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1.
Article in English | MEDLINE | ID: mdl-39276030

ABSTRACT

CONTEXT: With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. OBJECTIVE: This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. METHODS: 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. RESULTS: At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. CONCLUSION: Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

2.
Ecotoxicol Environ Saf ; 285: 117075, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39305778

ABSTRACT

Off-target pesticide drift in paddy fields following unmanned aerial vehicle (UAV) spraying was evaluated using cellulose deposition samplers (CDSs). An analytical method for quantifying ferimzone Z and E isomers deposited on CDSs was developed using LC-MS/MS. The suitability of the CDS method was confirmed by comparing deposition patterns on CDSs with residue levels in rice plant samples. To assess pesticide deposition in paddy fields, CDSs were strategically placed at varying distances from target areas, followed by UAV spraying. The fungicide agrochemicals were applied with and without adjuvants, and wind direction affected the drift trajectory for all treatment groups. Adjuvants, particularly soy lecithin as the major component, significantly enhanced pesticide deposition within the spray pathway while reducing drift rates relatively by 47.9-68.0 %. Higher wind speeds were found to exacerbate drift, but adjuvant-treated sprays showed less variability in deposition patterns under these conditions. Pesticide residues in harvested brown rice were found to be below the maximum residue limits (MRLs), ensuring safety for consumption. These findings highlight the importance of selecting appropriate adjuvants in UAV-based pesticide applications to optimize deposition efficiency and minimize environmental contamination.

3.
Article in English | MEDLINE | ID: mdl-39311388

ABSTRACT

CONTEXT: Studies have associated obesity with peri-pubertal hyperandrogenemia. However, these studies were performed in academic centers and could have been influenced by selection bias. OBJECTIVE: To investigate if free testosterone levels are elevated in peri-pubertal girls with obesity. DESIGN/SETTING: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 databases. PARTICIPANTS: 1,299 girls aged 6-18 years residing in U.S. MAIN OUTCOME MEASURES: Mean free testosterone concentration (calculated from total testosterone and sex hormone-binding globulin). RESULTS: Among girls aged 6-9 years, mean (95% CI) free testosterone was 0.33 pg/ml (0.28-0.38) in healthy weight girls vs. 0.86 pg/ml (0.67-1.05) in girls with obesity. Among girls aged 10-14 years, free testosterone was 2.29 pg/ml (2.05-2.53) in healthy weight girls vs. 4.10 pg/ml (3.60-4.60) in girls with obesity. Among girls aged 15-18 years, free testosterone was 3.33 pg/ml (2.96-3.70) in healthy weight girls and 5.64 pg/ml (4.93-6.36) in girls with obesity. Girls with obesity in all age groups had higher free testosterone levels compared to healthy weight girls. In each age group, the 95% CIs for free testosterone did not overlap between healthy weight vs. obesity subgroups. A multiple regression model accounted for 42% of the variance in free testosterone (R2=0.42), and both weight and age categories were independent predictors of free testosterone (p<0.0001 for each). CONCLUSION: In a nationally-representative sample of U.S. girls, obesity is associated with elevated free testosterone, suggesting an important relationship between obesity and peri-pubertal hyperandrogenemia.

4.
Mol Oncol ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39297393

ABSTRACT

To enhance the efficacy of radiotherapy (RT) in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), we explored targeting ferroptosis, a regulated cell death process. We developed a gene signature associated with ferroptosis using Cox proportional hazard modeling in HPV-negative HNSCC patients who underwent RT. This ferroptosis-related gene signature (FRGS) was a significant predictor of overall survival and recurrence-free survival in HPV-negative HNSCC patients who received RT. Subtype B of the FRGS, characterized by decreased expression of ferroptosis inducers [nuclear receptor coactivator 4 (NCOA4) and natural resistance-associated macrophage protein 2 homolog/divalent metal transporter 1 (NRAMP2/DMT1)] and increased expression of suppressors [phospholipid hydroperoxide glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1)], was associated with poorer prognosis, potentially indicating the inhibition of ferroptosis. Furthermore, our in vitro and in vivo studies demonstrated that treatment with statins, such as atorvastatin and simvastatin, induced ferroptosis and sensitized radioresistant HNSCC cells to irradiation, improving radiosensitivity and potentially enhancing the response to RT. Additionally, in xenograft models, the combination of statins and RT led to a significant reduction in tumor initiation. These findings provide valuable insights for enhancing treatment and improving prognosis in HPV-negative HNSCC by targeting ferroptosis and utilizing statins to sensitize tumors to RT-induced cell death.

