bluuebunny/crossref_metadata_2025 huggingface dataset:
The concept and legal regime of innovative vehicles: general theoretical issues
Authors: Sergeev Alexey Mikhailovich
Published: December 2024

The subject of the research of this scientific article is the complex problems of legal regulation of new types of vehicles belonging to the category of innovative. The author focuses on the existing terminological haphazardness and insufficient definiteness of the conceptual apparatus, which makes it difficult to develop, understand and apply the norms of law to these means. The theoretical foundations of the definition of the term "innovative vehicles" are investigated, including their classification and specifics of operation, and attention is also drawn to the intersectoral aspects of legal regulation, which implies the interaction of various legal disciplines. The article explores the need to develop common approaches and criteria for the legal regulation of such technological innovations aimed at ensuring the safety, efficiency and harmonious integration of innovative vehicles into the existing legal system. The research methodology includes general scientific and special (legal) methods of scientific analysis, namely, a systematic analysis of normative legal acts, formal legal and dogmatic approaches to the study of legislation. The presence of a significant technical and economic component in the operation of innovative vehicles has led to the appeal to an interdisciplinary methodology. The scientific novelty of the article lies in a systematic approach to the study of the legal regulation of innovative vehicles, which includes the development of a single conceptual framework and criteria for their classification. For the first time, the author substantiates the importance of an interdisciplinary approach, emphasizing the need to integrate the norms of various branches of law in order to ensure adequate regulation in a rapidly developing technology. The conclusions can be summarized as follows: 1) The existing terminology in the field of innovative vehicles requires systematization to ensure legal certainty. 2) The legal regime of such vehicles should take into account their features, including the level of automation and interaction with traditional transport. 3) Effective regulation is impossible without an integrated approach that unites different branches of law, such as civil, administrative and criminal law. 4) It is necessary to develop additional measures to ensure the safety of the operation of innovative vehicles on the roads. 5) It is important to take into account international experience and apply it to the formation of domestic legislation in this area.
Sports rights of players and the possibility of their pledge
Authors: Ahunzyanov Danis Fanisovich
Published: December 2024

The article is devoted to analyzing the legal aspects of managing and disposing of players sports rights, including the possibilities of their use in security transactions, particularly as pledge. The research focuses on the differences in the definition and handling of sports rights in key team sports disciplines such as football and hockey, considering the provisions of Russian legislation and the regulations of international sports federations. Special attention is given to transfer agreements and their legal nature, as well as restrictions imposed by sports regulators on the disposal of economic rights, affecting their defensibility. The author identifies regulatory contradictions and proposes ways to resolve them, significantly expanding the understanding of the legal field of sports transfers, covering new aspects of their use and regulation. The article employs scientific methods, including the analysis of legal practice and theoretical research of normative acts. The author also conducts a comparative analysis of the regulations of international and national sports federations. This allows for a comprehensive assessment of the peculiarities of regulating sports rights in various sports disciplines and legal systems. The scientific novelty of the work lies in the thorough investigation of the ways of disposing of sportsman’ (players) sports rights in the context of their use in security transactions, particularly as pledge. The work identifies gaps in the existing regulation and offers well-argued ways to address them. The author demonstrates how changes in regulations can affect the legal nature of sports rights and their practical application in transactions. The potential opportunities for sports organizations and clubs to attract financing through the mechanisms of sports rights pledge are outlined, which could significantly enhance the investment attractiveness of the sports industry and facilitate a gradual move away from state funding of sports, opening new horizons for its development and independent functioning.
THE CONTRIBUTION OF INTELLECTUAL PROPERTY AWARENSSS AND THE MOTIVATION OF COMIC CREATORS TO PRODUCT INNOVATION
Authors:   Universitas Indonesia, Rangga Wiwesa Ngurah , Setiawati Rahmi , Bintang Apriliyanto Dani ,   Universitas Indonesia, Wan Zainodin Dr Wan Hartini , Anindya Ravinta Putri ,   Universitas Indonesia
Published: December 2024

Comics are not only in the artistic sector but also in the industrial sector, which has economic value in society and is included in the creative industry. As works of creativity, the comic industry needs to be recognized as intellectual works that have economic value and receive legal protection. Therefore, it is necessary to know the role of awareness of intellectual property rights and the motivation of comic creators in innovating in developing their products and measuring understanding of comics as a part of the creative industry. The population of this research is high school/vocational school and university students in Indonesia. The sample was selected by simple random sampling and obtained from 64 people. Data collection techniques used questionnaires, then processed using descriptive and inferential statistics with multiple linear regression techniques. The study results show an awareness contribution to intellectual property rights and comic creators' motivation to develop comic product innovation. Currently, the comic industry has become a big business and a source of material for other creative industry sectors. Behind it all, two main problems were identified in this industrial sector, namely: (1) the lack of public awareness of intellectual property rights, and (2) the lack of publication in the comic industry sub-sector which caused it to be less well known and in demand by the public. This finding can increase the country's comic industry and significantly contribute to Indonesia's creative economy.
PERAN ACCOUNT EXECUTIVE DALAM MENINGKATKAN AWARENESS PROGRAM YOUTUBE JAMILO TV
Authors:   Universitas Indonesia, ayu ningtyas putri , Widi Satria Hardika ,   Universitas Indonesia, Dini Kamila Anisah ,   Universitas Indonesia
Published: December 2024

