bluuebunny/crossref_metadata_2025 huggingface dataset:
PERLAWANAN RAKYAT MORONENE TAUBONTO TERHADAP IMPERIALISME BELANDA: 1911-1941
Authors: Rahdan Muhammad , Hadara Ali , Aslim Aslim
Published: January 2022

Penelitian ini bertujuan untuk mengetahui (1) latar belakang perlawanan Rakyat Moronene atas imperialisme Belanda di Taubonto, (2) strategi perlawanan Rakyat Moronene atas imperialisme Belanda di Taubonto, dan (3) dampak perlawanan Rakyat Moronene atas imperialisme Belanda di Taubonto. Penelitian ini menggunakan metode sejarah dengan melalui lima tahapan-tahapan kerja sebagai berikut (1) Pemilihan Topik, (2) Heuristik sumber, (3) Kritik sumber, (4) Interpretasi sumber, (5) Historiografi. Hasil penelitian menunjukkan bahwa: (1) Latar belakang perlawanan rakyat Moronene didasari oleh semangat perjuangan atas keinginan untuk berdikari tanpa campur tangan pihak Belanda. Semangat masyarakat Moronene dikobarkan oleh Sangia Dowo seorang Raja Moronene yang melakukan perlawanan. (2) Strategi perlawanan rakyat Moronene saat melawan Belanda dilakukan dengan bergerilya dan serangan terang-terangan melalui pembelian senjata perang ke pihak Portugis. (3) Perlawanan rakyat Moronene menyebabkan gugurnya banyak Raja Moronene salah satunya yaitu Raja Sangia Dowo. Sangia Dowo meninggal diracun oleh Belanda melalui perjamuan makan malam dalam rangka pertemuan saat melakukan gencatan senjata. Kekalahan Kerajaan Moronene menyebabkan jatuhnya wilayah tersebut ke Pemerintahan Belanda. Kekalahan tersebut menyebabkan rakyat Moronene menderita akibat pemungutan pajak yang tinggi dan kebijakan kerja rodi oleh Belanda.
TREATMENT OF LEAD CONTAMINATED WASTE SLUDGE USING THE WILD RADISH VEGETABLE SPECIES Raphanus raphanistrum
Authors:   Universidad de las Fuerzas Armadas ESPE, Pino Vallejo Marco Vinicio ,   Instituto Superior Tecnológico República Federal de Alemania, Román Latorre Ana María ,   Universidad de las Fuerzas Armadas ESPE, Haro Robayo Margarita Del Pilar ,   Universidad de las Fuerzas Armadas ESPE, Andrade Orozco Ana Patricia ,   Universidad Nacional de Chimborazo, Perugachi Cahueñas Nelly Patricia ,   Escuela Superior Politécnica de Chimborazo
Published: January 2022

Sludge generated in the treatment of urban wastewater must be properly treated as it may contain concentrations of heavy metals or the presence of pathogenic microorganisms. The wastewater treatment plant in the main parish of Penipe, Chimborazo province, Ecuador, consists of an Imhoff tank in whose sedimentation chambers the waste sludge from physical treatment is digested under anaerobic conditions. The sludge is discharged into an open-air drying bed and does not receive treatment to stabilize it. Laboratory analysis determined that the sludge contains 24.23 mg.kg-1 of lead and is considered a potentially hazardous waste. The aim of the research is to treat the contaminated sludge by means of phytoextraction. The plant species known as wild radish (Raphanus raphanistrum) was sown in the residual mud and the treatment was biomonitoring for 91 days. Mud samples were taken every 15 days and by laboratory analysis a decrease in lead concentration was identified, identifying a root absorption efficiency of 16.40%.
PkM PADA ANAK USIA SEKOLAH DASAR: MENGEMBANGKAN BUDAYA LITERASI DI LINGKUNGAN TAWANG BRAK DESA TAWANGSARI, KEC. GARUM KAB. BLITAR
Authors: Poernamawatie Fahmi , Winarni Yuli
Published: January 2022

The purpose of this community service activity is to help children of primary school age get used to writing and reading. This habit is expected to increase children's reading interest and develop their reading literacy culture.The implementation of this activity is done through various way of exercises, such as: reading exercises, rewriting and retelling. Children are also accustomed to read Al-Qur’an and praying together. Drawing and coloring are also steps taken by the community service team to hone children's creativity. Watching films and entrepreneurship exercises to complement this activity, so that children have broad insights and also practice to improve financial literacy.Even though this activity still not showing the significant impact to the reading and writing skills of the children, but this activity gives benefits in terms of increasing the interest in reading, writing, and retelling something new. Enterpreneurial skills of some participants have have also created at the end of the activity. To achieve more optimal results, this activities should be done regularly with well-planned schedule.
DAMPAK PANDEMI COVID-19 TERHADAP IMPLEMENTASI MAKING INDONESIA 4.0
Authors: Irawan Shiddiq Ardhi
Published: January 2022

