bluuebunny/crossref_metadata_2025 huggingface dataset:
Administrative Liability for Violations of Fire Safety Requirements at Rental Facilities
Authors: Shatokhin A. Yu.
Published: January 2021

The article examines the issue of administrative liability of the lessee and the lessor for violations of fire safety requirements in the existing legal regime for leasing buildings (premises). The urgency of the issue under study is substantiated based, first of all, on the existing contradictory judicial practice. The article analyzes the normative legal acts of the Russian Federation that regulate rental legal relations and administrative liability for violation of fire safety requirements, examines specific law enforcement acts, including those of the Constitutional and Supreme Court of the Russian Federation, studies publications of foreign authors on similar issues. The position of a number of judicial authorities on the impossibility of changing the public obligations of the parties to fulfill the fire safety requirements established by the legislation of the Russian Federation by a lease agreement that regulates only their civil obligations is criticized. The study revealed the characteristic features of a lease agreement, such as: direct transfer of things for temporary possession and use, or for temporary use; the temporary nature of the parties' agreement; concessionality of the contract. Considered, proposed by a number of authors, the classification of fire safety requirements into capital (constructive) and regime (operational, functional) and their author's definitions of these terms, based on the results of which their artificiality and incorrectness are justified. The Author has developed a law-based dichotomous classification and corresponding terminology. The possibility of classifying all fire safety requirements into social and technical requirements has been substantiated. It is proposed to consider as social requirements a set of legal norms that establish the rules of human behavior, the procedure for organizing production and (or) maintaining territories, buildings, structures, premises of organizations in order to ensure fire safety. The requirements of a technical nature should include a set of legal norms aimed at protecting people and property from the effects of hazardous fire factors directly related to the structural space-planning features of premises, buildings, technological equipment installed in it, and engineering systems. The following conceptual thesis has been formulated – the lessor is obliged to fulfill at his own expense the fire safety requirements of a technical nature established for the leased property, and the lessee is obliged to maintain the property in good condition, bear the cost of its maintenance and comply with fire safety requirements of a social nature, unless otherwise provided law, other legal acts or lease agreement. The author proposes to reflect the issue of the division of administrative responsibility between the lessee and the lessor at the level of the Supreme Court of the Russian Federation, in the next review of judicial practice.
An efficient image cryptography mechanism based on the hybridization of standard encryption algorithms
Authors: Ranjan Vivek , Patidar Kailash , Kushwaha Rishi
Published: January 2021

In our approach the combination of RC4 and Blowfish algorithms with chaos mapping (RC4BC) has been presented for the image encryption. In the first phase image dataset has been considered. Then weight values have been calculated based on the image pixels. It has been calculated based on the attribute pixel, corelated pixels and the analytical factors of the edges. Then substitution has been performed through RC4 encryption mechanism. The substitution has been performed based on 8 sub blocks for the first time. After that different random substation has been applied based on the reallocation of bytes up to 16 rounds. Final substitution has been performed by the blowfish and chaos mapping. By this method the pixels of the images are rotated and shuffled with the XOR operation along with 16-byte reshuffling in each iteration. A total of 50 rounds have been considered for the shuffling, rotation and mapping. Then for comparative analysis peak signal to noise ratio (PSNR) and mean square error (MSE) have been calculated. Our results show that it is efficient in terms of MSE and PSNR values.
TATHWIR MANHAJ TA'LIIM AL LUGAH AL 'ARABIYYAH AL ITTISOLIYYAT BI DAAR MUHIBBI AL 'ARABIYYAH AL JAAMI'AH AL ISLAMIYYAH AL HUKUUMIYYAH PEKALONGAN
Authors: Rosyid M. Fairuz , Syahid Nur
Published: January 2021

The purpose of this research to examine the development ofcommunicative curriculum conducted by arabic institutions Dar MuhibAl-‘Arobiyah. The data were collected through correspondence anddocumentation. The method of this research is qualitative, the data analysisuses data triangulation, that is: data reduction, data presentation, andconclusion. The primary data sources in this study were teachers, students,and curriculum documents. The result of this research can be concluded thatthe development of communicative arabic language Dar Muhibbi al ’Arabiyyahstated not effective. It cause the methods, media, and evaluations used thatare used not relevant to the communicative objectives that have been decided.The Methods, media, and evaluations are more directed to memorizing manyvocabulary thah the practice of using sentences in dialogue. Suggestions: 1)The communicative learning focused on the process of producing senteceswith multiplying conversations; 2)The asatidz/teachers to apply the processof developing curriculum by existing frameworks example, Hilda Tabamodel.
ALTERNATIF PEMBELAJARAN MAHARAH QIRA’AH DENGAN KISAH-KISAH DALAM AL-QUR’AN
Authors: Robbani A. Syahid , Haqqy Ahmad Muzayyan
Published: January 2021

