Geometric and dosimetric evaluation of deep learning based auto-segmentation for clinical target volume on breast cancer.

BACKGROUND: Recently, target auto-segmentation techniques based on deep learning (DL) have shown promising results. However, inaccurate target delineation will directly affect the treatment planning dose distribution and the effect of subsequent radiotherapy work. Evaluation based on geometric metrics alone may not be sufficient for target delineation accuracy assessment. The purpose of this paper is to validate the performance of automatic segmentation with dosimetric metrics and try to construct new evaluation geometric metrics to comprehensively understand the dose-response relationship from the perspective of clinical application. MATERIALS AND METHODS: A DL-based target segmentation model was developed by using 186 manual delineation modified radical mastectomy breast cancer cases. The resulting DL model were used to generate alternative target contours in a new set of 48 patients. The Auto-plan was reoptimized to ensure the same optimized parameters as the reference Manual-plan. To assess the dosimetric impact of target auto-segmentation, not only common geometric metrics but also new spatial parameters with distance and relative volume ( R V ${R}_V$ ) to target were used. Correlations were performed using Spearman's correlation between segmentation evaluation metrics and dosimetric changes. RESULTS: Only strong (|R2 | > 0.6, p < 0.01) or moderate (|R2 | > 0.4, p < 0.01) Pearson correlation was established between the traditional geometric metric and three dosimetric evaluation indices to target (conformity index, homogeneity index, and mean dose). For organs at risk (OARs), inferior or no significant relationship was found between geometric parameters and dosimetric differences. Furthermore, we found that OARs dose distribution was affected by boundary error of target segmentation instead of distance and R V ${R}_V$ to target. CONCLUSIONS: Current geometric metrics could reflect a certain degree of dose effect of target variation. To find target contour variations that do lead to OARs dosimetry changes, clinically oriented metrics that more accurately reflect how segmentation quality affects dosimetry should be constructed.

Occurrence of bisphenol diglycidyl ethers and bisphenol analogs, and their associations with DNA oxidative damage in pregnant women.

Bisphenol diglycidyl ethers (BDGEs) and Bisphenol A and its analogs (bisphenols) may have the same exposure routes and coexposure phenomenon in sensitive populations such as pregnant women. Previous biomonitoring studies on BDGEs are limited. Levels of fifteen bisphenols, six BDGEs and the DNA oxidative damage biomarker 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured in the urine of pregnant women recruited in south China (n = 358). We aimed to provide the occurrence of bisphenols and BDGEs in pregnant women, and to investigate the potential relationship between their exposure and oxidative stress. Bisphenol A, bisphenol S, bisphenol F, bisphenol AP and all BDGEs (except for BADGE·2HCl) were frequently detected. The total concentrations of all bisphenols and BDGEs were 0.402-338 and 0.104-32.5 ng/mL, with geometric means of 2.87 and 2.48 ng/mL, respectively. BFDGE was the most abundant chemical of BDGEs, with a median concentration of 0.872 ng/mL, followed by BADGE·H2O·HCl (0.297 ng/mL). Except for pre-pregnancy obesity, maternal age/height, employment, fasting in the morning and parity did not affect the urinary concentrations of BDGEs. Significant and weak correlations were observed between concentrations (unadjusted) of total bisphenols and BDGEs (r = 0.389, p < 0.01), indicating their similar sources and exposure routes. The biomarker 8-OHdG was detected in all samples, with concentrations ranging from 1.98 to 32.6 ng/mL (median: 9.96 ng/mL). Levels of 8-OHdG were positively correlated with urinary several bisphenol concentrations (adjusted ß range: 0.037-0.089, p < 0.05) but were not correlated with those of BDGEs. Further studies should focus on whether BDGEs and bisphenols exert combined effects on oxidative stress. Our study provides the first BDGEs exposure data in pregnant women and indicated that BDGEs exposure was highly prevalent in pregnant women as early as 2015 in south China.

A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant.

BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients. METHODS: In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for ≤7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symptoms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function measured by spirometry. RESULTS: Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [-0.43, 0.63] log10 copies/ml; p = 0.72) or the shorter symptom-duration subgroup (-0.12 [-0.94, 0.69] log10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated. CONCLUSIONS: Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients.

Patterned Hybrid Wettability Surfaces for Fog Harvesting.

