Clinical outcome in hypertensive patients treated with amlodipine plus bisoprolol or plus valsartan.

OBJECTIVE: Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V). METHODS: A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments. RESULTS: Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83-1.18), ASCVD event (aHR 0.97, 95% CI 0.84-1.12), and heart failure (aHR 1.06, 95% CI 0.87-1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52-0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups. CONCLUSIONS: There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Bioreduction of Se(IV) by Lactiplantibacillus plantarum NML21 and synthesis of selenium nanospheres Se(0).

Selenium nanospheres (SeNPs) show less toxicity and greater bioavailability than selenite salts. This research demonstrated the substantial tolerance and efficient conversion of Se(IV) into SeNPs by Lactiplantibacillus plantarum NML21. The bioreduction process of Se(IV) and the properties of SeNPs, including their morphology, particle size, and stability, were investigated with techniques including SEM, EDX, TEM, XPS, FT-IR, dynamic light scattering, XRD, and Raman spectroscopy. Under high selenium stress, certain cells displayed significant deformation and rupture, and released SeNPs as the main product of the bioreduction of Se(IV). These SeNPs were red, amorphous, zero-valent, and spherical, with an average diameter of 160 nm. Spectroscopic analysis highlighted that the functional groups of CO and CO are key to the bioreduction of Se(IV). The study suggested preliminary mechanisms for the bioreduction of Se(IV) and the formation and release of SeNPs by lactic acid bacteria. NML21 may therefore be a promising candidate for SeNPs synthesis.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Sub-high amylose maize starch: an ideal substrate to generate starch with lower digestibility by fermentation of Qu.

BACKGROUND: The fermentation of Qu (FQ) is a novel method to modify the properties of starch to expand its application and especially to increase the resistant starch (RS) content. Using waxy maize starch (WMS) as a fermentation substrate can increase the RS content significantly but it may be time consuming and not cost effective due to the almost negligible RS content of WMS. To solve this problem, we hypothesized that sub-high amylose starch (s-HAMS), with an amylose content close to 50% could be an ideal substrate for FQ. RESULTS: The results showed that FQ did not change the shape and the particle size of starch granules, the gelatinization peak (Tp), or the conclusion temperature (Tc), but the slowly digested starch content declined. Rapidly digested starch content fluctuated during FQ and the amylose content decreased within 36 h and then increased. Within 24h, FQ significanlty increased these values: the RS content, relative crystallinity (RC), the ratio of FTIR absorbances at 1047/1022cm-1, the diffraction peak at 19.8° in X-ray diffraction (XRD), and the gelatinization onset temperature (To) increased significantly, within 24 h of FQ. However, after 24 h of fermentation, the RS content, RC, the ratio of FTIR absorbances at 1047/1022 cm-1, and gelatinization enthalpy (ΔH) decreased significantly. CONCLUSION: Sub-high amylose starch is more suitable for FQ to produce low digestibility starch, and the increase in RS may be due to the formation of 'amylose-lipid' complexes (RS5). © 2024 Society of Chemical Industry.

Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Risk of Hemorrhagic Stroke among Patients Treated with High-Intensity Statins versus Pitavastatin-Ezetimibe: A Population Based Study.

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

HS-SPME-GC-MS Combined with Orthogonal Partial Least Squares Identification to Analyze the Effect of LPL on Yak Milk's Flavor under Different Storage Temperatures and Times.

Flavor is a crucial parameter for assessing the sensory quality of yak milk. However, there is limited information regarding the factors influencing its taste. In this study, the effects of endogenous lipoprotein lipase (LPL) on the volatile flavor components of yak milk under storage conditions of 4 °C, 18 °C and 65 °C were analyzed via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with orthogonal partial least-squares (OPSL) discrimination, and the reasons for the changes in yak milk flavors were investigated. Combined with the difference in the changes in volatile flavor substance before and after the action of LPL, LPL was found to have a significant effect on the flavor of fresh yak milk. Fresh milk was best kept at 4 °C for 24 h and pasteurized for more than 24 h. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to characterize the volatile components in yak milk under various treatment conditions. Twelve substances with significant influence on yak milk flavor were identified by measuring their VIP values. Notably, 2-nonanone, heptanal, and ethyl caprylate exhibited OAV values greater than 1, indicating their significant contribution to the flavor of yak milk. Conversely, 4-octanone and 2-heptanone displayed OAV values between 0.1 and 1, showing their important role in modifying the flavor of yak milk. These findings can serve as monitoring indicators for assessing the freshness of yak milk.

A 3D lung lesion variational autoencoder.

In this study, we develop a 3D beta variational autoencoder (beta-VAE) to advance lung cancer imaging analysis, countering the constraints of conventional radiomics methods. The autoencoder extracts information from public lung computed tomography (CT) datasets without additional labels. It reconstructs 3D lung nodule images with high quality (structural similarity: 0.774, peak signal-to-noise ratio: 26.1, and mean-squared error: 0.0008). The model effectively encodes lesion sizes in its latent embeddings, with a significant correlation with lesion size found after applying uniform manifold approximation and projection (UMAP) for dimensionality reduction. Additionally, the beta-VAE can synthesize new lesions of varying sizes by manipulating the latent features. The model can predict multiple clinical endpoints, including pathological N stage or KRAS mutation status, on the Stanford radiogenomics lung cancer dataset. Comparisons with other methods show that the beta-VAE performs equally well in these tasks, suggesting its potential as a pretrained model for predicting patient outcomes in medical imaging.

