bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementasi Pembelajaran Kontekstual dengan Strategi REACT (Relating, Experiencing, Applying, Cooperating, Dan Tranferring)
Authors: Kholisiyah Nurul , Yuanita Dianis Izztul
Published: March 2021

Kemampuan siswa terhadap pelajaran matematika di MI perlu terus ditingkatkan, mengingat perkembangan dunia saat ini menuntut berbagai perhitungan yang lebih rumitid. Tidak terkecuali siswa di Madrasah Ibtidaiyah Daya Muda Al-Islam  Takat Kampungbaru Tanjunganom Nganjuk yang saat ini masih tergolong rendah. Terlihat dari nilai ulangan semester II tahun pelajaran 2015/2016, yaitu: dari 119 siswa hanya 21% yang tuntas belajar secara klasikal (dikatakan tuntas apabila nilainya 75) sedangkan yang tidak tuntas 79%. Mengatasi permasalahan di atas, diperlukan strategi REACT yang menekankan pada aktivitas siswa secara penuh, baik fisik maupun mental.Fakus penelitian dalam tesis ini adalah: (1) Bagaimana proses pembelajaran kontekstual dengan strategi REACT  pada mata pelajaran matematika di MI Daya Muda Al-Islam. (2) Kemampuan apa saja yang nampak dalam pembelajaran kontekstual dengan strategi REACT pada mata pelajaran matematika di MI Daya Muda Al-Islam. Hasil penelitian ini adalah: (1) Proses pembelajaran kontekstual dengan strategi REACT pada mata pelajaran matematika di MI Daya Muda Al-Islam dilakukan dengan 4 proses tahapan, pertama proses relating siswa diberi rumus kemudian mengaitkannya dengan kehidupan nyata, kedua proses experiencing yaitu siswa melakukan eksplorasi rumus dengan pengalaman nyata siswa, ketiga siswa menerapkan pengalaman dalam kehidupan nyata untuk memecahkan soal matematika, keempat proses cooperating siswa bersama dengan kelompoknya melakukan diskusi untuk memecahkan soal bersama-sama, kelima proses tranferring siswa melakukan presentasi dari hasil diskusi bersama kelompoknya setelah memecahkan soal matematika. (2) Kemampuan siswa yang nampak dalam pembelajaran kontekstual dengan strategi REACT pada mata pelajaran matematika di MI Daya Muda Al-Islam adalah: pertama  kemampuan relating siswa sudah cukup baik hal ini dibuktikan dengan hasil tes ulangan harian.Kemampuan experiencing dengan 8 indikator sudah mencapai nilai rata-rata yang baik. Kemampuan applying dari 5 indikator,3 aspek kurang baik. Kemampuan cooperating siswa,  6 siswa  dengan 5 indikator sudah menunjukkan nilai rata-rata yang baik, Kemampuan tranferring siswa rata-rata sudah baik, walaupun siswa masih berlum terbiasa mengkomunikasikan hasil diskusi dengan presentasi di depan kelas.
Plastic In Skincare Cosmetics: An Investigation of the Acceptance of Plastic Packaging and Micro-Plastics When Buying Skincare Products
Authors: Mehn Audrey , Vogt Virginia Odessa Nisha
Published: March 2021

Never before has so much plastic existed within the environment as is currently the case. Cosmetics are a significant part of the plastic problem, both in terms of microplastics in the ingredients and through plastic-containing packaging. Generation Y is often seen as being environmentally conscious and sustainable. Contrary to this, however, Generation Y has proven to be carefree when buying plastic cosmetics. This article is intended to clarify the question of why German women of Generation Y buy plastic-contaminated, caring facial cosmetics, even though they are aware of possible damage. Results of an online survey (N=337) and a qualitative survey with experts revealed that the leading causes for the purchase of plastic-containing, caring cosmetics include the lack of plastic-free alternative products, the lack of transparency of product declarations and the enormous amount of time involved in the search for plastic-free cosmetic.
GOAL SETTING THEORY: THE EFFECT OF INCENTIVE MODERATION ON INDIVIDUAL PERFORMANCE
Authors:   Economics and Business Faculty, Soegijapranata Catholic University Semarang Indonesia, Hartono Yudi , Murniati Monika Palupi ,   Economics and Business Faculty, Soegijapranata Catholic University Semarang Indonesia
Published: March 2021

This study uses goal-setting theory and reinforcement theory to explain the formation of individual motivation in achieving goals. Testing the effect of goal specificity used the experimental method to test the impact of goal specificity, different goal difficulty on the same quota incentive system as the 2x2x1 experimental design. This study's findings confirm the goal-setting theory shown from the higher achievement of participants' goals when participants are given specific and challenging goals than participant goals in different variations of goal specificity and goal difficulty. This study found that participants have a greater focus on goal specificity in driving goal attainment behavior. The findings of this study confirm the reinforcement theory shown from achieving goals that exceed targets. Positive consequences become arguments for individuals to do the same action
Penerapan Aspek Environmental Dalam Arsitektur Sustainable Pada Perancangan Stasiun Kereta Api Pekanbaru
Authors: Ihsan Muhammad Rafi
Published: March 2021

