bluuebunny/crossref_metadata_2025 huggingface dataset:
Radical Neo-Paganism: The Transmission of Discontinuous Identity from Plutarch to Montaigne to Shakespeare’s Antony and Cleopatra
Authors: Vitkus Daniel
Published: May 2023

The chapter traces the transmission of a fundamental philosophical concept, what Jonathan Dollimore has called “discontinuous identity.”  This concept was defined by ancient philosophers and is found in Plutarch’s writings. Later it became a part of Montaigne’s early modern description of selfhood in his “Apology for Raymond Sebond.” It then appears in Shakespeare’s Antony and Cleopatra as a form of theatrical character. Through the adaptive strategies of Montaigne and Shakespeare’s Renaissance humanism, a modern definition of subjectivity and consciousness emerges. Shakespeare’s dramatization of discontinuous identity and neo-pagan materialism in Antony and Cleopatra is deployed, the chapter argues, to question certain aspects of conventional Christian teaching that promote monotheism and autocratic authority. Instead, Shakespeare’s tragedy points the way toward a modern materialism that rejects essence, celebrates flux, and declares all matter sacred.
Falstaff’s Party
Authors: Gray Patrick
Published: May 2023

In this chapter, Gray asks what biases we ourselves bring to bear when we attempt to make sense of Shakespeare and Montaigne. In the interests of securing these authors as allies for secularism, individualism and antinomianism, many modern critics have mistaken their doubts for their beliefs, reading them against the grain of their thought’s development over time. In keeping with multiple passages in the Essays in which Montaigne sets out his opposition to the Protestant Reformation, recent work by George Hoffmann and Philippe Desan has shown that Montaigne was in practice much more committed to the truth of Catholic dogma and its political defence than many Montaignistes both past and present have made him out to be. A compelling array of new scholarship, meanwhile, associated with the post-9/11 ‘religious turn’ in Shakespeare studies has demonstrated Shakespeare’s substantive, sympathetic engagement with Christianity and rendered untenable a former critical consensus that Shakespeare is indifferent to religion. By reconnecting Shakespeare to the vernacular literature of the late Middle Ages, including biblical drama, morality plays and medieval romance, as well as the Bible itself, this research calls into question the claim sometimes associated with Burckhardt that Shakespeare represents a sharp departure from English culture before the Reformation: a new articulation of individualism, a new form of more autonomous selfhood, or, in Harold Bloom’s grandiose phrase, ‘the invention of the human’. For Gray, as well as these other critics, Shakespeare is at least as closely tied to the Middle Ages as he is to modernity.
Afterword
Authors: Maus Katharine Eisaman
Published: May 2023

The chapter discusses the contributions the volume makes from a Shakespearean's perspective, emphasizing the idea of imaginary conversations. It frames its discussion by reference to Van Loon's Lives, a set of imaginary dinner conversations with the mighty dead. Many of the chapters in Shakespeare and Montaigne in effect imagine such a conversation, and the Afterword notes a variety of ways the Venn diagram intersection of Shakespeare and Montaigne seems enriched by acknowledgement of the differences in their genres and their social situations.
Introduction
Authors: Altuntaş-Çakır Ravza
Published: May 2023

The introduction examines the debate on the rise of democracy in the Muslim world with reference to Vali Nasr. By rethinking the hitherto acclaimed Turkish model, it criticises pragmatic Islamic approaches to democracy and instead offers a normative and interpretative approach. A conceptual difference is made in the introduction between Muslim democracy and Islamic democracy. A rationale is provided for the construction of a Muslim democracy framework inspired by a cross-fertilisation of Muslim and Western multiculturalist political thought.
Heidegger and the Stiftung der Wahrheit
Authors: Rosenthal Adam R.
Published: May 2023

Chapter Five looks at two of Heidegger’s most important writings on poetry, or Dichtung: ‘The Origin of the Work of Art’ and ‘On the Essence of Language.’ It demonstrates that, in each case, Heidegger understands the essence of poetry to consist in giving. For him, it is no longer either the poetic subject, the divine, or Nature, which gives, but the work itself, which gives space for the gift to appear as such. In this way, the chapter argues, Heidegger reverses the traditional association between poetry and giving, while maintaining that they possess an essential relation.
Poetry Lost and Found in Howe, Goldsmith, and Philip
Authors: Rosenthal Adam R.
Published: May 2023

This chapter turns to twentieth and twenty-first century poetics. It argues that the same problems that haunted earlier explorations of the place of poetry can now be found, in these later periods, through the figure of ‘the given.’ Looking at constrain poetics in Christian Bök, found poetry in Susan Howe, conceptual poetry in Kenneth Goldsmith, and issues of linguistic inheritance and colonialism in M. NourbeSe Philip, this chapter demonstrates how the problem of ‘the given’ troubles contemporary authors. No longer simply a question of divine inspiration, or the role of the poet as giver, the gift enters these poets’ works as a matter of inheritance that can neither simply be embraced, nor dismissed, but that must be worked through.
Conclusion: The Birth of Lyric in the Homeric Hymn to Hermes
Authors: Rosenthal Adam R.
Published: May 2023

The Conclusion examines the myth of lyric’s origin in the Homeric Hymn to Hermes. It shows how the problems that later come to trouble Romantic and post-Romantic poets, in the relationship between poetic gift and poetic commodity, can already be found in seed in the Hymn. The relationship between poem and gift, it concludes, is one therefore that is constitutive for poetry.
Potential Mechanism of CDC42 Promoting HCC Metastasis
Authors: Tang Miaoling , Feng Rongni , Li Jun
Published: May 2023

Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing morbidity and mortality worldwide. The migration and motility of HCC tumor cells are enhanced by the formation of invadopodia, which comprise membrane protrusions at the leading edge. Previous studies have showed that cell division cycle 42 (CDC42) plays an essential role in remodeling the cytoskeleton, which is associated with invadopodia formation and thus mediates cellular movement. Therefore, aberrant expression of CDC42 is hypothesized to promote tumor cell migration. In this review, we discuss the important role of CDC42 activation induced by guanine nucleotide-exchange factors (GEFs), which function as upstream regulators to activate CDC42, thereby mediating HCC invasion and metastasis by facilitating invadopodia formation. Furthermore, inhibitors targeting the CDC42-GEF interaction might be developed as an intervention against HCC metastasis.
Novel Drug Development for Treatment of COVID-19 by In Silico Analysis: Identification of SARS-Cov-2 Inhibiting Streptomyces Compounds
Authors: Kumar Jayant , Gholap Prachiti , Pillai Thulasi G
Published: May 2023

In accordance with the present epidemiological paradigm, viral mutations of the virus are on the rise, and their natural effects are being selected for at a higher rate than normal. According to the World Health Organization (WHO), the global COVID-19 pandemic induced by the Delta and Omicron strain of the SARS-CoV-2 virus could propagate and disseminate more rapidly than other viruses thanks to its many mutations, and these also caused some very significant health problems. The established medications would eventually start to lose their efficacy since the variation mutated more quickly than the original stain. As protein spikes are the point of origin or epitome for the mutations to take place, it would be most effective to target the remaining vital enzymes by binding the proteins with the largest pocket sizes. The objective of the current work is to employ in-silico analysis to discover the streptomyces chemicals that suppress the SARS-CoV-2 virus as well as its mutated strains thus promoting a healthy body. Based on the drug likeness property of compounds when subjected to molecular docking, a total of 14 compounds were identified and selected from the PUBCHEM database that showed highest binding energy with the targeted Receptor Binding Domain. The compounds namely - Streptomyces tanashiensis; Thaxtomin A; Bafilomycin A1 from Streptomyces griseus and few others as mentioned further on more research would support and confirm the utilizing of these to create new medications to treat the novel SARS-CoV-2 infectious strains.
Understanding Chromosome Replication and Segregation Unit of Mycobacterium and Its Comparative Analysis with Model Organisms: From Drug Targets to Drug Identification
Authors: Jain Preeti
Published: May 2023

Bacterium maintains its pathogenicity in the host by continuing replication and adopting temporal and spatial coordination of cell division steps such as cell wall synthesis, DNA replication, chromosome segregation, Z ring assembly, septum formation and finally cytokinesis. This multistep process requires spatiotemporal assembly of macromolecular complexes and is probably regulated by redundant and multifunctional activities of cell replication and division proteins. Two macromolecular assemblies of peptidoglycan biosynthesis, known as elongasome and divisome are known to drive the division of mother cell into two daughter cells and are characterized by the presence of signature protein complexes. Though the exact composition of macromolecular complexes is yet to be defined in Mycobacterium, the presence of some conserved proteins demonstrates the preservation of elementary units. Along with elongasome and divisome complexes, chromosome replication and segregation proteins are very important to understand as these proteins are very essential for bacilli survival, sustenance, and pathogenesis. In this review, along with presenting the differential features of Mycobacterium cell division process, we are comparing chromosome replication and segregation proteins of Mycobacterium with other bacterial species as we aim to identify structural and functional differences between these proteins in different species. In this review, we have also listed the potential drugs that can be tested to target Mycobacterium chromosome replication and segregation proteins. We expect that based on these differences identified, researchers would be able to direct their research in the characterization of Mycobacterium specific drug.
UNDERSTANDING CARDIOLIPIN’S FUNCTION IN NEURODEGENERATIVE DISEASES
Authors: Ferguson David
Published: May 2023

Cardiolipin (CL), also known as diphosphatidyglycerol, is localized and synthesized exclusively in the mitochondria. This glycerophospholipid was first characterized by Mary Pangborn and McFarlane in 1941. Presently, CL is considered a potential therapeutic target for several neurodegenerative diseases (NDDs). Recent developments in the field of lipidomics indicate that the ratio of monolysocardiolipin-to-native CL is a valuable biomarker for diagnosing NDDs such as Barth Syndrome (BTHS). In this review, the role of lipidomics in understanding the function of CL in NDDs is reviewed.
OPTIMALISASI TEKNOLOGI INFORMASI DAN KOMUNIKASI DI SMK MUHAMMADIYAH HARUMANSARI
Authors: Dian Nursantika  , Dwi Astuti Aprijani  , Dian Nurdiana  , Andri Suryadi
Published: May 2023

