bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembatasan Kebebasan Beragama Dan Berkeyakinan Di Indonesia Serta Implikasinya
Authors: Manese Rohit Mahatir
Published: April 2021

This article aims to describe caused the restriction of religion and belief freedom and its implications in Indonesia. The author’s argument on the ownership that limitation of the religion and belief freedom in Indonesia which have mainstreams about religious values and blasphemy. It causes diversity in Indonesia to limited pluralism experience. With the perspective of pluralism, limiting the religion and belief freedom is carried out by the state makes ancestral religions which is not declared as official religions. Apart from making the state that recognizes only six religions, this statement contradicts the Universal Declaration of Human Rights (UDHR) and the International Covenant. By using the literature review method, this article finds that the religion and belief freedom in Indonesia experiences delimited pluralism so this condition brings to negotiated on ancestral religions and intolerance to minority groups.
Keywords: Freedom of Religion and Belief; Religious Value; Delimited Pluralism; Discrimination; Intolerance.
Machine Learning and Metaheuristic Methods for Renewable Power Forecasting: A Recent Review
Authors: Alkabbani Hanin , Ahmadian Ali , Zhu Qinqin , Elkamel Ali
Published: April 2021

The global trend toward a green sustainable future encouraged the penetration of renewable energies into the electricity sector to satisfy various demands of the market. Successful and steady integrations of renewables into the microgrids necessitate building reliable, accurate wind and solar power forecasters adopting these renewables' stochastic behaviors. In a few reported literature studies, machine learning- (ML-) based forecasters have been widely utilized for wind power and solar power forecasting with promising and accurate results. The objective of this article is to provide a critical systematic review of existing wind power and solar power ML forecasters, namely artificial neural networks (ANNs), recurrent neural networks (RNNs), support vector machines (SVMs), and extreme learning machines (ELMs). In addition, special attention is paid to metaheuristics accompanied by these ML models. Detailed comparisons of the different ML methodologies and the metaheuristic techniques are performed. The significant drawn-out findings from the reviewed papers are also summarized based on the forecasting targets and horizons in tables. Finally, challenges and future directions for research on the ML solar and wind prediction methods are presented. This review can guide scientists and engineers in analyzing and selecting the appropriate prediction approaches based on the different circumstances and applications.
Comparing the Emergence of Technical and Social Sciences Research in Artificial Intelligence
Authors: Ligo Alexandre K. , Rand Krista , Bassett Jason , Galaitsi S. E. , Trump Benjamin D. , Jayabalasingham Bamini , Collins Thomas , Linkov Igor
Published: April 2021

Applications of Artificial Intelligence (AI) can be examined from perspectives of different disciplines and research areas ranging from computer science and security, engineering, policymaking, and sociology. The technical scholarship of emerging technologies usually precedes the discussion of their societal implications but can benefit from social science insight in scientific development. Therefore, there is an urgent need for scientists and engineers developing AI algorithms and applications to actively engage with scholars in the social sciences. Without collaborative engagement, developers may encounter resistance to the approval and adoption of their technological advancements. This paper reviews a dataset, collected by Elsevier from the Scopus database, of papers on AI application published between 1997 and 2018, and examines how the co-development of technical and social science communities has grown throughout AI's earliest to latest stages of development. Thus far, more AI research exists that combines social science and technical explorations than AI scholarship of social sciences alone, and both categories are dwarfed by technical research. Moreover, we identify a relative absence of AI research related to its societal implications such as governance, ethics, or moral implications of the technology. The future of AI scholarship will benefit from both technical and social science examinations of the discipline's risk assessment, governance, and public engagement needs, to foster advances in AI that are sustainable, risk-informed, and societally beneficial.
Trace Element Signatures in Pyrite and Marcasite From Shallow Marine Island Arc-Related Hydrothermal Vents, Calypso Vents, New Zealand, and Paleochori Bay, Greece
Authors: Nestmeyer Mark , Keith Manuel , Haase Karsten M. , Klemd Reiner , Voudouris Panagiotis , Schwarz-Schampera Ulrich , Strauss Harald , Kati Marianna , Magganas Andreas
Published: April 2021