Pekanbaru is one of the big cities in Indonesia with a high population mobility. However, the city is not accompanied by the provision of fast and economical public transportation. The common public transportation facilities which are available in Pekanbaru, namely buses and travel, are considered as a quite economical, but require a long time to travel. Meanwhile, other transportation facilities, namely planes, are considered fast but less economical. Therefore, an economical and fast alternative public transportation, namely train, is needed. To meet this need, a railway station is required in Pekanbaru. The development condition in Pekanbaru which are getting faster and denser can adversely affect the environment. So, environmentally friendly and sustainable development is needed in the form of station designs that meet environmental aspects in sustainable architecture. The research method used is qualitative in the form of field data collection and literature study related to the topic of discussion.
Kajian Karakteristik Arsitektur Omah Sengen Etnis Jawe Di Banten Lor
Authors: Khamdevi Muhammar
Published: March 2021

Berbeda dengan wilayah Banten Kidul (Banten Selatan) yang didiami oleh etnis Sunda Banten, wilayah Banten Lor (Banten Utara) justru didiami oleh suku Jawe (Jawa) yang ada sejak jaman Kesultanan Banten. Kesultanan ini merupakan wilayah bawahan dari Kesultanan Cirebon dan selain itu juga memiliki kedekatan hubungan politik dengan Kesultanan Palembang. Di wilayah ini terdapat beberapa rumah tradisional yang bernama Omah Sengen (Rumah Dulu) atau Omah Panggang Pe, terutama di Cilegon dan di Serang. Sayangnya rumah tradisional ini tidak begitu mendapat perhatian lebih dari kajian arsitektur dan sebentar lagi jumlahnya akan semakin menyusut bahkan lenyap. Maka penelitian ini menjadi penting untuk mencoba meneliti dan mendokumentasikan karakter arsitekturnya. Penelitian ini menggunakan metode penelitian kualitatif dengan pendekatan studi kasus, dengan cara menganalisis karakteristik bangunannya secara arsitektural; spasial, fisik dan figural, dan stilistik. Bagaimanakah karakteristik rumah tradisional di Banten Lor? Penelitian ini diharapkan dapat menambah dan melengkapi referensi-referensi keilmuan, terutama mengenai rumah tradisional di wilayah Banten.
Pengaruh Digital dalam Presentasi Karya Arsitek
Authors: Pandu Aria Zabdi Alias Dian , Purwanto LMF
Published: March 2021

Perkembangan teknologi digital beberapa dasawarsa terakhir secara signifikan mengubah cara arsitek bekerja. Revolusi digital dalam beberapa dekade terakhir ini memungkinkan kita untuk tidak hanya mengkonstruksi bangunan secara fisik, tetapi juga secara virtual. Presentasi merupakan tahap penting dalam sebuah pekerjaan arsitektur. Presentasi yang dilakukan arsitek adalah upaya untuk mengkomunikasikan sebuah informasi, yang berupa ide-ide dari sang arsitek. Klien sebagai penerima infomasi berasal dari berbagai kalangan dan latar belakang serta kemampuan spasial (spatial intelligence) yang berbeda. Oleh karena itu, berbagai upaya dilakukan agar presentasi yang dilakukan oleh arsitek lebih mudah diterima oleh klien Perkembangan presentasi arsitek ini dipengaruhi oleh perkembangan teknologi digital. Arsitektur adalah salah satu bidang yang rutin menjadi pengguna temuan-temuan teknologi. Teknologi-teknologi terkini diaplikasikan dalam berbagai perangkat lunak arsitektur, salah satunya adalah penggunaan teknologi Virtual Reality dan Augmented Reality yang semula diaplikasikan dalam konsol permainan kini diintegrasikan dalam Builidng Information Modelling (BIM). Di masa mendatang, penggunaan teknologi dalam penyajian karya arsitektur terus akan berkembang sesuai dengan perkembangan teknologi digital yang ada.
AN OVER VIEW OF ALTERNATE DISPUTE RESOLUTION FROM THE CONTRACTUAL PERSPECTIVE IN EUROPE
Authors: Khan Asif , Ansari Ali Raza , Soomro Nishan-E-Hyder , Arafa Ahmed
Published: March 2021

The Alternative Dispute Resolution ("ADR") is an alternative conflict settlement strategy. It follows the main objective of solving conflicts between parties stunningly through the help of independent professionals and renowned personalities. Today the role of the ADR is more important, and the number of agreements with ADR is increasing. One of the reasons for this development is that the ADR is usually more efficient and time-saving compared to normal justice delivering procedures. The current paper examines the most popular techniques for the solution of alternative disputes within the EU, through mediation. This paper associates ADR development and the European Law Legislative International Trade Conciliation (2002) along with other Laws and ADR services, such as ICC and different Laws related to the services. It then conjointly makes comparisons between the bound “member state” MS Courts to observe problems concerning ADR. Additionally, it recognizes the ADR in the light of the right to valid remedy (European Union Principles). To administer a deep insight into the subject, the paper describes additionally the ADR origin, its features, and relevance. Hence, this paper will shed light on the issues faced by parties in ADR concerning agreements and shall thereby, provide a solution to overcome the same.
Clinical Response to Xultophy Possibly Varies from Each Different Metabolic Function
Authors: Hiroshi Bando , Kazuki Sakamoto , Tomoya Ogawa , Naoki Kondo , Shigeki Hatakeyama , Toshiharu Kobayashi , Noboru Iwatsuki
Published: March 2021