Account Executive is an important role in an advertising company. An Account Executive here is responsible for monitoring the progress of the project, making minutes of meetings in detail, minimizing internal team errors so that the project runs smoothly in order to achieve the targets and objectives of the program. This paper aims to explore the role of the Account Executive in planning to increase awareness of the Offside Jon! #PilDun2022Edition Jamilo TV is owned by Ibnu Jamilo who collaborated with Bhumi Pictures to create a YouTube program for the 2022 World Cup edition. This program was produced for one month from 20 November to 20 December 2022 using the AISAS method as its marketing communications strategy. The research was carried out qualitatively, using the participatory observation method and unstructured observation of aspects in the digital field. Even though there were several gaps in the planning of the production process, in the end this program received good enthusiasm from the audience. With the achievement of 20 episodes, it was watched more than 270 thousand times on YouTube with a total of 2 brand partnerships in 2 episodes, as well as 102.9 thousand views on Instagram and 2.64 million on Tiktok Jamilo TV. It is hoped that this article will become a useful up-to-date reference for Account Executives involved in digital media platforms, practitioners, institutions and companies in maintaining awareness of their programs in the midst of the rapid era of digitalization.
Influence of energetic heavy ion sputtering on lifetime of alloy target
Authors: NI Weirong , HUANG Hailong , LU Xiaoyong , WANG Xiaodong ,   Research Institude of Physical and Chemical Engineering of Nuclear Industry, Tianjin 300180, China,   Science and Technology on Particle Transport and Separation Laboratory, Tianjin 300180, China,   School of Mechanical Engineering and Automation, Northeastern University, Shenyang 110167, China
Published: December 2024

When energetic heavy ions are incident on negatively charged structure that collects and deposits ions, ion sputtering will occur. Metal wire is a structure commonly used for accelerating ions, the incidence of continuous high-throughput ions can cause surface loss of metal wire, affecting the service performance and lifespan of the metal wire. The SRIM software commonly used for calculating sputtering yield cannot consider the multi-body interaction problem contained in the alloy crystal structure. So, there is a significant error in calculating the sputtering yield of high-energy ions incident on alloy target. Based on the molecular dynamics method and Langevin temperature control model, the calculation model of ion sputtering parameters of energetic metal ions incident on alloy target is established in this work. The model is used to calculate the sputtering yield under the conditions of intact surface lattice of the target material and long-term incident surface lattice damage. The damages to the cathode metal wire under different incident ion fluences are further calculated, and the cross-sectional characterization of the metal wire is carried under typical working condition. The results show that the discrepancy between the experimental value and the theoretical value is less than 10%, which verifies the accuracy and applicability of the theoretical model. Based on this model, the search direction for sputtering resistant materials is proposed, meanwhile, a theoretical optimization is carried out to improve the service life of metal wire, and a method of using Ni-Ti alloy to improve the service life of metal wires is proposed, which is of great significance for predicting the service life of the metal wire under different conditions.
Ligand response of guanidine-IV riboswitch at single-molecule level
Authors: Gao Lingzhi , Chen Dian , Liu Yu
Published: December 2024

Riboswitches represent a class of non-coding RNA that possess the unique ability to specifically bind ligands and, in response, regulate gene expression. A recent report unveiled a type of riboswitch, known as the guanidine-IV riboswitch, which responds to guanidine levels to regulate downstream genetic transcription. However, the precise molecular mechanism through which the riboswitch senses its target ligand and undergoes conformational changes remain elusive. This gap in understanding has impeded the potential applications of this riboswitch. To bridge this knowledge gap, our study investigated the conformational dynamics of the guanidine-IV riboswitch RNA upon ligand binding. We employed single-molecule fluorescence resonance energy transfer (smFRET) to dissect the behaviors of the aptamer, terminator, and full-length riboswitch. Our findings indicated that the aptamer portion exhibited higher sensitivity to guanidine compared to the terminator and full-length constructs. Additionally, we utilized Position-specific Labelling of RNA (PLOR) combined with smFRET to observe, at the single-nucleotide and single-molecule level, the structural transitions experienced by the guanidine-IV riboswitch during transcription. Notably, we discovered that the influence of guanidine on the riboswitch RNA’s conformations was significantly reduced after the transcription of 88 nucleotides. Furthermore, we proposed a folding model for the guanidine-IV riboswitch in the absence and presence of guanidine, thereby providing insights into its ligand-response mechanism.
Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis-dependent functional plasticity
Authors: Cox Donal J , Connolly Sarah A , Ó Maoldomhnaigh Cilian , Brugman Aenea AI , Sandby Thomas Olivia , Duffin Emily , Gogan Karl M , Ó Gallchobhair Oisin , Murphy Dearbhla M , O'Rourke Sinead A , O'Connell Finbarr , Nadarajan Parthiban , Phelan James J , Gleeson Laura E , Basdeo Sharee A , Keane Joseph
Published: December 2024