Kegiatan pengabdian kepada masyarakat (PkM) Program Studi Sistem Informasi Universitas Terbuka bertujuan untuk membantu mengatasi masalah yang ditemui di masyarakat, dengan menerapkan ilmu bidang teknologi informasi dan komunikasi (TIK).  Kebutuhan untuk memanfaatkan TIK dalam menyelesaikan masalah administrasi dan pembelajaran sangat dibutuhkan, terutama di sekolah-sekolah, termasuk Sekolah Menengah Kejuruan (SMK) Muhammadiyah Harumansari yang berada di wilayah Garut. Untuk meningkatkan keterampilan tenaga pendidik dan guru dalam memanfaatkan TIK, SMK Muhammadiyah Harumansari bekerja sama dengan Program Studi Sistem Informasi Universitas Terbuka yang diwujudkan dalam kegiatan PkM. Tujuan PkM adalah untuk: (1) meningkatkan kemampuan tenaga pendidik dan guru dalam memanfaatkan Microsoft Office; (2) memberikan pelatihan membuat daftar isi secara otomatis dan membuat mail merge sederhana menggunakan Ms Word; (3) memberikan pengenalan dasar Ms Excel, yang terdiri dari operator, fungsi perhitungan, fungsi logika, dan fungsi lookup; (4) membuat slide presentasi menggunakan Ms PowerPoint. Strategi yang dilakukan adalah langsung mempraktikkan menggunakan Microsoft Office di komputer dan memberikan contoh fungsi-fungsi atau fitur-fitur yang digunakan terkait masing-masing materi. Meskipun pelatihan dilakukan secara daring, namun tidak mengurangi kualitas penyampaian pembelajaran, karena peserta dapat langsung mencoba dan dapat menunjukkan hasil kerjanya kepada tim PkM melalui share screen dan tugas individu. Dampak dari kegiatan PkM ini adalah tenaga pendidik dan guru di SMK Muhammadiyah Harumansari mendapat pengetahuan praktis pemanfaatan Microsoft Office, yang dapat digunakan untuk meningkatkan kinerjanya serta dapat digunakan pada kegiatan sehari-hari dalam menunjang pekerjaannya sebagai tenaga pendidik dan guru.
PENDAMPINGAN PEMBUATAN HERBARIUM KERING PADA GURU SD DI KECAMATAN MINASATE’NE KABUPATEN PANGKEP
Authors: Makkatenni  , Jalil  , Husnaeni  , Rustam  , Avelyn Pingkan Komuna
Published: May 2023

Kecamatan Minasate’ne  merupakan salah satu kecamatan  yang ada di wilayah  Kabupaten Pangkajene dan Kepulauan (Pangkep) yang berjarak sekitar 47 km dari Kantor UPBJJ-UT Makassar kearah utara atau sekitar 1 km dari Pangkajene ibu kota Kabupaten Pangkep. Pemberdayaan masyarakat tentang pendampingan pembuatan herbarium kering pada guru SD di Kecamatan Minasate’ne Kabupaten Pangkep yang dilaksanakan dengan tujuan  mendapatkan pengetahuan dan keterampilan tentang:(1) pengertian herbarium (2) cara pembuatan herbarium kering  dan (3) praktik pembuatan herbarium kering. Kegiatan pengabdian masyarakat dilaksanakan selama satu tahun. Metode yang digunakan dalam kegiatan pengabdian ini adalah ceramah, tanya jawab dan demonstrasi tentang cara pembuatan herbarium kering.  Kegiatan  monitoring dan  evaluasi dilaksanakan untuk melihat sejauh mana keberhasilan pengabdian masyarakat yang telah dialakukan khususnya pembuatan herbarium kering. Keterlaksanaan pengabdian kepada masyarakat didasarkan atas terpenuhinya indikator-indikator proses pengabdian masyarakat dan produk yang dihasilkan. Hasil evaluasi menunjukkan bahwa peserta sangat antusias dalam mengikuti pelatihan serta aktif dalam mengajukan pertanyaan pada saat pemaparan materi oleh nara sumber. Dapat disimpulkan bahwa pengabdian masyarakat telah diimplementasikan sesuai dengan rencana dimulai dari pengertian herbarium, cara pembuatan herbarium kering dan praktik pembuatan herbarium kering. Hal ini  dapat dilihat dari keberhasilan  peserta  yang telah mengikuti kegiatan abdimas telah berhasil  menerapkan  pengetahuan dan pengalaman kepada teman sejawat, bahkan kepada murid-muridnya di kelas.Herbarium kering yang telah dibuat disimpan dalam bingkai dan album yang siap digunakan sebagai alat perga dalam mengajarkan IPA di SD.
REVITALISASI BUMDESA DALAM UPAYA PENGUATAN KELEMBAGAAN, PENGELOLAAN KEUANGAN DAN MANAJERIAL DI KABUPATEN LEBONG PROVINSI BENGKULU
Authors: Dwi Kristanti  , Abdul Aziz Zulhakim  , Mimi Kurnia Nengsih
Published: May 2023

