The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Cholangiocarcinoma imaging: from diagnosis to response assessment.

Cholangiocarcinoma (CCA), a highly aggressive primary liver cancer arising from the bile duct epithelium, represents a substantial proportion of hepatobiliary malignancies, posing formidable challenges in diagnosis and treatment. Notably, the global incidence of intrahepatic CCA has seen a rise, necessitating a critical examination of diagnostic and management strategies, especially due to presence of close imaging mimics such as hepatocellular carcinoma (HCC) and combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). Hence, it is imperative to understand the role of various imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), elucidating their strengths, and limitations in diagnostic precision and staging accuracy. Beyond conventional approaches, there is emerging significance of functional imaging tools including positron emission tomography (PET)-CT and diffusion-weighted (DW)-MRI, providing pivotal insights into diagnosis, therapeutic assessment, and prognostic evaluation. This comprehensive review explores the risk factors, classification, clinical features, and role of imaging in the holistic spectrum of diagnosis, staging, management, and restaging for CCA, hence serving as a valuable resource for radiologists evaluating CCA.

STUB1 increases adiponectin expression by inducing ubiquitination and degradation of NR2F2, thereby reducing hepatic stellate cell activation and alleviating non-alcoholic fatty liver disease.

BACKGROUND: Adiponectin (APN) has exhibited ameliorating effects on non-alcoholic fatty liver disease (NAFLD). This study investigates the roles of APN and its regulatory molecules in hepatic stellate cell (HSC) activation and the progression of NAFLD. METHODS: Mice were subjected to a high-fat diet (HFD) to establish NAFLD models. Liver tissue was examined for lipid metabolism, fibrosis, and inflammation. Mouse 3T3-L1 adipocytes were exposed to palmitic acid (PA) to mimic a high-fat environment. The conditioned medium (CM) from adipocytes was collected for the culture of isolated mouse HSCs. Gain- or loss-of-function studies of APN, nuclear receptor subfamily 2 group F member 2 (NR2F2), and STIP1 homology and U-box containing protein 1 (STUB1) were performed to analyze their roles in NAFLD and HSC activation in vivo and in vitro. RESULTS: APN expression was poorly expressed in HFD-fed mice and PA-treated 3T3-L1 adipocytes, which was attributed to the transcription inhibition mediated by NR2F2. Silencing of NR2F2 restored the APN expression, ameliorating liver steatosis, fibrosis, and inflammatory cytokine infiltration in mouse livers and reducing HSC activation. Similarly, the NR2F2 silencing condition reduced HSC activation in vitro. However, these effects were counteracted by artificial APN silencing. STUB1 facilitated the ubiquitination and protein degradation of NR2F2, and its upregulation mitigated NAFLD-like symptoms in mice and HSC activation, effects reversed by the NR2F2 overexpression. CONCLUSION: This study highlights the role of STUB1 in reducing HSC activation and alleviating NAFLD by attenuating NR2F2-mediated transcriptional repression of APN.

miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization.

Previous studies have found that miR-335 is highly expressed in type II diabetes mellitus (T2DM) models and is related to insulin secretion, but there are few studies on the regulatory effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. This study aims to explore the effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. Blood glucose (insulin tolerance tests, glucose tolerance tests) and body weight of the T2DM model were measured; macrophages from adipose tissue were isolated and cultured, and the number of macrophages was detected by F4/80 immunofluorescence assay; the Real-time quantitative polymerase chain reaction (qPCR) assay and Western blot assay were used to detect the miR-335-3p expression levels, insulin-like growth factor 1 (IGF-1), M1-polarizing genes (inducible nitric oxide synthase [iNOS] and TNF-α) as well as M2-polarizing genes (IL-10 and ARG-1). The targeting link between miR-335-3p and IGF-1 was confirmed using bioinformatics and dual luciferase assay. The results showed that miR-335-3p expression level in adipose tissue of the T2DM model was significantly decreased, and the mice's body weight and blood glucose levels dropped considerably, miR-335-3p inhibited the number of macrophages, inhibiting the iNOS and TNF-α relative mRNA expression levels, and up-regulated the IL-10 and ARG-1 relative mRNA expression levels, miR-335-3p negatively regulated target gene IGF-1, IGF-1 significantly increased the iNOS and TNF-α mRNA and protein expression levels, decreasing the IL-10 and ARG-1 mRNA and protein expression levels, indicating that miR-335-3p could affect the T2DM process by regulating macrophage polarization via IGF-1.