To realize the effective learning of reading skills, of course, it takesmedia or good learning materials. That way, learning of reading skills willnot feel boring for teachers or students. One of the alternatives that can beused in learning of reading skills is the stories in the Qur’an that are full ofeducational values. This research aims to find alternative learning of readingskills with stories in the Qur’an. This research is a type of library research.The results of this study show that with perfection and privilege in terms oflanguage that the Qur’an has, allows everyone to delve into this especially inArabic learning, especially reading skills. This can be applied in the learningof reading skills by practicing reading (converting the symbol of writing intosound) and understand what is in the reading with the stories in the Qur’an.Both aspects are very important in reading skills. Among the stories in theQur’an that can be used as an alternative in the learning of reading skills isthe story of the patience of the prophet ‘Ayyub in surah Al-Anbiya’ verses83-84, the story of the obedience of the prophet Ibrahim and the prophetIshmael in surah As-Shaffat verses 100-111, the story of the prophet Musawho helped two women drink his cattle in surah Al-Qashash verses 21-24 andthe story of Qarun who was so arrogant that the earth was swallowed upin surah Al-Qashash verses 76-86. Other stories contained in the Qur’an canalso still be used as the alternative learning of reading skills while sticking tothe goal of learning to be achieved.
PENGARUH KEFASIHAN MEMBACA AL-QUR’AN TERHADAP KETERAMPILAN MEMBACA PADA BIDANG STUDI BAHASA ARAB
Authors: Junaidi Junaidi , Mulianah Baiq
Published: January 2021

This study aims to determine the effect of fluency in readingal-quran on reading skills in Arabic for Class X MA. Yusuf Abdussatar,Kediri Village, Kediri District, West Lombok. This approach is quantitativeresearch, because the data collected is in the form of numbers. In this study,there are several instruments that researchers use in collecting the requiredresearch data, including: (1) Observation guidelines / guides, this can be inthe form of columns containing the variables to be observed. (2) Interviewguidelines, namely. A collection of questions made as a guide in interviewingrespondents. (3) Questionnaire, namely, a data collection tool in the formof written questions addressed to respondents. (4) Documentation, namely,a data collection tool in the form of columns containing the situation andconditions of the research object. The data analysis used is the CausalComprativ study, which is used to explain the correlation or relationshipbetween two variables. The conclusion from the results of this study isthat there is an effect of reading fluency in the Qur’an on reading skills inthe field of study in Arabic for Class X MA. Yusuf Abdussatar Kediri, WestLombok, 2019-2020 Academic Year. This is evidenced by the number thatthe researcher got after conducting the research with the results obtained byrcount is (0.041) while the r table tested at a significant level of 5% with thetotal population (N) = 20 is 0, 012. This fact shows that rcount is greater thanr table (0.014> 0.012) thus the correlation value obtained from this study issignificant.
Current and future trends in periodontal tissue engineering and bone regeneration
Authors: Galli Matthew , Yao Yao , Giannobile William V. , Wang Hom-Lay
Published: January 2021