The scarcity of fresh water resources has become increasingly serious in recent years, posing threats to the survival of mankind. The ability of the animals and plants in arid areas to collect water from moisture and fog has drawn attention worldwide. Inspired by the synergistic fog harvesting mode of natural organisms with superhydrophilic and superhydrophobic patterning, a composite membrane with a concave-convex morphology and hybrid wettability was prepared aiming at efficient fog harvesting. The hybrid wettability surface was obtained by chemically modifying the superhydrophilic PAN substrate with 1H,1H,2H,2H-perfluorooctyltrichlorosilane using iron mesh as the mask. The porous PAN substrate was prepared by the non-solvent-induced phase separation (NIPS) method. Fog harvesting is a three-step process: condensation, coalescence, and rapid transportation of water droplets. The area and ratio of the hydrophilic/hydrophobic regions were tuned by adjusting the mesh number of the iron meshes. Under the optimal condition, the fog harvesting efficiencies of 40.3 and 74.2 mg·cm-2·min-1 were obtained when the fog yields were 0.05 and 0.1 L·min-1, respectively. The present work provides an alternative strategy for addressing the shortage of fresh water resources.

Proteomics and metabolomics analysis of nasal lavage fluid in chronic rhinosinusitis with nasal polyps.

KEY POINTS: An integrated proteomics and metabolomics were used to investigate the pathogenesis of CRSwNP. Amino acid metabolism and mitochondrial dysfunction play key roles in the pathogenesis of CRSwNP.

Plasma levels of bone morphogenic protein-4 are downregulated in elderly hypertensive patients with heart failure with preserved ejection fraction.

OBJECTIVE: This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients. METHODS: A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis. RESULTS: Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively. CONCLUSIONS: Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases.

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well as the downstream signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell malignancies by interfering with BCR signaling has been clinically validated by some covalent inhibitors, but suboptimal kinase selectivity may lead to some adverse effects, which also makes the clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors, in which BGB-8035 is located in the ATP binding pocket and has similar hinge binding to ATP but exhibits high selectivity over other kinases (EGFR, Tec, etc.). With an excellent pharmacokinetic profile as well as demonstrated efficacy studies in oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to that of BGB-3111.

Serum response factor promotes axon regeneration following spinal cord transection injury.

Studies have shown that serum response factor is beneficial for axonal regeneration of peripheral nerves. However, its role after central nervous system injury remains unclear. In this study, we established a rat model of T9-T10 spinal cord transection injury. We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time, reached its peak on the 7th day, and then gradually decreased. To investigate the role of serum response factor, we used lentivirus vectors to overexpress and silence serum response factor in spinal cord tissue. We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury. Qualitative observation of biotinylated dextran amine anterograde tracing showed that overexpression of serum response factor increased nerve fibers in the injured spinal cord. Additionally, transmission electron microscopy showed that axon and myelin sheath morphology was restored. Silencing serum response factor had the opposite effects of overexpression. These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury. The underlying mechanism may be related to the regulation of axonal regeneration.

Analysis of interreader agreement in structured reports of pelvic multiparametric magnetic resonance imaging using the METastasis Reporting and Data System for Prostate Cancer guidelines.

PURPOSE: To evaluate interreader agreement on pelvic multiparametric magnetic resonance imaging (mpMRI) interpretation among radiologists using a structured reporting tool based on the METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) guidelines. METHODS: A structured report for follow-up pelvic mpMRI for advanced prostate cancer (APC) patients was formulated based on MET-RADS-P guidelines. In total, 163 paired pelvic mpMRI examinations were performed from December 2017 to February 2021 on 105 patients with APC. These were retrospectively reviewed by two senior and two junior radiologists for metastatic lesion detection and were categorized by these readers using primary/secondary response assessment categories (RACs), with and without the structured report. Interreader agreement regarding metastasis detection and RAC scores was evaluated with Cohen's kappa and weighted Cohen's kappa statistics (K), respectively. RESULTS: The two senior radiologists showed higher agreement with the reference standard for metastasis detection using the structured report (S1: K = 0.83; S2: K = 0.73) compared with the conventional report (S1: K = 0.72; S2: K = 0.61). Junior radiologists showed similar results (J1: 0.66 vs. 0.59; J2: 0.65 vs. 0.57). The overall agreement between the two senior radiologists was excellent for the primary RAC pattern using the structured reports (K = 0.81) and was substantial for secondary RAC categorization (K = 0.75). The interreader agreement of the two junior radiologists was substantial for both primary and secondary RAC values (K = 0.76, 0.68). CONCLUSION: Good interreader agreement was found for the follow-up assessment of APC patients between radiologists, where the pelvic mpMRI was reported using MET-RADS-P guidelines. This improvement applied to both metastatic lesion detection and qualitative RAC assessment.

