bluuebunny/crossref_metadata_2025 huggingface dataset:
Pertanggungjawaban Pidana Oknum Syahbandar Dalam Tindak Pidana Penyalahgunaan Wewenang Dibidang Pelayaran
Authors: Aldin Aldin , Haris Oheo K. , Hidayat Sabrina
Published: November 2021

Penelitian ini bertujuan: 1. Untuk mengetahui dan menganalisis kualifikasi tindak pidana penyalahgunaan wewenang di bidang pelayaran yang dilakukan oleh oknum syahbandar yang dapat dimintakan pertanggungjawaban pidana; 2. Untuk mengetahui dan menganalisis pertanggungjawaban pidana oknum syahbandar dalam tindak pidana penyalahgunaan wewenang di bidang pelayaran.Tipe penelitian yang penulis gunakan dalam penelitian adalah penelitian normatif atau doktrinal. Teknik pengumpulan bahan hukum yang mendukung dan berkaitan dengan pemaparan penelitian ini adalah studi dokumen (studi kepustakaan).Hasil penelitian menunjukkan bahwa:1. Dalam perkara Nomor 37/Pid.Sus/202/PN.Smp, terdakwa Mihtafol Arifin menerbitkan surat persetujuan berlayar kepada kapal KLM Sinar Sumekar yang tidak dilengkapi dengan dokumen tentang kelaikan lautan kapal sebagaimana dimaksud dalam Pasal 117 Ayat (2) Undang-Undang Nomor 17 Tahun 2008 Tentang Pelayaran, juga tidak dilengkapi dengan alat komunikasi sebagaimana dimaksud dalam Pasal 131 Ayat (2) Undang-Undang Nomor 17 Tahun 2008 Tentang Pelayaran. Pada kasus penerbitan Surat Persetujuan berlayar sebagaimana yang tertuang dalam perkara Nomor 37/Pid.Sus/202/PN.Smp, terkualifikasi sebagai tindak pidana penyalahgunaan wewenang sesuai dengan teori detournement de pouvoir karena Mihtafol Arifin menyalahgunakan wewenang yang di berikan kepadanya dengan cara menerbitkan Surat Persetujuan Berlayar yang tidak sesuai prosedur kepada kapal KLM. Sinar Sumekar sebagaimana amanat Undang-Undang Nomor 17 Tahun 2008 Tentang Pelayaran. Dalam perkara ini pasal yang diterapkan adalah Pasal 336 Ayat (1) Undang-Undang Nomor 17 Tahun 2008 Tentang Pelayaran, karena Mihtafol Arifin melanggar ketentuan Pasal 336 Ayat (1) Undang-Undang Nomor 17 Tahun 2008 Tentang Pelayaran, 2. Dalam perkara Nomor 37/Pid.Sus/202/PN.Smp, terdakwa Mihtafol Arifin dapat mempertanggungjawabkan perbuatannya karena pertanggungjawaban pidana seseorang tergantung pada unsur mens rea. Selain itu, untuk dapat mempertanggungjawabkan perbuatannya, subjek hukum (oknum syahbandar) tersebut telah memenuhi unsur: a) Adanya kemampuan bertanggungjawab dari pelaku, b) Adanya unsur kesalahan dalam tindakan pelaku, c) Adanya unsur melawan hukum dan d) Tidak adanya keadaan tertentu yang memaafkan tindakan pelaku.
Analisis Peraturan Gubernur Tanpa Dasar Peraturan Daerah dalam Penyelenggaraan Otonomi Daerah
Authors: Sumarfa Sumarfa , Tatawu Guasman , Jafar Kamaruddin
Published: November 2021

