搜索结果：discussions

Vertebral compression fractures (VCFs) are potential complications following spine stereotactic body radiation therapy (SBRT). However, limited data exist on prognostic factors underlying VCF development following SBRT. The objective of this clinical cohort investigation was to evaluate risk factors for VCF development, VCF type (de novo or progressive), and VCF severity, following SBRT for spinal metastases. A retrospective analysis was performed on a prospectively maintained database of 600 SBRT treatments (779 vertebral segments) for spinal metastases from 2002 to 2024. Exclusion criteria consisted of benign tumors, prior lesion-specific surgical intervention, and <1 month of follow-up. Logistic regression and Fine-Gray subdistribution hazard modeling was performed to evaluate predictors of VCF development. The median follow-up was 8 months (range, 1-251 months). Fifty-seven (10%) VCFs were identified following SBRT: 29 (5%) de novo VCFs and 28 (5%) progressive VCFs. The median time-to-VCF was 6 months (range, 1-83 months). The 1- and 3-year cumulative incidence of VCF was 11% (95% CI, 8.1%-15%) and 21% (95% CI, 15%-27%), respectively. On multivariable analysis, female sex (odds ratio [OR], 1.06; 95% CI, 1.02-1.11; P = .007), lumbar lesions (OR, 1.05; 95% CI, 1.00-1.11; P = .049), and pre-existing VCF (OR, 1.01; 95% CI, 1.00-1.02; P = .009) were significantly associated with any VCF development, whereas a greater Spinal Instability Neoplastic Scores (SINS) at SBRT trended toward significance (OR, 1.07; 95% CI, 1.00-1.14; P = .060). Osteolytic disease (OR, 1.04; 95% CI, 1.00-1.07; P = .042) and epidural tumor extension (OR, 1.04; 95% CI, 1.01-1.07; P = .022) were associated with de novo VCF development, whereas only pre-existing VCF (OR, 1.08; 95% CI, 1.04-1.12; P < .001) was significantly associated with progressive VCF development. Thirty-three (58%) VCFs required subsequent surgical stabilization. On multivariable analysis, lumbar lesions (OR, 1.07; 95% CI, 1.02-1.12; P = .004), pre-existing VCF (OR, 1.07; 95% CI, 1.01-1.13; P = .026), and a greater SINS at SBRT (OR, 1.02; 95% CI, 1.01-1.02; P = .002) were significantly associated with VCFs requiring stabilization. This large clinical cohort investigation successfully identified patient subgroups with increased risks of developing VCFs following spine SBRT for metastatic disease. Identifying these at-risk subpopulations may guide additional follow-up surveillance and consideration of individualized discussions regarding potential conservative or stabilization management approaches, particularly for those patients with multiple underlying risk factors.

The American Society of Hematology convened 2 multidisciplinary panels to develop guidelines for the management of acute lymphoblastic leukemia (ALL) among adolescents and young adults (AYAs). The objectives of this study are to (1) describe the process for selecting and prioritizing outcomes for 32 research questions relevant to the guideline development, (2) summarize the prioritized outcomes, and (3) describe the frequency of reporting of those outcomes in existing studies of AYAs with ALL. The panels prioritized outcomes for each of the 19 questions on frontline management, 9 on the management of relapsed/refractory disease, and 4 related to both topics. A 3-step process was used: (1) initial identification of outcomes, (2) online survey of all panel members to rate each outcome's importance, and (3) iterative discussions among the panels to finalize the prioritized outcomes. We examined the frequency with which each prioritized outcome was reported for systematically reviewed research questions. The panels prioritized 34 unique outcomes across questions (median, 7 outcomes per question). The most common outcomes were overall survival (27 questions [84% of questions]); relapse-, event-, disease-, or progression-free survival/relapse (27 questions [84%]); and quality of life (26 questions [81%]). Across 16 systematic reviews for which we found at least 1 study, each prioritized outcome was reported by a median of 25% (interquartile range, 20-48; range 0-79) of the studies. The outcomes prioritized by multidisciplinary guideline panels can inform future primary studies, systematic reviews, and guidelines on ALL, other blood cancers, and AYAs. Future research should involve the development and adoption of a core outcome set for ALL.