Two patients with Type 2 Diabetes Mellitus (T2DM) were treated with Xultophy. Xultophy consists of degludec and liraglutide (IDegLira). It is the combination of long-acting insulin and Glucagon like Peptide-1 Receptor Agonist (GLP-1RA) and is characteristic for effective agent for improving glucose variability for patients with T2DM. However, clinical responses are not always satisfactory due to different complication and background of each patient. We have experienced two impressive T2DM cases. Case 1 was 59-year-old male with hypertension for 20 years and T2DM for 3 years. He was treated on Novolin 30R 30/21 units twice a day, and after that Xultophy 32 doses brought him successful glucose profile. Case 2 was 78-year-old male with hypertension, bronchial asthma, hyperuricemia, and others with heavy alcohol drinking for 50 years. He was formerly treated by Insulin detemir, Liraglutide, exenatide and Degludec/NovoRapid, but has been recently unstable in glucose control. Xultophy up to 40 doses could not successfully improve glucose variability. One of the less responsiveness to Xultophy would be due to impaired liver function. Clinical progress of both cases associated with several perspectives from various points of view are discussed in this article.
2. Simondon as a Neo-Scholastic?
Authors: Fredrikzon Johan
Published: March 2021

Johan Fredrikzon spent one and a half years as a visiting research assistant at the Film and Media Studies Program at Yale University 2018/2019. Some months before he arrived, a two-day workshop on Simondon was held by the Yale-Düsseldorf Working Group on Philosophy and Media, titled Modes of Technical Objects, with scholars from the US and Germany. Fredrikzon decided to engage a few of the workshop participants for this special issue of Sensorium, with the purpose to discuss perspectives on Simondon as a theoretical instrument for thinking technology, how the French philosopher matters in their work, and why there seems to be a revival in the interest in the writing of Simondon these days. On behalf of the Sensorium journal, the interviewer would like to thank the three interviewees for their generous participation.

About John Durham Peters:

John Durham Peters is María Rosa Menocal Professor of English and of Film & Media Studies at Yale University. Peters has been a creative force in media studies for many years and his thinking continues to influence academic environments throughout the world. His book The Marvelous Clouds: Toward a Philosophy of Elemental Media (Chicago, 2015) was an attempt to rethink the concept of media by including weather, dolphins and fire to the infrastructural landscape of digital communications and climate change. His new book, in cooperation with Kenneth Cmiel, is called Promiscuous Knowledge: Information, Image, and Other Truth Games in History (Chicago, 2020).
Simondon’s Technical Culture and a Politics of Problems
Authors: Daechsel Stefano
Published: March 2021

There is a timeliness to Gilbert Simondon’s call in On the Mode of Existence of Technical Objects (1958) for a technical culture that fosters a ”genuine awareness of technical realities.” Writing in the context of mid-20th century France, Simondon worried about a lack of technological understanding and envisaged a technical culture in which technological education would be considered as essential as literacy to meaningful participation in society. Sixty years on, the need for widespread technological awareness is greater than ever. The aim of this article is to clarify and support this claim by examining it through the lens of a politics of problems that can be found in Deleuze’s Difference and Repetition (1968).
Cybernetics: The Macy Conferences
Authors: Fredrikzon Johan
Published: March 2021

Claus Pias (ed.), Cybernetics: The Macy Conferences 1946–1953. The Complete Transactions (Diaphanes, 2016)
Multimodal Analysis of the Tissue Response to a Bone-Anchored Hearing Implant: Presentation of a Two-Year Case Report of a Patient With Recurrent Pain, Inflammation, and Infection, Including a Systematic Literature Review
Authors: Johansson Martin L. , Calon Tim G.A. , Omar Omar , Shah Furqan A. , Trobos Margarita , Thomsen Peter , Stokroos Robert J. , Palmquist Anders
Published: March 2021

