bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia
Authors: Shinjyo Noriko , Kita Kiyoshi
Published: November 2021

Metabolic syndromes are frequently associated with dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and cognitive impairment. In addition, growing evidence suggests the link between infections and brain disorders, including Alzheimer’s disease. The immune system and energy metabolism are in an intricate relationship. Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced CNS infection susceptibility. Thus, infection and metabolic imbalance can be intertwined to each other in the etiology of brain disorders, including dementia. Insulin and leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and obesity, which are characterized by insulin resistance and leptin signaling deficiency. Examples include human immunodeficiency virus (HIV) infection and periodontal disease caused by an oral pathogenPorphyromonas gingivalis. This review explores potential interactions between infectious agents and insulin and leptin signaling pathways, and discuss possible mechanisms underlying the relationship between infection, metabolic dysregulation, and brain disorders, particularly focusing on the roles of insulin and leptin.
Novel Toolboxes for the Investigation of Activity-Dependent Myelination in the Central Nervous System
Authors: Heflin Jack Kent , Sun Wenjing
Published: November 2021

Myelination is essential for signal processing within neural networks. Emerging data suggest that neuronal activity positively instructs myelin development and myelin adaptation during adulthood. However, the underlying mechanisms controlling activity-dependent myelination have not been fully elucidated. Myelination is a multi-step process that involves the proliferation and differentiation of oligodendrocyte precursor cells followed by the initial contact and ensheathment of axons by mature oligodendrocytes. Conventional end-point studies rarely capture the dynamic interaction between neurons and oligodendrocyte lineage cells spanning such a long temporal window. Given that such interactions and downstream signaling cascades are likely to occur within fine cellular processes of oligodendrocytes and their precursor cells, overcoming spatial resolution limitations represents another technical hurdle in the field. In this mini-review, we discuss how advanced genetic, cutting-edge imaging, and electrophysiological approaches enable us to investigate neuron-oligodendrocyte lineage cell interaction and myelination with both temporal and spatial precision.
Relationship Between PTEN and Angiogenesis of Esophageal Squamous Cell Carcinoma and the Underlying Mechanism
Authors: Yang Chenbo , Chen Chao , Xiao Qiankun , Wang Xiaoqian , Shou Yuwei , Tian Xiangyu , Wang Shuaiyuan , Li Hui , Liang Yinghao , Shu Jiao , Chen Kuisheng , Sun Miaomiao
Published: November 2021

Esophageal squamous cell carcinoma (ESCC) has high morbidity and mortality rates owing to its ability to infiltrate and metastasize. Microvessels formed in early-stage ESCC promote metastasis. Phosphatase and tensin homolog (PTEN) mediates macrophage polarization, but its effect and mechanism on early ESCC angiogenesis are unclear. To explore the molecular mechanism underlying early ESCC metastasis through blood vessels, we investigated the relationship between PTEN/phosphoinositide 3-kinase (PI3K)/p-AKT protein levels, number of infiltrated macrophages, and angiogenesis in ESCC and ESCC-adjacent normal esophageal mucosa tissues from 49 patients. Additionally, PTEN was overexpressed or silenced in the esophageal cancer cell line EC9706, and its supernatant served as conditioning medium for M1 tumor-associated macrophages (TAMs). The culture medium of macrophages served as conditioning medium for esophageal tumor-associated vascular endothelial cells (TECs) to study the biological behavior of PTEN-plasmid, PTEN-siRNA, and control TECs. We found that M1 TAM infiltration in ESCC tissues was low, whereas M2 TAM infiltration was high. Microvessel density was large, PTEN was down-regulated, and the PI3K/AKT pathway was activated in ESCC specimens. These parameters significantly related to the depth of tumor invasion, lymph node metastasis, and pathological staging of ESCC. Silencing of PTEN in EC9706 cells significantly activated the PI3K/AKT signaling pathway in macrophages, promoting M1-to-M2 TAM polarization and enhancing TECs’ ability to proliferate, migrate, invade, form tubes, and secrete vascular endothelial growth factor. We believe that PTEN silencing in esophageal cancer cells activates the PI3K/AKT signaling pathway in macrophages via the tumor microenvironment, induces M2 TAM polarization, and enhances the malignant behavior of TECs, thereby promoting ESCC angiogenesis. Our findings lay an empirical foundation for the development of novel diagnostic and therapeutic strategies for ESCC.
Case Report: Reactive Lymphohistiocytic Proliferation in Infant With a Novel Nonsense Variant of IL2RG Who Received BCG Vaccine
Authors: Yahya Amal M. , Al-Hammadi Suleiman , AlHashaykeh Nidal O. , Alkaabi Salwa S. , Elomami Abdulghani S. , AlMulla Asia A. , Alremeithi Majed M. , Kabbary Rewan M. , Vijayan Ranjit , Souid Abdul-Kader
Published: November 2021