Optimal infant and young child feeding (IYCF) practices, particularly exclusive breastfeeding (EBF) for the first 6&#x202f;months, are critical for child survival and development. In low- and middle-income countries, EBF prevalence is commonly estimated using maternal 24-h recall, which may overestimate true practices. This study quantified discrepancies between self-reported and directly observed feeding behaviors and explored socio-cultural determinants of IYCF in rural eastern Ethiopia. A sequential explanatory mixed-methods study was conducted among 106 mother-infant dyads with monthly maternal-recall surveys and two in-home observation sessions in a 79-infant subsample. Discrepancies were examined using chi-square or Fisher's exact tests. To contextualize findings, 26 semi-structured interviews and five focus group discussions with caregivers and community influencers were conducted and thematically analyzed. Cumulative 24&#x202f;h recall across the first 6&#x202f;months classified 70% of infants <6&#x202f;months as EBF. Stricter WHO criteria reduced prevalence (18%; p&#x202f;=&#x202f;0.002). Direct observation confirmed early supplementation: 77% of infants <6&#x202f;months received non-breastmilk substances, 5% met WHO criteria under survey and observation. Surveys indicated timely complementary feeding (6-8&#x202f;months) in 55% of infants, 30% introduced early, 15% late. Key EBF barriers included prelacteal feeding, perceptions of milk insufficiency, seasonal food insecurity, and elder influence. Traditional postpartum rest (ulma) facilitated early breastfeeding, but its protective role diminished as mothers resumed livelihoods. True EBF is markedly lower than 24&#x202f;h recall estimates, highlighting the need for improved approaches and culturally tailored interventions that address feeding rituals, food insecurity, and elder's social influence, while leveraging protective traditions like ulma.

Japan's aging population has increased emergency presentations among patients near the end of life, yet formal palliative care training for emergency physicians remains limited. The U.S.-developed Education in Palliative and End-of-Life Care for Emergency Medicine (EPEC-EM) program offers structured education in communication and symptom management. We piloted a cultural adaptation of selected modules for the Japanese emergency care context. A multidisciplinary Japan-United States team adapted three modules (Trajectories & Prognoses, Breaking Bad News, and Dyspnea Management) through an iterative process involving preliminary redesign, pilot delivery, and refinement across four online sessions. Concepts such as goals-of-care discussions and communication around limiting resuscitation required clearer explanation for Japanese physicians. Iterative revisions improved clarity and cultural relevance. This pilot demonstrates the feasibility of culturally adapting EPEC-EM for Japan. The process provides a foundation for developing a tailored curriculum and informs future broader implementation.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age, typically diagnosed through a combination of clinical evaluation, laboratory testing, and ultrasonography. However, this multimodal diagnostic pathway is often time-consuming, costly, and dependent on resource availability, thereby limiting its accessibility in real-world clinical settings. In this study, we propose AutoPCOS, a stepwise multimodal intelligent framework for flexible PCOS risk stratification and diagnostic support. Using a publicly available Kaggle PCOS dataset, features were categorized into three modalities: clinical, laboratory, and ultrasound data. Based on data availability, four predictive models were constructed: (1) clinical-only, (2) clinical + laboratory, (3) clinical + ultrasound, and (4) full multimodal models. Random Forest was employed as the primary classifier, with comparisons against Logistic Regression, Support Vector Machine, Decision Tree, and Gradient Boosting. Subgroup analyses were conducted based on body mass index (BMI) and menstrual cycle patterns. The proposed framework demonstrated robust predictive performance across different data availability scenarios. Notably, the models achieved strong performance in subgroups with BMI < 24 and irregular menstrual cycles, with precision values reaching &#x2265; 0.929. Comparative analysis confirmed the effectiveness of the Random Forest model. Furthermore, the integration of a knowledge base and the Lingshu large language model enabled interpretable risk explanations and personalized recommendations. AutoPCOS provides a flexible and resource-aware framework for PCOS risk assessment that adapts to varying clinical conditions and data accessibility. By supporting stepwise decision-making and enhancing interpretability, the system shows potential as a practical tool for both patients and healthcare providers. Future work will focus on validation using real-world clinical datasets and improving model generalizability.