The industrial revolution is a process of change in which human work in various fields is replaced by machines. Currently the world has entered the era of the industrial revolution 4.0 so that the process of producing goods or services is much more efficient than before. Therefore, since 2017 the Ministry of Industry has made a roadmap for the Implementation of Making Indonesia 4.0 to accelerate the development of the manufacturing industry in Indonesia. In the process of achieving this goal, Indonesia is one of the countries most affected by the COVID-19 pandemic which began in early 2020. The activity plans that have been prepared in the roadmap must be adjusted because most of their budget has been reallocated or refocused for handling the impact of the COVID-19 pandemic. -19, this study aims to determine the implementation of Making Indonesia 4.0 on the impact of the covid-19 pandemic in terms of policies and budget allocations. The method used is a literature study and descriptive analysis using quantitative and qualitative data types. Based on the results of the descriptive analysis, information was obtained that the 2020 budget allocation for the Implementation of Making Indonesia 4.0 included the refocusing of 63.4% of the initial ceiling. With this refocusing, it is necessary to reconstruct the national priority programs contained in the roadmap for the Implementation of Making Indonesia 4.0 and redesign. financing so that not all national programs use the state budget.
PENGEMBANGAN KEBIJAKAN STANDAR BIAYA MASUKAN (SBM): BIAYA KONSUMSI KEGIATAN PENDIDIKAN DAN PELATIHAN
Authors: Mahfudin Mahfudin
Published: January 2022

There is no specific regulation in input cost standard regarding the consumption costs of education and training activities causing a high variation in the allocation of unit costs in the consumption. This study aims to determine the need and urgency of special arrangements for education and training consumption costs. The study was conducted using a qualitative descriptive method with data sourced from budget work plans and interviews with several education and training units. The results showed that the unit compiles the allocation costs by referring to one meeting consumption unit as the highest limit. The unit requires special arrangements for training consumption costs. The recommendation from this study is that the regulation of consumption costs for training activities is given at a maximum of 80% of the unit cost of meeting consumption. This arrangement will answer the needs of the unit in making a cost reference, as an efficiency measure and establishing a similarity  allocation.
KAWASAN EKONOMI KHUSUS DAN PERTUMBUHAN EKONOMI DAERAH: BUKTI EMPIRIS KEK SEI MANGKEI
Authors: Widianto Yanuar Wahyu
Published: January 2022

Penelitian ini bertujuan untuk mengetahui dampak keberadaan kawasan ekonomi khusus Sei Mangkei di Kabupaten Simalungun terhadap pertumbuhan ekonomi daerah. Motivasi penelitian ini berawal dari kenyataan bahwa besarnya jumlah insentif belanja perpajakan Indonesia dan masifnya pembentukan kawasan ekonomi khusus di Indonesia. Penelitian ini menggunakan data makro level kabupaten atau kota dari tahun 2000 hingga 2018 karena kendala ketersediaan data mikro. Penelitian ini meneliti dampak kausal dari keberadaan kawasan ekonomi khusus pada pertumbuhan ekonomi kabupaten atau kota yang diukur dari Produk Domestik Regional Bruto (PDRB). Untuk kabupaten Simalungun yang mempunyai kawasan ekonomi khusus, kami menghitung kontrafaktualnya dengan membangun synthetic control. Kami menemukan bahwa keberadaan kawasan ekonomi khusus  berdampak signifikan terhadap pertumbuhan ekonomi kabupaten atau kota. Namun begitu, dampak yang dihasilkan masih relatif kecil. Nilai perbandingan manfaat dan biaya yang hanya sebesar 0,52 dapat menjadi acuan Pemerintah untuk terus berhati-hati dalam menyempurnakan kebijakan KEK.
Decellularization Following Fixation of Explanted Aortic Valves as a Strategy for Preserving Native Mechanical Properties and Function
Authors: Singh Manisha , Park Clara , Roche Ellen T.
Published: January 2022

Mechanical or biological aortic valves are incorporated in physical cardiac simulators for surgical training, educational purposes, and device testing. They suffer from limitations including either a lack of anatomical and biomechanical accuracy or a short lifespan, hence limiting the authentic hands-on learning experience. Medical schools utilize hearts from human cadavers for teaching and research, but these formaldehyde-fixed aortic valves contort and stiffen relative to native valves. Here, we compare a panel of different chemical treatment methods on explanted porcine aortic valves and evaluate the microscopic and macroscopic features of each treatment with a primary focus on mechanical function. A surfactant-based decellularization method after formaldehyde fixation is shown to have mechanical properties close to those of the native aortic valve. Valves treated in this method were integrated into a custom-built left heart cardiac simulator to test their hemodynamic performance. This decellularization, post-fixation technique produced aortic valves which have ultimate stress and elastic modulus in the range of the native leaflets. Decellularization of fixed valves reduced the valvular regurgitation by 60% compared to formaldehyde-fixed valves. This fixation method has implications for scenarios where the dynamic function of preserved valves is required, such as in surgical trainers or device test rigs.
5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury
Authors: Chen Hang-yu , Li Xiao-xiao , Li Chao , Zhu Hai-chuan , Hou Hong-yan , Zhang Bo , Cheng Li-ming , Hu Hui , Lu Zhong-xin , Liu Jia-xing , Yang Ze-ruo , Zhang Lei , Xu Nuo , Chen Long , He Chuan , Dong Chao-ran , Ge Qing-gang , Lin Jian
Published: January 2022

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited.

Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19.

Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77–0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89–0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84–0.95).

Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.
A Century of Brain Regeneration Phenomena and Neuromorphological Research Advances, 1890s–1990s—Examining the Practical Implications of Theory Dynamics in Modern Biomedicine
Authors: Stahnisch Frank W.
Published: January 2022

The modern thesis regarding the “structural plastic” properties of the brain, as reactions to injuries, to tissue damage, and to degenerative cell apoptosis, can hardly be seen as expendable in clinical neurology and its allied disciplines (including internal medicine, psychiatry, neurosurgery, radiology, etc.). It extends for instance to wider research areas of clinical physiology and neuropsychology which almost one hundred years ago had been described as a critically important area for the brain sciences and psychology alike. Yet the mounting evidence concerning the range of structural neuroplastic phenomena beyond the significant early 3 years of childhood has shown that there is a progressive building up and refining of neural circuits in adaptation to the surrounding environment. This review essay explores the history behind multiple biological phenomena that were studied and became theoretically connected with the thesis of brain regeneration from Santiago Ramón y Cajal’s pioneering work since the 1890s to the beginning of the American “Decade of the Brain” in the 1990s. It particularly analyzes the neuroanatomical perspectives on the adaptive capacities of the Central Nervous System (CNS) as well as model-like phenomena in the Peripheral Nervous System (PNS), which were seen as displaying major central regenerative processes. Structural plastic phenomena have assumed large implications for the burgeoning field of regenerative or restorative medicine, while they also pose significant epistemological challenges for related experimental and theoretical research endeavors. Hereafter, early historical research precursors are examined, which investigated brain regeneration phenomena in non-vertebrates at the beginning of the 20th century, such as in light microscopic studies and later in electron microscopic findings that substantiated the presence of structural neuroplastic phenomena in higher cortical substrates. Furthermore, Experimental physiological research in hippocampalin vivomodels of regeneration further confirmed and corroborated clinical physiological views, according to which “structural plasticity” could be interpreted as a positive regenerative CNS response to brain damage and degeneration. Yet the underlying neuroanatomical mechanisms remained to be established and the respective pathway effects were only conveyed through the discovery of neural stem cells in in adult mammalian brains in the early 1990s. Experimental results have since emphasized the genuine existence of adult neurogenesis phenomena in the CNS. The focus in this essay will be laid here on questions of the structure and function of scientific concepts, the development of research schools among biomedical investigators, as well as the impact of new data and phenomena through innovative methodologies and laboratory instruments in the neuroscientific endeavors of the 20th century.
Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation
Authors: Enrich Carlos , Lu Albert , Tebar Francesc , Rentero Carles , Grewal Thomas
Published: January 2022

Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10–30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this “Mini Review” we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.
Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment
Authors: Oliveira Anny Carolline Silva , Rezende Luisa , Gorshkov Vladimir , Melo-Braga Marcella Nunes , Verano-Braga Thiago , Fernandes-Braga Weslley , Guadalupe Jorge Luís de Melo , de Menezes Gustavo Batista , Kjeldsen Frank , de Andrade Hélida Monteiro , Andrade Luciana de Oliveira
Published: January 2022

Trypanosoma cruzi invades non-professional phagocytic cells by subverting their membrane repair process, which is dependent on membrane injury and cell signaling, intracellular calcium increase, and lysosome recruitment. Cells lacking lysosome-associated membrane proteins 1 and 2 (LAMP1 and LAMP2) are less permissive to parasite invasion but more prone to parasite intracellular multiplication. Several passages through a different intracellular environment can significantly change T. cruzi’s gene expression profile. Here, we evaluated whether one single passage through LAMP-deficient (KO) or wild-type (WT) fibroblasts, thus different intracellular environments, could influence T. cruzi Y strain trypomastigotes’ ability to invade L6 myoblasts and WT fibroblasts host cells. Parasites released from LAMP2 KO cells (TcY-L2−/−) showed higher invasion, calcium signaling, and membrane injury rates, for the assays in L6 myoblasts, when compared to those released from WT (TcY-WT) or LAMP1/2 KO cells (TcY-L1/2−/−). On the other hand, TcY-L1/2−/− showed higher invasion, calcium signaling, and cell membrane injury rates, for the assays in WT fibroblasts, compared to TcY-WT and TcY-L1/2−/−. Albeit TcY-WT presented an intermediary invasion and calcium signaling rates, compared to the others, in WT fibroblasts, they induced lower levels of injury, which reinforces that signals mediated by surface membrane protein interactions also have a significant contribution to trigger host cell calcium signals. These results clearly show that parasites released from WT or LAMP KO cells are distinct from each other. Additionally, these parasites’ ability to invade the cell may be distinct depending on which cell type they interact with. Since these alterations most likely would reflect differences among parasite surface molecules, we also evaluated their proteome. We identified few protein complexes, membrane, and secreted proteins regulated in our dataset. Among those are some members of MASP, mucins, trans-sialidases, and gp63 proteins family, which are known to play an important role during parasite infection and could correlate to TcY-WT, TcY-L1/2−/−, and TcY-L2−/− biological behavior.
Experimental Models of COVID-19
Authors: Caldera-Crespo Luis A. , Paidas Michael J. , Roy Sabita , Schulman Carl I. , Kenyon Norma Sue , Daunert Sylvia , Jayakumar Arumugam R.
Published: January 2022