Airway macrophages (AM) are the predominant immune cell in the lung and play a crucial role in preventing infection, making them a target for host directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte-derived macrophages (MDM; as a model of blood derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM do not decrease oxidative phosphorylation unlike MDM which shift to ‘Warburg’-like metabolism. IFN-γ priming promoted cytokine secretion in AM. Blocking glycolysis with 2-deoxyglucose significantly reduced IFN-γ driven cytokine production in AM, indicating that IFN-γ induces functional plasticity in human AM, which is mechanistically mediated by glycolysis. Directly comparing responses between macrophages, AM were more responsive to IFN-γ priming and dependent on glycolysis for cytokine secretion than MDM. Interestingly, TNF production was under the control of glycolysis in AM and not in MDM. MDM exhibited glycolysis-dependent upregulation of HLA-DR and CD40, whereas IFN-γ upregulated HLA-DR and CD40 on AM independently of glycolysis. These data indicate that human AM are functionally plastic and respond to IFN-γ in a manner distinct from MDM. These data provide evidence that human AM are a tractable target for inhalable immunomodulatory therapies for respiratory diseases.
Novel Supine Isometric Hamstring Test: A Reliability Study
Authors: Gorman Barry T. , Kung Stacey , Welch Neil , Squillante Antonio
Published: December 2024

Background: Hamstring strain injuries are highly prevalent, particularly when the hamstrings are in a lengthened position; however, monitoring strength deficits and fatigue throughout a season is currently difficult due to a lack of practical, reliable tests that do not cause undue fatigue. Objective: The aim of the current study was to investigate the intersession reliability of a novel 90°hip: 40°knee isometric hamstring test (IHT) in the supine position. Methodology: This was a prospective, observational cohort study conducted on nine male participants (24 ± 3 years, 81.9 ± 6.4kg, 181.8 ± 5.3cm). Each participant completed two testing sessions of the 90°hip: 40°knee IHT using force platforms. Relative and absolute reliability of isometric peak force (IPF) were assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV%), respectively. Results: Relative reliability of the 90°hip: 40°knee IHT was considered “good” in the dominant limb (ICC = 0.92, Lower bound 95% Confidence Interval (CI) = 0.72) and “poor” in the non-dominant limb (ICC = 0.76, Lower bound 95% CI = 0.28). Absolute reliability was “acceptable” in both legs with 5.81% in the dominant limb and 9.65% in the non-dominant limb. Conclusion: The 90°hip: 40°knee IHT demonstrated moderate reliability overall, further research is required to discover the optimum IHT configuration which can be reliably executed at longer hamstring muscle lengths. This study provides foundational information for practitioners on a novel method of reliably testing hamstring isometric strength at longer muscle lengths.
A Cross-Sectional Study on Demographic Characteristics, Nutritional Knowledge, and Supplement Use Patterns
Authors: Maad Abdullah H. , Aljerf Loai , AlJerf Alissar , Rafaat Dayoob Carmen , Jehad Sukkar Anas , Alajlani Muaaz
Published: December 2024

Background: The indiscriminate use of dietary supplements among athletes poses significant risks, highlighting the need for awareness and education on the potential dangers associated with supplement misuse. Objective: To emphasize the importance of providing athletes with in-depth information on the risks of supplement misuse, including potential side effects, medication interactions, and the lack of regulation in supplement production. Method: This cross-sectional study employed stratified random sampling to recruit 204 athletes from Damascus, Syria. A pilot-tested online survey instrument captured demographic characteristics, athletic background, supplement use habits, and motivations. A standardized physical fitness assessment protocol evaluated cardiovascular endurance, muscular strength, and flexibility. Descriptive statistics, inferential statistics, and multivariate analysis examined relationships between physical fitness, nutritional practices, and athletic performance. Rigorous quality control measures ensured data reliability, including pilot testing, data cleaning, and strategies to minimize response bias and errors. Results: Through evidence-driven education, athletes and the general public can cultivate a discerning understanding of dietary supplements, thereby empowering informed decision-making amidst the vast and complex landscape of available products. Conclusion: The dissemination of technical information through educational campaigns is crucial in fostering a culture of informed decision-making within the sports community. By integrating evidence-based research with practical guidance, governmental and non-governmental organizations can empower individuals with the critical competencies required to make informed decisions about dietary supplement use in sports, ultimately promoting safe and effective athletic performance.
Consumer Preferences for Dehydrated Vegetables
Authors: Verma Anupama , Patidar Rishabh , Shrivastava P.
Published: December 2024