Role of Computed Tomography in Cardiac Electrophysiology.

With the increasing prevalence of arrhythmias, the use of electrophysiology (EP) procedures has increased. Recent advancements in computed tomography (CT) technology have expanded its use in pre-assessments and post-assessments of EP procedures. CT provides high-resolution images, is noninvasive, and is widely available. This article highlights the strengths and weaknesses of cardiac CT in EP.

Society of Radiologists in Ultrasound Consensus Conference Recommendations for Incidental Gallbladder Polyp Management: Interreader Agreement Among Ten Radiologists.

Background: The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations support less-aggressive management of small gallbladder polyps on ultrasound versus earlier approaches and may help standardize polyp evaluation by radiologists. Objective: To assess radiologists' interreader agreement in applying the SRU recommendations for management of incidental gallbladder polyps on ultrasound. Methods: This retrospective study included 105 patients (median age, 52 years; 75 women, 27 men) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003 and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using SRU recommendations, assessed one polyp per patient for risk category (extremely low-risk, low-risk, or indeterminate risk) and possible recommendation for surgical consultation. Five radiologists were considered less-experienced (<5 years), and five more-experienced (≥5 years). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. Results: For risk category assignments, interreader agreement was substantial among all readers (k=0.710), less-experienced readers (k=0.705), and more-experienced readers (k=0.692). For surgical consultation recommendations, interreader agreement was substantial among all readers (k=0.795) and more-experienced readers (kappa=0.740), and almost perfect among less-experienced readers (k=0.811). Of ten readers, a median of 5 (IQR, 2-8), 4 (IQR, 2-7), and 0 (IQR, 0-0) classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the fraction of polyps classified as extremely low risk ranged from 32-72%, as low risk from 24-65%, and as indeterminate risk from 0-8%. Of ten readers, a median of 0 (IQR, 0-1) recommended surgical consultation; the fraction of polyps receiving a surgical consultation recommendation ranged from 4-22%. A total of 102/105 polyps were nonneoplastic; 3/105 were neoplastic (all benign). Based on readers' most-common assessments for the nonneoplastic polyps, the risk category was extremely low risk in 53, low risk in 48, and indeterminate risk in 1; surgical consultation was recommended in 16. Conclusion: Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. Clinical Impact: The findings support overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Intra-patient variability of iodine quantification across different dual-energy CT platforms: assessment of normalization techniques.