Fluid conditions of shallow marine hydrothermal vent sites (<200 mbsl) in island arcs resemble those of subaerial epithermal systems. This leads to a distinct mineralization-style compared to deeper arc/back-arc (>200 mbsl) and mid-ocean ridge-related environments (>2000 mbsl). At Calypso Vents in the Bay of Plenty and Paleochori Bay at the coast of Milos Island, fluids with temperatures <200°C are emitted through volcaniclastic sediments in water depths <200 mbsl. The hydrothermal mineralization from these fluids is dominated by pyrite and marcasite showing diverse textures, including colloform alternations, semi-massive occurrences surrounding detrital grains, vein-type pyrite, and disseminated fine-grained assemblages. Pyrite and marcasite from Calypso SE show elevated concentrations of volatile elements (e.g., As, Sb, Tl, Hg) implying a vapor-rich fluid phase. By contrast, elements like Zn, Ag, and Pb are enriched in hydrothermal pyrite and marcasite from Calypso SW, indicating a high-Cl liquid-dominated fluid discharge. Hence, vapor-liquid element fractionation induced by fluid boiling is preserved in the seafloor mineralization at Calypso Vents. Hydrothermal mineralization at very shallow vent sites (<10 mbsl), like Paleochori Bay, are affected by wave action causing a seasonal migration of the seawater-fluid interface in the sediment cover. The δ34S composition of native S crusts and crystalline S (0.7–6.7‰) is indicative for host rock leaching and thermochemical reduction of seawater sulphate. By contrast, the highly negative δ34S signature of native S globules in sediments (−7.6 to −9.1‰) is related to microbial sulphate reduction or a subordinate magmatic fluid influx. Alunite-jarosite alteration (Paleochori Bay) and a mineral assemblage consisting of orpiment, realgar, and native S (Calypso Vents) may also suggest a contribution by an oxidised (sulphate-rich) low pH fluid of potential magmatic origin. However, fluid boiling is pervasive at Calypso Vents and Paleochori Bay, and the condensation of vapor-rich fluids in a steam-heated environment may produce a similar alteration and mineralization assemblage without a significant magmatic fluid influx, as known from some subaerial epithermal systems.
Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients
Authors: Fröhlich Eleonore , Wahl Richard
Published: April 2021

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on to describe the main effects of the metabolites and their potential use in medicine. One section addresses thyroid hormone levels in corona virus disease 19 (COVID-19). It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed.
Innate Mechanisms in Selective IgA Deficiency
Authors: Zhang Jingyan , van Oostrom Dèlenn , Li JianXi , Savelkoul Huub F. J.
Published: April 2021

Selective IgA deficiency (SIgAD), characterized by a serum IgA level below 0.07 mg/ml, while displaying normal serum levels of IgM and IgG antibodies, is the most frequently occurring primary immunodeficiency that reveals itself after the first four years after birth. These individuals with SIgAD are for the majority healthy and even when they are identified they are usually not investigated further or followed up. However, recent studies show that newborns and young infants already display clinical manifestations of this condition due to aberrancies in their immune defense. Interestingly, there is a huge heterogeneity in the clinical symptoms of the affected individuals. More than 50% of the affected individuals do not have clinical symptoms, while the individuals that do show clinical symptoms can suffer from mild to severe infections, allergies and autoimmune diseases. However, the reason for this heterogeneity in the manifestation of clinical symptoms of the individuals with SIgAD is unknown. Therefore, this review focusses on the characteristics of innate immune system driving T-cell independent IgA production and providing a mechanism underlying the development of SIgAD. Thereby, we focus on some important genes, including TNFRSF13B (encoding TACI), associated with SIgAD and the involvement of epigenetics, which will cover the methylation degree of TNFRSF13B, and environmental factors, including the gut microbiota, in the development of SIgAD. Currently, no specific treatment for SIgAD exists and novel therapeutic strategies could be developed based on the discussed information.
Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
Authors: Gong Wenping , Liang Yan , Mi Jie , Jia Zaixing , Xue Yong , Wang Jie , Wang Lan , Zhou Yusen , Sun Shihui , Wu Xueqiong
Published: April 2021

Background

Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines.

Methods

In this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT.

Results

Six immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ+ T lymphocytes, CD3+IFN-γ+ T lymphocytes, and the MP3RT-specific IgG antibody.