Patient portals support health management, yet enrollment remains low. This study evaluated whether timely email nudges increase patient portal enrollment compared with usual system portal invitations, whether message framing influences enrollment, and whether patients nudged to enroll go on to engage with the portal at similar rates as those who enroll organically. In this pre-registered randomized controlled trial at a large health system, 5009 patients aged &#x2265; 18 with recently released laboratory results were randomized over 15 days to: (1) an "Ease" email suggesting immediate access to laboratory results, upon enrollment, (2) a "Transparent" email outlining registration steps needed to access their results, or (3) no email. The primary outcome was portal enrollment within one week. Secondary outcomes included enrollment rates over four years and post-enrollment portal engagement. Post hoc analysis examined the impact of time-sensitive test results. Compared with control, receiving either nudge increased one-week portal enrollment (10.8% vs 3.9%; OR 2.99, P < .001). This difference remained significant through one year post-nudge (36.5% vs 33.1%; OR 1.23, P = .005). Message framing had no significant effect on enrollment. Among emailed patients, nudges were more effective with time-sensitive laboratory results (OR 1.46; P < .001). Among enrollees, long-term portal usage was similar across groups. Beyond standard marketing efforts, timely nudges highlighting the immediate benefit of accessing laboratory test results can meaningfully increase patient portal enrollment-especially when results are time-sensitive. These low-cost, one-time interventions can drive adoption without sacrificing long-term engagement.

Self-rated health is a robust measure of overall health status, encompassing an individual's physical, mental, and social health. This multidimensional characteristic highlights the potential of this variable in studies conducted in regions affected by major disasters. This study assessed the prevalence of poor self-rated health and its association with sociodemographic factors, health behaviors, multimorbidity, and place of residence among adult residents of Brumadinho, Minas Gerais State, Brazil, following the collapse of a mining tailings dam. It is a cross-sectional study based on baseline data from the Brumadinho Health Project, which was conducted in 2021 and included 2,771 individuals aged 18&#x202f;years or older. The outcome variable was poor self-rated health, while the exploratory variables included sociodemographic characteristics, health behaviors, multimorbidity, and place of residence (area directly affected by the disaster; region with mining activity; unexposed). The association between exploratory variables and the outcome was evaluated using logistic regression. The prevalence of poor self-rated health was 6.4% in the municipality's population, being higher in the region directly affected by the tailings mud (12.7%). The likelihood of perceiving health as poor or very poor was higher among women, current smokers, and those with multimorbidity and lower among those who reported consuming alcoholic beverages one or more times per month. Engaging in physical activities at recommended levels reduced the likelihood of poor self-rated health, but only among the unexposed - residents in areas unaffected by mud and without mining activity (p interaction&#x202f;=&#x202f;0.002). These results demonstrate that the residential context modifies the effect of physical activity on self-rated health, such that residents in areas affected by tailings mud or with mining activity do not benefit from engaging in physical activity at recommended levels, at least regarding health perception. Greater efforts to improve environmental conditions may be necessary in regions impacted by major disasters or environmental degradation due to mining processes.