Osseointegration is a well-established concept used in applications including the percutaneous Bone-Anchored Hearing System (BAHS) and auricular rehabilitation. To date, few retrieved implants have been described. A systematic review including cases where percutaneous bone-anchored implants inserted in the temporal bone were retrieved and analyzed was performed. We also present the case of a patient who received a BAHS for mixed hearing loss. After the initial surgery, several episodes of soft tissue inflammation accompanied by pain were observed, leading to elective abutment removal 14 months post-surgery. Two years post-implantation, the implant was removed due to pain and subjected to a multiscale and multimodal analysis: microbial DNA using molecular fingerprinting, gene expression using quantitative real-time polymerase chain reaction (qPCR), X-ray microcomputed tomography (micro-CT), histology, histomorphometry, backscattered scanning electron microscopy (BSE-SEM), Raman spectroscopy, and fluorescence in situ hybridization (FISH). Evidence of osseointegration was provided via micro-CT, histology, BSE-SEM, and Raman spectroscopy. Polymicrobial colonization in the periabutment area and on the implant, including that with Staphylococcus aureus and Staphylococcus epidermidis, was determined using a molecular analysis via a 16S-23S rDNA interspace [IS]-region-based profiling method (IS-Pro). The histology suggested bacterial colonization in the skin and in the peri-implant bone. FISH confirmed the localization of S. aureus and coagulase-negative staphylococci in the skin. Ten articles (54 implants, 47 patients) met the inclusion criteria for the literature search. The analyzed samples were either BAHS (35 implants) or bone-anchored aural epitheses (19 implants) in situ between 2 weeks and 8 years. The main reasons for elective removal were nonuse/changes in treatment, pain, or skin reactions. Most samples were evaluated using histology, demonstrating osseointegration, but with the absence of bone under the implants’ proximal flange. Taken together, the literature and this case report show clear evidence of osseointegration, despite prominent complications. Nevertheless, despite implant osseointegration, chronic pain related to the BAHS may be associated with a chronic bacterial infection and raised inflammatory response in the absence of macroscopic signs of infection. It is suggested that a multimodal analysis of peri-implant health provides possibilities for device improvements and to guide diagnostic and therapeutic strategies to alleviate the impact of complications.
Selenium Kinetics in Humans Change Following 2 Years of Supplementation With Selenomethionine
Authors: Patterson Blossom H. , Combs Gerald F. , Taylor Philip R. , Patterson Kristine Y. , Moler James E. , Wastney Meryl E.
Published: March 2021

Background

Selenium (Se) is a nutritionally essential trace element and health may be improved by increased Se intake. Previous kinetic studies have shown differences in metabolism of organic vs. inorganic forms of Se [e.g., higher absorption of selenomethionine (SeMet) than selenite (Sel), and more recycling of Se from SeMet than Sel]. However, the effects on Se metabolism after prolonged Se supplementation are not known.

Objective

To determine how the metabolism and transport of Se changes in the whole-body in response to Se-supplementation by measuring Se kinetics before and after 2 years of Se supplementation with SeMet.

Methods

We compared Se kinetics in humans [n = 31, aged 40 ± 3 y (mean ± SEM)] studied twice after oral tracer administration; initially (PK1), then after supplementation for 2 y with 200 µg/d of Se as selenomethionine (SeMet) (PK2). On each occasion, we administered two stable isotope tracers of Se orally: SeMet, the predominant food form, and selenite (Na276SeO3, or Sel), an inorganic form. Plasma and RBC were sampled for 4 mo; urine and feces were collected for the initial 12 d of each period. Samples were analyzed for tracers and total Se by isotope dilution GC-MS. Data were analyzed using a compartmental model, we published previously, to estimate fractional transfer between pools and pool masses in PK2.

Results

We report that fractional absorption of SeMet or Sel do not change with SeMet supplementation and the amount of Se absorbed increased. The amount of Se excreted in urine increases but does not account for all the Se absorbed. As a result, there is a net incorporation of SeMet into various body pools. Nine of the 11 plasma pools doubled in PK2; two did not change. Differences in metabolism were observed for SeMet and Sel; RBC uptake increased 247% for SeMet, urinary excretion increased from two plasma pools for Sel and from two different pools for SeMet, and recycling to liver/tissues increased from one plasma pool for Sel and from two others for SeMet. One plasma pool increased more in males than females in PK2.

Conclusions

Of 11 Se pools identified kinetically in human plasma, two did not increase in size after SeMet supplementation. These pools may be regulated and important during low Se intake.
D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes
Authors: Montt-Guevara Maria Magdalena , Finiguerra Michele , Marzi Ilaria , Fidecicchi Tiziana , Ferrari Amerigo , Genazzani Alessandro D. , Simoncini Tommaso
Published: March 2021

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.
Climate Change Leads to a Reduction in Symbiotic Derived Cnidarian Biodiversity on Coral Reefs
Authors: Goulet Tamar L. , Goulet Denis
Published: March 2021

Symbiotic relationships enable partners to thrive and survive in habitats where they would either not be as successful, or potentially not exist, without the symbiosis. The coral reef ecosystem, and its immense biodiversity, relies on the symbioses between cnidarians (e.g., scleractinian corals, octocorals, sea anemones, jellyfish) and multiple organisms including dinoflagellate algae (family Symbiodiniaceae), bivalves, crabs, shrimps, and fishes. In this review, we discuss the ramifications of whether coral reef cnidarian symbioses are obligatory, whereby at least one of the partners must be in the symbiosis in order to survive or are facultative. Furthermore, we cover the consequences of cnidarian symbioses exhibiting partner flexibility or fidelity. Fidelity, where a symbiotic partner can only engage in symbiosis with a subset of partners, may be absolute or context dependent. Current literature demonstrates that many cnidarian symbioses are highly obligative and appear to exhibit absolute fidelity. Consequently, for many coral reef cnidarian symbioses, surviving changing environmental conditions will depend on the robustness and potential plasticity of the existing host-symbiont(s) combination. If environmental conditions detrimentally affect even one component of this symbiotic consortium, it may lead to a cascade effect and the collapse of the entire symbiosis. Symbiosis is at the heart of the coral reef ecosystem, its existence, and its high biodiversity. Climate change may cause the demise of some of the cnidarian symbioses, leading to subsequent reduction in biodiversity on coral reefs.
Feature Selection Using Approximate Conditional Entropy Based on Fuzzy Information Granule for Gene Expression Data Classification
Authors: Zhang Hengyi
Published: March 2021