Conclusions

Taken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3+IFN-γ+ T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.
Bioactive Synthetic Peptides for Oral Tissues Regeneration
Authors: Bermúdez Mercedes , Hoz Lía , Montoya Gonzalo , Nidome Mikado , Pérez-Soria Adriana , Romo Enrique , Soto-Barreras Uriel , Garnica-Palazuelos Julio , Aguilar-Medina Maribel , Ramos-Payán Rosalío , Villegas-Mercado Carlos
Published: April 2021

Regenerative therapy in oral tissues has gained relevance since tissue loss due to congenital or acquired diseases as well as trauma is a major health problem worldwide. Regeneration depends on the natural capacity of the body and the use of biomaterials and bioactive molecules that can module the processes to replace lost or damaged tissues and restore function. The combined use of scaffolds, cells, and bioactive molecules such as peptides is considered the best approach to achieve tissue regeneration. These peptides can induce diverse cellular processes as they can influence cell behavior and also can modify scaffold properties, giving as a result the enhancement of cell adhesion, proliferation, migration, differentiation, and biomineralization that are required given the complex nature of oral tissues. Specifically, synthetic peptides (SP) have a positive influence on scaffold biocompatibility since in many cases they can mimic the function of a natural peptide or a full-length protein. Besides, they are bioactive molecules easy to produce, process, and modify, and they can be prepared under well-defined and controlled conditions. This review aims to compile the most relevant information regarding advances in SP for dental and periodontal tissue regeneration, their biological effects, and their clinical implications. Even though most of the SP are still under investigation, some of them have been studied in vitro and in vivo with promising results that may lead to preclinical studies. Besides there are SP that have shown their efficacy in clinical trials such as P11-4 for enamel regeneration or caries prevention and ABM/P-15 for cementum, periodontal ligament (PDL), and alveolar bone on a previously calculus- and biofilm-contaminated zone. Also, some SP are commercially available such as PTH1-34 and PepGen P-15 which are used for bone defects treatment.
Outcomes of Sepsis and Septic Shock in Cancer Patients: Focus on Lactate
Authors: López René , Pérez-Araos Rodrigo , Baus Fernanda , Moscoso Camila , Salazar Álvaro , Graf Jerónimo , Montes José Miguel , Samtani Suraj
Published: April 2021

The number of oncological patients (OP) admitted to intensive care units (ICU) for sepsis/septic shock has dramatically increased in recent years. The definition of septic shock has been modified, adding hyperlactatemia as a severity biomarker for mortality. However, it remains poorly reported in septic OP. We performed a retrospective analysis from a prospective database of sepsis/septic shock patients admitted to our ICU between September 2017 and September 2019 and followed until day 90. We identified 251 patients and 31.9% had active oncological comorbidity, mainly solid tumor (81.3%). Septic shock criteria were met for 112 (44.6%). Hyperlactatemia was observed in 136 (54.2%) patients and this was associated with a lower survival rate. Overall 90-day mortality was 15.1%. In OP vs. non-OP, hyperlactatemia was more frequent (65% vs. 49.1%, p = 0.013) and associated with lower survival (65.4% vs. 85.7%, p = 0.046). In OP, poor performance status was also associated with lower survival (HR 7.029 [1.998–24.731], p = 0.002) In an adjusted analysis, cancer was associated with lower 90-day survival (HR 2.690 [1.402–5.160], p = 0.003). In conclusion, septic OP remains a high mortality risk group in whom lactate levels and performance status could help with better risk stratification.
How Genetics Might Explain the Unusual Link Between Malaria and COVID-19
Authors: Rusmini Marta , Uva Paolo , Amoroso Antonio , Tolomeo Manlio , Cavalli Andrea
Published: April 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) pandemic has been the subject of a large number of studies in recent times. Here, starting from the evidence that in Italy, the areas with the lowest number of COVID-19 cases were those with the highest incidence of malaria in the early 1900's, we explore possible inverse relationships between malaria and COVID-19. Indeed, some genetic variants, which have been demonstrated to give an advantage against malaria, can also play a role in the incidence and severity of SARS-CoV-2 infections (e.g., the ACE2 receptor). To verify this scientific hypothesis, we here use public data from whole-genome sequencing (WGS) experiments to extrapolate the genetic information of 46 world populations with matched COVID-19 data. In particular, we focus on 47 genes, including ACE2 and genes which have previously been reported to play a role in malaria. Only common variants (>5%) in at least 30% of the selected populations were considered, and, for this subset, we correlate the intra-population allele frequency with the COVID-19 data (cases/million inhabitants), eventually pinpointing meaningful variants in 6 genes. This study allows us to distinguish between positive and negative correlations, i.e., variants whose frequency significantly increases with increasing or decreasing COVID-19 cases. Finally, we discuss the possible molecular mechanisms associated with these variants and advance potential therapeutic options, which may help fight and/or prevent COVID-19.
Incidental Unruptured Intracranial Aneurysms Do Not Impact Outcome in Patients With Acute Cerebral Infarction
Authors: Wu Xuan , Duan Zuowei , Liu Yihui , Zhou Changwu , Jiao Zhiyun , Zhao Yi , Tang Tieyu
Published: April 2021

