Hyperphosphatemia is a recognized on-target adverse event of erdafitinib, a pan-fibroblast growth factor receptor (pan-FGFR) tyrosine kinase inhibitor with Food and Drug Administration approval to treat advanced urothelial cell carcinoma with FGFR2/3 mutations. This study hypothesized that hyperphosphatemia is a biomarker for drug activity and is associated with improved overall survival (OS) and other oncologic end points in phase 2/3 clinical trials. Data from the phase 2 BLC2001 and cohorts 1 and 2 of the phase 3 THOR clinical trials were pooled; only patients who received erdafitinib were included. Kaplan-Meier and Cox proportional hazards models were used to examine the effect of hyperphosphatemia (as classified by Common Terminology Criteria for Adverse Events [CTCAE] grade) on OS, progression-free survival (PFS), and objective response rate (ORR). A total of 409 subjects (median age, 66 years; interquartile range, 60-72 years) who met the inclusion criteria were pooled from the THOR and BLC2001 clinical trials, of whom 78.4% had hyperphosphatemia. Subjects with CTCAE grade 3+ hyperphosphatemia had improved OS (hazard ratio [HR], 0.21; 95% CI, 0.05-0.86; p = .031) and PFS (HR, 0.16; 95% CI, 0.04-0.67; p = .012) in multivariable Cox proportional hazards models compared to patients without hyperphosphatemia. In this secondary analysis of the BLC2001 and THOR trials, higher CTCAE hyperphosphatemia grades were associated with improved OS, PFS, and ORR. These findings suggest that hyperphosphatemia may serve as a potential biomarker of erdafitinib activity, and warrant prospective validation.
Achieving ultrahigh wear-resistance in structural coatings requires integrating high intrinsic strength with the ability to sustain plastic deformation. Here, we report a dual-phase nanocrystalline FeCoNiTi multiprincipal element alloy (MPEA) coating that attains a high yield strength of 3.3 GPa, a strain-hardening rate of 9.21 GPa, and an ultralow wear rate of 1.1 × 10-6 mm3/(N·m), surpassing most reported MPEA coatings. The coating is synthesized via rapid electrical-current-activated sintering, during which amorphized FeCoNiTi powders crystallize into a uniform fine-grained FCC matrix (∼32.5 nm) with ∼40 vol % ordered coherent L12 nanoprecipitates. Addition of Ti promotes compositional segregation and L12 phase formation, which facilitates twinning-induced plasticity and enhances strain hardening. The in situ formation of a TiO2 tribo-film also provides a lubrication effect. Furthermore, the twin-mediated deformation suppresses strain localization and grain boundary sliding. This work establishes a rapid and robust pathway for designing high-performance antiwear coatings through alloying-driven phase selection and defect engineering.
Purpose To investigate the association between impaired lung function and pulmonary perfusion defect percentage (QDP) using phase-resolved functional lung (PREFUL) MRI. Materials and Methods In this prospective study (March 2023-July 2024), participants underwent spirometry to assess lung function, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Lung function was classified as either normal or impaired, with the impaired category including airflow obstruction (AO), restrictive physiology (RP), and preserved ratio impaired spirometry (PRISm). Additionally, all participants underwent PREFUL MRI for ventilation and perfusion assessment and CT for emphysema evaluation. Linear regression models were used to evaluate associations between QDP and pulmonary function status, and restricted cubic spline (RCS) analysis was applied to explore potential nonlinear relationships. Results A total of 287 participants were included (mean age ± SD, 60 years ± 13; 228 males). Compared with normal spirometry, PRISm (β = 3.20; 95% CI: 1.40, 5.01; P = .002), RP (β = 3.88; 95% CI: 1.63, 6.12; P = .002), and AO (β = 8.49; 95% CI: 6.59, 10.39; P < .001) were significantly associated with QDP. Lower FEV1% predicted, FVC% predicted, and FEV1/FVC ratio, as well as increased emphysema percentage, were associated with higher QDP. RCS analysis revealed nonlinear associations between pulmonary function indicators and QDP. Subgroup analysis demonstrated significant interactions between lung function impairment and factors such as body mass index and age. Conclusion Impaired lung function was associated with increased pulmonary perfusion defects as detected by PREFUL MRI. Keywords: Thorax, MR-Functional Imaging, Preserved Ratio Impaired Spirometry, Phase-resolved Functional Lung, Perfusion Defects, Ventilation Defects, Lung Emphysema Chinese Clinical Trial Registry: ChiCTR2300077789 and ChiCTR2300074883 Supplemental material is available for this article. © RSNA, 2026.