5.
Psychol Methods ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298189

ABSTRACT

Although the interest in latent growth models (LGMs) with categorical indicator variables has recently increased, there are still difficulties regarding the selection of estimation methods and the interpretation of model estimates. However, difficulties in estimating and interpreting categorical LGMs can be avoided by understanding the scaling process. Depending on which parameter constraint methods are selected at each step of the scaling process, the scale applied to the model changes, which can produce significant differences in the estimation results and interpretation. In other words, if a different method is chosen for any of the steps in the scaling process, the estimation results will not be comparable. This study organizes the scaling process and its relationship with estimation methods for categorical LGMs. Specifically, this study organizes the parameter constraint methods included in the scaling process of categorical LGMs and extensively considers the effect of parameter constraints at each step on the meaning of estimates. This study also provides evidence for the scale suitability and interpretability of model estimates through a simple illustration. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

6.
Mult Scler Relat Disord ; 91: 105859, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39236649

ABSTRACT

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disease affecting the central nervous system that may require long-term immunotherapy in relapsing cases. While immunotherapies utilized in neuromyelitis optica spectrum disorder have shown varying efficacy in MOGAD, intravenous immunoglobulin G (IVIG) recently emerged as a promising treatment. Tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, has been reported to be effective in refractory MOGAD in several case studies, where tocilizumab was introduced primarily due to rituximab failure. METHODS: This retrospective study was conducted in a single center and focused on MOGAD patients receiving tocilizumab therapy, who have shown limited response to various immunotherapies, including intravenous immunoglobulin G (IVIG) maintenance. RESULTS: This study included four patients, three adults, and one child. They experienced a median of 9 attacks (range 6-9) throughout their disease course despite at least two immunotherapies. All patients transitioned to tocilizumab after experiencing a median of two relapses (range 1-3) while on IVIG maintenance for a median of 21.9 months (range 21.3-49.6 months). Following the monthly tocilizumab administration at a dose of 8g/kg, all patients remained relapse-free with a median follow-up duration of 25.0 months (range 9.8-51.3 months) without reported adverse events. CONCLUSION: Targeting the IL-6 pathway appears to offer therapeutic benefits in highly relapsing MOGAD patients who poorly respond to IVIG maintenance therapy.

7.
Arthritis Rheumatol ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39262222

ABSTRACT

OBJECTIVES: Osteoarthritis (OA) is the most common degenerative disease worldwide with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol-lowering drugs in suppressing OA development in mice, and uncover the cholesterol-lowering mechanisms that effectively impede OA progression. METHODS: Five clinically approved cholesterol-lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to DMM-induced OA mice fed a 2% high-cholesterol diet. Gene expression linked to cholesterol metabolism were determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra-articular injection of either its inhibitor or adenovirus. RESULTS: Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol-lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high-density lipoprotein cholesterol that is crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via downregulation of apolipoprotein A1 binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression. CONCLUSIONS: Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for OA.