Why do buyers purchase certain products but not others? How do they determine how much to purchase? Under what circumstances does a sensible customer spend his money and what is his goal? These are some of the important questions to which we seek answers. The overall vegetable production for 2023-24 is expected to be around 205.80 million tonnes, screening a balanced trend. Substantial growths are expected in crops like tomato, cabbage, cauliflower, tapioca, bottle gourd, pumpkin and cucumber. Globally, it has been estimated that 42% of all of fruit and vegetable calories produced are ultimately wasted. Our sample consisted of a total of 100 participants who have been consuming the dehydrated vegetables. The study was conducted in the year 2023-24. Our focus in the physical sampling exercise was on important locations around Jabalpur, MP. Due to the location VAM Agro, selection of Jabalpur, Madhya Pradesh as study area for examining scope of dehydrated vegetables with specific reference to VAM Agro Processing Private Limited was therefore quite strategic and justified. We relied on convenient sampling in picking the study participants. It was found that more male members are there in the dehydrated vegetable consumer group in comparison with females. Of the major proportion of consumers interested in dehydrated vegetables, 78% fall within the age bracket of 21-25 years. 40 per cent of the respondents use them in instant foods such as potato chips and ready-to-eat foods, citing convenience and speed. A cool, dry place was best preferred by most consumers for storing their dehydrated vegetables, as it allows quality maintenance and prevents spoilage from moisture.
Beyond Silicon
MOS
: An Electrical Study on Interface and Gate Dielectrics with
ac
Admittance Techniques
Authors: Lin Dennis H.C. , Vais Abhitosh , Gaur Abhinav , Brammertz Guy , Alian AliReza , Nyns Laura , Sioncke Sonja , Delabie Annelies , Asselberghs Inge , Radu Iuliana , Collaert Nadine , De Meyer Kristin , Heyns Marc
Published: May 2019

Recent developments in complimentary metal–oxide semiconductor (CMOS)‐driven compound semiconductors (III–V), Germanium (Ge) and two‐dimensional (2‐D) materials technologies provide new opportunities in advancing the performance envelope of MOS device as well as the relevant electrical characterization techniques. Understanding the electrical characteristics of the metal–oxide–semiconductor (MOS) interface and defects through capacitance‐voltage (CV), conductance voltage (GV) and ac‐transconductance responses can lead to more realistic assessments of the oxide–semiconductor material systems and accurate performance predictions. In this article, interface trap density distributions
D
it
(
E
) of Germanium, III–V compound semiconductors are characterized and/or illustrated. The characterization, modeling and temperature dependence of oxide border traps are presented as the defect study probes beyond the oxide–semiconductor interface. Finally, an investigation on 2‐D materials based MOS devices extends the ac admittance techniques beyond conventional semiconductor materials.
The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML
Authors: Dunlap Jennifer B. , Leonard Jessica , Rosenberg Mara , Cook Rachel , Press Richard , Fan Guang , Raess Philipp W. , Druker Brian J. , Traer Elie
Published: May 2019

Acute myeloid leukemia (AML) is a genetically heterogeneous disease with a clinical course predicted by recurrent cytogenetic abnormalities and/or gene mutations. The NPM1 insertion mutations define the largest distinct genetic subset, ∼30% of AML, and is considered a favorable risk marker if there is no (or low allelic ratio) FLT3 internal tandem duplication (FLT3 ITD) mutation. However, ∼40% of patients with mutated NPM1 without FLT3 ITD still relapse, and the factors that drive relapse are still not fully understood. We used a next‐generation sequencing panel to examine mutations at diagnosis; clearance of mutations after therapy, and gain/loss of mutations at relapse to prioritize mutations that contribute to relapse. Triple mutation of NPM1, DNMT3A and IDH1/2 showed a trend towards inferior overall survival in our discovery dataset, and was significantly associated with reduced OS in a large independent validation cohort. Analysis of relative variant allele frequencies suggests that early mutation and expansion of DNMT3A and IDH1/2 prior to acquisition of NPM1 mutation leads to increased risk of relapse. This subset of patients may benefit from allogeneic stem cell transplant or clinical trials with IDH inhibitors.
Paternal heritage in Jujuy province (Northwest Argentina): Evidence for sex‐biased gene flow and genetic drift effects
Authors: Alfonso‐Sánchez Miguel A. , Gómez‐Pérez Luis , Dipierri José E. , Peña José A.
Published: May 2019

Objectives

This study aimed to explore the diversity of paternal lineages in Jujuy province (Argentina) by analyzing Y chromosome markers. Furthermore, we examined among‐population genetic variability based both on paternally (NRY haplotypes) and maternally (mtDNA haplogroups) inherited markers. We sought to evaluate the impact of sex‐biased gene flow on genetic background in Jujuy, and contribute data on the microevolutionary forces acting in this zone.

Methods

DNA from 149 males from five Jujuy regions were analyzed for 12 non‐recombining Y (NRY) markers. Genetic heterogeneity among Jujuy regions was evaluated through population differentiation tests. To identify potential genetic boundaries in Jujuy, analysis of molecular variance (AMOVA) and the Monmonier's algorithm implemented in the Barrier v2.2 software were employed.

Results

A clear divergence between Jujuy highlands and lowlands for NRY haplotypes was found. A marked discrepancy between genetic structuring for paternal lineages and the lack of geographical pattern for mitogenomes was confirmed by all statistical analyses.