Benefits and risks evaluation of recombinant human growth hormone replacement therapy in children with GHD after craniopharyngioma surgery.

OBJECTIVES: Childhood-onset craniopharyngiomas (CPs) have a high incidence of growth hormone deficiency (GHD) leading to growth failure and metabolic disorders. We aim to evaluate the benefits and risks of recombinant human growth hormone replacement therapy (GHRT) in postoperative children. METHODS: We retrospectively analyzed auxological and metabolic parameters and adverse events before and after GHRT of 44 children after CP surgery. RESULTS: The median duration of GHRT was 24 months (IQR, 12.5-36). Growth velocity (GV) increased significantly after different treatment duration (TD) compared with baseline (p<0.001) and attained the greatest GV of 12.06 ± 4.16 cm/year at TD6. The mean height standard deviation score (HtSDS) from -3.20 ± 1.16 at baseline improved significantly to -1.51 ± 1.32 at TD36 (p<0.001). There were significant increases in insulin-like growth factor-1 SDS (IGF-1SDS), insulin-like growth factor binding protein 3 SDS (IGFBP-3SDS), bone age (BA), and BA/chronological age (CA) (p<0.05). There was a significant reduction in waist-to-hip ratio (WHR), but there were no significant changes in weight SDS (WtSDS) or BMISDS. Low-density lipoprotein-cholesterol (LDL-C) levels and the incidence of hypercholesterolemia decreased (p<0.05). Three patients (6.8%) had tumor recurrence after 15, 30, and 42 months, respectively. A patient had residual tumor enlargement after 3 months. There was no adverse influence on glucose metabolism or any severe adverse events. CONCLUSIONS: GHRT effectively accelerates GV, increases HtSDS, and improves lipid profiles without unfavorable effects on glucose metabolism. The benefits are clear and the risks of adverse events are low.

Association of diabetes mellitus and glycemic control with left ventricular function and deformation in patients after acute myocardial infarction: a 3 T cardiac magnetic resonance study.

BACKGROUND: Diabetes mellitus (DM) is considered a major risk factor for myocardial infarction (MI), and MI patients with DM have a poor prognosis. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients after acute MI. MATERIALS AND METHODS: One hundred thirteen MI patients without DM [MI (DM-)], 95 with DM [MI (DM+)] and 71 control subjects who underwent CMRscanning were included. LV function, infarct size and LV global peak strains in the radial, circumferential and longitudinal directions were measured. MI (DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV global myocardial strain for all MI patients and MI (DM+) patients were assessed using multivariable linear regression analyses. RESULTS: Compared with control subjects, both MI (DM-) and MI (DM+) patients presented higher LV end-diastolic and end-systolic volume index and lower LV ejection fraction. LV global peak strains progressively declined from the control group to the MI(DM-) group to the MI(DM+) group (all p < 0.05). Subgroup analysis showed that LV global radial PS and longitudinal PS were worse in MI(MD+) patients with poor glycemic control than in those with good glycemic control (all p < 0.05). DM was an independent determinant of impaired LV global peak strain in radial, circumferential and longitudinal directions in patients after acute MI (ß = - 0.166, 0.164 and 0.262, both p < 0.05). The HbA1c level was independently associated with a decreased LV global radial PS (ß = - 0.209, p = 0.025) and longitudinal PS (ß = 0.221, p = 0.010) in MI (DM+) patients. CONCLUSIONS: DM has an additive deleterious effect on LV function and deformation in patients after acute MI, and HbA1c was independently associated with impaired LV myocardial strain.

Noninvasive assessment of myocardial work during left ventricular isovolumic relaxation in patients with diastolic dysfunction.

BACKGROUND: This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD). METHODS: This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC. RESULTS: The total myocardial work during IVR (MWIVR), myocardial constructive work during IVR (MCWIVR), myocardial wasted work during IVR (MWWIVR), and myocardial work efficiency during IVR (MWEIVR) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWEIVR and MCWIVR were significantly correlated with the LV E/e' ratio and left atrial volume index, MWEIVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWEIVR corrected by IVRT also exhibited a significant correlation with tau. CONCLUSIONS: MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function.