Pseudo-targeted lipidomics insights into lipid discrepancies between yak colostrum and mature milk based on UHPLC-Qtrap-MS.

Yak milk is essential to maintain the normal physiological functions of herders in Tibetan areas of China. However, the lipid components of yak colostrum (YC) and mature milk (YM) have not been systematically studied. We employed a quantitative lipidomics to comprehensively describe the alterations in the milk lipid profile of lactating yaks. Herein, totally 851 lipids from 28 lipid subclasses in YC and YM were identified and screened for 43 significantly different lipids (SDLs; variable importance in projection > 1, fold change < 0.5 or > 2 with P < 0.05), with cholesterol ester (CE, 16:0) and triacylglycerol (TAG, 54:6 (20:5), 50:1 (16:0), 56:6 (20:5)) were the potential lipid biomarkers. Fourteen SDLs were modulated downwards, and 29 SDLs were modulated upwards in YM. Moreover, by analyzing lipid metabolic pathways in these SDLs, glycerophospholipid metabolism was the most critical. Our results furnish integral lipid details for evaluating yak milk's nutritional quality.

Socioeconomic Disparity in the Effect of SARS-CoV-2 on Outpatient Visits among People with Type 2 Diabetes in Taiwan.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak posed impact on healthcare. This study evaluated the effect of SARS-CoV-2 outbreak on the outpatient visits of patients with type 2 diabetes and determined the most affected groups. We analyzed Taiwan's National Health Insurance data, including 1,922,702 patients diagnosed with type 2 diabetes from 2018 to 2021. Group-based trajectory modelling identified four distinct outpatient visit patterns, namely, consistently high (Group 1, 74.2%), low-to-high (Group 2, 8.1%), high-to-low (Group 3, 6.0%) and consistently low (Group 4, 11.7%) utilization. Logistic regression was used to analyze correlations between trajectory types and patients' demographics and health statuses. Group 3 members had higher odds of being male [adjusted odds ratio (aOR) = 1.04, 95% confidence interval (CI) 1.03-1.05] and earning below 20,000 New Taiwan Dollar monthly (aOR = 1.29, 95% CI 1.26-1.31) than those in Group 1. However, they were less likely to be under 80 years old (aOR = 0.70-0.97), from lower median family income regions (aOR = 0.81-0.89) or possess a Charlson Comorbidity Index score > 2 (aOR = 0.67, 95% CI 0.66-0.68). Patients with lower income in affluent areas displayed the highest likelihood of falling into Group 3. Patients with type 2 diabetes and low income from wealthy areas were vulnerable during the pandemic. This result emphasizes the need to target resources and support for this subgroup during such crises.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

2023 TAMIS/TSOC/TACVPR Consensus Statement for Patients with Acute Myocardial Infarction Rehabilitation.

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.

Omics analyses of Rehmannia glutinosa dedifferentiated and cambial meristematic cells reveal mechanisms of catalpol and indole alkaloid biosynthesis.

BACKGROUND: Rehmannia glutinosa is a rich source of terpenoids with a high medicinal reputation. The present study compared dedifferentiated cells (DDCs) and cambial meristematic cells (CMCs) cell cultures of R. glutinosa for terpenoid (catalpol) and indole alkaloid (IA) biosynthesis. In this regard, we used widely targeted metabolomics and transcriptome sequencing approaches together with the comparison of cell morphology, cell death (%), and catalpol production at different time points. RESULTS: We were able to identify CMCs based on their morphology and hypersensitivity to zeocin. CMCs showed higher dry weight content and better catalpol production compared to DDCs. The metabolome analysis revealed higher concentrations of IA, terpenoids, and catalpol in CMCs compared to DDCs. The transcriptome sequencing analysis showed that a total of 27,201 genes enriched in 139 pathways were differentially expressed. The higher catalpol concentration in CMCs is related to the expression changes in genes involved in acetyl-CoA and geranyl-PP biosynthesis, which are precursors for monoterpenoid biosynthesis. Moreover, the expressions of the four primary genes involved in monoterpenoid biosynthesis (NMD, CYP76A26, UGT6, and CYP76F14), along with a squalene monooxygenase, exhibit a strong association with the distinct catalpol biosynthesis. Contrarily, expression changes in AADC, STR, and RBG genes were consistent with the IA biosynthesis. Finally, we discussed the phytohormone signaling and transcription factors in relation to observed changes in metabolome. CONCLUSIONS: Overall, our study provides novel data for improving the catalpol and IA biosynthesis in R. glutinosa.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

360° Stereo Image Composition With Depth Adaption.

360° images and videos have become an economic and popular way to provide VR experiences using real-world content. However, the manipulation of the stereo panoramic content remains less explored. In this paper, we focus on the 360° image composition problem, and develop a solution that can take an object from a stereo image pair and insert it at a given 3D position in a target stereo panorama, with well-preserved geometry information. Our method uses recovered 3D point clouds to guide the composited image generation. More specifically, we observe that using only a one-off operation to insert objects into equirectangular images will never produce satisfactory depth perception and generate ghost artifacts when users are watching the result from different view directions. Therefore, we propose a novel per-view projection method that segments the object in 3D spherical space with the stereo camera pair facing in that direction. A deep depth densification network is proposed to generate depth guidance for the stereo image generation of each view segment according to the desired position and pose of the inserted object. We finally combine the synthesized view segments and blend the objects into the target stereo 360° scene. A user study demonstrates that our method can provide good depth perception and removes ghost artifacts. The per-view solution is a potential paradigm for other content manipulation methods for 360° images and videos.