OBJECTIVES: To investigate intra-patient variability of iodine concentration (IC) between three different dual-energy CT (DECT) platforms and to test different normalization approaches. METHODS: Forty-four patients who underwent portal venous phase abdominal DECT on a dual-source (dsDECT), a rapid kVp switching (rsDECT), and a dual-layer detector platform (dlDECT) during cancer follow-up were retrospectively included. IC in the liver, pancreas, and kidneys and different normalized ICs (NICPV:portal vein; NICAA:abdominal aorta; NICALL:overall iodine load) were compared between the three DECT scanners for each patient. A longitudinal mixed effects analysis was conducted to elucidate the effect of the scanner type, scan order, inter-scan time, and contrast media amount on normalized iodine concentration. RESULTS: Variability of IC was highest in the liver (dsDECT vs. dlDECT 28.96 (14.28-46.87) %, dsDECT vs. rsDECT 29.08 (16.59-62.55) %, rsDECT vs. dlDECT 22.85 (7.52-33.49) %), and lowest in the kidneys (dsDECT vs. dlDECT 15.76 (7.03-26.1) %, dsDECT vs. rsDECT 15.67 (8.86-25.56) %, rsDECT vs. dlDECT 10.92 (4.92-22.79) %). NICALL yielded the best reduction of IC variability throughout all tissues and inter-scanner comparisons, yet did not reduce the variability between dsDECT vs. dlDECT and rsDECT, respectively, in the liver. The scanner type remained a significant determinant for NICALL in the pancreas and the liver (F-values, 12.26 and 23.78; both, p < 0.0001). CONCLUSIONS: We found tissue-specific intra-patient variability of IC across different DECT scanner types. Normalization mitigated variability by reducing physiological fluctuations in iodine distribution. After normalization, the scanner type still had a significant effect on iodine variability in the pancreas and liver. CLINICAL RELEVANCE STATEMENT: Differences in iodine quantification between dual-energy CT scanners can partly be mitigated by normalization, yet remain relevant for specific tissues and inter-scanner comparisons, which should be taken into account at clinical routine imaging. KEY POINTS: • Iodine concentration showed the least variability between scanner types in the kidneys (range 10.92-15.76%) and highest variability in the liver (range 22.85-29.08%). • Normalizing tissue-specific iodine concentrations against the overall iodine load yielded the greatest reduction of variability between scanner types for 2/3 inter-scanner comparisons in the liver and for all (3/3) inter-scanner comparisons in the kidneys and pancreas, respectively. • However, even after normalization, the dual-energy CT scanner type was found to be the factor significantly influencing variability of iodine concentration in the liver and pancreas.

Diagnostic performance and feasibility of dual-layer detector dual-energy CT for characterization of urinary stones in patients of different sizes.

BACKGROUND: Urinary stones are frequently encountered in urology and are typically identified using non-contrast CT scans. Dual-energy CT (DECT) is a valuable imaging technique that produces material-specific images and allows for precise assessment of stone composition by estimating the effective atomic number (Zeff), a capability not achievable with the conventional single-energy CT's attenuation measurement method. PURPOSE: To investigate the diagnostic performance and image quality of dual-layer detector DECT (dlDECT) in characterizing urinary stones in patients of different sizes. METHODS: All consecutive dlDECT examinations with stone protocol and presence of urinary stones between July 2018 and November 2019 were retrospectively evaluated. Two radiologists independently reviewed 120 kVp and color-overlay Zeff images to determine stone composition (reference standard = crystallography) and image quality. The objective analysis included image noise and Zeff values measurement. RESULTS: A total of 739 urinary stones (median size 3.7 mm, range 1-35 mm) were identified on 177 CT examinations from 155 adults (mean age, 57 ± 15 years, 80 men, median weight 82.6 kg, range 42.6-186.9 kg). Using color-overlay Zeff images, the radiologists could subjectively interpret the composition in all stones ≥ 3 mm (n = 491). For stones with available reference standards (n = 74), dlDECT yielded a sensitivity of 80% (95%CI 44-98%) and a specificity of 98% (95%CI 92-100%) in visually discriminating uric acid from non-uric acid stones. Patients weighing > 90 kg and ≤ 90 kg had similar stone characterizability (p = 0.20), with 86% of stones characterized in the > 90 kg group and 87% in the ≤ 90 kg group. All examinations throughout various patients' weights revealed acceptable image quality. A Zeff cutoff of 7.66 accurately distinguished uric acid from non-uric acid stones (AUC = 1.00). Zeff analysis revealed AUCs of 0.78 and 0.91 for differentiating calcium-based stones from other non-uric stones and all stone types, respectively. CONCLUSION: dlDECT allowed accurate differentiation of uric acid and non-uric acid stones among patients with different body sizes with acceptable image quality. CLINICAL IMPACT: The ability to accurately differentiate uric acid stones from non-uric acid stones using color-overlay Zeff images allows for better tailored treatment strategies, helping to choose appropriate interventions and prevent potential complications related to urinary stones in patient care.