We present here a male young infant with X-linked severe combined immunodeficiency (MIM#300400) due to the novel nonsense variant of IL2RG (interleukin 2 receptor, gamma; MIM#308380), NM_000206.2(IL2RG):c.820_823dup p.Ser275Asnfs*29. He developed aggressive reactive lymphohistiocytic proliferation after receiving the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine at birth. This report advocates for modifying the current practice of early use of BCG. The natural history of his disease also suggests considering IL2RG variants as a potential cause of “X-linked recessive Mendelian susceptibility to mycobacterial disease” (MSMD). His reactive lymphohistiocytic proliferation and massive hepatosplenomegaly simulated hemophagocytic lymphohistiocytosis (HLH, likely triggered by the BCG disease). This entity was masked by the absence of fever and markedly elevated inflammatory biomarkers. Thus, his findings stimulate discussion on the need to modify the diagnostic criteria of HLH, in order to accommodate conditions, such IL2RG variants that block systemic inflammation.
Long-Term Outcomes and Prognosticators of Pediatric Primary Dilated Cardiomyopathy in an Asian Cohort
Authors: Wang Po-Yuan , Tseng Wei-Chieh , Fu Chun-Min , Wu Mei-Hwan , Wang Jou-Kou , Chen Yih-Sharng , Chou Nai-Kuan , Wang Shoei-Shen , Chiu Shuenn-Nan , Lin Ming-Tai , Lu Chun-Wei , Chen Chun-An
Published: November 2021

Background: Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy. The epidemiological profiles and prognosticators of clinical outcomes in Asian populations are not well elucidated.

Methods: Data of 104 children aged <18 years with a diagnosis of primary DCM from January 1990 to December 2019 in our institutional database were retrospectively investigated. Relevant demographic, echocardiographic, and clinical variables were recorded for analysis. A P <0.05 was considered statistically significant.

Results: The median age at diagnosis was 1.4 years (interquartile range = 0.3–9.1 years), and 52.9% were males. During a median follow-up duration of 4.8 years, 48 patients (46.2%) were placed on the transplantation waitlist, and 52.1% of them eventually received heart transplants. An exceptionally high overall waitlist mortality rate was noted (27.1%), which was even higher (43.5%) if the diagnostic age was <3 years. The 1-, 5-, and 10-year transplant-free were 61.1, 48.0, and 42.8%. Age at diagnosis >3 years and severe mitral regurgitation at initial diagnosis were independent risk factors for death or transplantation (hazard ratios = 2.93 and 3.31, respectively; for both, P <0.001). In total, 11 patients (10.6%) experienced ventricular function recovery after a median follow-up of 2.5 (interquartile range = 1.65–5) years. Younger age at diagnosis was associated a higher probability of ventricular function recovery.

Conclusions: Despite donor shortage for heart transplantation and subsequently high waitlist mortality, our data from an Asian cohort indicated that transplant-free long-term survival was comparable with that noted in reports from Western populations. Although younger patients had exceptionally higher waitlist mortality, lower diagnostic age was associated with better long-term survival and higher likelihood of ventricular function recovery.
Systematic Survey of the Alteration of the Faecal Microbiota in Rats With Gastrointestinal Disorder and Modulation by Multicomponent Drugs
Authors: Wu Yue , Wu Yang , Wu Hongwei , Wu Changxun , Ji Enhui , Xu Jing , Zhang Yi , Wei Junying , Zhao Yi , Yang Hongjun
Published: November 2021

Gastrointestinal disorder (GID) is a global health disease which leads to heavy public medical burden. Disorders in the intestinal flora have been found in gastrointestinal disorder patients. However, the interaction between GID and the intestinal flora in faecal has not been studied comprehensively. In addition, multicomponent drugs represented by traditional Chinese medicine (TCM) are widely used for treating GID, but their modulation of the intestinal flora has not been investigated. Therefore, in this study, a high-throughput sequencing strategy was used to investigate alterations in the intestinal flora in a rat GID model, followed by an investigation of the modulation by a representative TCM, Xiaoerfupi (XEFP) granule. The results showed that in rats with GID, the relative abundances of Erysipelotrichaceae, Lachnospiraceae, Streptococcaceae increased and that of Ruminococcaceae decreased. At the macro level, the levels of LysoPC(16:0), LysoPC(20:2), LysoPC(15:0), LysoPC(20:2 (11Z, 14Z)), LysoPC(20:1), LysoPC(15:0), LysoPC(20:0) and LysoPE (0:0/20:0) in serum increased and levels of PC(36:4), PC(38:4), PC(o-36;4), PE (MonoMe(13,5)/MonoMe(11,5)) decreased. The imbalance of metabolites was restored by XEFP through ether lipid metabolism pathway. Increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio of the GID rats was restored by XEFP as well. Moreover, XEFP can relief the symptoms of GID rats by increasing bacteria Ruminococcaceae and decreasing Streptococcaceae, Erysipelotrichaceae and Lachnospiraceae in faecal microbiota level. This study represents a comprehensive survey of the interaction between GID and the intestinal flora and a systematic evaluation of modulation by a multicomponent drug.
Augmented Renal Clearance: What Have We Known and What Will We Do?
Authors: Luo Yifan , Wang Yidan , Ma Yue , Wang Puxiu , Zhong Jian , Chu Yang
Published: November 2021