COVID-19 is the most consequential pandemic of the 21stcentury. Since the earliest stage of the 2019-2020 epidemic, animal models have been useful in understanding the etiopathogenesis of SARS-CoV-2 infection and rapid development of vaccines/drugs to prevent, treat or eradicate SARS-CoV-2 infection. Early SARS-CoV-1 research using immortalizedin-vitrocell lines have aided in understanding different cells and receptors needed for SARS-CoV-2 infection and, due to their ability to be easily manipulated, continue to broaden our understanding of COVID-19 disease inin-vivomodels. The scientific community determined animal models as the most useful models which could demonstrate viral infection, replication, transmission, and spectrum of illness as seen in human populations. Until now, there have not been well-described animal models of SARS-CoV-2 infection although transgenic mouse models (i.e. mice with humanized ACE2 receptors with humanized receptors) have been proposed. Additionally, there are only limited facilities (Biosafety level 3 laboratories) available to contribute research to aid in eventually exterminating SARS-CoV-2 infection around the world. This review summarizes the most successful animal models of SARS-CoV-2 infection including studies in Non-Human Primates (NHPs) which were found to be susceptible to infection and transmitted the virus similarly to humans (e.g., Rhesus macaques, Cynomolgus, and African Green Monkeys), and animal models that do not require Biosafety level 3 laboratories (e.g., Mouse Hepatitis Virus models of COVID-19, Ferret model, Syrian Hamster model). Balancing safety, mimicking human COVID-19 and robustness of the animal model, the Murine Hepatitis Virus-1 Murine model currently represents the most optimal model for SARS-CoV-2/COVID19 research. Exploring future animal models will aid researchers/scientists in discovering the mechanisms of SARS-CoV-2 infection and in identifying therapies to prevent or treat COVID-19.
Characterization of the Pathology, Biochemistry, and Immune Response in Kunming (KM) Mice Following Fasciola gigantica Infection
Authors: Mei Xuefang , Zhang Yaoyao , Quan Chenyu , Liang Yiying , Huang Weiyi , Shi Wei
Published: January 2022

As a putative model of Fasciola gigantica infection, detailed data in Kunming (KM) mice infected with F. gigantica are lacking. In this study, KM mice were orally infected with 15 metacercaria for 8 weeks. Macroscopic and microscopic changes, serum biochemistry, cytokine responses, and changes in parasite-specific immunoglobulin G (IgG) antibody levels were monitored at 1, 3, 5, 7, and 8 weeks post-infection (wpi), respectively. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased after infection, while that of albumin (ALB) decreased, which was positively correlated with the degree of liver damage. Between 5 and 7 wpi, the mice showed symptoms of anemia and weight loss, possibly caused by the decrease of alkaline phosphatase (ALP). Moreover, the changing tendencies of the levels of globulin (GLB) and parasite-specific IgG antibody were similar, suggesting a potential correlation between GLB production and adaptive immune response in the host. Coordinated variations in interferon gamma (IFN-γ) and interleukin 4 (IL-4) indicated a mixed T helper 1 (Th1)/Th2 cellular immune response. Furthermore, the serum IgG antibody increased after infection and peaked at 5 wpi, and it was positively correlated with the average parasite burdens. The worms collected from mice were approximately 1 cm in length at 8 wpi, their digestive and reproductive systems were well developed, and no eggs were found in the uterus. To the best of our knowledge, this is the first report describing detailed histological, biochemical, and immunological indices in KM mice infected with F. gigantica, which provides basic information on KM mice against infection with F. gigantica.
Predictors of Permanent Pacemaker Implantation in Patients After Transcatheter Aortic Valve Replacement in a Chinese Population
Authors: Zhang Jiaqi , Chi Chengwei , Tian Simiao , Zhang Shulong , Liu Jihong
Published: January 2022

Background: Permanent pacemaker (PPM) implantation is the main complication of transcatheter aortic valve replacement (TAVR). Few studies have evaluated the requirement for PPM implantation due to ECG changes following TAVR in a Chinese population.

Objective: Our study aimed to evaluate the incidence and predictors of PPM implantation in a cohort of Chinese patients with TAVR.

Methods: We retrospectively evaluated 39 consecutive patients with severe native aortic stenosis referred for TAVR with a self-expandable prosthesis, the Venus A valve (Venus MedTech Inc., Hangzhou, China), from 2019 to 2021 at the Heart Center of Affiliated Zhongshan Hospital of Dalian University. Predictors of PPM implantation were identified using logistic regression.

Results: In our study, the incidence of PPM implantation was 20.5%. PPM implantation occurs with higher risk in patients with negative creatinine clearance (CrCl), dyslipidemia, high Society of Thoracic Surgeons (STS) Morbimortality scores, and lead I T wave elevation. TAVR induced several cardiac electrical changes such as increased R wave and T wave changes in lead V5. The main independent predictors of PPM implantation were new-onset left bundle branch block (LBBB) (coef: 3.211, 95% CI: 0.899–7.467, p = 0.004) and lead I T wave elevation (coef: 11.081, 95% CI: 1.632–28.083, p = 0.016).

