bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
Authors: Pantoom Supansa , Pomorski Adam , Huth Katharina , Hund Christina , Petters Janine , Krezel Artur , Hermann Andreas , Lukas Jan
Published: October 2021

Macroautophagy/autophagy plays an important role in cellular copper clearance. The means by which the copper metabolism and autophagy pathways interact mechanistically is vastly unexplored. Dysfunctional ATP7B, a copper-transporting ATPase, is involved in the development of monogenic Wilson disease, a disorder characterized by disturbed copper transport. Using in silico prediction, we found that ATP7B contains a number of potential binding sites for LC3, a central protein in autophagy pathway, so-called LC3 interaction regions (LIRs). The conserved LIR3, located at the C-terminal end of ATP7B, was found to directly interact with LC3B in vitro. Replacing the two conserved hydrophobic residues W1452 and L1455 of LIR3 significantly reduced interaction. Furthermore, autophagy was induced in normal human hepatocellular carcinoma cells (HepG2) leading to enhanced colocalization of ATP7B and LC3B on the autophagosome membranes. By contrast, HepG2 cells deficient of ATP7B (HepG2 ATP7B-/-) showed autophagy deficiency at elevated copper condition. This phenotype was complemented by heterologous ATP7B expression. These findings suggest a cooperative role of ATP7B and LC3B in autophagy-mediated copper clearance.
Prospects of Integrated Photovoltaic-Fuel Cell Systems in a Hydrogen Economy: A Comprehensive Review
Authors: Ogbonnaya Chukwuma , Abeykoon Chamil , Nasser Adel , Turan Ali , Ume Cyril Sunday
Published: October 2021

Integrated photovoltaic-fuel cell (IPVFC) systems, amongst other integrated energy generation methodologies are renewable and clean energy technologies that have received diverse research and development attentions over the last few decades due to their potential applications in a hydrogen economy. This article systematically updates the state-of-the-art of IPVFC systems and provides critical insights into the research and development gaps needed to be filled/addressed to advance these systems towards full commercialisation. The design methodologies, renewable energy-based microgrid and off-grid applications, energy management strategies, optimisations and the prospects as self-sustaining power source were covered. IPVFC systems could play an important role in the upcoming hydrogen economy since they depend on solar hydrogen which has almost zero emissions during operation. Highlighted herein are the progresses as well as the technical challenges requiring research efforts to solve to realise numerous potential applications of IPVFC systems such as in unmanned aerial vehicles, hybrid electric vehicles, agricultural applications, telecommunications, desalination, synthesis of ammonia, boats, buildings, and distributed microgrid applications.
The Effectiveness of Intervening on Social Isolation to Reduce Mortality during Heat Waves in Aged Population: A Retrospective Ecological Study
Authors: Orlando Stefano , Mosconi Claudia , De Santo Carolina , Gialloreti Leonardo Emberti , Inzerilli Maria Chiara , Madaro Olga , Macinelli Sandro , Ciccacci Fausto , Marazzi Maria Cristina , Palombi Leonardo , Liotta Giuseppe
Published: October 2021

Background: Heat waves are correlated with increased mortality in the aged population. Social isolation is known as a vulnerability factor. This study aims at evaluating the correlation between an intervention to reduce social isolation and the increase in mortality in the population over 80 during heat waves. Methods: The study adopts a retrospective ecologic design. We compared the excess mortality rate (EMR) in the over 80 population during heat waves in urban areas of Rome (Italy), where a program to reduce social isolation was implemented compared to others where it was not implemented. We measured mortality of the summer periods from 2015 to 2019 compared with 2014 (a year without heat waves). Winter mortality, cadastral income and proportion of over 90 were included in the multivariate Poisson regression. Results: The EMR in the intervention and controls was 2.70% and 3.81%, respectively. Rate ratio 0.70 (c.i. 0.54 - 0.92, p-value 0.01). The Incidence Rate Ratio (IRR) of the interventions with respect to the controls is 0.76 (c.i. 0.59 - 0.98). After adjusting for other variables, the IRR was 0.44 (c.i. 0.32 - 0.60). Conclusions: Reducing social isolation could limit the impact of heat waves on the mortality of the elderly population.
On the applied mathematics, artificial intelligence and computer calculations development
Authors: Malinetskii Georgii Gennadyevich , Smolin Vladimir Sergeevich
Published: October 2021