9.
Nat Commun ; 15(1): 7802, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242547

ABSTRACT

Stretchable optoelectronic devices are typically realized through a 2D integration of rigid components and elastic interconnectors to maintain device performance under stretching deformation. However, such configurations inevitably sacrifice the area ratio of active components to enhance the maximum interconnector strain. We herein propose a 3D buckled height-alternant architecture for stretchable OLEDs that enables the high active-area ratio and the enhanced maximum strain simultaneously. Along with the optimal dual serpentine structure leading to a low critical buckling strain, a pop-up assisting adhesion blocking layer is proposed based on an array of micro concave structures for spatially selective adhesion control, enabling a reliable transition to a 3D buckled state with OLED-compatible processes. Consequently, we demonstrate stretchable OLEDs with both the high initial active-area ratio of 85% and the system strain of up to 40%, which would require a lateral interconnector strain of up to 512% if it were attained with conventional 2D rigid-island approaches. These OLEDs are shown to exhibit reliable performance under 2,000 biaxial cycles of 40% system strain. 7 × 7 passive-matrix OLED displays with the similar level of the initial active-area ratio and maximum system strain are also demonstrated.

10.
J Org Chem ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298278

ABSTRACT

Azo compounds such as diethyl azodicarboxylate have been used in oxidative coupling reactions to generate iminium ions from tertiary amines. However, the requirement of stoichiometric amounts of azo compounds limits their large-scale applications. Herein, we present an aerobic oxidative α-cyanation of tertiary amines using catalytic amounts of an azo compound or hydrazine. The developed protocol provides a practical and ecofriendly route for α-cyanated tertiary amines, using molecular oxygen as the terminal oxidant.

11.
Cells ; 13(17)2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39273014

ABSTRACT

Overcoming temozolomide (TMZ)-resistance is a major challenge in glioblastoma therapy. Therefore, identifying the key molecular player in chemo-resistance becomes urgent. We previously reported the downregulation of PDCD10 in primary glioblastoma patients and its tumor suppressor-like function in glioblastoma cells. Here, we demonstrate that the loss of PDCD10 causes a significant TMZ-resistance during treatment and promotes a rapid regrowth of tumor cells after treatment. PDCD10 knockdown upregulated MGMT, a key enzyme mediating chemo-resistance in glioblastoma, accompanied by increased expression of DNA mismatch repair genes, and enabled tumor cells to evade TMZ-induced cell-cycle arrest. These findings were confirmed in independent models of PDCD10 overexpressing cells. Furthermore, PDCD10 downregulation led to the dedifferentiation of glioblastoma cells, as evidenced by increased clonogenic growth, the upregulation of glioblastoma stem cell (GSC) markers, and enhanced neurosphere formation capacity. GSCs derived from PDCD10 knockdown cells displayed stronger TMZ-resistance and regrowth potency, compared to their parental counterparts, indicating that PDCD10-induced stemness may independently contribute to tumor malignancy. These data provide evidence for a dual role of PDCD10 in tumor suppression by controlling both chemo-resistance and dedifferentiation, and highlight PDCD10 as a potential prognostic marker and target for combination therapy with TMZ in glioblastoma.


Subject(s)
Apoptosis Regulatory Proteins , Drug Resistance, Neoplasm , Glioblastoma , Temozolomide , Humans , Glioblastoma/pathology , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/drug therapy , Temozolomide/pharmacology , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Cell Line, Tumor , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Gene Expression Regulation, Neoplastic/drug effects , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/drug effects , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/drug therapy , Membrane Proteins/metabolism , Membrane Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Cell Proliferation/drug effects , DNA Modification Methylases/metabolism , DNA Modification Methylases/genetics , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , DNA Repair Enzymes/metabolism , DNA Repair Enzymes/genetics
12.
Article in English | MEDLINE | ID: mdl-39250688

ABSTRACT

INTRODUCTION: We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery. METHODS: We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high-risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki-67 labeling index >20%. RESULTS: Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5-month median follow-up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5-year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high-risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001). CONCLUSION: Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence.

