bluuebunny/crossref_metadata_2025 huggingface dataset:
Penerapan E-voting dalam Pemilihan Wali Nagari di Kamang Hilia Kecamatan Kamang Magek Kabupaten Agam Tahun 2017
Authors: Anggara Fery , Asril Asrinaldi , Putera Roni Ekha
Published: October 2021

Penelitian ini bertujuan untuk menganalisis Penerapan e-voting dalam Pemilihan wali nagari di Nagari Kamang Hilia Kecamatan Kamang Magek Kabupaten Agam. Penelitian ini dilatarbelakangi oleh adanya Pemilihan wali nagari yang menggunakan perangkat elektronik (e-voting) di Kabupaten Agam. Pemerintah Kabupaten Agam pada tahun 2017 melaksanakan Pemilihan wali nagari berbasis elektronik disebut dengan e-voting. Pemilihan wali nagari ini dilaksanakan di 28 nagari dimana Nagari Kamang Hilia menjadi nagari terbaik dalam pelaksanaannya. Dengan tingkat partisipasi bukan yang tertinggi. Sehingga peneliti tertarik untuk melihat bagaimana penerapan e-voting pada Pemilihan wali nagari Kamang Hilia. Metode yang digunakan dalam penelitian ini adalah metode penelitian kualitatif dengan jenis dan tipe studi kasus. Teknik pengumpulan data menggunakan wawancara dan dokumentasi. Menguji keabsahan data yang di dapat di lapangan menggunakan teknik triangulasi sumber. Pemilihan informan dilakukan dengan teknik purposive sampling. Penelitian ini menggunakan Konsep e-voting Crannor dan Cytron yang menggunakan empat desain utama e-voting yaitu: Accuracy, Privacy, Invulnerability, Verifiability dan tiga desain tambahan yaitu: Convenience, Flexibility, Mobility. Hasil dari penelitian ini menjelaskan dan menggambarkan bagaimana penerapan e-voting dalam Pilwana di Nagari Kamang Hilia. Adapun penerapan e-voting dalam Pilwana Nagari Kamang Hiilia tahun 2017 sudah dilaksanakan secara maksimal, meskipun ada beberapa kendala. Seperti sudah terpenuhinya indikator Accuracy, Privacy, Invulnerability dan Verifiability akan tetapi pada indikator Convenience, Flexibility masih belum terlaksana dengan baik dan pada indikator Moblity tidak terpenuhi karena metode yang dipakai tidak bersifat jarak jauh atau tidak menggunakan internet.
ИЗМЕНЕНИЯ ЭТНИЧЕСКОГО СОСТАВА НАСЕЛЕНИЯ МОСКВЫ ВО ВРЕМЯ ПЕРВОЙ МИРОВОЙ ВОЙНЫ
Authors: Григорян Г.Ш.
Published: October 2021

В годы Первой мировой войны происходили массовые миграции беженцев из прифронтовых районов вглубь России, что оказало существенное влияние на изменение этнического состава Москвы. В городе резко возросла доля этнических групп, ранее преобладавших в западных губерниях империи, это было нехарактерно для предвоенного периода. Однако недостаток сведений в изданной статистике усложняет для исследователей анализ влияния мигрантов военного времени на долю таких наиболее многочисленных этнических групп Москвы как: русские, евреи, немцы, поляки, литовцы, латыши, эстонцы, белорусы, украинцы, татары, армяне. Также определенную сложность представляет недоучет всех военных мигрантов, так как значительная их часть не регистрировалась в качестве беженцев, не попадая в статистику. Ввод в научный оборот ведомостей о числе жителей Москвы по вероисповеданиям за 1908–1916 гг., позволяет частично восполнить такой пробел и оценить динамику этнического состава населения города. Кроме того, сделана попытка выяснить общую численность всех военных мигрантов, находившихся в Москве перед революцией 1917 г., а также выделить беженцев-белорусов из общей численности православных и католиков. Предложенный метод сопоставления конфессиональной и этнической принадлежности не дает точного совпадения, однако с учетом привлечения дополнительных источников, позволяет выявить тенденции в изменениях этнического состава населения города, а также проанализировать факторы, влиявшие на динамику численности отдельных групп этнических меньшинств.
During the First World War, there were massive migrations of refugees from the front-line areas deep into Russia, which significantly affected the ethnic structure of the Moscow population. In the city, the share of ethnic groups that predominated in the empire’s western provinces increased sharply compared with the pre-war period. However, the lack of information in the published statistics makes it difficult for researchers to analyze how wartime migrants influenced the share of numerous ethnic groups in Moscow as Russians, Jews, Germans, Poles, Lithuanians, Latvians, Estonians, Belarusians, Ukrainians, Tatars, and Armenians. The author analyzed statements of the Moscow residents by religion for 1908–1916, which allowed him to partially fill this knowledge gap and assess the dynamics of the ethnic structure of the city. The proposed method of equating confession with ethnicity does not give an exact match. However, along with additional sources, it allows us to identify trends in the ethnic structure of the city and analyze the factors that influenced the size of certain ethnic minorities.
miR-181a-2-3p Stimulates Gastric Cancer Progression via Targeting MYLK
Authors: Li Jianjie , Xu Xiaoyue , Liu Chunhui , Xi Xiaoxue , Wang Yang , Wu Xiaotang , Li Hua
Published: October 2021

Background: The abnormal expression of miRNAs facilitates tumorigenesis and development. miR-181a-2-3p is up-regulated in various cancers, yet its mechanism in gastric cancer (GC) remains elusive.

Objective: To understand mechanism of miR-181a-2-3p stimulating GC cell progression via targeting Myosin Light Chain Kinase (MYLK) expression.

Methods: Downstream genes of miRNA of interest were predicted in TargetScan and miRTarBase. qRT-PCR and western blot were applied to assess miR-181a-2-3p and MYLK expression in GC cells and normal cells. Dual-luciferase and RIP assays were completed to assess binding of miR-181a-2-3p and MYLK. Cell Counting Kit-8 (CCK-8) assay was conducted for detecting viability of AGS and SNU-1 cells, while Transwell tested migratory and invasive abilities of cells. Nude mouse transplantation tumor experiment was performed to assay tumor growth in vivo.

Results: miR-181a-2-3p was notably increased in human GC cell lines, while MYLK was remarkably down-regulated. RIP and dual-luciferase assay disclosed that miR-181a-2-3p targeted MYLK and repressed MYLK. Forced miR-181a-2-3p expression fostered GC cell proliferation, invasion, migration, and fostered tumor growth in vivo. Promoting effect of miR-181a-2-3p on GC cells was reversed when miR-181a-2-3p and MYLK were simultaneously overexpressed.

Conclusion: miR-181a-2-3p facilitated GC cell progression by targeting MYLK, and it may be a pivotal prognostic biomarker in investigating molecular mechanism of GC.
Ultrasound-Induced Amino Acid-Based Hydrogels With Superior Mechanical Strength for Controllable Long-Term Release of Anti-Cercariae Drug
Authors: Ling Liying , Zhu Lei , Li Yibao , Liu Chunhua , Cheng Linxiu
Published: October 2021

Stimulus-responsive hydrogels are significantly programmable materials that show potential applications in the field of biomedicine and the environment. Ultrasound as a stimulus can induce the formation of hydrogels, which exhibit the superior performance of different structures. In this study, we reported an ultrasound-induced supramolecular hydrogel based on aspartic acid derivative N,N′-diaspartate-3,4,9,10-perylene tetracarboxylic acid imide, showing superior performance in drug release. The results show that the driving force of this ultrasonic induced hydrogel could be attributed to hydrogen bonding and π-π interaction. The rheological and cytotoxicity test illustrate excellent mechanical properties and biocompatibility of the hydrogel. The anti-Schistosoma japonicum cercariae (CC) drug release results show large drug loadings (500 mg/ml) and long-term release (15 days) of this hydrogel. This study demonstrates that this hydrogel may serve as a slow-release platform for anti-CC.
Subject-Specific Head Model Generation by Mesh Morphing: A Personalization Framework and Its Applications
Authors: Li Xiaogai
Published: October 2021

Finite element (FE) head models have become powerful tools in many fields within neuroscience, especially for studying the biomechanics of traumatic brain injury (TBI). Subject-specific head models accounting for geometric variations among subjects are needed for more reliable predictions. However, the generation of such models suitable for studying TBIs remains a significant challenge and has been a bottleneck hindering personalized simulations. This study presents a personalization framework for generating subject-specific models across the lifespan and for pathological brains with significant anatomical changes by morphing a baseline model. The framework consists of hierarchical multiple feature and multimodality imaging registrations, mesh morphing, and mesh grouping, which is shown to be efficient with a heterogeneous dataset including a newborn, 1-year-old (1Y), 2Y, adult, 92Y, and a hydrocephalus brain. The generated models of the six subjects show competitive personalization accuracy, demonstrating the capacity of the framework for generating subject-specific models with significant anatomical differences. The family of the generated head models allows studying age-dependent and groupwise brain injury mechanisms. The framework for efficient generation of subject-specific FE head models helps to facilitate personalized simulations in many fields of neuroscience.
Biomechanical Evaluation of the Effect of Minimally Invasive Spine Surgery Compared with Traditional Approaches in Lifting Tasks
Authors: Rasmussen John , Iversen Kristoffer , Engelund Bjørn Keller , Rasmussen Sten
Published: October 2021

Fusion of spinal vertebrae can be accomplished by different surgical approaches. We investigated Traditional Open Spine Surgery (TOSS) versus Minimally Invasive Spine Surgery (MISS). While TOSS sacrifices spine muscles originating or inserting on the affected vertebrae, MISS seeks to minimize the approach-related morbidity and preserve the tendon attachments of the muscles in the area. We captured 3-D motions of the full body of one healthy subject performing a variety of 10 kg box lifting operations representing activities-of-daily-living that are likely to challenge the spine biomechanically. The motion data were transferred to a full-body biomechanical model with a detailed representation of the biomechanics of the spine, and simulations of the internal spine loads and muscle forces were performed under a baseline configuration and muscle configurations typical for TOSS respectively MISS for the cases of L3/L4, L4/L5, L5/S1, L4/S1 and L3/L5 fusions. The computational model was then used to investigate the biomechanical differences between surgeries. The simulations revealed that joint reaction forces are more affected by both surgical approaches for lateral lifting motions than for sagittal plane motions, and there are indications that individuals with fused joints, regardless of the approach, should be particularly careful with asymmetrical lifts. The MISS and TOSS approaches shift the average loads of different muscle groups in different ways. TOSS generally leads to higher post-operative muscle loads than MISS in the investigated cases, but the differences are smaller than could be expected, given the differences of surgical technique.
Magnetic Nanoparticles and Magnetic Field Exposure Enhances Chondrogenesis of Human Adipose Derived Mesenchymal Stem Cells But Not of Wharton Jelly Mesenchymal Stem Cells
Authors: Labusca Luminita , Herea Dumitru-Daniel , Emanuela Minuti Anca , Stavila Cristina , Danceanu Camelia , Plamadeala Petru , Chiriac Horia , Lupu Nicoleta
Published: October 2021

Purpose: Iron oxide based magnetic nanoparticles (MNP) are versatile tools in biology and medicine. Adipose derived mesenchymal stem cells (ADSC) and Wharton Jelly mesenchymal stem cells (WJMSC) are currently tested in different strategies for regenerative regenerative medicine (RM) purposes. Their superiority compared to other mesenchymal stem cell consists in larger availability, and superior proliferative and differentiation potential. Magnetic field (MF) exposure of MNP-loaded ADSC has been proposed as a method to deliver mechanical stimulation for increasing conversion to musculoskeletal lineages. In this study, we investigated comparatively chondrogenic conversion of ADSC-MNP and WJMSC with or without MF exposure in order to identify the most appropriate cell source and differentiation protocol for future cartilage engineering strategies.

Methods: Human primary ADSC and WJMSC from various donors were loaded with proprietary uncoated MNP. The in vitro effect on proliferation and cellular senescence (beta galactosidase assay) in long term culture was assessed. In vitro chondrogenic differentiation in pellet culture system, with or without MF exposure, was assessed using pellet histology (Safranin O staining) as well as quantitative evaluation of glycosaminoglycan (GAG) deposition per cell.

Results: ADSC-MNP complexes displayed superior proliferative capability and decreased senescence after long term (28 days) culture in vitro compared to non-loaded ADSC and to WJMSC-MNP. Significant increase in chondrogenesis conversion in terms of GAG/cell ratio could be observed in ADSC-MNP. MF exposure increased glycosaminoglycan deposition in MNP-loaded ADSC, but not in WJMSC.

Conclusion: ADSC-MNP display decreased cellular senescence and superior chondrogenic capability in vitro compared to non-loaded cells as well as to WJMSC-MNP. MF exposure further increases ADSC-MNP chondrogenesis in ADSC, but not in WJMSC. Loading ADSC with MNP can derive a successful procedure for obtaining improved chondrogenesis in ADSC. Further in vivo studies are needed to confirm the utility of ADSC-MNP complexes for cartilage engineering.
Single-Cell Genomics: Catalyst for Cell Fate Engineering
Authors: Li Boxun , Hon Gary C.
Published: October 2021

As we near a complete catalog of mammalian cell types, the capability to engineer specific cell types on demand would transform biomedical research and regenerative medicine. However, the current pace of discovering new cell types far outstrips our ability to engineer them. One attractive strategy for cellular engineering is direct reprogramming, where induction of specific transcription factor (TF) cocktails orchestrates cell state transitions. Here, we review the foundational studies of TF-mediated reprogramming in the context of a general framework for cell fate engineering, which consists of: discovering new reprogramming cocktails, assessing engineered cells, and revealing molecular mechanisms. Traditional bulk reprogramming methods established a strong foundation for TF-mediated reprogramming, but were limited by their small scale and difficulty resolving cellular heterogeneity. Recently, single-cell technologies have overcome these challenges to rapidly accelerate progress in cell fate engineering. In the next decade, we anticipate that these tools will enable unprecedented control of cell state.
Assessing the Biodegradation of Vulcanised Rubber Particles by Fungi Using Genetic, Molecular and Surface Analysis
Authors: Andler R. , D’Afonseca V. , Pino J. , Valdés C. , Salazar-Viedma M.
Published: October 2021

Millions of tonnes of tyre waste are discarded annually and are considered one of the most difficult solid wastes to recycle. A sustainable alternative for the treatment of vulcanised rubber is the use of microorganisms that can biotransform polymers and aromatic compounds and then assimilate and mineralise some of the degradation products. However, vulcanised rubber materials present great resistance to biodegradation due to the presence of highly hydrophobic cross-linked structures that are provided by the additives they contain and the vulcanisation process itself. In this work, the biodegradation capabilities of 10 fungal strains cultivated in PDA and EM solid medium were studied over a period of 4 weeks. The growth of the strains, the mass loss of the vulcanised rubber particles and the surface structure were analysed after the incubation period. With the white rot fungi Trametes versicolor and Pleurotus ostreatus, biodegradation percentages of 7.5 and 6.1%, respectively, were achieved. The FTIR and SEM-EDS analyses confirmed a modification of the abundance of functional groups and elements arranged on the rubber surface, such as C, O, S, Si, and Zn, due to the biological treatment employed. The availability of genomic sequences of P. ostreatus and T. versicolor in public repositories allowed the analysis of the genetic content, genomic characteristics and specific components of both fungal species, determining some similarities between both species and their relationship with rubber biodegradation. Both fungi presented a higher number of sequences for laccases and manganese peroxidases, two extracellular enzymes responsible for many of the oxidative reactions reported in the literature. This was confirmed by measuring the laccase and peroxidase activity in cultures of T. versicolor and P. ostreatus with rubber particles, reaching between 2.8 and 3.3-times higher enzyme activity than in the absence of rubber. The integrative analysis of the results, supported by genetic and bioinformatics tools, allowed a deeper analysis of the biodegradation processes of vulcanised rubber. It is expected that this type of analysis can be used to find more efficient biotechnological solutions in the future.
Hox Proteins in the Regulation of Muscle Development
Authors: Poliacikova Gabriela , Maurel-Zaffran Corinne , Graba Yacine , Saurin Andrew J.
Published: October 2021

Hox genes encode evolutionary conserved transcription factors that specify the anterior–posterior axis in all bilaterians. Being well known for their role in patterning ectoderm-derivatives, such as CNS and spinal cord, Hox protein function is also crucial in mesodermal patterning. While well described in the case of the vertebrate skeleton, much less is known about Hox functions in the development of different muscle types. In contrast to vertebrates however, studies in the fruit fly, Drosophila melanogaster, have provided precious insights into the requirement of Hox at multiple stages of the myogenic process. Here, we provide a comprehensive overview of Hox protein function in Drosophila and vertebrate muscle development, with a focus on the molecular mechanisms underlying target gene regulation in this process. Emphasizing a tight ectoderm/mesoderm cross talk for proper locomotion, we discuss shared principles between CNS and muscle lineage specification and the emerging role of Hox in neuromuscular circuit establishment.
Immune Signatures Combined With BRCA1-Associated Protein 1 Mutations Predict Prognosis and Immunotherapy Efficacy in Clear Cell Renal Cell Carcinoma
Authors: Gao Ze , Chen Junxiu , Tao Yiran , Wang Qiong , Peng Shirong , Yu Shunli , Zeng Jianwen , Li Kaiwen , Xie Zhongqiu , Huang Hai
Published: October 2021

Immunotherapy is gradually emerging in the field of tumor treatment. However, because of the complexity of the tumor microenvironment (TME), some patients cannot benefit from immunotherapy. Therefore, we comprehensively analyzed the TME and gene mutations of ccRCC to identify a comprehensive index that could more accurately guide the immunotherapy of patients with ccRCC. We divided ccRCC patients into two groups based on immune infiltration activity. Next, we investigated the differentially expressed genes (DEGs) and constructed a prognostic immune score using univariate Cox regression analysis, unsupervised cluster analysis, and principal component analysis (PCA) and validated its predictive power in both internal and total sets. Subsequently, the gene mutations in the groups were investigated, and patients suitable for immunotherapy were selected in combination with the immune score. The prognosis of the immune score-low group was significantly worse than that of the immune score-high group. The patients with BRCA1-associated protein 1 (BAP1) mutation had a poor prognosis. Thus, this study indicated that establishing an immune score model combined with BAP1 mutation can better predict the prognosis of patients, screen suitable ccRCC patients for immunotherapy, and select more appropriate drug combinations.
Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and Metabolic Plasticity of Cancer Cells During Metastasis
Authors: Urra Félix A. , Fuentes-Retamal Sebastián , Palominos Charlotte , Rodríguez-Lucart Yarcely A. , López-Torres Camila , Araya-Maturana Ramiro
Published: October 2021

The role of metabolism in tumor growth and chemoresistance has received considerable attention, however, the contribution of mitochondrial bioenergetics in migration, invasion, and metastasis is recently being understood. Migrating cancer cells adapt their energy needs to fluctuating changes in the microenvironment, exhibiting high metabolic plasticity. This occurs due to dynamic changes in the contributions of metabolic pathways to promote localized ATP production in lamellipodia and control signaling mediated by mitochondrial reactive oxygen species. Recent evidence has shown that metabolic shifts toward a mitochondrial metabolism based on the reductive carboxylation, glutaminolysis, and phosphocreatine-creatine kinase pathways promote resistance to anoikis, migration, and invasion in cancer cells. The PGC1a-driven metabolic adaptations with increased electron transport chain activity and superoxide levels are essential for metastasis in several cancer models. Notably, these metabolic changes can be determined by the composition and density of the extracellular matrix (ECM). ECM stiffness, integrins, and small Rho GTPases promote mitochondrial fragmentation, mitochondrial localization in focal adhesion complexes, and metabolic plasticity, supporting enhanced migration and metastasis. Here, we discuss the role of ECM in regulating mitochondrial metabolism during migration and metastasis, highlighting the therapeutic potential of compounds affecting mitochondrial function and selectively block cancer cell migration.
Identification of Myoferlin, a Potential Serodiagnostic Antigen of Clonorchiasis, via Immunoproteomic Analysis of Sera From Different Infection Periods and Excretory-Secretory Products of Clonorchis sinensis
Authors: Ma Xiao-Xiao , Qiu Yang-Yuan , Chang Zhi-Guang , Gao Jun-Feng , Jiang Rui-Ruo , Li Chun-Lin , Wang Chun-Ren , Chang Qiao-Cheng
Published: October 2021

Clonorchiasis, which is caused by Clonorchis sinensis, is an important foodborne disease worldwide. The excretory-secretory products (ESPs) of C. sinensis play important roles in host-parasite interactions by acting as causative agents. In the present study, the ESPs and sera positive for C. sinensis were collected to identify proteins specific to the sera of C. sinensis (i.e., proteins that do not cross-react with Fasciola hepatica and Schistosoma japonicum) at different infection periods. Briefly, white Japanese rabbits were artificially infected with C. sinensis, and their sera were collected at 7 days post-infection (dpi), 14 dpi, 35 dpi, and 77 dpi. To identify the specific proteins in C. sinensis, a co-immunoprecipitation (Co-IP) assay was conducted using shotgun liquid chromatography tandem-mass spectrometry (LC-MS/MS) to pull down the sera roots of C. sinensis, F. hepatica, and S. japonicum. For the annotated proteins, 32, 18, 39, and 35 proteins specific to C. sinensis were pulled down by the infected sera at 7, 14, 35, and 77 dpi, respectively. Three proteins, Dynein light chain-1, Dynein light chain-2 and Myoferlin were detected in all infection periods. Of these proteins, myoferlin is known to be overexpressed in several human cancers and could be a promising biomarker and therapeutic target for cancer cases. Accordingly, this protein was selected for further studies. To achieve a better expression, myoferlin was truncated into two parts, Myof1 and Myof2 (1,500 bp and 810 bp), based on the antigenic epitopes provided by bioinformatics. The estimated molecular weight of the recombinant proteins was 57.3 ku (Myof1) and 31.3 ku (Myof2). Further, both Myof1 and Myof2 could be probed by the sera from rabbits infected with C. sinensis. No cross-reaction occurred with the positive sera of S. japonica, F. hepatica, and negative controls. Such findings indicate that myoferlin may be an important diagnostic antigen present in the ESPs. Overall, the present study provides new insights into proteomic changes between ESPs and hosts in different infection periods by LC-MS/MS. Moreover, myoferlin, as a biomarker, may be used to develop an objective method for future diagnosis of clonorchiasis.
Facts and Gaps in Exercise Influence on Arrhythmogenic Cardiomyopathy: New Insights From a Meta-Analysis Approach
Authors: Martínez-Solé Julia , Sabater-Molina María , Braza-Boïls Aitana , Santos-Mateo Juan J. , Molina Pilar , Martínez-Dolz Luis , Gimeno Juan R. , Zorio Esther
Published: October 2021

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac condition characterized by fibrofatty myocardial replacement, either at the right ventricle, at the left ventricle, or with biventricular involvement. Ventricular arrhythmias and heart failure represent its main clinical features. Exercise benefits on mental and physical health are worldwide recognized. However, patients with ACM appear to be an exception. A thorough review of the literature was performed in PubMed searching for original papers with the terms “ARVC AND sports/exercise” and “sudden cardiac death AND sports/exercise.” Additional papers were then identified through other sources and incorporated to the list. All of them had to be based on animal models or clinical series. Information was structured in a regular format, although some data were not available in some papers. A total of 34 papers were selected and processed regarding sports-related sudden cardiac death, pre-clinical models of ACM and sport, and clinical series of ACM patients engaged in sports activities. Eligible papers were identified to obtain pooled data in order to build representative figures showing the global incidence of the most important causes of sudden cardiac death in sports and the global estimates of life-threatening arrhythmic events in ACM patients engaged in sports. Tables and figures illustrate their major characteristics. The scarce points of controversy were discussed in the text. Fundamental concepts were summarized in three main issues: sports may accelerate ACM phenotype with either structural and/or arrhythmic features, restriction may soften the progression, and these rules also apply to phenotype-negative mutation carriers. Additionally, remaining gaps in the current knowledge were also highlighted, namely, the applicability of those fundamental concepts to non-classical ACM phenotypes since left dominant ACM or non-plakophillin-2 genotypes were absent or very poorly represented in the available studies. Hopefully, future research endeavors will provide solid evidence about the safest exercise dose for each patient from a personalized medicine perspective, taking into account a big batch of genetic, epigenetic, and epidemiological variables, for instance, in order to assist clinicians to provide a final tailored recommendation.
Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation
Authors: Corporan Daniella , Segura Ana , Padala Muralidhar
Published: October 2021

Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte.

Methods: Twenty-four male Sprague-Dawley rats (350–400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes.

Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae.

Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.
Cardiac Function After Cardiotoxic Treatments for Childhood Cancer—Left Ventricular Longitudinal Strain in Screening
Authors: Niemelä Jussi , Ylänen Kaisa , Suominen Anu , Pushparajah Kuberan , Mathur Sujeev , Sarkola Taisto , Jahnukainen Kirsi , Eerola Anneli , Poutanen Tuija , Vettenranta Kim , Ojala Tiina
Published: October 2021

Background: The majority of childhood cancer survivors (CCSs) have been exposed to cardiotoxic treatments and often present with modifiable cardiovascular risk factors. Our aim was to evaluate the value of left ventricular (LV) longitudinal strain for increasing the sensitivity of cardiac dysfunction detection among CCSs.

Methods: We combined two national cohorts: neuroblastoma and other childhood cancer survivors treated with anthracyclines. The final data consisted of 90 long-term CCSs exposed to anthracyclines and/or high-dose chemotherapy with autologous stem cell rescue and followed up for > 5 years and their controls (n = 86). LV longitudinal strain was assessed with speckle tracking (Qlab) and LV ejection fraction (EF) by three-dimensional echocardiography (3DE).

Results: Of the CCSs, 11% (10/90) had abnormal LV longitudinal strain (i.e., < -17.5%); of those, 70% (7/10) had normal 3DE LV EF. Multivariable linear model analysis demonstrated that follow-up time (p = 0.027), sex (p = 0.020), and BMI (p = 0.002) were significantly associated with LV longitudinal strain. Conversely, cardiac risk group, hypertension, age, cumulative anthracycline dose or exposure to chest radiation were not.

Conclusion: LV longitudinal strain is a more sensitive method than LV EF for the detection of cardiac dysfunction among CCSs. Therefore, LV longitudinal strain should be added to the screening panel, especially for those with modifiable cardiovascular risk factors.
Predicting All-Cause Mortality Risk in Atrial Fibrillation Patients: A Novel LASSO-Cox Model Generated From a Prospective Dataset
Authors: Chen Yu , Wu Shiwan , Ye Jianfeng , Wu Muli , Xiao Zhongbo , Ni Xiaobin , Wang Bin , Chen Chang , Chen Yequn , Tan Xuerui , Liu Ruisheng
Published: October 2021

Background: Although mortality remains high in patients with atrial fibrillation (AF), there have been limited studies exploring machine learning (ML) models on mortality risk prediction in patients with AF.

Objectives: This study sought to develop an ML model that captures important variables in order to predict all-cause mortality in AF patients.

Methods: In this single center prospective study, an ML-based mortality prediction model was developed and validated using a dataset of 2,012 patients who experienced AF from November 2018 to February 2020 at the First Affiliated Hospital of Shantou University Medical College. The dataset was randomly divided into a training set (70%, n = 1,223) and a validation set (30%, n = 552). A total of 122 features were collected for variable selection. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms were used for variable selection. Ten ML models were developed using variables selected by LASSO or RF. The best model was selected and compared with conventional risk scores. A nomogram and user-friendly online tool were developed to facilitate the mortality predictions and management recommendations.

Results: Thirteen features were selected by the LASSO regression algorithm. The LASSO-Cox model achieved an area under the curve (AUC) of 0.842 in the training dataset, and 0.854 in the validation dataset. A nomogram based on eight independent features was developed for the prediction of survival at 30, 180, and 365 days following discharge. Both the time dependent receiver operating characteristic (ROC) and decision curve analysis (DCA) showed better performances of the nomogram compared to the CHA2DS2-VASc and HAS-BLED models.

Conclusions: The LASSO-Cox mortality predictive model shows potential benefits in death risk evaluation for AF patients over the 365-day period following discharge. This novel ML approach may also provide physicians with personalized management recommendations.
Effects of Intermittent Compared With Continuous Energy Restriction on Blood Pressure Control in Overweight and Obese Patients With Hypertension
Authors: He Chao-Jie , Fei Ye-Ping , Zhu Chun-Yan , Yao Ming , Qian Gang , Hu Hui-Lin , Zhai Chang-Lin
Published: October 2021

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period.

Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids.

Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was −7.0 [0.6] kg vs. −6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was −7 [0.7] mmHg vs. −7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was −6 [0.5] mmHg vs. −5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial.

Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension.

Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000040468.
Aliased Flow Signal Planimetry by Cardiovascular Magnetic Resonance Imaging for Grading Aortic Stenosis Severity: A Prospective Pilot Study
Authors: Mantini Cesare , Khanji Mohammed Y. , D'Ugo Emilia , Olivieri Marzia , Caputi Cristiano Giovanni , Bufano Gabriella , Mastrodicasa Domenico , Calvo Garcia Darien , Rotondo Domenico , Candeloro Matteo , Tana Claudio , Cademartiri Filippo , Ionescu Adrian , Caulo Massimo , Gallina Sabina , Ricci Fabrizio
Published: October 2021

Objectives: Transthoracic echocardiography (TTE) is the standard technique for assessing aortic stenosis (AS), with effective orifice area (EOA) recommended for grading severity. EOA is operator-dependent, influenced by a number of pitfalls and requires multiple measurements introducing independent and random sources of error. We tested the diagnostic accuracy and precision of aliased orifice area planimetry (AOAcmr), a new, simple, non-invasive technique for grading of AS severity by low-VENC phase-contrast cardiovascular magnetic resonance (CMR) imaging.

Methods: Twenty-two consecutive patients with mild, moderate, or severe AS and six age- and sex-matched healthy controls had TTE and CMR examinations on the same day. We performed analysis of agreement and correlation among (i) AOAcmr; (ii) geometric orifice area (GOAcmr) by direct CMR planimetry; (iii) EOAecho by TTE-continuity equation; and (iv) the “gold standard” multimodality EOA (EOAhybrid) obtained by substituting CMR LVOT area into Doppler continuity equation.

Results: There was excellent pairwise positive linear correlation among AOAcmr, EOAhybrid, GOAcmr, and EOAecho (p < 0.001); AOAcmr had the highest correlation with EOAhybrid (R2 = 0.985, p < 0.001). There was good agreement between methods, with the lowest bias (0.019) for the comparison between AOAcmr and EOAhybrid. AOAcmr yielded excellent intra- and inter-rater reliability (intraclass correlation coefficient: 0.997 and 0.998, respectively).

Conclusions: Aliased orifice area planimetry by 2D phase contrast imaging is a simple, reproducible, accurate “one-stop shop” CMR method for grading AS, potentially useful when echocardiographic severity assessment is inconclusive or discordant. Larger studies are warranted to confirm and validate these promising preliminary results.
Physical Process Contributions to the Development of a Super Explosive Cyclone Over the Gulf Stream
Authors: Zhang Shuqin , Liu Chunlei , Xu Jianjun , Zhang Shaojing , Tang Ruoying , Huang Zhefan , Zheng Yanzhu , Guan Zhuoqiang , Mao Hongfei , Xue Yufeng
Published: October 2021

Contributions of different physical processes to the development of a super explosive cyclone (SEC) migrating over the Gulf Stream with the maximum deepening rate of 3.45 Bergeron were investigated using the ERA5 atmospheric reanalysis from European Centre for Medium-Range Weather Forecasts (ECMWF). The evolution of the SEC resembled the Shapiro-Keyser model. The moisture transported to the bent-back front by easterlies from Gulf Stream favored precipitation and enhanced the latent heat release. The bent-back front and warm front were dominated by the water vapor convergence in the mid-low troposphere, the cyclonic-vorticity advection in the mid-upper troposphere and the divergence in the upper troposphere. These factors favored the rapid development of the SEC, but their contributions showed significant differences during the explosive-developing stage. The diagnostic results based on the Zwack-Okossi equation suggested that the early explosive development of the SEC was mainly forced by the diabatic heating in the mid-low troposphere. From the early explosive-developing moment to maximum-deepening-rate moment, the diabatic heating, warm-air advection and cyclonic-vorticity advection were all enhanced significantly, their combination forced the most explosive development, and the diabatic heating had the biggest contribution, followed by the warm-air advection and cyclonic-vorticity advection, which is different from the previous studies of ECs over the Northwestern Atlantic. The cross section of these factors suggested that during the rapid development, the cyclonic-vorticity advection was distributed and enhanced significantly in the mid-low troposphere, the warm-air advection was strengthened significantly in the mid-low and upper troposphere, and the diabatic heating was distributed in the middle troposphere.
Large-Scale Implementation of Bioenergy With Carbon Capture and Storage in the Swedish Pulp and Paper Industry Involving Biomass Supply at the Regional Level
Authors: Karlsson Sebastian , Eriksson Anders , Normann Fredrik , Johnsson Filip
Published: October 2021

Bioenergy with carbon capture and storage (BECCS) has been identified as a possible major contributor to efforts to reach ambitious climate targets through the provision of negative emissions–offsetting residual fossil emissions in “hard-to-abate” sectors and accomplishing net-negative emissions. The pulp and paper industry is the single largest consumer of biomass in Sweden, with many large point sources of biogenic CO2 emissions that could be captured. This work investigates the biomass supply required for large-scale implementation of BECCS in the pulp and paper industry. Logging residues are considered as a fuel to supply the additional energy demand imposed by the capture plant, and the potential of these residues is evaluated in a case study that includes four pulp and paper mills located in regions of Sweden with different conditions for biomass supply. Two of the mills are located in southern Sweden, where there is strong competition for logging residues from the heating sector, and two of the mills are located in northern Sweden, where the competition is weaker. We show that implementing carbon capture at the four pulp and paper mills using regional logging residues to supply the additional heat demand required by the capture process (the reboiler heat demand) has the potential to capture around 4.6 Mt CO2/year. The results also show that the fuel share of the capture cost, i.e., the cost to supply the reboiler heat demand with regional logging residues, is 22–30 €/tCO2 captured, where the lower value corresponds to regions with weaker competition for logging residues (in this study, northern Sweden). In regions that have competition for logging residues, the possibility to increase the regional supply of logging residues to fuel the capture process while maintaining mill production output is limited, which in turn limits the possibilities to generate negative emissions via BECCS. In contrast, in regions with a low level of competition and strong availability of logging residues, there is an additional potential for logging residues to cover the additional heat demand required for CCS implementation.
Performance Improvement of KCS (Kalina Cycle System) 34 by Replacing Throttle Valve With Single-Screw Expander
Authors: Zhang Xinxin , Li Zhenlei , Wang Jingfu , Wu Yuting , Ma Chongfang
Published: October 2021

