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1.
Article in English | MEDLINE | ID: mdl-38963605

ABSTRACT

PURPOSE: To determine if an explainable artificial intelligence (XAI) model enhances the accuracy and transparency of predicting embryo ploidy status based on embryonic characteristics and clinical data. METHODS: This retrospective study utilized a dataset of 1908 blastocyst embryos. The dataset includes ploidy status, morphokinetic features, morphology grades, and 11 clinical variables. Six machine learning (ML) models including Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Support Vector Machine (SVM), AdaBoost (ADA), and Light Gradient-Boosting Machine (LGBM) were trained to predict ploidy status probabilities across three distinct datasets: high-grade embryos (HGE, n = 1107), low-grade embryos (LGE, n = 364), and all-grade embryos (AGE, n = 1471). The model's performance was interpreted using XAI, including SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) techniques. RESULTS: The mean maternal age was 38.5 ± 3.85 years. The Random Forest (RF) model exhibited superior performance compared to the other five ML models, achieving an accuracy of 0.749 and an AUC of 0.808 for AGE. In the external test set, the RF model achieved an accuracy of 0.714 and an AUC of 0.750 (95% CI, 0.702-0.796). SHAP's feature impact analysis highlighted that maternal age, paternal age, time to blastocyst (tB), and day 5 morphology grade significantly impacted the predictive model. In addition, LIME offered specific case-ploidy prediction probabilities, revealing the model's assigned values for each variable within a finite range. CONCLUSION: The model highlights the potential of using XAI algorithms to enhance ploidy prediction, optimize embryo selection as patient-centric consultation, and provides reliability and transparent insights into the decision-making process.

2.
Sensors (Basel) ; 24(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39001151

ABSTRACT

Extracting the flight trajectory of the shuttlecock in a single turn in badminton games is important for automated sports analytics. This study proposes a novel method to extract shots in badminton games from a monocular camera. First, TrackNet, a deep neural network designed for tracking small objects, is used to extract the flight trajectory of the shuttlecock. Second, the YOLOv7 model is used to identify whether the player is swinging. As both TrackNet and YOLOv7 may have detection misses and false detections, this study proposes a shot refinement algorithm to obtain the correct hitting moment. By doing so, we can extract shots in rallies and classify the type of shots. Our proposed method achieves an accuracy of 89.7%, a recall rate of 91.3%, and an F1 rate of 90.5% in 69 matches, with 1582 rallies of the Badminton World Federation (BWF) match videos. This is a significant improvement compared to the use of TrackNet alone, which yields 58.8% accuracy, 93.6% recall, and 72.3% F1 score. Furthermore, the accuracy of shot type classification at three different thresholds is 72.1%, 65.4%, and 54.1%. These results are superior to those of TrackNet, demonstrating that our method effectively recognizes different shot types. The experimental results demonstrate the feasibility and validity of the proposed method.

3.
Drug Alcohol Rev ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982724

ABSTRACT

INTRODUCTION: This study aimed to investigate the prevalence of different forms of harm from others' drinking (HFOD), predictors and the relationship with multi-dimensional quality of life among young adults in an emerging alcohol market in Asia-Taiwan. METHODS: Data were extracted from a 2018 household survey with national representativeness on substance use experiences. The analytic sample comprised 4901 participants aged 18-34. Eight items were used to measure HFOD experiences. Five-dimensional quality of life was assessed by the EQ-5D-5L. Multivariable regressions with complex survey analyses were performed to estimate the prevalence and risk association. RESULTS: Almost 4.2% of young adults experienced any form of HFOD; psychological harm occurred more prevalently than physical harm (3.7% and 1.5%, respectively). Those aged 25-29 and 30-34 had a two- to three-fold risk of HFOD compared with those aged 18-24. Both non-drunk drinking and drunk drinking were associated with an increased risk of psychological HFOD (adjusted odds ratio 2.36 and 5.89, respectively), whereas the risk of physical HFOD was related only to drunk drinking (adjusted odds ratio 7.8). Psychological HFOD victimisation emerged as the strongest predictor for deteriorated quality of life (adjusted b -0.14; 95% confidence interval -0.24, -0.04), especially in the dimensions of pain/discomfort and anxiety/depression. Among HFOD victims, only 33% sought help. DISCUSSION AND CONCLUSIONS: The HFOD among young adults, commonly exhibited in psychological form, was linked with deteriorated quality of life; nonetheless, young HFOD victims are under-recognised. When devising interventions for alcohol harm, developmental perspectives should be integrated into policies implemented in healthcare and community settings.

