Science Progress最新文献

ObjectiveSimultaneous bilateral cochlear implantation has been shown to provide long-term benefits in children suffering from severe-to-profound hearing loss. However, very little research has been conducted on long-term benefits in Mandarin-speaking children. We aimed to (1) evaluate tone perception with simultaneous bilateral cochlear implants (CIs) compared to unilateral CIs; and (2) evaluate early auditory and speech skills.MethodsThe longitudinal study was comprised of 20 participants, 10 with unilateral and 10 with simultaneous bilateral CIs. Participants received a CI at a mean age of 1.3 (SD ± 0.2) years. The Mandarin Early Speech Perception test, auditory thresholds, and influence of environmental factors were measured pre-operatively and after 24 months. Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), and LittlEARS Auditory Questionnaire (LEAQ) were measured pre-operatively and after 6, 12, and 24 months.ResultsAfter 24 months of device use, tone perception scores tended to be higher in the bilateral CI group than in the unilateral group, although the difference did not reach statistical significance (p = 0.058). Over the 24-month follow-up period, CAP, SIR, and LEAQ scores showed significant improvements in both groups (all p < 0.05).ConclusionsTone perception and early auditory and speech skills in Mandarin-speaking children were better with simultaneous bilateral CI implantation compared to unilateral after 24 months of use.

ObjectivesFluid management in critically ill obese patients is challenging due to the risk of fluid overload when using standard weight-based formulas. This study aims to evaluate the association between hydration status and mortality in elderly obese critically ill patients with acute kidney injury (AKI).MethodsThis retrospective cohort study included elderly obese critically ill patients with AKI admitted to a tertiary care ICU between January 2020 and December 2022. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Fluid overload was defined as body weight-adjusted fluid balance >10%. The primary outcome was 90-day all-cause mortality. Statistical analyses included Kaplan-Meier survival curves and multivariate Cox regression.ResultsA total of 539 elderly obese critically ill patients with AKI were included, of whom 244 (45.3%) developed fluid overload. During the 90-day follow-up, 209 patients (38.8%) died. Patients with fluid overload had significantly higher 90-day mortality compared to those without fluid overload (50.4% vs. 29.2%, P < 0.01). Kaplan-Meier analysis showed a higher mortality risk for fluid-overloaded patients (P < 0.01). Multivariate Cox regression indicated that fluid overload (HR = 2.04, 95% CI: 1.24-3.36, P < 0.01) and SOFA score (HR = 1.13, 95% CI: 1.04-1.22, P < 0.01) were independent predictors of increased mortality.ConclusionsFluid overload is significantly associated with increased 90-day mortality in elderly obese critically ill patients with AKI.

ObjectiveHepatocellular carcinoma (HCC) has a poor prognosis, necessitating novel biomarkers. The role of LSM7 (Like-Sm protein 7), an RNA-binding protein, in HCC remains unclear.MethodsWe employed a multiomics strategy using transcriptomic data from TCGA, GTEx, GEO, and ICGC to evaluate LSM7's expression and prognostic value. A protein-protein interaction (PPI) network was constructed via STRING, followed by Gene Ontology/KEGG/Gene Set Enrichment Analysis (GSEA) functional enrichment analysis. The relationship between LSM7 and the immune infiltration landscape was assessed using single-sample GSEA (ssGSEA) and the TISCH single-cell database. Drug sensitivity was analyzed using Genomics of Drug Sensitivity in Cancer, and structure-based virtual screening was performed on the ZINC library to identify potential LSM7 inhibitors. Key findings were validated in clinical samples and MHCC97H cells and Huh-7 cells using Western blot, IHC, and MTT assays.ResultsLSM7 was significantly overexpressed in HCC, correlating with adverse clinicopathological features (higher histological grade, elevated AFP levels, vascular invasion) and shorter overall survival, identifying it as an independent risk factor. Functionally, LSM7 was implicated in processes such as hormone regulation. Immune analysis revealed that high LSM7 expression was associated with altered immune cell abundance, upregulation of immune checkpoints, and a higher Tumor Immune Dysfunction and Exclusion score, suggesting a role in immune evasion. The high-LSM7 group showed increased sensitivity to drugs like sorafenib. Virtual screening identified Velpatasvir as a top LSM7-targeting candidate, with in vitro validation confirming that it inhibits MHCC97H cells and Huh-7 cells proliferation and downregulates LSM7 protein in a concentration- and time-dependent manner.ConclusionsBy integrating multiomics strategy and experimental validation, this study suggests that LSM7 may play a role in HCC progression and influence the tumor immune microenvironment. LSM7 may serve as a potential biomarker and therapeutic target, and Velpatasvir appears to be a candidate agent worthy of further investigation.