Imaging of Urinary Bladder and Ureteral Endometriosis with Emphasis on Diagnosis and Technique.

Endometriosis is a chronic inflammatory gynecological condition affecting 10-15% of women in the reproductive age group. The urinary tract is the second most common extragenital organ system affected by endometriosis, and the urinary bladder and ureter are the two most common sites involved. Involvement of the urinary bladder can cause chronic debilitating symptoms, whereas ureteral involvement may lead to asymptomatic loss of renal function. Both conditions are frequently unsuspected, leading to a delay in diagnosis. Therefore, it is important to recognize this entity early, for which knowledge of imaging appearances and techniques is helpful. In this review article, we describe (a) endometriosis background, pathogenesis, definitions and clinical symptoms, (b) imaging appearance, with emphasis on ultrasound and MRI findings of urinary bladder and ureteric endometriosis, (c) ultrasound technique and MRI sequences useful for making the correct diagnosis, (d) overview of the treatment options and key imaging findings that are important to the surgeon for surgical planning, and (e) a structured reporting template useful for multidisciplinary patient management.

Dual-Energy Computed Tomography to Photon Counting Computed Tomography: Emerging Technological Innovations.

Computed tomography (CT) has seen remarkable developments in the past several decades, radically transforming the role of imaging in day-to-day clinical practice. Dual-energy CT (DECT), an exciting innovation introduced in the early part of this century, has widened the scope of CT, opening new opportunities due to its ability to provide superior tissue characterization. The introduction of photon-counting CT (PCCT) heralds a paradigm shift in CT scanner technology representing another significant milestone in CT innovation. PCCT offers several advantages over DECT, such as improved spectral resolution, enhanced tissue characterization, reduced image artifacts, and improved image quality.

Can 1.25 mm thin-section images generated with Deep Learning Image Reconstruction technique replace standard-of-care 5 mm images in abdominal CT?

BACKGROUND: CT image reconstruction has evolved from filtered back projection to hybrid- and model-based iterative reconstruction. Deep learning-based image reconstruction is a relatively new technique that uses deep convolutional neural networks to improve image quality. OBJECTIVE: To evaluate and compare 1.25 mm thin-section abdominal CT images reconstructed with deep learning image reconstruction (DLIR) with 5 mm thick images reconstructed with adaptive statistical iterative reconstruction (ASIR-V). METHODS: This retrospective study included 52 patients (31 F; 56.9±16.9 years) who underwent abdominal CT scans between August-October 2019. Image reconstruction was performed to generate 5 mm images at 40% ASIR-V and 1.25 mm DLIR images at three strengths (low [DLIR-L], medium [DLIR-M], and high [DLIR-H]). Qualitative assessment was performed to determine image noise, contrast, visibility of small structures, sharpness, and artifact based on a 5-point-scale. Image preference determination was based on a 3-point-scale. Quantitative assessment included measurement of attenuation, image noise, and contrast-to-noise ratios (CNR). RESULTS: Thin-section images reconstructed with DLIR-M and DLIR-H yielded better image quality scores than 5 mm ASIR-V reconstructed images. Mean qualitative scores of DLIR-H for noise (1.77 ± 0.71), contrast (1.6 ± 0.68), small structure visibility (1.42 ± 0.66), sharpness (1.34 ± 0.55), and image preference (1.11 ± 0.34) were the best (p<0.05). DLIR-M yielded intermediate scores. All DLIR reconstructions showed superior ratings for artifacts compared to ASIR-V (p<0.05), whereas each DLIR group performed comparably (p>0.05, 0.405-0.763). In the quantitative assessment, there were no significant differences in attenuation values between all reconstructions (p>0.05). However, DLIR-H demonstrated the lowest noise (9.17 ± 3.11) and the highest CNR (CNRliver = 26.88 ± 6.54 and CNRportal vein = 7.92 ± 3.85) (all p<0.001). CONCLUSION: DLIR allows generation of thin-section (1.25 mm) abdominal CT images, which provide improved image quality with higher inter-reader agreement compared to 5 mm thick images reconstructed with ASIR-V. CLINICAL IMPACT: Improved image quality of thin-section CT images reconstructed with DLIR has several benefits in clinical practice, such as improved diagnostic performance without radiation dose penalties.

Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy, which primarily occurs in the elderly. Cellular senescence is considered to be closely associated with the occurrence and progression of malignant tumors including MM, and lncRNA can mediate the process of cellular senescence by regulating key signaling pathways such as p53/p21 and p16/RB. However, the role of cellular senescence related lncRNAs (CSRLs) in MM development has never been reported. Herein, we identified 11 CSRLs (AC004918.5, AC103858.1, AC245100.4, ACBD3-AS1, AL441992.2, ATP2A1-AS1, CCDC18-AS1, LINC00996, TMEM161B-AS1, RP11-706O15.1, and SMURF2P1) to build the CSRLs risk model, which was confirmed to be highly associated with overall survival (OS) of MM patients. We further demonstrated the strong prognostic value of the risk model in MM patients receiving different regimens, especially for those with three-drug combination of bortezomib, lenalidomide, and dexamethasone (VRd) as first-line therapy. Not only that, our risk model also excels in predicting the OS of MM patients at 1, 2, and 3 years. In order to verify the function of these CSRLs in MM, we selected the lncRNA ATP2A1-AS1 which presented the largest expression difference between high-risk groups and low-risk groups for subsequent analysis and validation. Finally, we found that down-regulation of ATP2A1-AS1 can promote cellular senescence in MM cell lines. In conclusion, the CSRLs risk model established in present study provides a novel and more accurate method for predicting MM patients' prognosis and identifies a new target for MM therapeutic intervention.

What is needed by parents of constipated infants and toddlers: A cross-sectional study in China.

Background: Childhood functional constipation is a worldwide problem that affects the intestinal function of children and the quality of life of their families. Treatment and management of the disease need to be carried out at home by parents. Assessment of caregiving needs is an important link in planning and implementing the intervention. This study aimed to assess the caregiving needs of parents of FC infants and toddlers. Methods: The researchers recruited convenience samples of parents from an outpatient pediatric constipation clinic of a children's medical center. Totally 211 fathers/mothers were recruited. Nursing needs were measured by a questionnaire, and associations between nursing needs and potential factors were examined using multiple regression analysis. Results: The vast majority of participants (88.7%) expressed the need of receiving support from professionals, and only 44 (20.85%) had obtained help from medical staff. The needs of parents mainly include information needs, health needs, psychological needs, and social needs. Of all the needs, the highest score was for information needs (3.87 ± 0.69), followed by the dimension of health needs (3.74 ± 0.82). Results showed statistically significant differences in parental education, place of residence, age of children, duration of FC, defecation frequency, difficulty of defecation, and stool traits in nursing needs (p < 0.05). The regression model explained 64.2% of the variance of nursing needs. Conclusions: Information needs were the major concern for parents, and the unmet needs of parents should be addressed during treatment and care. When developing care plans and providing health education, it should be adjusted according to the specific conditions of the child and parents to improve the compliance of the parents with treatment and care.

Efficacy of short-chain polypeptide-based EEN formulas in alleviating intestinal injury in children with Crohn's disease: a single-center study in China.