4.
bioRxiv ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39026892

ABSTRACT

Human genetic studies have nominated Cadherin-like and PC-esterase Domain-containing 1 ( CPED1 ) as a candidate target gene mediating bone mineral density (BMD) and fracture risk heritability. Recent efforts to define the role of CPED1 in bone in mouse and human models have revealed complex alternative splicing and inconsistent results arising from gene targeting, making its function difficult to interpret. To better understand the role of CPED1 in adult bone mass and morphology, we turned to zebrafish, an emerging model for orthopaedic research. We analyzed two different cped1 mutant lines and performed deep phenotyping to characterize more than 200 measures of adult vertebral, craniofacial, and lean tissue morphology. We also examined alternative splicing of zebrafish cped1 and gene expression in various cell/tissue types. Our studies fail to support an essential role of cped1 in adult zebrafish bone. Specifically, homozygous mutants for both cped1 mutant alleles, which are expected to result in loss-of-function and impact all cped1 isoforms, exhibited no significant differences in the measures examined when compared to their respective wildtype controls, suggesting that cped1 does not significantly contribute to these traits. We identified sequence differences in critical residues of the catalytic triad between the zebrafish and mouse orthologs of CPED1, and discuss how these differences, as well as distinct alternative splicing, could underlie different functions of CPED1 orthologs in the two species. Our studies demonstrate that cped1 is not required for normal adult zebrafish bone mass, lean mass, or bone and lean mass morphology, adding to evidence that variants at 7q31.31 can act independently of CPED1 to influence BMD and fracture risk.

5.
Nutrients ; 16(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38931275

ABSTRACT

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.


Subject(s)
Gastrointestinal Microbiome , Lactobacillus plantarum , Lactococcus lactis , Muscle Strength , Physical Endurance , Probiotics , Humans , Probiotics/administration & dosage , Double-Blind Method , Male , Physical Endurance/physiology , Female , Adult , Young Adult , Oxygen Consumption , Muscle, Skeletal/physiology , Exercise/physiology
6.
Int J Mol Sci ; 25(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38928347

ABSTRACT

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.


Subject(s)
Colorectal Neoplasms , Fluorouracil , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Fluorouracil/therapeutic use , Chemotherapy, Adjuvant/methods , Male , Female , Middle Aged , Aged , Biomarkers, Tumor/genetics , Retrospective Studies , Adult , Genotype , N-Acetylgalactosaminyltransferases/genetics , Prognosis , Treatment Outcome
8.
Int J Bipolar Disord ; 12(1): 20, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38865039

ABSTRACT

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

9.
Chronobiol Int ; : 1-13, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860554

ABSTRACT

Breakfast skipping and late-evening snack are prevalent in young adults. This randomized controlled intervention aimed to evaluate the influence of meal habit recommendations on young adults' body composition and blood pressure. Nonpregnant adults (≥20 y old) who were eligible for bioelectrical impedance analysis examination (neither pacemaker installed nor medications that would affect body composition, like diuretics or corticosteroids) were enrolled after they provided informed consent (n = 125). Subjects were randomized into three groups, every group receiving one of the following recommendations: (a) daily breakfast consumption (within 2 h after waking up), (b) avoidance of late-evening snacks (after 21:00h or within 4 h before sleep, with the exception of water), and (c) both recommendations. Body composition and blood pressure were measured before randomization at baseline and at the follow-up 1 y later. Intent-to-treat analysis showed that the recommendation of daily breakfast may contribute to a lower increment of diastolic blood pressure by 3.23 mmHg (95% CI: 0.17-6.28). Receiving the breakfast recommendation was associated with more reduction of total body fat percent by 2.99% (95% CI: 0.23-5.74) and percent trunk fat by 3.63% (95% CI: 0.40-6.86) in inactive youths. Recommendation of avoiding late-evening snack did not significantly affect the outcome measures (ClinicalTrials.gov Identifier: NCT03828812).