A transition from the industrial to the post-industrial phase of the development of civilization takes place currently. In the traditional phase of development (until the twentieth century), the researchers and thinkers focus was on the nature study. In the industrial times (XX century) - the machines world was comprehended and developed. The most important result of this period was the creation of computers. Now the world is entering to the post-industrial phase, where the focus is on the person. This is changing applied mathematics, computer reality. There is a bifurcation in which a significant part of applied mathematics is becoming an industry. A number of promising innovative projects draw attention in this context. There is a transition from "continuous" to "discrete" mathematics, largely associated with the development of cryptography. Another feature of the moment is the neural network revolution in machine learning, which gave a new powerful impetus to the artificial intelligence (AI) development progress. It led to the widespread use of devices and systems that solve "intelligent" problems at the human level and above. The possibilities for solving very complex problems are limited by means that contradict the established views that thinking and reason are based on the soul, which has limitless possibilities. The strong AI (general AI, AGI) creating problem is not in building devices with magical capabilities, but in creating limited systems that can learn to solve many of the problems available. An important AGI property should be cooperation with people, taking into account civilizational norms. This property has not only a technical side, it depends on social relations. Sustainable development requires an agency approach to AGI. Modern applied mathematics has faced fundamental difficulties in complex problems. Multiple increases in the performance of computing systems did not lead to breakthrough results. As new paradigms, "analog" computing systems working with the use of new principles are neural networks and quantum computers. It is shown that these approaches, at best, can help to solve the "past tasks", and not the "future tasks" associated with the post-industrial phase of the development of civilization. The domestic applied mathematics efforts should be used to solve the central problems of the post-industrial society development in Russia using interdisciplinary approaches. This can make it possible to return to the number of countries with advanced technologies in the most important modern production areas. The alternative directions of the science development related to the human capabilities expansion are considered. The key one is related to AI, which can change reality. The article pays special attention to alternative approaches to AI development.
Atuação da Fisioterapia Frente ás Disfunções Sexuais Masculinas: disfunção erétil e ejaculação precoce
Authors: Bemvenuto Rayssa Pereira , Carvalho Fabio Oliveira de , Souza Elenilton Correia de
Published: October 2021

Introdução: as disfunções sexuais masculinas são alterações no funcionamento do sistema genital masculino, ocasionando déficits funcionais. Entre as disfunções mais comuns, estão: a disfunção erétil (DE), que é definida como uma incompetência persistente de dar início e manter uma ereção satisfatória, a qual permita ter um desempenho sexual suficiente; e a ejaculação precoce (EP), que é detalhada como a dificuldade de reter a ejaculação, e/ou mantê-la por mais de um minuto durante a penetração ou diante de outra forma de estimulação sexual. Em detrimento aos problemas de disfunções sexuais, os homens têm buscado alternativas para amenizar os sintomas, fazendo uso de drogas lícitas e ilícitas, acarretando prejuízos à saúde, levando a um quadro de drogadição, toxicodependência e até ao óbito. Pensando nessa perspectiva, a atuação da fisioterapia frente a essas disfunções se faz extremamente necessária a fim de reestabelecer o quadro funcional dos homens de forma segura e eficiente, priorizando um atendimento não medicamentoso e convencional. Objetivo: desse artigo é compreender a atuação fisioterapêutica nas disfunções sexuais masculinas. Método: Nesse trabalho, é uma revisão integrativa em que se aplicaram os Descritores em Ciências da Saúde (DeCS), tais como: “sexual dysfunction”, “men”, “physical therapy”, limitando-se aos idiomas português, inglês e espanhol, aos estudos com seres humanos, aos temas em conformidade a esse trabalho e aos textos na íntegra, com restrições temporais de 2010 a 2020, para os artigos, e tendo suas consultas realizadas nas bases de dados: Scientific Electronic Library Online (SciELO, 2 artigos), Medical Literature Analysis and Retrieval System Online (Medline, 307 artigos/PubMed, 243 artigos), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS, 7 artigos), Biblioteca Virtual em Ciências da Saúde (BVS, 320 artigos). Resultados: Se mostraram positivos e eficientes, pois, a atuação da fisioterapia frente a essas disfunções apresenta efeitos promissores no reestabelecimento do quadro funcional desses pacientes. Discussão: O uso da cinesioterapia, eletroterapia, vacuoterapia e terapias por ondas de choque de baixa intensidade têm se mostrado eficazes na melhora da ejaculação precoce e disfunção erétil. Conclusão: É notório observar que a atuação da fisioterapia na saúde pélvica é eficiente e eficaz, pois, através de anamnese, exame físico, testes e escalas funcionais, avaliará o paciente de forma individual e empática, a fim de utilizar os recursos próprios e indicados para cada paciente, visando fortalecer os músculos do assoalho pélvico e melhorar o fluxo peniano, aprimorando o desempenho sexual satisfatório e devolvendo qualidade de vida, autoestima e saúde biopsicossocial para os pacientes e a família.

Palavras-chave: Disfunções sexuais; Fisioterapia; Homem.
The relationship between fish length and otolith size and weight of Acanthopagrus arabicus Iwatsuki, 2013 (Sparidae) collected from the Iraqi marine waters
Authors:   School of Environmental and Animal Sciences, Unitec Institute of Technology, 139 Carrington Road, Mt Albert, Auckland 1025, New Zealand, Jawad Laith , Qasim Audai ,   Marine Science Centre, University of Basrah, Basrah, Iraq, Al-Zaidy Faleh Musa ,   Marine Science Centre, University of Basrah, Basrah, Iraq, Waryani Baradi ,   Department of Fresh Water Biology and Fisheries, University of Sindh, Jamshoro, Sindh Pakistan, Rutkayová Jitka ,   University of South Bohemia, Faculty of Agriculture, Department of Animal Science, České Budějovice, Czech Republic
Published: October 2021