Conclusions

Genetic structuring of paternal lineages is most likely caused by admixture processes that have occurred since colonial times in the Jujuy lowlands. Immigrants were predominantly male that settled in the lower altitude zones, due to the steep orography of the region. Input of allochthonous male lineages because of gene flow toward the lowlands would have increased diversity of NRY markers, thus compensating for drift effects. Likewise, limited input of allochthonous mitogenomes would have promoted genetic drift, a key factor in the shaping of diversity of maternal lineages across Jujuy subpopulations, irrespective of altitude.
A heterozygous, intragenic deletion of CNOT2 recapitulates the phenotype of 12q15 deletion syndrome
Authors: Alesi Viola , Loddo Sara , Calì Federica , Orlando Valeria , Genovese Silvia , Ferretti Daniele , Calacci Chiara , Calvieri Giusy , Falasca Roberto , Ulgheri Lucia , Drago Fabrizio , Dallapiccola Bruno , Baban Anwar , Novelli Antonio
Published: May 2019

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms.
Learning from learning logs: A case study of metacognition in the primary school classroom
Authors: Branigan Heather E. , Donaldson David I.
Published: May 2019

Structured thinking activities (STAs) are pedagogical tools used to support metacognition in classrooms. Despite their popularity, little is known about how pupils use STAs as platforms to think about and manage their own thinking (i.e. as metacognitive tools). This case study investigated pupils’ use of STAs in relation to metacognition throughout a school year. We focus on two 8‐year‐old pupils, Amy and Laura, as they completed two specific STAs through weekly class meets and termly achievement logs. Data were triangulated through participant observation, qualitative interviews and analysis of written texts. We found clear differences between Laura's and Amy's written STAs, however observation and interviews revealed that engagement with STAs was similar beyond that suggested by the written evidence alone. Whereas Amy used easily spelt ‘stock’ responses, Laura used ‘bare minimum’ responses to meet teacher expectations. As such, neither Amy nor Laura used STAs as metacognitive tools, however in negotiating STAs, both exhibited strategic regulatory skills indicative of metacognition. Whilst our findings highlight that pupils may still be developing explicit metacognitive knowledge necessary to take full advantage of STAs, we highlight the clear value of persistent approaches to using STAs as tools to support developing metacognition, particularly in association with teacher–pupil interactions.
The diagnostic and prognostic value of red cell distribution width in cardiovascular disease; current status and prospective
Authors: Parizadeh Seyed M. , Jafarzadeh‐Esfehani Reza , Bahreyni Amirhossein , Ghandehari Maryam , Shafiee Mojtaba , Rahmani Farzad , Parizadeh Mohammar R. , Seifi Sima , Ghayour‐Mobarhan Majid , Ferns Gordon A. , Avan Amir , Hassanian Seyed M.
Published: May 2019

The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions.
Meta‐Omics‐ and Metabolic Modeling‐Assisted Deciphering of Human Microbiota Metabolism
Authors: Sieow Brendan Fu‐Long , Nurminen Toni Juhani , Ling Hua , Chang Matthew Wook
Published: May 2019

The human microbiota is a complex community of commensal, symbiotic, and pathogenic microbes that play a crucial role in maintaining the homeostasis of human health. Such a homeostasis is maintained through the collective functioning of enzymatic genes responsible for the production of metabolites, enabling the interaction and signaling within microbiota as well as between microbes and the human host. Understanding microbial genes, their associated chemistries and functions would be valuable for engineering systemic metabolic pathways within the microbiota to manage human health and diseases. Given that there are many unknown gene metabolic functions and interactions, increasing efforts have been made to gain insights into the underlying functions of microbiota metabolism. This can be achieved through culture‐independent metagenomic approaches and metabolic modeling to simulate the microenvironment of human microbiota. In this article, the recent advances in metagenome mining and functional profiling for the discovery of the genetic and biochemical links in human microbiota metabolism as well as metabolic modeling for simulation and prediction of metabolic fluxes in the human microbiota are reviewed. This review provides useful insights into the understanding, reconstruction, and modulation of the human microbiota guided by the knowledge acquired from the basic understanding of the human microbiota metabolism.
Pharmacokinetic and tissue distribution studies of cassane diterpenoids, in rats through an ultra‐high‐performance liquid chromatography–Q exactive hybrid quadrupole–Orbitrap high‐resolution accurate mass spectrometry
Authors: Wang Miao , Wang Da , Gao Changjiu , Li Xianzhe , Sha Luping , Zhao Qiang , Gao Huiyuan , Wu Zhaohua
Published: May 2019