In order to recover the energy loss due to the throttling in the path of ammonia-lean solution in the Kalina Cycle System (KCS) 34, two redesigned cycles, in which single-screw expanders that can perform two-phase expansion are used to replace the throttle valve, are proposed in this paper. The results show that the thermal efficiency and net work of two redesigned cycles are higher than those of the original KCS 34. With the concentration increase of ammonia-water mixture, the work produced by the single-screw expander B in two redesigned cycles gradually decreases, and the difference between the work produced in two redesigned cycles also gradually decreases. The original KCS 34 and two redesigned cycles have high exergy efficiency. The highest cycle exergy efficiency of 56.59% can be obtained in the II-redesigned cycle when the evaporation pressure is 3.0 MPa and ammonia-water concentration is 0.75.
Satellite-Based Analysis of Spatial–Temporal Distributions of NH3 and Factors of Influence in North China
Authors: Zhi-li Deng , Qian-qian Zhang , Xing-ying Zhang
Published: October 2021

NH3 is an important part of the global nitrogen cycle as the most important atmospheric alkaline gas. NH3 reacts rapidly with acidic substances and accelerates the generation of particulate matter (PM2.5), which has important effects on the atmosphere and climate change. In this study, satellite NH3 column data were used to analyze spatial and temporal distributions of NH3 in China, and because of high concentrations and rates of change, North China was selected for more detailed analysis. Qualitative analysis was conducted to understand the relations between concentrations of NH3 and those of SO2 and NO2. Last, the random forest method was used to quantify relations between concentrations of atmospheric NH3 and factors influencing those concentrations, such as meteorological factors, NH3 self-emission, and concentrations of SO2 and NO2. Satellite-retrieved NH3 column concentrations showed an increasing trend during the 11 years from 2008 to 2018, and the rate of increase in summer was faster than that in winter. In those 11 years, NH3 self-emission had the greatest influence on NH3 concentrations. Concentrations of SO2 and NO2 had some effect and were negatively correlated with NH3 concentrations. The effect of SO2 on NH3 concentration was greater than that of NO2. Atmospheric NH3 concentration was also affected by meteorological conditions (temperature, relative humidity, pressure, and wind). In summer, temperature is the most important factors of meteorological conditions and relative humidity is the most important factors in winter. Therefore, to better control atmospheric NH3 concentrations, it is particularly important to formulate practical NH3 emission reduction policies and to consider the effects of SO2 and NO2 emission reduction policies.
Gene4HL: An Integrated Genetic Database for Hearing Loss
Authors: Huang Shasha , Zhao Guihu , Wu Jie , Li Kuokuo , Wang Qiuquan , Fu Ying , Zhang Honglei , Bi Qingling , Li Xiaohong , Wang Weiqian , Guo Chang , Zhang Dejun , Wu Lihua , Li Xiaoge , Xu Huiyan , Han Mingyu , Wang Xin , Lei Chen , Qiu Xiaofang , Li Yang , Li Jinchen , Dai Pu , Yuan Yongyi
Published: October 2021

Hearing loss (HL) is one of the most common disabilities in the world. In industrialized countries, HL occurs in 1–2/1,000 newborns, and approximately 60% of HL is caused by genetic factors. Next generation sequencing (NGS) has been widely used to identify many candidate genes and variants in patients with HL, but the data are scattered in multitudinous studies. It is a challenge for scientists, clinicians, and biologists to easily obtain and analyze HL genes and variant data from these studies. Thus, we developed a one-stop database of HL-related genes and variants, Gene4HL (http://www.genemed.tech/gene4hl/), making it easy to catalog, search, browse and analyze the genetic data. Gene4HL integrates the detailed genetic and clinical data of 326 HL-related genes from 1,608 published studies, along with 62 popular genetic data sources to provide comprehensive knowledge of candidate genes and variants associated with HL. Additionally, Gene4HL supports the users to analyze their own genetic engineering network data, performs comprehensive annotation, and prioritizes candidate genes and variations using custom parameters. Thus, Gene4HL can help users explain the function of HL genes and the clinical significance of variants by correlating the genotypes and phenotypes in humans.