Penelitian ini bertujuan untuk menganalisis peraturan gubernur yang diterbitkan tanpa dasar hukum peraturan daerah memiliki legitimasi hukum. Tujuan lainnya adalah untuk menganalisis sinkronisasi hukum peraturan gubernur yang diterbitkan lebih dahulu terhadap peraturan daerah yang dibentuk. Penyelenggaraan pemerintahan daerah terdapat kondisi yang membutuhkan penanganan segera akan tetapi belum memiliki peraturan daerah sebagai dasar hukum sehingga dijumpai tindakan diskresi pemerintah daerah dengan pembentukan Peraturan Gubernur Sulawesi Tenggara Nomor 35 Tahun 2012 Tentang Kebutuhan dan Harga Enceran Tertinggi Pupuk Bersubsidi Untuk Sektor Pertanian Tahun 2013. Penelitian ini menggunakan penelitian hukum melalui pendekatan undang-undang dan konseptual hukum. Adapun hasil penelitian ini adalah peraturan gubernur yang diterbitkan tanpa dasar peraturan daerah memiliki legitimasi hukum terbatas karena secara hierarki peraturan gubernur merupakan peraturan pelaksana dari peraturan daerah dalam konsep otonomi daerah, hal ini diatur dalam Undang-Undang Nomor 12 tahun 2011 tentang Pembentukan Peraturan Perundang-undangan dan Undang-Undang Nomor 23 tahun 2014 tentang Pemerintahan Daerah serta teori hukum yang relevan. Bahwa untuk menjamin kepastian hukum, keberlakuan hukum perlu dilakukan sinkronisasi secara vertikal. sinkronisasi vertikal dengan mengedepankan asas hukum Lex superior derogat legi inferior. Langkah sinkronisasi vertikal yaitu peraturan gubernur yang telah diterbitkan diperbaharui menjadi peraturan daerah setelah itu diterbitkan peraturan gubernur yang baru. Sinkronisasi hukum mempunyai peranan menjaga keselarasan dan mencegah tumpang tindihnya peraturan perundang-undangan. Terdapat rekomendasi antara lain perlu adanya peraturan tentang mekanisme sinkronisasi peraturan gubernur menjadi peraturan daerah dan Dewan Perwakilan Rakyat Daerah perlu meningkatkan kinerjanya dibidang legislasi agar mencegah terjadi penerbitan peraturan gubernur lebih dahulu daripada peraturan daerahnya.
Konkurensi Kewenangan Penerbitan Izin Usaha Pertambangan Kepada Pemerintah Daerah Dalam Prinsip Otonomi Daerah
Authors: Herwanto Lulu , Sinapoy Muh. Sabaruddin , Jafar Kamaruddin
Published: November 2021

Tujuan penelitian ini memfokuskan pada masalah sebagai berikut: 1) Untuk mengetahui Apakah Penerbitan IUP merupakan kewenangan Provinsi atau Kabupaten/Kota. 2) Untuk mengetahui hubungan kewenangan antara pemerintah, pemerintah daerah dalam penerbitan IUP. Penelitian ini menggunakan tipe penelitian hukum Normatif dengan menggunakan beberapa pendekatan yaitu pendekatan perundang-undangan, pendekatan perbandingan, pendekatan komparatif, dan pendekatan konseptual. Berdasarkan hasil penelitian menujukan bahwa (1) Berdasarkan asas desentralisasi kewenangan penerbitan IUP ada pada pemerintah kabupaten/kota dengan normatifnya pada Pasal 8 jo. Pasal 37 Undang-Undang Republik Indonesia Nomor 4 Tahun 2009 tentang Pertambangan Mineral dan Batu Bara. Dengan dasar tersebut maka prinsip otonomi daerah sebagaimana berdasarkan pada asas desentralisasi sudah seharusnya diimplementasikan dengan sungguh-sungguh dan bertanggung jawab oleh pemerintah pusat ke pemerintah daerah mengingat bahwa karakteristik dan watak dari bangsa dan negara Indonesia yang beraneka ragam tercermin dalam Bhinneka Tunggal Ika merupakan suatu identitas nasional yang tidak dapat diingkari oleh siapa pun juga sehingga dalam penyelenggaraan pemerintahan di daerah sesuai dengan karakternya dan kekayaan alam masing-masing untuk dapat mengimplementasikan dari kebinekaan daerah otonom maka konsep pelaksanaan otonomi daerah diperluas lagi dengan menggunakan asas desentralisasi asimetris. (2) Hubungan kewenangan penerbitan IUP sebagaimana yang terdapat dalam Undang-Undang Republik Indonesia Nomor 4 Tahun 2009 secara normatif sudah mencerminkan prinsip dasar negara demokrasi yang diimplementasikan berdasarkan asas desentralisasi tanpa mengurangi prakarsa negara Indonesia sebagai Negara Kesatuan yang menjunjung tinggi falsafah hidup bangsa Indonesia yaitu Pancasila sebagai dasar ideologi bangsa dan negara khususnya dalam penyelenggaraan pemerintahan di daerah baik itu dalam bermasyarakat, berbangsa dan bernegara.
Perlindungan Hukum Terhadap Istri dalam Perkawinan yang Tidak Dicatat Secara Hukum
Authors: Nuraeni Nuraeni , Haris Oheo K. , Handrawan Handrawan , Yuningsih Deity
Published: November 2021