Kelegalitasan menjadi permasalahan yang dihadapi oleh pengelola BUMDesa, tidak terkecuali BUMDesa-BUMDesa yang berada di Kabupaten Lebong. Dari 93 BUMDesa yang ada, belum ada BUMDesa yang berbadan hukum jika dibandingkan dengan BUMDesa yang ada di berbagai Kabupaten di Provinsi Bengkulu. BUMDesa Sumber Urip Mangkurajo yang berada di Desa Mangkurajo dan BUMDesa Amanah Bersama merupakan BUMDesa yang di pandang cukup potensial di Kabupaten Lebong dilihat dari BUMDesa tersebut memiliki potensi yang cukup menjanjikan dan mendapat dukungan penuh dari Pemerintah setempat, namun belum memiliki badan hukum. Tahapan pelaksanaan yang dilakukan melalui 4 tahap yaitu pengidentifikasian masalah, pelatihan kelembagaan, keuangan dan manajerial, pendampingan pembuatan program kerja (Proker), serta pendampingan Pendaftaran Badan Hukum. Output dari kegiatan Abdimas ini yaitu Program Kerja dan Sertifikat Berbadan Hukum dari Kemenkumham. Pada kegiatan ini Tim melakukan pelatihan dan pendampingan di dua BUMDesa yang yang dinilai lebih baik  dari diseleksi Tim dari 93 BUMDesa yang ada di Kabupaten Lebong. Namun pada tahap pendampingan pembuatan Proker BUMDesa Amanah Bersama memutuskan untuk belum melanjutkan ke Badan Hukum dikarenakan keterbatasan Sumber Daya Manusia. Pada tanggal 13 Juni 2022 pengajuan Badan Hukum BUMDesa Sumber Urip Mangkurajo disetujui oleh Kemenkumham yang disahkan dengan sertifikat nomor AHU-0426.AH.01.33 TAHUN 2022.
KEWIRAUSAHAAN BERBASIS DIGITAL SEBAGAI UPAYA PEMBERDAYAAN DAN PENINGKATAN PRODUKTIVITAS UMKM DI DESA LULUT
Authors: Gunawan Wiradharma  , Meirani Harsasi  , Melisa Arisanty
Published: May 2023

Beberapa masalah yang dihadapi UMKM di Desa Lulut, Kecamatan Klapanunggal, Kabupaten Bogor adalah pemasaran dan keterampilan menggunakan teknologi. UMKM di Desa Lulut memerlukan pengembangan usaha berbasis teknologi agar dapat bersaing dengan usaha-usaha baru yang bersifat online. Tujuan diadakannya kegiatan pengabdian kepada masyarakat ini adalah untuk meningkatkan kompetensi bisnis berbasis digital untuk UMKM sebagai upaya peningkatan kinerja dan produktivitas sehingga berdampak pada peningkatan kualitas produk, kegiatan pemasaran yang efektif dan efisien, serta pembuatan laporan yang tepat pada UMKM di Desa Lulut. Metode yang digunakan dalam penelitian ini adalah observasi, wawancara, dan kuisioner. Materi dalam upaya pengembangan UMKM berbasis digital adalah wirausaha di era digital. Hasil kegiatan ini menunjukkan bahwa setelah dilakukan pelatihan terjadi peningkatan pengetahuan dan persepsi terkait wirausaha di era digital pada UMKM dan masyarakat di Desa Lulut sebesar 11-25%. Perubahan yang paling signifikan terlihat pada pemahaman pelaku UMKM terhadap proses identifikasi peluang usaha di era digital. Hal tersebut tentunya membantu pelaku UMKM untuk membuat perencanaan, pengelolaan, dan pemasaran produknya dengan melihat pada peluang usaha yang ada sesuai tren dan perilaku konsumen saat ini. Dengan demikian, upaya yang dapat dilakukan adalah menumbuhkan jiwa kewirausahaan dan bergerak dari sistem konvensional menjadi sistem usaha berbasis online. Selain itu, hasil kegiatan ini menunjukkan bahwa pelaku usaha sangat menyambut positif kegiatan ini serta memberikan manfaat dan inspirasi dalam menjalankan UMKM-nya secara online.
PEMBENTUKAN PUSAT KREATIF DESA MELALUI PEMBERDAYAAN PEMUDA DALAM MENGEMBANGKAN KETERAMPILAN PEMASARAN DIGITAL PRODUK UMKM DI DESA GEMBONGAN, KECAMATAN GEDEG, KABUPATEN MOJOKERTO
Authors: Tri Dyah Prastiti  , Yunianto Nugroho  , Dwi Sambada  , Suparti  , Barokah Widuroyekti
Published: May 2023

Permasalahan seputar sosial ekonomi masih banyak ditemui di masyarakat, terutama di daerah pedesaan. Permasalahan tersebut, misalnya pengangguran, kemiskinan bahkan tindak kejahatan. Di sisi lain,  selalu ada potensi yang bisa dikembangkan dari setiap desa baik berupa sumber daya manusia maupun sumber daya alam sebagai solusi dari permasalahan sosial dan ekonomi yang ada. Sayangnya sering kali masyarakat di desa belum mampu mengembangkan potensi-potensi tersebut karena belum memiliki ilmu, wawasan dan kreatifitas untuk mengelolanya. Kondisi saat ini wawasan tentang  pasar  dan kreatifitas biasanya dimiliki oleh para pemuda terutama golongan milenial. Namun banyak pemuda di  Desa Gembongan tidak mendapatkan kesempatan atau dukungan untuk pengembangan potensinya. Padahal jika mereka diberi pelatihan dan pendampingan manajemen bisnis sosial digital dan wadah untuk berkreasi dan berkolaborasi terutama dengan usaha-usaha mikro, mereka pasti mampu mengembangkan potensi desanya. Sebagai solusi adalah memberikan wadah berupa Pusat Kreatif Desa, yang  akan membuat proses bisnis yang dikembangkan menjadi ebih efektif karena adanya pembagian tugas melalui skema kolaborasi multi pihak. Kelompok pemuda yang dekat dengan perkembangan pasar dan teknologi saat ini bisa fokus berkreasi sebagai pengelola dan  mengembangkan  potensi industri-industri rumahan milik warga desanya yang kebanyakan lemah dalam hal manajemen. Untuk itu Pusat Kreatif Desa yang dikembangkan oleh dosen UT sebagai kegiatan abdimas perlu direalisasikan di Desa Gembongan, Gedeg, Mojokerto, Jawa Timur, mengingat Desa Gembongan memiliki potensi yang bisa dikembangkan dan sumber daya manusia yang bisa diberdayakan sebagai upaya untuk mengurangi permasalahan sosial di desa tersebut. Metode pelaksanaan meliputi 1) identifikasi  masalah masyarakat di Desa Gembongan, riset potensi di Desa Gembongan dan sosialisasi mengenai konsep Pusat Kreatif Desa Gembongan; 2) pembekalan mengenai Bisnis Sosial Digital kepada para pemuda penggerak Pusat Kreatif Desa; 3) pendampingan kegiatan dan 4) evaluasi kegiatan. Hasil dan dampak terhadap pemuda desa Gembongan dari kegiatan ini yaitu para pemuda penggerak telah memiliki wadah berkreasi dan mampu memiliki keahlian yang diperlukan untuk membantu mengembangkan industri-industri rumahan yang ada di Desa Gembongan. Lebih lanjut diharapkan para pemuda di desa Gembongan bisa terus didukung untuk mampu mengembangkan perusahaan professional hasil dari mereka berkolaborasi dengan berbagai pihak.
Net cleaning impacts Atlantic salmon gill health through microbiome dysbiosis
Authors: Elsheshtawy Ahmed , Clokie Benjamin Gregory James , Albalat Amaya , Nylund Are , Isaksen Trond Einar , Napsøy Indrebø Elisabeth , Andersen Linda , Moore Lindsey Jane , MacKenzie Simon
Published: May 2023

