The cerebellum computes frequency dynamics for motions with numerical precision and cross-individual uniformity.

Cross-individual variability is considered the essence of biology, preventing precise mathematical descriptions of biological motion1-7 like the physics law of motion. Here we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in-vivo electrophysiology and optogenetics in mice, we confirmed that deep cerebellar neurons encoded frequencies via populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism was consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform, or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validated the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating-current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for brain-computer interface for motor control.

Squamoid Eccrine Ductal Carcinoma Displays UV-Mutations and Intermediate Gene Expression Relative to Squamous Cell Carcinoma, Microcystic Adnexal Carcinoma, and Porocarcinoma.

Squamoid eccrine ductal carcinoma is a rare infiltrative tumor with morphologic features intermediate between squamous cell carcinoma (SCC) and sweat gland carcinomas such as microcystic adnexal carcinoma. Although currently classified as a sweat gland carcinoma, it has been debated whether squamoid eccrine ductal carcinoma is better classified as a variant of SCC. Furthermore, therapeutic options for patients with advanced disease are lacking. Here, we describe clinicopathologic features of a cohort of 15 squamoid eccrine ductal carcinomas from 14 unique patients, with next generation sequencing DNA profiling for 12 cases. UV-signature mutations were the dominant signature in the majority of cases. TP53 mutations were the most highly recurrent specific gene alteration, followed by mutations in NOTCH genes. Recurrent mutations in driver oncogenes were not identified. By unsupervised comparison of global transcriptome profiles in squamoid eccrine ductal carcinoma (n=7) to SCC (n=10), porocarcinoma (n=4), and microcystic adnexal carcinoma (n=4), squamoid eccrine ductal carcinomas displayed an intermediate phenotype between SCC and sweat gland tumors. Squamoid eccrine ductal carcinoma displayed significant higher expression of 364 genes (including certain eccrine markers) and significant lower expression of 525 genes compared to other groups. Our findings support the classification of squamoid eccrine ductal carcinoma as a carcinoma with intermediate features between SCC and sweat gland carcinoma.

Integrative Drug Screening and Multiomic Characterization of Patient-derived Bladder Cancer Organoids Reveal Novel Molecular Correlates of Gemcitabine Response.

BACKGROUND AND OBJECTIVE: Predicting response to therapy for each patient's tumor is critical to improving long-term outcomes for muscle-invasive bladder cancer. This study aims to establish ex vivo bladder cancer patient-derived organoid (PDO) models that are representative of patients' tumors and determine the potential efficacy of standard of care and curated experimental therapies. METHODS: Tumor material was collected prospectively from consented bladder cancer patients to generate short-term PDO models, which were screened against a panel of clinically relevant drugs in ex vivo three-dimensional culture. Multiomic profiling was utilized to validate the PDO models, establish the molecular characteristics of each tumor, and identify potential biomarkers of drug response. Gene expression (GEX) patterns between paired primary tissue and PDO samples were assessed using Spearman's rank correlation coefficients. Molecular correlates of therapy response were identified using Pearson correlation coefficients and Kruskal-Wallis tests with Dunn's post hoc pairwise comparison testing. KEY FINDINGS AND LIMITATIONS: A total of 106 tumors were collected from 97 patients, with 65 samples yielding sufficient material for complete multiomic molecular characterization and PDO screening with six to 32 drugs/combinations. Short-term PDOs faithfully represent the tumor molecular characteristics, maintain diverse cell types, and avoid shifts in GEX-based subtyping that accompany long-term PDO cultures. Utilizing an integrative approach, novel correlations between ex vivo drug responses and genomic alterations, GEX, and protein expression were identified, including a multiomic signature of gemcitabine response. The positive predictive value of ex vivo drug responses and the novel multiomic gemcitabine response signature need to be validated in future studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Short-term PDO cultures retain the molecular characteristics of tumor tissue and avoid shifts in expression-based subtyping that have plagued long-term cultures. Integration of multiomic profiling and ex vivo drug screening data identifies potential predictive biomarkers, including a novel signature of gemcitabine response. PATIENT SUMMARY: Better models are needed to predict patient response to therapy in bladder cancer. We developed a platform that uses short-term culture to best mimic each patient's tumor and assess potential sensitivity to therapeutics.

Phototactic/Photosynthetic/Magnetic-Powered Chlamydomonas Reinhardtii-Metal-Organic Frameworks Micro/Nanomotors for Intelligent Thrombolytic Management and Ischemia Alleviation.

Thrombosis presents a critical health threat globally, with high mortality and incidence rates. Clinical treatment faces challenges such as low thrombolytic agent bioavailability, thrombosis recurrence, ischemic hypoxia damage, and neural degeneration. This study developed biocompatible Chlamydomonas Reinhardtii micromotors (CHL) with photo/magnetic capabilities to address these needs. These CHL micromotors, equipped with phototaxis and photosynthesis abilities, offer promising solutions. A core aspect of this innovation involves incorporating polysaccharides (glycol chitosan (GCS) and fucoidan (F)) into ferric Metal-organic frameworks (MOFs), loaded with urokinase (UK), and subsequently self-assembled onto the multimodal CHL, forming a core-shell microstructure (CHL@GCS/F-UK-MOF). Under light-navigation, CHL@GCS/F-UK-MOF is shown to penetrate thrombi, enhancing thrombolytic biodistribution. Combining CHL@GCS/F-UK-MOF with the magnetic hyperthermia technique achieves stimuli-responsive multiple-release, accelerating thrombolysis and rapidly restoring blocked blood vessels. Moreover, this approach attenuates thrombi-induced ischemic hypoxia disorder and tissue damage. The photosynthetic and magnetotherapeutic properties of CHL@GCS/F-UK-MOF, along with their protective effects, including reduced apoptosis, enhanced behavioral function, induced Heat Shock Protein (HSP), polarized M2 macrophages, and mitigated hypoxia, are confirmed through biochemical, microscopic, and behavioral assessments. This multifunctional biomimetic platform, integrating photo-magnetic techniques, offers a comprehensive approach to cardiovascular management, advancing related technologies.

Risk and impact of cytomegalovirus infection in lymphoma patients treated with bendamustine.

Bendamustine is used to treat lymphoma with excellent efficacy but is known for its immunosuppressive effect. Cytomegalovirus (CMV) reactivation after bendamustine use has been reported. We aim to address the impact of CMV infection in lymphoma patients treated with bendamustine-containing regimens. We retrospectively analyzed lymphoma patients at Taipei Veterans General Hospital in Taiwan between September 1, 2010, and April 30, 2022. Clinically significant CMV infection (CS-CMVi) was defined as the first CMV reactivation after bendamustine use necessitating CMV therapy. Patients' baseline characteristics and laboratory data were recorded. The primary endpoint of the study was CS-CMVi. A time-dependent covariate Cox regression model was used to estimate the risk factors of CS-CMVi and mortality. A total of 211 lymphoma patients treated with bendamustine were enrolled. Twenty-seven (12.8%) had CS-CMVi. The cumulative incidence was 10.1 per 100 person-years during the three-year follow-up period. In the multivariate analysis, lines of therapy before bendamustine ≥ 1 (95% CI 1.10-24.76), serum albumin < 3.5 g/dL (95% CI 2.63-52.93), and liver disease (95% CI 1.51-28.61) were risk factors for CS-CMVi. In conclusion, CS-CMVi (95% confidence interval [CI] 1.23-10.73) was one of the major independent risk factors of mortality. Lines of therapy before bendamustine ≥ 1, hypoalbuminemia, and liver disease were risk factors for CS-CMVi in lymphoma patients treated with bendamustine.

Sequential management of burn wound healing stages through biointelligence-inspired platelet extracellular vesicle-encapsulated photodynamic diferuloylmethane.

The process of wound healing is a complex, multi-phase phenomenon crucial for optimal tissue regeneration. Traditional drug delivery systems often target specific phases of wound repair, neglecting the dynamic interplay among the stages. This limitation highlights the need for comprehensive delivery systems that cater to the holistic needs of wound healing, enhancing tissue regeneration efficiency. Herein, we explored the utility of platelet-derived extracellular vesicles (pEVs) as carriers for the phototherapeutic diferuloylmethane (DIF), resulting in a formulation termed DIF@pEVs, which is designed to sequentially address the distinct phases of wound healing. Initially, upon exposure to light, administered DIF@pEVs generate photodynamic therapy-derived reactive oxygen species during the early inflammatory phase. This generation of ROS aims to modulate the inflammatory response, induce the protective mechanisms of heat shock proteins, and kickstart the tissue regeneration process. Following this initial phase, the remaining DIF and pEVs persist in promoting tissue repair and regeneration. Ultimately, it reduces inflammation, speeds up the healing process, and promotes vascular and follicular formation in a model of burn wound skin damage, thereby supporting skin regeneration. The deployment of DIF@pEVs represents an advancement in regenerative medicine, providing a precise, versatile approach to fostering regeneration across a wide range of clinical scenarios.

Spermatozoon-propelled microcellular submarines combining innate magnetic hyperthermia with derived nanotherapies for thrombolysis and ischemia mitigation.

Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.

The role of extensive lymph node dissection in the new grading system for lung adenocarcinoma.

OBJECTIVES: This study evaluates the prognostic impact of the new grading system for lung adenocarcinoma, stratified by lymphadenectomy extent. MATERIALS AND METHODS: We analyzed 1258 lung adenocarcinoma patients who underwent curative resections between 2006 and 2017. We analyzed overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) across tumor grades and lymphadenectomy extent, categorized as IASLC-R0 (complete resection) or R(un) (uncertain resection). RESULTS: The median age of cohort was 63 and 41.9 % were male. The majority had undergone lobectomy. The distribution of tumors was 274 grade 1, 558 grade 2, and 426 grade 3 cases. After a median follow-up time of 102 months, the 10-year OS/CSS/RFS rates worsened significantly across grade 1-3: 92.4/99.3/92.3 %, 77.8/87.5/71.7 %, and 63.6/70.2/52.0 %, respectively (p < 0.001). Multivariate Cox regression analysis identified grade 3, R(un) lymphadenectomy, higher Charlson Comorbidity Index, smoking history, thoracotomy, higher pathology stage, and angiolymphatic invasion as independent prognostic factors for lower OS, CSS, and RFS. Furthermore, grade 3 patients benefited significantly from IASLC-R0 lymphadenectomy, showing significantly better OS and RFS than those who underwent R(un) lymphadenectomy (p = 0.007 for OS, p = 0.001 for RFS, post-propensity score matching). Among grade 3 tumors underwent R0 or R(un) resections found the incidence rates of local, distant, and simultaneous local and distant recurrence were 8.5 % vs 13.7 %, 11.0 % vs 12.2 %, and 11.0 % vs 20.6 %, respectively. CONCLUSION: Surgical outcomes for lung adenocarcinoma have declined across grades 1-3. IASLC-R(un) treatment worsens OS and RFS in grade 3. Intensive monitoring and adjuvant therapy should be considered when patients with grade 3 lung adenocarcinoma undergo R(un) lymphadenectomy.

Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

BACKGROUND/AIM: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited. PATIENTS AND METHODS: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared. RESULTS: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C ß-lactamases, and carbapenemase. CONCLUSION: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required.

Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. MATERIALS AND METHODS: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. RESULTS: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). CONCLUSION: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.

Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-ß-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL10 for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) µg/kg_bw/day and 22.82 (18.09) µg/kg_bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 µg/kg_bw/day recommended by the WHO (EFSA).

Family trajectories among immigrants and their descendants in three European countries: A multistate approach in comparative research.

This study investigates partnership changes and childbearing among immigrants and their descendants in the UK, France, and Germany. Our analysis of longitudinal data shows, first, significant diversity in family trajectories among immigrants and their descendants in Europe. Immigrants from other European countries and their descendants tend to cohabit prior to marriage, and their fertility in unions is often similar to that of the native population. In contrast, South Asians and Turkish populations exhibit marriage-centred family behaviour with elevated third-birth rates. Individuals of sub-Saharan African or Caribbean origin display higher rates of non-marital family transitions. Second, we observe some changes in partnership and childbearing patterns across migrant generations; these are stronger for fertility than for partnership patterns. Third, migration background is particularly associated with partnership patterns, whereas the destination country context influences childbearing patterns. We expect some patterns to persist across future migrant generations (e.g. preference for marriage vs cohabitation), whereas others are likely to vanish (e.g. large families).

Estimating the risk of major adverse cardiac events following radiotherapy for left breast cancer using a modified generalized Lyman normal-tissue complication probability model.

BACKGROUND: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT). MATERIALS AND METHODS: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups. RESULTS: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D50 = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D50 = 30 Gy) compared to the low-comorbidity group (D50 = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively. CONCLUSION: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT.

The Relationship Between Carotid Artery Stenosis and the Development of Open-Angle Glaucoma: A Long-term Cohort Study in Taiwan.

PURPOSES: To determine the relationship between carotid artery stenosis (CAS) and the development of open-angle glaucoma (OAG) in the Taiwanese population. METHODS: This retrospective cohort study was conducted using Chang Gung Research Database. Cox-proportional hazards model was applied to calculate the hazard ratio for OAG between CAS and the control cohort. RESULTS: Among 19,590 CAS patients, 17,238 had mild CAS (<50%), 1,895 had moderate CAS (50-69%), and 457 had severe CAS (≥70%). The CAS cohort had a higher proportion of several comorbidities. After adjusting for comorbidities, no significant difference in OAG development was found between CAS and control cohorts. Matching for key comorbidities, no significant differences in OAG incidence were found between matched cohorts (P = .869). Subdividing the matched CAS cohort by stenosis severity: mild (<50%), moderate (50-69%), and severe (≥70%), a statistically significantly lower OAG risk was observed in patients with mild CAS stenosis (HR: 1.12, 95% CI = 1.03-1.21, P = .006). Kaplan-Meier analysis revealed reduced OAG incidence in CAS patients who underwent surgical intervention, compared to the control cohort (P <.001). Subgroup analysis revealed that patients in the mild CAS stenosis group, those who underwent surgical intervention exhibited a reduced OAG risk (HR: 0.29, 95% CI = 0.15-0.58, P = .001). CONCLUSIONS: No statistically significant differences in OAG risk were observed between patients with CAS and the control cohort. The severity of CAS appears to influence OAG risk, with surgical intervention potentially offering protective effects, particularly in patients with mild CAS stenosis (<50%), suggesting that enhanced ocular perfusion post-surgery may act as a protective factor against OAG development.

Esophagectomy in patients with esophageal squamous cell carcinoma and distant nodal metastasis.

The role of surgery in oligometastatic esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the oncological outcomes after esophagectomy in patients with ESCC with distant lymph node (LN) metastasis. Patients with ESCC and nodal metastasis treated with chemoradiotherapy or chemotherapy followed by esophagectomy between 2010 and 2020 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients with distant LN metastasis (dLN+) and exclusively regional LN metastasis (dLN-). The cohort comprised 69 dLN+ and 111 dLN- patients. Survival was significantly better in the dLN- group than in the dLN+ group (5-year OS, 51.9% vs. 25.5%, P < 0.001; RFS, 47.2% vs. 18.1%, P < 0.001). Stratified by the yp stage, 49 (44.1%) dLN- and 30 (43.5%) dLN+ patients achieved a pathological complete response (pCR). In the dLN- and dLN+ groups, the OS rates were significantly higher in the pCR group than in the non-pCR group (dLN-: 76.7% vs. 32.4%, P < 0.001; dLN+: 39.6% vs. 14.2%; P = 0.002). The dLN-/pCR group had the best OS, significantly outperforming the dLN-/non-pCR and dLN+/pCR groups. OS did not differ between the dLN-/non-pCR and dLN+/pCR groups. The dLN+/non-pCR group had the worst OS. The RFS analysis paralleled the OS findings. Patients with dLN+ disease had worse outcomes than their dLN- counterparts, irrespective of the pCR status. The survival rates were poor but comparable between the dLN+/pCR and dLN-/non-pCR groups. Adjuvant therapy may be required for dLN+ patients following systemic treatment and surgery, even after achieving pCR.

Leveraging a Longitudinally Linked Dataset to Assess Recurrence of Severe Maternal Morbidity.