Conclusion: New-onset LBBB and lead I T wave elevation were the main independent predictors of PPM implantation in patients undergoing TAVR. Clinical indications such as negative CrCl, dyslipidemia, high STS Morbimortality scores, and an increased T wave elevation before TAVR should be treated with caution to decrease the need for subsequent PPM implantation.
Stable Rates of Obstructive Hypertrophic Cardiomyopathy in a Contemporary Era
Authors: Butzner Michael , Leslie Douglas L. , Cuffee Yendelela , Hollenbeak Christopher S. , Sciamanna Christopher , Abraham Theodore
Published: January 2022

Hypertrophic cardiomyopathy is the most common genetic heart disease in the US, with an estimated prevalence of 1 in 500. However, the extent to which obstructive hypertrophic cardiomyopathy is clinically recognized is not well-established. Therefore, the objective of this study was to estimate the annual prevalence of clinically diagnosed oHCM in the US from 2016 to 2018. Data from the MarketScan® database were queried from years 2016 to 2018 to identify patients with ≥1 claim of oHCM (International Statistical Classification of Disease and Related Health Problems diagnosis code: I42.1). Prevalence rates for oHCM were calculated and stratified by sex and age. In 2016, 4,612 unique patients had clinical diagnosis of oHCM, resulting in an estimated oHCM prevalence of 1.65 per 10,000. The prevalence of oHCM in males and females was 2.07 and 1.26, respectively. Prevalence of oHCM was highest in patients 55–64 years of age (4.82). Prevalence of oHCM generally increased with age, from 0.36 per 10,000 in those under 18 to 4.82 per 10,000 in those 55–65. Trends in prevalence of oHCM over time, including by sex and age group, remained similar and consistent in 2017 and 2018. The prevalence of oHCM was stable over the 3-year time period, including higher rates of oHCM in males and patients aged 55–64 years. These results suggest that the majority of privately insured patients with oHCM are undiagnosed in the US and reinforce the need for policies and research to improve the clinical identification of oHCM patients in the US.
Diagnosis and Outcome of Cardiac Paragangliomas: A Retrospective Observational Cohort Study in China
Authors: Dong Xueqi , Meng Xu , Zhang Ting , Zhao Lin , Liu Fang , Han Xu , Liu Yecheng , Zhu Huadong , Zhou Xianliang , Miao Qi , Zhang Shuyang
Published: January 2022

Background: Cardiac paragangliomas (CPGLs) are rare neuroendocrine tumors that are easily overlooked and difficult to diagnose. Detailed comprehensive data regarding CPGL diagnosis and outcome are lacking.

Methods: We retrospectively analyzed a cohort of 27 CPGL patients. This cohort represents the largest such cohort reported to date.

Results: The prevalence of trilogy symptoms (concurrent palpitations, hyperhidrosis, and headache) was frequent (9/27, 33.3%). Sensitivity of echocardiography and contrast-enhanced computed tomography for localization of CPGL were 81.8% and 87%, respectively. Octreotide scintigraphy showed 100% sensitivity for detecting GPCLs, while sensitivity of I131-metaiodoben-zylguanidine scintigraphy was only 32.9%. Multiple tumors were found in 29.6% of patients. Most CPGLs originated from the epicardium or root of the great vessels (92.9%) and were mostly supplied by the coronary arteries and their branches (95.7%). Twenty-four patients underwent surgical treatment. Although local invasion was present in 40.0% of patients, it did not affect long-term outcome. Mean follow-up was 6.9 ± 3.6 years. Biochemical remission was achieved in 85% of patients. The recurrence rate was 15%.

Conclusions: Manifestations of CPGLs are non-specific and they can be difficult to detect on imaging examinations. Octreotide scintigraphy should be performed in patients with suspected paragangliomas to screen for multiple lesions. Surgical resection of CPGLs can achieve symptom relief and biochemical remission.
Benefits and Pitfalls of the Perceval Sutureless Bioprosthesis
Authors: Dokollari Aleksander , Ramlawi Basel , Torregrossa Gianluca , Sá Michel Pompeu , Sicouri Serge , Prifti Edvin , Gelsomino Sandro , Bonacchi Massimo
Published: January 2022

Objective: To highlight the main target points covered by clinical studies on the Perceval sutureless valve for surgical aortic valve replacement (SAVR) and raise a point of discussion for further expansion of its use when compared with stented bioprostheses (SB) and transcatheter aortic valve replacement (TAVR).

Methods: We reviewed clinical trials and retrospective studies published up to date and compared the outcomes in terms of mortality, myocardial infarction (MI) stroke, paravalvular leak (PVL), permanent pacemaker implantation (PPI), bleeding and long-term outcomes.

Results: Clinical studies showed that 30-day mortality ranged from 0–4% for Perceval and 2.9–7% for TAVR. The incidence of PVL (Perceval 1.9–19.4 vs. TAVR 9–53.5%), PPI (Perceval 2–11.2 vs. TAVR 4.9–25.5%), stroke (Perceval 0 vs. TAVR 0–2.8%), MI (Perceval 0 vs. TAVR 0–3.5%), were all higher in the TAVR group. Compared to other SB, mortality ranged from 0–6.4% for Perceval and 0–5.9% for SB. The incidence of PVR (Perceval 1–19.4 vs. SB 0–1%), PPI (Perceval 2–10.7 vs. SB 1.8–8.5%), stroke (Perceval 0–3.7 vs. SB 1.8–7.3%) and MI (Perceval 0–7.8 vs. SB 0–4.3%) were comparable among the groups. In patients with a bicuspid aortic valve, mortality rate was (0–4%) and PVL incidence was (0–2.3%). However, there was a high incidence of PPI (0–20%), and stroke (0–8%). Long-term survival ranged between 96.7–98.6%.

