bluuebunny/crossref_metadata_2025 huggingface dataset:
PERLINDUNGAN HUKUM TERHADAP KELALAIAN PEMENUHAN PEMBAYARAN NAFKAH ANAK PASCA PERCERAIAN BERDASARKAN PUTUSAN PENGADILAN AGAMA BLITAR
Authors: Pratiwi Rufia Wahyuning
Published: June 2021

Penelitian ini dilatar belakangi oleh adanya beberapa permasalahan yang ada di Pengadilan Agama Blitar, dengan beberapa pengaduan masyarakat terkait tentang lalainya mantan suami dalam kewajibannya memberikan nafkah kepada anaknya pasca perceraian.  Karena anak adalah manusia kecil yang butuh perlindungan dan butuh diperlakukan secara manusiawi, dan sila kemanuasian yang adil dan beradab maupun misi dalam maqoshidussyariah hifdhul nafsi dan hifdhul nasl (melindungi jiwa dan keturunan) dalam syariah Islam harus terwujud. Tujuan penelitian ini agar supaya para pencari keadilan cerdas dan paham akan hukum serta langkah-langkah yang harus ditempuh dalam menghadapi suatu permasalahan hukum guna tegaknya hukum dan terwujudnya keadilan. Hasil penelitian ini memperoleh bahwa hasil pertama mengetahui penyebab adanya kelalaian terhadap pemenuhan pembayaran nafkah anak pasca perceraian, sehingga perlu ditelaah ulang tentang putusan hakim yang bisa menjadi tolak ukur telah adanya jiwa kemanusian demi tegaknya hukum dan rasa keadilan yang dirasakan oleh pencari keadilan. Kedua, mencari solusi tepat agar produk pengadilan yang berupa putusan benar-benar bisa mencerminkan nilai-nilai kemanusiaan, keadilan yang benar-benar bisa melindungi kepentingan para pencari keadilan.Kata kunci: anak, perceraian, perlindungan, hukum This research is motivated by a number of problems that exist in the Blitar Religious Court, with some related public complaints about the negligence of ex-husband in his obligation to provide for their children after divorce. Because children are little people who need protection and need to be treated humanely, and the precepts of fair and civilized humanity and mission in maqoshidussyariah hifdhul nafsi and hifdhul nasl (protecting souls and offspring) in Islamic sharia must be realized. The purpose of this study is so that justice seekers are smart and understand the law and steps that must be taken in dealing with a legal problem in order to uphold the law and the realization of justice. The results of this study found that the first result found out the cause of negligence in fulfilling child income payments after divorce, so it was necessary to review the judge's decision that could become a benchmark for the existence of a humanitarian spirit for the sake of law enforcement and a sense of justice felt by justice seekers. Second, finding the right solution so that court products in the form of decisions can truly reflect human values, justice which can truly protect the interests of justice seekers.Keywords: child, divorce, protection, law
DEKRIMINALISASI BAGI PENYALAHGUNA, KORBAN PENYALAHGUNAAN DAN PECANDU NARKOTIKA MENURUT UNDANG-UNDANG NOMOR 35 TAHUN 2009 TENTANG NARKOTIKA
Authors: Saikhu M.
Published: June 2021

Penyalahgunaan dan peredaran gelap Narkoba menjadi permasalahan serius hampir di setiap Negara, tidak terkecuali di Indonesia. Karena kenyataan menunjukkan bahwa jumlah Pecandu di Indonesia semakin hari semakin meningkat. Hal ini tentunya harus mendapatkan penanganan yang lebih serius dari semua komponen, baik pemerintah maupun swasta. Sebagaimana diamanatkan dalam Undang-undang Nomor 35 Tahun 2009 tentang Narkotika, Penyalahguna Narkotika wajib direhabilitasi, yang diperkuat dalam Surat Edaran Mahkamah Agung Nomor 4 Tahun 2010 tentang penempatan Penyalahguna, bahwa Korban Penyalahguna dan Pecandu Narkotika ditempatkan ke dalam Lembaga  Rehabilitasi Medis dan Sosial. Undang Undang Nomor 35 Tahun 2009 tentang Narkotika mengatur double track  system pemidanaan, yaitu hakim dapat memutuskan hukuman pidana penjara dan dapat memutuskan tindakan rehabilitasi bagi Penyalahguna Narkotika. Hakim berperan sangat penting sesuai amanat Undang Undang untuk melakukan dekriminalisasi sehingga permintaan berkurang. Langkah ini bisa mengurangi suplai yang berdampak pada penanggulangan masalah Narkoba di Indonesia.Kata kunci: Narkotika; Penyalahgunaan; DekriminalisasiAbuse and trafficking in illegal drugs is a serious problem in almost every country, no exception in Indonesia. Because the fact shows that the number of addicts in Indonesia is increasing the day. This should certainly get more serious handling from all components, both government and private. As mandated in law number 35 year 2009 concerning narcotics, narcotic abusers is obliged to be rehabilitated, which was strengthened in the circular letter of the Supreme Court No. 4 year 2010 on the placement of abusers, that abusers victims and narcotics addicts were placed into the institute. Medical and social rehabilitation. Law Number 35 year 2009 about narcotics set up double track system Pemidanaan, that is, the judge can decide the prison sentence and can decide the rehabilitation action for abusers narcotics. The judge plays a crucial role according to the law's mandate to decriminalize so that demand decreases. This step can reduce supply that has an impact on the prevention of drug problems in Indonesia. Keywords: narcotics; Abuse Of
Analisis Ketersediaan dan Kebutuhan Ruang Terbuka Hijau Publik pada Kawasan Perkotaan Bintuni di Wilayah Distrik Manimeri
Authors: Wibowo Jendro Edy , Wahyudi Wahyudi , Siburian Rima Herlina
Published: June 2021