This study investigates optical solitons in magneto-optic waveguides while preserving the generalized anti-cubic structure of nonlinear self-phase modulation. A novel ${\varphi }^6$-model expansion technique is proposed, and its application in magneto-optic waveguides is explored. The ${\varphi }^6$ approach provides an accurate and efficient method to solve wave propagation problems in magneto-optic media, enabling improved modeling of light behavior by incorporating the combined effects of electric and magnetic fields within a unified framework. To address the challenges arising from the nonlinear magneto-optic effects on waveguide characteristics, the method yields precise dispersion relations, field distributions, and transmission properties. This technique facilitates the design of magneto-optic waveguides with tailored characteristics for next-generation photonic systems. By offering a reliable and accurate modeling framework, the ${\varphi }^6$ approach contributes to the development of more precise and efficient magneto-optic devices, advancing photonic integration, communication, and sensing technologies.

ObjectiveColorectal cancer (CRC) patients with high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR) had heterogeneous pathology and distinct prognoses. This study aimed to examine the difference in the gene expression profile of dMMR/MSI-H CRC patients with different disease stages and explore the different molecular mechanisms of disease progression.MethodsA total of 47 patients with dMMR/MSI-H CRC were enrolled and retrospectively studied, including 27 stage II and 20 stage IV patients. Each patient had paired tumor tissue and white blood cell samples, which were analyzed by next-generation sequencing (NGS) of 416 cancer-relevant genes. Pathway enrichment analysis was then performed to analyze the disease stage-specific signaling pathways.ResultsA total of 2878 mutation sites, spanning 378 mutated genes, were detected from the 47 dMMR/MSI-H CRC patients. The mutation frequencies of SMARCA4, EPHA3, MTHFR, RAD50, and PDGFRB were significantly higher in stage II patients than in stage IV patients (p < 0.05), whereas the stage II patients had significantly lower mutation frequencies of TSC2, FGFR1, PTPN13, SMAD3, and STK11 than stage IV patients (p < 0.05). Sixty-three mutated genes were unique to stage II tumors, while 36 mutated genes were exclusively present in stage IV tumors. Pathway analyses demonstrated the PI3K-AKT pathway was shared by both stage II and stage IV tumors, whereas multiple other signaling pathways showed disease stage-specific enrichment.ConclusionThere were profound differences in mutational profile and molecular mechanisms between stage II and stage IV dMMR/MSI-H CRC.

ObjectivesThis study evaluates artificial intelligence (AI) reasoning capabilities in gynecologic cancer genetic counseling, comparing the performance of ChatGPT and DeepSeek models to guide patient-centered AI implementation in clinical genetics.MethodsUsing 40 National Comprehensive Cancer Network-aligned counseling scenarios, we conducted blinded dual-oncologist evaluations of two large language models. Methodological rigor included model anonymization, a pre-calibrated scoring framework, and validated metrics (Global Quality Scale and Patient Education Materials Assessment Tool) assessing informational coherence, understandability, and actionability.ResultsDeepSeek demonstrated superior informational breadth (mean character difference: -609.0, p < .0001) and visual communication (diagram integration, p < .01), with 49-fold greater probability in recommending clear and actionable actions (p < .01, OR = 49.0). ChatGPT excelled in concise summarization (22% faster response generation, p = .013).ConclusionStrategic AI model selection-leveraging DeepSeek's visually-rich, structured educational approach for complex information, and ChatGPT's concise, rapid summarization for efficient communication-enhances patient-centered genetic education when combined with clinician oversight. This framework supports healthcare's digital transformation by optimizing human-AI collaboration in hereditary cancer care.

Wellbore instability in deep hard-brittle shale formations, primarily induced by hydration-driven strength degradation upon interaction with water-based fluids, poses a critical challenge to hydrocarbon extraction. Conventional triaxial testing for assessing shale hydration behavior is often constrained by substantial sample requirements, extended duration, and high operational costs. In response, this study develops an efficient alternative approach centered on the indentation hardness method. While standard indentation tests are typically limited to hardness and plasticity coefficients, this work establishes theoretical models-based on contact mechanics, elasticity theory, and the Mohr-Coulomb criterion-to derive elastic modulus, Poisson's ratio, and uniaxial compressive strength from indentation data. Experimental analysis of homogenized Longmaxi shale revealed a dense, low-porosity microstructure dominated by non-expansive clay minerals and quartz. Freshwater immersion tests displayed a three-stage absorption trend-rapid, slow, and stable-reaching near-saturation after 72 hours. Pronounced mechanical degradation was observed within the initial 300 hours of immersion, characterized by marked reductions in compressive strength, elastic modulus, and indentation hardness, alongside a stepwise increase in Poisson's ratio; this degradation trend decelerated thereafter. Validation experiments confirmed that single-point indentation hardness measurements provide mechanical equivalence to uniaxial compression responses. As a result, indentation testing on shale chips following fluid immersion offers an efficient and reliable means of evaluating time-dependent fluid-rock interactions. The proposed methodology minimizes core material requirements, enhances operational efficiency, and mitigates the influence of heterogeneity, thereby offering considerable practical value for shale hydration assessment and wellbore stability forecasting.