Conclusions: The Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its implantation speed, the reduced cardiopulmonary bypass time, the reduced aortic cross-clamp time and the shorter intensive care unit and hospital length of stay.
The Complex Interplay of Inflammation, Metabolism, Epigenetics, and Sex in Calcific Disease of the Aortic Valve
Authors: Ferrari Silvia , Pesce Maurizio
Published: January 2022

Calcification of the aortic valve is one of the most rapidly increasing pathologies in the aging population worldwide. Traditionally associated to cardiovascular risk conditions, this pathology is still relatively unaddressed on a molecular/cellular standpoint and there are no available treatments to retard its progression unless valve substitution. In this review, we will describe some of the most involved inflammatory players, the metabolic changes that may be responsible of epigenetic modifications and the gender-related differences in the onset of the disease. A better understanding of these aspects and their integration into a unique pathophysiology context is relevant to improve current therapies and patients management.
Turning Platelets Off and On: Role of RhoGAPs and RhoGEFs in Platelet Activity
Authors: Comer Shane P.
Published: January 2022

Platelet cytoskeletal reorganisation is a critical component of platelet activation and thrombus formation in haemostasis. The Rho GTPases RhoA, Rac1 and Cdc42 are the primary drivers in the dynamic reorganisation process, leading to the development of filopodia and lamellipodia which dramatically increase platelet surface area upon activation. Rho GTPases cycle between their active (GTP-bound) and inactive (GDP-bound) states through tightly regulated processes, central to which are the guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs catalyse the dissociation of GDP by inducing changes in the nucleotide binding site, facilitating GTP binding and activating Rho GTPases. By contrast, while all GTPases possess intrinsic hydrolysing activity, this reaction is extremely slow. Therefore, GAPs catalyse the hydrolysis of GTP to GDP, reverting Rho GTPases to their inactive state. Our current knowledge of these proteins is constantly being updated but there is considerably less known about the functionality of Rho GTPase specific GAPs and GEFs in platelets. In the present review, we discuss GAP and GEF proteins for Rho GTPases identified in platelets, their regulation, biological function and present a case for their further study in platelets.
You Don't Need an App—Conducting Mobile Smoking Research Using a Qualtrics-Based Approach
Authors: Cui Yong , Robinson Jason D. , Rymer Rudel E. , Minnix Jennifer A. , Cinciripini Paul M.
Published: January 2022

With the increasing availability of smartphones, many tobacco researchers are exploring smartphone-delivered mobile smoking interventions as a disseminable means of treatment. Most effort has been focused on the development of smartphone applications (apps) to conduct mobile smoking research to implement and validate these interventions. However, developing project-specific smartphone apps that work across multiple mobile platforms (e.g., iOS and Android) can be costly and time-consuming. Here, using a hypothetical study, we present an alternate approach to demonstrate how mobile smoking cessation and outcome evaluation can be conducted without the need of a dedicated app. Our approach uses the Qualtrics platform, a popular online survey host that is used under license by many academic institutions. This platform allows researchers to conduct device-agnostic screening, consenting, and administration of questionnaires through Qualtrics's native survey engine. Researchers can also collect ecological momentary assessment data using text messaging prompts with the incorporation of Amazon Web Services' Pinpoint. Besides these assessment capabilities, Qualtrics has the potential for delivering personalized behavioral interventions through the use of JavaScript code. By customizing the question's web elements in Qualtrics (e.g., using texts, images, videos, and buttons), researchers can integrate interactive web-based interventions and complicated behavioral and cognitive tasks into the survey. In conclusion, this Qualtrics-based methodology represents a novel and cost-effective approach for conducting mobile smoking cessation and assessment research.
Northeastern Patagonian Glacier Advances (43°S) Reflect Northward Migration of the Southern Westerlies Towards the End of the Last Glaciation
Authors: Leger Tancrède P. M. , Hein Andrew S. , Goldberg Daniel , Schimmelpfennig Irene , Van Wyk de Vries Maximillian S. , Bingham Robert G. ,   ASTER Team
Published: January 2022

