bluuebunny/crossref_metadata_2025 huggingface dataset:
UPAYA PEMBERDAYAAN MASYARAKAT MELALUI PRODUKSI DAN PEMASARAN SUSU KEDELAI
Authors: Hartanti Dyah Yunita , Sutrawati Mimi
Published: May 2022

Kegiatan pengabdian pada masyarakat (PPM) ini dilakukan dengan pemberdayaan masyarakat kelompok Tani Pelita Kusuma di Desa Bumi Harjo, Kecamatan Pinang Raya Kabupaten Bengkulu Utara. Tujuan dari kegiatan ini adalah untuk mengaktifkan kembali produksi susu kedelai yang sebelumnya terhenti karena beberapa kendala.  Melalui kegiatan PPM ini diharapkan dapat memperbaiki kinerja kelompok Tani Pelita Kusuma dalam produksi, tata kelola keuangan, dan pemasaran. Program ini dilakukan melalui beberapa tahap, yakni 1) produksi susu kedelai siap saji; 2) transfer teknologi pengemasan susu kedelai; 3) Pemasaran produk dan aspek manajemen keuangan. Program kerja ini terlaksana dengan baik dengan pelatihan dan pendampingan anggota kelompok tani. Setelah kegiatan ini terjadi peningkatan kuantitas dan kualitas produksi olahan susu kedelai di kelompok Tani Pelita Kusuma. Pemasaran produk dan manajemen keuangan sangat penting untuk keberlanjutan usaha ini di masa yang akan datang. COMMUNITY EMPOWERMENT EFFORT THROUGH SOYMILK PRODUCTION AND MARKETING. This community service activity (PPM) is carried out by empowering the Pelita Kusuma farmer group community in Bumi Harjo Village, Pinang Raya District, North Bengkulu Regency. The purpose of this activity is to reactivate the production of soymilk which was previously stopped due to several obstacles. Through this PPM activity, it is expected to improve the performance of the Pelita Kusuma farmer group in production, financial management, and marketing. This program is carried out through several stages, namely 1) the production of ready-to-eat soy milk; 2) transfer of soy milk packaging technology; 3) Product marketing and financial management aspects. This work program is well implemented with the training and mentoring of farmer group members. After this activity, there was an increase in the quantity and quality of processed soymilk production in the Pelita Kusuma Farmer group.
Mathematical Modeling of the Endocrine System
Authors: Bulgakova S. , Romanchuk N. , Treneva E.
Published: May 2022

Hormones, having their own unique rhythms of secretion, have a systemic effect on all organs and systems of the human body. Combined mathematical modeling and experimental approaches have shown that these rhythms are the result of regulatory processes occurring at many levels of the body and require constant dynamic balancing, especially in response to stimuli. In a review of the literature, we have shown how such a hybrid approach has been successfully applied to unravel the complex mechanisms of regulation of carbohydrate metabolism (metabolic axis), hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. In addition, the prospects for further development of this direction are shown.
The Effect of IGV Wake on Axial Compressor Rotor at Low Reynolds Numbers
Authors:   Gas-turbine/Institute of Engineering Thermophysics， Chinese Academy of Sciences, Li Lin , Zhang Yanfeng ,   Gas-turbine/Institute of Engineering Thermophysics， Chinese Academy of Sciences, Han Ge ,   Gas-turbine/Institute of Engineering Thermophysics， Chinese Academy of Sciences
Published: May 2022

Periodic wakes not only affect the characteristics of the surface boundary layer of the blades of a compressor and cause profile losses, but also influence the vortical structures of secondary flow and lead to corresponding losses. Thus, understanding the physical mechanisms of unsteady interactions to eliminate such losses is important for improving the performance of blades of the compressor, particularly at a low Reynolds number (Re). To understand the influence of upstream wakes on the structure of the flow field and the flow mechanism in the boundary layer, this study numerically simulated a one-stage high-pressure unsteady compressor under different Reynolds numbers. The discussion focuses on the unsteady characteristics of the mechanisms of interaction between upstream wakes and the boundary layer in the highpressure compressor. The results indicate that laminar separation was suppressed and promoted at high and low Re, respectively, resulting in corresponding changes in the losses. In addition, the influence of the wake on boundary layer transition weakened with a decrease in Re. It still caused the position of reattachment of the boundary layer to change during transition, which significantly affected the performance of the compressor.
Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model
Authors: Stempien A. , Josvai M. , de Lange W. J. , Hernandez J. J. , Notbohm J. , Kamp T. J. , Valdivia H. H. , Eckhardt L. L. , Maginot K. R. , Ralphe J. C. , Crone W. C.
Published: May 2022