Lipids, particularly phosphoinositides, are increasingly recognized as important markers and causal regulators in cancer progression. Less appreciated, however, are the functional consequences of changes in phospholipid acyl chain length and saturation. These alterations reshape membrane biophysics and rewire membrane-associated signaling complexes, suggesting that acyl-chain remodeling represents an emerging regulatory layer in cancer biology. Distinct tumor types or their models exhibit characteristic acyl chain profiles, often shifting toward shorter, more saturated chains that alter physical and functional interactions. Stress conditions and the tumor microenvironment further diversify these profiles, linking acyl chain composition to cellular plasticity, invasiveness, and metastatic potential. In this review, we summarize the molecular factors and enzymatic pathways that govern phospholipid acyl chain remodeling in cancer and examine their relevance to dynamic protein interaction networks. We describe how dysregulated lipid metabolism at the fatty acid level intersects with oncogenic signaling and highlight emerging chemical biology and multi-omics approaches that enable interrogation of protein-phospholipid interaction networks in physiological contexts. Together, these developments position acyl chain-resolved lipid analysis as a central challenge in chemical biology, requiring new probe design and integrative data frameworks to decode lipid-protein interaction networks in cancer. Finally, we discuss how emerging tools for acyl chain-resolved lipid analysis and targeted modulation reveal how membrane remodeling rewires signaling pathways and reshapes the tumor lipid-protein interactome, opening new opportunities for cancer diagnosis and therapeutic intervention.

Erectile dysfunction (ED) is often treated with phosphodiesterase type 5 inhibitors (PDE5i). However, some patients do not respond effectively to this treatment, making regenerative therapy a potential alternative. This study aims to evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) secretome in patients with severe ED who are unresponsive to sildenafil therapy. In this clinical anatomy pilot study, 15 male patients with severe ED unresponsive to sildenafil were administered intracavernosal injections of 0.5 cc of UC-MSC secretome into each corpus cavernosum at the Andrology Clinic of RSUD Dr. Soetomo (Dr. Soetomo General Academic Hospital) in Surabaya, Indonesia, between January 2024 and May 2024 and at RS Universitas Indonesia between January 2025 and May 2025. Therapy safety was evaluated based on local bleeding, hematoma, infection, and pain, while efficacy was measured using the Erection Hardness Score (EHS), International Index of Erectile Function-5 (IIEF-5), reports of morning erections, stretched penis length (SPL), flaccid penis length (FPL), penis circumference, and Penile Doppler Color Ultrasound to evaluate peak systolic velocity (PSV), resistive index (RI), intima-media thickness (IMT), shear wave elastography (SWE), and strain ratio (SR). Significant improvements were observed in EHS, IIEF-5, morning erections, SPL, FPL, penis circumference, PSV, SWE, and SR after therapy. Pain was temporary and subsided within a few minutes. No significant differences in local bleeding, hematoma, and infection were observed. There was a difference in the IMT of the cavernous artery that was not statistically significant, while RI could not be analyzed. These findings suggest that UC-MSC secretome is safe and effective as an alternative therapy for severe ED unresponsive to sildenafil, as evidenced by significant changes in EHS, IIEF-5, morning erections, SPL, FPL, penis circumference, PSV, SWE, and SR post- therapy with the potential for temporary pain. Further research is needed to support the development of regenerative therapy for the treatment of ED unresponsive to conventional treatments.