Introduction

Net biofouling has a significant impact for the global salmon industry in the seawater grow-out stage in terms of its management. Current mitigation strategies occur primarily through the regular removal of biofouling using in situ cleaning. While in situ net cleaning is effective there is uncertainty as to whether the equipment or dispersed material has an impact upon the fish in the cages. Through direct contact with the environment, the significant surface area of the gill including its microbiome is directly exposed to the acute environmental changes generated by net cleaning. This study aimed to provide a detailed understanding of the impact of in situ net cleaning on Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) gill health.

Methods

Three field trials were conducted on commercial fish farms in western Norway. Fouling organisms on net pens and flushed particles during in situ cleaning were identified and screened for major fish pathogens. Hydrographic profile measurements were performed to measure the impact on water quality. Gill samples were examined for histopathological changes, immune gene expression, and the prevalence of major pathogens. 16S rRNA amplicon sequencing was employed to explore the impact of net cleaning on gill microbiome.

Results and discussion

Data obtained from these trials identified a diversity of fouling species including hydroids, algae, skeleton shrimps, and filter feeders on net pens, a direct impact on measured water quality indicators, a moderate change in gill inflammatory and antigen presentation activity at the level of mRNA, and a large significant change in gill microbiome. Observed changes in gill microbial community involved a decrease in bacterial richness coupled to an increase in identified bacterial genera related to negative health consequences. Parallel analyses for pathogens load in biofouling organisms and flushed particles highlighted the presence of several fish bacteria and parasites. However, minor changes were detected in salmon gill pathogen diversity and loading. Our results suggest that biofouling organisms may act as transient reservoirs for some fish pathogens but not viruses and that gill microbial dysbiosis could be related to the host stress response during and post net cleaning.
Chitosan and chito-oligosaccharide: a versatile biopolymer with endless grafting possibilities for multifarious applications
Authors: Mohite Popat , Shah Sunny R. , Singh Sudarshan , Rajput Tanavirsing , Munde Shubham , Ade Nitin , Prajapati Bhupendra G. , Paliwal Himanshu , Mori Dhaval D. , Dudhrejiya Ashvin V.
Published: May 2023

Chito-oligosaccharides (COS), derived from chitosan (CH), are attracting increasing attention as drug delivery carriers due to their biocompatibility, biodegradability, and mucoadhesive properties. Grafting, the process of chemically modifying CH/COS by adding side chains, has been used to improve their drug delivery performance by enhancing their stability, targeted delivery, and controlled release. In this review, we aim to provide an in-depth study on the recent advances in the grafting of CH/COS for multifarious applications. Moreover, the various strategies and techniques used for grafting, including chemical modification, enzymatic modification, and physical modification, are elaborated. The properties of grafted CH/COS, such as stability, solubility, and biocompatibility, were reported. Additionally, the review detailed the various applications of grafted CH/COS in drug delivery, including the delivery of small drug molecule, proteins, and RNA interference therapeutics. Furthermore, the effectiveness of grafted CH/COS in improving the pharmacokinetics and pharmacodynamics of drugs was included. Finally, the challenges and limitations associated with the use of grafted CH/COS for drug delivery and outline directions for future research are addressed. The insights provided in this review will be valuable for researchers and drug development professionals interested in the application of grafted CH/COS for multifarious applications.
The odyssey to next-generation computers: cognitive computers (κC) inspired by the brain and powered by intelligent mathematics
Authors: Wang Yingxu , Widrow Bernard , Hoare C. A. R. , Pedrycz Witold , Berwick Robert C. , Plataniotis Konstantinos N. , Rudas Imre J. , Lu Jianhua , Kacprzyk Janusz
Published: May 2023

