Enhanced photocatalytic hydrogen production via water splitting using cobalt-based organic nanofibers under visible light irradiation.

This study focuses on the development of cobalt-based organic nanofibers as efficient photocatalysts for hydrogen production via water splitting under visible light irradiation. The depletion of fossil fuels necessitates the exploration of alternative energy sources, with hydrogen emerging as a promising candidate due to its clean and renewable nature. While conventional photocatalysts have shown potential, their limited activity under visible light and fast electron-hole recombination hinder their efficiency. In this work, cobalt acetate/poly(vinyl alcohol) (CoAc/PVA) nanofibers were electrospun and treated in a novel reactor design under water gas atmosphere at 160 °C to produce continuous, smooth, and stable nanobelts. The nanofibers displayed a band gap energy of 2.29 eV, indicating strong absorption in the visible light range. Detailed characterization using FTIR, XPS, SEM, and TGA confirmed the formation of organic-inorganic hybrid nanofibers with uniform cobalt distribution. Hydrogen production experiments showed that the proposed nanofibers significantly outperformed Co3O4 nanofibers, with an optimal hydrogen generation rate of 3.266 mmol gcat -1 s-1 at 70 vol% methanol. Furthermore, the treated nanofibers demonstrated good stability over multiple cycles, maintaining a constant hydrogen production rate after the third run. The study highlights the advantages of cobalt-based organic nanofibers in overcoming the limitations of traditional photocatalysts, providing a novel route for sustainable hydrogen production.

Optimizing target and diaphragmatic configuration, and dosimetric benefits using continuous positive airway pressure in stereotactic ablative radiotherapy for lung tumors.

PURPOSE: This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. MATERIALS AND METHODS: We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. RESULTS: Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm3 vs. 4.09 cm3; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm3 vs. 22.52 cm3, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. CONCLUSION: This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management.

COL8A2 Activation Enhances Function of Corneal Endothelial Cells through HIPPO Signaling/Mitochondria Pathway.

Corneal endothelial cells (CECs) are essential for maintaining corneal transparency and hydration through their barrier and pump functions. The COL8A2 gene encodes a component of the extracellular matrix of the cornea, which is crucial for the normal functioning of these cells. Mutations in COL8A2 are linked to corneal dystrophies, emphasizing the gene's importance in corneal health. The purpose of this research is to explore the effects of COL8A2 activation within CECs, to understand its contribution to cellular behavior and health. COL8A2 CRISPR/dCas9 activation system (aCOL8A2) was used to activate the COL8A2. In rats, wound healing and mitochondrial function were assessed after COL8A2 activation. As a result, aCOL8A2 promoted wound healing of rat corneal endothelium by increasing mitochondrial membrane potential. In cultured human CECs, proteomic analysis was performed to screen and identify the differential protein profiles between control and aCOL8A2 cells. Western blot was used to validate the differential proteins from both cells. Mitochondrial function and intracellular distribution were assessed by measuring ATP production and mitochondrial membrane potential. In cultured human CECs, aCOL8A2 increased COL8A2 and phospho-YAP levels. Transendothelial electrical resistance (TEER) was increased and actin cytoskeleton was attenuated by aCOL8A2. Gene ontology analysis revealed that the proteins were mainly involved in the regulation of folate biosynthesis, ECM-receptor interaction, cell differentiation, NADP activity and cytoskeleton. ATP production was increased, mitochondrial membrane potential was polarized and mitochondrial distribution was widespread in the aCOL8A2 group. In conclusion, aCOL8A2 induces a regulatory cascade affecting mitochondrial positioning and efficiency, mediated by alterations in the cytoskeletal architecture and the YAP signaling pathway. This sequence of events serves to bolster the functional capacities of corneal endothelial cells, including their pump and barrier functions, essential for corneal health and transparency.

Prognosis of Nonconcurrent Bilateral Achilles Tendon Rupture Is Worse Than Unilateral Achilles Tendon Rupture: Patient-Reported Outcomes at Minimum 2-Year Follow-up.

