To identify donor, lenticule preparation, recipient, and operative factors associated with 1-year Descemet membrane endothelial keratoplasty (DMEK) success in the Diabetes Endothelial Keratoplasty Study (DEKS). This prospective cohort study was a pre-specified secondary analysis of the DEKS randomized, double-masked, multi-center clinical trial. Individuals undergoing DMEK to treat corneal endothelial dysfunction at 28 clinical sites. Eyes undergoing DMEK were randomized to receive a cornea from a donor without or with diabetes in a 2:1 ratio. Donor, tissue preparation, recipient and operative factors were recorded prospectively. The study excluded eyes with a prior penetrating keratoplasty or glaucoma tube shunt. Graft failures were classified as follows. If the recipient stroma was cloudy in the first postoperative week and did not clear or required a regraft within 8 weeks, it was classified as primary donor failure in the absence of operative complications, or as early failure associated with operative complications. If the recipient stroma cleared in the first postoperative week or cleared after being cloudy in the first postoperative week and later required a regraft or became cloudy without clearing for 90 days, it was classified as late failure. Proportional hazards and logistic regression were used to estimate risk ratios. DMEK success rate at 1 year RESULTS: Of 1421 DMEK grafts, 1374 (97%) were clear at 1 year, 32 were primary donor failures, 12 were early failures, and 3 were late failures. The 78 cases (5.5%) with operative complications had a reduced success rate (88%; hazard ratio for graft failure 4.0, 95% CI 1.9-8.6, p<0.001). Three additional factors were associated with slightly higher graft success rates in multivariate analysis without reaching the defined statistical significance threshold of P<.01: baseline donor endothelial cell density ≥ 2500 vs. <2500 cells/mm2 (97% vs. 95% success, P=.03), tissue peeled by surgeon vs. eye bank (99% vs. 96% success, P=.02), and recipient diabetes status: no vs. yes (97% vs. 94% success, P=.02). DMEK was highly successful across a wide range of donor, lenticule preparation, recipient, and surgical technique variations. Not surprisingly, graft success was lower in cases with operative complications.
Metaphyseal sleeves are increasingly utilized in revision total knee arthroplasty (rTKA) to obtain zonal fixation in the metaphysis and improve implant survivorship. However, radiographic factors associated with long-term sleeve survival remain poorly defined. We previously characterized a cohort of aseptically failed tibial sleeves. This study compared those rare failures to long-term surviving sleeves, assessing whether lack of medial baseplate support and undersized sleeves and stems are more common in aseptic failures. A retrospective review was performed of patients undergoing rTKA with tibial metaphyseal sleeves at a single academic institution (2011 to 2025). There were 18 aseptically failed sleeves identified and compared to a cohort of surviving sleeves with a minimum 3-year follow-up. Stem canal fill ratios (CFRs) were measured on antero-posterior (AP) and lateral radiographs using the Parsley method. A novel area fill ratio was calculated using ImageJ software, comparing implant area to tibial canal area over the sleeve and stem length. The medial baseplate support was classified as unsupported with greater than two mm of gapping or greater than two mm of cement mantle in lieu of augments. Optimal matching by age, sex, and BMI (body mass index) created a matched subgroup for comparison. There were 53 surviving-sleeve patients identified (mean follow-up 6.7 years (range, 3.0 to 13.6 years)). All stem and sleeve fill ratios-Parsley CFRs, distal 4-cm stem area fill ratios, and metaphyseal sleeve area fill ratios-were significantly greater in both the unmatched (n = 53) and matched (n = 31) surviving cohorts versus the 18 failing sleeves (all P < 0.05). The medial baseplate support was present in 77.4% of unmatched and 74.2% of matched survivors versus 44.4% of failures (P = 0.017 and P = 0.064, respectively). Greater metaphyseal sleeve fill, greater diaphyseal stem fill, and the presence of medial baseplate support were each associated with long-term sleeve survivorship following rTKA. These findings support maximizing zonal fixation in rTKA with the use of a sleeve.
Smallholder dairy farmers in Ethiopia face low productivity and food insecurity, in part due to limited use of artificial insemination (AI) and overstretched extension systems. Artificial insemination (AI) requires accurate estrus detection, timely communication, and quick technician response, which are difficult to achieve in rural areas with limited service. This study analysed how ICT-based extension is associated with partial substitution for weak institutional service delivery to improve AI adoption and use, milk productivity, and food security in central Ethiopia. We use survey data from 571 households and apply a double-hurdle model to analyse adoption and use intensity, an endogenous switching regression to analyse impacts on milk productivity and food security, and a structural equation model to examine mediation effects. ICT-based extension is associated with higher AI adoption and use, increased yields, and reduced food insecurity, with greater benefits for those with more education, cooperative membership, market access, and mobile coverage. ICT-based extension is associated with reduced coordination failures, but deeper structural constraints persist, highlighting the need for investment in education, connectivity, and targeted interventions.
Patient safety and diagnostic quality are central to modern histopathology practice. Current incident investigation approaches often rely on root cause analysis; however, its routine use as a universal method is insufficient to address the highly variable, cognitive, sociotechnical and multifactorial nature of histopathology errors. In practice, incidents range from simple technical failures to complex system-level events requiring distinct investigative strategies. A key limitation of current practice is the lack of proportionality, where similar methods are applied irrespective of case complexity. In addition, corrective actions frequently target the immediate error without adequately considering the broader system context, potentially increasing workload, introducing new risks or degrading long-term service performance and operational sustainability. In this narrative review, we propose a practical five-stage systems framework for incident management in histopathology. This framework integrates proportional incident classification, structured systems investigation, prospective evaluation of corrective actions to minimise unintended consequences, implementation of system-level improvements and continuous performance monitoring. By selectively applying established human factors and quality improvement methodologies according to incident complexity, the framework shifts incident management from retrospective error investigation towards proactive system optimisation and continuous organisational learning. Ultimately, it provides a practical, scalable approach that improves diagnostic reliability, reduces recurrence, enhances efficiency and ensures that corrective actions are effective, sustainable and aligned with real-world laboratory practice.
Intolerance to 5-aminosalicylic acid (5-ASA) is linked to poorer outcomes in ulcerative colitis (UC), but its impact on progression to difficult-to-treat (D2T) disease and the contribution of specific intolerance phenotypes remain uncertain. We evaluated the long-term prognostic impact of 5-ASA intolerance phenotypes and post-intolerance treatment status. This retrospective cohort study included 919 patients with UC. Cumulative incidence functions were compared using Gray's test, treating death and colectomy as competing events when assessing progression to D2T. Multivariable models were adjusted for baseline covariates and immunomodulator use. Landmark analyses and sensitivity analyses using secondary failure of ≥ 2 mechanisms of action after advanced therapy initiation were performed. Among 919 patients, 145 (15.8%) were classified as 5-ASA intolerant, including 83 with acute intolerance syndrome (AIS) and 62 with non-AIS phenotypes. Overall intolerance was independently associated with an increased risk of D2T progression (subdistribution hazard ratio [sHR] 2.07, 95% confidence interval [CI] 1.14-3.75), but not with colectomy. The excess risk was largely driven by AIS (sHR: 3.25, 95% CI: 1.64-6.45). Landmark analyses showed that 5-ASA users at 90 or 365 days exhibited a lower cumulative incidence of D2T progression than non-users. Furthermore, following advanced therapy initiation, overall 5-ASA intolerance was not associated with secondary failure of ≥ 2 mechanisms of action, whereas AIS remained independently associated with this outcome. Progression to D2T UC among patients with 5-ASA intolerance is largely attributable to AIS. Careful characterization of 5-ASA phenotype may improve risk stratification and inform individualized therapeutic strategies in UC management.
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are central regulators of cardiovascular development and stress responses and have been implicated in the cardiovascular toxicity of tyrosine kinase inhibitors. While ERK signaling in cardiomyocytes has been extensively investigated, the isoform- and cell-specific contribution of ERK2 in vascular smooth muscle cells (VSMCs) to cardiac dysfunction remains incompletely understood. To address this issue, we generated mice with systemic deletion of Erk1 (Erk1-/-), SM22α-Cre-mediated deletion of Erk2 (SM22α-E2KO; targeting VSMCs and cardiomyocytes), and α-myosin heavy chain-Cre-mediated deletion of Erk2 in cardiomyocytes alone (MHCα-E2KO). SM22α-E2KO mice developed progressive eccentric left ventricular hypertrophy, systolic dysfunction, impaired exercise capacity, and markedly reduced survival, whereas MHCα-E2KO and Erk1-/- mice exhibited preserved cardiac structure and function under basal conditions. Vascular functional studies revealed enhanced phenylephrine-induced vasoconstriction and impaired acetylcholine-mediated relaxation in SM22α-E2KO mice, despite preserved ERK2 expression in aortic endothelial cells. Aortic RhoA/Rho-kinase activity was significantly increased in SM22α-E2KO mice, and pharmacological inhibition of Rho-kinase normalized vascular hypercontractility. Transcriptomic analyses of the heart demonstrated downregulation of excitation-contraction coupling and metabolic pathways, accompanied by activation of inflammatory and fibrotic signaling. Notably, partial loss of Erk1 further exacerbated mortality and cardiac dysfunction in SM22α-E2KO mice, indicating a compensatory role of ERK1 in the setting of ERK2 deficiency. Collectively, these findings identify ERK2 signaling in VSMCs as a critical determinant of vascular tone and cardiac systolic function and demonstrate that combined vascular and myocardial ERK2 deficiency promotes heart failure through Rho-kinase-dependent vascular dysfunction.
Claustral ant queens found colonies in sealed, food-free chambers, making colony founding both energetically constrained and vulnerable to fungal disease. Recent experiments show that queens cannibalise infected larvae, thereby removing potential sources of conidia while recovering nutrients for further oviposition. We develop a deterministic four-compartment model for queen reserves, healthy brood, infected brood, and environmental spores to investigate how hygienic cannibalism shapes founding success under fungal challenge. The analysis reveals a nested threshold structure. An energetic persistence threshold determines whether brood recycling can offset maintenance and brood-production costs in the absence of infection; conditional on energetic viability, a pathogen invasion threshold determines whether a rare fungal infection can grow from the disease-free founding state. When energetic support is sufficient, the coexistence conditions reduce to a scalar equation for infected brood density, implying that at most two endemic equilibria can occur and yielding explicit criteria for a unique endemic state versus bistability between extinction and a high-infection endemic state. Bifurcation analysis further shows that varying cannibalism can generate both forward and backward transitions in pathogen establishment and, in some regimes, stable infection oscillations. Simulations show that stronger hygienic cannibalism shifts founding outcomes from collapse to chronic but viable infection and, for low-yield pathogens, to infection clearance, whereas increasing conidial yield enlarges the region of founding failure. Sensitivity analysis identifies recycling efficiencies, cannibalism rate, brood-production cost, transmission, conidial yield, and spore decay as the strongest determinants of reserves, brood, infection, and successful founding. Together, these results show how energetic constraints and hygienic cannibalism jointly determine whether claustral founding clears infection, persists under chronic disease, or collapses under fungal challenge.
Diabetes mellitus (DM), a prevalent chronic metabolic disorder with a global prevalence over 10.5%, features persistent hyperglycemia-induced micro-/macro-vascular lesions and severe complications. Conventional DM management suffers from high risks of cross-infection or hypoglycemia, poor compliance, and failure to address the multi-faceted needs of integrated diagnosis and nonspecific treatment for complications. Microneedles (MNs), a minimally invasive platform that painlessly penetrates the stratum corneum to access interstitial fluid (ISF) or deliver therapeutics, has emerged as a transformative solution for DM care. Despite significant progress in developing MN-based systems for glucose monitoring, insulin delivery, and treatment of complications, challenges remain in achieving precise drug release, high loading capacity, long-term stability, and clinical translation. This review comprehensively summarizes the latest advances in MN-based platforms for DM management, covering three major glucose detection modalities with improved sensitivity and portability, gastrointestinal and glucose-responsive transdermal MNs for insulin delivery, fully integrated close-loop MN platforms, and MN applications in diabetic wound healing and other complications (ketoacidosis diagnosis, vascular disorders, neuropathy, depression). By addressing the critical gaps in scattered research, this work holds great significance for advancing minimally invasive, integrated, and patient-centered treatment models, ultimately improving the prognosis and quality of life for DM patients worldwide.