Cognitive computers (κC) are intelligent processors advanced from data and information processing to autonomous knowledge learning and intelligence generation. This work presents a retrospective and prospective review of the odyssey toward κC empowered by transdisciplinary basic research and engineering advances. A wide range of fundamental theories and innovative technologies for κC is explored, and a set of underpinning intelligent mathematics (IM) is created. The architectures of κC for cognitive computing and Autonomous Intelligence Generation (AIG) are designed as a brain-inspired cognitive engine. Applications of κC in autonomous AI (AAI) are demonstrated by pilot projects. This work reveals that AIG will no longer be a privilege restricted only to humans via the odyssey to κC toward training-free and self-inferencing computers.
Shared Genetic Etiology of Primary Dilated Cardiomyopathy and Ischemic Dilated Cardiomyopathy
Authors: Sun Yang , Xiao Lei , Li Ke , Wang Hong , Song Xiuli , Li Zongzhe , Li Chenze , Chen Yanghui , Li Shiyang , Huang Jin , Tan Lun , Hu Dong , Yu Ting , Li Rui , Wang Hong , Jin Li , Shi Leming , Marian Ali J. , Wang Dao Wen
Published: May 2023

Background: Mutations in genes encoding sarcomere and cytoskeletal proteins are major causes of primary dilated cardiomyopathy (DCM). Likewise, ischemic myocardial injury is a major cause of secondary cardiac remodeling, which, in a subset, is severe and resembles DCM. The latter is referred to as ischemic dilated cardiomyopathy (IDCM). We postulated the presence of pathogenic and likely pathogenic variants (PVs and LPVs, respectively) in genes known to cause primary DCM might predispose the heart to severe cardiac dilatation and dysfunction post myocardial ischemic injury, i.e., IDCM.

Methods: We performed whole-exome sequencing in 1,041 patients with primary DCM, 215 patients with IDCM, and 414 healthy controls. Indices of cardiac size and function were similar between those with primary and ischemic DCM. PVs and LPVs, including the truncating variants in 36 genes known to cause primary DCM were identified and compared among the three groups.

Results: Pathogenic variants and LPVs were detected in 266 individuals, comprised of 215/1,041 (20.7%) patients with DCM, 27/215 (12.6%) patients with IDCM, and 24/414 (5.8%) control individuals. PVs and LPVs in the TTN gene were the most common and detected in 130/1,041 (12.5%) of patients with DCM, 15/215 (7.0%) of cases with IDCM, and 10/414 (2.4%) control individuals. Of 135 TTNtv, 118 involved exons that were >90% spliced in. These variants were found in 120/1,041 (11.5%) of DCM patients, 6/215 (2.8%) of IDCM cases, and only in 1/414 (0.2%) of the control population (p < 0.001 among the three groups).

Conclusions: Pathogenic variants and LPVs in genes known to cause primary DCM are enriched in patients with IDCM, suggesting that such variants function as susceptibility alleles for cardiac dilatation and dysfunction in post myocardial ischemic injury. Thus, IDCM shares a partial genetic etiology with the primary DCM.
Deep learning approach for analyzing chest x-rays to predict cardiac events in heart failure
Authors: Kusunose Kenya , Hirata Yukina , Yamaguchi Natsumi , Kosaka Yoshitaka , Tsuji Takumasa , Kotoku Jun’ichi , Sata Masataka
Published: May 2023

Background

A deep learning (DL) model based on a chest x-ray was reported to predict elevated pulmonary artery wedge pressure (PAWP) as heart failure (HF).

Objectives

The aim of this study was to (1) investigate the role of probability of elevated PAWP for the prediction of clinical outcomes in association with other parameters, and (2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF.

Methods

We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP. Readmission following HF and cardiac mortality were the primary endpoints.

Results

Probability of elevated PAWP was associated with diastolic function by echocardiography. During a median follow-up period of 58 months, 57 individuals either died or were readmitted. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge was associated with event free survival, independent of elevated left atrial pressure (LAP) based on echocardiographic guidelines (p < 0.001). In sequential Cox models, a model based on clinical data was improved by elevated LAP (p = 0.005), and increased further by probability of elevated PAWP (p < 0.001). In contrast, the addition of pulmonary congestion interpreted by a doctor did not statistically improve the ability of a model containing clinical variables (compared p = 0.086).

Conclusions

This study showed the potential of using a DL model on a chest x-ray to predict PAWP and its ability to add prognostic information to other conventional clinical prognostic factors in HF. The results may help to enhance the accuracy of prediction models used to evaluate the risk of clinical outcomes in HF, potentially resulting in more informed clinical decision-making and better care for patients.
Case report: Acute pericarditis following hepatic microwave ablation for liver metastasis
Authors: Pavon Anna Giulia , Rubimbura Vladimir , Nowacka Anna , Hocquelet Arnaud , Schwitter Jurg , Rotzinger David C.
Published: May 2023

Hepatic microwave ablation (MWA) is a growing treatment modality in the field of primary and secondary liver cancer. One potential side effect is thermal damage to adjacent structures, including the pericardium if the hepatic lesion is located near the diaphragm. Hemorrhagic cardiac tamponade is known to be a rare but potentially life-threatening complication. Here we present the first case of cardiac complication following MWA treatment in a 55-year-old man who presented with late cardiac tamponade. Adequate and timely management is essential, and clinicians should be fully aware of the need to perform early transthoracic echocardiography to detect signs of pericardial effusion when cardiac involvement is suspected.
Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing
Authors: Pohl Greta Marie , Göz Manuel , Gaertner Anna , Brodehl Andreas , Cimen Tolga , Saguner Ardan M. , Schulze-Bahr Eric , Walhorn Volker , Anselmetti Dario , Milting Hendrik
Published: May 2023

Background

Arrhythmogenic cardiomyopathy can be caused by genetic variants in desmosomal cadherins. Since cardiac desmosomal cadherins are crucial for cell-cell-adhesion, their correct localization at the plasma membrane is essential.