Backgroud: Approximately 5%-7% of patients who have had Achilles tendon rupture (ATR) suffer from contralateral ATR. However, no studies have evaluated the clinical outcomes of contralateral ATR in patients with an existing ATR. Therefore, in this study, we aimed to investigate patient-reported ankle function and activity levels in patients with nonconcurrent bilateral ATR. Methods: We retrospectively reviewed the data of 222 patients with an acute ATR who presented at our 2 institutions between 2005 and 2017. All patients had a minimum 2-year follow-up period, with no other major injuries to the ankle joint. Of these patients, 17 patients had nonconcurrent bilateral ATR. Patient-reported outcomes were assessed by telephone interview, using the Achilles tendon Total Rupture Score (ATRS), the ankle activity score, and a patient satisfaction questionnaire. Telephonic interviews were conducted by 2 authors, using a prepared script to minimize bias owing to individual interviewers. Results: The mean age of the patients was 45.1 ± 9.8 years, and 89% were men. Patients with nonconcurrent bilateral ATR had significantly lower values in terms of ATRS, ankle activity score, and satisfaction with current activity level, compared to patients who had unilateral ATR (p < 0.001, p = 0.027, and p = 0.012, respectively). Conclusions: Patients with nonconcurrent bilateral ATR had poorer ankle function, activity levels, and satisfaction than those with unilateral ATR in terms of patient-reported outcome measures with an intermediate-term result and a 2-year minimum follow-up period. These results emphasize the importance of the impact of contralateral injury on the prognosis of patients with ATR and the need for efforts to prevent contralateral rupture.

Image quality-based dose optimization in pediatric cone-beam computed tomography: A pilot methodological study.

Purpose: This study aimed to propose a methodological approach for reducing the radiation dose in pediatric conebeam computed tomography (CBCT), focusing exclusively on balancing image quality with dose optimization. Materials and Methods: The dose-area product (DAP) for exposure was reduced using copper-plate attenuation of an X-ray source. The thickness of copper (Cu) was increased from 0 to 2.2 mm, and 10 different DAP levels were used. The QUART DVT_AP phantom and pediatric radiologic dentiform were scanned under the respective DAP levels. The contrast-to-noise ratio (CNR), image homogeneity, and modulation transfer function (MTF) were analyzed using the QUART DVT_AP phantom. An expert evaluation (overall image grade, appropriateness of field of view, artifacts, noise, and resolution) was conducted using pediatric dentiform images. The critical DAP level was determined based on phantom and dentiform analysis results. Results: CNR and image homogeneity decreased as the DAP was reduced; however, there was an inflection point of image homogeneity at Cu 1.6 mm (DAP=138.00 mGy·cm2), where the value started increasing. The MTF showed constant values as the DAP decreased. The expert evaluation of overall image grades showed "no diagnostic value" for dentiform images with Cu 1.9-2.2 mm (DAP=78.00-103.33 mGy·cm2). The images with Cu 0-1.6 mm (DAP=138.00-1697.67 mGy·cm2) had a "good," "moderate," or "poor but interpretable" grade. Conclusion: Reducing DAP beyond a 1.6-mm Cu thickness degraded CBCT image quality. Image homogeneity and clinical image grades indicated crucial decision points for DAP reduction in pediatric CBCT scans.

5'-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNAGly(GCC) to produce 5'-tRHs (5'-tRH-GlyGCC) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. Levels of 5'-tRH-GlyGCC positively affect cancer cell proliferation and modulate mRNA isoform biogenesis both in vitro and in vivo; these effects require co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identify as binding proteins of 5'-tRH-GlyGCC. In addition, under ER stress in vivo, we observe simultaneous induction of IRE1α and 5'-tRH-GlyGCC expression in mouse organs and a distantly related organism, Cryptococcus neoformans. Thus, collectively, our findings indicate an evolutionarily conserved function for IRE1α-generated 5'-tRH-GlyGCC in cellular adaptation upon ER stress.

Style harmonization of panoramic radiography using deep learning.

OBJECTIVES: This study aimed to harmonize panoramic radiograph images from different equipment in a single institution to display similar styles. METHODS: A total of 15,624 panoramic images were acquired using two different equipment: 8079 images from Rayscan Alpha Plus (R-unit) and 7545 images from Pax-i plus (P-unit). Among these, 222 image pairs (444 images) from the same patients comprised the test dataset to harmonize the P-unit images with the R-unit image style using CycleGAN. Objective evaluations included Frechet Inception Distance (FID) and Learned Perceptual Image Patch Similarity (LPIPS) assessments. Additionally, expert evaluation was conducted by two oral and maxillofacial radiologists on transformed P-unit and R-unit images. The statistical analysis of LPIPS employed a Student's t-test. RESULTS: The FID and mean LPIPS values of the transformed P-unit images (7.362, 0.488) were lower than those of the original P-unit images (8.380, 0.519), with a significant difference in LPIPS (p < 0.05). The experts evaluated 43.3-46.7% of the transformed P-unit images as R-unit images, 20.0-28.3% as P-units, and 28.3-33.3% as undetermined images. CONCLUSIONS: CycleGAN has the potential to harmonize panoramic radiograph image styles. Enhancement of the model is anticipated for the application of images produced by additional units.