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by an arrhythmogenic mechanism involving disruption of calcium handling. This genetic disease can lead to sudden death in children and young adults during physical or emotional stress. Prior CPVT studies have focused on calcium handling, but mechanical functionality has rarely been investigated in vitro. In this research we combine stem cell-derived cardiomyocytes from a CPVT patient (RyR2-H2464D mutation) and a healthy familial control with an engineered culture platform to evaluate mechanical function of cardiomyocytes. Substrates with Young’s modulus ranging from 10 to 50 kPa were used in conjunction with microcontact printing of ECM proteins into defined patterns for subsequent attachment. Digital Image Correlation (DIC) was used to evaluate collections of contracting cells. The amplitude of contractile strain was utilized as a quantitative indicator of functionality and disease severity. We found statistically significant differences: the maximum contractile strain was consistently higher in patient samples compared to control samples on all substrate stiffnesses. Additionally, the patient cell line had a statistically significantly slower intrinsic contraction rate than the control, which agrees with prior literature. Differences in mechanical strain have not been previously reported, and hypercontractility is not a known characteristic of CPVT. However, functional changes can occur as the disease progresses, thus this observation may not represent behavior observed in adolescent and adult patients. These results add to the limited studies of mechanical function of CPVT CMs reported in literature and identify functional differences that should be further explored.
Mix and Match: Promoters and Terminators for Tuning Gene Expression in the Methylotrophic Yeast Ogataea polymorpha
Authors: Wefelmeier Katrin , Ebert Birgitta E. , Blank Lars M. , Schmitz Simone
Published: May 2022

The yeast Ogataea polymorpha is an upcoming host for bio-manufacturing due to its unique physiological properties, including its broad substrate spectrum, and particularly its ability to utilize methanol as the sole carbon and energy source. However, metabolic engineering tools for O. polymorpha are still rare. In this study we characterized the influence of 6 promoters and 15 terminators on gene expression throughout batch cultivations with glucose, glycerol, and methanol as carbon sources as well as mixes of these carbon sources. For this characterization, a short half-life Green Fluorescent Protein (GFP) variant was chosen, which allows a precise temporal resolution of gene expression. Our promoter studies revealed how different promoters do not only influence the expression strength but also the timepoint of maximal expression. For example, the expression strength of the catalase promoter (pCAT) and the methanol oxidase promoter (pMOX) are comparable on methanol, but the maximum expression level of the pCAT is reached more than 24 h earlier. By varying the terminators, a 6-fold difference in gene expression was achieved with the MOX terminator boosting gene expression on all carbon sources by around 50% compared to the second-strongest terminator. It was shown that this exceptional increase in gene expression is achieved by the MOX terminator stabilizing the mRNA, which results in an increased transcript level in the cells. We further found that different pairing of promoters and terminators or the expression of a different gene (β-galactosidase gene) did not influence the performance of the genetic parts. Consequently, it is possible to mix and match promoters and terminators as independent elements to tune gene expression in O. polymorpha.
The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes
Authors: Hamasaki Eriko , Wakita Natsuki , Yasuoka Hiroki , Nagaoka Hikaru , Morita Masayuki , Takashima Eizo , Uchihashi Takayuki , Takeda Tetsuya , Abe Tadashi , Lee Ji-Won , Iimura Tadahiro , Saleem Moin A , Ogo Naohisa , Asai Akira , Narita Akihiro , Takei Kohji , Yamada Hiroshi
Published: May 2022

Dynamin is an endocytic protein that functions in vesicle formation by scission of invaginated membranes. Dynamin maintains the structure of foot processes in glomerular podocytes by directly and indirectly interacting with actin filaments. However, molecular mechanisms underlying dynamin-mediated actin regulation are largely unknown. Here, biochemical and cell biological experiments were conducted to uncover how dynamin modulates interactions between membranes and actin in human podocytes. Actin-bundling, membrane tubulating, and GTPase activities of dynamin were examined in vitro using recombinant dynamin 2-wild-type (WT) or dynamin 2-K562E, which is a mutant found in Charcot-Marie-Tooth patients. Dynamin 2-WT and dynamin 2-K562E led to the formation of prominent actin bundles with constant diameters. Whereas liposomes incubated with dynamin 2-WT resulted in tubule formation, dynamin 2-K562E reduced tubulation. Actin filaments and liposomes stimulated dynamin 2-WT GTPase activity by 6- and 20-fold, respectively. Actin-filaments, but not liposomes, stimulated dynamin 2-K562E GTPase activity by 4-fold. Self-assembly-dependent GTPase activity of dynamin 2-K562E was reduced to one-third compared to that of dynamin 2-WT. Incubation of liposomes and actin with dynamin 2-WT led to the formation of thick actin bundles, which often bound to liposomes. The interaction between lipid membranes and actin bundles by dynamin 2-K562E was lower than that by dynamin 2-WT. Dynamin 2-WT partially colocalized with stress fibers and actin bundles based on double immunofluorescence of human podocytes. Dynamin 2-K562E expression resulted in decreased stress fiber density and the formation of aberrant actin clusters. Dynamin 2-K562E colocalized with α-actinin-4 in aberrant actin clusters. Reformation of stress fibers after cytochalasin D-induced actin depolymerization and washout was less effective in dynamin 2-K562E-expressing cells than that in dynamin 2-WT. Bis-T-23, a dynamin self-assembly enhancer, was unable to rescue the decreased focal adhesion numbers and reduced stress fiber density induced by dynamin 2-K562E expression. These results suggest that the low affinity of the K562E mutant for lipid membranes, and atypical self-assembling properties, lead to actin disorganization in HPCs. Moreover, lipid-binding and self-assembly of dynamin 2 along actin filaments are required for podocyte morphology and functions. Finally, dynamin 2-mediated interactions between actin and membranes are critical for actin bundle formation in HPCs.
DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy
Authors: Man Xiaxia , Li Qi , Wang Baogang , Zhang He , Zhang Songling , Li Ziyi
Published: May 2022

Breast cancer has become a leading cause of cancer-related deaths in women worldwide. DNA methylation has been revealed to play an enormously important role in the development and progression of breast cancer. DNA methylation is regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT2, and DNMT3. DNMT3 family has three members: DNMT3A, DNMT3B, and DNMT3L. The roles and functions of DNMT1 in breast cancer have been well reviewed. In this article, the roles of DNMT3A and DNMT3B in breast tumorigenesis and development are reviewed. We also discuss the SNP and mutations of DNMT3A and DNMT3B in breast cancer. In addition, we summarize how DNMT3A and DNMT3B are regulated by non-coding RNAs and signaling pathways in breast cancer, and targeting the expression levels of DNMT3A and DNMT3B may be a promising therapeutic approach for breast cancer. This review will provide reference for further studies on the biological functions and molecular mechanisms of DNMT3A and DNMT3B in breast cancer.
DNA-PAINT Imaging Accelerated by Machine Learning
Authors: Zhu Min , Zhang Luhao , Jin Luhong , Chen Jincheng , Zhang Yongdeng , Xu Yingke
Published: May 2022

DNA point accumulation in nanoscale topography (DNA-PAINT) is an easy-to-implement approach for localization-based super-resolution imaging. Conventional DNA-PAINT imaging typically requires tens of thousands of frames of raw data to reconstruct one super-resolution image, which prevents its potential application for live imaging. Here, we introduce a new DNA-PAINT labeling method that allows for imaging of microtubules with both DNA-PAINT and widefield illumination. We develop a U-Net-based neural network, namely, U-PAINT to accelerate DNA-PAINT imaging from a widefield fluorescent image and a sparse single-molecule localization image. Compared with the conventional method, U-PAINT only requires one-tenth of the original raw data, which permits fast imaging and reconstruction of super-resolution microtubules and can be adopted to analyze other SMLM datasets. We anticipate that this machine learning method enables faster and even live-cell DNA-PAINT imaging in the future.
Anti-RAFLS Triterpenoids and Hepatoprotective Lignans From the Leaves of Tujia Ethnomedicine Kadsura heteroclita (Xuetong)
Authors: Wang Mengyun , Jiang Sai , Hussain Nusrat , Zafar Salman , Xie Qingling , Huang Feibing , Mao Linxi , Li Bin , Jian Yuqing , Wang Wei
Published: May 2022

A pair of 3,4-seco-cycloartane triterpenoid isomers with a rare peroxy bridge, namely, xuetonins A and B (1 and 2), four new lignans xuetonlignans A–D (3–6), a new sesquiterpene xuetonpene (7), and a new natural product xuetonin C (8), along with 43 known compounds, were obtained from the leaves of Tujia ethnomedicine, Kadsura heteroclita. Their structures and configurations were determined with the help of a combination of 1D- and 2D-NMR, HRESIMS spectra, electronic circular dichroism (ECD), and X-ray diffraction data. Compounds 2, 10, 13–15, and 17–19 showed moderate-to-potent activity against rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) with IC50 values of 19.81 ± 0.26, 12.73 ± 0.29, 5.70 ± 0.24, 9.25 ± 0.79, 5.66 ± 0.52, 11.91 ± 0.44, 13.22 ± 0.27, and 15.94 ± 0.36 μM, respectively. Furthermore, compounds 22, 25, and 31 exhibited significant hepatoprotective effects against N-acetyl-p-aminophenol (APAP)–induced toxicity in HepG2 cells at 10 μM, and the cell viability increased by 12.93, 25.23, and 13.91%, respectively, compared with that in the model group (cf. bicyclol, 12.60%).
Mechanism-Dependent Selectivity: Fluorocyclization of Unsaturated Carboxylic Acids or Alcohols by Hypervalent Iodine
Authors: Su Jiaqi , Shu Siwei , Li Yinwu , Chen Yong , Dong Jinxiang , Liu Yan , Fang Yanxiong , Ke Zhuofeng
Published: May 2022