10.
Front Public Health ; 12: 1406524, 2024.
Article in English | MEDLINE | ID: mdl-38894993

ABSTRACT

Backgrounds: Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military. Methods: A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline. Results: At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05). Conclusion: A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS.


Subject(s)
Metabolic Syndrome , Military Personnel , Humans , Male , Female , Adult , Military Personnel/statistics & numerical data , Metabolic Syndrome/epidemiology , Taiwan/epidemiology , Incidence , Young Adult , Adolescent , Alcohol Drinking/epidemiology , Alcohol Drinking/adverse effects , Substance-Related Disorders/epidemiology , Risk Factors , Areca/adverse effects , Cohort Studies
11.
Medicina (Kaunas) ; 60(5)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38792880

ABSTRACT

Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004-1.025), 1.044 (1.004-1.085) and 3.697 (1.149-11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.


Subject(s)
Biomarkers , Lipoproteins, LDL , Malondialdehyde , Renal Dialysis , Vascular Stiffness , Humans , Male , Female , Renal Dialysis/adverse effects , Renal Dialysis/methods , Vascular Stiffness/physiology , Middle Aged , Cross-Sectional Studies , Malondialdehyde/blood , Biomarkers/blood , Lipoproteins, LDL/blood , Aged , Pulse Wave Analysis/methods , Ankle Brachial Index/methods , ROC Curve , Risk Factors , Logistic Models , Adult , Oxidative Stress/physiology
12.
J Bone Miner Metab ; 42(3): 335-343, 2024 May.
Article in English | MEDLINE | ID: mdl-38801451

ABSTRACT

INTRODUCTION: Patients with multiple sclerosis (MS) commonly present musculoskeletal disorders characterized by lower bone mineral density (BMD) and muscle weakness. However, the underlying etiology remains unclear. Our objective is to identify shared pleiotropic genetic effects and estimate the causal relationship between MS and musculoskeletal disorders. MATERIALS AND METHODS: We conducted linkage disequilibrium score regression (LDSR), colocalization, and Mendelian randomization (MR) analyses using summary statistics from recent large-scale genome-wide association studies (GWAS), encompassing MS, falls, fractures, and frailty. Additional MR analyses explored the causal relationship with musculoskeletal risk factors, such as BMD, lean mass, grip strength, and vitamin D. RESULTS: We observed a moderate genetic correlation between MS and falls (RG = 0.10, P-value = 0.01) but not between MS with fracture or frailty in the LDSR analyses. MR revealed MS had no causal association with fracture and frailty but a moderate association with falls (OR: 1.004, FDR q-value = 0.018). We further performed colocalization analyses using nine SNPs that exhibited significant associations with both MS and falls in MR. Two SNPs (rs7731626 on ANKRD55 and rs701006 on OS9 gene) showed higher posterior probability of colocalization (PP.H4 = 0.927), suggesting potential pleiotropic effects between MS and falls. The nine genes are associated with central nervous system development and inflammation signaling pathways. CONCLUSION: We found potential pleiotropic genetic effects between MS and falls. However, our analysis did not reveal a causal relationship between MS and increased risks of falls, fractures, or frailty. This suggests that the musculoskeletal disorders frequently reported in MS patients in clinical studies are more likely attributed to secondary factors associated with disease progression and treatment, rather than being directly caused by MS itself.


Subject(s)
Accidental Falls , Fractures, Bone , Frailty , Genome-Wide Association Study , Mendelian Randomization Analysis , Multiple Sclerosis , Polymorphism, Single Nucleotide , Humans , Multiple Sclerosis/genetics , Frailty/genetics , Fractures, Bone/genetics , Fractures, Bone/epidemiology , Polymorphism, Single Nucleotide/genetics , Risk Factors , Bone Density/genetics , Linkage Disequilibrium/genetics , Female
13.
Int J Med Sci ; 21(6): 1117-1128, 2024.
Article in English | MEDLINE | ID: mdl-38774761