The last glacial termination was a key event during Earth’s Quaternary history that was associated with rapid, high-magnitude environmental and climatic change. Identifying its trigger mechanisms is critical for understanding Earth’s modern climate system over millennial timescales. It has been proposed that latitudinal shifts of the Southern Hemisphere Westerly Wind belt and the coupled Subtropical Front are important components of the changes leading to global deglaciation, making them essential to investigate and reconstruct empirically. The Patagonian Andes are part of the only continental landmass that fully intersects the Southern Westerly Winds, and thus present an opportunity to study their former latitudinal migrations through time and to constrain southern mid-latitude palaeo-climates. Here we use a combination of geomorphological mapping, terrestrial cosmogenic nuclide exposure dating and glacial numerical modelling to reconstruct the late-Last Glacial Maximum (LGM) behaviour and surface mass balance of two mountain glaciers of northeastern Patagonia (43°S, 71°W), the El Loro and Río Comisario palaeo-glaciers. In both valleys, we find geomorphological evidence of glacier advances that occurred after the retreat of the main ice-sheet outlet glacier from its LGM margins. We date the outermost moraine in the El Loro valley to 18.0 ± 1.15 ka. Moreover, a series of moraine-matching simulations were run for both glaciers using a spatially-distributed ice-flow model coupled with a positive degree-day surface mass balance parameterisation. Following a correction for cumulative local surface uplift resulting from glacial isostatic adjustment since ∼18 ka, which we estimate to be ∼130 m, the glacier model suggests that regional mean annual temperatures were between 1.9 and 2.8°C lower than present at around 18.0 ± 1.15 ka, while precipitation was between ∼50 and ∼380% higher than today. Our findings support the proposed equatorward migration of the precipitation-bearing Southern Westerly Wind belt towards the end of the LGM, between ∼19.5 and ∼18 ka, which caused more humid conditions towards the eastern margins of the northern Patagonian Ice Sheet a few centuries ahead of widespread deglaciation across the cordillera.
Decrease in Salivary Serotonin in Response to Probiotic Supplementation With Saccharomyces boulardii in Healthy Volunteers Under Psychological Stress: Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Karbownik Michał Seweryn , Kręczyńska Joanna , Wiktorowska-Owczarek Anna , Kwarta Paulina , Cybula Magdalena , Stilinović Nebojša , Pietras Tadeusz , Kowalczyk Edward
Published: January 2022

Background

Bacterial probiotics are thought to exert a serotonergic effect relevant to their potential antidepressant and pro-cognitive action, but yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii affects the level of salivary serotonin under psychological stress and identify the factors associated with it.

Methods

Healthy medical students were randomized to ingest Saccharomyces boulardii CNCM I-1079 or placebo before a stressful event. Salivary serotonin concentration was assessed before and at the end of supplementation. Moreover, obtained results were compared to psychological, biochemical, physiological and sociodemographic study participants data.

Results

Data of thirty-two participants (22.8 ± 1.7 years of age, 16 males) was available for the main analysis. Supplementation with Saccharomyces boulardii decreased salivary serotonin concentration under psychological stress by 3.13 (95% CI 0.20 to 6.07) ng/mL, p = 0.037, as compared to placebo. Salivary serotonin was positively correlated with salivary metanephrine (β = 0.27, 95% CI 0.02 to 0.52, p = 0.031) and pulse rate (β = 0.28, 95% CI 0.05 to 0.50, p = 0.018), but insignificantly with anxiety, depression, eating attitudes and information retrieval.

Conclusions

Saccharomyces boulardii CNCM I-1079 may be distinct from bacterial probiotics in its salivary serotonergic effect, which appears positively linked to symapathoadrenal markers. The study requires cautious interpretation, and further investigation.
Meal-Related Asprosin Serum Levels Are Affected by Insulin Resistance and Impaired Fasting Glucose in Children With Obesity
Authors: Corica Domenico , Pepe Giorgia , Aversa Tommaso , Currò Monica , Curatola Selenia , Li Pomi Alessandra , Alibrandi Angela , Ientile Riccardo , Wasniewska Malgorzata
Published: January 2022

Asprosin physiologically increases in fasting conditions and decreases with refeeding and has been implicated in glucose homeostasis. An alteration of meal-related circadian oscillation of asprosin has been suggested in adults affected by type 2 diabetes mellitus.

Aims of this study were to test the hypothesis of an alteration in the meal-related variation of asprosin levels in non-diabetic children and adolescents with obesity and to assess which metabolic variables condition this variation in non-diabetic children and adolescents with obesity. This is a cross-sectional study which included 79 children and adolescents with obesity. Children underwent clinical and biochemical assessments, including oral glucose tolerance test (OGTT), and liver ultrasound evaluation. Asprosin serum levels were measured by an enzyme-linked immunosorbent assay at a fasting state and at the 120-minute OGTT timepoint (2h-postprandial asprosin). Fasting and 2h-postprandial asprosin serum levels did not significantly differ in the entire study population (374.28 ± 77.23 vs 375.27 ± 81.26;p=0.837). 55.7% of patients had a significant increase in 2h-postprandial asprosin compared with fasting levels. The asprosin level increase condition was significantly associated with HOMA-IR (OR,1.41; 95%CI,1.005-1.977; p=0.047), fasting glycaemia (OR,1.073; 95%CI,1.009-1.141;p=0.024) and HOMA-B (OR,0.99; 95%CI,0.984-0.999; p=0.035). Moreover, the IFG condition was associated with the increase in asprosin levels (OR, 3.040; 95%CI, 1.095-8.436; p=0.033), even after adjustment for HOMA-IR, BMI SDS, sex and pubertal stage. Insulin resistance and IFG influence meal-related changes of asprosin serum levels in our study population of obese, non-diabetic, children. Alteration of asprosin circadian secretion might be an early biomarker of impaired glucose regulation in obese children with insulin resistance.
Do Fossil-Fuel Price Distortions Impact the Low-Carbon Transition in China’s Energy Intensive Industries?
Authors: Wang Xiaolei , Liang Shuang , Wang Hui , Huang Shaohua , Liao Binbin
Published: January 2022