Fish specimens (n=75) of A. arabicus were collected from the marine waters of Iraq at Khor al-Zubair. Collection was conducted in the period February–September 2019 at depth of 10–25 m. Relationships between fish length and otolith length, width and weight were calculated for the Arabian yellowfin seabream, Acanthopagrus arabicus using linear models. This study represents the first data available on the relationship of fish size and otolith size and weight for A. arabicus in the Arabian Gulf area. The various relationships between fish length otolith length, width and weight were calculated: Y = -1E – 0.06X2 + 0.0106X + 5.2628, Y = 4E – 06X2 + 0.0077X + 2.1834, and Y = 9E – 07X2 + 0.0013X – 0.191 respectively.
Book Leverage in Islamic Banking in Indonesia
Authors: Shaferi Intan , Safitri Julia
Published: October 2021

The purpose of this study is to examine how book leverage is in Islamic banks in Indonesia. The leverage book shows how the use of debt in Islamic banking. This study will give the results of how the lag leverage, profitability with the size of the company as the control have an effect on the book leverage of Islamic banking. This study uses Islamic banking data in Indonesia with a research period of four years, namely 2016-2019. This study used secondary data from Islamic banking and analyzed using regression. The results showed that there is an influence between lag leverage, profitability, and company size on the book leverage of Islamic banking in Indonesia.
THE CORRELATION BETWEEN EFL ANXIETY AND STUDENTS’ READING COMPREHENSION”.
Authors: Rama Asri Nofa
Published: October 2021

The objective of the current study examined whether there was any significant correlation between foreign language classroom anxiety and students’ reading comprehension. In this regard, hopefully, this study provided English language lecturers to recognize the most provoking factor that affect learning a foreign language, such anxiety and helped students to solve language anxiety to become better English language students. This researcher was conducted at Lakidende University, particularly 32 university students of English Language Teaching Department who enrolled in academic year 2018/2019. The data were obtained from students’ reading comprehension test and questionnaire that is Foreign Language Classroom Anxiety Scale (FLCAS) and to analyze the data this study applied Pearson Correlation analysis. The finding revealed that there was a significant relationship between foreign language classroom anxiety and students’ reading comprehension, p (.061) 0.05. Meanwhile, the strength of correlation between reading anxiety and students’ reading comprehension was categorized “moderate” according to table Guidelines of Interpreting Pearson's Correlation Coefficient (r =.381). It might be the fact that most of students frequently experienced moderate level of foreign language classroom anxiety in their reading comprehension class.
BECOMING A MOTHER: THE TRANSITION TO MOTHERHOOD IN CHIMAMANDA NGOZI ADICHIE’S ZIKORA
Authors: Roifah Miftahur
Published: October 2021

In patriarchal society, motherhood is viewed as a responsibility for women although not all are willing or able to carry it on.  To become a mother, a woman has to experience a challenging phase in life and ready to sacrifice everything they have. Feminist critics see motherhood as a complex issue operating patriarchal institution that regulates, dominates, and oppresses women. What is more, some women are not ready with the consequences during the transition to motherhood and bear the status of becoming a mother that often results in having a hard time. To bring this issue into discussion, this study is going to explore the crises that Zikora has to undergo in her transition to become a mother. Zikora is the protagonist in Chimamanda Ngozi Adichie's short story, Zikora. In analyzing the issue, this study applies the theory of motherhood by Andrienne Rich and uses a qualitative approach with a close reading method. The result of the study shows that motherhood brings women to a new world full of challenges. Motherhood requires not only physical strenght but also mental strenght and self control so that whatever the crises are, women can bear them and overcome the obstacles they are facing.
COVID-19 pandemic as a challenge to constitutional legal order
Authors: Varlamova Nataliya
Published: October 2021

The COVID-19 pandemic is certainly an emergency, it has affected almost all countries in the world and has a serious impact on the functioning of their authorities. In the current state of emergency, states have two strategies of action: to overcome it within the framework of the existing constitutional order and the current legal regulation, or to introduce a special legal regime. Today, the choice of these options for responding to the COVID-19 pandemic is being actively discussed by politicians and experts. Each of them has its pros and cons. In the event of a refusal to declare a state of emergency, the usual rules and procedures are used, which also allow the establishment of additional restrictions on human rights necessary in connection with the pandemic. This approach is attractive because it prevents the spread of panic and demonstrates that the state does not intend to resort to “draconian” measures. At the same time, a formal declaration of a state of emergency fosters awareness of the gravity of the situation and mobilizes society to combat it. Furthermore, this forces the state to openly declare what restrictions it is going to introduce, substantiate the actual existence of an emergency situation and the need for the measures used, and also indicate the time frame for this regime. This creates certain guarantees that the additional restrictions imposed on human rights will not apply to normal conditions. A state of emergency usually presupposes the concentration of public authority in the body (bodies) of executive power, often specially created for a given period, which in their activities largely replaces the parliament and regional authorities. However, in a pandemic, the “level of emergency” manifests itself differently in different regions of the country, which requires decentralization of governance, the involvement of regional authorities and civil society institutions. But the establishment of the necessary restrictive measures at the regional level very often contradicts the constitutional guarantees of human rights and freedoms, which cannot be corrected by the regional authorities, which “erodes” the constitutional order. The greatest danger is the abuse of emergency powers and their use for political purposes, as well as the preservation of certain emergency measures and the introduced legal regulation after the end of the emergency situation (actually existing or officially declared).
Legal restrictions on the right of association in political parties and their interpretation in court decisions: comparative legal analysis
Authors: Vershinin Andrey
Published: October 2021

