancer prognosis. Inflammatory response biomarkers are recognized as promising prognostic factors for mortality in patients with cancer. This study aims to evaluate the prognostic significance of the systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), inflammatory prognostic index (IPI), and C-reactive protein-albumin-lymphocyte (CALLY) index. Weighted Cox regression analyses, restricted cubic spline models, Kaplan-Meier survival curves, and receiver operating characteristic analyses were performed to assess the predictive value of the 6 inflammatory markers for mortality. Subgroup analyses and sensitivity analyses were conducted to examine associations within specific subpopulations. Cox regression models demonstrated that SIRI, NLR, IPI, and CALLY were significant predictors of all-cause mortality (tertile 3 vs tertile 1; hazard ratio [HR]: SIRI: 1.72, 95% CI 1.29-2.27; NLR: 1.33, 95% CI 1.02-1.74; IPI: 1.48, 95% CI 1.14-1.92; CALLY: 0.66, 95% CI 0.51-0.85). IPI (HR 1.91, 95% CI 1.11-3.27) and CALLY (HR 0.53, 95% CI 0.31-0.90) were significantly associated with cancer-specific mortality, whereas only SIRI was able to predict cardiovascular mortality (P value for trend=.04). Dose-response relationships were observed between the 6 inflammatory markers and mortality outcomes. Kaplan-Meier survival curves further illustrated significant differences between tertile groups (log-rank test, P<.001). The 6 inflammatory indices exhibited moderate predictive ability for all-cause mortality. IPI yielded the highest area under the curve (AUC) for cancer-specific mortality (AUC=0.6338), and SIRI was the most efficient predictor of cardiovascular mortality (AUC=0.687). No significant interactions were observed between the 6 inflammatory markers and most subgroup variables. SIRI, NLR, IPI, and CALLY represent convenient and cost-effective prognostic tools for predicting mortality in patients with cancer. In contrast, SII and PLR may not be reliable prognostic biomarkers.

Use of piperacillin-tazobactam (TZP) as treatment for bloodstream infections (BSIs) has increased over time in Europe, as has antimicrobial resistance to TZP in some European countries. To evaluate mortality associated with TZP-resistant BSIs in the Danish health care system. In this cohort study, data collected in near real time were obtained from Danish national health registers from November 15, 2018, through November 21, 2024. Participants were patients aged 18 years or older with monomicrobial Escherichia coli or Klebsiella pneumoniae BSI, restricted to the first positive (index) blood culture with a TZP-susceptibility test result during the follow-up period. E coli or K pneumoniae BSI and a TZP susceptibility test classified as TZP resistant or TZP susceptible. Thirty-day mortality hazard ratios (HRs) for BSIs with TZP-resistant vs TZP-susceptible bacteria were estimated from the index date (blood culture) until death, emigration, or end of the observation period. Mortality was drawn from Danish national health registers, with no restriction on in-hospital or postdischarge mortality. Univariable and multivariable models adjusted a priori for self-reported gender, age, comorbidity, year, length of hospital stay until BSI, total length of inpatient stays in the prior year, and BSI in the prior 6 months with species other than that in the index culture. The study population included 34&#x202f;379 patients (median overall age, 76 years [IQR, 66-83 years]; 51.5% male). Among 28&#x202f;649 patients (81.9%) with E coli BSI, 1689 (5.9%) had a TZP-resistant BSI; among 6314 patients (18.1%) with K pneumoniae BSI, 597 (9.5%) had a TZP-resistant BSI. There was no loss to follow-up, and about 1% of participants were right-censored by the end of the observation period (E coli: 343 [1.2%]; K pneumoniae, 88 [1.4%]). Mortality was similar for patients with TZP-resistant and TZP-susceptible BSI after adjusting for baseline risk factors (E coli: crude HR, 1.22 [95% CI, 1.08-1.38]; adjusted HR [AHR], 1.09 [95% CI, 0.94-1.27]; K pneumoniae: crude HR, 1.27 [95% CI, 1.05-1.52]; AHR, 1.15 [95% CI, 0.94-1.41]). In this cohort study of patients with monomicrobial E coli or K pneumoniae BSI, there was no significant difference in mortality for patients with BSI caused by TZP-resistant vs TZP-susceptible bacteria after adjustment for baseline risk factors. The result is important given increasing TZP resistance in Denmark and other countries.