Isotope-selective rotational control of asymmetric-top molecules is a challenging task owing to their complex rotational dynamics. Here, we extend a simulation framework for isotope-selective rotational control to the water isotopologues H2O and T2O, and numerically identify pulse conditions that maximize isotope contrast in an equimolar gas-phase mixture driven by nonresonant, linearly polarized double pulses. We examine three characteristic rotational periods associated with ΔJ = 1 transitions from the ground state and find that TrotB+C=1/B+C provides the strongest synchronization for isotope contrast. To quantify isotope-selective rotational contrast, we define a rotational contrast metric based on the three-dimensional alignments of H2O and T2O. When the pulse delay is synchronized to TrotB+C, the metric reaches a maximum value of 1.99 at 10 K; further optimization of the pulse delay and intensity ratio increases the metric to 2.20. These results demonstrate that appreciable isotope-selective contrast can be achieved even in the H2O/T2O system, where the small polarizability anisotropy makes alignment control inherently difficult, and establish a versatile route toward isotope-selective rotational control of more complex asymmetric-top molecules.
Recent advancements in immuno-oncology have significantly improved cancer treatments. Compared with traditional clinical trials, the toxicity of these novel therapies is generally low and tolerable, shifting the focus from solely managing toxicity to improving efficacy. Furthermore, such treatments can be costly, and thus it is crucial to identify a low-dose regimen with a good therapeutic effect for broader drug accessibility. Instead of solely identifying the optimal biological dose (OBD) in a phase I/II trial, we emphasize finding a more economical but effective dose. Current methods typically aim to determine the minimum effective dose (MED) based on a predefined efficacy target, which may not reflect the best balance between efficacy and dosage. This paper introduces the minimum noninferiority dose (MND), derived from the OBD, which eliminates the need for artificially setting an efficacy target. The MND ensures the dose maintains efficacy within a reasonable range below the OBD while keeping the dosage as low as possible. Through leveraging the calibration-free odds (CFO) design to monitor toxicity, we further propose a novel Bayesian two-stage design, called CFO-MND, by incorporating a trade-off between dose and efficacy as well as adaptive randomization. Our model-free approach is versatile and applicable to a wide range of scenarios. Furthermore, we incorporate causal inference into the CFO-MND design by introducing the placebo equivalent dose. This allows for preliminary estimation of the drug's average treatment effect at the MND, which provides valuable information for subsequent trials.