The article examines the issue of exercising the freedom of association in political parties in Russia in a comparative analysis with the leading democratic countries of the world. Modern democracies cannot be imagined without political parties, which are the representors of the interests of their voters in legislative bodies and local government bodies. The development of civil society and the entire political system in the country depends on how the freedom of association in political parties and the access of parties to participate in elections is realized. The development of legislation on political parties in the Russian Federation proceeded unevenly. In the first years after the adoption of the Constitution the legislative body did not introduce strict requirements for parties. The adoption of a special federal law on political parties in 2001 became a turning point in the development of the party system. The author identifies two large blocks of restrictions on the creation of parties. The first is legislative restrictions, the second is the restrictions that arise from the unfair activities of legislative and law enforcement agencies. In this work, legislative restrictions are compared with restrictions in other democracies, as well as based on legal positions developed by the European Court of Human Rights. The author comes to the opinion that some restrictions on the creation of parties are not necessary now, in the meantime they significantly narrow the possibilities of party creation and political competition. First, we are talking about a ban on the creation of regional parties. The Constitutional Court in its legal positions indicated that this restriction is temporary and will be lifted over time. Within the framework of this work, the author will give suggestions on changing the approach to the creation of political parties in Russia, which should affect the emergence of new strong parties at different levels of public authority. The author believes that a system of “controlled multiparty system” has developed in Russia, which is implemented both in changing the legislation on political parties based on the interests of the “party in power” and the practice of the registration body, which prevents the formation of new parties claiming to redistribute the existing distribution of forces. Based on the analysis of the legislation on political parties, law enforcement practice, decisions of the Constitutional Court of the Russian Federation, the ECHR and the legislation of foreign countries, the author proposes approaches to reforming the existing party system, which include small cosmetic changes and large-scale changes in approaches to the creation of parties.
Theory and practice of mixing procedural models in the Pre-trial Chamber of the International Criminal Court mechanism of functioning
Authors: Pechegin Denis
Published: October 2021

The increasing interpenetration of the main models of the process and the approval of international standards for the production of criminal cases raise the question of the development and improvement of the form of legal proceedings in the category of the most relevant in modern science. On the one hand, the attention of many scientists is focused on strengthening the competitive core of the process and ensuring, as far as possible, a balance of power between the parties. On the other hand, it is stated that legal proceedings that do not pursue the goal of achieving material truth, especially due to the absolute nature of the principle of competition, lead to excessive formalism that has nothing to do with fair trial. The solution to the problem of combining trial models (the balance of adversarial and investigative cores) is seen in the International Criminal Court. The procedure of criminal proceedings in the International Criminal Court is the result of special scientific modeling taking into account the indicated doctrinal trends, and the degree of generalization of approaches of leading legal families in the structure of the Rome Statute of the International Criminal Court is so high that it allows us to speak about the universality of this procedural system. If the predecessors of the International Criminal Court preference were really given only one started (so, the ICTY was based on the example of the Anglo-Saxon adversarial procedure model with the “American accent”), the Rome Statute of the International Criminal Court reflected the trend to the initial formation of a balanced trial procedures designed to overcome the deviations in the balance of power by introducing an adversarial process with “inquisitorial” elements: for example, the Pre-trial Chamber, duties of the Prosecutor fully and objectively investigate the circumstances of the case, the duties of the court of first instance to establish the truth in the case. However, this does not mean any disregard for the adversarial core at the pre-trial stage. The article is devoted to theoretical and practical aspects of the combination of adversarial and investigative cores in the activities of the pre-trial Chamber of the International criminal court and reflects the results of a study led by professor Anita Ušacka, honorary doctor of law, in the preparation of a Commentary to the Rome Statute in Russian.
Judgment of the Supreme Court of Canada of February 28, 2020, on Nevsun v. Araya: a “quiet revolution” in the assessment of the status of corporations under public international law?
Authors: Rusinova Vera , Ganina Olga
Published: October 2021

The article analyses the Judgment of the Supreme Court of Canada on the Nevsun v. Araya case, which deals with the severe violations of human rights, including slavery and forced labor with respect of the workers of Eritrean mines owned by a Canadian company “Nevsun”. By a 5 to 4 majority, the court concluded that litigants can seek compensation for the violations of international customs committed by a company. This decision is underpinned by the tenets that international customs form a part of Canadian common law, companies can bear responsibility for violations of International Human Rights Law, and under ubi jus ibi remedium principle plaintiffs have a right to receive compensation under national law. Being a commentary to this judgment the article focuses its analysis on an issue that is of a key character for Public International Law, namely on the tenet that international customs impose obligations to respect human rights on companies and they can be called for responsibility for these violations. This conclusion is revolutionary in the part in which it shifts the perception of the companies’ legal status under International Law. The court’s approach is critically assessed against its well-groundness and correspondence to the current stage of International law. In particular, the authors discuss, whether the legal stance on the Supreme Court of Canada, under which companies can bear responsibility for violations of International Human Rights Law is a justified necessity or a head start.
The Venice Commission and the European Court of Human Rights: common grounds
Authors: Kovler Anatoly , Fokin Evgeniy
Published: October 2021