Augmented renal clearance (ARC) is a phenomenon of increased renal function in patients with risk factors. Sub-therapeutic drug concentrations and antibacterial exposure in ARC patients are the main reasons for clinical treatment failure. Decades of increased research have focused on these phenomena, but there are still some existing disputes and unresolved issues. This article reviews information on some important aspects of what we have known and provides suggestion on what we will do regarding ARC. In this article, we review the current research progress and its limitations, including clinical identification, special patients, risk factors, metabolism, animal models and clinical treatments, and provide some promising directions for further research in this area.
Parental Punishment and Adolescents’ Loneliness: A Moderated Mediation Model of General Self-Concept and Teacher–Student Relationships
Authors: Luo Yun , Wu Anyi , Zhang Hui
Published: November 2021

Background: Loneliness adversely affects physical and mental health; therefore, it is necessary to explore its related influencing factors and mechanisms. This study investigated the mediating role of general self-concept in the association between parental punishment (PP) and adolescent loneliness and as well as the moderating role of teacher–student relationships (TSR) in Chinese students.

Methods: Data were obtained from 1,169 Chinese students (10–18years old) using several self-report questionnaires: the Egna Minnen av Barndoms Uppfostran (EMBU), Self-Description Questionnaire (SDQ), Teacher–Student Relationships Scale (TSR), and UCLA Loneliness Scale. Data were analyzed with IBM SPSS 22.0, and the PROCESS macro program.

Results: (1) Parental punishment had a positive predictive effect on adolescent loneliness, (2) parental punishment predicted adolescent loneliness not only directly but also indirectly through the mediating effect of general self-concept, and (3) teacher–student relationships moderated the influence of PP on adolescent loneliness.

Conclusion: Adolescent loneliness is less affected by parental punishment when TSRs are better. Additionally, when adolescents are punished less by their parents and have good teacher–student relationships, they have higher general self-concepts.

Limitations: This study’s cross-sectional research design was unable to show causal relationships among the factors influencing adolescent loneliness.
Relationships Between Achievement Goal Orientations, Learning Engagement, and Academic Adjustment in Freshmen: Variable-Centered and Person-Centered Approaches
Authors: Wang Haiying , Xu Mingxue , Xie Xiaochun , Dong Yuan , Wang Weichen
Published: November 2021

Academic adjustment is a principal determining factor of undergraduate students’ academic achievement and success. However, studies pay little attention to freshmen’s antecedent variables of academic adjustment. This study aimed to examine the mechanisms underlying the relationship between achievement goal orientations and academic adjustment in freshmen using variable- and person-centered approaches. A sample of 578 freshmen (aged 18.29±1.04years, 58.5% female) completed questionnaires on achievement goal orientations, learning engagement, and academic adjustment. Latent profile analysis of achievement goal orientations revealed four groups: low-motivation (11.1%), approach-oriented (9.5%), average (52.8%), and multiple (26.6%). In the mediating analysis, results of the variable-centered approach showed that learning engagement mediated the effects of the mastery-approach and performance-avoidance goals on academic adjustment. For the person-centered approach, we selected the average type as the reference profile, and the analysis revealed that compared with the reference profile, learning engagement partially mediated the link between the approach-oriented profile and academic adjustment. The current study highlights the important role that achievement goal orientations and learning engagement play in academic adjustment. We discuss the implications and limitations of the findings.
Prevalence of Dementia in China in 2015: A Nationwide Community-Based Study
Authors: Qi Shige , Yin Peng , Zhang Han , Zhang Qingjun , Xiao Yize , Deng Ying , Dong Zhong , Shi Yan , Meng Jun , Peng Dantao , Wang Zhihui
Published: November 2021

Objective: This study aims to estimate the prevalence of dementia and Alzheimer's disease (AD) and associated risk factors among the general Chinese population.

Methods: We carried out a nationwide study including 24,117 participants aged 60 years and older in China using a multistage clustered sampling. Dementia and AD were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association. Face-to-face interviews were administered by the trained interviewers to obtain information on demographics, lifestyle factors, and previous diseases.

Results: The overall weighted prevalence of dementia was 4.22% (95%CI 2.27–6.17%) for people aged 60 years and older, was higher in women than in men and increased with age. Daily tea drinking and daily exercises were the protective factors for both dementia and AD. Engaging in social and intellectual activities was significantly associated with a lower risk of dementia and AD.