Perkawinan yang tidak tercatat adalah perkawinan yang tidak resmi menurut Undang-Undang Nomor 16 Tahun 2019 Tentang Perkawinan. Dasar hakim menerapkan Pasal 351 ayat (3) KUHP dalam putusan Nomor 146/Pid.Sus/2017/PN.Srl adalah dengan memperhatikan fakta-fakta hukum bahwa Perkawinan yang tidak resmi atau tidak tercatat tersebut menjadi problematik hukum, karena meskipun sah, akan tetapi dalam ketentuan negara perkawinan tersebut tidak mempunyai kekuatan hukum, suatu perbuatan hukum yang tidak mempunyai kekuatan hukum maka tidak dapat diakui oleh negara sebagai alas hak untuk mengurus segala kepentingan yang berkaitan dengan negara (karena tidak tercatat pada administrasi perkawinan negara) Namun berbeda halnya dengan pertimbangan hakim pada pengadilan Negeri pada Putusan Nomor 323/Pid.Sus/2016/PN.Gto, Majelis hakim memberikan pendapat bahwa Terdakwa melakukan pemukulan terhadap korban yang merupakan istri sah secara agama namun tidak di catatkan secara hukum. Oleh sebab itu, majelis hakim memberikan pertimbangan bahwa unsur lingkup rumah tangga dalam undang-undang PKDRT telah terpenuhi. 2) Berdasarkan Pasal 10 a UU PKDRT, selain itu bentuk perlindungan hukum yang diberikan kepada istri sebagai korban KDRT yang tidak tercatat pernikahannya secara hukum yaitu korban berhak mendapatkan perlindungan dari keluarga, kepolisian, kejaksaan, pengadilan, advokat, lembaga sosial, atau pihak lainnya baik sementara maupun berdasarkan penetapan pemerintah perlindungan dari keadilan.
PEMANFAATAN INTENSITAS SINAR MATAHARI UNTUK PANEL SURYA SEBAGAI SUMBER DAYA MENGGUNAKAN POWER INVERTER DC KE AC DAYA RENDAH
Authors: Koesmarijanto  , Muzakhim Imammudin Azam , Darmono Hendro
Published: November 2021

Energi bersih dan terbarukan dengan memanfaatkan intesitas sinar (energi) matahari pada sistem pembangkitan listrik tenaga surya. Sel surya dapat mengubah secara langsung energi sinar matahari dari diatomik menjadi energi listrik. Pembangkit Listrik Tenaga Surya (PLTS) dirancang sesuai kebutuhan dari skala rumah tangga sampai skala besar dengan teknologi yang mudah diadopsi oleh masyarakat. Energi matahari yang dikonversikan menjadi energi listrik dengan memanfaatkan panel surya digunakan sebagai energi alternatif yang dimanfaatkan untuk perumahan yang berada di daerah terpencil atau untuk keperluan yang lain. Tujuan penelitian ini mendesain sistem pembangkit tenaga surya dengan daya rendah untuk daerah yang belum terjangkau oleh aliran listrik atau memanfaatkan energi panel surya saat aliran listrik kondisi padam. Hasil variabel uji penelitian ini adalah tegangan yang dihasilkan kondisi konstan pada aki sebesar 12 Volt untuk mendorong inverter power dc ke ac menjadi tegangan 220 Volt. Tegangan Panel Surya sesuai spesifikasi tanpa beban (open circuit) sebesar 21,8 V dan diukur sebesar 19,8 V kondisi siang hari (cerah) jam 12.30 wib, sedangkan tegangan aki sebesar 12,61 V tanpa beban. Tegangan panel surya sebesar 19,8 V dibebani aki mengalami penurunan menjadi  14,4 V pada Solar Charge Controller, . Efisiensi panel surya sebesar 16,83 %.
Navigating the Light-Sheet Image Analysis Software Landscape: Concepts for Driving Cohesion From Data Acquisition to Analysis
Authors: Gibbs Holly C. , Mota Sakina M. , Hart Nathan A. , Min Sun Won , Vernino Alex O. , Pritchard Anna L. , Sen Anindito , Vitha Stan , Sarasamma Sreeja , McIntosh Avery L. , Yeh Alvin T. , Lekven Arne C. , McCreedy Dylan A. , Maitland Kristen C. , Perez Lisa M.
Published: November 2021

From the combined perspective of biologists, microscope instrumentation developers, imaging core facility scientists, and high performance computing experts, we discuss the challenges faced when selecting imaging and analysis tools in the field of light-sheet microscopy. Our goal is to provide a contextual framework of basic computing concepts that cell and developmental biologists can refer to when mapping the peculiarities of different light-sheet data to specific existing computing environments and image analysis pipelines. We provide our perspective on efficient processes for tool selection and review current hardware and software commonly used in light-sheet image analysis, as well as discuss what ideal tools for the future may look like.
Downregulated Ferroptosis-Related Gene STEAP3 as a Novel Diagnostic and Prognostic Target for Hepatocellular Carcinoma and Its Roles in Immune Regulation
Authors: Yan Yuanliang , Liang Qiuju , Xu Zhijie , Huang Jinzhou , Chen Xi , Cai Yuan , Peng Bi , Yi Qiaoli
Published: November 2021