Interaction of international justice bodies with expert organizations has not been the subject of an analysis performed by legal scholars. Meanwhile, cooperation between the European Commission for Democracy through Law (better known as Venice Commission) and the European Court of Human Rights makes it possible to establish many touch points in their activities. Despite the obvious differences in their status and subject competences both bodies are distinguished by the similarity of methodological approaches as evolutive interpretation of law, doctrine of margin of appreciation, conceptual framework. In the last decade the convergence of legal positions of the European Venice Commission and the European Court has noticeably increased. This is particularly evident in the reports of the Venice Commission and the European Court Grand Chamber’s judgments. The Commission’s 2020 report on individual access to constitutional justice, presented by a former judge of the European Court of Justice and now a member of the Venice Commission, Angelika Nussberger, is an illustrative example of this convergence of the positions of both institutions on the highly sensitive area of public relations. The practice of providing amicus curiae expert opinions by the Commission at the request of the European Court has also become more widespread. Dozens of judgments of the ECHR of the last decade contain lengthy references to the legal positions of the Commission. The article analyzes some of them. The authors conclude that this methodology strengthens the credibility of the reasoning for the Commission’s Opinions and the Court’s judgments. In the judgments of the European Court in cases concerning Russia there are also some references to the legal positions of the Venice Commission. This applies primarily to decisions on the implementation of civil and political rights of citizens. The article also analyses some of the acts of the Commission and the Court that have similar subjects of consideration. The authors conclude that the interaction of the Venice Commission and the European Court provides a unique example of the synergy of judicial interpretation of law and the opinions of the expert community. First of all, these are the issues of the functioning of the justice systems, the participation of citizens in political life, the electoral system, and freedom of speech. Ultimately, both institutions are involved in the realization of the quasi-utopia of creating a common European legal space.
Inter-American Court of Human Rights: a review of practice for 2020
Authors: Parra Vera Oscar , Jesús Pérez Edward
Published: October 2021

This article presents a grasp of the Inter-American Court of Human Rights’ most important case law of 2020. As is developed within the paper, during 2020, the Court made important developments on Inter-American case-law which will have relevant incidence for the region. Many of the major developments that will be studied in this paper concern the right to nondiscrimination; economic, social and cultural rights; detention conditions, and some important advances on rights protection within the COVID-19 context.
Pregnancy Complications and Risk of Uterine Rupture Among Women With Singleton Pregnancies in China
Authors: Tao Jing , Mu Yi , Chen Peiran , Xie Yanxia , Liang Juan , Zhu Jun
Published: October 2021

Background: The goal of this study was to investigate whether pregnancy complications are associated with an increased risk of uterine rupture (UR) and how that risk changes with gestational age. Methods: We obtained all data from China’s National Maternal Near Miss Surveillance System (NMNMSS) between 2012 and 2018. Poisson regression analysis was used to assess the risk of UR with pregnancy complications (preeclampsia, gestational diabetes mellitus, placental abruption, placenta previa and placenta percreta) among 9,454,239 pregnant women. Furthermore, we analysed the risks of UR with pregnancy complications in different gestational age groups. Results: Compared with women without pregnancy complications, those with different complications (except for preeclampsia) had a 1- to 3-fold greater risk of UR. These associations also persisted in women without a previous caesarean delivery. Moreover, an increased risk of UR before term birth was observed among women with gestational diabetes mellitus, placental abruption and placenta percreta. A large for gestational age (LGA) foetus increased the risk of UR in women with gestational diabetes mellitus, especially at 32 to 36 weeks gestation. Conclusions: Better quality antenatal care and early intervention for women with these pregnancy complications are needed to minimize the incidence of UR.
The Role of HOX Genes as Potential Biomarkers in Colorectal Cancer: A Systematic Review
Authors: Martinou Eirini , Falgari Giulia , Angelidi Angeliki , Bagwan Izhar
Published: October 2021