The ASTRUM-005 phase 3 randomized clinical trial showed substantial survival benefit from adding serplulimab to chemotherapy for previously untreated extensive-stage small cell lung cancer (ES-SCLC). However, the long-term outcomes are unclear. To investigate the efficacy, safety, patient-reported outcomes (PROs), and exploratory biomarker findings from ASTRUM-005 at an extended follow-up. This international, double-blind, phase 3 randomized clinical trial enrolled patients from September 12, 2019, to April 27, 2021 in China, Russia, Ukraine, Poland, Turkey, and Georgia. Eligible patients had histologically or cytologically confirmed ES-SCLC with no prior systemic therapy. Patients were followed up through May 7, 2024, and the data analysis of this prespecified, secondary analysis lasted from August to September 2024. The median follow-up duration was 42.4 months (range, 0.2-55.2). Patients were randomized in a 2:1 ratio to receive intravenous serplulimab (4.5 mg/kg; serplulimab group) or placebo (placebo group), which was combined with up to 4 cycles of carboplatin and etoposide every 3 weeks. The primary end point was overall survival (OS). Secondary end points included other efficacy end points, safety, and PROs. A total of 585 patients (median [range] age was 63 [28-76] years in the serplulimab group and 62 [31-83] years in the placebo group) with previously untreated ES-SCLC, and 389 (66.5%) were randomly assigned to the serplulimab group and 196 (33.5%) to the placebo group. Baseline characteristics were balanced across treatment groups. At data cutoff, 280 OS events (72.0%) in the serplulimab group and 166 (84.7%) in the placebo group were observed. Compared with the placebo group, the serplulimab group showed more favorable efficacy (median OS, 15.8 [95% CI, 13.9-17.4] vs 11.1 [95% CI, 10.0-12.4] months; hazard ratio, 0.60; 95% CI, 0.49-0.73; P < .001). The serplulimab group showed improved OS rates at 4 years compared with the placebo group (21.9% vs 7.2%). Grade 3 or higher serplulimab-related or placebo-related treatment-emergent adverse events occurred for 136 (35.0%) and 57 patients (29.1%) in the respective groups. A PRO analysis revealed consistent trends of improved overall health, dyspnea, and pain in both groups and faster recovery from alopecia in the serplulimab group. This secondary analysis of a randomized clinical trial demonstrated long-term benefit from adding serplulimab to chemotherapy for previously untreated patients with ES-SCLC, supporting this therapy as a first-line standard of care for this patient population. ClinicalTrials.gov Identifier: NCT04063163.
This trial evaluated co-administration of the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) and an Omicron XBB.1.5-based COVID-19 mRNA vaccine in ≥50-year-olds. This phase 3, open-label, multi-center trial randomized ≥50-year-olds 1:1 to co-administration (Co-Ad group) or sequential administration approximately one month apart (Control group) of adjuvanted RSVPreF3 and the COVID-19 mRNA vaccine. Primary objectives were to demonstrate non-inferiority of humoral immune responses at one month post-vaccination in terms of RSV-A, RSV-B, and SARS-CoV-2 neutralizing titers, with the upper limit of the 95% confidence interval (CI) of adjusted geometric mean titer (GMT) group ratios (Control/Co-Ad) ≤1.50. Secondary objectives included assessment of reactogenicity up to four days and safety up to six months after vaccination. Overall, 833 participants were vaccinated (Co-Ad: 417; Control: 416). Non-inferiority was achieved for RSV-A (GMT ratio: 1.12 [95% CI: 0.97-1.28]) and RSV-B (GMT ratio: 1.08 [95% CI: 0.94-1.23]), and marginally missed for SARS-CoV-2 Omicron XBB.1.5 (GMT ratio: 1.31 [95% CI: 1.13-1.51]). Within four days post-vaccination, the most frequently reported solicited events were administration-site pain, myalgia, and fatigue. Most solicited events were of mild-to-moderate intensity, and the overall median duration was ≤three days and comparable between groups. Unsolicited and serious adverse events were generally balanced between groups. Adjuvanted RSVPreF3 co-administered with a COVID-19 mRNA vaccine maintained an acceptable safety profile in ≥50-year-olds. The marginal miss of the non-inferiority criterion for SARS-CoV-2 does not suggest clinically relevant interference. Therefore, the results support the co-administration of these vaccines.