Background: This study was to examine the patients with acute cerebral infarction (ACI) treated at a single center over 9 years and who underwent Unruptured intracranial aneurysm (UIA) screening by three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA), and to explore the factors associated with outcomes.

Methods: The outcome was the modified Rankin scale (mRS) score at 90 days after stroke onset. The outcome was classified into a good outcome (mRS score of 0–2 points) and poor outcome (mRS score of 3–6 points).

Results: UIAs were found in 260 (6.5%) of 4,033 patients with ACI; 2,543 (63.1%) had a good outcome, and 1,490 (36.9%) had a poor outcome. There was no difference in outcomes between the two groups (P = 0.785). The multivariable analysis showed that age (OR = 1.009, 95%CI: 1.003–1.014, P = 0.003), diabetes (OR = 1.179, 95%CI: 1.035–1.342, P = 0.013), ischemic stroke history (OR = 1.451, 95%CI: 1.256–1.677, P < 0.001), and baseline NIHSS score (OR = 1.034, 95%CI: 1.018–1.050, P < 0.001) were independently associated with the 90-day outcomes in patients with ACI. The presence of incidental UIA was not associated with outcomes after ACI.

Conclusions: Age, diabetes, ischemic stroke history, and baseline NIHSS score were independently associated with the early outcomes of patients with ACI.
Safety and Tolerability of Burst-Cycling Deep Brain Stimulation for Freezing of Gait in Parkinson’s Disease
Authors: Wong Joshua K. , Hu Wei , Barmore Ryan , Lopes Janine , Moore Kathryn , Legacy Joseph , Tahafchi Parisa , Jackson Zachary , Judy Jack W. , Raike Robert S. , Wang Anson , Tsuboi Takashi , Okun Michael S. , Almeida Leonardo
Published: April 2021

Background: Freezing of gait (FOG) is a common symptom in Parkinson’s disease (PD) and can be difficult to treat with dopaminergic medications or with deep brain stimulation (DBS). Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation (BCDBS) delivers current in various frequencies of bursts (e.g., 4, 10, or 15 Hz), while maintaining an intra-burst frequency identical to conventional DBS.

Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG.

Methods: Ten PD subjects with STN or GPi DBS and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state.

Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS.

Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy.
Is COVID-19 Keeping us Up at Night? Stress, Anxiety, and Sleep Among Adult Twins
Authors: Tsang Siny , Avery Ally R. , Seto Edmund Y. W. , Duncan Glen E.
Published: April 2021