Conclusions: A large number of population with dementia posed a significant challenge to China where the population is rapidly aging. The increase of public awareness, building more care facilities, and training dementia specialists and professional caregivers are all urgently needed and should be the future priorities of dementia care in China.
An Update on the Lived Experience of Dry Mouth in Sjögren's Syndrome Patients
Authors: Ngo Di Ying Joanna , Thomson William Murray
Published: November 2021

This paper aims to provide an update on research findings on the lived experience of dry mouth in Sjögren's Syndrome (SS) patients. Dry mouth is a significant condition that impacts on the daily lives of people with SS. There will first be a summary of the definition, etiology, and manifestation of dry mouth in SS patients. There will next be an overview of the measurement of the impact of dry mouth on the quality of life in SS patients. This will include a deliberation of both quantitative and qualitative methods. Lastly, there will be discussion on the consequences of dry mouth, with a focus on qualitative studies that seek to understand patients' physical, emotional, and social domains of life.
An Evaluation of Current Preventative Measures Used in Equine Practice to Maintain Distal Forelimb Functionality: A Mini Review
Authors: Clarke Emily J. , Gillen Alex , Turlo Agnieszka , Peffers Mandy J.
Published: November 2021

Horses are used in a variety of equestrian disciplines predisposing them to musculoskeletal injury or disease including osteoarthritis and tendinopathy. As a result, a number of preventative measures are used within equine medicine and husbandry, ranging from therapeutic shoeing to the use of nutraceuticals. Despite their popularity and routine use evidence base and clinical outcomes are variable, bringing into question the efficacy of these prophylactic measures. In recent years a small number of studies have been performed examining the effect of specific strategies in order to quantify the preventative and protective claims such modalities have on joint and forelimb health. Few have robustly demonstrated a capacity to protect the limb by reducing inflammation, or promoting regenerative pathways. This review focusses on performance horses specifically, and the resounding theme that emerges in current research is the need for longitudinal studies to inform scientific conclusions surrounding single and multi-modal use. Furthermore, there is a requirement to prioritise evidence-based medicine to inform optimal clinical practice.
Addressing Patients’ Alcohol Consumption–A Population-Based Survey of Patient Experiences
Authors: Lid Torgeir Gilje , Karlsson Nadine , Thomas Kristin , Skagerström Janna , O'Donnell Amy , Abidi Latifa , Nilsen Per
Published: November 2021

Objectives: To identify the proportion of the population that had experienced that alcohol was addressed in health care the previous year, to explore experiences and perceived effects of addressing alcohol, and to investigate the proportion of risky drinkers in the population.

Methods: Cross-sectional national web-based survey with 1,208 participants. Socio-demographic data, alcohol consumption (AUDIT-C), and experiences with alcohol conversations were investigated.

Results: Approximately four in five respondents had visited health care the past 12 months, and one in six reported having experienced addressing alcohol. Women and older respondents were less likely to report having experienced alcohol conversations compared to other groups. Risky drinkers were not more likely to have experienced an alcohol conversation, but reported longer duration of alcohol conversations and more frequently perceived addressing alcohol as awkward or judgmental. Almost a third of respondents were classified as risky drinkers.

Conclusion: The proportion experiencing addressing alcohol in routine health care is low, also among risky drinkers, and risky drinkers more frequently experienced the conversations as judgmental. More sensitive and relevant ways of addressing alcohol in health care is needed.
β-Cyclodextrin-Calcium Complex Intercalated Hydrotalcites as Efficient Catalyst for Transesterification of Glycerol
Authors: Liu Guanhao , Yang Jingyi , Xu Xinru
Published: November 2021

β-cyclodextrin derivative intercalated MgAl-hydrotalcites (β-CD-Ca/LDH) was synthesized to convert glycerol into high value-added glycerol carbonate(GC) by transesterification of dimethyl carbonate (DMC) and glycerol in this paper. β-cyclodextrin-metal complexes and β-CD-Ca/LDH was characterized by XRD, FT-IR, SEM, XPS and nitrogen adsorption-desorption. The enrichment of organic reactants in the hydrophobic cavity of β-cyclodextrin improved the collision probability of reactants. The intercalation of β-cyclodextrin-calcium complex (β-CD-Ca) increased the pore size and basic strength of catalyst. The experiment results showed that the glycerol conversion was 93.7% and the GC yield was 91.8% catalyzed by β-CD-Ca/LDH when the molar ratio of DMC and glycerol was 3:1, the catalyst dosage was 4 wt.%, the reaction temperature was 75 °C and the reaction time was 100 min while the glycerol conversion was 49.4% and the GC yield was 48.6% catalyzed by MgAl-LDH under the same conditions.
Poisoning Effect of CO: How It Changes Hydrogen Electrode Reaction and How to Analyze It Using Differential Polarization Curve
Authors: Seri Osami , Furumata Kazunao
Published: November 2021