Cassane diterpenoids (CA) are considered as the main active constituents of medicinal plants belonging to the Caesalpinia genus. Three cassane derivatives, bonducellpin G (BG), 7‐O‐acetyl‐bonducellpin C (7‐O‐AC) and caesalmin E (CE), isolated from Caesalpinia minax Hance seeds, showed strong anti‐inflammatory activity. In this paper, pharmacokinetics (BG, 7‐O‐AC, CE) and tissue distribution (7‐O‐AC, CE) properties were studied for the first time using a reliable, sensitive and rapid UHPLC–Q‐Orbitrap HR‐MS to develop new anti‐inflammatory agents. A novel quantitative method with full scan in positive ion mode was used to determine the contents of compounds. They were separated using acetonitrile–water (0.1% formic acid) as gradient mobile phase. The calibration curve displayed good linearity and the lower limit of quantitation was 0.005–0.02 μg/mL for all analytes. Meanwhile, the absorption, distribution, metabolism, excretion (ADME) property was predicted using PreADMET web. The pharmacokinetic parameters indicated that they were absorbed quickly, eliminated rapidly together with high blood concentration. The results of tissue distribution demonstrated that CE was distributed rapidly and widely among tissues, and stomach was the main tissue site of CE and 7‐O‐AC, followed by small intestine/liver. This study indicates that the structures and dosages of active CA should be modified to help improve the absorption rate and residence time, and the findings are helpful for the pharmaceutical design of CA derivatives.
Age at menarche and epithelial ovarian cancer risk: A meta‐analysis and Mendelian randomization study
Authors: Yang Huijun , Dai Hongji , Li Lian , Wang Xin , Wang Peishan , Song Fengju , Zhang Ben , Chen Kexin
Published: May 2019

Age at menarche (AAM) was found to be associated with ovarian cancer risk in previous observational studies. However, the causality of this association remains unclear. Here, after systematic meta‐analyses, we performed two‐sample Mendelian randomization (MR) analyses to evaluate the causal effect of AAM in epithelial ovarian cancer (EOC) etiology. We performed meta‐analyses including 11 410 cases and 1 163 117 noncases to quantitatively evaluate the association between AAM and ovarian cancer risk. In MR analyses, we used 25 single nucleotide polymorphisms (SNPs) associated with AAM for Chinese and 390 SNPs for Europeans as instrumental variables. MR estimates were calculated using inverse‐variance weighted methods from 1044 cases and 1172 controls in a Chinese genome‐wide association study and validated by the Ovarian Cancer Association Consortium and Consortium of Investigators of Modifiers of BRCA1/2 studies with 29 396 cases and 68 502 controls of European ancestry. In meta‐analyses, we observed an inverse association (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.93 to 1.00, P = 0.036) between per year older AAM and ovarian cancer risk in case–control studies, but no association was observed in cohort studies. In MR analyses, the OR of EOC risk per year increase in AAM was 0.81 (95% CI = 0.67 to 0.97, P = 0.026) in Chinese and 0.94 (95% CI = 0.90 to 0.98, P = 0.003) in Europeans, respectively. Our study supports a causal association between AAM and EOC risk.
Helicobacter pylori‐induced YAP1 nuclear translocation promotes gastric carcinogenesis by enhancing IL‐1β expression
Authors: Wu Yujiao , Shen Li , Liang Xiuming , Li Shuyan , Ma Lin , Zheng Lixin , Li Tongyu , Yu Han , Chan Hillary , Chen Chunyan , Yu Jingya , Jia Jihui
Published: May 2019

Gastric cancer (GC) is one of the most common and malignant pathologies, and a significant portion of GC incidences develops from Helicobacter pylori (Hp)‐induced chronic gastritis. Although the exact mechanisms of GC are complex and poorly understood, gastric carcinogenesis is a good model to investigate how inflammation and infection collaboratively promote tumorigenesis. Yes‐associated protein 1 (YAP1) is the key effector of the Hippo pathway, which is silenced in most human cancers. Herein, we verified the tumor‐promoting effect of YAP1 in vitro, in vivo, and in human specimens. We revealed that YAP1 displays nuclear translocation and works with TEAD to activate transcription of the crucial inflammatory cytokine IL‐1β in gastric cells infected with Hp. As IL‐1ß accounts for inflammation‐associated tumorigenesis, this process can lead to gastric carcinogenesis. Thus, in addition to activating proliferation genes, YAP1 also plays a major role in inflammation amplification by activating inflammatory cytokine genes. Excitingly, our research demonstrates that transfection of mutant plasmid YAP‐5SA/S94A or addition of the drug verteporfin, both of which are thought to disrupt the YAP1‐TEAD interaction, can arrest the carcinogenesis process. These findings can provide new approaches to GC treatment.
Relationship in context: Processes in school‐based counselling in Hong Kong
Authors: Harrison Mark Gregory
Published: May 2019

Aims

Little is known about the processes taking place in school‐based counselling, particularly in Hong Kong, where the sociocultural environment may influence these processes. This study investigated students’ engagement with counselling from the perspective of students and school counsellors in Hong Kong.

Method

Semi‐structured interviews were carried out with 25 ethnically Chinese students and eight counsellors over three schools in Hong Kong. Data were analysed thematically within a critical realist paradigm.

Results

Four themes were developed which captured students’ experiences of school‐based counselling: “Counselling embedded into the life of the school”; “Fears about counselling”; “Building a counselling relationship”; and “An ongoing but limited source of support.” A top‐level theme called “Relationship in context” encompassed the four themes.