In response to the COVID-19 pandemic, a variety of social distancing measures to mitigate the virus outbreak have been implemented. These measures may have unintended consequences on individuals’ well-being, such as increased stress, anxiety, and sleep disruptions. We investigated the extent to which individuals’ mental health status is associated with perceived changes in sleep amount and sleep quality among a sample of adult twin pairs (N= 909 pairs; 77% MZ, 23% DZ), less than a month after the outbreak was declared a pandemic by the World Health Organization. About half of participants reported no change in sleep amount (50.1%) or sleep quality (55.6%). Approximately one-third of the participants had increased amount of sleep (29.8%), and 32.9% reported a decrease in sleep quality. We found that stress and anxiety levels were associated with sleep reduction (ORs = 2.36 and 3.12 for stress and anxiety, respectively) and poorer sleep quality (ORs = 2.45 and 3.73 for stress and anxiety, respectively), even after taking into account between-family confounds. A much smaller association was observed between levels of stress and anxiety and increased sleep amount (ORs = 1.42 and 1.60 for stress and anxiety, respectively) and sleep quality (OR = 1.21 and 1.29 for stress and anxiety, respectively), which was no longer significant after controlling for between-family confounds. Our results demonstrate that stress and anxiety associated with the COVID-19 pandemic and social distancing measures may be linked to reduced sleep amount and quality.
Gene4PD: A Comprehensive Genetic Database of Parkinson’s Disease
Authors: Li Bin , Zhao Guihu , Zhou Qiao , Xie Yali , Wang Zheng , Fang Zhenghuan , Lu Bin , Qin Lixia , Zhao Yuwen , Zhang Rui , Jiang Li , Pan Hongxu , He Yan , Wang Xiaomeng , Luo Tengfei , Zhang Yi , Wang Yijing , Chen Qian , Liu Zhenhua , Guo Jifeng , Tang Beisha , Li Jinchen
Published: April 2021

Parkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD. In conclusion, Gene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.
The Role of Adjuvant Chemotherapy in Metaplastic Breast Carcinoma: A Competing Risk Analysis of the SEER Database
Authors: Lan Tian , Lu Yunyan , Zheng Ruzhen , Shao Xiying , Luo Hua , He Junling , Yang Huifen , Xu Haibin , Wang Xiaojia , Hu Zujian
Published: April 2021

Purpose: Chemotherapy is the clinically recommended treatment for patients with operable metaplastic breast carcinoma (MBC); however, its impact remains controversial. This study investigated the possible role of chemotherapy in the treatment of MBC.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify the operable MBC patients. The competing risk analysis along with the propensity score matching (PSM) method was performed to evaluate the effect of chemotherapy. Moreover, a competing risk nomogram was built to identify prognosis in patients with MBC.

Results: Of the 1137 patients with MBC, 775 received chemotherapy and 362 did not receive chemotherapy. The 5-year cumulative incidence of breast cancer-specific death (BCSD) showed similar outcomes in both the Chemo and No-Chemo groups (21.1 vs. 24.3%, p = 0.57). Chemotherapy showed no apparent association with BCSD (HR, 1.07; 95% CI, 0.72–1.60; p = 0.72), even after subgroup analysis or PSM. Race, tumor size, lymph node status, and radiation were identified as the significant factors for MBC after a penalized variable selection process. In addition, a competing risk nomogram showed relatively good accuracy of prediction with a C-index of 0.766 (95% CI, 0.700–0.824).

Conclusion: Our findings demonstrated that chemotherapy did not improve BCSD for operable MBC patients. Thus, it may indicate the need to reduce exposure to the current chemotherapy strategies for patients with resectable MBC. Additionally, some novel treatment strategies are required urgently to identify and target the potential biomarkers.
Case Report: Bilateral Renal Cell Carcinoma With Different Histological and Morphological Features, Clear Cell and Cystic Thyroid-Like Follicular Subtype
Authors: Ni Jinsong , Cui Ni , Wang Yanfang , Liu Jixuan
Published: April 2021

Thyroid-like follicular renal cell carcinoma is a rare subtype of renal cell carcinoma that has only been recently recognized, as most cases involve a solid tumor in one kidney. In this study, we report a rare case of bilateral renal cell carcinoma wherein the tumor in the left kidney was diagnosed as clear cell carcinoma, while the tumor in right kidney as thyroid-like follicular renal cell carcinoma. The difference between this case and the ones described in previous reports is that thyroid-like follicular renal cell carcinoma showed cystic changes on imaging. This suggests that when renal cystic lesions are encountered, we should consider the possibility of such rare tumors.
Stress Hyperglycemia in Children and Adolescents as a Prognostic Indicator for the Development of Type 1 Diabetes Mellitus
Authors: Argyropoulos Theodoros , Korakas Emmanouil , Gikas Aristofanis , Kountouri Aikaterini , Kostaridou-Nikolopoulou Stavroula , Raptis Athanasios , Lambadiari Vaia
Published: April 2021