Methods

Nine desmocollin-2 variants at five positions from various public genetic databases (p.D30N, p.V52A/I, p.G77V/D/S, p.V79G, p.I96V/T) and three additional conserved positions (p.C32, p.C57, p.F71) within the prodomain were investigated in vitro using confocal microscopy. Model variants (p.C32A/S, p.V52G/L, p.C57A/S, p.F71Y/A/S, p.V79A/I/L, p.I96l/A) were generated to investigate the impact of specific amino acids.

Results

We revealed that all analyzed positions in the prodomain are critical for the intracellular transport. However, the variants p.D30N, p.V52A/I and p.I96V listed in genetic databases do not disturb the intracellular transport revealing that the loss of these canonical sequences may be compensated.

Conclusion

As disease-related homozygous truncating desmocollin-2 variants lacking the transmembrane domain are not localized at the plasma membrane, we predict that some of the investigated prodomain variants may be relevant in the context of arrhythmogenic cardiomyopathy due to disturbed intracellular transport.
A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis
Authors: Mendes-de-Almeida Daniela P. , Kehdy Fernanda S. G. , Martins-Gonçalves Remy , Bokel Joanna , Grinsztejn Eduarda , Mouta Nunes de Oliveira Patrícia , Maia Maria de Lourdes de Sousa , Hoagland Brenda , Wagner Cardoso Sandra , Grinsztejn Beatriz , Siqueira Marilda M. , Kurtz Pedro , Bozza Patricia T. , Garcia Cristiana C.
Published: May 2023

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.
Adapting a mobile app to support patients with anorexia nervosa following post-acute care: perspectives from eating disorder treatment center stakeholders
Authors: Haas Anneliese , Laboe Agatha A. , McGinnis Claire G. , Firebaugh Marie-Laure , Shah Jillian , Bardone-Cone Anna M. , Pike Kathleen M. , Taylor C. Barr , Wilfley Denise E. , Fitzsimmons-Craft Ellen E.
Published: May 2023

Introduction

Anorexia nervosa (AN) is a harmful, life-threatening illness. Patients with severe AN often receive acute treatment but, upon discharge, experience high relapse rates. Evidence-based, outpatient treatment following acute care is critical to preventing relapse; however, numerous barriers (e.g., location, financial limitations, low availability of providers) preclude individuals from accessing treatment. mHealth technologies may help to address these barriers, but research on such digital approaches for those with AN is limited. Further, such technologies should be developed with all relevant stakeholder input considered from the outset. As such, the present study aimed to garner feedback from eating disorder (ED) treatment center providers on (1) the process of discharging patients to outpatient services, (2) their experiences with technology as a treatment tool, and (3) how future mHealth technologies may be harnessed to offer the most benefit to patients in the post-acute period.

Methods

Participants (N = 11, from 7 ED treatment centers across the United States) were interviewed. To analyze the data for this study, each interview was manually transcribed and analyzed using components of Braun and Clarke's six-phase thematic analysis framework (Braun & Clarke, 2006).

Results

Participants indicated proactively securing outpatient care for their patients, but mentioned several barriers their patients face in accessing evidence-based ED treatment. All participants had some experience using various technologies for treatment (e.g., teletherapy, self-monitoring apps), and mentioned a high level of interest in the development of a new app to be used by patients recently discharged from acute treatment for AN. Participants also offered suggestions of effective and relevant content for a potential app and adjunctive social networking component for post-acute care of AN.

Discussion

Overall, participants expressed positive attitudes toward the integration of an app into the care flow, suggesting the high potential benefit of harnessing technology to support individuals recovering from AN.
Recovering the Effects of Subgrid Heterogeneity in Simulations of Radionuclide Transport Through Fractured Media
Authors: Williams Thomas , Sanglas Jordi , Trinchero Paolo , Gai Guanqun , Painter Scott L. , Selroos Jan-Olof
Published: May 2023

Groundwater flow and contaminant transport through fractured media can be simulated using Discrete Fracture Network (DFN) models which provide a natural description of structural heterogeneity. However, this approach is computationally expensive, with the large number of intersecting fractures necessitated by many real-world applications requiring modeling simplifications to be made for calculations to be tractable. Upscaling methods commonly used for this purpose can result in some loss of local-scale variability in the groundwater flow velocity field, resulting in underestimation of particle travel times, transport resistance and retention in transport calculations. In this paper, a transport downscaling algorithm to recover the transport effects of heterogeneity is tested on a synthetic Brittle Fault Zone model, motivated by the problem of large safety assessment calculations for geological repositories of spent nuclear fuel. We show that the variability in the local-scale velocity field which is lost by upscaling can be recovered by sampling from a library of DFN transport paths, accurately reproducing DFN transport statistic distributions and radionuclide breakthrough curves in an upscaled model.
Snow and meteorological conditions at Villum Research Station, Northeast Greenland: on the adequacy of using atmospheric reanalysis for detailed snow simulations
Authors: Krampe Daniela , Kauker Frank , Dumont Marie , Herber Andreas
Published: May 2023