Periodontal tissue engineering involves a multi-disciplinary approach towards the regeneration of periodontal ligament, cementum and alveolar bone surrounding teeth, whereas bone regeneration specifically applies to ridge reconstruction in preparation for future implant placement, sinus floor augmentation and regeneration of peri-implant osseous defects. Successful periodontal regeneration is based on verifiable cementogenesis on the root surface, oblique insertion of periodontal ligament fibers and formation of new and vital supporting bone. Ultimately, regenerated periodontal and peri-implant support must be able to interface with surrounding host tissues in an integrated manner, withstand biomechanical forces resulting from mastication, and restore normal function and structure. Current regenerative approaches utilized in everyday clinical practice are mainly guided tissue/bone regeneration-based. Although these approaches have shown positive outcomes for small and medium-sized defects, predictability of clinical outcomes is heavily dependent on the defect morphology and clinical case selection. In many cases, it is still challenging to achieve predictable regenerative outcomes utilizing current approaches. Periodontal tissue engineering and bone regeneration (PTEBR) aims to improve the state of patient care by promoting reconstitution of damaged and lost tissues through the use of growth factors and signaling molecules, scaffolds, cells and gene therapy. The present narrative review discusses key advancements in PTEBR including current and future trends in preclinical and clinical research, as well as the potential for clinical translatability.
Meningkatkan Motivasi Belajar Siswa Melalui Penerapan Model Discovery Learning Kelas VIII-A SMPN 2 Piani
Authors: Apriyadi Ahmad , Sukmawati R Ati
Published: January 2021

Penelitian ini bertujuan untuk meningkatkan motivasi belajar dan hasil belajar siswa kelas VIII-A SMPN 2 Piani melalui model discovery learning. Penelitian ini merupakan  Penelitian Tindakan Kelas (PTK). Siklus I terdiri dari dua kali pertemuan, dan siklus II terdiri dari tiga kali pertemuan. Subjek penelitian ini adalah siswa kelas VIII-A SMPN 2 Piani, yang terdiri dari 9 orang siswa laki-laki dan 11 orang siswa perempuan. Objek penelitan adalah motivasi belajar dan hasil belajar siswa dalam pembelajaran tekanan zat dengan menerapkan model discovery learning. Instrumen penelitian terdiri dari lembar observasi motivasi belajar siswa dan tes hasil belajar. Berdasarkan hasil penelitian diperoleh bahwa motivasi siswa dari siklus I dan siklus II mengalami peningkatan, dari kurang termotivasi menjadi termotivasi. Hasil Belajar siswa kelas VIII-A juga mengalami kenaikan ketuntasan belajar pada siklus I mencapai 65% selanjutnya pada siklus II menjadi 95% (melebihi batas ketuntasan klasikal= 80%). Sehingga model pembelajaran discovery learning dapat dijadikan salah satu cara untuk meningkatkan motivasi dan hasil belajar siswa.This study aims to improve learning motivation and student learning outcomes in class VIII-A at SMPN 2 Piani through a discovery learning model. This study is a classroom tidiness study. Cycles I are two encounters and cycles II are three encounters. The study was done by applying the discovery learning model. Action class consists of twenty pullings of research subjects made up nine male students and eleven female students. The object of research is the motivation to learn and the results of students degrees in the pressure of learning by applying the discovery learning model. The research instrument consisted of learning motivation sheets and learning achievement tests. Based on the research results, it was found that the motivation of students from cycle I and cycle II had increased, from less motivated to be motivated. Learning outcomes of class VIII-A students also experienced an increase in learning completeness in the first cycle reaching 65%; then in the second cycle, it became 95% (exceeding the classical completeness limit = 80%). So the discovery learning model can be a way to increase the motivation and learning result.
Pengembangan Bahan Ajar Suhu dan Kalor Menggunakan Pembelajaran Generatif
Authors: Hidayat Ahmad , Zainuddin Zainuddin , Misbah Misbah
Published: January 2021