Meskipun merupakan daerah otonomi baru, ketersediaan ruang terbuka hijau di pusat pemerintahan Teuk BintunimemenuhikriteriaPeraturan Menteri Pekerjaan Umum No. 05 tahun 2008. Penelitian ini bertujuan untuk menganalisis ketersedian ruang terbuka hijau saat ini dan menperkirakan kebutuhan untuk sepuluh tahun kedepan denganÂ  pendekatan jumlah penduduk. Metode survey lapangan, pemetaan menggunakan Citra Satelit Resolusi Sangat Tinggi dan Citra lansat serta Â softawar GIS digunakan untuk menganalisis data digital. Hasil penelitian menunjukkan bahwa ketersediaan ruang terbuka hijau publik pada kawasan perkotaan diwilayah distrik Manimeri terdiri dari hutan kota (22,12 ha) sudah terpenuhi, jalur hijau jalan (17,94 ha), lapangan olahraga (4,56 ha), median jalan (0,914 ha), sempadan sungai (155,15 ha), taman kelurahan (0,21 ha) dan taman pemakaman umum (1,77 ha).Â  Kebutuhan ruang terbuka hijau publik berdasarkan pendekatan jumlah penduduk sepuluh tanun kedepan bagi Taman rukun tetangga 0,95 ha, Taman rukun warga 0,48 ha, Taman kelurahan/kampung 0,29 Ha. Taman kecamatan/distrik 0,1902 ha dan Taman kota 0,2853 ha.Â  Pemenuhan kriteria RTH publik berdasarlan Permen PU No 05 Tahun 2008, untuk jenis RTH hutan kota secara umum terpenuhi, jenis RTH jalur hijau jalan seluruhnya terpenuhi, jenis RTH median jalan secara umum tidak terpenuhi, jenis RTH sempadan sungai seluruhnya terpenuhi, jenis RTH taman kelurahan secara umum tidak terpenuhi dan jenis RTH taman pemakaman umum secara umum tidak terpenuhi.
MODELING AND IDENTIFICATION OF BALL SCREW FEED DRIVE SYSTEMS
Authors: Asy M. A. , Hassan S. A. , Elsaroukh M. H , Elsaroukh M. H
Published: June 2021

In this paper, the ball screw feed drive system is
simulated and it?s frequency response is studied. Various
parameters effect on the dynamic behavior of the ball
screw system have been investigated. Ball screw feed drive
system is used in high speed machine tools due to their
high efficiency. Estimation of the dynamic behavior of ball
screw feed drive mechanism is very important in the
industrial processes in order to get high demand for
precision and accuracy in machine tools. Optimizing the
drive operation can provide significant cost savings. A four
degree of freedom system, lumped parameter model is
used for modeling a single axis ball screw feed drive
system and use it to study and analyze vibrations in this
model. The mathematical modeling provides an important
information about frequency response when applying
different levels of table mass, stiffness of the nut, axial
stiffness of the ball screw shaft and torsional stiffness of
the ball screw on the system, to describe the effects of these
parameters on the system dynamic behavior. The study of
dynamic response of ball screw feed drive system provides
a better performance control and better understanding of
ball screw dynamics.
Mobile Application for Recording the Results of Laboratory Research of a Synthetic Chemist
Authors: Dmitrieva Yu.
Published: June 2021

This article discusses an application for mobile devices with the Android operating system that allows you to record the results of laboratory research of a synthetic chemist. An overview of the basic functionality of the Chemical Notes mobile application is presented.
Reading Bonhoeffer amid the Hong Kong Protests
Authors: Lam Jason
Published: June 2021

This essay reflects on how the people of Hong Kong have read the life and thought of Dietrich Bonhoeffer and found inspiration for their own struggle against authoritarianism, specifically following the pro-democracy movement in recent years. The purpose here is not to offer a first-hand interpretation of Bonhoeffer's works, but rather to present a historical exercise in sorting through contextual readings of Bonhoeffer. In what follows we will first offer a review of the church's participation in the protests that took place in Hong Kong during the second half of 2019 and articulate the relevance of Bonhoeffer's thought for the situation. Secondly, we will reflect on several important concepts concerning how Bonhoeffer transformed from a seeming ‘pacifist’ into a participant of the anti-Nazi movement. Next, some important figures involved in the Hong Kong democracy movement who are interested in Bonhoeffer will be examined. They are not Christians in the usual sense and thus offer us a good opportunity for examining why Bonhoeffer's late thought can gain ‘this-worldly’ acceptance. Interestingly, through this process we find that the particular contextual reading conditioned by Hong Kong's recent socio-political turbulence has offered occasions to rethink and develop some of Bonhoeffer's important concepts treated in existing scholarship. 1
Leadership Communication and Power: Measuring Leadership in the U.S. House of Representatives from Social Media Data
Authors: Ebanks Daniel , Yan Hao , Alvarez R. Michael , Das Sanmay , Sinclair Betsy
Published: June 2021