To understand the unprecedented difference between 6-endo and 5-exo selectivity in hypervalent iodine (III) promoted fluorocyclization of unsaturated carboxylic acids or alcohols by difluoroiodotoluene, density functional theory (DFT) studies have been performed to systematically compare both the previous proposed “fluorination first and cyclization later” mechanism and the alternative “cyclization first and fluorination later” mechanism. Our results revealed that the selectivity is mechanism-dependent. The unsaturated alcohol prefers the fluorination first and the 6-endo-tet cyclization later pathway, leading to the experimentally observed 6-endo ether product. In contrast, the unsaturated carboxylic acid plausibly undergoes the 5-exo-trig cyclization first and the fluorination later to the experimentally observed 5-exo lactone product. The pKa property of the functional group of the substrate is found to play a key role in determining the reaction mechanism. The provided insights into the mechanism-dependent selectivity should help advance the development of fluorocyclization reactions with hypervalent iodine reagents.
Lysosomal Targeted Cyclometallic Iridium(Ⅲ) Salicylaldehyde-Coumarin Schiff Base Complexes and Anticancer Application
Authors: Xu Ruixi , Wu Yuting , Liu Zhe , Liu Jinfeng , Liu Xicheng
Published: May 2022

Natural coumarin derivatives and cyclometallic iridium (Ⅲ) (IrⅢ) complexes have attracted much attention in the field of anticancer. In this study, six coumarin-modified cyclometallic IrⅢ salicylaldehyde Schiff base complexes ([(ppy)2Ir(O^N)]/[(ppy-CHO)2Ir(O^N)]) were designed and synthesized. Compared with coumarin and IrⅢ complex monomers, target complexes exhibited favorable cytotoxic activity toward A549 and BEAS-2B cells. These complexes could induce extensive apoptosis of A549 cell (late apoptosis), which was represented by the disturbance of cell cycle (G1-phase) and the accumulation of intracellular reactive oxygen species, exhibiting an anticancer mechanism of oxidation. With the help of suitable fluorescence of these complexes, no conflict with the probes, confocal detection confirmed that complexes showed an energy-dependent cellular uptake mechanism and triggered lysosome-mediated apoptosis in A549 cell line. Above all, our findings reveal the design of a lysosomal targeting cyclometallic IrⅢ Schiff base complexes and provide a new idea for the design of integrated drugs for diagnosis and treatment.
The Influence of Police Reporting Styles on the Processing of Crime Related Information
Authors: Eerland Anita , van Charldorp Tessa
Published: May 2022

Police records drawn up during or after a suspect's police interrogation play a crucial role in judicial systems and should therefore be factual representations of what occurred in the spoken interrogation. Within the judicial domain, however, little is known about how style of reporting (i.e., the specific language used) affects the interpretation of these facts. Furthermore, the relationship between police record ‘quality’ and variations in judgment of guilt, credibility or reliability has not been studied to date. In three studies, we investigated the influence of three commonly used recording styles (i.e., monolog, recontextualized and question-answer style) on judgments of guilt, credibility, and reliability in fictitious criminal cases. We hypothesized that participants would (1) find records in the question-answer style more credible and reliable than those in the monolog or recontextualized style, and (2) consider the recontextualized style to be the least credible and reliable. Experiment 1 showed that the Q&A style was perceived as more reliable than the other two styles. Experiment 2, a replication in which we also tested new hypotheses based on explorative analyses of Experiment 1, showed no effects of reporting style. To investigate whether the discrepancy in results was due to different scenarios, a third experiment that made use of multiple scenarios was conducted. We found effects of reporting style on perceived accuracy, imageability, and understandability. In sum, this study showed that factors as subtle as reporting style might impact the processing of information in contexts where only factual information should be taken into account.
Prediction of Type-2 Diabetes Mellitus Disease Using Machine Learning Classifiers and Techniques
Authors: Ahamed B. Shamreen , Arya Meenakshi Sumeet , Nancy V Auxilia Osvin
Published: May 2022

The technological advancements in today's healthcare sector have given rise to many innovations for disease prediction. Diabetes mellitus is one of the diseases that has been growing rapidly among people of different age groups; there are various reasons and causes involved. All these reasons are considered as different attributes for this study. To predict type-2 diabetes mellitus disease, various machine learning algorithms can be used. The objective of using the algorithm is to construct a predictive model to critically predict whether a person is affected by diabetes. The classifiers taken are logistic regression, XGBoost, gradient boosting, decision trees, ExtraTrees, random forest, and light gradient boosting machine (LGBM). The dataset used is PIMA Indian Dataset sourced from UC Irvine Repository. The performance of these algorithms is compared in reference to the accuracy obtained. The results obtained from these classifiers show that the LGBM classifier has the highest accuracy of 95.20% in comparison with the other algorithms.
Deer Exclusion Regenerates Native Plant Functional Responses, but Not Species Richness in an Eastern Serpentine Savannah
Authors: Richins Allyson E. , Hulshof Catherine M.
Published: May 2022