Penelitian bertujuan untuk menghasilkan bahan ajar suhu dan kalor menggunakan pembelajaran generatif yang layak digunakan dalam proses pembelajaran. Tujuan penelitian secara khusus yaitu untuk mendeskripsikan: 1) validitas bahan ajar, 2) kepraktisan bahan ajar, dan 3) efektivitas bahan ajar. Penelitian ini merupakan pengembangan bahan ajar menggunakan model ADDIE, dengan subjek uji coba 23 siswa kelas XI MIPA 2 SMA Negeri 12 Banjarmasin. Data penelitian diperoleh dari lembar validasi, lembar pengamatan keterlaksanaan RPP, dan tes hasil belajar. Hasil penelitian menunjukkan bahwa: 1) validitas bahan ajar berkategori tinggi, 2) kepraktisan bahan ajar berkategori sangat praktis, dan 3) efektivitas bahan ajar berkategori sedang. Disimpulkan bahwa bahan ajar suhu dan kalor menggunakan pembelajaran generatif layak digunakan dalam proses pembelajaran pada materi suhu dan kalor di tingkat SMA. Hasil penelitian ini digunakan sebagai rekomendasi bagi guru dan calon guru dalam memilih bahan ajar yakni dengan menggunakan pembelajaran generatif.The research aims to produce heat and temperature teaching materials using generative learning suitable for the learning process. The purpose of the research is to describe: 1) the validity of teaching materials, 2) the practicality of teaching materials, 3) the effectiveness of teaching materials, and 4) reduction of students' misconceptions. This research uses the ADDIE model, with the test subjects 23 students of class XI MIPA 2 high school 12 Banjarmasin. The research data were obtained from validation sheets, observation sheets of the lesson plans' implementation, and learning achievement tests. The results showed that: 1) the validity of teaching materials is high category, 2) the practicality of very practical categorical teaching materials, and 3) the effectiveness of medium categorized teaching materials. It was concluded that the temperature and heat teaching material using generative learning was feasible to be used in the learning process on the temperature and heat material at the high school level.
Pengembangan LKPD Berbasis STEM untuk Melatihkan Keterampilan Proses Sains Siswa Melalui Inkuiri Terbimbing
Authors: Mahjatia Nanda , Susilowati Eko , Miriam Sarah
Published: January 2021

Penelitian ini dilatar belakangi oleh belum terlatihnya keterampilan proses sains peserta didik di salah satu sekolah di Kota Banjarmasin. Tujuan penelitian ini untuk mengembangkan Lembar Kerja Peserta didik (LKPD) berbasis STEM untuk melatihkan keterampilan proses sains dan mendeskripsikan kelayakan yang dilihat dari:1) Validitas LKPD; 2) Kepraktisan LKPD; 3) Efektivitas LKPD; 4) Pencapaian keterampilan proses sains; dan 5) Pencapaian STEM.  Metode Penelitian dan Pengembangan digunakan dalam penelitian ini melalui tahap pengembangan model ADDIE dengan objek uji coba 22 peserta didik kelas XI MIPA 2 dan subjek LKPD berbasis STEM bertempat di salah satu sekolah di kota Banjarmasin. Hasil Penelitian ini menunjukkan: 1) Validitas LKPD berkategorikan valid. 2) LKPD yang dikembangkan dinyatakan praktis, karena angket respon dari peserta didik berkategorikan praktis. 3) Efektivitas LKPD yang dikembangkan diukur dari N-gain dimana nilai dari N-gain yang didapat berkategorikan sedang yang berarti efektif. 4) Pencapaian KPS melalui LKPD berbasis STEM yang didapat secara keseluruhan sangat baik dan mengalami peningkatan disetiap pertemuan. 5) Pencapaian STEM melalui LKPD berbasis STEM yang didapat secara keseluruhan sangat baik dan mengalami peningkatan disetiap pertemuan. Disimpulkan bahwa LKPD berbasis STEM untuk melatihkan keterampilan proses sains peserta didik layak digunakan dalam proses pembelajaran di tingkat SMA.This research was motivated by the untrained science process skills of students in a school in Banjarmasin City. The purpose of this study was to develop STEM-based student worksheets to train science process skills and describe the feasibility as seen from 1) the validity of the student worksheets; 2) practicality of student worksheets; 3) The effectiveness of student worksheets; 4) Achievement of science process skills; and 5) Achievement of STEM. The Research and Development method used in this study through the ADDIE model development stage with the test object of 22 students of class XI MIPA 2 and STEM-based student worksheets subjects located in one of the schools in the city Banjarmasin. The results of this study indicate: 1) The validity of student worksheets is categorized as valid. 2) The developed student worksheets were declared practical because the students' response questionnaire was categorized as practical. 3) The effectiveness of the developed student worksheets is measured from the N-gain where the N-gain value is categorized as a medium, which means effective. 4) The overall achievement of science process skills through STEM-based student worksheets is very good and has increased in every meeting. 5) Achievement of STEM through STEM-based student worksheets which is as a whole, is very good and has increased in every meeting. It was concluded that the STEM-based student worksheets to train students' science process skills was appropriate for use in the learning process at the high school level.
Pengembangan Bahan Ajar Model Quantum Teaching pada Materi Fluida Statis untuk Melatih Keterampilan Proses Sains Siswa
Authors: Ramadhan Taufik , Arifuddin Muhammad , Mastuang Mastuang
Published: January 2021