ObjectiveQuantify recruitment of Native Hawaiian and Pacific Islander (NHPI) participants from 22 Alzheimer's disease (AD) clinical trials over 5 years and utilize choropleth maps as a visual tool to identify where in the Hawaiian community recruited participants are located in order to better inform future recruitment efforts and improve equity and population diversity for future AD clinical trials.MethodsA retrospective chart review was conducted at a dual-site origin clinical trial center in Hawai'i. Inclusion criteria were a diagnosis of mild cognitive impairment and participation in one or more AD clinical trials conducted between 2020 and 2024. Demographic information of clinical trial participants was collected via chart review and included self-identified race/ethnicity, age, residence, and number of clinical trials the patient has participated in. Clinical trial participants were categorized by ZIP codes established by the US Census Bureau. Differences across race/ethnicity groups were assessed using either Pearson's Chi-squared test or Fisher's exact test.ResultsA total of 244 patients participated across the state of Hawai'i in 22 AD clinical trials between 2020 and 2024. Of this total, 169 (69%) patients provided their race/ethnicity, and 75 (31%) did not provide their race/ethnicity. White patients had the highest percentage of participation (44%), followed by Asian patients (34%) and NHPI patients (15%). The population distribution visualized in this study's choropleth maps suggests that NHPI were under-recruited from the west side of O'ahu.ConclusionsOur retrospective study applied choropleth maps to visualize the recruitment data and patterns of AD clinical trials. By utilizing choropleth maps to analyze recruitment areas, the NHPI community and other underrepresented populations may benefit from targeted, culturally informed recruitment strategies.

To address the limitations of flux regulation in traditional permanent magnet synchronous generators and the low power density of electrically excited generators, an interior double-radial asymmetric permanent magnet (PM) and salient-pole electromagnetic hybrid excitation generator are introduced in this study. Equations for the no-load induced electromotive force, the voltage adjustment range, and the total harmonic distortion (THD) are derived theoretically through the analysis of generator parameter relationships. The optimization parameters include the offset angles of the double-layer asymmetric PMs and the structural parameters of the salient-pole rotor. A multi-objective optimization model is established with the no-load induced electromotive force amplitude, the voltage adjustment range, and the THD as the objectives. Samples are generated by Latin Hypercube Sampling, followed by sensitivity analysis of the optimization parameters. The optimization parameters are then screened using Pareto front analysis and a defined parameter matching coefficient. The optimal magnet pole parameters are determined. As a result of optimization, the no-load induced electromotive force amplitude increases by 18.7%, the voltage adjustment range expands by 17.6%, and the THD decreases by 38.2%. Finally, a prototype is fabricated and tested, and the results confirm both the accuracy of the theoretical analysis and the effectiveness of the optimization method. The output characteristics of the designed generator are thereby significantly improved.

ObjectiveTraditional indicators of obesity, such as body mass index (BMI), fail to precisely capture the independent impact of fat distribution on gallstone disease (GSD). This study aimed to investigate the nonlinear association between body fat ratio (BFR) and the risk of GSD and to identify a critical threshold value.MethodWe conducted a cross-sectional observational analysis of 1952 adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). BFR was measured by dual-energy X-ray absorptiometry, and GSD was defined by standardized questionnaire data. Weighted logistic regression, restricted cubic spline (RCS), and threshold effect models were employed to examine the association between BFR and GSD risk, as well as to determine the inflection point.ResultsA significant J-shaped nonlinear association was observed between BFR and GSD risk (P for non-linearity < 0.001). Threshold analysis identified 29.1% (95% CI: 27.5-30.7%) as the critical inflection point, beyond which each 1% increase in BFR was associated with a 14% higher odds of GSD (OR = 1.14, 95% CI: 1.09-1.19). After multivariate adjustment, each additional 1% increase in BFR remained independently associated with a 7% increased risk (OR = 1.07, 95% CI: 1.02-1.13). Compared with participants in the lowest quartile, those in the highest quartile (BFR≥39.2%) exhibited a 2.66-fold higher risk of GSD. Subgroup analyses demonstrated stronger associations in males (OR ≈ 1.12 per 1% BFR increase) and Hispanics (OR ≈ 1.20 per 1% BFR increase).ConclusionsBFR of ≥29.1% represents a critical threshold beyond which GSD risk significantly increases. These findings suggest an association that warrants further investigation into whether routine monitoring of BFR could serve as a valuable screening tool in high-risk populations, and precise intervention strategies should consider gender and ethnic differences to effectively mitigate metabolic-related gallstone disease.