Plants are particularly vulnerable to physical disturbance in low productivity areas, due to the high energetic cost of replacing lost tissue. In the eastern United States, serpentine savannahs are fragmented ecosystems with high concentrations of rare endemic plant species, low concentrations of soil nutrients, and severe deer overpopulation. This study assessed the recovery of flowering plants in a serpentine savannah when deer were excluded. Plant count, flower count, vegetative area, and plant height of 10 serpentine plant species were compared inside and outside of deer exclusion structures throughout an entire growing season. Throughout the growing season and across the plant community, deer exclusion consistently increased values for all plant response traits measured. Species that responded most strongly to deer exclusion included Arabis lyrata (Brassicaceae, the wide ranging lyre-leaf rockcress) and the serpentine near-endemic Symphyotrichum depauperatum (a serpentine aster known only in the eastern US). The slender knotweed, Polygonum tenue performed worse in excluded areas, which may indicate exclusion by more competitive species, or, alternatively, local scarcity. Overall, species richness did not increase in excluded plots, which may indicate that years of deer overbrowsing have depleted the local seed banks. While longer term studies might reveal different results, this study showed significant differences in vegetation response traits between excluded and unexcluded areas in just one year. We recommend that further restoration efforts should include reintroductions of locally extirpated species, in combination with deer exclusion to allow rare serpentine plant communities and their seedbanks to recover from intense overbrowsing pressure.
Alcohol Dehydrogenases as Catalysts in Organic Synthesis
Authors: de Miranda Amanda Silva , Milagre Cintia D. F. , Hollmann Frank
Published: May 2022

Alcohol dehydrogenases (ADHs) have become important catalysts for stereoselective oxidation and reduction reactions of alcohols, aldehydes and ketones. The aim of this contribution is to provide the reader with a timely update on the state-of-the-art of ADH-catalysis. Mechanistic basics are presented together with practical information about the use of ADHs. Current concepts of ADH engineering and ADH reactions are critically discussed. Finally, this contribution highlights some prominent examples and future-pointing concepts.
Fractal Geometry Illustrated Left Atrial Appendage Morphology That Predicted Thrombosis and Stroke in Patients With Atrial Fibrillation
Authors: Lei Chuxiang , Gao Qi , Wei Runjie , Li Qijie , Liu Xingli , Wu Lingmin , Yao Yan , Fan Hongguang , Zheng Zhe
Published: May 2022

Background

This study aims to correlate the morphological complexity of left atrial appendage (LAA) with thrombosis and stroke in patients with atrial fibrillation (AF).

Methods

The training cohort consisted of 46 patients with AF (age 55.8 ± 7.2 years, 73.9% men) who were referred for radiofrequency catheter ablation. An independent validation cohort consisting of 443 patients with AF was enrolled for further verification. All patients in the training cohort underwent both transesophageal echocardiography (TEE) and enhanced computed tomography (CT). Fractal dimension (FD) analysis was performed to evaluate the morphological complexity of LAAs quantitatively. Clinical and imaging manifestations, FD of LAAs, and diagnostic accuracy were investigated and compared between patients with AF in both training and validation cohorts.

Results

In the training cohort, LAAs (n = 22) with thrombi had significantly higher FD than those without thrombi (n = 24) h 0.44 ± 0.07 vs. 2.35 ± 0.11, p = 0.003). Receiver-operating characteristic (ROC) analysis suggested that the diagnostic accuracy of FD combined with a CHA2DS2-VaSc score was significantly higher than that of the CHA2DS2-VaSc score alone in low- to moderate-risk patients with AF (area under the curve 0.8479 vs. 0.6958, p = 0.009). The results were also validated in an independent external validation cohort and demonstrated that increased FD was associated with stroke. Hemodynamic analysis revealed that LAAs with thrombi and high FD were prone to blood stasis and lower blood flow rate.

Conclusion

LAA morphological complexity is closely associated with thrombosis and stroke in patients with paroxysmal AF. A new risk assessment system combining CHA2DS2-VaSc score and FD has a higher diagnostic accuracy in predicting LAA thrombosis.
Alcohol Abuse Associated With Increased Risk of Angiographic Vasospasm and Delayed Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage Requiring Mechanical Ventilation
Authors: Zhao Lei , Cheng Chao , Peng Liwei , Zuo Wei , Xiong Dong , Zhang Lei , Mao Zilong , Zhang Jin'an , Wu Xia , Jiang Xue , Wang Peng , Li Weixin
Published: May 2022

Objective

Although alcohol abuse has been indicated to cause cerebral aneurysm development and rupture, there is limited data on the impact of alcohol abuse on outcomes after an aneurysmal subarachnoid hemorrhage (aSAH). This study aims to investigate whether alcohol abuse increases the risk of angiographic vasospasm and delayed cerebral ischemia (DCI) in critically ill patients with aSAH.

Methods

We conducted a secondary analysis based on a retrospective study in a French university hospital intensive care unit (ICU). Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. Patients were segregated according to alcohol abuse (yes or no). Multivariable logistic regression analysis was used to identify the independent risk factors associated with angiographic vasospasm and DCI.

Results

The patient proportion of alcohol abuse was dramatically greater in males than that in females (p < 0.001). The Simplified Acute Physiology Score II (SAPSII) score on admission did not show a statistical difference. Neither did the World Federation of Neurosurgical Societies (WFNS) and Fisher scores. Patients with alcohol abuse were more likely to develop angiographic vasospasm (OR 3.65, 95% CI 1.17–11.39; p = 0.0260) and DCI (OR 3.53, 95% CI 1.13–10.97; p = 0.0294) as evidenced by multivariable logistic regression analysis.