Ochratoxin A (OTA) poses significant health risks and is prevalent in various plant-based foods, necessitating rapid and reliable on-site detection methods. In this study, a lateral flow aptasensor integrating magnetic solid-phase extraction (MSPE) with enzyme-catalyzed colorimetric signal transduction was developed for the rapid determination of OTA. To facilitate field deployment, a portable integrated MSPE device featuring adjustable rotation speed and duration, as well as automated magnetic separation, was designed to enable efficient sample pretreatment under on-site conditions. Polydopamine-coated magnetic beads were employed for MSPE due to their suitability for batch sample processing. Moreover, enzyme-catalyzed colorimetry was introduced as an alternative signal transduction strategy in lateral flow assays. The proposed aptasensor exhibited good specificity and satisfactory sensitivity, with a limit of detection of 0.30 ng/mL. Acceptable accuracy and precision were achieved, with recoveries of 91.1-97.2% and relative standard deviations below 15%. The method was further validated by analyzing commercially available food samples, with results showing good agreement with the standard HPLC method. This integrated strategy enables reliable on-site detection of OTA in complex food matrices by combining efficient magnetic sample pretreatment with enhanced enzyme-catalyzed colorimetric signal transduction.
The pathophysiological changes of lung perfusion and ventilation in fibrosing interstitial lung diseases (F-ILD) remain inadequately characterized. This study aimed to analyze lung perfusion and ventilation characteristics in F-ILD patients using phase-resolved functional lung magnetic resonance imaging (PREFUL MRI) as well as their correlation with the severity of F-ILD. This cross-sectional study prospectively included 30 patients diagnosed with F-ILD (19 males, 64.6 ± 9.5 years) and 30 age- and sex-matched normal controls. All participants underwent PREFUL MRI as well as pulmonary function tests. High-resolution CT (HRCT) was performed for the patient cohort. Ventilation and perfusion-related parameters obtained from PREFUL MRI were analyzed and correlated with PFTs and fibrotic lesions identified on HRCT. Compared with normal controls, F-ILD patients showed significant differences in mean perfusion (7.55% vs 4.60%), Mean Ventilation (13.95% vs 18.65%), Perfusion Defect (QDPexclusive) (3.65% vs 15.50%), ventilation-perfusion matched non-defect percentage (VQMnon-defect) (87.55% vs 70.10%), and ventilation-perfusion matched defect percentage (VQMdefect) (0.15% vs 1.35%) (all p < 0.05). Mean perfusion correlated positively with DLCO SB (single breath) %pred (ρ = 0.682, p < 0.001) and DLCO/VA (alveolar volume) %pred (ρ = 0.634, p < 0.001), while QDPexclusive correlated negatively with these parameters. Mean perfusion showed negative correlations with honeycombing, fibrotic lesions, and total interstitial lesion burden on HRCT, whereas QDPexclusive correlated positively with these abnormalities (all p < 0.05). PREFUL MRI provides a quantitative functional evaluation of ventilation and perfusion in F-ILD patients, demonstrating strong correlations with pulmonary function parameters and fibrotic lesions. It shows potential as a valuable monitoring tool enabling severity assessment of F-ILD. PREFUL MRI provides a non-invasive, free-radiation method in the assessment of ventilation and perfusion in F-ILD, enabling severity evaluation. In patients with F-ILD, lung perfusion decreased, and ventilation increased. Lung ventilation and perfusion correlated with lung function parameters in F-ILD; however, they are similar between idiopathic pulmonary fibrosis (IPF) and other types of F-ILD. After controlling demographics, PREFUL MRI perfusion parameters (mean perfusion and QDPexclusive) remain significant, independent predictors of gas-exchange capacity and fibrotic burden.
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While supersonic cooling revolutionized spectroscopic studies of neutral molecules, cooling molecular ions remains far more challenging, especially for ions generated from electrospray ionization (ESI). Cryogenic cooling has been transformative, particularly for ESI-produced ions, by enabling intrinsically cold spectroscopic interrogation of solution-phase species transferred into the gas phase. This perspective focuses on cryogenic photoelectron spectroscopy (PES) and photodetachment spectroscopy (PDS) of complex anions produced by ESI and cooled in a 3D Paul trap, a platform that has been widely adopted because of its relative simplicity and robust performance. We discuss the technical evolution from the initial ESI-PES for solution species to cryogenic ESI-PES with a magnetic-bottle analyzer, and the current cryogenic PDS and high-resolution photoelectron imaging. We emphasize significant advances enabled by coupling the cryogenic 3D Paul trap first to ESI sources-highlighting studies of temperature-dependent phenomena, solution-phase chemistry in the gas phase, nonvalence excited states, vibrationally induced autodetachment, and resonant PES-and more recently to a laser-vaporization cluster source, demonstrating more effective vibrational cooling for cluster ions than supersonic expansion.