The hydrogen electrode reaction (HER) on Pt electrode in a H2SO4 solution when CO gas was injected/stopped was studied using polarization resistance curve. In order to elucidate and confirm the CO poisoning effect, a few curve techniques were proposed. Applying them, the kinetic parameters such as the number of electrons transferred (z) and the cathodic transfer coefficient (αc) were determined. The HER in a 0.5 mol dm−3 H2SO4 solution saturated with H2 was confirmed as a reversible reaction having z = 2. When the above solution was injected with CO, the reversible HER changed to an irreversible reaction having z = 1 and αc ≈ 0.6. Once we stopped the CO injection, alteration from the irreversible to quasireversible reaction was gradually made after several cyclic polarizations. The proposed curve techniques can provide a reliable way to determine the kinetic parameters changing among reversible, irreversible, and quasireversible reactions.
Diversifying Arena of Drug Synthesis: In the Realm of Lipase Mediated Waves of Biocatalysis
Authors: Verma Sahil , Choudhary Rahul Narayanlal , Kanadje Akash Prakash , Banerjee Uttam Chand
Published: November 2021

Hydrolases, being most prominent enzymes used in industrial processes have left no stone unturned in fascinating the pharmaceutical industry. Lipases, being a part of acyl hydrolases are the ones that function similarly to esterases (except an interfacial action) wherein they generally catalyze the hydrolysis of ester bonds. Be it in terms of stereoselectivity or regioselectivity, lipases have manifested their promiscuous proficiency in rendering biocatalytic drug synthesis and intermediates thereof. Industrial utilization of lipases is prevalent since decades ago, but their distinctive catalytic competencies have rendered them suitable for maneuverability in various tides of biocatalytic industrial process development. Numbers of exquisite catalysts have been fabricated out of lipases using nanobiotechnology whereby enzyme reusability and robustness have been conferred to many of the organic synthesis procedures. This marks a considerable achievement of lipases in the second wave of biocatalysis. Furthermore, in the third wave an advent of genetic engineering has fostered an era of customized lipases for suitable needs. Be it stability or an enhanced efficacy, genetic engineering techniques have ushered an avenue for biocatalytic development of drugs and drug intermediates through greener processes using lipases. Even in the forthcoming concept of co-modular catalytic systems, lipases may be the frontiers because of their astonishing capability to act along with other enzymes. The concept may render feasibility in the development of cascade reactions in organic synthesis. An upcoming wave demands fulfilling the vision of tailored lipase whilst a far-flung exploration needs to be unveiled for various research impediments in rendering lipase as a custom fit biocatalyst in pharmaceutical industry.
A Review of Electrical Assisted Photocatalytic Technologies for the Treatment of Multi-Phase Pollutants
Authors: Yuan Chung-Shin , Ie Iau-Ren , Zheng Ji-Ren , Hung Chung-Hsuan , Lin Zu-Bei , Shih Ching-Hsun
Published: November 2021

This article reviews the fundamental theories and reaction mechanisms of photocatalytic technologies with the assistance of electrical field for degrading multi-phase pollutants. Photo(electro)catalysis including photocatalytic oxidation (PCO) and photoelectrocatalytic oxidation (PECO) have been a potential technologies applied for the treatment of organic and inorganic compounds in the wastewaters and waste gases, which has been treated as a promising technique by using semiconductors as photo(electro)catalysts to convert light or electrical energy to chemical energy. Combining photocatalytic processes with electrical field is an option to effectively decompose organic and inorganic pollutants. Although photocatalytic oxidation techniques have been used to decompose multi-phase pollutants, developing efficient advanced oxidation technologies (AOTs) by combining photocatalysis with electrical potential is urgently demanded in the future. This article reviews the most recent progress and the advances in the field of photocatalytic technologies combined with external electrical field, including the characterization of nano-sized photo(electro)catalysts, the degradation of multi-phase pollutants, and the development of electrical assisted photocatalytic technologies for the potential application on the treatment of organic and inorganic compounds in the wastewaters and waste gases. Innovative oxidation techniques regarding photo(electro)catalytic reactions with and without oxidants are included in this review article.
The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer
Authors: Coschi Courtney H. , Juergens Rosalyn A.
Published: November 2021

Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management.
Minimum Message Length Inference of the Exponential Distribution with Type I Censoring
Authors: Makalic Enes , Schmidt Daniel Francis
Published: November 2021

Data with censoring is common in many areas of science and the associated statistical models are generally estimated with the method of maximum likelihood combined with a model selection criterion such as Akaike’s information criterion. This manuscript demonstrates how the information theoretic minimum message length principle can be used to estimate statistical models in the presence of type I random and fixed censoring data. The exponential distribution with fixed and random censoring is used as an example to demonstrate the process where we observe that the minimum message length estimate of mean survival time has some advantages over the standard maximum likelihood estimate.
Measurement of the Temperature Using the Tomographic Representation of Thermal States for Quadratic Hamiltonians
Authors: López-Saldívar Julio A. , Man’ko Margarita A. , Man’ko Vladimir I.
Published: November 2021