Glioblastoma (GBM) remains one of the most aggressive primary brain tumors, with poor prognosis, high recurrence, and limited therapeutic options. Although substantial progress has been made in drug development, effective clinical translation is still constrained by inefficient delivery across the blood brain barrier (BBB) and blood brain tumor barrier (BBTB), insufficient tumor accumulation, intratumoral heterogeneity, acquired therapeutic resistance, and dose limiting systemic toxicity. Nanomedicine offers a promising strategy to address these barriers through tunable physicochemical properties, flexible surface functionalization, improved pharmacokinetics, and controllable drug release. In this review, we systematically summarize recent advances in nanomedicine enabled GBM therapy from four interrelated perspectives: the optimization of nanomaterial properties, the development of goal-oriented targeting strategies, the rationalization of delivery routes, and the engineering of smart stimuli-responsive nano-systems. Rather than only cataloguing representative nanoplatforms, we emphasize how material parameters, biological targeting mechanisms, delivery routes, and release behaviors are mechanistically linked to BBB or BBTB penetration, tumor accumulation, therapeutic efficacy, and translational feasibility. Importantly, we also incorporate a key failure case analysis of representative clinical and preclinical studies, highlighting why promising nanotherapeutic concepts may fail because of inadequate intratumoral distribution, insufficient survival benefit, poor patient selection, manufacturing complexity, safety concerns, or impractical trial design. By integrating delivery mechanisms, cross platform comparison, translational barriers, and future optimization principles, this review provides a critical and forward looking framework for the rational design of precise, effective, and clinically translatable nanomedicine strategies for GBM treatment.
Effective antiretroviral therapy has transformed HIV into a manageable chronic condition, provided viral suppression is maintained through routine viral load (VL) monitoring. Access to frequent VL testing remains limited, particularly outside centralized clinical settings. Decentralized and at-home HIV VL testing requires low-volume systems designed for patient operation. These systems must distinguish true viral suppression from test failure. Many approaches lack internal process verification, which makes negative results ambiguous. Here, we present ViraLite, an ultracompact, battery-powered HIV VL monitoring system that integrates reverse transcription loop-mediated isothermal amplification (RT-LAMP) with an RNase P internal process control, machine learning-assisted fluorescence analysis for one-pot multiplexing, and smartphone-guided operation. We evaluated ViraLite using 45 clinically archived plasma samples and benchmarked it against reverse transcription quantitative polymerase chain reaction (RT-qPCR). The internal process control identified 17 inconclusive tests that would otherwise be misclassified as negative. Among valid tests, ViraLite achieved 93.3% sensitivity and 100% specificity versus RT-qPCR. ViraLite enables decentralized HIV VL testing with low sample volume and interpretable negative results. This capability can expand monitoring beyond traditional clinic workflows and addresses a key barrier to patient-operated VL testing.
Mid-stage embryos of different species often look more alike than early embryos or adults. Early and late development diverge, leading to a broad-narrow-broad hourglass pattern. I propose that mid-embryogenesis coincides with protocol waists, narrow interfaces that standardize communication between otherwise distinct processes. For example, continuous spatial geometry is translated into a morphogen gradient protocol readable by gene regulatory networks. This architecture arises because the physical space-time geometry of early development cannot directly instruct late gene regulatory programs. They require a translator. The need for domain translation distinguishes protocols from generic canalization and bottlenecks. Translation protocols explain the hourglass: a protocol screens off upstream inputs, allowing early diversification, and decouples downstream responses, enabling late radiation. A protocol waist often remains evolutionarily frozen as the essential common language that keeps these diverging halves compatible. Perturbations of protocol waists tend to cause widespread system failure, concentrating fragility. Protocol waists provide a framework to interpret domain translators, such as morphogen gradients for geometry-to-molecules, Notch/Delta lateral inhibition for topology-to-fates, the vertebrate segmentation clock for time-to-space and Hox axial patterning for position-to-identity. Sequential domain translators form a protocol stack, matching the common architecture of robust complex systems in engineering.