For patients with advanced non-small cell lung cancer (NSCLC) and programmed cell death 1 ligand 1 (PD-L1) expression of 50% or higher, programmed cell death 1 protein or PD-L1 (PD-[L]1) inhibitor monotherapy is commonly used as first-line therapy; however, whether adding chemotherapy improves outcomes in this population remains unknown. To compare overall survival (OS) and progression-free survival (PFS) associated with PD-(L)1 inhibitor monotherapy vs chemoimmunotherapy in treatment-naive patients with advanced NSCLC and high PD-L1 expression. PubMed, Embase, and major oncology conference proceedings were searched for phase 3 randomized clinical trials (RCTs) published before August 3, 2025. Eligible studies were phase 3 RCTs that enrolled patients with untreated advanced NSCLC, evaluated PD-(L)1 inhibitor monotherapy or chemoimmunotherapy vs chemotherapy alone, and reported outcomes in patients with high PD-L1 expression. Hazard ratios (HRs) for OS and PFS were extracted from published studies and synthesized using inverse variance methods. Additional analyses included meta-regression, network meta-analysis, and reconstructed individual patient data from published Kaplan-Meier curves. Primary outcome was OS; secondary outcome was PFS. Among 24 trials including 5546 patients with PD-L1-high NSCLC, 16 evaluated chemoimmunotherapy and 8 PD-(L)1 inhibitor monotherapy. Compared with chemotherapy, survival was improved by both chemoimmunotherapy (OS: HR, 0.63 [95% CI, 0.56-0.72]; P < .001; PFS: HR, 0.44 [95% CI, 0.39-0.49]; P < .001) and PD-(L)1 inhibitor monotherapy (OS: HR, 0.74 [95% CI, 0.69-0.80]; P < .001; PFS: HR, 0.70 [95% CI, 0.65-0.76]; P < .001). Tests for subgroup differences suggested improved benefit with chemoimmunotherapy compared to PD-(L)1 inhibitor monotherapy (OS: χ21 = 4.1; P = .04; I2 = 75.8%; PFS: χ21 = 48.1; P < .001; I2 = 97.9%), consistent with meta-regression analyses (OS: HR, 0.85 [95% CI, 0.72-1.00]; P = .048; PFS: HR, 0.61 [95% CI, 0.50-0.75]; P < .001) and network meta-analyses (OS: HR, 0.85 [95% CI, 0.73-0.99]; PFS: HR, 0.61 [95% CI, 0.50-0.75]). In the reconstructed individual patient data analysis, median OS was longer with chemoimmunotherapy (n = 704 patients) compared to PD-(L)1 inhibitor monotherapy (n = 1706 patients) (29.2 months [95% CI, 25.2-35.4] vs 19.8 months [95% CI, 18.3-21.7]; HR, 0.74 [95% CI, 0.66-0.82]; P < .001). Similarly, median PFS was significantly longer with chemoimmunotherapy (n = 701 patients) compared to PD-(L)1 inhibitor monotherapy (n = 1706 patients) (11.3 months [95% CI, 10.3-13.5] vs 6.8 months [95% CI, 6.2-7.1]; HR, 0.67 [95% CI, 0.60-0.75]; P < .001). In this meta-analysis of phase 3 RCTs, chemoimmunotherapy was associated with significantly improved OS and PFS compared with PD-(L)1 inhibitor monotherapy in patients with advanced NSCLC and high PD-L1 expression. Prospective trials are needed to confirm these findings.