ABSTRACT

In this study, we developed a microfluidic device that is able to monitor cell biology under continuous PM2.5 treatment. The effects of PM2.5 on human alveolar basal epithelial cells, A549 cells, and uncovered several significant findings were investigated. The results showed that PM2.5 exposure did not lead to a notable decrease in cell viability, indicating that PM2.5 did not cause cellular injury or death. However, the study found that PM2.5 exposure increased the invasion and migration abilities of A549 cells, suggesting that PM2.5 might promote cell invasiveness. Results of RNA sequencing revealed 423 genes that displayed significant differential expression in response to PM2.5 exposure, with a particular focus on pathways associated with the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Real-time detection demonstrated an increase in ROS production in A549 cells after exposure to PM2.5. JC1 assay, which indicated a loss of mitochondrial membrane potential (ΔΨm) in A549 cells exposed to PM2.5. The disruption of mitochondrial membrane potential further supports the detrimental effects of PM2.5 on A549 cells. These findings highlight several adverse effects of PM2.5 on A549 cells, including enhanced invasion and migration capabilities, altered gene expression related to ROS pathways, increased ROS production and disruption of mitochondrial membrane potential. These findings contribute to our understanding of the potential mechanisms through which PM2.5 can impact cellular function and health.


Subject(s)
Cell Movement , Cell Survival , Lung Neoplasms , Membrane Potential, Mitochondrial , Particulate Matter , Reactive Oxygen Species , Humans , Particulate Matter/adverse effects , Reactive Oxygen Species/metabolism , A549 Cells , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Cell Movement/drug effects , Membrane Potential, Mitochondrial/drug effects , Cell Survival/drug effects , Lab-On-A-Chip Devices , Mitochondria/metabolism , Mitochondria/drug effects , Neoplasm Invasiveness/genetics , Gene Expression Regulation, Neoplastic/drug effects , Microfluidics/methods
14.
Neuroimage ; : 120653, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38795798

ABSTRACT

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17-28 years; seven men, one woman) underwent dynDTIlow-b using a clinical 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7% and 4.94%, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5% of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of S(b=0 s/mm2) was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

15.
Hepatol Commun ; 8(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38696369

ABSTRACT

BACKGROUND: Human genetic studies have identified several mitochondrial amidoxime-reducing component 1 (MTARC1) variants as protective against metabolic dysfunction-associated steatotic liver disease. The MTARC1 variants are associated with decreased plasma lipids and liver enzymes and reduced liver-related mortality. However, the role of mARC1 in fatty liver disease is still unclear. METHODS: Given that mARC1 is mainly expressed in hepatocytes, we developed an N-acetylgalactosamine-conjugated mouse Mtarc1 siRNA, applying it in multiple in vivo models to investigate the role of mARC1 using multiomic techniques. RESULTS: In ob/ob mice, knockdown of Mtarc1 in mouse hepatocytes resulted in decreased serum liver enzymes, LDL-cholesterol, and liver triglycerides. Reduction of mARC1 also reduced liver weight, improved lipid profiles, and attenuated liver pathological changes in 2 diet-induced metabolic dysfunction-associated steatohepatitis mouse models. A comprehensive analysis of mARC1-deficient liver from a metabolic dysfunction-associated steatohepatitis mouse model by metabolomics, proteomics, and lipidomics showed that Mtarc1 knockdown partially restored metabolites and lipids altered by diet. CONCLUSIONS: Taken together, reducing mARC1 expression in hepatocytes protects against metabolic dysfunction-associated steatohepatitis in multiple murine models, suggesting a potential therapeutic approach for this chronic liver disease.


Subject(s)
Disease Models, Animal , Gene Knockdown Techniques , Hepatocytes , Animals , Mice , Hepatocytes/metabolism , Liver/metabolism , Male , RNA, Small Interfering/genetics , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/prevention & control , Mice, Inbred C57BL
16.
J Xray Sci Technol ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38728198

ABSTRACT

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

17.
J Am Soc Mass Spectrom ; 35(5): 960-971, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38616559

ABSTRACT

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.