The World Health Organization surgical safety checklist (WHO SSC) provides a standardized framework for preoperative safety procedures. However, studies have revealed substantial variation in adherence, with items being skipped or misunderstood and nurses likely to be less involved than other operating room (OR) professional groups. We introduce a 16-item team timeout checklist (TTOC) that clarifies and adds safety-critical items to the existing WHO before skin incision timeout and is led by nurses to improve information exchange, closed-loop communication, and encouraging participation of all professional groups. Using a prospective pre-post interventional design, we live-coded all team communication during on-site observations in the OR focusing on the pre-incision phase. Surgical teams were first observed during a pre-intervention period without the TTOC checklist and subsequently during a post-intervention period after implementation of the TTOC checklist. The TTOC was evaluated on four communication outcomes critical for patient safety: information exchange of checklist items, measured as the percentage of the 16 items that were verbally communicated among team members (eg, team introduction, surgical site, allergies), participation rates of different professional groups, frequency of explicit coordination behaviors (eg, instruction, information request, speaking up) and the frequency of closed-loop communication sequences, defined as information request followed by information upon request within 30 seconds. A total of 155 teams were observed, including 78 teams in the pre-intervention phase without TTOC use and 77 teams in the post-intervention phase using the TTOC, resulting in 13,127 coded communication events. The median information exchange increased from 62.5% (interquartile range [IQR] 50-68.8) in the pre-intervention phase to 100% (IQR 100-100) in the post-intervention phase (P < .001). For 15 of all 16 subitems, the odds of exchanging information were significantly higher after TTOC implementation than before TTOC implementation (odds ratios range 10.8-1896, all 95% confidence intervals [CIs] excluded 1). Participation rates increased for circulating nurses, scrub nurses, surgical residents, and anesthesia (all P < .05) but not for lead surgeons. Mean (standard deviation [SD]) closed-loop communication patterns per operation were more frequent with (20.4 [10.7]) than without the TTOC (16.4, [7.24]), P = .004. In our study, the nurse-led TTOC significantly improved the exchange of safety-critical items during the pre-incision phase, facilitated closed-loop communication, and empowered the participation of various professional groups. These findings suggest integrating the TTOC with the WHO SSC before-incision protocol may have important advantages.

Concerns regarding weight changes during hormonal contraceptive use may influence health care-seeking behavior and contraceptive use patterns. While semaglutide use for weight management has increased substantially among women of reproductive age, the association of hormonal contraception use with semaglutide initiation remains unexplored. To investigate the association between hormonal contraception use and subsequent initiation of semaglutide therapy among females of reproductive age. This nested case-control study used Danish health registers to identify all females aged 12 to 49 years from January 1, 1996, to December 31, 2023. Eligible participants included females who filled their first prescription for semaglutide with no prior fill of prescriptions for drugs to lower glucose levels (semaglutide users). The date of first semaglutide prescription fill was the index date. Semaglutide users were each matched by birth year to 10 nonusers (nonuser controls) with no prior use of drugs to lower glucose levels. Data were analyzed from November 25, 2025, to May 18, 2026. Hormonal contraception use was summarized based on the chronological order of all hormonal contraceptives for which individuals had filled prescriptions from 12 years of age (or study entry) until the index date. First filled prescription of semaglutide of any dose. A total of 22&#x202f;694 cases and 229&#x202f;640 matched controls (249 634 participants; median age, 37 [IQR, 30-44] years) were included in the analysis. All hormonal contraception utilization patterns were associated with semaglutide initiation compared with nonuser controls. Among utilization patterns involving a single contraceptive type, adjusted hazard ratios ranged from 1.42 (95% CI, 1.34-1.51) for combined oral tablets to 1.63 (95% CI, 1.46-1.82) for progestin-only intrauterine devices. For utilization patterns involving 2 or more contraceptive types, adjusted hazard ratios ranged from 1.64 (95% CI, 1.47-1.82) for combined oral tablets followed by progestin-only oral tablets to 2.11 (95% CI, 1.97-2.25) for other utilization patterns. Adjustment for body mass index attenuated but did not eliminate associations. Subgroup analyses by age, educational attainment, income, parity, immigrant status, and semaglutide type showed consistent associations across most utilization patterns. In this nationwide case-control study, use of hormonal contraception was associated with subsequent semaglutide initiation across all utilization patterns compared with controls, highlighting a need to examine factors associated with weight management in females.