Tujuan penelitian ini ialah menghasilkan produk pengembangan bahan ajar model quantum teaching pada materi fluida statis untuk melatih keterampilan proses sains siswa. Subjek untuk penelitian ini merupakan siswa kelas XI MIPA 2 di SMAN 12 Banjarmasin sebanyak 25 siswa. Penelitian ini merupakan penelitian pengembangan dengan menggunakan model pengembangan ADDIE. Pengumpulan data penelitian dilakukan dengan teknik observasi dan tes. Hasil dari penelitian menunjukkan bahwa 1) Hasil validasi bahan ajar memperoleh nilai rata-rata dalam kategori valid; 2) Kepraktisan bahan ajar berdasarkan keterlaksanaan rencana pelaksanaan pembelajaran memperoleh kategori sangat praktis; 3) Efefektivitas bahan ajar berdasarkan tes hasil belajar memperoleh kategori sedang; dan 4) Pencapaian keterampilan proses sains berkategori sangat baik. Simpulan dari penelitian ini bahwa bahan ajar model quantum teaching  pada materi fluida statis layak digunakan untuk melatih keterampilan proses sains siswa.This research aims to produce a product, namely the quantum teaching model of teaching materials on static fluid material to train students' science process skills. The subjects for this research were 25 students of class XI MIPA 2 at SMAN 12 Banjarmasin. This research is development research using the ADDIE development model. Research data collection was carried out by observation and test techniques. The study results indicate that 1) The results of the validation of teaching materials obtain an average value in the valid category 2). The material's practicality based on the feasibility of the lesson plan implementation gets a very practical category 3). The effectiveness of teaching materials based on the learning result test obtained the medium category 4). The achievement of science process skills was categorized as very good. This research concludes that the quantum teaching model teaching materials on static fluid material are suitable for training students' science process skills.
Analysis of Expression Profiles of mRNA and lncRNA in Oviduct During Estrus Phase of Sheep (Ovis Aries) with Two Fecundity (FecB Gene) Genotypes
Authors: Chen Weihao , Li Zhifeng , Sun Wei , Chu Mingxing
Published: January 2021

Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.
COVID-19 plasma deep proteome reveals distinct signatures in severe patients
Authors: Suvarna Kruthi , Biswas Deeptarup , Pai Medha Gayathri J , Acharjee Arup , Bankar Renuka , P. Viswanthram , Salkar Akanksha , Verma Ayushi , Mukherjee Amrita , Choudhury Manisha , Ghantasala Saicharan , Ghosh Susmita , Singh Avinash , Banerjee Arghya , Badaya Apoorva , Bihani Surbhi , Mantri Krishi , Burli Ananya , Roy Jyotirmoy , Srivast Alisha , Agrawal Sachee , Shrivastav Om , Shastri Jayanthi , Srivast Sanjeeva
Published: January 2021

Prognosis and management of COVID-19 severity is a challenge even after months of the pandemic. Host plasma proteome alterations carry insights into the physiological alterations in response to the infection. Here we employed a mass spectrometry-based label-free quantitative proteomics approach to study alteration in plasma proteome in a cohort of 73 patients (20 COVID negative, 18 non-severe, and 33 severe) to understand the disease dynamics for addressing this challenge. Of the 1200 proteins detected in the patient plasma, 38 proteins were differentially expressed between non-severe and severe groups. The host proteins such as Angiotensinogen, apolipoprotein B, SERPINA3, SERPING1, and Fibrinogen gamma chain identified in LFQ analysis were further validated using targeted mass spectrometry assay. Utilizing our proteomics dataset, we identified multiple drugs that could inhibit the upregulated proteins involved in disease pathogenesis of these 2 FDA-approved drugs Selinexor and Ponatinib, which showed promise of being re-purposed for potential therapeutics of COVID-19. Plasma proteome identified significant dysregulation in the pathways related to peptidase activity, regulated exocytosis, blood coagulation, complement activation, leukocyte activation involved in immune response, and response to glucocorticoid biological processes during severe SARS-CoV-2 infection. Further, the results suggest that COVID-19 severity can be prognosticated using specific biomarkers of severity, and few of these proteins are excellent targets for re-purposed drugs.
Effect of Metformin on the Epigenetic Age of Peripheral Blood in Patients With Diabetes Mellitus (DM)
Authors: Li Man , Duan Lei , Cai Yulun , Hao Benchuan , Chen Jianqiao , Liu Hongbin
Published: January 2021

Background: Metformin has been proved to have anti-aging effect. However, studies on how metformin affects global epigenetic regulation and its effect on the epigenetic clock in the diabetes mellitus (DM) patients is limited. This study aims to investigate the impact of metformin on the epigenetic age in subjects with type 2 DM.Methods: We collected the peripheral blood of metformin group and the no metformin group of the 32 DM patients. Epigenetic clock was used to estimate the epigenetic age acceleration of the two groups.Results: The results were presented as the following: 1) the metformin slow down the epigenetic age of the DM patients by an average of 2.77 years. 2) we observed a significant enrichment in the regulation of histone methyl-transferase activity (H3K9 specific) 3) we identified 144 differentially methylated positions (DMPs), the top 20 cytosine–guanine dinucleotides (CpGs) and their associate genes with the most consistent changes in the DNA methylation profile were selected: EPM2AIP1, MUC17, FNDC1, HLA-DOB, TRPC4, ESRRB, ADCY2. The major functions of most top-level differential methylation sites and the cellular signaling pathways they represent are related to aging process.Conclusions: Here we demonstrated that metformin could perform an anti-aging effect by slow down the epigenetic clock.
Burden of Oral Anticoagulation in Embolic Stroke of Undetermined Source without Atrial Fibrillation
Authors: Witte Klaus , Tsivgoulis Georgios , Reynolds Matthew , Tsintzos Stelios , Eggington Simon , Ismyrloglou Eleni , de Brouwer Bonnie , Lyon Julie , Huynh Marianne , Egea Marta , Ziegler Paul , Franco Noreli , Joglekar Rashmi , Rosemas Sarah , Liu Shufeng , Thijs Vincent
Published: January 2021

Objective: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies.Methods: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective.Results: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient’s lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5,953-£7,018 per patient (UK), €6,683-€7,368 (Netherlands), €4,933-€9,378 (Spain), AUD$5,353-6,539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $1,716-$12,473 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years).Conclusions: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.
Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses
Authors: Lu Rong , CONTRERAS-TRUJILLO HUMBERTO , EERDENG JIYA , AKRE SAMIR , JIANG DU , JORAPUR APARNA , VERGEL-RODRIGUEZ MARY , ANDREASIAN AREEN , HARTON LISA , Bramlett Charles , GALA BASIA , Nogalska Anna , Chan Lai , Xiao Gang , LEE JAE-WOONG , MÜSCHEN MARKUS , MERCHANT AKIL
Published: January 2021

Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression signatures respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover an unexpected yet common form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression signatures. Our integrated system directly and effectively interrogates the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV
Authors: Giron Leila , Palmer Clovis , Liu Qin , Yin Xiangfan , Papasavvas Emmanouil , Damra Mohammad , Goldman Aaron , Tang Hsin-Yao , Johnston Rowena , Mounzer Karam Mounzer , Kostman Jay , Tebas Pablo , Landay Alan , Montaner Luis , Jacobson Jeffrey , Li Jonathan , Abdel-Mohsen Mohamed
Published: January 2021

Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74-76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.
Impact of Lenvatinib on Renal Function: Long-term Analysis of Differentiated Thyroid Cancer Patients
Authors: Masaki Chie , Sugino Kiminori , Kobayashi Sakiko , Hosoi Yoshie , Ono Reiko , Yamazaki Haruhiko , Akaishi Junko , Hames Kiyomi , Tomoda Chisato , Suzuki Akifumi , Matsuzu Kenichi , Ohkuwa Keiko , Kitagawa Wataru , Nagahama Mitsuji , Ito Koichi
Published: January 2021