Subject(s)
Drug Contamination , Plant Preparations , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Electrospray Ionization/methods , Humans , Plant Preparations/analysis , Plant Preparations/chemistry , Emergency Medical Services/methods
18.
Foods ; 13(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611334

ABSTRACT

In addition to maintaining good exercise and dietary habits, recent studies have shown that probiotics may have potential benefits for muscle mass and strength. It is worth noting that the effects may vary depending on the specific strains used. To date, no studies have analyzed the effects of Lactiplantibacillus brevis in this context. Here, we combine the L. brevis strain GKEX with resistance training to further understand its effects on muscle mass, thickness, performance, and fat loss. In a six-week intervention for a double-blind randomized trial, 52 healthy subjects were divided into two groups (10 male and 16 female participants in each group): a placebo group (two capsules/day, containing 0 CFU of GKEX per capsule) and a GKEX group (two capsules/day, containing 1 × 1010 CFU of GKEX per capsule). Before the intervention, no differences were observed between the two groups in any of the tests (body composition, muscle thickness, exercise performance, and blood parameters). However, supplementation with GKEX significantly improved muscle mass and thickness, as well as grip strength, muscle strength, and explosive performance, when compared to the associated parameters before the intervention. Additionally, GKEX supplementation promoted a reduction in the body fat percentage (p < 0.05). Through analysis of the change amount, we observed that GKEX supplementation yielded significantly improved benefits when compared to the placebo group (p < 0.05). In summary, our findings support the notion that a six-week resistance exercise training program combined with L. brevis GKEX supplementation has superior additive effects that enhance muscle mass and strength performance, while also reducing body fat percentage. This intervention can promote muscle gain and fat loss.

19.
Abdom Radiol (NY) ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662208

ABSTRACT

PURPOSE: The purpose of our study is to investigate image quality, efficiency, and diagnostic performance of a deep learning-accelerated single-shot breath-hold (DLSB) against BLADE for T2-weighted MR imaging (T2WI) for gastric cancer (GC). METHODS: 112 patients with GCs undergoing gastric MRI were prospectively enrolled between Aug 2022 and Dec 2022. Axial DLSB-T2WI and BLADE-T2WI of stomach were scanned with same spatial resolution. Three radiologists independently evaluated the image qualities using a 5-scale Likert scales (IQS) in terms of lesion delineation, gastric wall boundary conspicuity, and overall image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in measurable lesions. T staging was conducted based on the results of both sequences for GC patients with gastrectomy. Pairwise comparisons between DLSB-T2WI and BLADE-T2WI were performed using the Wilcoxon signed-rank test, paired t-test, and chi-squared test. Kendall's W, Fleiss' Kappa, and intraclass correlation coefficient values were used to determine inter-reader reliability. RESULTS: Against BLADE, DLSB reduced total acquisition time of T2WI from 495 min (mean 4:42 per patient) to 33.6 min (18 s per patient), with better overall image quality that produced 9.43-fold, 8.00-fold, and 18.31-fold IQS upgrading against BALDE, respectively, in three readers. In 69 measurable lesions, DLSB-T2WI had higher mean SNR and higher CNR than BLADE-T2WI. Among 71 patients with gastrectomy, DLSB-T2WI resulted in comparable accuracy to BLADE-T2WI in staging GCs (P > 0.05). CONCLUSIONS: DLSB-T2WI demonstrated shorter acquisition time, better image quality, and comparable staging accuracy, which could be an alternative to BLADE-T2WI for gastric cancer imaging.

20.
Nat Commun ; 15(1): 3534, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38670989

ABSTRACT

Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.


Subject(s)
Adenosine Triphosphate , Glutamate-Ammonia Ligase , Glutamic Acid , Glutamine , Manganese , Nanostructures , Neurons , Polyphosphates , Glutamate-Ammonia Ligase/metabolism , Humans , Polyphosphates/chemistry , Polyphosphates/metabolism , Polyphosphates/pharmacology , Nanostructures/chemistry , Adenosine Triphosphate/metabolism , Cell Line, Tumor , Glutamic Acid/metabolism , Glutamic Acid/toxicity , Neurons/metabolism , Neurons/drug effects , Glutamine/metabolism , Manganese/metabolism , Manganese/chemistry , Biocompatible Materials/chemistry
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