Energy intensive industries (EIIs) in China are predominantly reliant on fossil fuels. Consequently, such high fossil fuel dependency has amplified carbon emission levels and blocked the low-carbon transition. It is inappropriate to discuss the solution of the dependency before investigating fossil-fuel price distortion and its impact on the industrial energy consumption. Therefore, this paper built a dynamic trans-log cost function model based on provincial panel data of China’s Ells between 2004 and 2016, to investigate inter-fuel substitution effects caused by own price elasticities and cross price elasticities, and analyzed the impact of fossil-fuel price distortions on low-carbon transition. The level of price distortions in coal, gasoline and diesel was evaluated, based on which the CO2 mitigation potentials in China’s EIIs were estimated. Results show that: 1) in each EII sector, the own price elasticities of all fuels were negative while the cross price elasticities among coal, oil and electricity were positive, suggesting substitution effect exists; 2) the average level of price distortions in coal, gasoline and diesel is 7.48, 11.1 and 32.19%, respectively, which means the prices of coal tend to be more market- oriented than the other two fuels; 3) removing coal price distortions can potentially reduce CO2 emissions in China’s EIIs by 905.78 million tons, while the effects of removing oil price distortions were uncertain, unless the substitution of coal for oil was restrained. Therefore, there is still much room for improvement in China’s fossil-fuel market reform. Possible policies are required to improve the production in EIIs and the low-carbon transition by adopting cleaner energy resources to substitute fossil-fuels.
The Fiscal Hedging and Green Financing: Sustainability Challenges for Developing World
Authors: Chunyu Leng , Ali Syed Ahtsham , Tan Ci , Yin Weihua , Kouser Robina , Gulzar Fatima
Published: January 2022

The global community has set intensive targets in Sustainable Development Goals (SDGs) to better people’s lives after closing the Millennium Development Goals (MDGs). It corresponds to the 2030 aspirations of the United Nations to enhance and promote the sustainable development of human society. The current paper explores the impact of fiscal hedging and R&D in energy Using a green-energy system in SDGs. To do this, we used TOPSIS and QARDL methodologies on a 21-year dataset of South and Southeast Asian economies from 2000 to 2020. The study results show that fiscal hedging contributes favourably to the environmental degradation of the underlying economy. Research and development (R&D) in renewables has contributed negatively to ecological degradation and SDGs in the economies of South & Southeast Asia. This study suggests policy guidelines for advanced and developing economies based on fiscal stability and technical innovation through R&D to meet SDG.
Potential for Return on Investment in Rehabilitation-Oriented Blue Carbon Projects: Accounting Methodologies and Project Strategies
Authors: Duncan Clare , Primavera Jurgenne H. , Hill Nicholas A. O. , Wodehouse Dominic C. J. , Koldewey Heather J.
Published: January 2022

Opportunities to boost climate change mitigation and adaptation (CCMA) and sustainable conservation financing may lie in enhancing blue carbon sequestration, particularly in developing nations where coastal ecosystems are extensive and international carbon markets offer comparatively attractive payments for environmental stewardship. While blue carbon is receiving increased global attention, few credit-generating projects are operational, due to low credit-buyer incentives with uncertainty in creditable emissions reductions and high project costs. Little empirical guidance exists for practitioners to quantify return-on-investment (ROI) and viability of potential projects, particularly for rehabilitation where multiple implementation options exist with diverse associated costs. We map and model drivers of mangrove natural regeneration (NR) using remote sensing (high-resolution satellite imagery segmentation and time-series modeling), and subsequent carbon sequestration using field- and literature-derived data, across abandoned aquaculture ponds in the Philippines. Using project-specific cost data, we then assess ROI for a hypothetical rehabilitation-focused mangrove blue carbon project at a 9.68 ha abandoned pond over a 10-year timeframe, under varied rehabilitation scenarios [NR vs. assisted natural regeneration (ANR) with planting], potential emissions reduction accreditation methodologies, carbon prices and discount rates. NR was faster in lower-lying ponds with lower tidal exposure (greater pond dike retention). Forecasted carbon sequestration was 3.7- to 5.2-fold and areal “greenbelt” regeneration 2.5- to 3.4-fold greater in our case study under ANR than NR. Variability in modeled sequestration rates drove high uncertainty and credit deductions in NR strategies. ROI with biomass-only accreditation was low and negative under NR and ANR, respectively. ROI was greater under ANR with inclusion of biomass and autochthonous soil carbon; however, neither strategy was highly profitable at current voluntary market carbon prices. ANR was the only scenario that fulfilled coastal protection greenbelt potential, with full mangrove cover within 10 years. Our findings highlight the benefits of ANR and soils inclusion in rehabilitation-oriented blue carbon projects, to maximize carbon sequestration and greenbelt enhancement (thus enhance pricing with potential bundled credits), and minimize forecasting uncertainty and credit-buyers’ perceived risk. An ANR rehabilitation strategy in low-lying, sea-facing abandoned ponds with low biophysical intervention costs may represent large blue carbon CCMA opportunities in regions with high aquaculture abandonment.