Blood-based biomarkers offer a promising, minimally invasive approach to Alzheimer's disease (AD) diagnosis, yet validation in admixed populations remains limited. We investigated whether plasma biomarkers predict CSF-defined AD pathology in a Brazilian cohort. Seventy-eight older adults [including individuals with mild cognitive impairment (MCI), subjective cognitive decline (SCD), and cognitively unimpaired controls] underwent cognitive testing, neuroimaging, and plasma biomarker assessment. CSF data were available for symptomatic participants (MCI and SCD; n = 61), and regression and ROC analyses were performed in the subset with both CSF and APOE genotyping data (n = 53). Plasma A&#x3b2;42, p-Tau181, p-Tau217, t-Tau, and derived ratios were quantified. Multivariable logistic regression and ROC analyses evaluated prediction of abnormal CSF p-Tau181/A&#x3b2;42 and t-Tau/A&#x3b2;42, adjusting for age, sex, and APOE &#x3b5;4 status. Approximately 25% of individuals with MCI exhibited abnormal CSF p-Tau181/A&#x3b2;42 and t-Tau/A&#x3b2;42 ratios. Moderate correlations were observed between plasma and CSF biomarkers (r > 0.4), particularly for A&#x3b2;42/p-Tau217 and p-Tau217. In adjusted models, plasma p-Tau217 and the A&#x3b2;42/p-Tau217 ratio independently predicted abnormal CSF pathology. Each one standard deviation increase in p-Tau217 was associated with 3.53-4.83-fold higher odds of abnormal CSF (p &#x2264; 0.003). In contrast, higher A&#x3b2;42/p-Tau217 ratios were associated with substantially lower odds of pathology, with each one standard deviation increase corresponding to a 91%-93% reduction in risk (p &#x2264; 0.002). The ratio showed stronger associations than p-Tau217 alone. ROC analyses demonstrated good discrimination. For CSF p-Tau181/A&#x3b2;42, A&#x3b2;42/p-Tau217 achieved an AUC of 0.88 (83% sensitivity, 85% specificity), compared with 0.83 for p-Tau217. For CSF t-Tau/A&#x3b2;42, both biomarkers yielded AUCs of 0.89. Plasma A&#x3b2;42/p-Tau217 and p-Tau217 effectively identify CSF-defined AD pathology in an admixed cohort. While higher p-Tau217 levels were associated with increased odds of pathology, higher A&#x3b2;42/p-Tau217 ratios were associated with lower pathological burden and demonstrated stronger effect sizes, supporting the added value of combining amyloid and tau biomarkers. These findings provide initial evidence for local validation of blood-based AD biomarkers in Brazil.

Determining serotype-specific, age-stratified dengue virus (DENV) and Zika virus (ZIKV) seroprevalence rates is crucial for implementing vaccines and vector control strategies. Therefore, we sought to assess the age-stratified seroprevalence of monotypic or multitypic exposure in a community cohort in Sri Lanka. DENV-specific serostatus was assessed in 4161 children aged 4 to 16 years, using an in-house DENV-specific IgG enzyme-linked immunosorbent assay (ELISA), and results were compared with those of a widely used commercial assay (Panbio Dengue IgG Indirect ELISA). We also used a multiplexed, microsphere-based serological assay to characterize monotypic vs multitypic responses and to differentiate exposure rates to different DENV serotypes and ZIKV in a subcohort of children (n = 604). By IgG ELISA, DENV seropositivity was 72.34% (3010/4161), and the seropositivity rate significantly increased with age (Spearman r = 1.0, P = .003). The estimated force of infection was 0.16 (95% credible interval, 0.14-0.17). Of the 604 individuals tested by Luminex, 258 (42.7%) had a monotypic dengue response, whereas 209 (34.9%) had a multitypic response. Moreover, 100 (16.5%) had evidence of a past infection to Zika, while 20 (3.33%) children had antibodies only to ZIKV. Of the 258 individuals with evidence of a monotypic response to DENV, DENV2 (56.83%) and DENV1 (30.57%) accounted for the most infections. There was an inverse correlation between exposure to ZIKV and age (Spearman r = -0.72, P = .007). An overall 72.3% of children were seropositive for dengue, with 42.7% having been infected with only 1 DENV in the past. The data suggest that prior immunity to DENV may reduce the risk of ZIKV infection, which should be further assessed.