Shoulder Traction as a Possible Risk Factor for C5 Palsy in Anterior Cervical Surgery: A Cadaveric Study.

Background and Objectives: Many risk factors for postoperative C5 palsy (PC5P) have been reported regarding a "cord shift" after a posterior approach. However, there are few reports about shoulder traction as a possible risk factor of anterior cervical surgery. Therefore, we assessed the stretched nerve roots when shoulder traction was applied on cadavers. Materials and Methods: Eight cadavers were employed in this study, available based on age and the presence of foramen stenosis. After dissecting the sternocleidomastoid muscle of the cadaver, the shoulder joint was pulled with a force of 2, 5, 8, 10, 15, and 20 kg. Then, the stretched length of the fifth nerve root was measured in the extra-foraminal zone. In addition, the same measurement was performed after cutting the carotid artery to accurately identify the nerve root's origin. After an additional dissection was performed so that the superior trunk of the brachial plexus could be seen, the stretched length of the fifth and sixth nerve roots was measured again. Results: Throughout the entire experiment, the fifth nerve root stretched out for an average of 1.94 mm at 8 kg and an average of 5.03 mm at a maximum force of 20 kg. In three experiments, the elongated lengths of the C5 nerve root at 8 kg and 20 kg were 1.69/4.38 mm, 2.13/5.00 mm, and 0.75/5.31 mm, respectively, and in the third experiment, the elongated length of the C6 nerve root was 1.88/5.44 mm. Conclusions: Although this was a cadaveric experiment, it suggests that shoulder traction could be the risk factors for PC5P after anterior cervical surgery. In addition, for patients with foraminal stenosis and central stenosis, the risk would be higher. Therefore, the surgeon should be aware of this, and the patient would need sufficient explanation.

Therapeutic single-cell landscape: methotrexate exacerbates interstitial lung disease by compromising the stemness of alveolar epithelial cells under systemic inflammation.

BACKGROUND: Interstitial lung disease (ILD) poses a serious threat in patients with rheumatoid arthritis (RA). However, the impact of cornerstone drugs, including methotrexate (MTX) and TNF inhibitor, on RA-associated ILD (RA-ILD) remains controversial. METHODS: Using an SKG mouse model and single-cell transcriptomics, we investigated the effects of MTX and TNF blockade on ILD. FINDINGS: Our study revealed that MTX exacerbates pulmonary inflammation by promoting immune cell infiltration, Th17 activation, and fibrosis. In contrast, TNF inhibitor ameliorates these features and inhibits ILD progression. Analysis of data from a human RA-ILD cohort revealed that patients with ILD progression had persistently higher systemic inflammation than those without progression, particularly among the subgroup undergoing MTX treatment. INTERPRETATION: These findings highlight the need for personalized therapeutic approaches in RA-ILD, given the divergent outcomes of MTX and TNF inhibitor. FUNDING: This work was funded by GENINUS Inc., and the National Research Foundation of Korea, and Seoul National University Hospital.

Validation of the Scoliosis Japanese Questionnaire-27 in Korean patients with adolescent idiopathic scoliosis.

We sought to evaluate the reliability and validity of the Korean adaptation of the Scoliosis Japanese Questionnaire-27 (SJ-27). This involved translating the English SJ-27 into Korean and back-translating it, followed by completing all stages of the cross-cultural adaptation process. Subsequently, the Korean SJ-27, along with the validated Scoliosis Research Society-22 (SRS-22) questionnaire, was administered to 140 consecutive idiopathic scoliosis patients wearing a brace. Reliability was determined using kappa statistics to assess agreement for each item, the intraclass correlation coefficient (ICC), and Cronbach's α. Construct validity was established by comparing responses on the SJ-27 with those on the SRS-22 using Pearson's correlation coefficient. All items showed kappa statistics indicating agreement above 0.6. The SJ-27 demonstrated excellent test-retest reliability (ICC=0.91). Internal consistency measured by Cronbach's α was very good (α = 0.898). The Korean version of the SJ-27 exhibited significant correlations with both the total score and individual domain scores of the SRS-22. The adapted Korean SJ-27 was effectively translated and showed acceptable measurement properties, making it suitable for assessing outcomes in Korean-speaking patients with idiopathic scoliosis.