Hyperglycemia is a common manifestation in the course of severe disease and is the result of acute metabolic and hormonal changes associated with various factors such as trauma, stress, surgery, or infection. Numerous studies demonstrate the association of adverse clinical events with stress hyperglycemia. This article briefly describes the pathophysiological mechanisms which lead to hyperglycemia under stressful circumstances particularly in the pediatric and adolescent population. The importance of prevention of hyperglycemia, especially for children, is emphasized and the existing models for the prediction of diabetes are presented. The available studies on the association between stress hyperglycemia and progress to type 1 diabetes mellitus are presented, implying a possible role for stress hyperglycemia as part of a broader prognostic model for the prediction and prevention of overt disease in susceptible patients.
Intrauterine Hypoxia Changed the Colonization of the Gut Microbiota in Newborn Rats
Authors: Sun Yan , Li Lei , Song Jiayu , Mao Wei , Xiao Kaihao , Jiang Chunming
Published: April 2021

Background: Accumulating evidence suggests a connection between the gut microbiota and neonatal diseases. Hypoxia may play an important role in the intestinal lesions in neonates.

Objective: This study aims to determine whether the gut microbiota differs between intrauterine hypoxic rats and healthy controls and to identify the factors that influence the changes in the gut microbiota.

Methods: We constructed an intrauterine hypoxia model in rats and collected the intestinal contents of intrauterine hypoxic newborn rats and normal newborn rats within 4 h and on the seventh day after birth. They were divided them into the intrauterine hypoxia first-day group (INH1), intrauterine hypoxia seventh-day group (INH7), normal first-day group (NOR1), and normal seventh-day group (NOR7). The contents of the intestines were sequenced with 16S rRNA sequencing, the sequencing results were analyzed for biological information, and the differences in the diversity, richness, and individual taxa among the groups were analyzed.

Results: The abundance of the gut microbiota of neonatal rats with intrauterine hypoxia was higher than that of the control group rats. Intrauterine hypoxia altered the structural composition of the gut microbiota in neonatal rats. The INH1 group showed increased species richness, phylogenetic diversity, and β-diversity, and altered relative abundance in several taxa compared to those in the control group. The differences in the microbiota among the four groups were significantly higher than those within the group, and the differences in the abundance and diversity of the INH7 and NOR7 groups decreased after 7 days of suckling. Functional analysis based on the Cluster of Orthologous Groups (COG) suggested that 23 functional COG categories. There was no significant difference in the functional categories between the hypoxia group and the normal group.

Conclusion: Intrauterine hypoxia changed the initial colonization of the gut microbiota in neonatal rats. It could increase the species richness and β-diversity of the gut microbiota, and altered relative abundances of several taxa.
Lack of Awareness of the Impact of Improperly Disposed Of Medications and Associated Factors: A Cross-Sectional Survey in Indonesian Households
Authors: Alfian Sofa D. , Insani Widya N. , Halimah Eli , Qonita Nabilla A. , Jannah Siti S. , Nuraliyah Nisa M. , Supadmi Woro , Gatera Vesara A. , Abdulah Rizky
Published: April 2021

Introduction: Disposal of unused medications through environmentally unsafe routes is common in Indonesia. The lack of awareness of the impact of improperly disposed of medications is a significant contributing factor. The objectives of this study were to identify factors associated with lack of awareness of the impact of improperly disposed of unused medications and to assess the associations of awareness with medication disposal practices among the general population in Indonesia.

Patients and methods: An observational cross-sectional survey was conducted using nonprobability sampling in Bandung, Indonesia, from November 2017 to January 2018 among respondents who were older than 18 years, had used any medication in the past, were literate, and had signed an informed consent document. Disposal practices and awareness regarding the impact of improperly disposed of unused medications were collected using an online- and a paper-based pre-validated questionnaire. The paper-based questionnaires were distributed to respondents in public places such as city center, markets, and religious places. Binary logistic regression was performed to assess associations of sociodemographic and other related factors with a lack of awareness. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported.