Background: Colorectal cancer (CRC) is worldwide the third leading cause of cancer-related death, and despite therapeutic advances, survival remains low. Emerging evidence shows that Homeobox (HOX) genes are important in carcinogenesis, and their dysregulation has been linked with metastatic potential and poor prognosis. This systematic review aims to present the current evidence on the role of HOX genes as biomarkers in CRC and the impact of their modulation in tumour growth and progression. Methods: MEDLINE, EMBASE, Web of Science and Cochrane databases were searched by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Eligible studies investigated two research questions: a) the clinicopathological and prognostic significance of HOX gene dysregulation in patients with CRC and b) the functional role of HOX genes in CRC progression. This study was registered in the international prospective register of systematic reviews (PROSPERO), CRD42020190953. Results: Twenty-five studies enrolling 3003 patients with stage I-IV CRC, showed that 26 out of 39 HOX genes were dysregulated in cancerous versus normal colon. Aberrant expression of HOX proteins was significantly related to tumour depth, nodal invasion, distant metastases, advanced stage and poor prognosis. Twenty-two preclinical studies showed that HOX proteins are crucially related to tumour growth and metastatic potential by affecting cell proliferation and altering the expression of epithelial-mesenchymal transition modulators. Conclusions: In conclusion, our findings suggest that HOX proteins play vital roles in CRC progression and significantly affect survival. Further research, though, is required to elucidate their potential role as biomarkers in CRC.
The Study of the Pathogenesis of Idiopathic Central Precocious Puberty Based on Gut Microbiota
Authors: Huang Congfu , Wu Bin , Yang Wei , Chen Junru , Yang Zhenyu , Li Yinhu , Chen Shufen , Wu Xiangling , Wu Liping , Liu Haiying
Published: October 2021

Object To analyze the correlation between gut microbiota (GM) and hyperandrogenemia, insulin resistance, carbohydrate metabolism, and explore whether the pathogenesis of idiopathic central precocious puberty (ICPP) and polycystic ovary syndrome (PCOS) is consistent based on GM. Methods In this study, we have recruited 27 ICPP (ICPP group) and 23 healthy children (healthy group), and collected the blood and fecal samples from the participants. Blood samples were tested for hormones, including the follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, and testosterone. DNA was extracted from fecal samples, and amplified and sequenced with 16S rDNA V3-V4 region. Finally, we annotated the sequencing results, counted the differences in hormone indicators and GM composition between the two groups, and analyzed the correlation with clinical indicators. At the same time, we reviewed the literature on GM and PCOS.Results Compared with the healthy group, the ICPP group exhibited significantly higher levels of the hormone and other indicators (P < 0.05). At the phylum level, the ICPP group showed significantly enriched Proteobacteria than the healthy group (4.85% vs 2.92%). At the genus level, the abundances of Roseburia and Prevotella were significantly higher in the ICPP group than those in the healthy group (7.55% vs 2.01%, 3.95% vs 0.19%), but Bacteroides were obviously decreased in the ICPP group (29.96% vs 44.91%). In addition, the potential associations underlying the sex hormonal secretion and the carbohydrate metabolism pathways of GM increased significantly in the ICPP group. Conclusion The alternations of GM in ICPP patients are closely related to carbohydrate metabolism, hyperandrogenism, and insulin resistance, indicating similar pathogenesis with polycystic ovary syndrome.
Runoff Prediction Model Based on Improved Convolutional Neural Network
Authors: Xu Yichao , Liu Yi , Jiang Zhiqiang , Yang Xin
Published: October 2021

Due to the influence of human regulation and storage factors, the runoff series monitored at the hydropower stations often show the characteristics of non-periodicity, which makes runoff prediction simulation difficult. This paper attempts to construct an improved one-dimensional convolutional neural network (CNN) model for runoff prediction simulation. The improved CNN model consists of two convolution layers and a full connection layer and uses LeakyRelu as the activation function. Based on the historical rainfall and runoff data of the ZheXi reservoir in Hunan Province, this paper uses the improved CNN model to simulate runoff prediction and compares the results with the traditional ANN model and the traditional CNN model. The results show that the improved CNN model is superior to the traditional ANN model and the traditional CNN model. It proves that the improved CNN model is suitable for the non-periodic runoff prediction simulation, and it can avoid the data problems such as gradient disappearance that may occur in the traditional neural network model.
Graph Neural Network for Integrated Water Network Partitioning and Dynamic District Metered Areas
Authors: RONG KEZHEN , Fu Minglei , CHEN JIAWEI , ZHENG LEJIN , ZHENG JIANFENG , YASEEN ZAHER MUNDHER
Published: October 2021

Water distribution systems (WDSs) are used to transmit and distribute water resources in cities. Water distribution networks (WDNs) are partitioned into district metered areas (DMAs) by water network partitioning (WNP), which can be used for leak control, pollution monitoring, and pressure optimization in WDS management. In order to overcome the limitations of optimal search range and the decrease of recovery ability caused by two-step WNP and fixed DMAs in previous studies, this study developed a new method combining a graph neural network to realize integrated WNP and dynamic DMAs to optimize WDS management and respond to emergencies. The proposed method was tested in a practical case study; the results showed that good hydraulic performance of the WDN was maintained and that dynamic DMAs demonstrated excellent stability in emergency situations, which proves the effectiveness of the method in WNP.
The Impact of The Pico Y Placa Policy On Fine Particulate Matter In Lima, Peru
Authors: Romero Yovitza , deSouza Priyanka , Duarte Fabio , Kinney Patrick , Ratti Carlo , Noel Julien
Published: October 2021