Ferroptosis, a distinct type of regulated cell death, has been reported to be involved in the tumorigenesis of liver hepatocellular carcinoma (LIHC). However, the precise functions and potential mechanisms of ferroptosis in LIHC were still poorly understood. Herein, we investigated the biological roles of ferroptosis-related gene STEAP3 in LIHC. STEAP3 was previously proved to serve a key regulator in ferroptosis via mediating the iron metabolism. Comprehensive bioinformatics from several databases revealed that STEAP3 was significantly downregulated in LIHC tissues and exhibited the favorable prognostic significance in LIHC patients. The downregulated STEAP3 was further confirmed in two LIHC cells Huh7 and MHCC97H using real-time PCR and western blot. And STEAP3 overexpression significantly inhibited the cell proliferation in Huh7 and MHCC97H cells. In addition, clinical data identified the relationship between STEAP3 expression and several clinicopathological parameters of LIHC patients, including histologic grade, alpha fetal protein (AFP) concentration, etc. Receiver operation characteristic (ROC) curve revealed STEAP3 as a potential diagnostic biomarker for LIHC patients. Moreover, the co-expression network of STEAP3 was explored to gain a better insight into its underlying signaling pathways. Finally, aberrant STEAP3 might participate in varieties of immune-associated signatures in LIHC pathogenesis, including immunostimulators, immunoinhibitors, chemokines, and chemokine receptors. Taken together, these findings could enhance our knowledge regarding the inhibitory roles and underlying biological significance of STEAP3 in LIHC tumorigenesis.
Paracrine Effects of Recombinant Human Adiponectin Promote Bone Regeneration
Authors: Gong Yanping , Wang Yang , Zhang Yiqing , Wang Liangchen , Wan Lijuan , Zu Yuan , Li Chunlin , Wang Xin , Cui Zhong-Kai
Published: November 2021

Bone regeneration is a delicate physiological process. Non-union and delayed fracture healing remains a great challenge in clinical practice nowadays. Bone and fat hold a close relationship to remain balanced through hormones and cytokines. Adiponectin is a well-known protein to maintain the hemostasis, which may be an interesting target for fracture healing. Herein, we provided a facile and efficient method to obtain high-purity and high-yield recombinant human adiponectin (ADPN). The biocompatibility and the pharmaceutical behaviors were evaluated in Sprague–Dawley rats. The paracrine effects of adiponectin on bone fracture healing were investigated with a rat tibia fracture model via intrabone injection. Significantly accelerated bone healing was observed in the medulla injection group, indicating the paracrine effects of adiponectin could be potentially utilized for clinical treatments. The underlying mechanism was primarily assessed, and the expression of osteogenic markers, including bone morphogenic protein 2, alkaline phosphatase, and osteocalcin, along with adiponectin receptor 1 (AdipoR1), was markedly increased at the fracture site. The increased bone healing of ADPN treatment may result from both enhanced osteogenic proliferation as well as differentiation. Cell experiments confirmed that the expression of osteogenesis markers increased significantly in ADPN treatment groups, while it decreased when the expression of AdipoR1 was knocked down by siRNA. Our study provided a feasible and efficacious way for bone fracture treatment with local administration of ADPN, which could be rapidly translated into the clinics.
Imbalance in the Gut Microbiota of Children With Autism Spectrum Disorders
Authors: Ding Hongfang , Yi Xinhao , Zhang Xiaohua , Wang Hui , Liu Hui , Mou Wei-Wei
Published: November 2021

Background

Autism spectrum disorder (ASD) are complex behavioral changes manifesting early in childhood, which impacts how an individual perceives and socializes with others. The study aims to assess the disparities in gut microbiota (GM) amongst healthy controls and children with ASD.

Methods

The study was performed on 25 children with ASD and 20 healthy children. Autistic symptoms were diagnosed and assessed with the Diagnostic and Statistical Manual for Mental Disorders and the Autism Treatment Evaluation Checklist (ATEC). Gastrointestinal (GI) symptoms were assessed with a GI Severity Index (GSI) questionnaire. The fecal bacteria composition was investigated by the high−throughput sequencing of the V3–V4 region of the 16S rRNA gene. The alpha diversity was estimated using the Shannon, Chao, and ACE indexes. The unweighted UniFrac analysis and the PCA plots were used to represent the beta diversity. LDA and LEfSe were used to assess the effect sizes of each abundant differential taxon.

Results

Children with high GSI scores had much higher ATEC Total scores than those with lower GSI-scores. GI symptoms were strongly associated with symptoms of ASD. There was no difference in Chao, ACE, and Shannon indexes between ASD patients and healthy controls. Both groups showed a significant microbiota structure clustering in the plotted PCAs and significant differences in its composition at the family, order, genus, and phyla levels. There were also noteworthy overall relative differences in Actinobacteria and Firmicutes between both groups.