OBJECTIVES: Among those with a severe maternal morbidity (SMM) event and a subsequent birth, we examined how the risk of a second SMM event varied by patient characteristics and intrapartum hospital utilization. METHODS: We used a Massachusetts population-based dataset that longitudinally linked in-state births, hospital discharge records, prior and subsequent births, and non-birth-related hospital utilizations for birthing individuals and their children from January 1, 1999, to December 31, 2018, representing 1,460,514 births by 907,530 birthing people. We restricted our study sample to 2,814 people who had their first SMM event associated with a singleton birth and gave birth a second time within the study period. Our outcome measure was recurrence of SMM in the second birth. We calculated the prevalence of SMM at second birth, compared SMM conditions between births, and estimated the adjusted risk ratios and 95% confidence intervals for having an SMM event at second birth among those who had an SMM at the first birth. We also examined overall hospital utilization including inpatient admissions, emergency room visits, and observational stays, and hospital utilization by interpregnancy intervals (IPIs) between the first and second birth. RESULTS: There were 2,814 birthing people with at least one birth after the first SMM singleton birth. Among those, 198 (7.0%) had a subsequent SMM. The percentage of people with a second SMM event varied by age, race/ethnicity, insurance, IPI, and history of hypertension at first case of SMM (all p < .05). Between births, people with a second SMM event had significantly higher proportions of inpatient admissions (60.1% vs. 33.2.0%; p < .001), emergency room visits (71.7% vs. 57.7%; p < .001), and observational stays (35.4% vs. 19.5%; p < .001) compared with those who did not experience a second SMM event. CONCLUSION: Hospital utilization after a birth with SMM might indicate an elevated risk of a second SMM event. Providers should counsel their patients about prevention and warning signs.

Using large language model (LLM) to identify high-burden informal caregivers in long-term care.

BACKGROUND: The rising global elderly population increases the demand for caregiving, yet traditional methods may not fully assess the challenges faced by vital informal caregivers. OBJECTIVE: To investigate the efficacy of Large Language Model (LLM) in detecting overburdened informal caregivers, benchmarking against rule-based and machine learning methods. METHODS: 1,791 eligible informal caregivers from Southern Taiwan and utilized their textual case summary reports for the LLM. We also employed structured questionnaire results for machine learning models. Furthermore, we leveraged the visualization of the LLM's attention mechanisms to enhance our understanding of the model's interpretative capabilities. RESULTS: The LLM achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 and an Area Under the Precision-Recall Curve (AUPRC) of 0.70, marking an 8% and 14% improvement over traditional methods. The visualization of the attention mechanism accurately reflected the evaluations of human experts, concentrating on descriptions of high-burden descriptions and the relationships between caregivers and recipients. CONCLUSION: This research demonstrates the notable capability of LLM to accurately identify high-burden caregivers in Long-term Care (LTC) settings. Compared to traditional approaches, LLM offers an opportunity for the future of LTC research and policymaking.

GDF-15 Attenuates the Epithelium-Mesenchymal Transition and Alleviates TGFß2-Induced Lens Opacity.

Purpose: We sought to evaluate the efficacy of growth differentiation factor (GDF)-15 treatment for suppressing epithelial-mesenchymal transition (EMT) and alleviating transforming growth factor ß2 (TGFß2)-induced lens opacity. Methods: To test whether GDF-15 is a molecule that prevents EMT, we pretreated the culture with GDF-15 in neural progenitor cells, retinal pigment epithelial cells, and lens epithelial cells and then treated with factors that promote EMT, GDF-11, and TGFß2, respectively. To further investigate the efficacy of GDF-15 on alleviating lens opacity, we used mouse lens explant culture to mimic secondary cataracts. We pretreated the lens culture with GDF-15 and then added TGFß2 to develop lens opacity (n = 3 for each group). Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure EMT protein and gene expression, respectively. Results: In cell culture, GDF-15 pretreatment significantly attenuated EMT marker expression in cultured cells induced by treatment with GDF-11 or TGFß2. In the lens explant culture, GDF-15 pretreatment also reduced mouse lens opacity induced by exposure to TGFß2. Conclusions: Our results indicate that GDF-15 could alleviate TGFß2-induced EMT and is a potential therapeutic agent to slow or prevent posterior capsular opacification (PCO) progression after cataract surgery. Translational Relevance: Cataracts are the leading cause of blindness worldwide, with the only current treatment involving surgical removal of the lens and replacement with an artificial lens. However, PCO, also known as secondary cataract, is a common complication after cataract surgery. The development of an adjuvant that slows the progression of PCO will be beneficial to the field of anterior complications.