Early identification of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients remains challenging using conventional parameters alone. This retrospective study aimed to assess whether combining left atrial (LA) reservoir strain (εs) with left ventricular (LV) longitudinal strain improves the discrimination of HFpEF among hypertensive patients. We included 50 hypertensive patients with HFpEF (HTN-HFpEF), 56 hypertensive patients without HFpEF, and 50 healthy controls. Cardiac magnetic resonance feature tracking (CMR-FT) was used to measure LV global longitudinal strain (LVGPLS) and strain rates, as well as LA εs, conduit (εe), and booster (εa) strains. Parameters were compared across the three groups. Binary logistic regression was performed to identify predictors of HTN-HFpEF, and receiver operating characteristic (ROC) curves were generated to calculate the area under the curve (AUC). From controls to HTN to HTN-HFpEF, LVGPLS and strain rate showed progressive impairment, while LAVImax and LAVImin progressively increased (all p < 0.001). Compared to the HTN group and healthy controls, the HTN-HFpEF group demonstrated significant impairment in LA functional and strain parameters (all p < 0.001). Binary logistic regression analyses revealed that LVMI, LAVImin, LAεs, and LVGPLS remained independently associated with HFpEF. LAεs alone showed the highest diagnostic performance (AUC = 0.790), and the combination of LAεs and LVGPLS further improved the AUC to 0.841. In conclusion, CMR-FT-derived LA strain demonstrates high discriminative ability for HFpEF in hypertensive patients. The combination of LAεs and LVGPLS offers optimal diagnostic value and may serve as a sensitive non-invasive biomarker for identifying HFpEF in this population.
Mean arterial pressure (MAP) guides hemodynamic management following heart transplantation, yet renal failure remains common. Tissue perfusion pressure (TPP), defined as MAP minus critical closing pressure, predicts acute kidney injury in non-transplant cardiac surgery. We hypothesized that postoperative TPP predicts continuous renal replacement (CRRT) requirement after heart transplantation. We analyzed all adult heart transplants at a single institution (01/2020-06/2025) and excluded multiorgan transplants, congenital heart disease, and patients requiring post-transplant extracorporeal membrane oxygenation support. Hourly TPP, MAP, and organ perfusion pressure (OPP; MAP - central venous pressure) were analyzed over 72 hours. Patients were stratified by post-transplant CRRT use. Predictive performance was compared using net reclassification improvement (NRI) across sequential 24-hour epochs. Of the 269 patients included, 47 (17.5%) required CRRT. Those needing CRRT more likely had circulatory death donors (55.3% vs 38.3%, p=0.035) using direct procurement and perfusion (14.9% vs 6.3%, p=0.037). Pre-transplant creatinine was greater in the CRRT group (1.5mg/dL vs 1.2, p=0.002). In the CRRT group, the median and mean TPP, OPP, and MAP within the first 72 hours were all lower (p < 0.01). Mean TPP demonstrated better prediction of CRRT compared to OPP (NRI 0.49, 95% CI 0.23-0.76, p<0.001) and MAP (NRI 0.39, 95% CI 0.11-0.68, p=0.007) within 24 hours post-transplant. After 24 hours, the predictive powers of median TPP, OPP, and MAP were similar. Early postoperative TPP independently predicted the need for CRRT after heart transplantation and demonstrated superior risk reclassification compared with conventional pressure-based hemodynamic metrics.
Percutaneous left ventricular assist devices (pLVAD, such as Impella), are increasingly used for cardiogenic shock (CS). Outcomes may differ between acute myocardial infarction - related CS (AMI-CS) and non-AMI CS due to differing pathophysiology and trajectories. Using the U.S.A. TriNetX Network (2016-2024), we identified adults with CS treated withpLVAD. AMI-CS was defined by MI within seven days of implantation; non-AMI CS included all patients with CS not attributable to acute MI, representing heterogeneous etiologies such as decompensated cardiomyopathy, myocarditis, valvular failure, pulmonary vascular causes, and arrhythmic shock. Patients with recent coronary artery bypass graft (CABG) were excluded. Propensity matching produced two balanced cohorts (n = 2,026 each). Among 6,873 AMI-CS and 4,521 non-AMI CS patients, matched groups were similar (mean age 63 years, 26% female). AMI-CS had higher mortality at 30 days (hazard ratio [HR] 1.19, p = 0.002), 90 days (HR 1.13, p = 0.02), and 180 days (HR 1.14, p = 0.007). Heart failure (HF) exacerbations (HR 1.21, p < 0.001) and pulmonary edema (HR 1.23, p = 0.005) were also more common in AMI-CS. Stroke, ventricular arrhythmias, cardiac arrest, acute kidney injury, major bleeding, vascular complications, and hemodialysis were comparable. AMI-CS patients supported with pLVAD experienced higher mortality and greater HF - related morbidity than non-AMI CS.
Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality and frequently requires urgent liver transplantation. Perioperative management is challenging due to severe hemodynamic instability, coagulopathy, systemic inflammation, and multiorgan dysfunction. Optimized anesthetic strategies combined with Patient Blood Management (PBM) principles may improve outcomes and reduce transfusion-related complications. We report the case of a 42-year-old woman with chronic cholestatic liver disease who developed ACLF with hepatic encephalopathy, systemic infection, and hepatorenal syndrome, requiring urgent liver transplantation with a deceased donor graft. Intermittent hemodialysis was initiated preoperatively due to renal dysfunction. The procedure was performed under total intravenous anesthesia with advanced multimodal monitoring, including invasive hemodynamic assessment and cerebral oximetry. Intraoperatively, the patient developed severe vasoplegia requiring high-dose vasoactive support. Fluid therapy followed a restrictive strategy, and coagulation management was guided by viscoelastic testing. Intraoperative blood conservation strategies, including cell salvage, were applied, and no allogeneic blood components or other blood-derived products were required. Postoperatively, the patient was admitted to the intensive care unit under vasoactive support, with progressive hemodynamic stabilization, recovery of renal function, and resolution of encephalopathy. She was discharged home without major complications. This case highlights the importance of individualized anesthetic management and strict application of PBM principles in urgent liver transplantation for ACLF. Advanced monitoring, goal-directed therapy, and restrictive transfusion strategies may contribute to improved perioperative stability and favorable postoperative recovery. This case report complies with the Declaration of Helsinki and the Declaration of Istanbul regarding ethical organ donation.
Air pollution, composed of several complex particles, is regarded as one of the major causes of adverse health outcomes, and particulate matter (PM), which occurs primarily as PM10, PM2.5, and PM0.1 according to its aerodynamic diameter, is considered to be the most dangerous fraction. It is known to impair the healthy functioning of organ systems, including the cardiovascular system, respiratory system, gastrointestinal system, and reproductive system. Upon inhalation, the respirable fraction of PM can travel through the olfactory bulb and reach the brain, disrupting the blood-brain barrier (BBB), or act through peripheral responses, thereby causing neuroinflammation and oxidative stress in the brain. PM exposure activates unfolded protein response (UPR) and proapoptotic signals like CHOP and caspase-12, which drive brain cell death. It also impairs oxidative phosphorylation, increases ROS, and initiates mitochondrial permeability transition, which results in neuronal energy failure. Upon entering the system, it compromises the autophagic flux and lysosomal integrity, leading to its accumulation. Although the systemic effects of PM are widely recognized, its capacity to penetrate the central nervous system (CNS) poses a significant biological concern. This review maps how PM alters CNS components, leading to neuroinflammation and ultimately neurotoxicity, and examines the upstream and downstream mechanisms underlying these actions.
The E-wave propagation index (EPI) has been proposed as a simple risk marker of left ventricular (LV) thrombus (LVT) formation. We sought to investigate the association between EPI and LVT in patients with heart failure with reduced ejection fraction (HFrEF). This was a retrospective cohort study on 768 patients with HFrEF. The EPI was measured as the velocity time integral of the transmitral E-wave divided by the LV length. The endpoint was LVT formation. Logistic regression was applied to investigate the association between EPI and LVT. Multivariable adjustments were made for age, mitral regurgitation, apical aneurysm, prior myocardial infarction, and LV ejection fraction (LVEF). Area under receiver operating characteristic curves was used to assess the optimal cut-off value for EPI. Of 768 HFrEF patients, 24 (3%) had developed LVT. The mean age was 66 years, 73% were men, and the mean LVEF was 28%. EPI was lower among those who had developed LVT (1.1 vs 1.3, p = 0.018), and EPI was significantly associated with LVT formation in univariable logistic regression (OR = 1.16 (1.0-1.3), per 0.1 decrease). This finding was unchanged after multivariable adjustments. The EPI provided an area under the curve of 0.68 with an optimal cutoff of 1.2. This cutoff had a sensitivity of 75%, specificity of 60%, positive predictive value of 6%, and negative predictive value of 99%. Patients with an EPI <1.2 had a four-fold increased risk of LVT (OR = 4.42 (1.73-11.25), p = 0.002). In patients with HFrEF, the EPI was independently associated with LVT formation. Additionally, an EPI > 1.2 indicates a low likelihood of developing LVT.