Classification is widely used in gene expression data analysis. Feature selection is usually performed before classification because of the large number of genes and the small sample size in gene expression data. In this article, a novel feature selection algorithm using approximate conditional entropy based on fuzzy information granule is proposed, and the correctness of the method is proved by the monotonicity of entropy. Firstly, the fuzzy relation matrix is established by Laplacian kernel. Secondly, the approximately equal relation on fuzzy sets is defined. And then, the approximate conditional entropy based on fuzzy information granule and the importance of internal attributes are defined. Approximate conditional entropy can measure the uncertainty of knowledge from two different perspectives of information and algebra theory. Finally, the greedy algorithm based on the approximate conditional entropy is designed for feature selection. Experimental results for six large-scale gene datasets show that our algorithm not only greatly reduces the dimension of the gene datasets, but also is superior to five state-of-the-art algorithms in terms of classification accuracy.
Gene Expression Signature of Traumatic Brain Injury
Authors: Ma Yawen , Liu Yunhui , Ruan Xuelei , Liu Xiaobai , Zheng Jian , Teng Hao , Shao Lianqi , Yang Chunqing , Wang Di , Xue Yixue
Published: March 2021

Background: Traumatic brain injury (TBI) is a brain function change caused by external forces, which is one of the main causes of death and disability worldwide. The aim of this study was to identify early diagnostic markers and potential therapeutic targets for TBI.

Methods: Differences between TBI and controls in GSE89866 and GSE104687 were analyzed. The two groups of differentially expressed genes (DEGs) were combined for coexpression analysis, and the modules of interest were performed using enrichment analysis. Hub genes were identified by calculating area under curve (AUC) values of module genes, PPI network analysis, and functional similarity. Finally, the difference in immune cell infiltration between TBI and control was calculated by ssGSEA.

Results: A total of 4,817 DEGs were identified in GSE89866 and 1,329 DEGs in GSE104687. They were clustered into nine modules. The genes of modules 1, 4, and 7 had the most crosstalk and were identified as important modules. Enrichment analysis revealed that they were mainly associated with neurodevelopment and immune inflammation. In the PPI network constructed by genes with top 50 AUC values in module genes, we identified the top 10 genes with the greatest connectivity. Among them, down-regulated RPL27, RPS4X, RPL23A, RPS15A, and RPL7A had similar functions and were identified as hub genes. In addition, DC and Tem were significantly up-regulated and down-regulated between TBI and control, respectively.

Conclusion: We found that hub genes may have a diagnostic role for TBI. Molecular dysregulation mechanisms of TBI are associated with neurological and immune inflammation. These results may provide new ideas for the diagnosis and treatment of TBI.
Role of the IL23/IL17 Pathway in Crohn’s Disease
Authors: Schmitt Heike , Neurath Markus F. , Atreya Raja
Published: March 2021

Crohn’s disease (CD) is a chronic relapsing disorder of the gastrointestinal tract and represents one of the main entities of inflammatory bowel disease (IBD). CD affects genetically susceptible patients that are influenced by environmental factors and the intestinal microbiome, which results in excessive activation of the mucosal immune system and aberrant cytokine responses. Various studies have implicated the pro-inflammatory cytokines IL17 and IL23 in the pathogenesis of CD. IL23 is a member of the IL12 family of cytokines and is able to enhance and affect the expansion of pathogenic T helper type 17 (Th17) cells through various mechanisms, including maintenance of Th17 signature genes, upregulation of effector genes or suppression of repressive factors. Moreover, IL17 and IL23 signaling is able to induce a cascade of pro-inflammatory molecules like TNF, IFNγ, IL22, lymphotoxin, IL1β and lipopolysaccharide (LPS). Here, IL17A and TNF are known to mediate signaling synergistically to drive expression of inflammatory genes. Recent advances in understanding the immunopathogenetic mechanisms underlying CD have led to the development of new biological therapies that selectively intervene and inhibit inflammatory processes caused by pro-inflammatory mediators like IL17 and IL23. Recently published data demonstrate that treatment with selective IL23 inhibitors lead to markedly high response rates in the cohort of CD patients that failed previous anti-TNF therapy. Macrophages are considered as a main source of IL23 in the intestine and are supposed to play a key role in the molecular crosstalk with T cell subsets and innate lymphoid cells in the gut. The following review focuses on mechanisms, pathways and specific therapies in Crohn’s disease underlying the IL23/IL17 pathway.
Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity
Authors: Lamadrid Patricia , Alonso-Peña Marta , San Segundo David , Arias-Loste Mayte , Crespo Javier , Lopez-Hoyos Marcos
Published: March 2021