Short-chain polypeptides are composed of three to nine amino acids, which can be absorbed by the intestinal tract without digestive enzymes and ATP energy. Crohn's disease (CD) is a chronic non-specific disease derived from inflammation and damage of the gastrointestinal tract. In this study, we aim to investigate the effect of short-chain polypeptide-based exclusive enteral nutrition (EEN) formulas on intestinal injury in Chinese children with active CD. From January 2013 to January 2019, a total of 84 consecutive children with a diagnosis of Crohn's disease (CD) in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, were divided into mild and moderate-to-severe active CD groups. Each group was further divided into two subgroups: drug group and short-chain polypeptide plus drug group. Tests were carried out on the levels of intestinal fatty acid binding protein (I-FABP) in the blood, fecal calprotectin (FC), and occludin protein in the intestinal mucosa 1 day before treatment and 8 weeks after treatment. Endoscopic and histopathological observations were detected to compare the changes in intestinal injury in children with active CD. After 8 weeks of treatment, the SES-CD scores and Chiu scores of the ileocecal area and terminal ileum of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD in short-chain polypeptide plus drug group were significantly lower than those in the drug group. The OD value of occludin in the terminal ileum and ileocecal area of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD after short-chain polypeptide-based EEN formulas and drug treatment was significantly higher than those in the drug group (p < 0.05). Meanwhile, the levels of FC and I-FABP were significantly decreased (p < 0.05). The results showed that short-chain polypeptide-based EEN formulas effectively alleviate intestinal injury in children with active CD.

A Study of the Mechanisms and Characteristics of Fluorescence Enhancement for the Detection of Formononetin and Ononin.

In this work, the origins for the spectral difference between two isoflavones, formononetin (F) and ononin (FG), are revealed via a comparison study of the fluorescence molecular structure. The fluorescence enhancement of FG in hot alkaline conditions is reported for the first time. For F, there is almost no fluorescence under acidic conditions, but when the pH is >4.8, its fluorescence begins to increase due to the deprotonation of 7-OH. Under a pH between 9.3 and 12.0, the anionic form of F produces a strong and stable fluorescence. The fluorescence quantum yield (Yf) of F is measured to be 0.042. FG shows only weak fluorescence in aqueous solutions under a wide range of pH until it is placed in hot alkaline solutions, which is attributed to the cleavage reaction of the γ-pyrone ring in FG. The Yf of FG is determined to be 0.020. Based on the fluorescence sensitization methods of F and FG, the quantitative analysis and detection of two substances can be realized. The limit of the detections for F and FG are 2.60 ng·mL-1 and 9.30 ng·mL-1, respectively. The linear detection ranges of F and FG are 11.7~1860 ng·mL-1 and 14.6~2920 ng·mL-1, respectively. Although the structural relationship between F and FG is glycoside and aglycone, under hot alkaline conditions, the final products after the cleavage and hydrolysis reactions are essentially different. The different fluorescence characteristics between F and FG pave a way for further identification and a quantitative analysis of the corresponding components in Chinese herbal medicine.

Application of Single-Cell Genomics in Cardiovascular Research.

Cardiovascular diseases (CVDs) are the leading cause of death in the global world. The emergence of single-cell technologies has greatly facilitated the research on CVDs. Currently, those single-cell technologies have been widely applied in atherosclerosis, myocardial infarction, cardiac ischemia-reperfusion injury, arrhythmia, hypertrophy cardiomyopathy, and heart failure, which are extremely helpful in elucidating the underlying mechanisms of CVDs from physiological and pathological perspectives at DNA, RNA, protein, post-transcriptional, post-translational, and metabolite levels. In this review, we would like to briefly introduce the current single-cell technologies, and will focus on the utilization of single-cell genomics in various heart diseases. Single-cell technologies have great potential in exploration of CVDs, and widespread application of single-cell genomics will promote the understanding and therapeutic treatments for CVDs.

Head CT deep learning model is highly accurate for early infarct estimation.

Non-contrast head CT (NCCT) is extremely insensitive for early (< 3-6 h) acute infarct identification. We developed a deep learning model that detects and delineates suspected early acute infarcts on NCCT, using diffusion MRI as ground truth (3566 NCCT/MRI training patient pairs). The model substantially outperformed 3 expert neuroradiologists on a test set of 150 CT scans of patients who were potential candidates for thrombectomy (60 stroke-negative, 90 stroke-positive middle cerebral artery territory only infarcts), with sensitivity 96% (specificity 72%) for the model versus 61-66% (specificity 90-92%) for the experts; model infarct volume estimates also strongly correlated with those of diffusion MRI (r2 > 0.98). When this 150 CT test set was expanded to include a total of 364 CT scans with a more heterogeneous distribution of infarct locations (94 stroke-negative, 270 stroke-positive mixed territory infarcts), model sensitivity was 97%, specificity 99%, for detection of infarcts larger than the 70 mL volume threshold used for patient selection in several major randomized controlled trials of thrombectomy treatment.