Background Nurses form the backbone of the healthcare system; their role is vital in healthcare delivery in terms of promotion, prevention, treatment, care, and rehabilitation. Nurse managers play a key role in patient care coordination and ensure quality nursing care. Apart from this, they also perform staff management, document administrative activities, and supervise hospital store activities. Efficient and effective nursing administration is essential for smooth functioning and safe patient care. Methods In an observational study in two phases, we estimated the time utilized by administrative nurses in different tasks. In the first phase, a questionnaire was developed for self-reporting various activities carried out by administrative nurses. In the second phase, activity sampling with 316 hours of observations and 15 344 nursing activities was recorded across the hospital to estimate actual time distribution and utilization of administrative nurses. Results Administrative nurses spent a major portion of their time in store management (28%), staff management (23%), and documentation (21%), and much less time for patient care supervision and teaching activities, i.e. 4%-8% of the total time available in a day. Conclusion We found that administrative nurses spent most of their time in three major activities: store management, staff management, and documentation. Their roles may need to be reviewed for them to spend more time in supervision of patient care and teaching activities.
 South African audiologists face clinical and systemic challenges because of resource constraints and workload pressures, yet their professional quality of life and the role of resilience remain underexplored.  To explore the professional quality of life of South African audiologists and to examine its association with resilience and coping.  A two-phase explanatory sequential mixed-methods design was employed. Phase 1 involved a cross-sectional web-based survey, incorporating the Professional Quality of Life Scale (v5), while phase 2 comprised semi-structured interviews. Quantitative data were analysed using descriptive and inferential statistics, and qualitative data were analysed using Braun and Clarke's reflexive thematic analysis.  Audiologists reported moderate compassion satisfaction (CS) and low burnout and secondary traumatic stress (STS). Burnout (BO) was negatively correlated with CS, while compassion fatigue (CF) was positively correlated with both BO and STS. A negative association was observed between STS and CS. Higher resilience was associated with better professional quality of life and qualitative findings highlighted emotional regulation, adaptability and support as key to sustaining professional fulfilment.  Organisational support plays an important role in promoting audiologists' well-being and professional engagement. Strengthening support structures and resilience practices may improve professional quality of life. There is also a need to enhance training through supervision, mentorship and the integration of resilience and coping skills into audiology curricula.Contribution: These findings can inform strategies to improve audiologists' well-being and guide institutional and policy responses.
The diagnosis of Alzheimer's disease (AD) has progressively depended on sophisticated neuroimaging methods alongside cognitive assessments. This study combines volumetric feature analysis with computational modeling techniques, focusing on spatial and temporal analysis, to categorize individuals as cognitively normal (CN), mild cognitive impairment (MCI), or AD using magnetic resonance imaging (MRI) data. In the initial phase, volumetric changes, comprising cortical thickness, white matter, grey matter, cerebrospinal fluid, and total intracranial volume, were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset utilizing the CAT12 toolbox in statistical parametric mapping (SPM). Linear regression was utilized on these variables over time to create slopes that reflect volumetric change rates, which then served as inputs for machine learning classifiers. The slopes of cortical thickness exhibited the greatest classification accuracy, reaching 82.5% with a random forest model for differentiating AD from CN individuals. During the second phase, a deep learning methodology was utilized, relying solely on the MRI scans and excluding the outcomes from the first phase. A pre-trained 3D ResNet-101 convolutional neural network (CNN) model extracted spatial characteristics from MRI volumes, whereas long short-term memory (LSTM) networks recorded temporal dynamics across subsequent annual scans. This hybrid CNN-LSTM design markedly improved classification performance, attaining 96.7% accuracy for AD against CN and enhancing the distinction of MCI cases. Nonetheless, discrepancies in MCI categorization were chiefly ascribed to the restricted access to annual MRI data and the model's pre-training on CN and AD cohorts. These findings highlight the potential of integrating volumetric statistical analysis with deep learning for automated AD categorization. This work enhances neuroimaging diagnostic methods by utilizing both spatial and temporal MRI data, enabling early diagnosis and better evaluation of disease development.