The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.
A Relocatable Ocean Modeling Platform for Downscaling to Shelf-Coastal Areas to Support Disaster Risk Reduction
Authors: Trotta Francesco , Federico Ivan , Pinardi Nadia , Coppini Giovanni , Causio Salvatore , Jansen Eric , Iovino Doroteaciro , Masina Simona
Published: March 2021

High-impact ocean weather events and climate extremes can have devastating effects on coastal zones and small islands. Marine Disaster Risk Reduction (DRR) is a systematic approach to such events, through which the risk of disaster can be identified, assessed and reduced. This can be done by improving ocean and atmosphere prediction models, data assimilation for better initial conditions and developing an efficient and sustainable impact forecasting methodology for Early Warnings Systems. A common user request during disaster remediation actions is for high-resolution information, which can be derived from easily deployable numerical models nested into operational larger-scale ocean models. The Structured and Unstructured Relocatable Ocean Model for Forecasting (SURF) enables users to rapidly deploy a nested high-resolution numerical model into larger-scale ocean forecasts. Rapidly downscaling the currents, sea level, temperature, and salinity fields is critical in supporting emergency responses to extreme events and natural hazards in the world’s oceans. The most important requirement in a relocatable model is to ensure that the interpolation of low-resolution ocean model fields (analyses and reanalyses) and atmospheric forcing is tested for different model domains. The provision of continuous ocean circulation forecasts through the Copernicus Marine Environment Monitoring Service (CMEMS) enables this testing. High-resolution SURF ocean circulation forecasts can be provided to specific application models such as oil spill fate and transport models, search and rescue trajectory models, and ship routing models requiring knowledge of meteo-oceanographic conditions. SURF was used to downscale CMEMS circulation analyses in four world ocean regions, and the high-resolution currents it can simulate for specific applications are examined. The SURF downscaled circulation fields show that the marine current resolutions affect the quality of the application models to be used for assessing disaster risks, particularly near coastal areas where the coastline geometry must be resolved through a numerical grid, and high-frequency coastal currents must be accurately simulated.
Environmental Heterogeneity Throughout the Clarion-Clipperton Zone and the Potential Representativity of the APEI Network
Authors: Washburn Travis W. , Jones Daniel O. B. , Wei Chih-Lin , Smith Craig R.
Published: March 2021

Environmental variables such as food supply, nodule abundance, sediment characteristics, and water chemistry may influence abyssal seafloor communities and ecosystem functions at scales from meters to thousands of kilometers. Thus, knowledge of environmental variables is necessary to understand drivers of organismal distributions and community structure, and for selection of proxies for regional variations in community structure, biodiversity, and ecosystem functions. In October 2019, the Deep CCZ Biodiversity Synthesis Workshop was conducted to (i) compile recent seafloor ecosystem data from the Clarion-Clipperton Zone (CCZ), (ii) synthesize patterns of seafloor biodiversity, ecosystem functions, and potential environmental drivers across the CCZ, and (iii) assess the representativity of no-mining areas (Areas of Particular Environmental Interest, APEIs) for subregions and areas in the CCZ targeted for polymetallic nodule mining. Here we provide a compilation and summary of water column and seafloor environmental data throughout the CCZ used in the Synthesis Workshop and in many of the papers in this special volume. Bottom-water variables were relatively homogenous throughout the region while nodule abundance, sediment characteristics, seafloor topography, and particulate organic carbon flux varied across CCZ subregions and between some individual subregions and their corresponding APEIs. This suggests that additional APEIs may be needed to protect the full range of habitats and biodiversity within the CCZ.
Analysis on Efficacy of Chitosan-Based Gel on Bone Quality and Quantity
Authors: Jayash Soher Nagi , Hashim Najihah Mohd , Misran Misni , Ibrahim Norliza , AL-Namnam Nisreen Mohammed , Baharuddin N. A.
Published: March 2021

Objectives: To assess and compare the quantity and the quality of the newly bone generated when using chitosan-based gel scaffold and osteoprotegerin-chitosan gel scaffold.

Methods: A total of 18 critical-sized defects on New Zealand white rabbit craniums were created. In 12 defects, either chitosan gel or osteoprotegerin-chitosan gel was implanted the last six defects were kept unfilled as a control. Bone formation was examined at 6 and 12 weeks. Bone’s specimens were scanned using the High-resolution peripheral quantitative computed tomography. Histological and histomorphometric analysis were carried out to compare the volume and area of regenerated bone.

Results: The results of the HR-pQCT showed that bone volume and densities in the osteoprotegerin-chitosan gel group were significantly higher than the chitosan gel and control groups whereas, the bone volume density in the chitosan gel group was significantly higher than the control group in both intervals time (p = 0.01, p = 000). No significant difference in bone volume between the chitosan gel and control groups (p = 0.506, p = 0.640) was observed. However, similar findings were shown in the histomorphometric analysis, with the highest new bone formation was observed in the OPG-chitosan gel group followed by the chitosan group. The mean percentage of new bone was greater at 12 weeks compared to 6 weeks in all groups.

Conclusions: Chitosan-based gel demonstrated a significant bone quantity and quality compared to unfilled surgical defects. Consistently, osteoprotegerin enhanced the chitosan gel in bone regeneration.
ICD-10-Coding of Medically Unexplained Physical Symptoms and Somatoform Disorders—A Survey With German GPs
Authors: Pohontsch Nadine J. , Zimmermann Thomas , Lehmann Marco , Rustige Lisa , Kurz Katinka , Löwe Bernd , Scherer Martin
Published: March 2021

Background:General practitioners (GPs) are reluctant to use codes that correspond to somatization syndromes.

Aim:To quantify GPs' views on coding of medically unexplained physical symptoms (MUPS), somatoform disorders, and associated factors.

Design and Setting:Survey with German GPs.

Methods:We developed six survey items [response options “does not apply at all (1)”—“does fully apply (6)”], invited a random sample of 12.004 GPs to participate in the self-administered cross-sectional survey and analysed data using descriptive statistics and logistic regression analyses.

Results:Response rate was 15.2% withN= 1,731 valid responses (54.3% female). Participants considered themselves familiar with ICD-10 criteria for somatoform disorders (M= 4.52;SD=.036) and considered adequate coding as essential prerequisite for treatment (M= 5.02;SD= 1.21). All other item means were close to the scale mean: preference for symptom or functional codes (M= 3.40;SD= 1.21), consideration of the possibility of stigmatisation (M= 3.30;SD= 1.35) and other disadvantages (M= 3.28;SD= 1.30) and coding only if psychotherapy is intended (M= 3.39;SD= 1.46). Exposure, guideline knowledge, and experience were most strongly associated with GPs' self-reported coding behaviour.

Conclusions:Subjective exposure, guideline knowledge, and experience as a GP, but no sociodemographic variable being associated with GPs' subjective coding behaviour could indicate that GPs offer a relatively homogeneous approach to coding and handling of MUPS and somatoform disorders. Strengthening guideline knowledge and implementation, and practise with simulated patients could increase the subjective competence to cope with the challenge that patients with MUPS and somatoform disorders present.
Ethical Challenges Related to the Novel Coronavirus (COVID-19) Outbreak: Interviews With Professionals From Saudi Arabia
Authors: Alahmad Ghiath , Richi Hanie , BaniMustafa Ala'a , Almutairi Adel F.
Published: March 2021

The new and dangerous coronavirus disease (COVID-19) has posed a serious challenge to the ability of healthcare systems of many countries to contain the spread of the disease and to mitigate its various consequences. The disease posed many ethical challenges both in itself and in the methods used in its management. Although the ethical principles that healthcare operates under are universal, a thorough understanding of the ethical difficulties it poses necessitates consideration of contextual, societal, and cultural factors. This study provides an in-depth exploration of the ethical challenges related to the COVID-19 pandemic outbreak in relation to healthcare providers, medical researchers, and decision-makers in Saudi Arabia. Four themes were extracted from participants' responses, namely, ethical challenges about disease-control measures, challenges to actions in certain groups, challenges regarding software programs, and finally ethics in research practices. Each theme likewise contained sub-themes. The themes and sub-themes were discussed in light of the ethical principles: autonomy, beneficence, non-beneficence, and justice, as well as other principles, such as protecting confidentiality, privacy, and preventing stigma and discrimination.
Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Implications for Inflammatory Bowel Diseases
Authors: Schulz-Kuhnt Anja , Neurath Markus F. , Wirtz Stefan , Atreya Imke
Published: March 2021

The occurrence of epithelial defects in the gut relevantly contributes to the pathogenesis of inflammatory bowel diseases (IBD), whereby the impairment of intestinal epithelial barrier integrity seems to represent a primary trigger as well as a disease amplifying consequence of the chronic inflammatory process. Besides epithelial cell intrinsic factors, accumulated and overwhelmingly activated immune cells and their secretome have been identified as critical modulators of the pathologically altered intestinal epithelial cell (IEC) function in IBD. In this context, over the last 10 years increasing levels of attention have been paid to the group of innate lymphoid cells (ILCs). This is in particular due to a preferential location of these rather newly described innate immune cells in close proximity to mucosal barriers, their profound capacity to secrete effector cytokines and their numerical and functional alteration under chronic inflammatory conditions. Aiming on a comprehensive and updated summary of our current understanding of the bidirectional mucosal crosstalk between ILCs and IECs, this review article will in particular focus on the potential capacity of gut infiltrating type-1, type-2, and type-3 helper ILCs (ILC1s, ILC2s, and ILC3s, respectively) to impact on the survival, differentiation, and barrier function of IECs. Based on data acquired in IBD patients or in experimental models of colitis, we will discuss whether the different ILC subgroups could serve as potential therapeutic targets for maintenance of epithelial integrity and/or mucosal healing in IBD.
Microbiome Community Structure and Functional Gene Partitioning in Different Micro-Niches Within a Sporocarp-Forming Fungus
Authors: Liu Dong , He Xinhua , Chater Caspar C. C. , Perez-Moreno Jesús , Yu Fuqiang
Published: March 2021