TGF-ß1 induced activations of Smad2 and miRNAs inhibit SF-1 and LRH-1 dependent CYP19 expression in rat Leydig cells †.

P450 aromatase, encoded by the Cyp19 gene, catalyzes the synthesis of estrogen, which is crucial for mammalian germ cell differentiation. We have previously shown that transforming growth factor beta 1 (TGF-ß1) attenuated the accumulation of steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1), and eventually reduced the transcription of Cyp19 in rat Leydig cells (LCs). Here we report that TGF-ß1 treatment induced phosphorylation of Smad2 and decreased the expression levels of SF-1 and LRH-1 by elevating the expression levels of microRNA-21-3p and microRNA-339-5p in vivo and in vitro. Furthermore, both TGF-ß1 treatment and over-expression of Smad2 inhibited the SF-1 or LRH-1-regulated promoter activity of the Cyp19 gene, and p-Smad2 physically interacted with SF-1 and LRH-1. Our findings collectively suggest that TGF-ß1 may inhibit the expression of CYP19 in LCs mainly through two ways. On one hand, TGF-ß1 acts through Smad2 to repress the accumulation of SF-1 and LRH-1 at post-transcriptional level by up-regulating specific microRNAs. On the other hand, TGF-ß1 inhibits the transcription activity of Cyp19 through the interaction of p-Smad2 with SF-1/LRH-1.

Trench-assisted 12-core 5-LP mode fiber with a low refractive index circle and a high refractive index ring.

We propose a homogeneous five-mode twelve-core fiber with a trench-assisted structure, combining a low refractive index circle and a high refractive index ring (LCHR). The 12-core fiber utilizes the triangular lattice arrangement. The properties of the proposed fiber are simulated by the finite element method. The numerical result shows that the worst inter-core crosstalk (ICXT) can achieve at -40.14 dB/100 km, which is lower than the target value (-30 dB/100 km). Since adding the LCHR structure, the effective refractive index difference between LP21 and LP02 mode is 2.8 × 10-3, which illustrates that the LP21 and LP02 modes can be separated. In contrast to without the LCHR, the dispersion of LP01 mode has an apparent dropping, which is 0.16 ps/(nm·km) at 1550 nm. Moreover, the relative core multiplicity factor can reach 62.17, which indicates a large core density. The proposed fiber can be applied to the space division multiplexing system to enhance the fiber transmission channels and capacity.

Ivabradine monotherapy in pediatric patients with focal atrial tachycardia: a single-center study.

This study investigated the efficacy of ivabradine monotherapy in pediatric patients with focal atrial tachycardia (FAT). We prospectively enrolled 12 pediatric patients (7.5 ± 4.5 years; six girls) with FAT who were resistant to conventional antiarrhythmics and received ivabradine as monotherapy. Patients were classified as having tachycardia-induced cardiomyopathy (TIC) if they had a left ventricular ejection fraction (LVEF) of < 50% and a left ventricular end-diastolic dimension (LVDD) z-score of > 2 due to tachycardia. Oral ivabradine was initiated at 0.1 mg/kg every 12 h, increased to 0.2 mg/kg every 12 h if no restoration of stable sinus rhythm was observed after two doses, and discontinued after 48 h if neither rhythm nor heart rate control was observed. Of these patients, six (50%) had incessant atrial tachycardia, and 6 had frequent short episodes of FAT. Six patients were diagnosed with TIC, and their mean LVEF and mean LVDD z-score were 36.2 ± 8.7% (range, 27-48%) and 4.2 ± 1.7 (range, 2.2-7.3), respectively. Finally, six patients achieved either rhythm (n = 3) or heart rate control (n = 3) within 48 h of ivabradine monotherapy. One patient achieved rhythm/heart rate control with ivabradine at a dose of 0.1 mg/kg every 12 h, while the others achieved rhythm/heart rate control at a dose of 0.2 mg/kg every 12 h. Five patients received ivabradine monotherapy for chronic therapy, one (20%) of whom had FAT breakthrough 1 month after discharge, and metoprolol was added. Neither FAT recurrence nor adverse effect (with or without beta-blocker) was observed during a median follow-up of 5 months. CONCLUSION: Ivabradine is well-tolerated and may provide early heart rate control in pediatric FAT and can be considered early, especially in the presence of left ventricular dysfunction. Further investigations are deserved to confirm the optimal dose and long-term efficacy in this population. WHAT IS KNOWN: • Focal atrial tachycardia (FAT) is the most common arrhythmia associated with tachycardia-induced cardiomyopathy (TIC) in children, and the efficacy of conventional antiarrhythmic medications in the treatment of FAT is poor. • Ivabradine is currently the only selective hyperpolarization-activated cyclic nucleotide-gated (HCN) inhibitor, which can effectively low HR without negative effect on blood pressure or inotropy. WHAT IS NEW: • Ivabradine (0.1-0.2 mg/kg every 12 h) can effectively suppress focal atrial tachycardia in 50% of pediatric patients. • Ivabradine provides early control of heart rate and hemodynamic stabilization in children with severe left ventricular dysfunction due to atrial tachycardia within 48 h.

CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis.

Cyclin-dependent kinase 13 (CDK13) has been suggested to phosphorylate RNA polymerase II and is involved in transcriptional activation. However, whether CDK13 catalyzes other protein substrates and how CDK13 contributes to tumorigenesis remain largely unclear. We here identify key translation machinery components, 4E-BP1 and eIF4B, as novel CDK13 substrates. CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. Polysome profiling analysis shows that MYC oncoprotein synthesis strictly depends on CDK13-regulated translation in colorectal cancer (CRC), and CDK13 is required for CRC cell proliferation. As mTORC1 is implicated in 4E-BP1 and eIF4B phosphorylation, inactivation of CDK13 in combination with the mTORC1 inhibitor rapamycin further dephosphorylates 4E-BP1 and eIF4B and blocks protein synthesis. As a result, dual inhibition of CDK13 and mTORC1 induces more profound tumor cell death. These findings clarify the pro-tumorigenic role of CDK13 by direct phosphorylation of translation initiation factors and enhancing protein synthesis. Therefore, therapeutic targeting of CDK13 alone or in combination with rapamycin may pave a new way for cancer treatment.

Clinical utilisation of multimodal quantitative magnetic resonance imaging in investigating muscular damage in Duchenne muscular dystrophy: a study on the association between gluteal muscle groups and motor function.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterised by progressive muscular weakness and atrophy. Currently, studies on DMD muscle function mostly focus on individual muscles; little is known regarding the effect of gluteal muscle group damage on motor function. OBJECTIVE: To explore potential imaging biomarkers of hip and pelvic muscle groups for measuring muscular fat replacement and inflammatory oedema in DMD with multimodal quantitative magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred fifty-nine DMD boys and 32 healthy male controls were prospectively included. All subjects underwent MRI examination of the hip and pelvic muscles with T1 mapping, T2 mapping and Dixon sequences. Quantitatively measured parameters included longitudinal relaxation time (T1), transverse relaxation time (T2) and fat fraction. Investigations were all based on hip and pelvic muscle groups covering flexors, extensors, adductors and abductors. The North Star Ambulatory Assessment and stair climbing tests were used to measure motor function in DMD. RESULTS: T1 of the extensors (r = 0.720, P < 0.01), flexors (r = 0.558, P < 0.01) and abductors (r = 0.697, P < 0.001) were positively correlated with the North Star Ambulatory Assessment score. In contrast, T2 of the adductors (r = -0.711, P < 0.01) and fat fraction of the extensors (r = -0.753, P < 0.01) were negatively correlated with the North Star Ambulatory Assessment score. Among them, T1 of the abductors (b = 0.013, t = 2.052, P = 0.042), T2 of the adductors (b = -0.234, t = -2.554, P = 0.012) and fat fraction of the extensors (b = -0.637, t = - 4.096, P < 0.001) significantly affected the North Star Ambulatory Assessment score. Moreover, T1 of the abductors was highly predictive for identifying motor dysfunction in DMD, with an area under the curve of 0.925. CONCLUSION: Magnetic resonance biomarkers of hip and pelvic muscle groups (particularly T1 values of the abductor muscles) have the potential to be used as independent risk factors for motor dysfunction in DMD.

Hypoxic cardiomyocyte-derived exosomes regulate cardiac fibroblast activation, apoptosis, migration and ferroptosis through miR-208a/b.