Lima has been ranked among the top most polluted cities in the Americas. Vehicular emissions are the dominant source of pollution in the city. In order to reduce congestion and pollution levels during the XVIII Pan- and Parapan-American Games, Lima government officials enacted the pico y placa policy to restrict the number of vehicles on certain heavily trafficked roads in the city at rush hours between Monday to Thursday based on the last digit of their license plates. This policy was retained after the Games. In this paper we evaluate the impact of this policy on fine particulate matter concentration levels (PM2.5) at a background site in the city using a difference-in-difference approach. We find that the policy resulted in increases on PM2.5 levels on Monday-Thursday compared to Friday-Sunday levels after the policy was enacted, compared to previous years. However, such an increase was not significant. These results suggest the need for additional policies to reduce pollution due to traffic in Lima. It also suggests the need to track the response to this policy over time to evaluate its efficacy.
An Effective Congestion and Interference Secure Routing Protocol for Internet of Things Applications in Wireless Sensor Network
Authors: Vankdothu Ramdas , Abdul Hameed Mohd
Published: October 2021

This paper provides an effective Wireless Sensor Network(WSN) routing solution for Internet of Things(IoT) applications cognizant of congestion, security, and interference. Because several sources try to deliver their packets to a destination simultaneously, which is a common case in IoT applications. The proposed congestion and interference aware safe routing protocol is claimed to work in networks with high traffic. The signal to interference ratio (SINR), congestion level, and survival factor is used in our suggested procedure to estimate the cluster head selection factor first. The adaptive fuzzy c-means clustering method clusters the network nodes based on the cluster head selection factor. After that, data packets are encrypted using Adaptive Quantum Logic-based packet coding. Finally, the Adaptive Krill Herd (AKH) optimization method identifies the least congested corridor, resulting in optimal data transmission routing. The exploratory findings show that the provided strategy outperforms previous methodologies in network performance, end-to-end delay, packet delivery ratio, and node remaining energy level.
Comparison and Validation of APRI and FIB-4 for Evaluating Liver Fibrosis in Chinese Hepatitis B Virus-infected Patients with Persistently Normal ALT, Mildly and Significantly Elevated ALT
Authors: Chen Shanshan , Gong Yuhan , Li Jie , Dai Xuan , Zhao Yueyue , Li Hong , Huang Haijun
Published: October 2021

Background: Many noninvasive models based on serum markers composition are used for the assessment of liver fibrosis, reducing the need for liver biopsy. However, most of the models have rarely been validated in Chinese hepatitis B patients. We aim to evaluate and validate chronic hepatitis B(CHB) patients with normal ALT, mildly and significantly elevated ALT levels.Methods: This single-center retrospective study enrolled 285 patients with CHB who underwent liver biopsy. There were 156 patients in normal ALT group, 85 patients in mildly elevated ALT group, and 44 patients in significantly elevated ALT group. The diagnostic accuracy of APRI and FIB-4 was evaluated by areas under the characteristic curves (AUROC) using the histological assessment of the fibrosis stages of the biopsy specimens as the standards.Results: Among 285 patients with CHB, 156 patients had normal ALT level, of which 65 (41.7%) had significant fibrosis(S2-4). The evaluation of significant fibrosis, AUROC in APRI and FIB-4 were 0.608, 0.634, 0.708 and 0.638, 0.679, 0.734 in normal ALT, mildly and significantly elevated ALT, respectively. The assessment of advanced fibrosis, AUROC in APRI and FIB-4 were 0.636, 0.751, 0.708 and 0.652, 0.763, 0.734 in normal ALT, mildly and significantly elevated ALT groups, respectively. Conclusions: APRI and FIB-4 may not be ideal noninvasive markers for evaluating liver fibrosis in Chinese HBV-infected patients with normal ALT levels. Compared with HBV-infected patients with normal ALT, APRI and FIB-4 had high accuracies in diagnosing liver fibrosis in patients with mildly and significantly elevated ALT.
A Durable 4-1BB-based CD19 CAR-T Cell for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Ying Zhitao , He Ting , Jin Shanzhao , Wang Xiaopei , Zheng Wen , Lin Ningjing , Tu Meifeng , Xie Yan , Ping Lingyan , Liu Weiping , Deng Lijuan , Ding Yanping , Hu Xuelian , Bu Bing , Lu Xin-an , Song Yuqin , Zhu Jun
Published: October 2021