Conclusions

This study shows the relationship between the clinical manifestations of Autistic symptoms and GI symptoms. ASD patients have dysbiosis of gut microbiota, which may be related to the onset of ASD. These findings may be beneficial for developing ASD symptoms by changing gut microbiota.
Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study
Authors: Hu Hangbin , Zhang Yan , Zhang Piaopiao , Wang Jie , Yuan Qing , Shi Weixiao , Zhang Sheng , Feng Haiting , Chen Yunbo , Yu Meihong , Chen Hongchao , Jiang Yan , Yang Qing , Qu Tingting
Published: November 2021

Objectives

Recently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463.

Methods

Retrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model.

Results

Among the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene blaKPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the blaKPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26–Tn3-tnpA–ISKpn27–blaKPC-2–ISKpn6–IS26). Plasmid from various species presented core blaKPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6.

Conclusions

In the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the blaKPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.
A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands
Authors: Hullegie Saskia , Schilder Anne G. M. , Marchisio Paola , de Sévaux Joline L. H. , van der Velden Alike W. , van de Pol Alma C. , Boeijen Josi A. , Platteel Tamara N. , Torretta Sara , Damoiseaux Roger A. M. J. , Venekamp Roderick P.
Published: November 2021

Introduction

Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands.

Material and Methods

Retrospective observational cohort study using routine health care data from the Julius General Practitioners’ Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods.

Results

OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively).

Discussion

GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic.
Microstratigraphic Analysis of Fossil Distribution in the Lower Hornerstown and Upper Navesink Formations at the Edelman Fossil Park, NJ
Authors: Voegele Kristyn K. , Ullmann Paul V. , Lonsdorf Tara , Christman Zachary , Heierbacher Michael , Kibelstis Brian J. , Putnam Ian , Boles Zachary M. , Walsh Shane , Lacovara Kenneth J.
Published: November 2021

Maastrichtian–Danian sediments of the Navesink and Hornerstown formations at the Jean and Ric Edelman Fossil Park of Rowan University in Mantua Township, New Jersey, have long intrigued paleontologists. Within the basal Hornerstown Formation occurs the Main Fossiliferous Layer (MFL), a regionally well-known and diverse bonebed. The lithostratigraphic and chronostratigraphic position of this fossil layer have been debated for more than 50 years, fueling debate over its origin. Herein, we present the results of a microstratigraphic analysis of the fossil composition and distribution of the MFL undertaken to rectify these discrepancies. Through methodical top-down excavation, we recorded the three-dimensional position of every fossil encountered. Three-dimensional visualization and analyses of these data in ArcGIS Pro yielded an unprecedented view of this bonebed. Most reported discrepancies about the stratigraphic placement and thickness of the MFL can be explained by the presence of two distinct fossil assemblages within this interval that are occasionally combined into a single bonebed. The stratigraphically-lower assemblage, herein termed an “oyster layer”, is geometrically-tabular and exhibits low taxonomic diversity, high abundance of the oyster Pycnodonte, and moderate taxonomic richness. The stratigraphically-higher assemblage, the MFL, occurs approximately 9 cm higher in section and exhibits high values of taxonomic diversity, fossil abundance, and taxonomic richness. Sedimentological homogeneity throughout this interval suggests that these faunal contrasts arise from the two assemblages having formed via independent taphonomic pathways. Specifically, prevalence of Pycnodonte in the oyster layer implies formation by a selective mortality event, whereas the diversity of the MFL appears to reflect a more universal agent of mortality. Spatial variations in the stratigraphic distribution of fossils within the MFL in our excavation area indicate this assemblage does not form a simple, tabular layer as previously thought and may, in part, record original bathymetry. Importantly, our definition of the MFL and detailed characterization of its stratigraphic placement are essential for future studies on the taphonomic origin and chronostratigraphy of this bonebed. Universal use of this definition would allow researchers to confidently elucidate the exact lithostratigraphic positions of precise chronostratigraphic indicators within the MFL and accurately estimate the degree of time averaging of its fossils.
Salient Experiences in Student Development: Impact of an Undergraduate STEM Teacher Preparation Program
Authors: Sommers Amie S. , Johnson Kelly Gomez , Jakopovic Paula , Rivera Julio , Grandgenett Neal , Conrad John A. , Tapprich William E. , Cutucache Christine E.
Published: November 2021

The need for a comprehensive, high-quality pipeline for the development of undergraduate pre-service teachers, especially those that represent a diverse student body, within STEM disciplines is acute. Here, we studied the NoyceSCIENCE program to determine the most impactful experiences offered to undergraduates through the lens of student development theory. We used qualitative coding to analyze data collected from journals (n = 29) written by students of varying backgrounds, and at varying levels within the program (i.e., the Scholar and Intern level) over a 3-year program running period. We observed that faculty mentorship, the ability of undergraduates to mentor others, volunteer experiences, and learning directly from experts had the greatest influence on student development overall. For Scholars that participate for more than 1 year in the program, access to undergraduate mentoring and volunteering experiences contributed most to student development. We posit that these findings are broadly applicable to other science learning communities and STEM content-focused teacher preparation programs as they are program components that can be integrated in isolation or in their entirety.
Therapeutic Targeting of SGLT2: A New Era in the Treatment of Diabetes and Diabetic Kidney Disease
Authors: Shaffner James , Chen Bohan , Malhotra Deepak K. , Dworkin Lance D. , Gong Rujun
Published: November 2021