The Wigner and tomographic representations of thermal Gibbs states for one- and two-mode quantum systems described by a quadratic Hamiltonian are obtained. This is done by using the covariance matrix of the mentioned states. The area of the Wigner function and the width of the tomogram of quantum systems are proposed to define a temperature scale for this type of states. This proposal is then confirmed for the general one-dimensional case and for a system of two coupled harmonic oscillators. The use of these properties as measures for the temperature of quantum systems is mentioned.
Relaxation of Some Confusions about Confounders
Authors: Zlatniczki Ádám , Stippinger Marcell , Benkő Zsigmond , Somogyvári Zoltán , Telcs András
Published: November 2021

This work is about observational causal discovery for deterministic and stochastic dynamic systems. We explore what additional knowledge can be gained by the usage of standard conditional independence tests and if the interacting systems are located in a geodesic space.
Textual Adversarial Attacking with Limited Queries
Authors: Zhang Yu , Yang Junan , Li Xiaoshuai , Liu Hui , Shao Kun
Published: November 2021

Recent studies have shown that natural language processing (NLP) models are vulnerable to adversarial examples, which are maliciously designed by adding small perturbations to benign inputs that are imperceptible to the human eye, leading to false predictions by the target model. Compared to character- and sentence-level textual adversarial attacks, word-level attack can generate higher-quality adversarial examples, especially in a black-box setting. However, existing attack methods usually require a huge number of queries to successfully deceive the target model, which is costly in a real adversarial scenario. Hence, finding appropriate models is difficult. Therefore, we propose a novel attack method, the main idea of which is to fully utilize the adversarial examples generated by the local model and transfer part of the attack to the local model to complete ahead of time, thereby reducing costs related to attacking the target model. Extensive experiments conducted on three public benchmarks show that our attack method can not only improve the success rate but also reduce the cost, while outperforming the baselines by a significant margin.
Optimising Electrical Power Supply Sustainability Using a Grid-Connected Hybrid Renewable Energy System—An NHS Hospital Case Study
Authors: Kahwash Fadi , Barakat Basel , Taha Ahmad , Abbasi Qammer H. , Imran Muhammad Ali
Published: November 2021

This study focuses on improving the sustainability of electrical supply in the healthcare system in the UK, to contribute to current efforts made towards the 2050 net-zero carbon target. As a case study, we propose a grid-connected hybrid renewable energy system (HRES) for a hospital in the south-east of England. Electrical consumption data were gathered from five wards in the hospital for a period of one year. PV-battery-grid system architecture was selected to ensure practical execution through the installation of PV arrays on the roof of the facility. Selection of the optimal system was conducted through a novel methodology combining multi-objective optimisation and data forecasting. The optimisation was conducted using a genetic algorithm with two objectives (1) minimisation of the levelised cost of energy and (2) CO2 emissions. Advanced data forecasting was used to forecast grid emissions and other cost parameters at two year intervals (2023 and 2025). Several optimisation simulations were carried out using the actual and forecasted parameters to improve decision making. The results show that incorporating forecasted parameters into the optimisation allows to identify the subset of optimal solutions that will become sub-optimal in the future and, therefore, should be avoided. Finally, a framework for choosing the most suitable subset of optimal solutions was presented.
Determination of the Leakage Reactance of End Windings of a High-Power Synchronous Generator Stator Winding Using the Finite Element Method
Authors: Berhausen Sebastian , Paszek Stefan
Published: November 2021

The paper presents a description of the method and the results of calculating the leakage reactance of high-power synchronous generator end windings using the finite element method. This reactance is one of the components of the stator leakage reactance of synchronous generators. The calculations were carried out under the assumption of a three-dimensional field distribution in a synchronous generator. The thus calculated value of the leakage reactance of the end windings was compared with the calculation results obtained using traditional, analytical formulas known from the literature. The analysis of the influence of the reactance value of the end windings on the transient waveforms at a three-phase short-circuit of the stator windings was performed based on a two-dimensional field-circuit model.
Overview of the Tolerance Limit Calculations with Application to TSURFER
Authors: Abdel-Khalik Hany , Huang Dongli , Mertyurek Ugur , Marshall William , Wieselquist William
Published: November 2021

To establish confidence in the results of computerized physics models, a key regulatory requirement is to develop a scientifically defendable process. The methods employed for confidence, characterization, and consolidation, or C3, are statistically involved and are often accessible only to avid statisticians. This manuscript serves as a pedagogical presentation of the C3 process to all stakeholders—including researchers, industrial practitioners, and regulators—to impart an intuitive understanding of the key concepts and mathematical methods entailed by C3. The primary focus is on calculation of tolerance limits, which is the overall goal of the C3 process. Tolerance limits encode the confidence in the calculation results as communicated to the regulator. Understanding the C3 process is especially critical today, as the nuclear industry is considering more innovative ways to assess new technologies, including new reactor and fuel concepts, via an integrated approach that optimally combines modeling and simulation and minimal targeted validation experiments. This manuscript employs intuitive, analytical, numerical, and visual representations to explain how tolerance limits may be calculated for a wide range of configurations, and it also describes how their values may be interpreted. Various verification tests have been developed to test the calculated tolerance limits and to help delineate their values. The manuscript demonstrates the calculation of tolerance limits for TSURFER, a computer code developed by the Oak Ridge National Laboratory for criticality safety applications. The goal is to evaluate the tolerance limit for TSURFER-determined criticality biases to support the determination of upper, subcritical limits for regulatory purposes.
Artificial Negative Polarity Thunderstorm Cell Modeling of Nearby Incomplete Upward Discharges’ Influence on Elements of Monitoring Systems for Air Transmission Lines
Authors: Lysov Nikolay , Temnikov Alexander , Chernensky Leonid , Orlov Alexander , Belova Olga , Kivshar Tatiana , Kovalev Dmitry , Voevodin Vadim
Published: November 2021