Who leads and who follows in Congress? By leveraging the Twitter accounts of U.S. House of Representatives members, we develop a new understanding of House leadership power using natural language processing methods in new ways. Formal theoretic work on congressional leadership suggests a tension in legislative party members' policy stances as they balance coordination and information problems. When their coordination problem is more pressing, the model predicts that legislative members will follow their party leaders' policy positions. When the information problem is more acute, party members coordinate and give their leaders direction for the party's agenda. Specifically, we exploit the network structure of retweets to derive measures of House leadership centrality within each party. We also use Joint Sentiment Topic modeling to quantify the discussion space for House members on Twitter. Our results provide support for the theoretical insights.
Retirement transitions in the 21st century: A scoping review of the changing nature of retirement in Europe
Authors: Lassen Aske Juul , Vrangbæk Karsten
Published: June 2021

There are important transformations taking place regarding the ways to transition from work-life to retirement. The timing and pathways are changing and many individuals undergo long periods of being in-between working and retirement life. Yet, our cultural understandings of retirement tend to maintain a clear distinction between pre- and post-retirement life. While the changes in retirement trajectories is not new, the trend seems to have accelerated in recent decades. We focus on what is known from the literature about the tendencies in alternative retirement trajectories of healthy seniors in Europe since 2000.

We review some conceptual and political transitions in the societal understandings of retirement, followed by a scoping review in three sections: 1) Employment after retirement, 2) Self-employment, and 3) Unretirement. We conclude that while 21st century retirement trajectories are complex and understudied, there are some clear tendencies regarding who engages in such practices and why.
Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development
Authors: Taubenheim Jan , Kortmann Constantin , Fraune Sebastian
Published: June 2021

Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual maturation in virtually all animals and by that the two main environmental-dependent developmental decision points. Sexual maturation and metamorphosis are controlled by steroid receptors and thyroid receptors, respectively in vertebrates, while both processes are orchestrated by the ecdysone receptor (EcR) in insects. The regulation of these processes depends on environmental factors like nutrition, temperature, or photoperiods and by that NRs form evolutionary conserved mediators of phenotypic plasticity. While the mechanism of action for metamorphosis and sexual maturation are well studied in model organisms, the evolution of these systems is not entirely understood and requires further investigation. We here review the current knowledge of NR involvement in metamorphosis and sexual maturation across the animal tree of life with special attention to environmental integration and evolution of the signaling mechanism. Furthermore, we compare commonalities and differences of the different signaling systems. Finally, we identify key gaps in our knowledge of NR evolution, which, if sufficiently investigated, would lead to an importantly improved understanding of the evolution of complex signaling systems, the evolution of life history decision points, and, ultimately, speciation events in the metazoan kingdom.
Antimicrobial Peptides Human Beta-Defensin-2 and -3 Protect the Gut During Candida albicans Infections Enhancing the Intestinal Barrier Integrity: In Vitro Study
Authors: Fusco Alessandra , Savio Vittoria , Donniacuo Maria , Perfetto Brunella , Donnarumma Giovanna
Published: June 2021

The intestinal mucosa is composed of a monolayer of epithelial cells, which is highly polarized and firmly united to each other thanks to the presence of proteins complexes, called Tight junctions (TJs). Alteration of the mucus layer and TJs causes an increase in intestinal permeability, which can lead to a microbial translocation and systemic disorders. Candida albicans, in addition to its role of commensal, is an opportunistic pathogen responsible for disseminated candidiasis, especially in immunocompromised subjects where the dysbiosis leads to damage of the intestinal mucosal barrier . In this work, we used a line of intestinal epithelial cells able to stably express the genes that encodes human beta defensin-2 (HBD-2) and -3 (HBD-3) to monitor the invasion of C. albicans in vitro. Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The results obtained show that the presence of antimicrobial peptides improves the expression of TJs and increases the Trans Epithelial Electrical Resistence value. In addition, the invasive ability of C. albicans in transfected cells is significantly reduced, as well as the expression levels of genes involved in the apoptotic pathway. Through the study of interaction between antimicrobial peptides and microbiota we will be able in the future to better understand the mechanisms by which they exert the host defense function against intestinal pathogens.
Evaluating Risk and Possible Adaptations to Climate Change Under a Socio-Ecological System Approach
Authors: Haro Abi , Mendoza-Ponce Alma , Calderón-Bustamante Óscar , Velasco Julián A. , Estrada Francisco
Published: June 2021

Evidence suggests that climate change could drastically reduce Mexico's agricultural productivity with severe socio-ecological consequences. Population growth and the increasing demand of resources will exacerbate these impacts. Focusing on rainfed maize production, we evaluate the socio-ecological risk that municipalities currently face and how climate change could modify it. Municipalities were classified based on their biophysical and socioeconomic traits like temperature, precipitation, population, gross domestic product, marginalization, and agricultural subsidies. The study identifies municipalities that would face higher risk under climate change conditions, and it evaluates whether increases in agricultural subsidies could be effective for reducing the farmers' future risk. Our results show that during the 2010's, 36.8% of the municipalities and 15% of the population were at very high and high risk, respectively. By 2070, under a high-warming scenario these figures increase to 56.5 and 18.5%. We find that a generalized augment in agricultural subsidies is not enough to compensate for the effects of climate change on the socio-ecological risk of rainfed maize producers. We suggest that transformative adaptation is required for managing the agricultural risk that socio-ecological systems experience under climate change conditions. Such adaptation strategies should include poverty alleviation, promotion of resistant and native varieties of crops, capacity building to improve management and water use, sustainable technification, and soil restoration.
Decision-Making for Rewilding: An Adaptive Governance Framework for Social-Ecological Complexity
Authors: Butler James R. A. , Marzano Mariella , Pettorelli Nathalie , Durant Sarah M. , du Toit Johan T. , Young Juliette C.
Published: June 2021

Rewilding can be defined as the reorganisation or regeneration of wildness in an ecologically degraded landscape with minimal ongoing intervention. While proposals for rewilding are increasingly common, they are frequently controversial and divisive amongst stakeholders. If implemented, rewilding initiatives may alter the social-ecological systems within which they are situated and thus generate sudden and unforeseen outcomes. So far, however, much of the discourse on the planning and implementation of rewilding has focused on identifying and mitigating ecological risks. There has been little consideration of how rewilding could alter the human components of the social-ecological systems concerned, nor governance arrangements that can manage these dynamics. This paper addresses this gap by proposing a generic adaptive governance framework tailored to the characteristics of rewilding, based on principles of managing complex social-ecological systems. We integrate two complementary natural resource governance approaches that lend themselves to the contentious and unpredictable characteristics of rewilding. First, adaptive co-management builds stakeholder adaptive capacity through iterative knowledge generation, collaboration and power-sharing, and cross-scale learning networks. Second, social licence to operate establishes trust and transparency between project proponents and communities through new public-private partnerships. The proposed framework includes structural and process elements which incorporate a boundary organisation, a decision-into-practise social learning exercise for planning and design, and participatory evaluation. The latter assesses rewilding outcomes and pre-conditions for the continuation of adaptive governance and conservation conflict resolution.
Group A Streptococcus-Induced Activation of Human Plasminogen Is Required for Keratinocyte Wound Retraction and Rapid Clot Dissolution
Authors: Vu Henry M. , Hammers Daniel E. , Liang Zhong , Nguyen Gabrielle L. , Benz Mary E. , Moran Thomas E. , Higashi Dustin L. , Park Claudia J. , Ayinuola Yetunde A. , Donahue Deborah L. , Flores-Mireles Ana L. , Ploplis Victoria A. , Castellino Francis J. , Lee Shaun W.
Published: June 2021

Invasive outcomes of Group A Streptococcus (GAS) infections that involve damage to skin and other tissues are initiated when these bacteria colonize and disseminate via an open wound to gain access to blood and deeper tissues. Two critical GAS virulence factors, Plasminogen-Associated M-Protein (PAM) and streptokinase (SK), work in concert to bind and activate host human plasminogen (hPg) in order to create a localized proteolytic environment that alters wound-site architecture. Using a wound scratch assay with immortalized epithelial cells, real-time live imaging (RTLI) was used to examine dynamic effects of hPg activation by a PAM-containing skin-trophic GAS isolate (AP53R+S−) during the course of infection. RTLI of these wound models revealed that retraction of the epithelial wound required both GAS and hPg. Isogenic AP53R+S− mutants lacking SK or PAM highly attenuated the time course of retraction of the keratinocyte wound. We also found that relocalization of integrin β1 from the membrane to the cytoplasm occurred during the wound retraction event. We devised a combined in situ-based cellular model of fibrin clot-in epithelial wound to visualize the progress of GAS pathogenesis by RTLI. Our findings showed GAS AP53R+S− hierarchically dissolved the fibrin clot prior to the retraction of keratinocyte monolayers at the leading edge of the wound. Overall, our studies reveal that localized activation of hPg by AP53R+S−via SK and PAM during infection plays a critical role in dissemination of bacteria at the wound site through both rapid dissolution of the fibrin clot and retraction of the keratinocyte wound layer.
Thrombin Generation as a Method to Identify the Risk of Bleeding in High Clinical-Risk Patients Using Dual Antiplatelet Therapy
Authors: de Breet C. P. D. M. , Zwaveling S. , Vries M. J. A. , van Oerle R. G. , Henskens Y. M. C. , van't Hof A. W. J. , van der Meijden P. E. J. , Veenstra L. , ten Cate H. , Olie R. H.
Published: June 2021

Background: Patients using dual antiplatelet therapy after percutaneous coronary intervention are at risk for bleeding. It is currently unknown whether thrombin generation can be used to identify patients receiving dual antiplatelet therapy with increased bleeding risk.

Objectives: To investigate whether thrombin generation measurement in plasma provides additional insight into the assessment of bleeding risk for high clinical-risk patients using dual antiplatelet therapy.

Methods: Coagulation factors and thrombin generation in platelet-poor plasma were measured in 93 high clinical-risk frail patients using dual antiplatelet therapy after percutaneous coronary intervention. During 12-month follow-up, clinically relevant bleedings were reported. Thrombin generation at 1 and 6 months after percutaneous coronary intervention was compared between patients with and without bleeding events.

Results: One month after percutaneous coronary intervention, the parameters of thrombin generation, endogenous thrombin potential, peak height, and velocity index were significantly lower in patients with bleeding in the following months compared to patients without bleeding. At 6 months follow-up, endogenous thrombin potential, peak height, and velocity index were still (significantly) decreased in the bleeding group as compared to non-bleeders. Thrombin generation in the patients' plasma was strongly dependent on factor II, V, and VIII activity and fibrinogen.

Conclusion: High clinical-risk patients using dual antiplatelet therapy with clinically relevant bleeding during follow-up show reduced and delayed thrombin generation in platelet-poor plasma, possibly due to variation in coagulation factors. Thus, impaired thrombin-generating potential may be a “second hit” on top of dual antiplatelet therapy, increasing the bleeding risk in high clinical-risk patients. Thrombin generation has the potential to improve the identification of patients using dual antiplatelet therapy at increased risk of bleeding.
Swedish Youths as Listeners of Global Englishes Speakers With Diverse Accents: Listener Intelligibility, Listener Comprehensibility, Accentedness Perception, and Accentedness Acceptance
Authors: Jeong Hyeseung , Elgemark Anna , Thorén Bosse
Published: June 2021

As reflected in the concept of Global Englishes, English mediates global communication, where English speakers represent not merely those from English-speaking countries like United Kingdom or United States but also global people from a wide range of linguistic backgrounds, who speak the language with diverse accents. Thus, to communicate internationally, cultivating a maximized listening proficiency for and positive attitudes toward global Englishes speakers with diverse accents is ever more important. However, with their preference for American English and its popular culture, it is uncertain whether Swedish youth learners are developing these key linguistic qualities to be prepared for the globalized use of English. To address this, we randomly assigned 160 upper secondary students (mean age = 17.25) into six groups, where each group listened to one of six English speakers. The six speakers first languages were Mandarin, Russian/Ukrainian, Tamil, Lusoga/Luganda, American English, and British English. Through comparing the six student groups, we examined their listener intelligibility (actual understanding), listener comprehensibility (feeling of ease or difficulty), accentedness perception (perceiving an accent as native or foreign), and accentedness acceptance (showing a positive or negative attitude toward an accent) of diverse English accents. The results showed that the intelligibility scores and perception/attitude ratings of participants favored the two speakers with privileged accents–the American and British speakers. However, across all six groups, no correlation was detected between their actual understanding of the speakers and their perception/attitude ratings, which often had a strong correlation with their feelings of ease/difficulty regarding the speakers accents. Taken together, our results suggest that the current English education needs innovation to be more aligned with the national syllabus that promotes a global perspective. That is, students need to be guided to improve their actual understanding and sense of familiarity with Global English speakers besides the native accents that they prefer. Moreover, innovative pedagogical work should be undertaken to change Swedish youths’ perceptions and attitudes and prepare them to become open-minded toward diverse English speakers.
The Impact of Coding Apps to Support Young Children in Computational Thinking and Computational Fluency. A Literature Review
Authors: Papadakis Stamatis
Published: June 2021

Data that shows that young children can learn and acquire Computational Thinking (CT) skills has led governments and policymakers internationally to integrate CT into the curriculum, starting in the earliest grades. Researchers support the idea that this introduction must not solely focus on a problem-solving process skill (CT) but instead provide children with new ways to express themselves, supporting their cognitive, language, and socio-emotional development (Computational Fluency-CF). Coupled with the media and government’s rhetoric and an increasing number of apps offering various programming lessons, puzzles, and challenges, educators have been responsible for introducing young children to CT and CF using touchscreen technology. This paper presents a literature review (N= 21) of empirical studies on applying four coding apps to support young children’s learning of CT and CF. The main conclusion is that all apps positively affect the development of children’s CT skills. None of the apps can ultimately support the development of CF, although ScratchJr, with a “sandbox” approach, can better help students express themselves.
RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia
Authors: Liu Chan , Zhou Xiao-Rong , Ye Mu-Yao , Xu Xiang-Qing , Zhang Yu-Wei , Liu Hong , Huang Xian-Zhe
Published: June 2021

Objective

Hyperuricemia (HUA) is strongly associated with abnormal glucose metabolism and insulin resistance (IR). However, the precise molecular mechanism of HUA-induced IR is still unclear. Retinol binding protein 4 (RBP4) has been shown to induce IR in type 2 diabetes mellitus. This study was designed to clarify the relationship between RBP4 and HUA-induced IR and its potential mechanisms.

Methods

Patients with HUA were collected to detect the levels of plasma RBP4 and clinical biochemical indicators. Rats were fed with 10% high yeast and oteracil potassium (300 mg/kg) via intraperitoneal injection once daily for eight weeks, and gavage with adenine (100 mg/kg) once daily from the fifth week to induce the HUA model. Glucose consumption testing was performed to determine the capacity of glucose intake and consumption in 3T3-L1 adipocytes. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA and protein level of RBP4 and insulin receptor substrate-phosphatidylinositol 3-kinase-active protein kinase (IRS/PI3K/Akt) signaling pathway-related proteins.

Results

The levels of plasma RBP4 in both HUA patients and HUA rat models were significantly higher than that in the control groups. The level of plasma RBP4 was positively correlated with plasma uric acid, creatinine, fasting insulin, IR index, total cholesterol and triglyceride levels in patients with HUA. In HUA rats, the level of plasma RBP4 was positively correlated with plasma uric acid, IR index, and triglycerides. HUA rats also exhibited IR. After inhibition of RBP4 expression, the phosphorylation levels of the IRS/PI3K/Akt signaling pathway were increased, and IR was significantly improved.

Conclusion

HUA induced IR both in vitro and in vivo. RBP4 may be involved in HUA-induced IR by inhibiting IRS/PI3K/Akt phosphorylation. Our findings may provide a new insight for the treatment of IR caused by HUA.
Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease
Authors: Duan Suyan , Lu Fang , Song Dandan , Zhang Chengning , Zhang Bo , Xing Changying , Yuan Yanggang
Published: June 2021

Over decades, substantial progress has been achieved in understanding the pathogenesis of proteinuria in diabetic kidney disease (DKD), biomarkers for DKD screening, diagnosis, and prognosis, as well as novel hypoglycemia agents in clinical trials, thereby rendering more attention focused on the role of renal tubules in DKD. Previous studies have demonstrated that morphological and functional changes in renal tubules are highly involved in the occurrence and development of DKD. Novel tubular biomarkers have shown some clinical importance. However, there are many challenges to transition into personalized diagnosis and guidance for individual therapy in clinical practice. Large-scale clinical trials suggested the clinical relevance of increased proximal reabsorption and hyperfiltration by sodium-glucose cotransporter-2 (SGLT2) to improve renal outcomes in patients with diabetes, further promoting the emergence of renal tubulocentric research. Therefore, this review summarized the recent progress in the pathophysiology associated with involved mechanisms of renal tubules, potential tubular biomarkers with clinical application, and renal tubular factors in DKD management. The mechanism of kidney protection and impressive results from clinical trials of SGLT2 inhibitors were summarized and discussed, offering a comprehensive update on therapeutic strategies targeting renal tubules.
Investigation Into the Predictive Potential of Three-Dimensional Ultrasonographic Placental Volume and Vascular Indices in Gestational Diabetes Mellitus
Authors: Han Zhenyan , Zhang Yuan , Li Xuelan , Chiu Wei-Hsiu , Yin Yuzhu , Hou Hongying
Published: June 2021

Background

The use of ultrasonography in pregnancies complicated with gestational diabetes mellitus (GDM) can vary according to clinical practice. This study aims to compare the changes of placental volume (PV) and vascular indices measured by three-dimensional (3D) Power Doppler between pregnant women with and without GDM.

Materials and Methods

This was a prospective study of singleton pregnancies who took the early nuchal translucency examination from January 2018 to September 2019. Data on PV and vascular indices including vascularization index (VI), flow index (FI), and vascularization flow index (VFI) between pregnant women with and without GDM were measured by 3D Power Doppler ultrasound machine. Univariate and multivariate logistic regression determined the association between risk factors and GDM. Receiver operating characteristic (ROC) and area under the ROC curve (AUC) were applied to evaluate the diagnostic value of different parameters for GDM.

Results

Of the 141 pregnant women enrolled, 35 developed GDM and 106 did not. The maternal age and gravida in the GDM group were significantly higher than that in the non-GDM group. The PV, VI, FI, and VFI in the GDM group were significantly lower than that in the non-GDM group. There were no significant differences in other clinical parameters between the two groups. After adjustments in multivariate logistic regression analysis, significant differences were observed in VI [odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.951–1.002], FI (OR = 0.93, 955 CI: 0.86–1.00), and VFI (OR = 0.67, 95% CI = 0.52–0.87). ROC analysis indicated that the combination of maternal age, gravida, PV, and VFI was more accurate as a marker for detecting GDM than the PV, VI, FI, or VFI alone.

Conclusions

The 3D ultrasonography results suggest that PV and vascular indices (VI, FI, and VFI) during the first trimester may serve as potential markers for GDM diagnosis. The combination of maternal age, gravida, and sonographic markers may have good diagnostic values for GDM, which should be confirmed by further investigations.
The Linkage Among Sea Transport, Trade Liberalization and Industrial Development in the Context of CO2: An Empirical Investigation From China
Authors: Kalaycı Salih , Özden Cihan
Published: June 2021

The major goal of this paper is to focus on the linkage between sea transportation, trade liberalization and industrial development in the context of carbon dioxide emission. With this respect, it is attempted to analyze the effects of independent variables on the dependent variable carbon dioxide emission for China by using annual data ranging from 1960 to 2019 with the help of econometric methods such as fully modified least square, dynamic ordinary least square, canonical co-integrating regression, autoregressive distributed lag bound test and generalized moments method. According to the results of fully modified least square, dynamic ordinary least square and canonical co-integrating regression models, there is a significant long-term relationship between sea transportation, trade liberalization, industrial development and carbon dioxide emissions. On the other hand, short term autoregressive distributed lag bound test estimation results reveal that the main determinants of carbon dioxide emission in the short-run are industrial development and sea transportation. The empirical tests reveal important results for policy-makers in China.
Identification of key Genes and Pathways Associated With Thermal Stress in Peripheral Blood Mononuclear Cells of Holstein Dairy Cattle
Authors: Fang Hao , Kang Ling , Abbas Zaheer , Hu Lirong , Chen Yumei , Tan Xiao , Wang Yachun , Xu Qing
Published: June 2021

The objectives of the present study were to identify key genes and biological pathways associated with thermal stress in Chinese Holstein dairy cattle. Hence, we constructed a cell-model, applied various molecular biology experimental techniques and bioinformatics analysis. A total of 55 candidate genes were screened from published literature and the IPA database to examine its regulation under cold (25°C) or heat (42°C) stress in PBMCs. We identified 29 (3 up-regulated and 26 down-regulated) and 41 (15 up-regulated and 26 down-regulated) significantly differentially expressed genes (DEGs) (fold change ≥ 1.2-fold and P < 0.05) after cold and heat stress treatments, respectively. Furthermore, bioinformatics analyses confirmed that major biological processes and pathways associated with thermal stress include protein folding and refolding, protein phosphorylation, transcription factor binding, immune effector process, negative regulation of cell proliferation, autophagy, apoptosis, protein processing in endoplasmic reticulum, estrogen signaling pathway, pathways related to cancer, PI3K- Akt signaling pathway, and MAPK signaling pathway. Based on validation at the cellular and individual levels, the mRNA expression of the HIF1A gene showed upregulation during cold stress and the EIF2A, HSPA1A, HSP90AA1, and HSF1 genes showed downregulation after heat exposure. The RT-qPCR and western blot results revealed that the HIF1A after cold stress and the EIF2A, HSPA1A, HSP90AA1, and HSF1 after heat stress had consistent trend changes at the cellular transcription and translation levels, suggesting as key genes associated with thermal stress response in Holstein dairy cattle. The cellular model established in this study with PBMCs provides a suitable platform to improve our understanding of thermal stress in dairy cattle. Moreover, this study provides an opportunity to develop simultaneously both high-yielding and thermotolerant Chinese Holstein cattle through marker-assisted selection.
The Virulence of S. marcescens Strains Isolated From Contaminated Blood Products Is Divergent in the C. elegans Infection Model
Authors: Diamandas Alexander , Razon Mikhail R. , Ramirez-Arcos Sandra , Brassinga Ann Karen C.
Published: June 2021

Bacterial contamination of platelet concentrates (PCs) can occur during blood donation or PC processing, necessitating routine screening to identify contaminated products in efforts to prevent adverse transfusion reactions in recipient patients. Serratia marcescens is a common bacterial contaminant, and its resilient nature coupled with genetic promiscuity imbue this environmental bacterium with resistance to disinfectants and antibiotics enhancing bacterial virulence. In this study, we aim to understand adaptive survival mechanisms through genetic characterization of two S. marcescens strains, CBS11 and CBS12, isolated from PCs by Canadian Blood Services. Genomic analyses of the two strains indicated that CBS11 has one chromosome and one plasmid (pAM01), whereas CBS12 has no plasmids. Phylogenetic analyses show that CBS11 and CBS12 are non-clonal strains, with CBS11 clustering closely with clinical strain CAV1492 and less so with environmental strain PWN146, and CBS12 clustering with a clinical strain AR_0027. Interestingly, pAM01 was most closely related to PWN146p1, a plasmid found in S. marcescens PWN146 strain associated with pinewood nematode Bursaphelenchus xylophilus. Lastly, the genomic diversity of CBS11 and CBS12 was not reflected in the antibiotic resistance profiles as they were remarkably similar to one another, but was reflected in the virulence phenotypes assessed in the Caenorhabditis elegans nematode infection model, with CBS11 being more virulent then CBS12. Taken together, we suggest that S. marcescens environmental isolates that feature evolutionary diverse genomics are better equipped to adapt and thrive in varied environments, such as that of PCs, and therefore is as much of a concern as multi-drug resistance for human infection potential.
The Pandemic as a Rupture that Follows Rules: Comparing Governance Responses in India, USA, Sweden and Norway
Authors: Sareen Siddharth , Nielsen Kenneth Bo , Oskarsson Patrik , Remme Devyn
Published: June 2021

How a country responds to a rupture such as the COVID-19 pandemic can be revelatory of its governance. Governance entails not only the exercise but also the constitution of authority. The pandemic response thus presents a real-world disruption to verify or problematize some truisms about national governance and produce novel comparisons and insights. We present a comparative analysis across four established democratic nation-states. First, we identify concerns of relevance for national pandemic responses and map them to state characteristics. Next, we conduct thematic analyses of recent ruptures in India, the United States, Sweden and Norway, to form a baseline of truisms about governance responses to frontier moments such as this pandemic, and hypothesize their relative propensities across the concerns. We then compile comparative data on emergent pandemic responses during the first 90 days of respective, temporally proximate outbreaks. This combination enables us to link response characteristics to national propensities across the relevant concerns. We identify similarities and differences between what the pandemic responses reveal and the truisms of scholarship about the four countries state characteristics. We argue that ruptures in democratic governance contexts embody temporally discontiguous and country-specific patterns. They are conjunctures of particular possibilities for bounded reconfiguration. Such reconfiguration can intensify or shift the course of what the state is becoming. We argue that in our cases it accelerates shifts to authoritarianism (India and the United States), raises stark questions of national identity (Norway and Sweden) and underscores tensions between the reemergence of welfare states and the global project of neoliberalism. By revealing what sort of rules show resurgence across ruptures, our comparative analysis deepens a timely understanding of punctuated politics of reconfiguration of authority.
Alteration of Intestinal Microbiota Composition in Oral Sensitized C3H/HeJ Mice Is Associated With Changes in Dendritic Cells and T Cells in Mesenteric Lymph Nodes
Authors: Zhou Cui , Chen Ling-Ling , Lu Rui-Qi , Ma Wei-Wei , Xiao Rong
Published: June 2021

This research aimed to investigate the allergic reaction of C3H/HeJ mice after sensitization with ovalbumin (OVA) without any adjuvant and to analyze the association between intestinal microbiota and allergy-related immune cells in mesenteric lymph nodes (MLN). The allergic responses of C3H/HeJ mice orally sensitized with OVA were evaluated, and immune cell subsets in spleen and MLN and cytokines were also detected. The intestinal bacterial community structure was analyzed, followed by Spearman correlation analysis between changed gut microbiota species and allergic parameters. Sensitization induced a noticeable allergic response to the gavage of OVA without adjuvant. Increased levels of Th2, IL-4, CD103+CD86+ DC, and MHCII+CD86+ DC and decreased levels of Th1, Treg, IFN-γ, TGF-β1, and CD11C+CD103+ DC were observed in allergic mice. Furthermore, families of Lachnospiraceae, Clostridiaceae_1, Ruminococcaceae, and peprostreptococcaceae, all of which belonging to the order Clostridiales, were positively related to Treg and CD11C+CD103+ DC, while they were negatively related to an allergic reaction, levels of Th2, CD103+CD86+ DC, and MHCII+CD86+ DC in MLN. The family of norank_o_Mollicutes_RF39 belonging to the order Mollicutes_RF39 was similarly correlated with allergic reaction and immune cells in MLN of mice. To sum up, allergic reactions and intestinal flora disturbances could be induced by OVA oral administration alone. The orders of Clostridiales and Mollicutes_RF39 in intestinal flora are positively correlated with levels of Treg and CD11C+CD103+ DC in MLN of mice.
Immunomodulation Eliminates Inflammation in the Hippocampus in Experimental Autoimmune Encephalomyelitis, but Does Not Ameliorate Anxiety-Like Behavior
Authors: Kocovski Pece , Tabassum-Sheikh Nuzhat , Marinis Stephanie , Dang Phuc T. , Hale Matthew W. , Orian Jacqueline M.
Published: June 2021

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system, characterized by an unpredictable disease course and a wide range of symptoms. Emotional and cognitive deficits are now recognized as primary disease manifestations and not simply the consequence of living with a chronic condition, raising questions regarding the efficacy of current therapeutics for these specific symptoms. Mechanisms underlying psychiatric sequelae in MS are believed to be similar to those underlying pathogenesis, that is mediated by cytokines and other inflammatory mediators. To gain insight into the pathogenesis of MS depression, we performed behavioral assays in the murine experimental autoimmune encephalomyelitis (EAE) MS model, in the presence or absence of immunomodulation using the drug FTY720, an analogue of the lipid signaling molecule sphingosine-1-phosphate (S1P). Specifically, mice were challenged with the elevated plus maze (EPM) test, a validated experimental paradigm for rodent-specific anxiety-like behavior. FTY720 treatment failed to ameliorate anxiety-like symptoms, irrespective of dosage. On the other hand, it was effective in reducing inflammatory infiltration, microglial reactivity and levels of pro-inflammatory molecules in the hippocampus, confirming the anti-inflammatory capacity of treatment. To explore the absence of FTY720 effect on behavior, we confirmed expression of S1P receptors (S1PR) S1PR1, S1PR3 and S1PR5 in the hippocampus and mapped the dynamics of these receptors in response to drug treatment alone, or in combination with EAE induction. We identified a complex pattern of responses, differing between (1) receptors, (2) dosage and (3) hippocampal sub-field. FTY720 treatment in the absence of EAE resulted in overall downregulation of S1PR1 and S1PR3, while S1PR5 exhibited a dose-dependent upregulation. EAE induction alone resulted in overall downregulation of all three receptors. On the other hand, combined FTY720 and EAE showed generally no effect on S1PR1 and S1PR3 expression except for the fimbrium region, but strong upregulation of S1PR5 over the range of doses examined. These data illustrate a hitherto undescribed complexity of S1PR response to FTY720 in the hippocampus, independent of drug effect on effector immune cells, but simultaneously emphasize the need to explore novel treatment strategies to specifically address mood disorders in MS.
Interleukin-35 Suppresses Interleukin-9-Secreting CD4+ T Cell Activity in Patients With Hepatitis B-Related Hepatocellular Carcinoma
Authors: Zhang Qian , Yang Lanlan , Liu Siqi , Zhang Mengyao , Jin Zhenjing
Published: June 2021

Chronic hepatitis B virus (HBV) infection induces dysfunction of immune response and chronic liver damage. However, the mechanisms that account for HBV-related hepatocellular carcinoma (HCC) are poorly understood. The aim of present study was to investigate the modulatory role of interleukin (IL)-35, an immunosuppressive cytokine, to IL-9-secreting T cells in hepatitis B-related HCC. Twenty-two HBV-related HCC patients, twenty-seven chronic hepatitis B (CHB) patients, and eleven controls were enrolled. Serum IL-35 and IL-9 concentration was measured by ELISA. Peripheral and liver-infiltrating non-specific and HBV-specific Th9 and Tc9 cells were assessed by flow cytometry. The regulatory activity of IL-35 to peripheral and liver-infiltrating Th9 cells was assessed in co-culture system between CD8+ T cells and HepG2.2.15 cells. Serum IL-35 was up-regulated, while IL-9 was down-regulated in HBV-related HCC patients compared with in CHB patients and controls. Peripheral non-specific and HBV-specific Th9 cells, but not Tc9 cells, were decreased in HBV-related HCC patients. Liver-infiltrating non-specific and HBV-specific Th9 cells were also reduced in HCC tumor sites. CD8+ T cells from CHB and HBV-related HCC patients revealed decreased cytotoxicity compared with those from controls. Autologous Th9 cells mediated the elevation of CD8+ T cell cytotoxicity, and this process was depending on IL-9 secretion. Recombinant IL-35 stimulation inhibited IL-9 secretion and PU.1 mRNA expression in non-specific and HBV-specific Th9 cells, leading to the suppression of Th9-mediated CD8+ T cell cytotoxicity in CHB and HBV-related HCC patients. Our current data indicated that IL-35 might dampen non-specific and HBV-specific Th9 cells activity in HBV-related HCC patients.