Polynomial phase signals (PPS) are a staple of waveform design and analysis in sonar, radar, and communications fields. They also find application in the modeling of bioacoustic emissions, especially those of echolocating animals such as bats and odontocetes. This work presents a novel PPS waveform formulation that exploits some special properties of Chebyshev polynomials, such as orthogonality, recurrence relations, and equivalence to trigonometric functions. The result is the Chebyshev polynomial frequency modulation (CPSFM) family of waveforms, which prove useful in the modeling of bioacoustic signals and the approximation of non-polynomial-phase signals such as hyperbolic chirps. We demonstrate that the CPSFM model admits compact analytic expressions for fundamental continuous-time signal processing functions such as the Fourier transform, the convolution and correlation operations, and the ambiguity function. Derivations for these expressions using CPSFM are presented, along with their application to the analysis of biosonar emissions of Mexican free-tailed bats.
Recently, the demand for high-energy-density batteries in high-end consumer electronics has driven the iterative advancement of LiCoO2 (LCO) cathodes. For LCO, under conventional charging voltages (≤4.5 V vs. Li/Li+), its reversible capacity is only 140-180 mAh g-1, far below its theoretical capacity of 274 mAh g-1. Increasing the charging voltage (to 4.6 V or even higher) is expected to achieve reversible capacity exceeding 220 mAh g-1. However, LCO faces significant issues, including deep phase transitions, lattice O oxidation, severe side reactions, etc., resulting in rapid capacity decay. To solve these issues, a series of breakthroughs were attempted via tuning bulk phase, near-surface structure, and surface coating aspects, enabling the transition of high-capacity LCO from lab research toward practical application. This work aims to systematically summarize the intrinsic connections between failure mechanisms and modification strategies, and further refine the design principles for high-capacity LCO cathodes. By doing so, we provide insights for the next-generation LCO cathodes, thereby reinforcing the dominance of LCO not only in consumer electronics, but also in emerging fields such as drones and solid-state batteries.
The study compared the efficacy and safety of steady concentration peritoneal dialysis using the Carry Life UF system in the home setting over 4 weeks. Treatment with the Carry Life UF system resulted in increased ultrafiltration volume, sodium removal, and glucose ultrafiltration efficiency compared with a 2.5% dextrose control. The use of Carry Life UF in the home setting was well tolerated and safe with no unexpected adverse events. Steady concentration peritoneal dialysis (PD) is a novel therapy for improved fluid management. We compared the efficacy and safety of steady concentration PD using the Carry Life UF system with a standard 2.5% dextrose continuous ambulatory peritoneal dialysis exchange in the home setting. This is a prospective, multicenter, randomized, crossover study of adult patients on continuous ambulatory peritoneal dialysis using 2-4 exchanges per day, with at least one daily 2.5% dextrose exchange. The home phase lasted 4 weeks for each study arm. During the Carry Life UF arm, one daily 2.5% dextrose exchange was replaced with a Carry Life UF treatment 3 days/wk (1.5% dextrose solution for PD fill, 11 or 15 g/h glucose dose) and a 1.5% dextrose exchange 4 days/wk. The primary outcome was difference in ultrafiltration (UF) volume with 5-hour Carry Life UF treatment versus 5-hour 2.5% dextrose exchange (control). Secondary outcomes included adverse events, peritoneal sodium removal, and glucose UF efficiency. A total of 19 participants (mean [SD] age 56 [15] years, six women, seven with diabetes) completed the study. Peritoneal solute transfer rate categories were fast four, average 12, and slow three. The UF volume primary outcome was met as Carry Life UF was superior to control in a prespecified superiority margin of 250 ml, mean increase 381 ml, 95% confidence interval (CI; 285 to 477). For the Carry Life UF total group (11 and 15 g/h cohorts analyzed together), mean (SD) UF volume was 513 (251) versus 132 (172) ml for the control. The secondary outcome peritoneal sodium removal was greater with Carry Life UF versus control (mean increase 43 mmol/exchange, 95% CI 32 to 54). The secondary outcome glucose UF efficiency (UF volume in relation to glucose absorption) was enhanced with Carry Life UF versus control (mean increase 6.4 ml/g, 95% CI 3.7 to 9.1). Two serious adverse events (peritonitis) occurred in the home phase, one episode in each study arm. This 4-week home study of steady concentration PD using the Carry Life UF system demonstrated efficacy and safety. NCT05874804.