Recycled coarse aggregate (RA) is prone to deteriorating the performance of recycled aggregate concrete (RAC) due to inherent defects such as adhered old cement paste and internal micro - cracks, while calcined layered double hydroxides (CLDHs) exhibit significant potential for enhancing concrete performance. However, the synergistic mechanism between CLDHs and RA remains unclear. To address this, this study employs compressive strength, chloride ion (Cl-) penetrability, X - ray diffraction (XRD), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) to investigate the effects of varying CLDHs content (0%, 1%, 3%, 6%) and RA replacement rates (0%, 10%, 20%, 30%) on the mechanical properties, chloride ion permeability resistance, and microstructure of RAC. Results indicate that an appropriate combination of CLDHs and RA significantly improves RAC performance: the mix with 1% CLDHs and 20% RA increased the 28 d compressive strength by 10.3% compared to the reference group, while the combination of 3% CLDHs and 30% RA enhanced chloride ion penetration resistance by 19.1%, with electrical flux as low as approximately 1135 C, achieving a "low" permeability rating. Microstructural analysis confirms that the synergistic interaction of suitable CLDHs and RA promotes the formation of dense flocculent C - S - H gel, fills pores, reduces the proportion of harmful pores, increases the ratio of gel pores, thereby optimizing pore structure and enhancing system compactness. Additionally, it delays crack initiation and propagation, resulting in no penetrating cracks upon specimen failure. Based on these findings, an improved TOPSIS comprehensive evaluation model integrating the entropy weight (EW) method and the Analytic Hierarchy Process (AHP) was developed. This model systematically evaluates the chloride ion erosion resistance of Recycled Aggregate Concrete (RAC) by synthesizing multidimensional indicators such as compressive strength, electrical flux, and pore structure, thereby overcoming the limitation of single-factor weighting inherent in the entropy weight method. Concurrently, through economic analysis, an adjustable decision-making framework for RAC mix proportion selection under various corrosive environments has been proposed. This study elucidates the mechanism by which CLDHs and RA synergistically improve RAC performance, providing a theoretical foundation and methodological support for the engineering application of recycled concrete in aggressive environments.

The perioperative treatment landscape of muscle-invasive bladder cancer (MIBC) is rapidly evolving with the introduction of immune checkpoint inhibitor (ICI)- and antibody-drug conjugate (ADC)-based strategies. However, direct randomized comparisons among contemporary regimens are lacking, limiting the interpretation and positioning of treatments. We aimed to compare the efficacy of perioperative systemic treatment strategies for MIBC with a network meta-analysis (NMA) of randomized controlled trials (RCTs). PubMed, Embase, Web of Science, and congress abstracts were systematically searched up to 28 February 2026. Phase II-III RCTs enrolling patients with MIBC treated with perioperative systemic therapy initiated before radical cystectomy and reporting overall survival (OS), event-free survival (EFS), and/or pathological complete response (pCR) were included. A frequentist graph-theoretical NMA was carried out to compare three contemporary RCTs using a star-shaped network anchored to gemcitabine-cisplatin (GC) as the common comparator. Treatment ranking was estimated using P-scores. The primary outcome was OS. Secondary outcomes included EFS and pCR. In total, 2293 patients from three RCTs contributed to the primary network. Compared with GC, enfortumab vedotin-pembrolizumab (EVP) was associated with improved OS [hazard ratio (HR) 0.65], as was GC plus durvalumab (HR 0.75). EVP and GC plus durvalumab were also associated with improved EFS (EVP HR 0.53, GC plus durvalumab HR 0.68) and higher pCR rates [EVP odds ratio (OR) 2.62, GC plus durvalumab OR 1.57] compared with GC. Across evaluated endpoints, EVP consistently achieved the most relevant P-score-based ranking. Subgroup-specific and sensitivity analyses demonstrated a consistent treatment direction. In this NMA of RCTs, perioperative regimens incorporating ICIs and ADCs were associated with improved survival and pathologic response outcomes compared with GC alone. Given the sparse star-shaped network and the absence of closed loops, these findings should be interpreted as indirect comparative estimates rather than definitive evidence of treatment superiority, while still providing a clinically relevant framework for contextualizing contemporary perioperative regimens.