Results: Of 497 participating respondents, 433 and 64 respondents filled an online- or a paper-based questionnaire, respectively. Most respondents were female, aged between 18 and 30 years, and students/university students. Of 497 respondents, more than half (53.1%) were not aware that improper medication disposal could harm the environment and population health. Most respondents (79.5%) had never received information about proper medication disposal practices. The education level, the number of stored medications at home, and previous education about medication disposal practices were significantly associated with awareness of proper practices. In the multivariate analysis, only those with previous education about medication disposal practices were less likely to report a lack of awareness (OR: 0.043; 95% CI: 0.02–0.09). Respondents with a lack of awareness tended to dispose of their unused medications in the garbage or shared them with friends or relatives.

Conclusion: There is a clear need to increase awareness of the importance of proper medication disposal practices, in particular among the student population of Bandung city, Indonesia. Healthcare providers can play an important role by educating this specific population on the proper disposal of unused medications.
Caspase-11-Gasdermin D-Mediated Pyroptosis Is Involved in the Pathogenesis of Atherosclerosis
Authors: Jiang Mengqing , Sun Xuejing , Liu Suzhen , Tang Yan , Shi Yunming , Bai Yuanyuan , Wang Yujie , Yang Qiong , Yang Qize , Jiang Weihong , Yuan Hong , Jiang Qixia , Cai Jingjing
Published: April 2021

Background: Pyroptosis is a form of cell death triggered by proinflammatory signals. Recent studies have reported that oxidized phospholipids function as caspase-11 agonists to induce noncanonical inflammasome activation in immune cells. As the levels of oxidized phospholipids derived from ox-LDL are largely elevated in atherosclerotic lesions, this study sought to determine whether oxidized lipids trigger pyroptosis and subsequent inflammation in the pathogenesis of atherosclerosis.

Methods and Results: In our current study, after integrating transcriptomic data available from the Gene Expression Omnibus with data from hyperlipidemic mice and ox-LDL-treated peritoneal macrophages, we discovered that caspase-4/11-gasdermin D-associated inflammatory signaling was significantly activated. Consistently, the mRNA expression of caspase-4 and gasdermin D was upregulated in peripheral blood mononuclear cells from patients with coronary heart disease. In particular, the expression of caspase-4 was closely associated with the severity of lesions in the coronary arteries. An in vivo study showed that caspase-11-gasdermin D activation occurred in response to a high-fat/high-cholesterol (HFHC) diet in ApoE−/− mice, while caspase-11 deletion largely attenuated the volume and macrophage infiltration of atherosclerotic lesions. An in vitro mechanistic study showed that caspase-11-mediated inflammation occurred partly via gasdermin D-mediated pyroptosis in macrophages. Suppressing gasdermin D in HFHC-fed ApoE−/− mice via delivery of an adeno-associated virus markedly decreased lesion volume and infiltrating macrophage numbers.

Conclusion: Caspase-11-gasdermin D-mediated pyroptosis and the subsequent proinflammatory response in macrophages are involved in the pathogenesis of atherosclerosis. Therefore, targeting the caspase 11-gasdermin D may serve as an alternative strategy for the treatment of atherosclerosis.
Automated Close-Loop System for Three-Dimensional Characterization of Spatiotemporal Optical Vortex
Authors: Chen Jian , Lu Keyin , Cao Qian , Wan Chenhao , Hu Haifeng , Zhan Qiwen
Published: April 2021

Recent rapid advances in spatiotemporal optical pulses demand accurate characterization of the spatiotemporal structure of the produced light fields. We report an automated close-loop characterization system that is capable of reconstructing the three-dimensional intensity and phase structures of spatiotemporal wavepacket illustrated by characterizing spatiotemporal optical vortex in the spatiotemporal domain. The characterization technique is based on interfering a much shorter probe pulse with different slices of the object wavepacket along the temporal axis. A close-loop control program is developed to realize full automation of the data collection and reconstruction process. Experimental results of the intensity and phase distributions show that the designed close-loop system is efficient in quantitatively characterizing the generated spatiotemporal optical vortex. Such a linear characterization system can also be extended to measure many other kinds of spatiotemporal wavepacket and may find broad applications in spatiotemporal wavepacket studies.
Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model
Authors: van Weperen Valerie Y. H. , Dunnink Albert , Bossu Alexandre , Beekman Jet D. M. , Meijborg Veronique M. F. , de Bakker Jacques M. T. , Coronel Ruben , Varkevisser Rosanne , van der Heyden Marcel A. G. , Vos Marc A.
Published: April 2021

Introduction

Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.