Biomolecular condensates, which are membraneless organelles formed through liquid-liquid phase separation, serve as fields that regulate chemical reactions and functions by linking functionally related molecules. Accumulated data from the field of phase separation chemistry suggests that biomolecular condensates form and grow via the widely involved mechanisms, including diffusion-limited growth, fusion, and Ostwald ripening. However, tracking individual emerging or growing condensates is required to differentiate and quantify these mechanisms. In this study, we developed a label-free condensate growth analysis platform based on ultra-widefield dark-field microscopy and image analysis. Our system enables long-term detection for at least 30 min, high-time-resolution imaging at 0.1 s, and an ultra-wide imaging area of 5.8 mm2. Using this platform, we characterized the growth processes of approximately 10,000 condensates in two model proteins, HP1α and FUS, by counting the occurrences of the three growth mechanisms. For these two proteins, condensates form through diffusion-limited growth and unexpectedly primarily grow via fusion rather than Ostwald ripening, either simultaneously or with a short lag time. Our results demonstrate that the platform can analyze the formation and growth of various biomolecular condensates in vitro without labeling the sample.
Unilateral countermovement jump (CMJsingle) testing is commonly used after anterior cruciate ligament reconstruction (ACLR) to assess stretch-shortening cycle (SSC) function and return-to-sport readiness. However, the impact of ACLR on contralateral limb SSC function is poorly understood, which may impact the utility of the contralateral limb benchmark. Therefore, statistical parametric mapping (SPM) was employed to: (1) evaluate interlimb CMJsingle force-time and power-time deficits in athletes with ACLR; and (2) compare both limbs of athletes with ACLR to an enhanced CMJsingle benchmark from healthy control athletes. Canadian university athletes who returned to sport post-ACLR (n = 20) and healthy control athletes (n = 187) performed maximal CMJsingle testing on a force plate. The Sport Fitness Index (SFI) assessed perceived limb function, and healthy controls were divided into upper (GOODSFI) and lower (POORSFI) tertiles. Top-ranked jumpers with GOODSFI were sex- and sport-matched to ACLR athletes to obtain an enhanced CMJsingle benchmark (Control+ benchmark). Interlimb and between-group CMJsingle curves were compared using SPM. No interlimb differences were found in healthy athletes in the GOODSFI group. Healthy athletes in the POORSFI group demonstrated interlimb force and power deficits over 12% (p < 0.001) and 4% (p = 0.006) of the CMJsingle propulsion phase, respectively. Compared to the contralateral limb, the affected limb of the ACLR group showed reduced force and power over 8% (p < 0.001) of the CMJsingle propulsion phase. Conversely, the affected limb generated less force over 14% (p < 0.001) and less power over 22% (p < 0.001) of propulsion compared to the Control+ benchmark. The Control+ benchmark revealed larger SSC impairments in the affected limb compared to the contralateral limb benchmark during CMJsingle testing in athletes who had returned to sport post-ACLR. Further, healthy athletes with poor perceived limb function demonstrated interlimb SSC impairments similar to the ACLR group, highlighting value in combining biomechanical testing with psychosocial measures in university athletes. Level III, case-control study.