The article represents results of a physical simulation of incomplete upward leader discharges induced on air transmission lines’ elements, using charged artificial thunderstorm cells of negative polarity. The influence of such discharges on closely located model sensors (both of rod and elongated types) of digital monitoring systems, as well as on the models of receiver-transmission systems of local data collection (antennas), was determined. Effect of heterogeneity of electromagnetic field caused by incomplete upward discharges on frequency specter of signals generated on sensors and antennas was estimated. Wavelet analysis was carried out to determine the basic frequency diapasons of such signals. Based on experimental data obtained, suppositions about the extent of influence of nearby incomplete leader discharges on the functioning of currently used systems of transmission lines’ monitoring were made.
Doughnut-Shaped and Top Hat Solar Laser Beams Numerical Analysis
Authors: Catela Miguel , Liang Dawei , Vistas Cláudia R. , Garcia Dário , Tibúrcio Bruno D. , Costa Hugo , Almeida Joana
Published: November 2021

Aside from the industry-standard Gaussian intensity profile, top hat and non-conventional laser beam shapes, such as doughnut-shaped profile, are ever more required. The top hat laser beam profile is well-known for uniformly irradiating the target material, significantly reducing the heat-affected zones, typical of Gaussian laser irradiation, whereas the doughnut-shaped laser beam has attracted much interest for its use in trapping particles at the nanoscale and improving mechanical performance during laser-based 3D metal printing. Solar-pumped lasers can be a cost-effective and more sustainable alternative to accomplish these useful laser beam distributions. The sunlight was collected and concentrated by six primary Fresnel lenses, six folding mirror collectors, further compressed with six secondary fused silica concentrators, and symmetrically distributed by six twisted light guides around a 5.5 mm diameter, 35 mm length Nd:YAG rod inside a cylindrical cavity. A top hat laser beam profile (Mx2 = 1.25, My2 = 1.00) was computed through both ZEMAX® and LASCAD® analysis, with 9.4 W/m2 TEM00 mode laser power collection and 0.99% solar-to-TEM00 mode power conversion efficiencies. By using a 5.8 mm laser rod diameter, a doughnut-shaped solar laser beam profile (Mx2 = 1.90, My2 = 1.00) was observed. The 9.8 W/m2 TEM00 mode laser power collection and 1.03% solar-to-TEM00 mode power conversion efficiencies were also attained, corresponding to an increase of 2.2 and 1.9 times, respectively, compared to the state-of-the-art experimental records. As far as we know, the first numerical simulation of doughnut-shaped and top hat solar laser beam profiles is reported here, significantly contributing to the understanding of the formation of such beam profiles.
Is ortho-Cresol a Viable Lignocellulosic Blendstock? A Kinetic Study of Its Co-Oxidation within a Surrogate Fuel
Authors: Mergulhão Carolina S. , Fenard Yann , Vanhove Guillaume
Published: November 2021

The viability of the use of ortho-cresol as a bio-blendstock or antiknock additive from lignocellulosic biomass is assessed; Ignition delays of ortho-cresol within blends with iso-octane are measured with the ULille rapid compression machine, and compared with results from the literature; It is shown that ortho-cresol has a strong inhibiting effect on the reactivity towards ignition, most notably in the Negative Temperature Coefficient region; This effect is found to originate from competition with iso-octane on the OH radicals, where the reactivity of ortho-cresol with these radicals does not lead to radical chain-branching.
Multi-Time-Scale Optimal Scheduling in Active Distribution Network with Voltage Stability Constraints
Authors: Song Tianhao , Han Xiaoqing , Zhang Baifu
Published: November 2021

The uncertainty associated with loads and renewable-energy sources affects active distribution networks in terms of the operation and voltage stability on different time scales. To address this problem, a multi-time-scale voltage stability constrained optimal scheduling framework is proposed, which includes a day-ahead model with a coarse-grained time resolution and an intra-day model with a fine-grained time resolution. The day-ahead economic-scheduling model maps out a scheme to operate different types of devices with the aim of minimizing the network losses. Following the scheme, the intra-day corrective-adjustment model based on model predictive control is proposed to regulate the flexible devices, such as the energy storage systems and the photovoltaic converters. In particular, the proposed optimal scheduling framework embeds a voltage stability constraint which is constructed by using a novel index, defined based on the Distflow model Jacobian. As the index at each bus is a linear function of the locally measurable power flow variables, the proposed constraint does not introduce additional computational burdens. Simulation results demonstrate the necessity and effectiveness of the proposed multi-time-scale voltage stability constrained optimal scheduling model. The results also show that the variation trend of the proposed index is consistent with that of the commonly used voltage stability index.
A Method for Assessing the Impact of Changes in Demand for Coal on the Structure of Coal Grades Produced by Mines
Authors: Fuksa Dariusz
Published: November 2021