Backgroud
: CD19-directed chimeric antigen receptor T (CAR-T) cell therapy has shown great promise for cure of relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). Previous studies reported that 4-1BB-based CD19 CAR-T was more beneficial for the clinical outcomes than CD28-based CAR-T, especially lower rates of severe adverse events. However, the median progression-free survival (mPFS) of 4-1BB-based product Kymriah was shorter than that of the CD28-based Yescarta (2.9 v.s. 5.9 months), suggesting that the long-term effectiveness of Kymriah was limited. Thus, a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.
Methods
Here we presented a CD19 CAR-T (named IM19) with FMC63 scFv, 4-1BB and CD3ζ intracellular domain, which was manufactured into a memory T-enriched formulation and launched a clinical trial for treatemt of r/r B-NHL. The clinical outcomes of IM19 were evaluated in 22 r/r B-NHL patients in a Phase I/II trial with dose-escalation investigation (5×105, 1×106 and 3×106/kg).
Results
All patients received a single infusion of IM19 after 3-day conditional regimen. Cytokine release syndrome (CRS) occurred in 13 patients (59%), with 54.5% of grade 1–2 and 4.5% of grade 3, whereas Kymriah led to 22% of > grade 3 CRS. Only one patient showed > grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). At 6 months, the overall response rate was 47.62%, and the complete response rate was 42.86%. The mPFS of IM19 achieved 9 months and the 1-year overall survival rate was 78%.
Conclusions
These results demonstrated the safety and durable efficacy of IM19 with FMC63 scFv, 4-1BB and CD3ζ intracellular domain, that is promising for further development and clinical investigation.
Trial registration
: The registration date of the clinical trial is May 17, 2018(17/05/2018) and the trial registration numbers is NCT03528421.
Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma
Authors: Komatsu Shohei , Yano Yoshihiko , Fujishima Yoshimi , Ishida Jun , Kido Masahiro , Kuramitsu Kaori , Yamamoto Atsushi , Goto Tadahiro , Yanagimoto Hiroaki , Toyama Hirochika , Ueda Yoshihide , Kodama Yuzo , Fukumoto Takumi
Published: October 2021

Background
Atezolizumab plus bevacizumab therapy is the new standard treatment option for advanced hepatocellular carcinoma (HCC). The clinical details and sequential course after atezolizumab plus bevacizumab therapy remain to be determined.
Methods
From October 2020 to June 2021, 34 consecutive patients who received atezolizumab plus bevacizumab therapy were evaluated. Their clinical outcomes were assessed according to liver function classified by modified albumin-bilirubin (ALBI) grade 1 and 2a (1/2a) versus 2b and treatment line (first-line versus second- or later-line). Furthermore, the treatment sequence after atezolizumab plus bevacizumab therapy was also assessed.
Results
The objective response and disease control rates were 15.6% and 93.8%, respectively. The median proportions of ALBI scores at 1, 2, and 3 months relative to the baseline scores were 0.94, 0.97, and 0.93, respectively. The median proportions of α-fetoprotein (AFP) scores at 1, 2, and 3 months relative to the baseline scores were 0.98, 1.12, and 1.83, respectively. There were no significant differences in the changes in the proportions of AFP and ALBI scores according to both liver function and treatment line. Twelve patients were administered lenvatinib treatment after the failure of atezolizumab plus bevacizumab therapy. The proportions of AFP and ALBI scores at 1 month relative to the baseline scores were 0.55 and 0.81, respectively.
Conclusions
Atezolizumab plus bevacizumab therapy can be administered effectively for advanced HCC irrespective of patients’ liver function and treatment line. Lenvatinib administration after atezolizumab plus bevacizumab therapy can be effective, although special attention should be paid to the deterioration of liver function.
Adaptive Control for Quadrotors with Uncertain and Faulty Actuators
Authors: Han Qi , Liu Xiangbin , Liu Zhitao , Su Hongye
Published: October 2021

Two adaptive control strategies are presented in this paper for two types of quadrotors to cope with potential uncertainties and faults in the actuator system. The four actuators of the considered quadrotors are distinct and suffered from loss of effectiveness (LOE) as well. To accomandate unknown actuator parameters, a filter-based immersion and invariance (I&I) adaptive controllers are designed for attitude and altitude subsystems, respectively, and an integral backstepping controller is developed for the horizontal subsystem to achieve null steady-state error. Both simulation and experiment results are carried out to illustrate the effectiveness of trajectory tracking performance and fault-tolerant accomondation ability of the proposed control schemes.
Evaluation of the Interference of HbE on HbA1c Results on the Detection System Produced by Shenzhen Lifotronic
Authors: Hu Yaozong , Suo Minghuan , Xu Yan , Hu Wenyong , Hu Ting , Huang Jiamin , Wang Weijia , Chen Kang
Published: October 2021

Objective: To analyze the interference of HbE on the HbA1c results on detection systems manufactured by Shenzhen Lifotronic. Methods: Volunteers were recruited from Zhongshan city, Guangdong province during June 2020 to November 2020. A total of 55 specimens were obtained, including 40 cases without HbE(23 cases in normal group and 17 cases in diabetes group) and 15 cases with HbE variant. HbA1c of these two groups (normal and HbE group) were analyzed by Shenzhen Lifotronic H8, H9 and GH-900Plus, Bio-Rad Variant II Turbo 2.0 and D-10 from USA, Arkray HA-8180 from Japan, statistical analysis was conducted on the difference between detection results of normal group and HbE variant group. Bio-Rad Variant II Turbo 2.0 was used as the comparison system to calculate the bias and to evaluate the interference of HbE on each system. Results: In normal group, the results of each detection system were comparable to those of Variant II Turbo 2.0, with a bias of -6%~6%. In HbE variant group,system bias of H8, H9, GH-900Plus and D-10 was within -6% and 6%, and the results showed no significant difference (P>0.05), while the negative bias of HA-8180 showed significant difference (P<0.05). Conclusion Compared with Bio-Rad Variant II Turbo 2.0, HbA1c can be correctly detected by H8, H9 and GH-900Plus system without the interference of HbE.