CT image quality evaluation in the age of deep learning: trade-off between functionality and fidelity.

OBJECTIVE: To quantitatively compare DLIR and ASiR-V with realistic anatomical images. METHODS: CT scans of an anthropomorphic phantom were acquired using three routine protocols (brain, chest, and abdomen) at four dose levels, with images reconstructed at five levels of ASiR-V and three levels of DLIR. Noise power spectrum (NPS) was estimated using a difference image by subtracting two matching images from repeated scans. Using the max-dose FBP reconstruction as the ground truth, the structure similarity index (SSIM) and gradient magnitude (GM) of difference images were evaluated. Image noise magnitude (σ), frequency location of the NPS peak (fpeak), mean SSIM (MSSIM), and mean GM (MGM) were used as quantitative metrics to compare image quality, for each anatomical region, protocol, algorithm, dose level, and slice thickness. RESULTS: Image noise had a strong (R2 > 0.99) power law relationship with dose for all algorithms. For the abdomen and chest, fpeak shifted from 0.3 (FBP) down to 0.15 mm-1 (ASiR-V 100%) with increasing ASiR-V strength but remained 0.3 mm-1 for all DLIR levels. fpeak shifted down for the brain protocol with increasing DLIR levels. Three levels of DLIR produced similar image noise levels as ASiR-V 40%, 80%, and 100%, respectively. DLIR had lower MSSIM but higher MGM than ASiR-V while matching imaging noise. CONCLUSION: Compared to ASiR-V, DLIR presents trade-offs between functionality and fidelity: it has a noise texture closer to FBP and more edge enhancement, but reduced structure similarity. These trade-offs and unique protocol-dependent behaviors of DLIR should be considered during clinical implementation and deployment. KEY POINTS: • DLIR reconstructed images demonstrate closer noise texture and lower structure similarity to FBP while producing equivalent noise levels comparable to ASiR-V. • DLIR has additional edge enhancement as compared to ASiR-V. • DLIR has unique protocol-dependent behaviors that should be considered for clinical implementation.

Fluorescence, Absorption, Chromatography and Structural Transformation of Chelerythrine and Ethoxychelerythrine in Protic Solvents: A Comparative Study.

Chelerythrine (CH) and ethoxychelerythrine (ECH) are chemical reference substances for quality control of Chinese herbal medicines, and ECH is the dihydrogen derivative of CH. In this study, their fluorescence and absorption spectra, as well as their structural changes in different protic solvents were compared. It was observed that their emission fluorescence spectra in methanol were almost the same (both emitted at 400 nm), which may be attributed to the nucleophilic and exchange reactions of CH and ECH with methanol molecules with the common product of 6-methoxy-5,6-dihydrochelerythrine (MCH). When diluted with water, MCH was converted into CH, which mainly existed in the form of positively charged CH+ under acidic and near-neutral conditions with the fluorescence emission at 550 nm. With the increase of pH value of the aqueous solution, CH+ converted to 6-hydroxy-5,6-dihydrochelerythrine (CHOH) with the fluorescence emission at 410 nm. The fluorescence quantum yields of MCH and CHOH were 0.13 and 0.15, respectively, and both the fluorescence intensities were much stronger than that of CH+. It is concluded that CH and ECH can substitute each other in the same protic solvent, which was further verified by high-performance liquid chromatography. This study will help in the investigation of structural changes of benzophenanthridine alkaloids and will provide the possibility for the mutual substitution of standard substances in relevant drug testing.

Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3ß Signaling.

Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3ß at the middle-late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2ß-Aα expression. Moreover, GSK3ß inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3ß, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3ß, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3ß inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease.