bluuebunny/crossref_metadata_2025 huggingface dataset:
Framing Mass Hysteria Covid-19 dalam Berita Tempo dan Detikx
Authors: Rahman Khairul Arief , Laily Hamidah Izzatu
Published: April 2021

Coverage of the Coronavirus or Covid-19 in Indonesia was accompanied by confusion of information which resulted Mass Hysteria. Media criticism is also present as the vanguard of social control, which is not only limited to what and how it appeared, but also critically explores readiness from the political level of government to the social life of the affected community. How two "premium" media, namely Tempo and DetikX, build news construction about Covid-19? Then how do the media frame a topic or issue that has developed after Covid-19? and how is the concentration of the media in reporting on Mass Hysteria that developed after Covid-19 in Indonesia? This study takes news in March 2020, Especially on the main coverage presented by both media. This research uses qualitative research method and Pan and Kosicki's framing analysis model for explore data research. The Result is Tempo Magazine and DetikX generally drawing struggle toward Mass Hysteria and affair caused by Covid-19 on critics of handling policy government level and public with selectively choosing solution frame as shape of struggle.
Konstruksi Realitas Integritas Komisi Pemberantasan Korupsi (KPK) dalam Pemberitaan Media Online
Authors: Barizki Rezzi Nanda , Riyantie Mayang
Published: April 2021

The aim of this research is to know the construction of the reality of the reporting on the integrity of the KPK from the framing of online media Kompas.com and Detik.com. The paradigm used is constructivist, with the Entman’s framing analysis method, which means that it is preceded by the assumption that reality tends to have multiple faces (multiple reality). Therefore, this research will have a theoretical contribution to the public's understanding about the construction of mass media reality, and public awareness that the aspects of corruption prevention must be started by the actors of KPK itself (the issue of integrity), as well as for strengthening the anti-graft institution. The results showed that the reality construction formed by excellent reputation media such as Kompas.com and Detik.com will gain high public trust, especially in disclosing information on important state institutions, such as KPK. The similarity construction is related to the public criticism and demand about the existence of KPK as Supervisory Board; on the contrary, it oftentimes still stained by the violation allegation of the ethical code of its leaders. Moreover, there was internal conflict, decreased performance and public pessimism. As for the difference, Kompas.com built a positive image by the KPK's actions in overseeing state institutions and investigating several cases, while Detik.com delivered content on sympathetic social action, coordination with regional leaders, appreciation for the existence of KPK by a popular state figure.
Comparison Analysis of Developmentalism in Globalization Era: Indonesia Joko Widodo’s Presidency (2014-2019) and South Korea Moon Jae-In Presidency (2017-2020)
Authors: Mulyaman Darynaufal , Ismail Achmad , Carollina Nadya , Zefanya Morry
Published: April 2021

In the globalized age, freedom in capital and workforce movement, self expression, and information openness become vital, including in Asian countries like Indonesia and South Korea. Thus innovation and creativity have become an important key in recent eras. New kinds of innovation and creativity that are established by Asian countries sometimes are nostalgic policies by the previous regime of the government. Therefore, Indonesia still comes up with a kind of centralistic governance and planning with a twist of free and liberal market policy, a developmental style of New Order governance to some extent. Hence, why is developmentalism in Indonesia still relevant? Even when there are shifts in the regimes and globalization process of the world. This paper argues that the policy series that has been initiated in Indonesia under President Joko Widodo is still part of developmentalism because of the historical and political context in a broader sense on developmentalism, therefore still relevant in Indonesia. This paper also uses the South Korean case of current policy under President Moon Jae-In to compare and assign Indonesian developmentalism relevancy as South Korea can be seen as one of the successful examples of developmentalism yet liberal country.
U-LINK 2019 Workshop Assessment Results
Authors: Morgan Susan , Mosser Alexandra , Bixby John
Published: April 2021

This document summarizes the content of the 2019 Team Science Workshop offered to awardees of the U-LINK interdisciplinary pilot research funding program. It also presents the results of participants’ evaluation of the workshop.
BIMBINGAN DAN PELATIHAN TENTANG PENGEMBANGAN KEPRIBADIAN DAN ETIKA PADA ANGGOTA PKK RW 01 KELURAHAN JATIMULYO KECAMATAN LOWOKWARU KOTA MALANG
Authors: Mahmudatul Himmah  , Diana Eka Poernamawati  , Lilies Nur Ainie  , Eko Boedhi Santoso
Published: April 2021

Kegiatan pengabdian kepada masyarakat ini bertujuan untuk memberikan bimbingan dan pelatihan tentang pentingnya pengembangan kepribadian kepada masyarakat khususnya kaum wanita yang terorganisasi dalam kegiatan sosial kemasyarakatan khususnya kelompok PKK. Sesuai dengan tujuan dari organisasi ini adalah untuk memberikan pendidikan kesejahteraan keluarga dan masyarakat secara intensif agar para ibu-ibu sebagai pendidik paling pertama di keluarga dan anak- anaknya dirumah serta lingkungan masyarakat pada umumnya

Metode yang digunakan dalam kegiatan pengabdian ini adalah ceramah dan tanya jawab, yaitu penyampaian materi tentang karakter kepribadian dan cara mengembangkannya. Selain ceramah juga dilakukan diskusi dan Tanya Jawab untuk memberikan kesempatan kepada peserta dalam memahami lebih lanjut tentang materi yang disampaikan.Hasil dari kegiatan ini adalah bahwa para peserta memperoleh wawasan dan pemahaman (kognisi) tentang pentingnya etika dan cara mengembangkan diri khususnya dalam menghadapi perkembangan kehidupan di era globa ini, sehingga dapat menerapkan kepribadian yang efektif dalam kehidupan sehari-hari dan mudah beradaptasi dengan perkembangan teknologi.
Bimbingan Teknis Renovasi Pembangunan Musholla Nurul Hidayah Dan Tpq Az-Zahiroh Dusun Dermo Desa Mulyoagung Kecamatan Dau Kabupaten Malang
Authors: Qomariah  , Rinto Sasongko  , Sugiarti  , Sugeng Riyanto  , Sunarto Suryanto
Published: April 2021

Kegiatan pengabdian kepada masyarakat ini bertujuan untuk memberikan bimbingan dan pelatihan tentang pentingnya pengembangan kepribadian kepada masyarakat khususnya kaum wanita yang terorganisasi dalam kegiatan sosial kemasyarakatan khususnya kelompok PKK. Sesuai dengan tujuan dari organisasi ini adalah untuk memberikan pendidikan kesejahteraan keluarga dan masyarakat secara intensif agar para ibu-ibu sebagai pendidik paling pertama di keluarga dan anak- anaknya dirumah serta lingkungan masyarakat pada umumnya

Metode yang digunakan dalam kegiatan pengabdian ini adalah ceramah dan tanya jawab, yaitu penyampaian materi tentang karakter kepribadian dan cara mengembangkannya. Selain ceramah juga dilakukan diskusi dan Tanya Jawab untuk memberikan kesempatan kepada peserta dalam memahami lebih lanjut tentang materi yang disampaikan.Hasil dari kegiatan ini adalah bahwa para peserta memperoleh wawasan dan pemahaman (kognisi) tentang pentingnya etika dan cara mengembangkan diri khususnya dalam menghadapi perkembangan kehidupan di era globa ini, sehingga dapat menerapkan kepribadian yang efektif dalam kehidupan sehari-hari dan mudah beradaptasi dengan perkembangan teknologi.
PELATIHAN PEMBUATAN PRESENTASI INTERAKTIF UNTUK WARGA DAN PERANGKAT DESA KARANGDUREN, KEC.PAKISAJI, KAB. MALANG
Authors: Yuri Ariyanto  , Atiqah Nurul Asri  , Dwi Puspitasari  , Yoppy Yunhasnawa  , Bagas Satya Dian Nugraha
Published: April 2021

Di tingkat desa, banyak kendala yang dihadapi aparatur pemerintahan desa dalam upaya memberikan pelayanan pada masyarakatnya. Satu diantaranya yang kini menonjol adalah hambatan yang terkait dengan kurangnya pengetahuan dan keterampilan pemanfaatan teknologi informasi dan komunikasi, khususnya aplikasi untuk pembuatan presentasi interaktif. Didasari kenyataan itulah maka gagasan untuk melaksanakan kegiatan PKM (Pengabdian Kepada Masyarakat) berupa P Pelatihan Pembuatan Presentasi Interaktif Untuk Warga Dan Perangkat Desa Karangduren,Kec. Pakisaji, Kab. Malang.Melalui Kegiatan “PKM (Pengabdian Kepada Masyarakat) pada Desa Karangduren, Kec. Pakisaji, Kab. Malang ini dilakukan untuk membantu menyelesaikan permasalahan yang ada dalam penggunaan software microsoft office power point untuk pembuatan presentasi interaktif, sehingga permasalahan yang ada dalam pembuatan media presentasi yang menarik. Selain itu penyampian informasi dalam rapat maupun pengumuman yang ada di desa bisa disampaikan lebih menarik.
PELATIHAN PENGELASAN SMAW BAGI REMAJA KARANG TARUNA KELURAHAN TEMAS RT 5 / RW 7 KECAMATAN BATU KOTA BATU
Authors: Arif Rochman Fachrudin  , Fina Andika Frida Astuti  , Mira Esculenta Martawati  , Ahmad Hanif
Published: April 2021

Dalam Tri Darma Perguruan Tinggi, Perguruan Tinggi mempunyai peran yang sangat penting, yaitu salah satunya adalah ikut dalam mencerdaskan kehidupan bangsa dan negara sencara nyata di masyarakat. Salah satu langkahnya adalah menjadikan manusia bukan lagi menjadi obyek pembangunan tetapi menjadi subyek pembangunan. Sebagai subyek pembangunan tentunya diperlukan kemampuan dan kecakapan dalam penguasaan ilmu pengetahuan dan teknologi.Pemanfaatan teknologi pengelasan telah berkembang dan banyak digunakan dan dimanfaatkan ditengah masyarakat luas, baik untuk skala industri rumah tangga maupun untuk perbaikan perbaikan peralatan dirumah. Salah satu metode pengelasan adalah pengelasan SMAW, yaitu pengelasan dengan menggunakan busur listrik.Tujuan dari kegiatan ini adalah meningkatkan pengetahuan secara umum remaja karang taruna kampung teh kelurahan Temas Kecamatan Batu kota Batu, menambah ketrampilan kusus berupa pengelasan SMAW dan memberikan dorongan dan bantuan sehingga karang taruna kampung teh mampu mengadakan peralatan las.Manfaat dari kegiatan ini adalah memberikan pengetahuan dan melatih ketrampilan dalam pengelasan SMAW sehingga bisa digunakan untuk pengembangan pribadi maupun manfaat secara sosial.
Kepuasan Jamaah Masjid Haji Agus Salim Terhadap Sound Sistem Yang Terpasang
Authors: Azam Muzakhim Imammudin  , Farida Arinie Soelistianto  , Waluyo  , Hudiono  , Koesmarijanto
Published: April 2021

Indonesia merupakan negara muslim terbesar di dunia, dengan jumlah 264 juta penduduk yang tersebar di berbagai pulau. Dengan mayoritas penduduk Indonesia yang beragama muslim maka jumlah tempat peribadatan atau masjid jumlahnya sebanding dengan penduduknya. Saat ini terdapat sekitar 250 ribu masjid dan 550 ribu mushala. Namun dari jumlah tersebut tercatat ribuan masjid masih mempunyai peralatan dan penataan sistem tata suara yang buruk. Masjid Haji Agus Salim yang ada di jalan piranha atas kota malang termasuk dalam kategori mempunyai kualitas suara yang buruk. Pada pengabdian ini diusulkan pelatihan penataan dan instalasi sistem tata suara di Masjid Haji Agus Salim kota malang. Diharapkan dengan adanya pelatihan dan penataan sistem tata suara ini kualitas suara yang dihasilkan semakin bagus sehingga membuat nyaman masyarakat yang ingin beribadah. Hasil dari pelatihan ini menunjukkan bahwa sebanyak 20 jamaah masjid merasa sangat puas dengan tata suara yang ada di masjid haji agus salim.
Motståndets motstånd
Authors: Ryan Bengtsson Anna
Published: April 2021

This article focuses on how gendered power operates in the neoliberal welfare regime and the circumstances created for welfare professionals in Sweden to act politically. Based on interviews with key informants in two cases of collective resistance among midwives and social workers, attention is focused on the practices of power used by politicians and managers. Drawing on resistance theory and concepts developed through previous research on equality, the result shows how fear is created and used and how distance is upheld through different techniques of power, which serve to prevent both collective mobilization and avoid these issues of deteriorated working conditions and care being politicized in terms of inequality
BRCA1 and BRCA2 Tumor Suppressor Function in Meiosis
Authors: Li Qianyan , Engebrecht JoAnne
Published: April 2021

Meiosis is a specialized cell cycle that results in the production of haploid gametes for sexual reproduction. During meiosis, homologous chromosomes are connected by chiasmata, the physical manifestation of crossovers. Crossovers are formed by the repair of intentionally induced double strand breaks by homologous recombination and facilitate chromosome alignment on the meiotic spindle and proper chromosome segregation. While it is well established that the tumor suppressors BRCA1 and BRCA2 function in DNA repair and homologous recombination in somatic cells, the functions of BRCA1 and BRCA2 in meiosis have received less attention. Recent studies in both mice and the nematodeCaenorhabditis eleganshave provided insight into the roles of these tumor suppressors in a number of meiotic processes, revealing both conserved and organism-specific functions. BRCA1 forms an E3 ubiquitin ligase as a heterodimer with BARD1 and appears to have regulatory roles in a number of key meiotic processes. BRCA2 is a very large protein that plays an intimate role in homologous recombination. As women with no indication of cancer but carrying BRCA mutations show decreased ovarian reserve and accumulated oocyte DNA damage, studies in these systems may provide insight into why BRCA mutations impact reproductive success in addition to their established roles in cancer.
Fingolimod Potentiates the Antifungal Activity of Amphotericin B
Authors: Wei Lu-Qi , Tan Jing-Cong , Wang Yue , Mei Yi-Kun , Xue Jia-Yu , Tian Lei , Song Ke-Yu , Han Lu , Cui Ying-Chao , Peng Yi-Bing , Li Jing-Quan , Liu Ning-Ning , Wang Hui
Published: April 2021

Candida albicans (C. albicans) is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against C. albicans growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.
Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction
Authors: Ranjan Prabhat , Kumari Rajesh , Goswami Sumanta Kumar , Li Jing , Pal Harish , Suleiman Zainab , Cheng Zhongjian , Krishnamurthy Prasanna , Kishore Raj , Verma Suresh Kumar
Published: April 2021

Background: Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function.

Methods and Results: Exosomes were isolated from cardiac fibroblast (FB)-conditioned media and characterized by nanoparticle tracking analysis and electron microscopy. ECs were isolated from mouse heart. ECs were treated with exosomes isolated from FB-conditioned media, following FB culture with TGF-β1 (TGF-β1-FB-Exo) or PBS (control) treatment. TGF-β1 significantly activated fibroblasts as shown by increase in collagen type1 α1 (COL1α1), periostin (POSTN), and fibronectin (FN1) gene expression and increase in Smad2/3 and p38 phosphorylation. Impaired endothelial cell function (as characterized by a decrease in tube formation and cell migration along with reduced VEGF-A, Hif1α, CD31, and angiopoietin1 gene expression) was observed in TGF-β1-FB-Exo treated cells. Furthermore, TGF-β1-FB-Exo treated ECs showed reduced cell proliferation and increased apoptosis as compared to control cells. TGF-β1-FB-Exo cargo analysis revealed an alteration in fibrosis-associated miRNAs, including a significant increase in miR-200a-3p level. Interestingly, miR-200a-3p inhibition in activated FBs, alleviated TGF-β1-FB-Exo-mediated endothelial dysfunction.

Conclusions: Taken together, this study demonstrates an important role of miR-200a-3p enriched within activated fibroblast-derived exosomes on endothelial cell biology and function.
Pathological Hyperinsulinemia and Hyperglycemia in the Impaired Glucose Tolerance Stage Mediate Endothelial Dysfunction Through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 Pathways
Authors: Liu Ran , Guan Shilin , Gao Zhongai , Wang Jingyu , Xu Jie , Hao Zhaohu , Zhang Yi , Yang Shaohua , Guo Zhenhong , Yang Juhong , Shao Hailin , Chang Baocheng
Published: April 2021

Background

Impaired glucose tolerance (IGT) is an important prediabetic stage characterized by elevated concentrations of glucose and insulin in the blood. The pathological hyperglycemia and hyperinsulinemia in IGT may regulate the expression of microRNA-21 (miR-21) and affect the downstream insulin signaling pathways, leading to endothelial cell dysfunction and early renal damage.

Methods

The individual and combined effects of insulin and glucose were investigated using human glomerular endothelial cells (HGECs). The expression levels of miR-21, and PTEN/AKT/eNOS and MAPK/ET-1 pathway proteins in the treated cells were measured. The levels of nitric oxide (NO) and endothelin-1 (ET-1) secreted by the cells were also measured. The role of miR-21 in mediating the regulatory effects of insulin and glucose was assessed by overexpression/inhibition of this miRNA using mimics/inhibitor.

Results

High (>16.7 mmol/L) concentration of glucose upregulated the expression of miR-21, leading to the activation and inhibition of the PTEN/AKT/eNOS and MAPK/ET-1 pathways, and upregulation of NO and downregulation of ET-1 secretion, respectively. High (>25 ng/mL) concentration of insulin downregulated the expression of miR-21, and lead to the activation of the MAPK/ET-1 and inhibition of the PTEN/AKT/eNOS pathway, thereby upregulating the expression of ET-1 and downregulating the secretion of NO. MiR-21 was observed to play a key role by directly controlling the activation of the insulin signaling pathways when the cells were cotreated with different concentrations of insulin and glucose. The expression of miR-21 was found to be dependent on the relative concentration of insulin and glucose. Under simulated conditions of the IGT stage (8.3 mmol/L glucose + 50 ng/mL insulin), the inhibitory effect of high insulin concentration on miR-21 expression in the cells attenuated the activation by high glucose concentration, resulting in the downregulation of miR-21, upregulation of ET-1 and downregulation of NO secretion.

Conclusion

Taken together, these results indicate that high insulin and glucose concentrations regulate the secretory function of glomerular endothelial cells in opposite ways by regulating the expression of miRNA-21. Pathological concentrations of insulin and glucose in the IGT stage may lead to a decrease in miR-21 expression, thereby disordering the secretion of vasoactive factors, resulting in renal tubule ischemia.
The Eye as a Transplantation Site to Monitor Pancreatic Islet Cell Plasticity
Authors: Ilegems Erwin , Berggren Per-Olof
Published: April 2021

The endocrine cells confined in the islets of Langerhans are responsible for the maintenance of blood glucose homeostasis. In particular, beta cells produce and secrete insulin, an essential hormone regulating glucose uptake and metabolism. An insufficient amount of beta cells or defects in the molecular mechanisms leading to glucose-induced insulin secretion trigger the development of diabetes, a severe disease with epidemic spreading throughout the world. A comprehensive appreciation of the diverse adaptive procedures regulating beta cell mass and function is thus of paramount importance for the understanding of diabetes pathogenesis and for the development of effective therapeutic strategies. While significant findings were obtained by the use of islets isolated from the pancreas, in vitro studies are inherently limited since they lack the many factors influencing pancreatic islet cell function in vivo and do not allow for longitudinal monitoring of islet cell plasticity in the living organism. In this respect a number of imaging methodologies have been developed over the years for the study of islets in situ in the pancreas, a challenging task due to the relatively small size of the islets and their location, scattered throughout the organ. To increase imaging resolution and allow for longitudinal studies in individual islets, another strategy is based on the transplantation of islets into other sites that are more accessible for imaging. In this review we present the anterior chamber of the eye as a transplantation and imaging site for the study of pancreatic islet cell plasticity, and summarize the major research outcomes facilitated by this technological platform.
A Step-by-Step Guide to Initialize and Calibrate Landscape Models: A Case Study in the Mediterranean Mountains
Authors: Suárez-Muñoz María , Mina Marco , Salazar Pablo C. , Navarro-Cerrillo Rafael M. , Quero José L. , Bonet-García Francisco J.
Published: April 2021

The use of spatially interactive forest landscape models has increased in recent years. These models are valuable tools to assess our knowledge about the functioning and provisioning of ecosystems as well as essential allies when predicting future changes. However, developing the necessary inputs and preparing them for research studies require substantial initial investments in terms of time. Although model initialization and calibration often take the largest amount of modelers’ efforts, such processes are rarely reported thoroughly in application studies. Our study documents the process of calibrating and setting up an ecophysiologically based forest landscape model (LANDIS-II with PnET-Succession) in a biogeographical region where such a model has never been applied to date (southwestern Mediterranean mountains in Europe). We describe the methodological process necessary to produce the required spatial inputs expressing initial vegetation and site conditions. We test model behaviour on single-cell simulations and calibrate species parameters using local biomass estimations and literature information. Finally, we test how different initialization data—with and without shrub communities—influence the simulation of forest dynamics by applying the calibrated model at landscape level. Combination of plot-level data with vegetation maps allowed us to generate a detailed map of initial tree and shrub communities. Single-cell simulations revealed that the model was able to reproduce realistic biomass estimates and competitive effects for different forest types included in the landscape, as well as plausible monthly growth patterns of species growing in Mediterranean mountains. Our results highlight the importance of considering shrub communities in forest landscape models, as they influence the temporal dynamics of tree species. Besides, our results show that, in the absence of natural disturbances, harvesting or climate change, landscape-level simulations projected a general increase of biomass of several species over the next decades but with distinct spatio-temporal patterns due to competitive effects and landscape heterogeneity. Providing a step-by-step workflow to initialize and calibrate a forest landscape model, our study encourages new users to use such tools in forestry and climate change applications. Thus, we advocate for documenting initialization processes in a transparent and reproducible manner in forest landscape modelling.
The Molecular Functions of MeCP2 in Rett Syndrome Pathology
Authors: Sharifi Osman , Yasui Dag H.
Published: April 2021

MeCP2 protein, encoded by the MECP2 gene, binds to DNA and affects transcription. Outside of this activity the true range of MeCP2 function is still not entirely clear. As MECP2 gene mutations cause the neurodevelopmental disorder Rett syndrome in 1 in 10,000 female births, much of what is known about the biologic function of MeCP2 comes from studying human cell culture models and rodent models with Mecp2 gene mutations. In this review, the full scope of MeCP2 research available in the NIH Pubmed (https://pubmed.ncbi.nlm.nih.gov/) data base to date is considered. While not all original research can be mentioned due to space limitations, the main aspects of MeCP2 and Rett syndrome research are discussed while highlighting the work of individual researchers and research groups. First, the primary functions of MeCP2 relevant to Rett syndrome are summarized and explored. Second, the conflicting evidence and controversies surrounding emerging aspects of MeCP2 biology are examined. Next, the most obvious gaps in MeCP2 research studies are noted. Finally, the most recent discoveries in MeCP2 and Rett syndrome research are explored with a focus on the potential and pitfalls of novel treatments and therapies.
CBP-JMF: An Improved Joint Matrix Tri-Factorization Method for Characterizing Complex Biological Processes of Diseases
Authors: Wang Bingbo , Ma Xiujuan , Xie Minghui , Wu Yue , Wang Yajun , Duan Ran , Zhang Chenxing , Yu Liang , Guo Xingli , Gao Lin
Published: April 2021

Multi-omics molecules regulate complex biological processes (CBPs), which reflect the activities of various molecules in living organisms. Meanwhile, the applications to represent disease subtypes and cell types have created an urgent need for sample grouping and associated CBP-inferring tools. In this paper, we present CBP-JMF, a practical tool primarily for discovering CBPs, which underlie sample groups as disease subtypes in applications. Differently from existing methods, CBP-JMF is based on a joint non-negative matrix tri-factorization framework and is implemented in Python. As a pragmatic application, we apply CBP-JMF to identify CBPs for four subtypes of breast cancer. The result shows significant overlapping between genes extracted from CBPs and known subtype pathways. We verify the effectiveness of our tool in detecting CBPs that interpret subtypes of disease.
Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases
Authors: Jaén Rafael I. , Sánchez-García Sergio , Fernández-Velasco María , Boscá Lisardo , Prieto Patricia
Published: April 2021

Inflammation is an a physiological response instead an essential response of the organism to injury and its adequate resolution is essential to restore homeostasis. However, defective resolution can be the precursor of severe forms of chronic inflammation and fibrosis. Nowadays, it is known that an excessive inflammatory response underlies the most prevalent human pathologies worldwide. Therefore, great biomedical research efforts have been driven toward discovering new strategies to promote the resolution of inflammation with fewer side-effects and more specificity than the available anti-inflammatory treatments. In this line, the use of endogenous specialized pro-resolving mediators (SPMs) has gained a prominent interest. Among the different SPMs described, lipoxins stand out as one of the most studied and their deficiency has been widely associated with a wide range of pathologies. In this review, we examined the current knowledge on the therapeutic potential of lipoxins to treat diseases characterized by a severe inflammatory background affecting main physiological systems, paying special attention to the signaling pathways involved. Altogether, we provide an updated overview of the evidence suggesting that increasing endogenously generated lipoxins may emerge as a new therapeutic approach to prevent and treat many of the most prevalent diseases underpinned by an increased inflammatory response.
Case Report: VEXAS Syndrome: From Mild Symptoms to Life-Threatening Macrophage Activation Syndrome
Authors: Staels Frederik , Betrains Albrecht , Woei-A-Jin F. J. Sherida H. , Boeckx Nancy , Beckers Marielle , Bervoets An , Willemsen Mathijs , Neerinckx Barbara , Humblet-Baron Stephanie , Blockmans Daniel Engelbert , Vanderschueren Steven , Schrijvers Rik
Published: April 2021

Recently, a novel disorder coined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was identified in patients with adult-onset inflammatory syndromes, often accompanied by myelodysplastic syndrome1. All patients had myeloid lineage-restricted somatic mutations in UBA1 affecting the Met41 residue of the protein and resulting in decreased cellular ubiquitylation activity and hyperinflammation. We here describe the clinical disease course of two VEXAS syndrome patients with somatic UBA1 mutations of which one with a mild phenotype characterized by recurrent rash and symmetric polyarthritis, and another who was initially diagnosed with idiopathic multicentric Castleman disease and developed macrophage activation syndrome as a complication of the VEXAS syndrome. The latter patients was treated with anti-IL6 therapy (siltuximab) leading to a resolution of systemic symptoms and reduction of transfusion requirements.
Tracking Marine Litter With a Global Ocean Model: Where Does It Go? Where Does It Come From?
Authors: Chassignet Eric P. , Xu Xiaobiao , Zavala-Romero Olmo
Published: April 2021

Plastic is the most abundant type of marine litter and it is found in all of the world’s oceans and seas, even in remote areas far from human activities. It is a major concern because plastics remain in the oceans for a long time. To address questions that are of great interest to the international community as it seeks to attend to the major sources of marine plastics in the ocean, we use particle tracking simulations to simulate the motions of mismanaged plastic waste and provide a quantitative global estimate of (1) where does the marine litter released into the ocean by a given country go and (2) where does the marine litter found on the coastline of a given country come from. The overall distribution of the modeled marine litter is in good agreement with the limited observations that we have at our disposal and our results illustrate how countries that are far apart are connected via a complex web of ocean pathways (see interactive websitehttps://marinelitter.coaps.fsu.edu). The tables summarizing the statistics for all world countries are accessible from the supplemental information in .pdf or .csv formats.
Explainable Machine Learning to Predict Successful Weaning Among Patients Requiring Prolonged Mechanical Ventilation: A Retrospective Cohort Study in Central Taiwan
Authors: Lin Ming-Yen , Li Chi-Chun , Lin Pin-Hsiu , Wang Jiun-Long , Chan Ming-Cheng , Wu Chieh-Liang , Chao Wen-Cheng
Published: April 2021

Objective: The number of patients requiring prolonged mechanical ventilation (PMV) is increasing worldwide, but the weaning outcome prediction model in these patients is still lacking. We hence aimed to develop an explainable machine learning (ML) model to predict successful weaning in patients requiring PMV using a real-world dataset.

Methods: This retrospective study used the electronic medical records of patients admitted to a 12-bed respiratory care center in central Taiwan between 2013 and 2018. We used three ML models, namely, extreme gradient boosting (XGBoost), random forest (RF), and logistic regression (LR), to establish the prediction model. We further illustrated the feature importance categorized by clinical domains and provided visualized interpretation by using SHapley Additive exPlanations (SHAP) as well as local interpretable model-agnostic explanations (LIME).

Results: The dataset contained data of 963 patients requiring PMV, and 56.0% (539/963) of them were successfully weaned from mechanical ventilation. The XGBoost model (area under the curve [AUC]: 0.908; 95% confidence interval [CI] 0.864–0.943) and RF model (AUC: 0.888; 95% CI 0.844–0.934) outperformed the LR model (AUC: 0.762; 95% CI 0.687–0.830) in predicting successful weaning in patients requiring PMV. To give the physician an intuitive understanding of the model, we stratified the feature importance by clinical domains. The cumulative feature importance in the ventilation domain, fluid domain, physiology domain, and laboratory data domain was 0.310, 0.201, 0.265, and 0.182, respectively. We further used the SHAP plot and partial dependence plot to illustrate associations between features and the weaning outcome at the feature level. Moreover, we used LIME plots to illustrate the prediction model at the individual level. Additionally, we addressed the weekly performance of the three ML models and found that the accuracy of XGBoost/RF was ~0.7 between weeks 4 and week 7 and slightly declined to 0.6 on weeks 8 and 9.

Conclusion: We used an ML approach, mainly XGBoost, SHAP plot, and LIME plot to establish an explainable weaning prediction ML model in patients requiring PMV. We believe these approaches should largely mitigate the concern of the black-box issue of artificial intelligence, and future studies are warranted for the landing of the proposed model.
Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model
Authors: Kumar Manoj , Rao Madhvi , Mathur Tarun , Barman Tarani Kanta , Joshi Vattan , Chaira Tridib , Singhal Smita , Pandya Manisha , Al Khodor Souhaila , Upadhyay Dilip J. , Masuda Nobuhisa
Published: April 2021

Pseudomonas aeruginosaforms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected withP. aeruginosaand improved their lung function. The present study was conducted to evaluate the effect of azithromycin onP. aeruginosabiofilm. We show that azithromycin exhibited a potent activity againstP. aeruginosabiofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restrictedP. aeruginosabiofilm formation by inhibiting the expression ofpelgenes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronicP. aeruginosalung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance ofP. aeruginosabiofilms compared to that in the placebo control. We conclude that azithromycin attenuatesP. aeruginosabiofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.
Accessory Chromosome-Acquired Secondary Metabolism in Plant Pathogenic Fungi: The Evolution of Biotrophs Into Host-Specific Pathogens
Authors: Witte Thomas E. , Villeneuve Nicolas , Boddy Christopher N. , Overy David P.
Published: April 2021

Accessory chromosomes are strain- or pathotype-specific chromosomes that exist in addition to the core chromosomes of a species and are generally not considered essential to the survival of the organism. Among pathogenic fungal species, accessory chromosomes harbor pathogenicity or virulence factor genes, several of which are known to encode for secondary metabolites that are involved in plant tissue invasion. Accessory chromosomes are of particular interest due to their capacity for horizontal transfer between strains and their dynamic “crosstalk” with core chromosomes. This review focuses exclusively on secondary metabolism (including mycotoxin biosynthesis) associated with accessory chromosomes in filamentous fungi and the role accessory chromosomes play in the evolution of secondary metabolite gene clusters. Untargeted metabolomics profiling in conjunction with genome sequencing provides an effective means of linking secondary metabolite products with their respective biosynthetic gene clusters that reside on accessory chromosomes. While the majority of literature describing accessory chromosome-associated toxin biosynthesis comes from studies ofAlternariapathotypes, the recent discovery of accessory chromosome-associated biosynthetic genes inFusariumspecies offer fresh insights into the evolution of biosynthetic enzymes such as non-ribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs) and regulatory mechanisms governing their expression.
Disruption of the MreB Elongasome Is Overcome by Mutations in the Tricarboxylic Acid Cycle
Authors: Barton Brody , Grinnell Addison , Morgenstein Randy M.
Published: April 2021

The bacterial actin homolog, MreB, is highly conserved among rod-shaped bacteria and essential for growth under normal growth conditions. MreB directs the localization of cell wall synthesis and loss of MreB results in round cells and death. Using the MreB depolymerizing drug, A22, we show that changes to central metabolism through deletion of malate dehydrogenase from the tricarboxylic acid (TCA) cycle results in cells with an increased tolerance to A22. We hypothesize that deletion of malate dehydrogenase leads to the upregulation of gluconeogenesis resulting in an increase in cell wall precursors. Consistent with this idea, metabolite analysis revealed that malate dehydrogenase (mdh) deletion cells possess elevated levels of several glycolysis/gluconeogenesis compounds and the cell wall precursor, uridine diphosphate N-acetylglucosamine (UDP-NAG). In agreement with these results, the increased A22 resistance phenotype can be recapitulated through the addition of glucose to the media. Finally, we show that this increase in antibiotic tolerance is not specific to A22 but also applies to the cell wall-targeting antibiotic, mecillinam.
The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors
Authors: Blair Tiffany C. , Alice Alejandro F. , Zebertavage Lauren , Crittenden Marka R. , Gough Michael J.
Published: April 2021

Analysis of tumor infiltration using conventional methods reveals a snapshot view of lymphocyte interactions with the tumor environment. However, lymphocytes have the unique capacity for continued recirculation, exploring varied tissues for the presence of cognate antigens according to inflammatory triggers and chemokine gradients. We discuss the role of the inflammatory and cellular makeup of the tumor environment, as well as antigen expressed by cancer cells or cross-presented by stromal antigen presenting cells, on recirculation kinetics of T cells. We aim to discuss how current cancer therapies may manipulate lymphocyte recirculation versus retention to impact lymphocyte exclusion in the tumor.
Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model
Authors: Goliwas Kayla F. , Ashraf Hannah M. , Wood Anthony M. , Wang Yong , Hough Kenneth P. , Bodduluri Sandeep , Athar Mohammad , Berry Joel L. , Ponnazhagan Selvarangan , Thannickal Victor J. , Deshane Jessy S.
Published: April 2021

Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditionalin vitrostudies fail to replicate the complexity of these interactions. Herein, we developed three-dimensional (3D) lung tumor models that mimic the human TME and demonstrate tumor-stromal crosstalk mediated by extracellular vesicles (EVs). EVs released by tumor cells, independent of p53 status, and fibroblasts within the TME mediate immunomodulatory effects; specifically, monocyte/macrophage polarization to a tumor-promoting M2 phenotype within this 3D-TME. Additionally, immune checkpoint inhibition in a 3D model that included T cells showed an inhibition of tumor growth and reduced hypoxia within the TME. Thus, perfused 3D tumor models incorporating diverse cell types provide novel insights into EV-mediated tumor-immune interactions and immune-modulation for existing and emerging cancer therapies.
Therapeutic Effect of Epidermal Growth Factor Combined With Nano Silver Dressing on Diabetic Foot Patients
Authors: Zhang Kaihua , Li Yiran , He Jiarui , Xu Jiasheng , Wan Yanhua , Wan Shasha , Wang Riwei , Zeng Qingfu
Published: April 2021

Objective: To investigate the clinical efficacy of epidermal growth factor combined with nano silver dressing in the treatment of diabetic foot wounds.

Methods: A total of 160 patients with diabetic foot ulcers admitted to the Second Affiliated Hospital of Nanchang University from 2015-06 to 2018-06 were selected to participate in the experiment. A randomized table method was used to randomly divide 160 patients into 4 groups: 40 in the epidermal growth factor group, 40 in the nano-silver dressing group, 40 in the combined group, and 40 in the saline control group (normal saline). The healing stage of the wound surface and the growth degree of granulation tissue were graded. Each group was given a dressing change every other day, and the time required for wound repairing to each healing stage was observed. After 2 and 4 weeks of treatment, the wound exudate was collected for bacterial culture.

Results: There was no significant difference in the time between the four groups of patients reaching the effective phase of treatment (level 1). Compared with the control group, the epidermal growth factor group and the combined group achieved a shorter time for wound repairing to healing stages 2 and 3, and the difference was significant (p < 0.05). The combined group had a shorter wound repairing time than the epidermal growth factor group (p < 0.05). Compared with the control group, the positive rate of bacteria in the combined group and the silver nanoparticles group was significantly lower after 2 and 4 weeks of treatment.

Conclusion: There is no significant difference in wound healing between the four groups during the clinically effective period. After this period, the combined use of recombinant epidermis Growth factors and nano-silver dressings have a significant effect on promoting wound healing and can effectively prevent infection.
Huanglong Antitussive Granule Relieves Acute Asthma Through Regulating Pulmonary Lipid Homeostasis
Authors: Yan Hua , Qian Guiying , Yang Rui , Luo Zichen , Wang Xianzheng , Xie Tong , Zhao Xia , Shan Jinjun
Published: April 2021

Background: Asthma is a respiratory disease with chronic airway inflammatory, and individuals with asthma exacerbations is one of the most frequent causes of hospitalization. Huanglong antitussive granule (HL Granule), a Chinese proprietary herbal medicine, has been proved to be effective in the clinical treatment of pulmonary disease. This study is devoted to the pharmacodynamics of HL Granule in acute asthma and the possible mechanism from the perspective of lipidomics.

Methods: Mice were divided into four groups, control group, acute asthma model group, HL Granule treatment and montelukast sodium treatment group. Acute asthma was induced by ovalbumin (OVA). Histopathology, pulmonary function and enzyme linked immunosorbent assay (ELISA) were used to validated model and effect of HL Granule. Lipids were detected by ultra-high-performance liquid chromatography coupled to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) and identified by MS-DAIL and built-in Lipidblast database. Differentially expressed lipids recalled in HL Granule treatment group were extracted for heatmap, enrichment analysis and correlation analysis.

Results: HL Granule was effective in decreasing airway hyperresponsiveness (AHR), airway inflammatory and the levels of IL-4 and IL-5. A total of 304 and 167 lipids were identified in positive and negative ion mode, respectively. Among these, 104 and 73 lipids were reserved in HL Granule group (FDR < 0.05), including acylcarnitine (ACar), fatty acid (FA), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylserine (PS), diglyceride (DG), triglyceride (TG), sphingomyelin (SM) and ceramide (Cer). Furthermore, 118 and 273 correlations among 47 and 96 lipids in the positive and negative were observed, with ether-linked phosphatidylethanolamine (PEe) and phosphatidylcholine (PCe) (FDR < 0.001, Spearman correlation coefficient r2 > 0.75).

Conclusion: HL Granule might improve pulmonary lipid homeostasis and could be used as an alternative or supplementary therapy in clinical for the treatment of asthma.
Metabolic Homeostasis in Life as We Know It: Its Origin and Thermodynamic Basis
Authors: Wilson David F. , Matschinsky Franz M.
Published: April 2021

Living organisms require continuous input of energy for their existence. As a result, life as we know it is based on metabolic processes that extract energy from the environment and make it available to support life (energy metabolism). This metabolism is based on, and regulated by, the underlying thermodynamics. This is important because thermodynamic parameters are stable whereas kinetic parameters are highly variable. Thermodynamic control of metabolism is exerted through near equilibrium reactions that determine. (1) the concentrations of metabolic substrates for enzymes that catalyze irreversible steps and (2) the concentrations of small molecules (AMP, ADP, etc.) that regulate the activity of irreversible reactions in metabolic pathways. The result is a robust homeostatic set point (−ΔGATP) with long term (virtually unlimited) stability. The rest of metabolism and its regulation is constrained to maintain this set point. Thermodynamic control is illustrated using the ATP producing part of glycolysis, glyceraldehyde-3-phosphate oxidation to pyruvate. Flux through the irreversible reaction, pyruvate kinase (PK), is primarily determined by the rate of ATP consumption. Change in the rate of ATP consumption causes mismatch between use and production of ATP. The resulting change in [ATP]/[ADP][Pi], through near equilibrium of the reactions preceding PK, alters the concentrations of ADP and phosphoenolpyruvate (PEP), the substrates for PK. The changes in ADP and PEP alter flux through PK appropriately for restoring equality of ATP production and consumption. These reactions appeared in the very earliest lifeforms and are hypothesized to have established the set point for energy metabolism. As evolution included more metabolic functions, additional layers of control were needed to integrate new functions into existing metabolism without changing the homeostatic set point. Addition of gluconeogenesis, for example, resulted in added regulation to PK activity to prevent futile cycling; PK needs to be turned off during gluconeogenesis because flux through the enzyme would waste energy (ATP), subtracting from net glucose synthesis and decreasing overall efficiency.