Conclusions

In this study, patients with alcohol abuse are at higher odds of angiographic vasospasm and DCI, which are related to poor prognosis following aSAH. These findings are important for the prevention and clinical management of aSAH.
Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease
Authors: Montavon Brittany , Winter Linda E. , Gan Qi , Arasteh Amirhossein , Montaño Adriana M.
Published: May 2022

Cardiovascular disease (CVD) in Mucopolysaccharidosis Type IVA (Morquio A), signified by valvular disease and cardiac hypertrophy, is the second leading cause of death and remains untouched by current therapies. Enzyme replacement therapy (ERT) is the gold-standard treatment for MPS disorders including Morquio A. Early administration of ERT improves outcomes of patients from childhood to adulthood while posing new challenges including prognosis of CVD and ERT’s negligible effect on cardiovascular health. Thus, having accurate biomarkers for CVD could be critical. Here we show that cathepsin S (CTSS) and elastin (ELN) can be used as biomarkers of extracellular matrix remodeling in Morquio A disease. We found in a cohort of 54 treatment naïve Morquio A patients and 74 normal controls that CTSS shows promising attributes as a biomarker in young Morquio A children. On the other hand, ELN shows promising attributes as a biomarker in adolescent and adult Morquio A. Plasma/urine keratan sulfate (KS), and urinary glycosaminoglycan (GAG) levels were significantly higher in Morquio A patients (p < 0.001) which decreased with age of patients. CTSS levels did not correlate with patients’ phenotypic severity but differed significantly between patients (median range 5.45–8.52 ng/mL) and normal controls (median range 9.61–15.9 ng/mL; p < 0.001). We also studied α -2-macroglobulin (A2M), C-reactive protein (CRP), and circulating vascular cell adhesion molecule-1 (sVCAM-1) in a subset of samples to understand the relation between ECM biomarkers and the severity of CVD in Morquio A patients. Our experiments revealed that CRP and sVCAM-1 levels were lower in Morquio A patients compared to normal controls. We also observed a strong inverse correlation between urine/plasma KS and CRP (p = 0.013 and p = 0.022, respectively) in Morquio A patients as well as a moderate correlation between sVCAM-1 and CTSS in Morquio A patients at all ages (p = 0.03). As the first study to date investigating CTSS and ELN levels in Morquio A patients and in the normal population, our results establish a starting point for more elaborate studies in larger populations to understand how CTSS and ELN levels correlate with Morquio A severity.
DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
Authors: Fischer Matthew A. , Mahajan Aman , Cabaj Maximilian , Kimball Todd H. , Morselli Marco , Soehalim Elizabeth , Chapski Douglas J. , Montoya Dennis , Farrell Colin P. , Scovotti Jennifer , Bueno Claudia T. , Mimila Naomi A. , Shemin Richard J. , Elashoff David , Pellegrini Matteo , Monte Emma , Vondriska Thomas M.
Published: May 2022

Background

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF.

Methods

We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort.

Results

A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort.

Conclusions

We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.
Associations Between Adult Triceps Skinfold Thickness and All-Cause, Cardiovascular and Cerebrovascular Mortality in NHANES 1999–2010: A Retrospective National Study
Authors: Li Weiya , Yin Han , Chen Yilin , Liu Quanjun , Wang Yu , Qiu Di , Ma Huan , Geng Qingshan
Published: May 2022

Background:

The association between triceps skinfold (TSF) thickness and mortality in previous studies was controversial. This study aimed to explore how TSF thickness affects all-cause, cardiovascular, and cerebrovascular mortality among the United States (U.S.) general population.

Methods

Our research included 25,954 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Participants were categorized by the baseline TSF quartiles [quartile 1 (Q1): < 11.8, (Q2): 11.8–17.4, (Q3): 17.4–25, and (Q4): ≥25; unit: millimeter (mm)]. Cox regression models were used to assess the association of TSF with all-cause, cardiovascular, and cerebrovascular mortality. The association between mid-arm muscle circumference (MAMC) and mortality was also explored. Subgroup analyses were conducted to assess heterogeneity in different subgroups.

Results

The highest TSF group (Q4) had the lowest risk to experience all-cause (HR, 0.46; 95% CI, 0.38–0.59; P < 0.001) and cardiovascular mortality (HR, 0.35; 95% CI, 0.23–0.54; P < 0.001) than the lowest TSF group (Q1) after multivariate adjustment. However, there was no relationship between TSF quartiles and cerebrovascular mortality (HR, 0.98; 95%CI, 0.42–2.30; P = 0.97). The protective effects of TSF thickness on mortality still existed after adjusting for BMI and MAMC. For every 1 mm increase in TSF thickness, the risk of all-cause and cardiovascular death decreased by 4% (HR, 0.96; 95% CI, 0.95–0.97; P < 0.001) and 6% (HR, 0.94; 95% CI, 0.93–0.96; P < 0.001), respectively. In the stratified analysis, the relationships between TSF and mortality risk were generally similar across all subgroups.