As the prevalence of diabetic kidney disease (DKD) continues to rise, so does the need for a novel therapeutic modality that can control and slow its progression to end-stage renal disease. The advent of sodium-glucose cotransporter-2 (SGLT2) inhibitors has provided a major advancement for the treatment of DKD. However, there still remains insufficient understanding of the mechanism of action and effectiveness of this drug, and as a result, its use has been very limited. Burgeoning evidence suggests that the SGLT2 inhibitors possess renal protective activities that are able to lower glycemic levels, improve blood pressure/hemodynamics, cause bodyweight loss, mitigate oxidative stress, exert anti-inflammatory and anti-fibrotic effects, reduce urinary albumin excretion, lower uric acid levels, diminish the activity of intrarenal renin-angiotensin-aldosterone system, and reduce natriuretic peptide levels. SGLT2 inhibitors have been shown to be safe and beneficial for use in patients with a GFR ≥30mL/min/1.73m2, associated with a constellation of signs of metabolic reprogramming, including enhanced ketogenesis, which may be responsible for the correction of metabolic reprogramming that underlies DKD. This article aims to provide a comprehensive overview and better understanding of the SGLT2 inhibitor and its benefits as it pertains to renal pathophysiology. It summarizes our recent understanding on the mechanisms of action of SGLT2 inhibitors, discusses the effects of SGLT2 inhibitors on diabetes and DKD, and presents future research directions and therapeutic potential.
Screening Candidate Effectors of the Bean Bug Riptortus pedestris by Proteomic and Transcriptomic Analyses
Authors: Fu Weichuan , Liu Xingzhou , Rao Cong , Ji Rui , Bing Xiaoli , Li Jinbu , Wang Yueying , Xu Hao
Published: November 2021

The damage of Riptortus pedestris is exceptional by leading soybean plants to keep green in late autumn. Identification of the salivary proteins is essential to understand how the pest-plant interaction occurs. Here, we have tried to identify them by a combination of proteomic and transcriptomic analyses. The transcriptomes of salivary glands from R. pedestris males, females and nymphs showed about 28,000 unigenes, in which about 40% had open reading frames (ORFs). Therefore, the predicted proteins in the transcriptomes with secretion signals were obtained. Many of the top 1,000 expressed transcripts were involved in protein biosynthesis and transport, suggesting that the salivary glands produce a rich repertoire of proteins. In addition, saliva of R. pedestris males, females and nymphs was collected and proteins inside were identified. In total, 155, 20, and 11 proteins were, respectively, found in their saliva. We have tested the tissue-specific expression of 68 genes that are likely to be effectors, either because they are homologs of reported effectors of other sap-feeding arthropods, or because they are within the top 1,000 expressed genes or found in the salivary proteomes. Their potential functions in regulating plant defenses were discussed. The datasets reported here represent the first step in identifying effectors of R. pedestris.
Progress on the Regulation of Ruminant Milk Fat by Noncoding RNAs and ceRNAs
Authors: Lu QinYue , Chen Zhi , Ji Dejun , Mao Yongjiang , Jiang Qianming , Yang Zhangping , Loor Juan J.
Published: November 2021

Milk fat is not only a key factor affecting the quality of fresh milk but also a major target trait forbreeding. The regulation of milk fat involves multiple genes, network regulation and signal transduction. To explore recent discoveries of pathway regulation, we reviewed the published literature with a focus on functional noncoding RNAs and epigenetic regulation in ruminants. Results indicate that miRNAs play key roles in the regulation of milk fat synthesis and catabolism in ruminants. Although few data are available, merging evidence indicates that lncRNAs and circRNAs act on milk fat related genes through indirect action with microRNAs or RNAs in the ceRNA network to elicit positive effects on transcription. Although precise regulatory mechanisms remain unclear, most studies have focused on the regulation of the function of target genes through functional noncoding RNAs. Data to help identify factors that can regulate their own expression and function or to determine whether self-regulation involves positive and/or negative feedback are needed. Despite the growing body of research on the role of functional noncoding RNA in the control of ruminant milk fat, most data are still not translatable for field applications. Overall, the understanding of mechanisms whereby miRNA, lncRNA, circRNA, and ceRNA regulate ruminant milk fat remains an exciting area of research.
Constitutive IFNα Protein Production in Bats
Authors: Bondet Vincent , Le Baut Maxime , Le Poder Sophie , Lécu Alexis , Petit Thierry , Wedlarski Rudy , Duffy Darragh , Le Roux Delphine
Published: November 2021

Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this symbiotic relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this, we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but were not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.
Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains
Authors: Grimm Clemens , Dickel Steffen , Grundmann Julian , Payen Didier , Schanz Julie , Zautner Andreas Erich , Tampe Björn , Moerer Onnen , Winkler Martin Sebastian
Published: November 2021

Background

CD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy.