Reliable and detailed measurements of atmospheric and snow conditions in the Arctic are limited. While modern atmospheric reanalyses could potentially replace the former, the latter can be principally simulated by dedicated snow modelling. However, because the uncertainties of reanalyses and modelling are still exceptionally large at high latitudes, a thorough analysis of the performance of atmospheric reanalyses and the snow model simulations are required. Specifically, we aim to answer the following questions for Villum Research Station (VRS), northeast Greenland: (1) What are the predominant snow and meteorological conditions? (2) What are systematic differences between the modern atmospheric reanalysis ERA5 and in situ measurements? (3) Can the snow model Crocus simulate reliably snow depth and stratigraphy? We systematically compare atmospheric in situ measurements and ERA5 reanalysis (November 2015–August 2018) and evaluate simulated and measured snow depth (October 2014–September 2018). Moreover, modelled and measured vertical profiles of snow density and snow specific surface area (SSA) are analysed for two days where a survey had taken place. We found good agreement between in situ and ERA5 atmospheric variables with correlation coefficients >0.84 except for precipitation, wind speed, and wind direction. ERA5’s resolution is too coarse to resolve the topography in the study area adequately, leading presumably to the detected biases. Crocus can simulate satisfactorily the evolution of snow depth, but simulations of SSA and density profiles, whether driven by ERA5 or in situ measurements are biased compared to measurements. Unexpectedly, measured snow depth agrees better with ERA5 driven simulation than with simulation forced with in situ measurements (explained variance: 0.73 versus 0.23). This is due to differences in snowfall, humidity and air temperature between both forcing datasets. In conclusion, ERA5 has great potential to force snow models but the use of Crocus in the Arctic is affected by limitations such as inappropriate parametrisations for Arctic snowpack evolution, but also by lack of process formulations such as vertical water vapour transport. These limitations strongly affect the accuracy of the vertical profiles of physical snow properties.
Revisiting Acker’s gendered organizational theory: what women overcome to stay in the superintendency
Authors: Clark-Saboda Jennifer L. , Lemke Melinda
Published: May 2023

Despite key improvements to social, political, and economic status, women remain underrepresented in key leadership positions across the United States, including the superintendency. Feminist research underscores that androcentric systems maintain, valorize, and reproduce the experiences and knowledge claims of upper middle-class, heterosexual, white men. Documented in related fields, gender inequity within public school systems is thus in part, the result of bias, discrimination, and highly gendered organizational practices. Part of a larger qualitative descriptive study conducted in spring 2021 of the COVID-19 pandemic, the purpose of this research was to examine normative culture within the New York State (NYS) Boards of Cooperative Educational Services (BOCES) superintendency, and how professional and personal supports affect women superintendents and ultimately their decision “to stay” in their position. The guiding research question for this part of the study asked how and why the NYS BOCES superintendency was gendered? Guided by and building upon Joan Acker’s gendered organizational theory, 32 semi-structured, in-depth interviews were completed with NYS BOCES women superintendents. The BOCES organization was purposefully selected, in contrast to one of the 731 NYS public school districts, because of the level of political and economic power that BOCES superintendents have at the state level – and to that end, the role of women leadership in a highly influential state educational organization. Overall, study results are consistent with Acker’s research, finding that the NYS BOCES is a highly gendered organization, and also in specific ways tied to contemporary context. Chief among these included that women superintendents face countless gender inequities and barriers associated with staying in their leadership role, but professional legacy, the extent to which the work benefited families, and appropriate work-life balance were motivating factors. Concluding with implications for research and practice, study findings are significant because this study is the first to empirically examine the NYS BOCES and the career trajectories of its women superintendents – and to do so from a feminist epistemological perspective and gendered theoretical framework focused creating transformative change within research and practice.
Serum uric acid: creatinine ratio (UCR) is associated with recurrence of atrial fibrillation after catheter ablation
Authors: Zhang Yujiao , Wang Yanxin , Yang Xuesong , Li Zhan , Shang Luxiang , Hou Yinglong
Published: May 2023

Background and aims

Studies showed that elevated preoperative serum uric acid(SUA) levels are associated with recurrence of atrial fibrillation(AF) after catheter ablation. UA:creatinine ratio(UCR - UA normalised for renal function) has appeared as a new biomarker and is considered to reflect endogenous UA levels preferably because it eliminates the influence of renal function. This study aimed to investigate the correlation between UCR and recurrence of AF after catheter ablation.

Methods and results

A total of 233 consecutive patients with symptomatic, drug-refractory AF underwent catheter ablation. All participants underwent history-taking, physical examination and blood biochemistry analysis at baseline. After a mean follow-up of 23.99 ± 0.76 months, recurrence ratios for each UCR quartile (from lowest quartile to highest) were 10.9%, 23.6%, 23.6%, and 41.8%, respectively (P = 0.005). Multivariate Cox regression analysis revealed that UCR was an independent predictor of AF recurrence (HR 1.217, 95%CI 1.008-1.468; P = 0.041). Subgroup analysis showed that UCR was associated with AF recurrence in paroxysmal AF (HR 1.426, 95% CI 1.092-1.8608; P = 0.009) and in male patients (HR 1.407, 95% CI 1.015-1.950; P = 0.04). A cut-off point of 4.475 for the UCR had sensitivity of 65.5% and specificity of 59.6% in predicting AF recurrence (P = 0.001).

Conclusion

Our results demonstrate that elevated preoperative UCR is associated with recurrence of AF after catheter ablation, and it indicate UCR maybe a predictive factor for the recurrence of AF.
Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis
Authors: Garruti Gabriella , Baj Jacek , Cignarelli Angelo , Perrini Sebastio , Giorgino Francesco
Published: May 2023

Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.