Conclusions

Higher TSF thickness was associated with lower all-cause and cardiovascular mortality, independent of BMI and MAMC. Our study revealed that the TSF thickness may be a convenient and credible indicator to predict mortality, especially in those with severe cardiovascular diseases.
The Association Between the Frequency of Annual Health Checks Participation and the Control of Cardiovascular Risk Factors
Authors: Lei Li , Tang Yongzhen , Zhang Qiuxia , Xiao Min , Dai Lei , Lu Junyan , Lin Xinxin , Lu Xiangqi , Luo Wei , Pan Jiazhi , Xin Xiaoyu , Qiu Shifeng , Li Yun , An Shengli , Xiu Jiancheng
Published: May 2022

Background

General health checks can help in controlling cardiovascular risk factors. However, few studies have investigated whether regular participation in annual health checks could further improve the control of cardiovascular risk factors compared with intermittent participation. Therefore, our study aimed to explore the association between the frequency of annual health check participation and the control of cardiovascular risk factors.

Methods

Residents aged ≥ 65 years or having chronic diseases (hypertension or diabetes) from 37 communities of Guangzhou, Guangdong, who participated in the Basic Public Health Service project between January 2015 and December 2019, were enrolled and divided into 3 groups (“Sometimes,” “Usually,” and “Always”) according to their frequencies of annual health check participation. Multivariable linear regression models were performed to assess the association between the frequency of annual health check participation and the control of cardiovascular risk factors. A subgroup analysis stratified by gender was also conducted.

Results

In total, 9,102 participants were finally included. Significant differences were identified between groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and serum creatinine. After fully adjusting for confounding factors, residents who always participated in the annual health check tended to have lower SBP (β = −4.36, 95% CI: −5.46; −3.26, p < 0.001), fasting glucose (β = −0.27, 95% CI: −0.38; −0.15, p < 0.001), and total cholesterol (β = −0.19, 95% CI: −0.26; −0.13, p < 0.001), compared with those who attended sometimes. Furthermore, gender did not alter these associations.

Conclusion

A higher frequency of annual health check participation was associated with lower SBP, fasting glucose, and total cholesterol.
Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults
Authors: Freeberg Kaitlin A. , Craighead Daniel H. , Martens Christopher R. , You Zhiying , Chonchol Michel , Seals Douglas R.
Published: May 2022

Background

Aging is the primary risk factor for cardiovascular diseases, the leading cause of death worldwide. Age-related increases in systolic blood pressure (SBP) link advancing age to cardiovascular disease risk. A key mechanism mediating the increase in SBP with aging is stiffening of the large elastic arteries, which occurs due to increases in oxidative stress, inflammation, and vascular smooth muscle tone. Nicotinamide adenine dinucleotide (NAD+) is a key molecule in energy metabolism and cellular functioning which declines with advancing age and chronic disease. Dietary supplementation with NAD+ precursors, such as nicotinamide riboside, boosts NAD+ bioavailability and may improve cardiovascular health. Here, we present the protocol for a randomized, controlled trial investigating the efficacy of 3 months of oral supplementation with nicotinamide riboside for decreasing SBP and arterial stiffness in midlife and older adults with initial above-normal (120–159 mmHg) SBP (ClinicalTrials.gov Identifier: NCT03821623). The primary outcome is casual (resting) SBP and secondary outcomes include 24-h SBP and aortic stiffness. Other outcomes include assessment of safety; tolerability; adherence; diastolic BP; systemic NAD+ bioavailability; and circulating biomarkers of oxidative stress, inflammation, and sympathoadrenal activity.

Methods

A randomized, double-blind, placebo-controlled, single-site parallel-group design clinical trial will be conducted in 94 (47/group) midlife and older (age ≥ 50 years) adults with initial above-normal SBP. Participants will complete baseline testing and then will be randomized to either nicotinamide riboside (500 mg, 2×/day, NIAGEN®; ChromaDex Inc.) or placebo supplementation. Outcome measures will be assessed again after 3 months of treatment.

Discussion

This study is designed to establish the safety and efficacy of the NAD+ boosting compound, nicotinamide riboside, for reducing casual and 24-h SBP and aortic stiffness in midlife and older adults with above-normal SBP at baseline, a population at increased risk of cardiovascular diseases.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03821623].
Anemoside B4 Inhibits Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Hyperplasia
Authors: Shan Dan , Qu Ping , Zhong Chao , He Luling , Zhang Qingshan , Zhong Guoyue , Hu Wenhui , Feng Yulin , Yang Shilin , Yang Xiao-feng , Yu Jun
Published: May 2022