Environmental risk factors-air pollution, noise, heat, chemical contamination, and light pollution-are increasingly recognized as key contributors to cardiovascular disease but remain underrepresented in clinical guidelines and public health strategies. This comprehensive review, developed under the auspices of the European Society of Cardiology (ESC), synthesizes current evidence on the cardiovascular consequences of environmental exposures. Building on prior ESC recommendations on air pollution, the consensus statement extends the focus to include climate change, urban heat islands, chemical pollutants, noise, and light pollution, highlighting their shared pathophysiological mechanisms: oxidative stress, inflammation, endothelial dysfunction, and circadian disruption. Epidemiological and experimental studies confirm that these exposures exacerbate the incidence of coronary artery disease, stroke, heart failure, arrhythmias, and hypertension-even at levels below existing regulatory thresholds. It is proposed the exposome framework as a conceptual tool to understand the cumulative lifetime impact of environmental hazards on cardiovascular health. Special attention is given to vulnerable populations, including children, the elderly, socioeconomically disadvantaged groups, and patients with pre-existing cardiovascular disease. The document outlines urgent research needs, such as the need for high-resolution exposure data, exploration of gene-environment interactions and molecular pathways, and the development of real-world and mechanistic studies assessing interventions. Mitigation strategies are discussed across individual, clinical, and policy levels, with a call for heart-healthy urban design, stricter emissions legislation, and equitable access to clean environments. Cardiologists are uniquely positioned to advocate for environmental cardiovascular health, bridging the gap between science, clinical care, and policy. This statement aims to accelerate that translation by raising awareness and promoting action across disciplines.

This cross-sectional study compared the differences, consistencies, and correlations of the measurements of anterior segment biological parameters between Sirius Plus and Pentacam AXL in a healthy population with myopia. Eighty patients with myopia (80 eyes) scheduled for refractive surgery at the Ophthalmology Department of the Third People's Hospital of Dalian from December 2024 to June 2025 were included. One eye was randomly selected for each participant, and measurements were taken using Sirius Plus and Pentacam AXL. Fourteen parameters related to the anterior segment were extracted. The differences in the measurements for anterior flat keratometry, anterior vertical/horizontal astigmatism, and anterior oblique astigmatism at 45&#xb0; between the two devices were not significant, whereas those for the other parameters were significant. The intraclass correlation coefficient values for anterior flat keratometry, anterior steep keratometry, and white-to-white were 0.965, 0.963, and 0.932, respectively. The goodness-of-fit analysis showed that the R 2 values for the anterior flat keratometry, anterior steep keratometry, central corneal thickness, white-to-white, corneal volume, and anterior chamber depth were all >0.85, which demonstrated a strong correlation. Anterior corneal keratometry and white-to-white had good correlation and consistency, indicating they are suitable mutual reference points for clinical practice.

Accurate preoperative imaging is essential in advanced epithelial ovarian cancer, where complete cytoreduction remains the strongest prognostic factor. This study evaluates the CT PAUSE score-a structured, domain-based reporting tool-for its utility in surgical planning and multi-disciplinary team (MDT) decision-making. In this prospective cross-sectional study between September 2022 to February 2024, 124 patients with FIGO stage III/IV ovarian cancer underwent 175 contrast-enhanced CT scans. PAUSE components-Peritoneal Cancer Index (PCI), Ascites/abdominal wall disease, Unfavourable sites, Small bowel/mesenteric disease, and Extra-peritoneal metastases-were prospectively scored during evaluation. Interobserver agreement was assessed in a subset of 30 cases. MDT triage using PAUSE resulted in a complete cytoreduction rate of 89.3%. A simplified nomogram based on upper abdominal disease volume showed discriminatory ability (area under the curve (AUC) [95% CI] = 0.820 [0.740-0.880]) and could be an alternative to the full radiological PCI-based nomogram (AUC) [95% CI] = 0.763 [0.677-0.835]), in busy clinical settings. Interobserver agreement was substantial for both nomogram scores, with higher reliability observed for the score derived from the upper abdominal disease-based nomogram (intraclass correlation coefficient (ICC) [95% CI] = 0.710 [0.582-0.825] versus 0.627 [0.460-0.778]; p < 0.001). CT PAUSE provides a structured approach to radiological reporting and may support more consistent MDT discussions and surgical triage in advanced ovarian cancer. Its performance in this cohort might suggest potential for integration into clinical workflows, pending further validation. There was no funding source for this study.