Due to the withdrawal of coal from power generation in the EU, mining companies in Poland are forced to adapt their production to the decreasing demand. Forecasting the volume of demand plays an important role in planning the volume of the mine’s output. The demand for coal is constantly changing, with a downward trend. This article presents a method that allows to assess the impact of the variable demand on mine profits and on the volumes of sales of individual coal grades. The proposed method is based on the Monte Carlo simulation and on a solution consisting of the optimization of the production and sales of coal by the mining company (the SIMPLEX algorithm). By using the Monte Carlo simulation to forecast the demand, unlike other commonly used methods, a sufficiently large set of real situations that may occur in the future can be obtained. The results allow us to conclude the extent of desirable adjustment of the structure of the mine’s production to the requirements of its consumers, as well as to predict in which direction these changes will proceed and with what probability. The usefulness of the developed method has been verified on the example of an existing hard coal mine.
Characteristics and Shareholder Wealth Effects of Mergers and Acquisitions Involving European Renewable Energy Companies
Authors: Wasilewski Mirosław , Zabolotnyy Serhiy , Osiichuk Dmytro
Published: November 2021

The present study documents a positive market reaction to mergers and acquisition (M&A) deals involving renewable energy companies. Acquirers record positive post-deal cumulative risk-adjusted returns upon taking over a renewable energy target, especially if the former also operates in the renewable energy sector. Such deals often involve purchases of majority equity stakes financed with acquirers’ stock rather than cash. Acquirers of renewable energy firms tend to be more profitable and cash-rich than their industry peers, yet they are less likely to be serial acquirers and channel cash reserves towards M&As. We evidence that the quality of corporate governance in the energy sector may play a substantial role in shaping the choice of targets; a director’s outside affiliations increase the likelihood of takeovers of non-energy firms, while the presence of outsiders on board appears to incentivize diversification into renewable energy. While acquisitions of renewable energy firms feature lower-than-average acquisition premia and generate positive short-term stock returns, they are found to exercise an overall negative short- and medium-term impact on the combined entities’ operating performance. Overall, capital markets appear to attach a sizeable premium to risky deals involving renewable energy firms, possibly in expectation of wealth accrual in the long term.
Structural and Parametric Optimization of S-CO2 Thermal Power Plants with a Pulverized Coal-Fired Boiler Operating in Russia
Authors: Rogalev Andrey , Kindra Vladimir , Komarov Ivan , Osipov Sergey , Zlyvko Olga
Published: November 2021

The Rankine cycle is widely used for electricity production. Significant weight and size characteristics of the power equipment working on superheated steam are the main disadvantages of such power plants. The transition to supercritical carbon dioxide (S-CO2) working fluid is a promising way to achieve a significant reduction in equipment metal consumption and to increase energy efficiency. This paper presents the results of thermodynamic analysis of S-CO2 thermal power plants (TPPs) utilizing the heat of combustion products of an energy boiler. It was found that the net efficiency of the developed S-CO2 TPP with a pulverized coal-fired boiler reached 49.2% at an initial temperature of 780 °C, which was 2% higher compared to the efficiency level of steam turbine power plants (STPPs) at a similar turbine inlet temperature.
Performance Effects of Network Structure and Ownership: The Norwegian Electricity Distribution Sector
Authors: Tobiasson Wenche , Llorca Manuel , Jamasb Tooraj
Published: November 2021

Transmission and distribution networks are capital intensive segments of the electricity sector and are generally considered natural monopolies. Due to their non-competitive nature, these are subject to independent regulation to prevent the abuse of monopolistic power and to induce competitive behaviour. Effective economic regulation of the electricity networks has become a key target in most developed economies after the 1980s. In Norway, incentive regulation and efficiency benchmarking were introduced in 1997. In Norway, the electricity grid is divided into three levels, namely, central, regional and distribution networks. In this paper, we study two overlooked aspects when analysing the performance of electricity networks: vertical integration and ownership structure. We use a stochastic frontier analysis approach to analyse the performance of Norwegian electricity distribution utilities for the period 2007–2014. We observe that vertical integration between distribution and regional transmission implies higher cost inefficiencies. This indicates that the efficiency gains due to separate management of the networks exceed the economies of coordination from vertical economies of scope. In addition, we find that council ownership entails higher efficiencies. This could be explained by the state having an interest in high-voltage electricity networks, rather than low-voltage ones, and the decentralised model from which the now centralised system was once developed.