Vascular smooth muscle cell (VSMC) phenotypic transformation, proliferation, and migration play a pivotal role in developing neointimal hyperplasia after vascular injury, including percutaneous transluminal angioplasty and other cardiovascular interventions. Anemoside B4 (B4) is a unique saponin identified from the Pulsatilla chinensis (Bge.) Regel, which has known anti-inflammatory activities. However, its role in modulating VSMC functions and neointima formation has not been evaluated. Herein, we demonstrate that B4 administration had a potent therapeutic effect in reducing neointima formation in a preclinical mouse femoral artery endothelium denudation model. Bromodeoxyuridine incorporation study showed that B4 attenuated neointimal VSMC proliferationin vivo. Consistent with thein vivofindings, B4 attenuated PDGF-BB-induced mouse VSMC proliferation and migrationin vitro. Moreover, quantitative RT-PCR and Western blot analysis demonstrated that B4 suppressed PDGF-BB-induced reduction of SM22α, SMA, and Calponin, suggesting that B4 inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Mechanistically, our data showed B4 dose-dependently inhibited the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase MAPK signaling pathways. Subsequently, we determined that B4 attenuated VSMC proliferation and migration in a p38 MAPK and AKT dependent manner using pharmacological inhibitors. Taken together, this study identified, for the first time, Anemoside B4 as a potential therapeutic agent in regulating VSMC plasticity and combating restenosis after the vascular intervention.
Assessment of Landslide Susceptibility of the Wiśnickie Foothills Mts. (The Flysch Carpathians, Poland) Using Selected Machine Learning Algorithms
Authors: Zydroń Tymoteusz , Demczuk Piotr , Gruchot Andrzej
Published: May 2022

Landslides are well-known phenomena that cause significant changes to the relief of an area’s terrain, often causing damage to technical infrastructure and loss of life. One of the possible means of reducing the negative impact of landslides on people’s lives or property is to recognize areas that are prone to their occurrence. The most common approach to this problem is preparing landslide susceptibility maps. These can factor in the actual location of landslides or the causal relationship between landslides and selected environmental factors. Creating a classification of landslide-prone areas is a challenging task when landslide density is not high and the area of analysis is large. We prepared shallow 10 m × 10 m resolution landslide susceptibility maps of the Wiśnickie Foothills (Western Carpathians, Poland) using eleven different machine learning algorithms derived from the Python libraries Scikit-learn and Imbalanced-Learn. The analyzed area is characterized by a mean density of 3.4 surficial landslides (composed of soils and rocks) per km2. We also compared different approaches to imbalanced sets of data: Logistic Regression, Naive Bayes, Random Forest, AdaBoost, Bagging, ExtraTrees (Extremely Randomized Trees), Easy Ensemble, Balanced Bagging, Balanced Random Forest, RUSBoost and a hybrid model combining Random Under Sampler and Multi-layer Perceptron algorithms. The environmental factors (slope inclination and aspect, distance from rivers, lithology, soil type and permeability, groundwater table depth, profile and plan curvature, mean annual rainfall) were categorized and divided into training (70%) and testing (30%) sets. Accuracy, recall, G-mean and area under receiver operating curve (AUC) were used to validate the quality of the models. The results confirmed that algorithms based on decision tree classifiers are suitable for preparing landslide susceptibility maps. We also found that methods that generate random undersampling subsets (Easy Ensemble, Balanced Bagging, RUSBoost) and ensemble methods (Bagging, AdaBoost, Extra-Trees) both yield very similar test results to those that use full sets of data for training. Relatively high-quality results can also be obtained by integrating the Random Under Sampler algorithm with the Multi-layer Perceptron algorithm.
Sedimentary Dynamics in the Distal Margin Around Isolated Carbonate Platforms of the Northern South China Sea
Authors: Chen Junjin , Wu Shiguo , Liu Shiqiao , Chen Wanli , Qin Yongpeng , Wan Xiaoming
Published: May 2022

The South China Sea (SCS) serves as an excellent case for studying “source-to-sink” sedimentary dynamics among the global marginal seas. Analysis of the grain size distribution enables reconstruction of the sediment transport processes and dynamic mechanisms. In this study, based on 232 surface sediment samples obtained from the distal margin of the northern SCS, grain size trend analysis (GSTA) and end-member analysis (EMA) were first applied to the deep-sea environment to reveal the sedimentary dynamics around isolated carbonate platforms. The Zhongsha Atoll and Xisha Archipelagos were the two main sources of gravity flows in the study area. The GSTA results indicate the dominant transport trends that sediments initially originated from the Zhongsha Atoll and Xisha Archipelagos, dispersed in surrounding areas, and eventually formed a deposition center in the Zhongsha Trough. Furthermore, the sediment transport trends in the northern, eastern, and southern boundaries of the study area bounded by the oceanic basin were driven by deep circulation with seasonal variations. The grain size distributions were unmixed into five end-members, with dominant modes of 0.62, 1.89, 3.31, 7.14, and 10.17 Ф, corresponding to coarse sand, medium sand, fine sand, fine silt, and clay, respectively. Gravity flows and deep circulation have a significant impact on the distribution of end-members in the study area. The contents of EM1, EM2, and EM3 decreased while EM4 and EM5 contents increased outward from the Zhongsha Atoll to deep-sea areas. Sediments with coarse grains are primarily retained in the Zhongsha Atoll, and sediments with fine grains can be transported by gravity flows from platforms to deep-sea areas and removed by deep currents. The sediment transport trends were consistent with the results of sediment sources, seafloor topography, and current observations. The results show that GSTA is applicable in deep-sea environments and its combination with EMA helps to better understand sedimentary dynamics.