Conclusions and implications

Counsellors’ embeddedness into the school’s organisational structure enabled them to act as an ongoing source of support, which students valued but which could also foster dependency. Counsellors taking on additional roles in the school led to confusion on the part of both students and counsellors and limited the effectiveness of counselling. Seeing counsellors as authority figures, being unwilling to disclose personal information outside the family and stigma around mental health issues were cultural perspectives which heightened students’ fears related to attending counselling. Trust was an essential precursor of developing a counselling relationship in which the counsellor was perceived as warm, non‐judgemental, caring and empathic. A sensitivity to the sociocultural context and the embeddedness of counsellors in the school organisation are essential to the effective implementation of school‐based counselling.
Elevated ventricular filling pressures and long‐term survival in adults post‐Fontan
Authors: Miranda William R. , Hagler Donald J. , Taggart Nathaniel W. , Borlaug Barry A. , Connolly Heidi M. , Egbe Alexander C.
Published: May 2019

Objective

To assess the association between elevated ventricular‐end diastolic pressures (VEDP) and pulmonary artery wedge pressure (PAWP) on long‐term survival in adult Fontan patients.

Background

The impact of ventricular filling pressures on long‐term survival in adults post‐Fontan palliation is unknown.

Methods

We included 148 adult Fontan patients (age ≥ 18 years) without atrioventricular valve prosthesis or pulmonary vein stenosis undergoing arterial and venous catheterization between December 1999 and November 2017. VEDP was defined as ≥12 mmHg and PAWP as >12 mmHg based on optimal cut‐offs for prediction of mortality on receiver‐operator curves (AUC 0.63 and 0.66, respectively).

Results

Mean age was 31.3 ± 9.2 years and 48.6% of patients were females. Most common congenital defects were tricuspid atresia (36.4%) and double‐inlet left ventricle (28.3%); 59.5% patients had atriopulmonary Fontan connections. Mean VEDP was 11.5 ± 4.7 mmHg and PAWP 10.6 ± 4.5 mmHg (correlation coefficient .76). During a follow‐up of 6.0 ± 4.8 years (median 5.4, IQR 1.4–9.4), there were 45 deaths (30.4%). Overall survival was lower in patients with VEDP ≥ 12 compared to those with VEDP < 12 mmHg (p = .02). Similarly, survival was lower in patients with PAWP>12 compared to patients with PAWP ≤ 12 mmHg (p < .0001). In the multivariate model, PAWP was an independent predictor of death (HR 1.1 per mmHg, 95% CI 1.02–1.15, p = .009) whereas VEDP was not (HR 1.1 per mmHg, 95% CI 1.0–1.13; p = .08).

Conclusion

PAWP but not VEDP was independently associated with long‐term overall mortality in adult Fontan patients. Perhaps PAWP rather than VEDP should be used in the risk stratification of these patients.
Identification of More Benign Cathode Materials for the Electrochemical Reduction of Levulinic Acid to Valeric Acid
Authors: Bisselink Roel J. M. , Crockatt Marc , Zijlstra Martin , Bakker Ivan J. , Goetheer Earl , Slaghek Ted M. , van Es Daan S.
Published: May 2019

The electrochemical production of valeric acid from the renewable bio‐based feedstock levulinic acid has the potential to replace the oxo‐process, which uses fossil‐based feedstock 1‐butylene. The electrochemical reduction of the ketone functionality in levulinic acid using lead or mercury cathodes has already been known for over 100 years. However, large‐scale electrochemical production of valeric acid might be limited, owing to the toxicity of these materials. In this study, we identified three additional cathode materials, cadmium, indium, and zinc, which selectively and efficiently produce valeric acid. Of these materials, indium and zinc are considered more benign. More specifically, at indium there is no formation of the side product γ‐valerolactone, thus resulting in the highest selectivity towards valeric acid. For the electrochemical reduction, a reaction mechanism involving the formation of an organometallic compound is proposed. Furthermore, a possible processing strategy is outlined to enable the continuous electrochemical production of valeric acid on a large scale.
Effect of carbonization temperature on the grindability of carbonaceous material produced from different coals
Authors: Yang Yumeng , Liu Jianzhong , Yuan Shao , Wang Zhihua , Cen Kefa
Published: May 2019

Carbonization experiments were conducted on four kinds of sub‐bituminous coal particles at a temperature range of 450–1200 °C. The effect of treating temperature on the grindability of produced carbonaceous materials was investigated, and its mechanism was analyzed through various means. Results show that the grindability of all coals, whether caking or slightly‐caking, exhibit the same variation trend with an increase in carbonization temperature. Moreover, the entire process can be divided into four stages. (1) After the most intense devolatilization stage, the grindability of carbonaceous material exhibited different degrees of increase compared with that of raw coal because of the development of a pore structure. (2) The first significant decrease in the grindability occurred from the plastic stage to the complete resolidification of the coal matrix. (3) After the aromatic polycondensation stage accompanied by a large amount of H2 release, the coal molecular structure became compact, such that the grindability of semi‐coke considerably decreased again. (4) At high temperatures, the coal matrix underwent graphitization, which changed semi‐coke to coke. The molecular structure of coal became ordered, and the grindability decreased again. The analysis shows that a change in the internal chemical structure of carbonaceous material has a much more pronounced effect on grindability than a change in its pore structure, except in the first stage. The constant compaction and regularization of the coal molecular structure continued happening throughout the entire process and play a decisive role in the change in grindability.
Deactivation mechanism of activated carbon supported copper oxide SCR catalysts in C2H4 reductant
Authors: Yang Li , Jia Yuanyuan , Cheng Jie , Wu Xin , He Jianlong , Liu Fang
Published: May 2019