To use bibliometric methods to deeply analyze the application of WeChat in China's mHealth field, outline its research panorama, and clarify research frontiers. Literature from January 2011 to December 2024 was sourced from the Web of Science Core Collection, and PubMed databases. The work has been registered in PROSPERO (ID: CRD420251060517). Bibliometrix, Biblioshiny, VOSviewer, GraphPad Prism, and Adobe Photoshop were used for bibliometric analysis and visualization of the included literature. A total of 1633 publications were initially retrieved, and 379 eligible documents were finally included after rigorous screening based on inclusion and exclusion criteria (1254 excluded). The annual publication output showed a sharp growth from 2016 to 2021 and entered a stable phase thereafter, while the citation count has maintained a steady upward trend since 2020. China was identified as the core contributing country in this research field. Among institutional contributors, Fujian Medical University ranked first in publication output, and Sun Yat-sen University exhibited outstanding citation impact. Keyword co-occurrence analysis identified two distinct research clusters, with one focusing on clinical practice and disease-oriented research, and the other centering on research scientificity and population health research. It reveals a growing and interdisciplinary research area, and the trends in publication outputs, citations, and research hotspots can serve as a guide for future research. This research thoroughly outlined the current state of WeChat in China's mHealth, addressed research gaps, and suggested future research directions to encourage innovative applications.

N 6-methyladenosine (m6A) is a pivotal RNA modification involved in diverse biological and pathological processes. Compared to the m6A detection methods based on second-generation sequencing, Nanopore direct RNA sequencing (DRS) offers the unique advantage of capturing native modifications. Here, we present Nanopore-m6A-Finder (NP-mFinder), a reference-free m6A prediction computational framework that employs the XGBoost model in the mRNA exonic region and a hard-voting ensemble of XGBoost and random forest models in the poly(A) region. NP-mFinder can determine m6A sites as well as estimate their methylation levels from Guppy basecalled DRS data. After training with DRS data of in vitro-transcribed RNA, NP-mFinder achieved high performance on held-out test datasets (area under the curve (AUC) &#x2248;0.90; accuracy, precision, recall, and F1-score >0.80). Comparing with canonical m6A detection methods, it recovered 20% of meRIP-seq-defined m6A sites in yeast, and 27% of our HEK293 site prediction overlapped with miCLIP calls. Although single-base overlap with existing DRS-based tools of EpiNano and mAFiA was limited, 73% of our identified m6A-containing genes were validated by at least one of them. Benchmarking our method with GLORI v2.0 revealed concordance of 28% at a site level and 85% at a gene level, as well as a mild correlation on m6A level estimations. Notably, NP-mFinder achieved 93% precision in detecting m6A within the "AAAAA" sequence context in the mRNA exonic region of HEK293T DRS data when compared to high-confidence m6A site annotation in GLORI v2.0, demonstrating the good performance of our method in the region possessing a stretch of continuous A-sequences. Moreover, our method predicted that m6A might exist in the human HEK293 poly(A) region, suggesting a possibly conserved phenomenon of a modified poly(A) tail beyond the previously reported T. brucei variant surface glycoprotein (VSG) transcripts. Together, these results established NP-mFinder as a robust and versatile tool for transcriptome-wide m6A profiling with DRS data at single-read resolution.

Osteoporotic vertebral compression fractures (OVCFs) present diagnostic challenges, especially in elderly patients with low bone density. Radiographic measurement is key to surgical decision-making, but their reliability in these patients with lower radiological density is questionable. What is the intra- and inter-rater reliability and responsiveness to the measurement of two commonly used radiographic parameters-vertebral kyphotic angle (VKA) and vertebral body height (VBH)-using two different DICOM software platforms for patients undergoing surgical treatment for OVCFs? Patients treated surgically for OVCFs were randomly extracted. Sagittal vertebral body deformity was evaluated using the VKA and the VBH (pre-operative, post-operative and change over time). One operator repeated measurements with one-month interval (intra-rater reliability), using two software platforms (OsiriX MD and Weasis). Three randomly assigned surgeons per platform performed blindly measurements (inter-rater). Reliability was assessed using intraclass correlation coefficients (ICC). Thirty-four patients (71% females; mean age 75.3&#xa0;&#xb1;&#xa0;9.4 years) were included. Intra-rater and inter-rater reliability were reported as good-to-excellent (ICC: 0.75-0.90) for VKA, and good-to-moderate (ICC: 0.50-0.75) for VBH. Reliability for measuring post-operative change was moderate for both outcomes. Both software platforms perform comparably with good agreement. This was the first study to assess the reliability and responsiveness of postoperative radiographic changes in OVCF surgery across two different software platforms. VKA is a more reliable measurement than VBH. These findings support using VKA to guide treatment and monitoring recovery, although measurement error remain important considerations in elderly patients with low bone density.

Doxorubicin (DOX) is a cornerstone chemotherapeutic for breast cancer; however, its clinical efficacy is limited by inefficient intracellular delivery and dose-limiting off-target toxicity. Microenvironment-responsive nanoplatforms offer a promising strategy to enhance tumor selectivity and therapeutic performance. A core-shell nanosystem (UTMD) was constructed by coating an NH2-MIL-88B(Fe) metal-organic framework (Fe-MOF) shell onto a UCNP@TiO2 scaffold. The Fe-MOF shell was designed as a dual pH- and glutathione (GSH)-responsive gatekeeper for controlled DOX release. The nanosystem was characterized for structural features, drug loading, and stimulus-responsive release behavior. Cellular uptake, intracellular trafficking, cytotoxicity, and redox-related biochemical changes were evaluated in MCF-7 breast cancer cells and HEK-293 normal cells. UTMD achieved high encapsulation efficiency (86.5%) and maintained stability under physiological conditions, while enabling accelerated DOX release in acidic and reducing environments. The nanosystem enhanced cellular internalization and promoted nuclear accumulation of DOX in MCF-7 cells. In addition, UTMD induced significant intracellular redox imbalance, characterized by GSH depletion, increased reactive oxygen species levels, and elevated lipid peroxidation, accompanied by mitochondrial membrane potential depolarization. These changes are consistent with ferroptosis-associated oxidative damage. Compared with free DOX, UTMD exhibited improved cytocompatibility in HEK-293 cells. The Fe-MOF shell functions as a microenvironment-responsive gatekeeper that coordinates controlled drug release with iron-mediated oxidative stress. This integrated design links chemotherapy with ferroptosis-associated mechanisms, improving therapeutic selectivity and mechanistic interpretability. UTMD represents a microenvironment-activated nanoplatform that enables controlled DOX delivery and ferroptosis-associated oxidative damage. This strategy enhances antitumor efficacy while reducing off-target toxicity, offering potential for improved breast cancer therapy.

White matter hyperintensities (WMH) are robust markers of vascular brain injury and predictors of poorer cognition, but their contributions may differ across racial and ethnic groups. We analyzed 3585 participants from the Health and Aging Brain Study-Health Disparities cohort (1264 non-Hispanic White [NHW], 1003 non-Hispanic Black [NHB], 1318 Hispanic). Baseline demographics, vascular risk factors, apolipoprotein E &#x3b5;4, magnetic resonance imaging-derived WMH, and domain-specific cognitive z scores were assessed. We used moderated mediation models to evaluate whether WMH mediated the age-cognition relationship by race/ethnicity. Greater WMH volume was associated with poorer memory, executive function, processing speed, and language (all p&#xa0;<&#xa0;0.01). Mediation by WMH varied across groups: WMH explained &#x2248; 30% of the age-cognition association in NHWs, 20% to 28% in NHBs, and 12% to 19% in Hispanics. WMHs consistently mediated age-related lower cognition, but group differences highlight the contribution of cardiometabolic, neuropathological, and social determinants beyond WMHs in NHB and Hispanic populations.