Thelephora ganbajun is a wild edible mushroom highly appreciated throughout China. The microbiomes of some fungal sporocarps have been studied, however, their potential functional roles currently remain uncharacterized. Here, functional gene microarrays (GeoChip 5.0) and amplicon sequencing were employed to define the taxonomic and functional attributes within three micro-niches of T. ganbajun. The diversity and composition of bacterial taxa and their functional genes differed significantly (p < 0.01) among the compartments. Among 31,117 functional genes detected, some were exclusively recorded in one sporocarp compartment: 1,334 genes involved in carbon (mdh) and nitrogen fixation (nifH) in the context; 524 genes influencing carbon (apu) and sulfite reduction (dsrB, dsra) in the hymenophore; and 255 genes involved in sulfur oxidation (soxB and soxC) and polyphosphate degradation (ppx) in the pileipellis. These results shed light on a previously unknown microbiome and functional gene partitioning in sporome compartments of Basidiomycota. This also has great implications for their potential ecological and biogeochemical functions, demonstrating a higher genomic complexity than previously thought.
The Assembly Switch Mechanism of FtsZ Filament Revealed by All-Atom Molecular Dynamics Simulations and Coarse-Grained Models
Authors: Lv Dashuai , Li Jingyuan , Ye Sheng
Published: March 2021

Bacterial cytoskeletal protein FtsZ binds and hydrolyzes GTP, and assembles into dynamic filaments that are essential for cell division. Here, we used a multi-scale computational strategy that combined all-atom molecular dynamics (MD) simulations and coarse-grained models to reveal the conformational dynamics of assembled FtsZ. We found that the top end of a filament is highly dynamic and can undergo T-to-R transitions in both GTP- and GDP-bound states. We observed several subcategories of nucleation related dimer species, which leading to a feasible nucleation pathway. In addition, we observed that FtsZ filament exhibits noticeable amounts of twisting, indicating a substantial helicity of the FtsZ filament. These results agree with the previously models and experimental data. Anisotropy network model (ANM) analysis revealed a polymerization enhanced assembly cooperativity, and indicated that the cooperative motions in FtsZ are encoded in the structure. Taken together, our study provides a molecular-level understanding of the diversity of the structural states of FtsZ and the relationships among polymerization, hydrolysis, and cooperative assembly, which should shed new light on the molecular basis of FtsZ’s cooperativity.
Characterization and Mechanism of Linearized-Microcystinase Involved in Bacterial Degradation of Microcystins
Authors: Wei Jia , Huang Feiyu , Feng Hai , Massey Isaac Yaw , Clara Tezi , Long Dingxin , Cao Yi , Luo Jiayou , Yang Fei
Published: March 2021

Microcystins (MCs) are extremely hazardous to the ecological environment and public health. How to control and remove MCs is an unsolved problem all over the world. Some microbes and their enzymes are thought to be effective in degrading MCs. Microcystinase can linearize microcystin-leucine-arginine (MC-LR) via a specific locus. However, linearized MC-LR is also very toxic and needs to be removed. How linearized MC-LR was metabolized by linearized-microcystinase, especially how linearized-microcystinase binds to linearized MC-LR, has not been defined. A combination of in vitro experiments and computer simulation was applied to explore the characterization and molecular mechanisms for linearized MC-LR degraded by linearized-microcystinase. The purified linearized-microcystinase was obtained by recombinant Escherichia coli overexpressing. The concentration of linearized MC-LR was detected by high-performance liquid chromatography, and linearized MC-LR degradation products were analyzed by the mass spectrometer. Homology modeling was used to predict the structure of the linearized-microcystinase. Molecular docking techniques on the computer were used to simulate the binding sites of linearized-microcystinase and linearized MC-LR. The purified linearized-microcystinase was obtained successfully. The linearized-microcystinase degraded linearized MC-LR to tetrapeptide efficiently. The second structure of linearized-microcystinase consisted of many alpha-helices, beta-strands, and colis. Linearized-microcystinase interacted the linearized MC-LR with hydrogen bond, hydrophobic interaction, electrostatic forces, and the Van der Waals force. This study firstly reveals the characterization and specific enzymatic mechanism of linearized-microcystinase for catalyzing linearized MC-LR. These findings encourage the application of MC-degrading engineering bacteria and build a great technique for MC-LR biodegradation in environmental engineering.
Gazing at Social Interactions Between Foraging and Decision Theory
Authors: D'Amelio Alessandro , Boccignone Giuseppe
Published: March 2021

Finding the underlying principles of social attention in humans seems to be essential for the design of the interaction between natural and artificial agents. Here, we focus on the computational modeling of gaze dynamics as exhibited by humans when perceiving socially relevant multimodal information. The audio-visual landscape of social interactions is distilled into a number of multimodal patches that convey different social value, and we work under the general frame of foraging as a tradeoff between local patch exploitation and landscape exploration. We show that the spatio-temporal dynamics of gaze shifts can be parsimoniously described by Langevin-type stochastic differential equations triggering a decision equation over time. In particular, value-based patch choice and handling is reduced to a simple multi-alternative perceptual decision making that relies on a race-to-threshold between independent continuous-time perceptual evidence integrators, each integrator being associated with a patch.