Current state‐of‐the‐art NH3‐SCR technology based on vanadium catalysts suffers problems associated with NH3 slip and poisoning of the catalyst and blockage of heat recovery steam generators (HRSG). If environmentally‐friendly catalysts capable of efficient operation at lower temperatures could be developed that used a reductant other than NH3, the issues with current state‐of‐the‐art SCR could be significantly lessened. Hence, in this study, activated carbon (AC) supported copper oxide‐based catalysts for SCR while using C2H4 as a reductant was discussed. Reaction testing of catalysts demonstrated high initial NO conversion with steeply declining activity over 2 h of testing when C2H4 was used as the reductant; in comparison, with the same catalyst and NH3 as the reductant, stable, long‐term NO conversion was achieved, but at a lower rate than the initial reactivity with C2H4. As a consequence, catalyst characterization studies were performed to assess deactivation mechanisms when C2H4 was the reductant. These studies included x‐ray diffraction, BET surface area and porosity, temperature programmed reduction, scanning electron microscopy, Raman spectroscopy and x‐ray photoelectron spectroscopy of both fresh and deactivated catalysts. The analytical results showed the surface area and porosity of the catalyst remained unchanged and the initially highly‐dispersed Cu species became agglomerated and more crystalline during reaction testing. Furthermore, carbon black was also detected on the catalyst surface after testing, presumably formed during the decomposition of C2H4. Both agglomeration of the active Cu species and blockage by carbon deposits would decrease the availability of active sites and lead to decreased catalytic activity.
Importance of anal cytology and screening for anal dysplasia in individuals living with HIV with an emphasis on women
Authors: Cimic Adela , Wilkin Timothy J. , Heymann Jonas J. , Alperstein Susan , Ellsworth Grant , Siddiqui Momin T.
Published: May 2019

Background

The incidence of squamous cell carcinoma of the anal canal has been increasing in high‐risk populations. To the authors’ knowledge, there is no international consensus regarding screening for squamous cell carcinoma of the anal canal, but screening is commonly comprised of a Papanicolaou (Pap) test in combination with digital anorectal examination followed by high‐resolution anoscopy if necessary. The current study focused on individuals living with HIV and particularly on women living with HIV.

Methods

In this 5‐year retrospective study, the authors identified 5982 Pap tests, 1848 of which had follow‐up biopsy within 6 months. The rate of atypical squamous cells of undetermined significance was 42%, and approximately 38.1% of cases with this interpretation were diagnosed as high‐grade squamous intraepithelial lesions on follow‐up biopsy. In addition, 82 women with anal cytology had long‐term follow‐up (>10 years) available.

Results

The authors investigated a relationship between cervicovaginal human papillomavirus (HPV) results, cervical pathology, CD4 T‐cell count, and CD4/8 ratio with the anal cytology interpretation. A statistical correlation was noted between the CD4 count and the CD4/8 ratio and the presence of anal dysplasia. Nearly one‐half of the women without cervicovaginal HPV positivity presented with anal dysplasia.

Conclusions

The results of the current study demonstrated that, among women living with HIV, screening for anal dysplasia should not be eschewed, regardless of lower genital tract pathology and/or HPV status. To the authors’ knowledge, the current study is the largest reported retrospective anal cytology cohort in individuals living with HIV.
“Real‐life” outcome of gastrointestinal tumor therapies: A single‐center comparative study
Authors: Buratti Thomas , Mair Maximilian , Mühlberger Nikolai , Mitterer Manfred
Published: May 2019

Background

Despite of the ongoing improvements in gastrointestinal oncology, it remains unclear whether results of randomized controlled trials are achievable in daily clinical practice of nonacademic environments.

Aim

This study aims at assessing a potential efficacy‐effectiveness gap in gastrointestinal cancer treatment.

Methods and Results

Data from 656 gastrointestinal cancer patients treated between 2007 and 2015 in a medium‐sized, nonacademic day hospital oncology unit in Italy were analyzed. Probability of survival and median overall survival as efficacy indicators and the occurrence of grades 3 to 4 adverse events as safety indicators were compared with randomized phase II/III trials of respective entities. Outcomes were well comparable between published data and the real‐life setting. In resectable gastroesophageal cancer, 1‐year survival after treatment initiation was greater (relative risks [RR] = 1.3, p = .007), while patients with adjuvant chemotherapy for pancreatic cancer exhibited inferior 2‐year survival (RR = 0.7, p = .048) compared with referenced trials. At our unit, neutropenia was less frequent (5.8% vs 27.8%, p = .039) in palliative chemotherapy for pancreatic cancer, as was peripheral neuropathy for stage II/III colon cancer (3.9% vs 12.5%, p = .027).

Conclusion

The “real‐life” findings of this study support the efficacy and safety data achieved in landmark trials of gastrointestinal oncology.