This systematic review and meta-analysis assessed the efficacy and safety of ferric carboxymaltose (FCM) in treating iron-deficiency anemia secondary to gastrointestinal bleeding. A comprehensive search across multiple databases identified randomized controlled trials comparing FCM with other iron formulations. A total of 13 publications, reporting 16 trials and involving 1939 patients, were included. Pooled analyses demonstrated that FCM led to significantly greater improvements in key anemia parameters compared to alternative iron therapies, including a higher hemoglobin response rate [risk ratio&#x2005;=&#x2005;1.24, 95% confidence interval (CI): 1.14-1.34], increased serum ferritin levels (mean difference&#x2005;=&#x2005;293.52, 95% CI: 168.76-418.27), and greater transferrin saturation (mean difference&#x2005;=&#x2005;9.71, 95% CI: 5.19-14.22). The overall incidence of drug-related adverse events was comparable between groups (risk ratio&#x2005;=&#x2005;0.82, 95% CI: 0.51-1.34); however, FCM was associated with a substantially increased risk of hypophosphatemia (risk ratio&#x2005;=&#x2005;21.00, 95% CI: 8.90-49.56). Notably, subgroup analysis confirmed that this therapeutic advantage remained consistent across both acute and chronic gastrointestinal bleeding settings. In conclusion, FCM is effective in correcting anemia in patients with gastrointestinal bleeding-related iron deficiency, despite a well documented risk of hypophosphatemia. Further research is warranted to optimize dosing strategies and identify patient subgroups most likely to benefit from FCM therapy.

Echocardiographic calculation of mitral regurgitant fraction (MR%) may complement variables used to assess myxomatous mitral valve disease (MMVD) severity. The geometric technique of calculating MR% uses four component variable measurements. Calculations using multiple measurements necessarily influence variability. The influence of disease severity on component measurements and MR% variability has not been explored. This study explored the contribution of component measurement variability and the markers of disease severity: left atrial-to-aortic ratio, R-R interval (RR) variability and heart rate on MR% variability. Echocardiographic studies from 109 dogs with MMVD were analysed. The co-efficient of variation (COV) was calculated from three measurements of each echocardiographic variable and calculated MR%. A multivariable linear regression model was devised modelling COV MR% as the outcome variable. The COV of MR% correlated negatively with MR% severity and decreased with increasing American College of Veterinary Internal Medicine stages. Component variables of MR% generally had variability <10% in all American College of Veterinary Internal Medicine stages. In a multivariable model, of the component variables, only COV aortic diameter measured between the open aortic leaflets at mid-systole in a right parasternal long-axis view showed positive correlation with MR% variability (2.17, P=0.010). However, MR% variability showed clearest association with left atrial-to-aortic ratio (-16.89, P=0.001) and variation in R-R interval (COV RR: 1.47, P=0.002, COV RR2 = -0.04, P=0.013). Modelling of retrospective data is a limitation of the present study. Variability of MR% is associated with disease severity. We propose beat-to-beat variation in component variables attributable to sinus arrhythmia is associated with variability of mitral regurgitation and echocardiographic calculation of MR% in dogs. These results provide insights into echocardiographic measurement variability in MMVD and assist interpretation of MR% at different disease stages.

Increasing the number of channels is essential for improving neural signal acquisition in wireless implantable brain-computer interfaces (iBCIs). However, more channels raise power consumption and data rates, placing additional demands on the limited energy supply and communication bandwidth of implanted devices. A central challenge is how to fully leverage the global spatiotemporal correlations within neural signals to further enhance compression efficiency while preserving the integrity of critical information. This paper proposes a three-dimensional (3D) spatiotemporal neural signal compression method based on compressed sensing for ultra-high-channel wireless neural recording systems. This approach comprises two components: a 3D spatiotemporal matrix representation of neural signals and three-dimensional compressed sensing (3D-CS). Unlike traditional methods that focus solely on spatial correlations among multi-channel neural signals, this approach exploits the spatiotemporal correlations inherent in ultra-high-channel neural signals. It represents neural signals as 3D spatiotemporal matrices while synchronizing action potentials (APs) and local field potentials (LFPs), enabling holistic compression. The method was validated using real-world data from a 1024-channel system. Results showed that after compression with this method, all APs remained intact, with all LFPs achieving a structural similarity index measure (SSIM) greater than 0.95. The average signal-to-noise and distortion ratio (SDNR) reached approximately 24.16 dB, achieving a total compression ratio (CR) of 156. The findings demonstrate that this approach provides an efficient, low-power data compression solution for ultra-high-channel wireless implantable brain-computer interfaces.