Studies have found that cardiomyocytes and cardiac fibroblasts (CFs) can communicate through exosomes, thereby affecting each other's biological functions, but there are few studies on the mechanism. miR-208a/b are specifically expressed in the heart and highly expressed in exosomes derived from various myocardial diseases. Hypoxia induced cardiomyocytes to secrete exosomes (H-Exo) with high expression of miR-208a/b. When H-Exo were added to CFs for co-culture, it was found that CFs took up exosomes, thereby upregulating the expression of miR-208a/b. H-Exo significantly promoted the viability and migration of CFs, enhanced the expression of α-SMA, collagen I and III, and promoted the secretion of collagen I and III. miR-208a or/and miR-208b inhibitors significantly attenuated the effects of H-Exo on CF biological functions. miR-208a/b inhibitors significantly enhanced the levels of apoptosis and caspase-3 activity in CFs, while H-Exo significantly attenuated the pro-apoptotic effects of miR-208a/b inhibitors. Further treatment of CFs with ferroptosis inducer Erastin found that H-Exo further enhanced the accumulation of ROS, MDA and Fe2+, the main indicators of ferroptosis, and inhibited the expression of GPX4, a key regulator of ferroptosis. miR-208a or/and miR-208b inhibitors significantly attenuated the effects of Erastin and H-Exo on ferroptosis. In conclusion, hypoxic cardiomyocyte-derived exosomes can regulate the biological functions of CFs through highly expressed miR-208a/b.

Mental Health Conditions- and Substance Use-Associated Emergency Department Visits during the COVID-19 Pandemic in Nevada, USA.

Background-Mental health conditions and substance use are linked. During the COVID-19 pandemic, mental health conditions and substance use increased, while emergency department (ED) visits decreased in the U.S. There is limited information regarding how the pandemic has affected ED visits for patients with mental health conditions and substance use. Objectives-This study examined the changes in ED visits associated with more common and serious mental health conditions (suicidal ideation, suicide attempts, and schizophrenia) and more commonly used substances (opioids, cannabis, alcohol, and cigarettes) in Nevada during the COVID-19 pandemic in 2020 and 2021 compared with the pre-pandemic period. Methods-The Nevada State ED database from 2018 to 2021 was used (n = 4,185,416 ED visits). The 10th Revision of the International Classification of Diseases identified suicidal ideation, suicide attempts, schizophrenia, and the use of opioids, cannabis, alcohol, and cigarette smoking. Seven multivariable logistic regression models were developed for each of the conditions after adjusting for age, gender, race/ethnicity, and payer source. The reference year was set as 2018. Results-During both of the pandemic years (2020 and 2021), particularly in 2020, the odds of ED visits associated with suicidal ideation, suicide attempts, schizophrenia, cigarette smoking, and alcohol use were all significantly higher than those in 2018. Conclusions-Our findings indicate the impact of the pandemic on mental health- and substance use-associated ED visits and provide empirical evidence for policymakers to direct and develop decisive public health initiatives aimed at addressing mental health and substance use-associated health service utilization, especially during the early stages of large-scale public health emergencies, such as the COVID-19 pandemic.

Rapid two-stage amplification in a single tube for simultaneous detection of norovirus GII and group a rotavirus.

The most prevalent viruses currently causing diarrhea are norovirus and rotavirus, and rapid and sensitive detection methods are essential for the early diagnosis of disease. The purpose of this study was to establish a sensitive single-tube two-stage nucleic acid amplification method-reverse transcription recombinase-assisted PCR (RT-RAP)-for simultaneous detection of norovirus GII and group A Rotavirus, with the first stage consisting of isothermal reverse transcription recombinase-aided amplification (RT-RAA) and the second stage consisting of qPCR (quantitative PCR). RT-RAP is more sensitive than either RT-RAA or qRT-PCR (quantitative RT-PCR) alone. And the addition of a barrier that can be disassembled after heating enabled the detection of samples within 1 h in a single closed tube. Sensitivity was 10 copies/reaction of norovirus (Novs) GII and group A rotavirus (RVA). In parallel, two hundred fecal specimens were used to evaluate the method and compare it with a commercial fluorescent quantitative RT-PCR. The data showed kappa values of 0.957 and 0.98 (p < 0.05) for detecting Novs GII and RVA by the two methods, indicating the potential of the newly established assay to be applied to clinical and laboratory testing.