Methods

Dofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.

Results

IVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p < 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p < 0.05 vs. high and middle rate).

Conclusion

In CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.
Development and Psychometric Properties of the Test of Passive Aggression
Authors: Schanz Christian G. , Equit Monika , Schäfer Sarah K. , Käfer Michael , Mattheus Hannah K. , Michael Tanja
Published: April 2021

Background:To date, most research on aggression in mental disorders focused on active-aggressive behavior and found self-directed and other-directed active aggression to be a symptom and risk-factor of psychopathology. On the other hand, passive-aggressive behavior has been investigated less frequently and only in research on psychodynamic defense mechanisms, personality disorders, and dysfunctional self-control processes. This small number of studies primarily reflects a lack of a reliable and valid clinical assessment of passive-aggressive behavior. To address this gap, we developed the Test of Passive Aggression (TPA), a 24-item self-rating scale for the assessment of self-directed and other-directed passive-aggressive behavior.

Method:Study 1 examined the internal consistency and factorial validity of the TPA in an inpatient sample (N= 307). Study 2 investigated the retest-reliability, internal consistency, and construct validity (active aggression, personality traits, impulsivity) of the TPA in a student sample (N= 180).

Results:In line with our hypothesis, Exploratory Structural Equation Modeling revealed an acceptable to good fit of a bi-factorial structure of the TPA (Chi-square-df-ratio= 1.98;RMSR= 0.05, fit.off = 0.96). Both TPA scales showed good to excellent internal consistency (α= 0.83–0.90) and 4-week retest-reliability (rtt= 0.86). Correlations with well-established aggression scales, measures of personality, and impulsivity support discriminant and convergent validity of the TPA.

Conclusions:The TPA is a reliable and valid instrument for the assessment of self-directed and other-directed passive-aggressive behavior.
How the Immune System Deploys Creativity: Why We Can Learn From Astronauts and Cosmonauts
Authors: de Vries Henderika , Khoury-Hanold William
Published: April 2021

In this interdisciplinary article, we investigate the relationship between creativity and the immune system; the creative features of the immune system and how the immune system and its role in regulating homeostasis might be related to creative cognition. We argue that within a multivariate approach of creativity, the immune system is a contributing factor. New directions for research are also discussed. When astronauts and cosmonauts venture into the new and extreme environment of outer space, their immune system needs to instantly adapt and find new answers to survive biologically and psychologically. Many astronauts report interest in creative activities and therefore represent an interesting group to investigate creativity in relation with the immune system. Little is known regarding (1) how the immune system interacts with and supports creative cognition and behavior, (2) if an individual’s immune system, interacting with cognition, adapts more originally to a new environment compared to another’s; in other words, if there is creativity in the domain of the immune system, and (3) the creative properties and functions of the immune system itself.
The Association Between Relationship Events and Experiences and Partner Evaluations: An Ideal Standards Perspective
Authors: Chesterman Susan , Karantzas Gery C. , Marshall Emma M.
Published: April 2021

Drawing on the Ideal Standards Model, the current study investigated whether the relationship events and experiences that occur on a given day in romantic relationships were associated with partner evaluations. Individuals in a current romantic relationship (N = 104) completed daily measures of positive and negative relationship events and experiences and partner evaluations for seven consecutive days. As hypothesized, findings demonstrated that on a given day negative relationship events and experiences were associated with evaluating partners as falling short of mate ideals, while positive relationship events and experiences were associated with evaluating partners as more closely meeting ideals. The findings demonstrate the importance of the relational context in evaluations of a partner against ideal standards.
BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson’s Disease
Authors: Cochen De Cock Valérie , Dotov Dobromir , Damm Loic , Lacombe Sandy , Ihalainen Petra , Picot Marie Christine , Galtier Florence , Lebrun Cindy , Giordano Aurélie , Driss Valérie , Geny Christian , Garzo Ainara , Hernandez Erik , Van Dyck Edith , Leman Marc , Villing Rudi , Bardy Benoit G. , Dalla Bella Simone
Published: April 2021

Taking regular walks when living with Parkinson’s disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients’ gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients’ gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered “easy to use” by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases “walk for exercise” duration thanks to high observance.

Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02647242.