13.
Anaesthesiologie ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271579

ABSTRACT

BACKGROUND: Benzodiazepines reduce postoperative nausea and vomiting (PONV); however, conflicting results have been reported regarding the use of remimazolam, a novel benzodiazepine. OBJECTIVE: This meta-analysis examines whether remimazolam reduces PONV incidence compared with propofol or volatile agents used in general anesthesia. MATERIAL AND METHODS: Electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, were searched on 31 July 2023. The primary outcome was the incidence of PONV. Secondary outcomes included PONV severity, rescue antiemetic use, amounts of remifentanil used, and participant satisfaction scores. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. The risk of bias (RoB) was assessed using the Cochrane RoB2 tool. RESULTS: A total of 1514 adult patients from 11 randomized controlled trials were included. The incidences of PONV in the remimazolam and control groups were 16.1% and 16.5%, respectively. Remimazolam did not increase the incidence of PONV (OR 0.62; 95% CI, 0.37-1.04; p = 0.0676; I2 = 48%). Subgroup analysis showed a significant reduction in PONV with remimazolam vs. volatile agents (OR 0.25; 95% CI, 0.13-0.47; P = 0.0000; I2 = 0%) but not vs. propofol (OR 1.04; 95% CI, 0.70-1.56; p = 0.8332; I2 = 0%). More remifentanil was used in the remimazolam group vs. the volatile group, with no significant difference between remimazolam and propofol groups. Participant satisfaction scores were higher with remimazolam. CONCLUSION: Remimazolam did not increase PONV risk compared to propofol and reduced PONV incidence compared to volatile agents, with higher participant satisfaction. To validate the present findings, further well-planned large clinical trials are required.

14.
Oncology ; : 1-16, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39278213

ABSTRACT

Introduction This study aims to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in two groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group). Methods From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival, progression-free survival, and safety. Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (P = 0.066) were 32.5% and 15.6%; the disease control rates (P = 0.556) were 67.5% and 73.3%; the median overall survival times (P = 0.339) were 224 days and 398 days; the median progression-free survival (P = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (P = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (P = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (P = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively. Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.

15.
Int J Surg Pathol ; : 10668969241271966, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285723

ABSTRACT

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive tumor characterized by translocation of the NUTM1 gene. To date, only about 20 NUT carcinomas arising from the thyroid have been reported in the literature, with the majority showing immunohistochemical markers indicative of squamous differentiation. We present a 29-year-old man with NUT carcinoma arising from thyroid follicular cells. Notably, the tumor cells expressed markers characteristic of thyroid follicular cells such as thyroglobulin, TTF1 and PAX8, without obvious histological and immunohistochemical features of squamous differentiation. Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

16.
Respir Care ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39256003

ABSTRACT

BACKGROUND: Appropriate hospital-to-home transitional care has been recognized for its positive impact on health care usage and health outcomes in patients with COPD. However, there is limited research assessing its effects on patient-centered outcomes, focusing on patient symptoms and experiences. METHODS: This single-blind randomized controlled trial included subjects diagnosed with COPD at one of 2 university hospitals in South Korea. The study included 179 subjects (transitional care group [transitional care], 87; usual care group [usual care], 92). The transitional care received transitional care comprising post-discharge care planning, personalized education, breathing exercises, telephone counseling, home visits, and referral to social services. We analyzed the effects of these interventions by comparing breathing symptoms and various patient-centered outcomes between the 2 groups. RESULTS: The Modified Medical Research Council scores (mean [SD], transitional care 1.3 [1.06], usual care 1.82 [1.1], P = .002) and COPD Assessment Test scores (transitional care 6.32 [5.5], usual care 9.43 [7.16], P = .001) in the intervention group demonstrated more significant improvement than did those in the usual care. Following intervention, the subjects exhibited enhanced awareness of their disease, an increased frequency of inhaler use (transitional care 49.69 [1.67], usual care 46.86 [7.92], P = .002), and lower depression and anxiety scores. Additionally, the transitional care outperformed the usual care in the domain of subject experience during hospitalization (transitional care 39.34 [6.14], usual care 37.5 [5.61], P = .036), preparedness before discharge (transitional care 34.54 [4.96], usual care 32.3 [5.09], P = .003), and post-discharge management (transitional care 34.72 [4.36], usual care 30.29 [4.26], P = .003). CONCLUSIONS: Evidence-based transitional care services can exert positive effects on patient-centered indices. Our findings can be used as evidence of the need to establish patient-centered transitional care as a form of universal care for patients with COPD.