Although binders constitute a minor mass fraction of electrode, they are indispensable for maintaining the mechanical integrity and electrochemical functionality of sodium-ion batteries (SIBs). Conventional binders are increasingly inadequate for high-capacity electrode materials, which typically suffer from severe volume fluctuations, unstable interfaces, and sluggish reaction kinetics. This review systematically elucidates the crucial relationship between the intrinsic properties of various electrode materials and the required functionalities of advanced binders. First, we delineate the primary failure mechanisms of different cathode and anode materials, translating these fundamental challenges into specific, material-tailored design criteria for polymeric binders. Subsequently, we present a comprehensive overview of state-of-the-art molecular design strategies for multifunctional binders. These approaches are categorized into four key domains: (1) enhancing mechanical robustness through superior adhesion and volume-change accommodation; (2) boosting electronic and ionic conductivity via precise polymer engineering; (3) stabilizing the solid-electrolyte interphase (SEI) and cathode-electrolyte interphase (CEI) utilizing targeted binder chemistries; and (4) ensuring electrode homogeneity by optimizing binder dispersion and interfacial affinity. Finally, we summarize current progress and provide a forward-looking perspective on the rational design of next-generation binders, paving the way for high-performance and durable SIBs suitable for large-scale energy storage applications.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most clinically significant extra-articular manifestations of rheumatoid arthritis and an important cause of morbidity and premature mortality. Its clinical spectrum ranges from asymptomatic radiographic abnormalities to rapidly progressive fibrosing lung disease with respiratory failure. Current evidence indicates that RA-ILD is biologically heterogeneous and arises from the interplay of mucosal autoimmunity, genetic susceptibility, epithelial injury, dysregulated innate and adaptive immune responses, and aberrant tissue repair. This heterogeneity has important implications for diagnosis, prognosis, and treatment selection. High-resolution computed tomography remains central to disease detection and radiologic phenotyping, while pulmonary function testing, serologic profiling, circulating biomarkers, and multidisciplinary discussion improve risk stratification and longitudinal assessment. Management should integrate the relative contribution of inflammation and fibrosis with current conditional guideline recommendations, and may include short-term glucocorticoids, conventional immunosuppressants, biologic or targeted synthetic disease-modifying antirheumatic drugs, antifibrotic therapy for documented progressive pulmonary fibrosis, and evaluation for pulmonary hypertension-associated ILD in advanced disease. However, clinical decision-making remains limited by the scarcity of randomized RA-ILD-specific trials, the lack of standardized definitions of disease progression, and uncertainty regarding optimal treatment sequencing. This review summarizes current understanding of the pathogenesis, risk factors, diagnostic evaluation, treatment strategies, and prognostic determinants of RA-ILD, with emphasis on phenotype-oriented management and practical issues relevant to respiratory and multidisciplinary care.
To characterize Bioelectrical Vector Analysis (BIVA) vector patterns in adults with excess adiposity defined by fat mass index (FMI) and to examine the implications of obesity-related vector displacement for the clinical interpretation of BIVA. We conducted a retrospective cross-sectional analysis of adults attending a tertiary obesity clinic. Excess adiposity was defined using sex-specific FMI thresholds based on NHANES criteria. Resistance and reactance were normalized for height (R/H, Xc/H), and BIVA patterns were described overall and stratified by sex and ethnicity. Sex- and ethnicity-specific tolerance ellipses (50th, 75th, 95th percentiles) were derived from bivariate normal models and visually compared with Piccoli/NHANES reference ellipses for elevated adiposity. Correlation structure and ellipse geometry were evaluated within each sex-ethnicity stratum. In 3072 adults with FMI-defined excess adiposity (723 men, 2349 women), impedance vectors showed a predominantly downward displacement characterized by lower Xc/H and lower phase angle, with variable R/H behavior across sex and ethnicity strata. This directional pattern was observed across the spectrum of FMI severity and remained stable across sex and major ethnic groups. Sex and ethnicity modulated mean vector position and ellipse dispersion but did not alter the overarching adiposity-related displacement. The correlation between R/H and Xc/H (r ≈ 0.63-0.75) was preserved in all strata, indicating intact underlying biophysical relationships. In adults with obesity, displacement of BIVA relative to classical reference ellipses primarily reflects the electrophysiological signature of excess adiposity rather than overt fluid overload or intrinsic cellular failure. These findings support the development of obesity-adjusted BIVA reference frameworks, further refined by sex and ethnicity, to improve the specificity and physiological interpretability of raw impedance measurements in obesity care.