Case Report

We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae. A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70.

Discussion

Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient’s own immunity by IFNγ was a plausible option to boost the patient’s immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies.

Conclusion

After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.
Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis
Authors: Meier Ute-Christiane , Cipian Richard Christopher , Karimi Abbas , Ramasamy Ranjan , Middeldorp Jaap Michiel
Published: November 2021

Roles for viral infections and aberrant immune responses in driving localized neuroinflammation and neurodegeneration in multiple sclerosis (MS) are the focus of intense research. Epstein-Barr virus (EBV), as a persistent and frequently reactivating virus with major immunogenic influences and a near 100% epidemiological association with MS, is considered to play a leading role in MS pathogenesis, triggering localized inflammation near or within the central nervous system (CNS). This triggering may occur directlyviaviral products (RNA and protein) and/or indirectlyviaantigenic mimicry involving B-cells, T-cells and cytokine-activated astrocytes and microglia cells damaging the myelin sheath of neurons. The genetic MS-risk factor HLA-DR2b (DRB1*1501β, DRA1*0101α) may contribute to aberrant EBV antigen-presentation and anti-EBV reactivity but also to mimicry-induced autoimmune responses characteristic of MS. A central role is proposed for inflammatory EBER1, EBV-miRNA and LMP1 containing exosomes secreted by viable reactivating EBV+ B-cells and repetitive release of EBNA1-DNA complexes from apoptotic EBV+ B-cells, forming reactive immune complexes with EBNA1-IgG and complement. This may be accompanied by cytokine- or EBV-induced expression of human endogenous retrovirus-W/-K (HERV-W/-K) elements and possibly by activation of human herpesvirus-6A (HHV-6A) in early-stage CNS lesions, each contributing to an inflammatory cascade causing the relapsing-remitting neuro-inflammatory and/or progressive features characteristic of MS. Elimination of EBV-carrying B-cells by antibody- and EBV-specific T-cell therapy may hold the promise of reducing EBV activity in the CNS, thereby limiting CNS inflammation, MS symptoms and possibly reversing disease. Other approaches targeting HHV-6 and HERV-W and limiting inflammatory kinase-signaling to treat MS are also being tested with promising results. This article presents an overview of the evidence that EBV, HHV-6, and HERV-W may have a pathogenic role in initiating and promoting MS and possible approaches to mitigate development of the disease.
How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?
Authors: Vultaggio Alessandra , Perlato Margherita , Nencini Francesca , Vivarelli Emanuele , Maggi Enrico , Matucci Andrea
Published: November 2021

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety. In fact they are mainly associated with immediate hypersensitivity reactions (HSRs). Development of ADAs is reduced by concomitant immunosuppressive treatment, while it is increased by longer intervals between drug administrations; thus, regular infusion regimens should be preferred to reduce HSRs. Once ADAs have formed, some procedures can be implemented to reduce the risk of HSRs. ADAs may belong to different isotype; the detection of IgE ADA is advisable to be assessed when high and early ADAs are detected, in order to reduce the risk of severe HRs. In patients who need to reintroduce the biological culprit, as alternative therapies are not available, drug desensitization (DD) may be applied. Desensitization should be conceptually dedicated to patients with an IgE-mediated HSR; however, it can be performed also in patients who had developed non-IgE-mediated HSRs. Although the underlying mechanisms behind successful DD has not been fully clarified, the DD procedure is associated with the inhibition of mast cell degranulation and cytokine production. Additionally, some data are emerging about the inhibition of drug-specific immune responses during DD.
The Multifaceted Roles of B Cells in the Thymus: From Immune Tolerance to Autoimmunity
Authors: Castañeda Justine , Hidalgo Yessia , Sauma Daniela , Rosemblatt Mario , Bono María Rosa , Núñez Sarah
Published: November 2021

