bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengembangan Bahan Ajar Model Discovery Learning Menggunakan Media Digital di SMA N 1 Terbanggi Besar
Authors: Umihani Umihani , Nurwahidin Muhammad , Pujianti Pujianti , Riswandi Riswandi
Published: January 2023

Guru sebagai motor penggerak dan pelaksana dalam pembelajaran peserta didik, dituntut harus memiliki kemampuan dalam menciptakan, mengembangkan, melaksanakan dan mengevaluasi setiap proses belajar mengajar didalam kelas. kurangnya variasi media pembelajaran yang menarik menyebabkan siswa merasa bosan dan pembelajaran terkesan monoton sehingga pada akhirnya siswa tidak fokus dalam belajar.  Penelitian ini bertujuan untuk mengetahui efektivitas. pengembangan bahan ajar model discovery learning dengan menggunakan media digital di SMA Negeri 1 Terbanggi Besar. Metode Penelitian ini adalah penelitian kuanititatif, jenis penelitian ini adalah penelitian quasi-experiment dengan menggunakan hasil pretest dan posttest. Populasi yang digunakan yaitu peserta didik kelas XI IPS yang berjumlah 30 orang peserta didik. Hasil penelitian diketahui efektivitas bahan ajar model discovery learning dengan menggunakan media digital Dapat dikatakan cukup efektif digunakan sebagai media pembelajaran di SMA Negeri 1 Terbanggi Besar. Dengan hasil perhitungan diatas diketahui nilai pretest dan posttest, diperoleh nilai skor N Gain sebesar 0,64 dengan kategori sedang sedangkan nilai persentase 64,00% dengan tafsiran Cukup Efektif.
X-Ray Photoelectron Spectroscopy of Polystyrene Composite Films
Authors: Goodson Mersaydes L , Lagle Richard , Guggilla Padmaja
Published: January 2023

In this paper, X-ray Photoelectron Spectroscopy (XPS) measurements were obtained to determine the chemical structure of these polystyrene (PS) doped and undoped thin films. The purpose is to analyze the graphs and binding energies of each element to determine. The XPS analysis of these pure PS compared doped PS thin film does show a tunable potential for optimum properties. PS has a relative basic host matrix, and it is our hypothesis that first, we can show that XPS can be a useful and resourceful tool in characterizing these thin films for chemical structure and binding information. Secondly, we intend to show that through the addition of dopants, we can affect the binding energies. The results show the impact on O1s binding energies ± 4.43-5.57 eV and for C1s ± 1.45 -9.37 eV. These analyses have been performed in several studies on polymer nanocomposite materials. Here, we introduce the use of the XPS analysis in recent notable polymer nanocomposite studies for various target applications.
Impact of Metabolic Syndrome on Retronasal Olfaction
Authors: Siena Cid , Anita Bannerman , Sara D Garduno-Diaz
Published: January 2023

As rates of metabolic syndrome (MS) rise globally, it is unclear how and if the risk factors associated with this condition impact flavor perception via the retronasal pathway, which is critical for experiencing the flavor of foods and drinks. This commentary discusses existing literature on the possible impacts of MS on retronasal olfaction by examining primary diagnostic criteria, including hypertension, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and excess visceral adipose tissue. Risk factors for MS including hypertension, obesity, and hyperglycemia appear to have a negative impact on the sensitivity of retronasal olfaction. Although most of the work cited in this communication affirms that MS does negatively affect the functionality of the olfactory system, it is important to note that research is divided on this determination. Although retronasal dysfunction is not considered a life threating condition, it drastically changes the landscape of sensory information perceived and impacts an individual’s quality of life. Further clinical research on the impact of MS on retronasal olfaction is warranted to provide insights into the intricacies of these pathways.
Video Feature Perpaduan Budaya Candi Cetho sebagai Media Informasi
Authors: Kabelen Nicholaus Wayong , Mauludiah Fadila Fitra
Published: January 2023

Indonesia memiliki keanekaragaman budaya dan peninggalan sejarah yang melimpah, salahsatunya ialah Candi Cetho. Candi ini memiliki arsitektur yang mirip dengan bangunan SukuMaya di Meksiko. Arca yang terdapat di candi ini pun apabila dilihat tidak mirip dengan orangJawa melainkan lebih mirip dengan orang Sumeria. Bahan andesit yang digunakan di CandiCetho berbeda dengan candi Hindu di masa kerajaan Majapahit yang pada saat itu dibangunmenggunakan bata merah. Solusi yang ditawarkan pada penelitian ini adalah pembuatan videofeature sebagai media informasi mengenai fakta dari sinkretisme yang terdapat pada candicetho. Candi Cetho dibangun pada masa setelah pengaruh Hindu-Budha sampai akhir masapenganut tersebut. Sehingga arsitektur di candi cetho masih bercampur dengan kebudayaanHindu-Budha dan juga kebudayaan lokal masayarakat sekitar. Dari narasumber yangditentukan juga sudah sesuai dengan penelitian ini. Berdasarkan kuisioner hasil dari penelitianini menunjukkan bahwa masyarakat sudah dapat memahami informasi dari video feature ini.Maka dari itu video feature ini sudah dapat diterima dengan baik oleh masyarakat.
Perancangan Buku Fotografi Esai "Hygge" untuk Menarik Minat Wisatawan dan Masyarakat di Kota Malang
Authors: Yosephine Tiffany , Nugroho Didit Prasetyo
Published: January 2023

Munculnya berbagai macam kafe di Kota Malang menimbulkan gaya hidup baru yaitu berkumpul bersama teman khususnya bagi generasi muda. Gaya hidup ini membuat kafe terus bermunculan di Kota Malang dengan konsep yang disukai oleh generasi ini, salah satunya yaitu konsep cozy. Tetapi hal ini membuat kafe yang terus bermunculan kurang memperhatikan kualitas dari segi suasana dan menu karena terlalu berfokus dengan interior cozy yang disukai generasi muda. Maka dari itu dibutuhkan media informasi yang bisa menarik wisatawan dan masyarakat dalam memilih dan mengunjungi kafe bukan hanya berdasarkan tren, melalui pembuatan perancangan yang bertujuan mendapatkan visualisasi konsep melalui media buku fotografi esai yang memuat informasi tentang 8 kafe dengan konsep cozy di Kota Malang. Metode perancangan yang digunakan yaitu metode perancangan komunikasi kreatif serta dipadukan dengan metode pengumpulan data kualitatif. Buku fotografi esai ini menggunakan gaya foto interior dan makanan, dengan ukuran buku 22,4 x 17 cm dengan total 248 halaman, full color, serta dijilid menggunakan hardcover laminasi doff. Kesimpulan perancangan ini adalah mendapatkan visualisasi konsep buku fotografi esai untuk memberikan informasi tentang kafe cozy melalui visualisasi foto yang diserta narasi melalui media buku dan media pendukung seperti bookmark, tote bag, photo sheet, sticker, tumbler, acrylic straw, diffuser, dan media pemasaran melalui sosial media Instagram.
Kritik Unsur Kearifan Lokal pada Label Kemasan Kopi Van Dillem Trenggalek
Authors: Rohmatillah Renzy Ayu
Published: January 2023

Penelitian ini mengkaji pemaknaan visual label kemasan kopi Van Dillem. Kopi ini merupakan produk daerah Trenggalek. Label kemasan produk ini dikaji untuk mengetahui bagaimana makna visualnya dan apakah makna visual tersebut berkaitan dengan kearifan lokal daerah Trenggalek. Penelitian ini menggunakan teknik pengumpulan data studi pustaka dan observasi. Penelitian ini menggunakan teori kritik seni Feldman yang mencakup empat tahap yakni deskripsi, analisis, interpretasi, dan evaluasi. Sebagai produk khas daerah Trenggalek, kopi Van Dillem membawa nama daerah untuk diperkenalkan kepada masyarakat luas. Cerminan ciri khas daerah dapat ditampilkan pada elemen-elemen visual label kemasan produk lokal untuk menegaskan wilayah produksinya. Hasil penelitian menunjukkan bahwa makna visual label kemasan produk kopi ini menampilkan unsur gambar kolonialisme. Unsur kolonialisme ini berhubungan dengan sejarah terciptanya produk kopi di Trenggalek.
Reconstructing trophic position over the past century for five Puget Sound fish species
Authors: Welicky RL , Feddern ML , Rolfe T , Leazer K , Moosmiller A , Fiorenza E , Maslenikov KP , Tornabene L , Holtgrieve GW , Wood CL
Published: January 2023

The comparison of historical and modern food web dynamics allows ecologists to test whether the trophic connectivity we observe today is ‘normal’ in its historical context. Fish densities and abundances have changed across time, making it likely that fish trophic interactions and their trophic positions have also changed. Historical trophic data of marine fishes can now be extracted from the tissues of fluid-preserved specimens held in natural history collections via compound-specific stable isotope analysis of amino acids (CSIA-AA) of nitrogen. We conducted CSIA-AA to quantify trophic position change over the past century in 5 ecologically important fishes of Puget Sound, Washington, USA: Pacific hake Merluccius productus, walleye pollock Gadus chalcogrammus, copper rockfish Sebastes caurinus, English sole Parophrys vetulus, and Pacific herring Clupea pallasii, and examined the canonical trophic (glutamic acid) and source (phenylalanine) amino acids. For all fishes except copper rockfish, trophic position, glutamic acid, and phenylalanine values remained similar across time. For copper rockfish, glutamic acid but not phenylalanine values increased over time, indicating an increase in this species’ trophic position. The observed increase in copper rockfish trophic position may be a function of diet switching and declining prey quality rather than a consequence of rockfish consuming higher trophic level prey. This study leverages more than 100 yr of trophic data of fishes representing various feeding guilds and demonstrates that some fish species may be more trophically resilient to major environmental change than expected. Efforts should be made to identify and conserve the trophic interactions of species experiencing change.
The Efficacy of Anti-TNFs in Immune-Mediated Disease
Authors: Humphry Nicola
Published: January 2023

TNF-α is produced in high concentrations in chronic inflammatory disease, resulting in excessive inflammation which eventually leads to organ damage. The advent of anti-TNF therapy in clinical practice 20 years ago represented a significant change in the management of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (RA), axial spondylarthritis (SpA), psoriasis, and inflammatory bowel disease (IBD).

There are five anti-TNFs approved for use in IMIDs: infliximab, adalimumab, golimumab, etanercept, and certolizumab pegol. The structural and pharmacological differences between these agents mean that they can have differential efficacy across IMIDs, and therefore the indications for which they are approved vary. This mini-review aims to summarise the current understanding of anti-TNF efficacy in those IMIDs for which they are approved, focussing on data from meta-analyses of randomised clinical trials (RCTs), and real-world studies.
Land monitoring materials as a basis for compiling a land survey project
Authors: Hutsuliak H. , Hutsuliak Yu. , Kaminetska O.
Published: January 2023

The article considers aspects of land monitoring as a basis for drawing up a land management project. It was determined that the development and mastering of systems of adaptive landscape farming is a sustainable reproduction of resources and the environment in the technological cycle of obtaining products of the required quantity and quality. In this context, one of the most important tasks is the formation of ecologically balanced agricultural landscapes, highly productive agroecosystems based on knowledge of the laws and regularities of the functioning of natural systems, taking into account the resource potential of lands and more in-depth adaptation of technological influences. It is suggested that the united territorial communities resolve the issue of providing their divisions with qualified personnel who will be able to ensure the local development of the territorial community on the basis of ecological and economic balanced use of natural resource potential. The proposed approach will make it possible to make assessments and analyzes of the actual and predictive state of land resources, will allow to choose directions that require priority decisions to be made to neutralize negative phenomena, to mitigate already developed negative processes and to carry out preventive measures where adverse factors have not yet made harmful influence, which, accordingly, will ensure the rational use of land and its preservation for the next generation.
Video games lexicon included in Spanish language: a multiple case study
Authors: Orta Casado Javier , Peña-Acuña Beatriz
Published: January 2023

In our current society, the lexical treasure that Spanish has is made up of numerous words that recognize the expressions of a group of speakers. Due to technological development, this reality is present in the Internet space and among consumers of online content, who discover and learn, from this multimodal tool, new terms that arise daily, giving rise to new words. For this reason, in this dissertation, we aim investigate and treat those terms of Spanish and English origin and even neologisms that make up the world of video games, with a viewing of 50 youtubers and an experimentation of 3 successful video games from which it will be obtained, terms which will be later collated to see how they are treated in the different dictionaries. Thirdly, the percentage of these terms will be obtained through the words collected in the reference corpus of Spanish and English. It will also be addressed what attention video games receive recently as a didactic multimodal tool for learning vocabulary.
The consumption and reggaeton´s language under debate among adolescents
Authors: González Gómez Isabel , Delgado-García Manuel
Published: January 2023

Music is not just a simple pastime, as it also contributes to the construction of identities, promotes cultural development or generates close affective ties between those who share the same musical preferences. In recent years, reggaeton has become very popular, a musical genre admired by youth and characterized by containing, in its lyrics, discriminatory messages towards women. In this sense, it is vitally important to question the impact exerted on adolescents, where it has penetrated with greater impetus, analyzing the possible consequences that it may have when building or reinforcing macho thoughts.

A qualitative research is proposed that tries to examine the perceptions of adolescents. Through two focus groups, the opinions of young people enrolled in the educational stages of 2nd ESO and 3rd ESO from two secondary education institutes in the province of Huelva are debated and confronted. During the focus group sessions, the participants question the relationship between different variables that emerge from the properties of the language used in some reggaeton lyrics, such as machismo or gender violence. The analysis of the speeches derived from the work sessions has been developed through the Maxqda software.

The results reveal a type of music that is expanding as a trend among adolescents, whose messages are not clearly discriminated or prosecuted and which tend to normalize certain discriminatory behaviors towards women and reinforce macho thinking among the male gender. For all these reasons, the educational system must promote the creation of a musical culture that invites adolescents to be aware of and critically judge the music they listen to daily.
Effect of collagen cross-linkers on dentin bond strength: A systematic review and network meta-analysis
Authors: Chen Huan , Sun Guangdi , Wang Huimin , Yu Shiyang , Tian Zilu , Zhu Song
Published: January 2023

Objective: This study aimed to evaluate the role of collagen cross-linkers in the bonding performance of the resin-dentin interface through a systematic review and a network meta-analysis.

Sources: The literature search was conducted in several databases like PubMed, EMBASE, Cochrane, Scopus and Web of Science from their inception till 30 April 2022.

Study selection: The inclusion criteria consisted of in vitro studies evaluating the micro-tensile and micro-shear bond strengths of different cross-linkers acting on dentin. Bayesian network meta-analysis was conducted using RStudio.

Data: Out of the 294 studies evaluated in the full-text analysis, 40 were included in the systematic review and meta-analysis. Most studies have used cross-linkers as primer (65.1%), followed by incorporating them into in adhesives and acid etching agents. The application methods of the adhesive system were classified as “etch-and-rinse (ER) adhesives” (77%) and “self-etching (SE) adhesives”. Moreover, there were six types of cross-linkers in this presented review, of which the most numerous were polyphenols.

Conclusion: Different application methods of cross-linkers, the long-term results showed that were only effective when used for longer durations, the immediate results were not statistically different. According to immediate and long-term results, etch-and-rinse (ER) adhesives showed a greater bonding performance than the control groups (p ≤ 0.05), whereas self-etching (SE) adhesives showed similar bond strength values (p ≥ 0.05). The result of network meta-analysis (NMA) showed that Dope like compound showed higher long-term bonding performance than other cross-linkers.

Clinical significance: Long-term clinical studies may be needed to determine the effect of the cross-linkers on the bonding properties.
Research progress of exosomes in pathogenesis, diagnosis, and treatment of ocular diseases
Authors: Feng Xinting , Peng Zhen , Yuan Lingyi , Jin Ming , Hu Haijian , Peng Xin , Wang Yaohua , Zhang Chun , Luo Zhiwen , Liao Hongfei
Published: January 2023

Exosomes are natural extracellular vesicles with a diameter of 30–150 nm, which exist in biological fluids and contain biomolecules related to the parent cell, such as proteins, nucleic acids, lipids, etc. It has a wide range of biological functions, and participates in the regulation of important physiological and pathological activities of the body. It can be used as a biomarker for early diagnosis of ocular diseases, a potential therapeutic target, a targeted drug carrier, and has a high potential for clinical application. In this paper, we summarized the genesis mechanism, biological functions, research and application progress of exosomes, focused on the engineering strategy of exosomes, and summarized the advantages and disadvantages of common engineering exosome preparation methods. Systematically combed the role of exosomes in corneal diseases, glaucoma, and retinal diseases, to provide a reference for further understanding of the role of exosomes in the pathogenesis, diagnosis, and treatment of ocular diseases. Finally, we further summarized the opportunities and challenges of exosomes for precision medicine. The extension of exosome research to the field of ophthalmology will help advance current diagnostic and therapeutic methods. Tiny exosomes have huge potential.
Intravenous AAV9 administration results in safe and widespread distribution of transgene in the brain of mini-pig
Authors: Lin Yingqi , Li Caijuan , Wang Wei , Li Jiawei , Huang Chunhui , Zheng Xiao , Liu Zhaoming , Song Xichen , Chen Yizhi , Gao Jiale , Wu Jianhao , Wu Jiaxi , Tu Zhuchi , Lai Liangxue , Li Xiao-Jiang , Li Shihua , Yan Sen
Published: January 2023

Animal models are important for understanding the pathogenesis of human diseases and for developing and testing new drugs. Pigs have been widely used in the research on the cardiovascular, skin barrier, gastrointestinal, and central nervous systems as well as organ transplantation. Recently, pigs also become an attractive large animal model for the study of neurodegenerative diseases because their brains are very similar to human brains in terms of mass, gully pattern, vascularization, and the proportions of the gray and white matters. Although adeno-associated virus type 9 (AAV9) has been widely used to deliver transgenes in the brain, its utilization in large animal models remains to be fully characterized. Here, we report that intravenous injection of AAV9-GFP can lead to widespread expression of transgene in various organs in the pig. Importantly, GFP was highly expressed in various brain regions, especially the striatum, cortex, cerebellum, hippocampus, without detectable inflammatory responses. These results suggest that intravenous AAV9 administration can be used to establish large animal models of neurodegenerative diseases caused by gene mutations and to treat these animal models as well.
Research progress and application of artificial intelligence in thyroid associated ophthalmopathy
Authors: Diao Jiale , Chen Xinxin , Shen Ya , Li Jian , Chen Yuqing , He Linfeng , Chen Sainan , Mou Pei , Ma Xiaoye , Wei Ruili
Published: January 2023

Thyroid-associated ophthalmopathy (TAO) is a complicated orbitopathy related to dysthyroid, which severely destroys the facial appearance and life quality without medical interference. The diagnosis and management of thyroid-associated ophthalmopathy are extremely intricate, as the number of professional ophthalmologists is limited and inadequate compared with the number of patients. Nowadays, medical applications based on artificial intelligence (AI) algorithms have been developed, which have proved effective in screening many chronic eye diseases. The advanced characteristics of automated artificial intelligence devices, such as rapidity, portability, and multi-platform compatibility, have led to significant progress in the early diagnosis and elaborate evaluation of these diseases in clinic. This study aimed to provide an overview of recent artificial intelligence applications in clinical diagnosis, activity and severity grading, and prediction of therapeutic outcomes in thyroid-associated ophthalmopathy. It also discussed the current challenges and future prospects of the development of artificial intelligence applications in treating thyroid-associated ophthalmopathy.
How to Resolve the Maximum Valuable Information in Complex NIR Signal: A Practicable Method Based on Wavelet Transform
Authors: Chen Jing , Lu Xiaoquan
Published: January 2023

A key problem in the field of near infrared (NIR) spectrum study is to obtain the valuable information from the complex NIR signal. A maximum information extraction method based on Wavelet Transform (WT) is proposed in this paper for helping the relative researchers to resolve the signal. The results show that the method can serve as an effective tool for obtaining the maximum valuable information in NIR study.
Automated Synthesis of 18F-BCPP-EF {2-tert-Butyl-4-Chloro-5-{6-[2-(2[18F]fluoroethoxy)-Ethoxy]-Pyridin-3-ylmethoxy}-2H-Pyridazin-3-One for Imaging of Mitochondrial Complex 1 in Parkinson’s Disease
Authors: Kaur Tanpreet , Brooks Allen F. , Liddell Katherine M. , Henderson Bradford D. , Hockley Brian G. , Bohnen Nicolaas I. , Albin Roger L. , Scott Peter J. H.
Published: January 2023

Mitochondrial complex I (MC-I) is an essential component of brain bioenergetics and can be quantified and studied using positron emission tomography (PET). A specific high affinity 18F radiotracer for MC-I enables monitoring of neurodegenerative disease progression and pathology via PET imaging. To facilitate clinical research studies tracking MC-I activity in Parkinson’s disease and other neurodegenerative diseases, a fully automated synthesis of the recently described 2-tert-butyl-4-chloro-5-{6-[2-(2[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F] BCPP-EF, [18F]1) was developed. We report the first automated synthesis [18F]BCPP-EF using a green radiochemistry approach. The radiotracer was synthesized with good radiochemical yield, excellent radiochemical purity, and high molar activity.
Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
Authors: Luo Zhujun , He Hao , Tang Tiantian , Zhou Jun , Li Huifang , Seeram Navindra P. , Li Dongli , Zhang Kun , Ma Hang , Wu Panpan
Published: January 2023

We previously reported that the structural modifications of pentacyclic triterpenoids including oleanolic acid resulted in enhanced hyaluronidase inhibitory activity but whether this applies to other pentacyclic triterpenoids such as betulinic acid (BA) is unknown. Herein, we synthesized BA derivatives with an α,β-unsaturated ketene moiety and evaluated for their: 1) hyaluronidase inhibitory activity and, 2) anti-inflammatory effects against lipopolysaccharides (LPS) induced inflammation. Compared to BA, the BA derivatives exerted improved anti-hyaluronidase activity (26.3%–72.8% vs. 22.6%) and anti-inflammatory effects by reducing nitrite production in BV2 cells (3.9%–46.8% vs. 3.4%) and RAW264.7 cells (22.7%–49.2% vs. 20.4%). BA derivatives inhibited LPS-induced production of pro-inflammatory cytokines in THP-1 cells (15.2%–22.4%). BA derivatives also exerted promising anti-inflammatory effects against hyaluronic acid fragment induced nitrite production (8.6%–35.6%) in THP-1 cells. BA derivatives showed augmented anti-hyaluronidase and anti-inflammatory effects but further biological evaluations using in vivo models are warranted to confirm their efficacy.
Electrochemically stable tunnel-type α-MnO2-based cathode materials for rechargeable aqueous zinc-ion batteries
Authors: De Luna Yannis , Alsulaiti Asma , Ahmad Mohammad I. , Nimir Hassan , Bensalah Nasr
Published: January 2023

The purpose of this study is the synthesis of α-MnO2-based cathode materials for rechargeable aqueous zinc ion batteries by hydrothermal method using KMnO4 and MnSO4 as starting materials. The aim is to improve the understanding of Zn2+ insertion/de-insertion mechanisms. The as-prepared solid compounds were characterized by spectroscopy and microscopy techniques. X-ray diffraction showed that the hydrothermal reaction forms α-MnO2 and Ce4+-inserted MnO2 structures. Raman spectroscopy confirmed the formation of α-MnO2 with hexagonal MnO2 and Ce-MnO2 structures. Scanning electron microscopy (SEM) confirmed the formation of nanostructured MnO2 (nanofibers) and Ce-MnO2 (nanorods). The electrochemical performance of MnO2 was evaluated using cyclic voltammetry (CV), galvanostatic charge-discharge (GCD) tests in half-cells. CV results showed the reversible insertion/de-insertion of Zn2+ ions in MnO2 and Ce-MnO2. GCD cycling tests of MnO2 and Ce-MnO2 at 2500 mA/g demonstrated an impressive electrochemical performance, excellent cycling stability throughout 500 cycles, and high rate capability. The excellent electrochemical performance and the good cycling stability of MnO2 and Ce-MnO2 nanostructures by simple method makes them promising cathode materials for aqueous rechargeable zinc-ion batteries.
Computational investigation on the antioxidant activities and on the Mpro SARS-CoV-2 non-covalent inhibition of isorhamnetin
Authors: Spiegel Maciej , Ciardullo Giada , Marino Tiziana , Russo Nino
Published: January 2023

In the present work, we report a computational study on some important chemical properties of the flavonoid isorhamnetin, used in traditional medicine in many countries. In the course of the study we determined the acid-base equilibria in aqueous solution, the possible reaction pathways with the •OOH radical and the corresponding kinetic constants, the complexing capacity of copper ions, and the reduction of these complexes by reducing agents such as superoxide and ascorbic anion by using density functional level of theory Density Functional Theory. Finally, the non-covalent inhibition ability of the SARS-CoV-2 main protease enzyme by isorhamnetin was examined by molecular dynamics (MD) and docking investigation.
Pre-epidemic evolution of the MRSA USA300 clade and a molecular key for classification
Authors: Bianco Colleen M. , Moustafa Ahmed M. , O’Brien Kelsey , Martin Michael A. , Read Timothy D. , Kreiswirth Barry N. , Planet Paul J.
Published: January 2023

Introduction

USA300 has remained the dominant community and healthcare associated methicillin-resistant Staphylococcus aureus (MRSA) clone in the United States and in northern South America for at least the past 20 years. In this time, it has experienced epidemic spread in both of these locations. However, its pre-epidemic evolutionary history and origins are incompletely understood. Large sequencing databases, such as NCBI, PATRIC, and Staphopia, contain clues to the early evolution of USA300 in the form of sequenced genomes of USA300 isolates that are representative of lineages that diverged prior to the establishment of the South American epidemic (SAE) clade and North American epidemic (NAE) clade. In addition, historical isolates collected prior to the emergence of epidemics can help reconstruct early events in the history of this lineage.

Methods

Here, we take advantage of the accrued, publicly available data, as well as two newly sequenced pre-epidemic historical isolates from 1996, and a very early diverging ACME-negative NAE genome, to understand the pre-epidemic evolution of USA300. We use database mining techniques to emphasize genomes similar to pre-epidemic isolates, with the goal of reconstructing the early molecular evolution of the USA300 lineage.

Results

Phylogenetic analysis with these genomes confirms that the NAE and SAE USA300 lineages diverged from a most recent common ancestor around 1970 with high confidence, and it also pinpoints the independent acquisition events of the of the ACME and COMER loci with greater precision than in previous studies. We provide evidence for a North American origin of the USA300 lineage and identify multiple introductions of USA300 into South and North America. Notably, we describe a third major USA300 clade (the pre-epidemic branching clade; PEB1) consisting of both MSSA and MRSA isolates circulating around the world that diverged from the USA300 lineage prior to the establishment of the South and North American epidemics. We present a detailed analysis of specific sequence characteristics of each of the major clades, and present diagnostic positions that can be used to classify new genomes.
Past, current, and potential treatments for cryptosporidiosis in humans and farm animals: A comprehensive review
Authors: Khan Shahbaz M. , Witola William H.
Published: January 2023

The intracellular protozoan parasite of the genusCryptosporidiumis among the leading causes of waterborne diarrheal disease outbreaks throughout the world. The parasite is transmitted by ingestion of infective oocysts that are highly stable in the environment and resistant to almost all conventional disinfection methods and water treatments. Control of the parasite infection is exceedingly difficult due to the excretion of large numbers of oocysts in the feces of infected individuals that contaminate the environment and serve as a source of infection for susceptible hosts including humans and animals. Drug development against the parasite is challenging owing to its limited genetic tractability, absence of conventional drug targets, unique intracellular location within the host, and the paucity of robust cell culture platforms for continuous parasite propagation. Despite the high prevalence of the parasite, the only US Food and Drug Administration (FDA)-approved treatment ofCryptosporidiuminfections is nitazoxanide, which has shown moderate efficacy in immunocompetent patients. More importantly, no effective therapeutic drugs are available for treating severe, potentially life-threatening cryptosporidiosis in immunodeficient patients, young children, and neonatal livestock. Thus, safe, inexpensive, and efficacious drugs are urgently required to reduce the ever-increasing global cryptosporidiosis burden especially in low-resource countries. Several compounds have been tested for bothin vitroandin vivoefficacy against the disease. However, to date, only a few experimental compounds have been subjected to clinical trials in natural hosts, and among those none have proven efficacious. This review provides an overview of the past and present anti-Cryptosporidiumpharmacotherapy in humans and agricultural animals. Herein, we also highlight the progress made in the field over the last few years and discuss the different strategies employed for discovery and development of effective prospective treatments for cryptosporidiosis.
Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis
Authors: Rosas Paola C. , Solaro R. John
Published: January 2023

The discovery that cardiac sarcomere proteins are substrates for S-glutathionylation and that this post-translational modification correlates strongly with diastolic dysfunction led to new concepts regarding how levels of oxidative stress affect the heartbeat. Major sarcomere proteins for which there is evidence of S-glutathionylation include cardiac myosin binding protein C (cMyBP-C), actin, cardiac troponin I (cTnI) and titin. Our hypothesis is that these S-glutathionylated proteins are significant factors in acquired and familial disorders of the heart; and, when released into the serum, provide novel biomarkers. We consider the molecular mechanisms for these effects in the context of recent revelations of how these proteins control cardiac dynamics in close collaboration with Ca2+ fluxes. These revelations were made using powerful approaches and technologies that were focused on thin filaments, thick filaments, and titin filaments. Here we integrate their regulatory processes in the sarcomere as modulated mainly by neuro-humoral control of phosphorylation inasmuch evidence indicates that S-glutathionylation and protein phosphorylation, promoting increased dynamics and modifying the Frank-Starling relation, may be mutually exclusive. Earlier studies demonstrated that in addition to cTnI as a well-established biomarker for cardiac disorders, serum levels of cMyBP-C are also a biomarker for cardiac disorders. We describe recent studies approaching the question of whether serum levels of S-glutathionylated-cMyBP-C could be employed as an important clinical tool in patient stratification, early diagnosis in at risk patients before HFpEF, determination of progression, effectiveness of therapeutic approaches, and as a guide in developing future therapies.
Cost-effectiveness of rhythm control strategy: Ablation versus antiarrhythmic drugs for treating atrial fibrillation in Korea based on real-world data
Authors: Kim Woojin , Kim Min , Kim Yun Tae , Park Woongbi , Kim Jin-bae , Kim Changsoo , Joung Boyoung
Published: January 2023

Background

Ablation-based treatment has emerged as an alternative rhythm control strategy for symptomatic atrial fibrillation (AF). Recent studies have demonstrated the cost-effectiveness of ablation compared with medical therapy in various circumstances. We assessed the economic comparison between ablation and medical therapy based on a nationwide real-world population.

Methods and findings

For 192,345 patients with new-onset AF (age ≥ 18 years) identified between August 2015 and July 2018 from the Korean Health Insurance Review and Assessment Service (HIRA) database, medical resource use data were collected to compare AF patients that underwent ablation (N = 2,131) and those administered antiarrhythmic drugs (N = 8,048). Subsequently, a Markov chain Monte Carlo model was built. The patients had at least one risk factor for stroke, and the base-case used a 20-year time horizon, discounting at 4.5% annually. Transition probabilities and costs were estimated using the present data, and utilities were derived from literature review. The costs were converted to US $ (2019). Sensitivity analyses were performed using probabilistic and deterministic methods. The net costs and quality-adjusted life years (QALY) for antiarrhythmic drugs and ablation treatments were $37,421 and 8.8 QALYs and $39,820 and 9.3 QALYs, respectively. Compared with antiarrhythmic drugs, incremental cost-effectiveness ratio of ablation was $4,739/QALY, which is lower than the willingness-to-pay (WTP) threshold of $32,000/QALY.

Conclusion

In symptomatic AF patients with a stroke risk under the age of 75 years, ablation-based rhythm control is potentially a more economically attractive option compared with antiarrhythmic drug-based rhythm control in Korea.
Glycation of LDL: AGEs, impact on lipoprotein function, and involvement in atherosclerosis
Authors: Poznyak Anastasia V. , Sukhorukov Vasily N. , Surkova Raisa , Orekhov Nikolay A. , Orekhov Alexander N.
Published: January 2023

Atherosclerosis is a complex disease, and there are many factors that influence its development and the course of the disease. A deep understanding of the pathological mechanisms underlying atherogenesis is needed to develop optimal therapeutic strategies and treatments. In this review, we have focused on low density lipoproteins. According to multiple studies, their atherogenic properties are associated with multiple modifications of lipid particles. One of these modifications is Glycation. We considered aspects related to the formation of modified particles, as well as the influence of modification on their functioning. We paid special attention to atherogenicity and the role of glycated low-density lipoprotein (LDL) in atherosclerosis.
The Need for Speed and Efficiency: A Brief Review of Small Molecule Antivirals for COVID-19
Authors: Puhl Ana C. , Lane Thomas R. , Urbina Fabio , Ekins Sean
Published: January 2023

While we currently have multiple highly effective vaccines approved for use against SARS-CoV-2 in the USA and other countries, there are far fewer small molecule antivirals approved to date. The emergence of the latest SARS-CoV-2 variant, Omicron which is heavily mutated in the spike protein, is also raising concerns about the effectiveness of these current vaccines and increasing the call for more therapeutic options. At the time of writing only remdesivir is approved by the FDA while molnupiravir (already approved in the United Kingdom) and Paxlovid (PF-07321332) have emergency use authorizations from the FDA. Repurposed molecules, such as dexamethasone and baricitinib, have been authorized for emergency use in some countries and are used in combination with remdesivir. After 2 years we are only now starting to see the progression of further molecules through animal models to assess their efficacy before clinical trials. As datasets accumulate from both in vitro and in vivo animal efficacy models, this may allow us to understand the physicochemical properties necessary for antiviral activity and enable the search for additional antivirals. We now summarize 25 small molecule drugs that are either approved, in the process of approval or in the pipeline for COVID which have both in vitro and in vivo data. We demonstrate that these drugs are structurally diverse and cover a wide chemistry space. This information may aid our understanding of what it takes to be a promising treatment for COVID-19 and propose how to discover antivirals faster and more efficiently for the next pandemic.
Stepwise correction of ECMWF ensemble forecasts of severe rainfall in China based on segmented hierarchical clustering
Authors: Gao Li , Zhao Zuosen , Qin Jun , Chen Quanliang , Cai Hongke
Published: January 2023

Ensemble forecast plays a vital role in numerical weather prediction. Hence, effectively extracting useful information from ensemble members to improve precipitation forecasting skills has always been an important issue. Using the ensemble forecast data on precipitation from the ECMWF-GEPS (Global Ensemble Prediction System), we propose a stepwise correction method, based on segmented hierarchical clustering (SHC), for forecast of daily precipitation. This method employs a segmented correction scheme, thereby generating more probabilistic forecast information and improving forecasts. Validations of the SHC method have been performed by comparison with two other methods, namely the ensemble-mean (EM) method and the direct hierarchical clustering (HC) method. Our results showed that deterministic forecast via SHC improved the ability to forecast heavy precipitation in short- and medium-range forecast timeframes. Therefore, SHC performed better than either EM or HC by effectively extending lead time to impending severe rainfall by 2–3 days relative to the other two methods. SHC also demonstrated better performance than the other methods through continuous forecast verification in summer 2021, and even had better effects in the forecast of multiple heavy-precipitation cases, including the Zhengzhou extreme rainfall on 20 July 2021. Overall, the SHC method has great potential for improving ensemble rainfall forecasts in the current operational system.
Coupling fraction model to interpret the motion of non-fully coupled strike-slip faults
Authors: Zou Zhenyu , Jiang Zaisen , Wu Yanqiang , Cui Yueju , Tang He
Published: January 2023

Despite coupling fractions being extensively used in the interseismic period, the coexistence of locking and creeping mechanisms and the correlation between the coupling fraction and locking depth remain poorly understood because of the lack of a physical model. To overcome these limitations, in this study, we propose a coupling fraction model for interpreting the motion of non-fully coupled strike-slip faults based on the classic two-dimensional strike-slip fault model and the superposition principle. The model was constructed using numerous tiny, alternating creeping and locking segments. The deformation produced by the model is the same as that of the classic two-dimensional strike-slip fault, except for the scale factor. The model and definition of the coupling fraction can be perfectly integrated. Based on the model, we put forward a varying decoupled fraction with depth model, which considers the depth-dependent coupling fraction. The two models provide deep insights into the deformation characteristics of quasi-arctangent curves produced by non-fully coupled strike-slip faults and the local and macroscopic characteristics of fault locking in the interseismic period.
The nature and controls on downstream change of channel sediment along the Shiyang River, Northwest China
Authors: Li Ping , Gao Hongshan , Yan Tianqi , Li Zongmeng , Wu Yajie , Liu Fenliang
Published: January 2023

The grain size composition and distribution of river sediments are important for understanding regional geomorphological evolution, source-sink processes and drainage ecology. The Shiyang River basin, an inland river system in northwestern China, provides an environmental context within which to investigate the relationship between sediment particle size and environmental factors. Based on the analysis of the grain size characteristics of modern riverbed sediments, basin geomorphological parameters and lithology, it is found that the median grain size (Md) of river sediments shows a decrease trend from upstream to downstream in the basin. One of the tributaries named the Jinta River shows an obvious downstream fining trend (exponentially decreasing) of Md, which is related to the old geomorphological development stages and relatively homogeneous lithology in the basin. The downstream fining trend of Md along the Xiying River, another tributary, shows complex fluctuations, which might be affected by the tectonically active, young geomorphic development stage, complex lithology of the basin, and the sediment confluence of tributaries. The gravel-sand transition zone occurs in the plain section of the river about 28 km out of the mountain, which is related to the combination of regional geomorphological features, river morphology and hydraulic sorting.
Effects of bariatric surgery on testosterone level and sexual function in men with obesity: A retrospective study
Authors: Chen Guoji , Sun Luping , Jiang Shuwen , Chen Xiaomei , Zhu Jie , Zhao Xin , Yu Shuqing , Dong Zhiyong , Chen Yuan , Zhang Wen , Yang Wah , Wang Cunchuan
Published: January 2023

Introduction

Bariatric surgeries induce well-documented weight loss and resolve obesity comorbidities. Sexual function is one of the aspects of life quality and may benefit from surgery. Few studies have revealed the impact of bariatric surgeries on sexual function in Chinese men with obesity.

Methods

This is a retrospective cohort study of patients undergoing bariatric surgery [laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB)]. Data were collected between September 2017 and February 2022. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate erectile function, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Sex hormones and other blood tests were evaluated before and at least 1 year after the surgery.

Results

Fifty-nine Chinese male patients completed the IIEF questionnaire. The multivariate logistic regression analysis revealed that body mass index (BMI) was the single independent risk factor of the severity of erectile dysfunction (ED). Preoperative testosterone levels had negative correlations with BMI and waist circumference. Thirty-seven patients completed the postoperative questionnaire with a mean follow-up of 23.2 months.

Conclusion

BMI and waist circumference were negatively correlated with testosterone levels. BMI was an independent risk factor for the severity of ED. LSG and LRYGB led to positive and sustained improvement in sexual function of men with obesity. The two procedures had a comparable effect, more subjects being needed. Sex hormone levels also could be reversible. However, more weight loss did not predict a positive change in sexual function. A greater BMI loss might predict a greater increase in testosterone.
The Role of Depletion of Gut Microbiota in Osteoporosis and Osteoarthritis: A Narrative Review
Authors: Guan Zhiyuan , Luo Liying , Liu Shengfu , Guan Zhiqiang , Zhang Qinggang , Li Xu , Tao Kun
Published: January 2023

Osteoporosis and osteoarthritis are common diseases in an aging society, are considered metabolic diseases, and affect the quality of life of older adults. In addition, the gut microbiome is considered an additional organ to regulate bone metabolism. In the past decade, people have been studying the relationship between gut microbiota and bone metabolism. The role and mechanism of the gut microbiota in regulating bone metabolism is very important to improve the development of osteoporosis and osteoarthritis. Depletion of the gut microbiota as a method of studying the role of the gut microbiota was provided strategies to enhance the role of the gut microbiota in regulating osteoporosis and osteoarthritis. In this review, we discuss how depletion of the gut microbiota affects osteoporosis and osteoarthritis.