17.
Biosens Bioelectron ; 267: 116766, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39265428

ABSTRACT

Pectobacterium carotovorum subsp. carotovorum (PCC) is a notorious plant pathogen responsible for severe soft rot in kimchi cabbage, which results in significant economic losses. To detect PCC rapidly and accurately in kimchi cabbage, we developed a surface-enhanced Raman scattering (SERS) substrate on which silver nanospheres (AgNSs), nanowires (AgNWs), and nanoseeds are combined on a polydimethylsiloxane (PDMS) platform. The incorporation of Ag nanoseeds creates a higher density of hotspots, which ensures a low detection limit of 1.001 CFU/mL. Electron microscopy and spectroscopic analyses confirmed the successful fabrication of the substrate and its enhanced sensitivity. The SERS substrate exhibits excellent selectivity by effectively distinguishing PCC from other bacteria commonly found in kimchi cabbage. The substrate gives rise to strong Raman signals across PCC concentrations ranging from 101 to 106 CFU/mL. Additionally, a predictive model was developed for accurately detecting PCC in real kimchi cabbage samples, and the results were validated by polymerase chain reaction measurements. A sensitive, selective, and rapid approach for PCC detection in kimchi cabbage that offers a promising improvement over existing methodologies is presented.

18.
Article in English | MEDLINE | ID: mdl-39229927

ABSTRACT

BACKGROUND: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics. METHODS: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort. RESULTS: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799). CONCLUSIONS: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

20.
Eur Radiol ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231829

ABSTRACT

OBJECTIVES: To generate sagittal T1-weighted fast spin echo (T1w FSE) and short tau inversion recovery (STIR) images from sagittal T2-weighted (T2w) FSE and axial T1w gradient echo Dixon technique (T1w-Dixon) sequences. MATERIALS AND METHODS: This retrospective study used three existing datasets: "Study of Health in Pomerania" (SHIP, 3142 subjects, 1.5 Tesla), "German National Cohort" (NAKO, 2000 subjects, 3 Tesla), and an internal dataset (157 patients 1.5/3 Tesla). We generated synthetic sagittal T1w FSE and STIR images from sagittal T2w FSE and low-resolution axial T1w-Dixon sequences based on two successively applied 3D Pix2Pix deep learning models. "Peak signal-to-noise ratio" (PSNR) and "structural similarity index metric" (SSIM) were used to evaluate the generated image quality on an ablations test. A Turing test, where seven radiologists rated 240 images as either natively acquired or generated, was evaluated using misclassification rate and Fleiss kappa interrater agreement. RESULTS: Including axial T1w-Dixon or T1w FSE images resulted in higher image quality in generated T1w FSE (PSNR = 26.942, SSIM = 0.965) and STIR (PSNR = 28.86, SSIM = 0.948) images compared to using only single T2w images as input (PSNR = 23.076/24.677 SSIM = 0.952/0.928). Radiologists had difficulty identifying generated images (misclassification rate: 0.39 ± 0.09 for T1w FSE, 0.42 ± 0.18 for STIR) and showed low interrater agreement on suspicious images (Fleiss kappa: 0.09 for T1w/STIR). CONCLUSIONS: Axial T1w-Dixon and sagittal T2w FSE images contain sufficient information to generate sagittal T1w FSE and STIR images. CLINICAL RELEVANCE STATEMENT: T1w fast spin echo and short tau inversion recovery can be retroactively added to existing datasets, saving MRI time and enabling retrospective analysis, such as evaluating bone marrow pathologies. KEY POINTS: Sagittal T2-weighted images alone were insufficient for differentiating fat and water and to generate T1-weighted images. Axial T1w Dixon technique, together with a T2-weighted sequence, produced realistic sagittal T1-weighted images. Our approach can be used to retrospectively generate STIR and T1-weighted fast spin echo sequences.

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