The thymus is home to a significant number of resident B cells which possess several unique characteristics regarding their origin, phenotype and function. Evidence shows that they originate both from precursors that mature intrathymically and as the entry of recirculating mature B cells. Under steady-state conditions they exhibit hallmark signatures of activated B cells, undergo immunoglobulin class-switch, and express the Aire transcription factor. These features are imprinted within the thymus and enable B cells to act as specialized antigen-presenting cells in the thymic medulla that contribute negative selection of self-reactive T cells. Though, most studies have focused on B cells located in the medulla, a second contingent of B cells is also present in non-epithelial perivascular spaces of the thymus. This latter group of B cells, which includes memory B cells and plasma cells, is not readily detected in the thymus of infants or young mice but gradually accumulates during normal aging. Remarkably, in many autoimmune diseases the thymus suffers severe structural atrophy and infiltration of B cells in the perivascular spaces, which organize into follicles similar to those typically found in secondary lymphoid organs. This review provides an overview of the pathways involved in thymic B cell origin and presents an integrated view of both thymic medullary and perivascular B cells and their respective physiological and pathological roles in central tolerance and autoimmune diseases.
Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems
Authors: Li Haixia , Liu Shan , Han Jinming , Li Shengxian , Gao Xiaoyan , Wang Meng , Zhu Jie , Jin Tao
Published: November 2021

Toll-like receptors (TLRs) are a class of proteins playing a key role in innate and adaptive immune responses. TLRs are involved in the development and progression of neuroimmune diseases via initiating inflammatory responses. Thus, targeting TLRs signaling pathway may be considered as a potential therapy for neuroimmune diseases. However, the role of TLRs is elusive and complex in neuroimmune diseases. In addition to the inadequate immune response of TLRs inhibitors in the experiments, the recent studies also demonstrated that partial activation of TLRs is conducive to the production of anti-inflammatory factors and nervous system repair. Exploring the mechanism of TLRs in neuroimmune diseases and combining with developing the emerging drug may conquer neuroimmune diseases in the future. Herein, we provide an overview of the role of TLRs in several neuroimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorder, Guillain-Barré syndrome and myasthenia gravis. Emerging difficulties and potential solutions in clinical application of TLRs inhibitors will also be discussed.
Integrating Oceanographic Data and Benthic Community Structure Temporal Series to Assess the Dynamics of a Marginal Reef
Authors: Biscaia Zamoner Julia , Aued Anaide Wrublevski , Macedo-Soares Luis Carlos Pinto , Picolotto Vitor André Passos , Eiras Garcia Carlos Alberto , Segal Bárbara
Published: November 2021

Reefs are the richest marine ecosystems. Their benthic communities generate structural complexity and participate in nutrient cycles, providing habitat and food for many marine species. These ecosystems have been threatened by local and global anthropogenic impacts and changes in community structure have led to loss of biodiversity, ecosystem function and services worldwide. Most studies about these structural changes have been conducted in Caribbean and Indo-Pacific coral reefs. In the Southwestern Atlantic, where reefs are naturally algae-dominated, these efforts are incipient, especially at oceanic islands where local anthropic impacts tend to be lower, and natural and climate-induced fluctuations might be easily detected. We conducted the first temporal assessment of benthic communities and the influence of oceanographic parameters between 2013 and 2019 in Fernando de Noronha (FNA), the largest Brazilian oceanic archipelago. We annually sampled benthic communities in FNA’s shallow reefs (2–21 m) using photoquadrats, quantified and gathered organisms in major groups according to their functional roles. We also characterized and tested “sea surface temperature,” “marine heatwaves,” “diffuse attenuation coefficient,” and “wave energy” influence for the same period. The most abundant groups were epilithic algal matrix (EAM; mean annual coverage: 23–60%), macroalgae (15–35%) and calcifiers (15–29%), followed by cyanobacteria (1–37%), suspension/filter-feeders (<2%), zoanthids (<1%) and other invertebrates (<0.1%). EAM was negatively correlated with “marine heatwaves” and positively correlated with “wave energy,” while macroalgae and calcifiers showed opposite responses to “marine heatwaves” and “wave energy,” respectively. Cyanobacteria was positively correlated with “marine heatwaves.” The dominance of EAM and macroalgae was already described for reefs along the Brazilian Province and we demonstrated the persistence of this structure over the years in FNA, with the exception of 2019 when there was a substantial increase of cyanobacteria after a strong marine heatwave. Our results suggest a flickering dynamic between EAM and macroalgae, which vary according to the oceanographic conditions, reinforcing its distinct dynamics from most tropical coral reefs. However, the increase of cyanobacteria added to projections of more frequent and stronger marine heatwaves worldwide indicate possible structural changes in this community. Continued monitoring of community and oceanographic drivers is key for better understanding and predicting changes in important marginal reefs.
Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications
Authors: Hindocha Sumeet , Campbell Des , Ahmed Merina , Giorgakoudi Kyriaki , Sharma Bhupinder , Yousaf Nadia , Molyneaux Philip , Hunter Benjamin , Kalsi Hardeep , Cui Wanyuan , Davidson Michael , Bhosle Jaishree , Minchom Anna , Locke Imogen , McDonald Fiona , O'Brien Mary , Popat Sanjay , Lee Richard W.
Published: November 2021

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.