Sacroiliac Joint Degeneration After Lumbar or Lumbosacral Fusion Surgery-A Comparative Study of the Number of Fused Segments and Sacral Fusion.

OBJECTIVE: In this study, we aimed to investigate whether multi-segment fusion or fusion-to-sacrum increases sacroiliac joint (SIJ) pathology compared with single-segment fusion or a non-fused sacrum. METHODS: This study included 116 patients who underwent lumbar or lumbosacral fusion and were followed up for 2 years. The patients were classified into single-segment fusion (n = 46) and multi-segment fusion (more than two levels, n = 70) groups and then reclassified into the non-fused sacrum (n = 68) and fusion-to-sacrum groups (n = 48). Preoperative and postoperative radiographs were used to evaluate radiographic parameters, and computed tomography (CT) was used to evaluate SIJ degeneration. Low back pain (LBP) was assessed using a visual analog scale (VAS, 0-10). Baseline and postoperative values were compared using a paired sample t-test. RESULTS: LBP VAS scores significantly differed at 6 months (single-segment fusion, 3.04±1.88; multi-segment fusion, 4.83±2.33; P < 0.001) and 2 years postoperatively (single-segment fusion, 3.3±2.2; multi-segment fusion, 4.78±2.59; P = 0.094). There was no significant difference in SIJ degeneration, as assessed by CT scan, between the 2 surgical groups: 14 (30%) and 19 (27%) patients in the single-segment and multi-segment (P = 0.701) fusion groups, respectively. The LBP VAS scale showed comparable differences at 1 (non-fused sacrum, 3±2.18; fusion-to-sacrum, 3.74±2.28; P = 0.090) and 2 years postoperatively (non-fused sacrum, 3.29±2.01; fusion-to-sacrum, 4.66±2.71; P = 0.095). CT scan revealed that 18 (26%) and 15 (31%) patients in the non-fused sacrum and fusion-to-sacrum groups, respectively, developed SIJ arthritis; however, there was no significant intergroup difference (P = 0.574). CONCLUSIONS: SIJ degeneration occurs independent of the number of fused segments or sacrum involvement.

A pH-Responsive Protein Assembly through Clustering of a Charge-Tunable Single Amino Acid Repeat.

Specific targeting of tumor cells is a key to achieving high therapeutic efficacy while minimizing off-target side effects. As a general approach to targeting diverse tumor cells, considerable attention has been paid to the tumor microenvironment, particularly its slightly acidic pH (6.5-6.8). However, existing pH-sensitive nanomaterials, based on organic polymers and proteins, often lack sufficient pH sensitivity and specificity. Here, we demonstrate a strategy to construct a pH-responsive protein assembly through clustering of a single amino acid repeat as a charge-tunable moiety. As a proof of concept, a histidine peptide with varying lengths was displayed on the surface of a ferritin assembly composed of 24 subunits by genetic fusion to a subunit. The resulting self-assembled ferritin particles, termed "pHerricle (pH-responsive ferritin particle)", were shown to exhibit a specific binding to tumor cells in response to pH changes through cooperative effects of histidine peptides. Increasing the histidine peptide length from 0 to 12 residues increased the pHerricle's cell-binding capacity by 21-fold and allowed modulation of the targetable pH range. General applicability as a tumor cell-targeting platform was shown by specific delivery of a cytotoxic cargo by the pHerricle into tumor cells of various origins in a pH-dependent manner.

Exposure to Radiofrequency Induces Synaptic Dysfunction in Cortical Neurons Causing Learning and Memory Alteration in Early Postnatal Mice.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

Comparative analysis of delivered and planned doses in target volumes for lung stereotactic ablative radiotherapy.

BACKGROUND: Adaptive therapy has been enormously improved based on the art of generating adaptive computed tomography (ACT) from planning CT (PCT) and the on-board image used for the patient setup. Exploiting the ACT, this study evaluated the dose delivered to patients with non-small-cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) and derived relationship between the delivered dose and the parameters obtained through the evaluation procedure. METHODS: SABR treatment records of 72 patients with NSCLC who were prescribed a dose of 60 Gy (Dprescribed) to the 95% volume of the planning target volume (PTV) in four fractions were analysed in this retrospective study; 288 ACTs were generated by rigid and deformable registration of a PCT to a cone-beam computed tomography (CBCT) per fraction. Each ACT was sent to the treatment planning system (TPS) and treated as an individual PCT to calculate the dose. Delivered dose to a patient was estimated by averaging four doses calculated from four ACTs per treatment. Through the process, each ACT provided the geometric parameters, such as mean displacement of the deformed PTV voxels (Warpmean) and Dice similarity coefficient (DSC) from deformation vector field, and dosimetric parameters, e.g. difference of homogeneity index (ΔHI, HI defined as (D2%-D98%)/Dprescribed*100) and mean delivered dose to the PTV (Dmean), obtained from the dose statistics in the TPS. Those parameters were analyzed using multiple linear regression and one-way-ANOVA of SPSS® (version 27). RESULTS: The prescribed dose was confirmed to be fully delivered to internal target volume (ITV) within maximum difference of 1%, and the difference between the planned and delivered doses to the PTV was agreed within 6% for more than 95% of the ACT cases. Volume changes of the ITV during the treatment course were observed to be minor in comparison of their standard deviations. Multiple linear regression analysis between the obtained parameters and the dose delivered to 95% volume of the PTV (D95%) revealed four PTV parameters [Warpmean, DSC, ΔHI between the PCT and ACT, Dmean] and the PTV D95% to be significantly related with P-values < 0.05. The ACT cases of high ΔHI were caused by higher values of the Warpmean and DSC from the deformable image registration, resulting in lower PTV D95% delivered. The mean values of PTV D95% and Warpmean showed significant differences depending on the lung lobe where the tumour was located. CONCLUSIONS: Evaluation of the dose delivered to patients with NSCLC treated with SABR using ACTs confirmed that the prescribed dose was accurately delivered to the ITV. However, for the PTV, certain ACT cases characterised by high HI deviations from the original plan demonstrated variations in the delivered dose. These variations may potentially arise from factors such as patient setup during treatment, as suggested by the statistical analyses of the parameters obtained from the dose evaluation process.

Safety, effectiveness, and usefulness of higher-dose tablets of generic pirfenidone in patients with IPF: a nationwide observational study in South Korea.

Background: Pirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®. Methods: A nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared. Results: Of the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were -1.5% and -2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen. Conclusion: The safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Deep Learning-Based Dynamic Risk Prediction of Venous Thromboembolism for Patients With Ovarian Cancer in Real-World Settings From Electronic Health Records.

PURPOSE: Patients with epithelial ovarian cancer (EOC) have an elevated risk for venous thromboembolism (VTE). To assess the risk of VTE, models were developed by statistical or machine learning algorithms. However, few models have accommodated deep learning (DL) algorithms in realistic clinical settings. We aimed to develop a predictive DL model, exploiting rich information from electronic health records (EHRs), including dynamic clinical features and the presence of competing risks. METHODS: We extracted EHRs of 1,268 patients diagnosed with EOC from January 2007 through December 2017 at the National Cancer Center, Korea. DL survival networks using fully connected layers, temporal attention, and recurrent neural networks were adopted and compared with multi-perceptron-based classification models. Prediction accuracy was independently validated in the data set of 423 patients newly diagnosed with EOC from January 2018 to December 2019. Personalized risk plots displaying the individual interval risk were developed. RESULTS: DL-based survival networks achieved a superior area under the receiver operating characteristic curve (AUROC) between 0.95 and 0.98 while the AUROC of classification models was between 0.85 and 0.90. As clinical information benefits the prediction accuracy, the proposed dynamic survival network outperformed other survival networks for the test and validation data set with the highest time-dependent concordance index (0.974, 0.975) and lowest Brier score (0.051, 0.049) at 6 months after a cancer diagnosis. Our visualization showed that the interval risk fluctuating along with the changes in longitudinal clinical features. CONCLUSION: Adaption of dynamic patient clinical features and accounting for competing risks from EHRs into the DL algorithms demonstrated VTE risk prediction with high accuracy. Our results show that this novel dynamic survival network can provide personalized risk prediction with the potential to assist risk-based clinical intervention to prevent VTE among patients with EOC.

Investigating the impact of environmental enrichment on proteome and neurotransmitter-related profiles in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.