Background: Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern for patients with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed. Method: This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated. Results: The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n=6), ≥60 by <90 mL/min/1.73 m2 (n=26), and ≥45 but <60 mL/min/1.73 m2 (n=8). Grade 3 proteinuria was associated with decline in eGFR (p=0.0283). Long observation period was also associated with a decrease in eGFR (p=0.0115), indicating that eGFR may decrease in a time-dependent manner. Conclusion: Lenvatinib can induce decline in eGFR, especially with treatment duration >2 years, regardless of baseline eGFR. Proteinuria is a risk factor for decline in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making must balance the benefits of lenvatinib continuation with allowed harm.
Normal reference intervals of prognostic nutritional index in healthy adults: A large multi-center observational study from Western China
Authors: Yang Guishu , Wang Dongsheng , Zu Ruiling , He Linbo , Zhang Guangjie , Yu Jianhong , Chen Yaping , Yin Hailin , Liao Yulin , Li Shi , Deng Yao , Zhang Kaijiong , Li Tian , Zhu Guiquan , Luo Huaichao
Published: January 2021

Background

It has been widely reported that the prognostic nutritional index (PNI) played a pivotal role in nutritional assessment of surgical patients and tumor prognosis. In order to improve the accuracy of evaluation in western China, we established reference intervals (RIs) of PNI in healthy controls.
Methods

A retrospective cohort study on healthy ethnic Han adults (18–79 years) was conducted to explore the influences of age, gender, study centers, and instruments on PNI and to establish RIs. The data came from a healthy routine examination center database and laboratory information system (LIS) of four centers in western China, and there were 200 persons selected randomly for verification of RIs.
Results

5,839 healthy candidates were enrolled. PNI showed a marked gender dependence, and males had significantly higher PNI than females across all ages (P < 0.01). We found that PNI is significantly different between age groups (P < 0.01), the value of PNI tended to decrease with age increasing. There is also an obvious influence of centers and instruments on PNI (P < 0.01).
Conclusions

We established reference intervals of PNI in healthy Han Chinese population in Western China, and validated successfully. Further established RIs will lead to better standardizations of PNI for clinical applications.
Projected shifts in loggerhead sea turtle habitat in the Northwest Atlantic Ocean due to climate change
Authors: Patel Samir , Winton Megan , Hatch Joshua , Haas Heather , Saba Vincent , Fay Gavin , Smolowitz Ronald
Published: January 2021

It is well established that sea turtles are vulnerable to atmospheric and oceanographic shifts associated with climate change. However, few studies have formally projected how their seasonal marine habitat may shift in response to warming ocean temperatures. Here we used a high-resolution global climate model and a large satellite tagging dataset to project changes in the future distribution of suitable thermal habitat for loggerheads along the northeastern continental shelf of the United States. Between 2009 and 2018, we deployed 196 satellite tags on loggerheads within the Middle Atlantic Bight (MAB) of the Northwest Atlantic continental shelf region, a seasonal foraging area. Tag location data combined with depth and remotely sensed sea surface temperature (SST) were used to characterize the species’ current thermal range in the MAB. The best-fitting model indicated that the habitat envelope for tagged loggerheads consisted of SST ranging from 11.0° - 29.7° C and depths between 0 – 105.0 m. The calculated core habitat consisted of temperatures between 15.0° – 28.0° C and at depths between 8.0 – 92.0 m and the highest probability of presence occurred in regions with SST between 17.7° – 25.3° C and at depths between 26.1 – 74.2 m. The habitat suitability model was then forced by a high-resolution global climate model under a doubling of atmospheric CO2 to project loggerhead probability of presence over the next 80 years. Our results suggest that loggerhead thermal habitat and seasonal duration will likely increase in northern regions of the NW Atlantic shelf. This change in spatiotemporal range for sea turtles in a region of high anthropogenic use may prompt adjustments to the localized protected species conservation measures.
Qualitative Interviews on The Diagnosis Process of Hepatitis B Among 50 Patients in Chongqing, China
Authors: zhou xiangxi , zhang fan , Ao yong , lu chun , li ting , xu xiang , zeng huan
Published: January 2021

Objective: To identify the obstacles preventing and controlling hepatitis B and put forward suggestions for its prevention and treatment by describing the discovery process of hepatitis B patients. Methods: We conducted face-to-face interviews with 50 hepatitis B patients in Chongqing, China from July to August 2019 by constructing a thematic analysis framework, which included interviewees’ social demographic characteristics, diagnosis approach, signs and symptoms at the time of discovery, feelings after diagnosis, and doctor’s instructions.Results: Most of the patients were firstly found hepatitis B via physical examination when patients were asymptomatic or had no obvious symptoms. The majority of them were shocked, frightened, and at a loss when they were diagnosed. The patients could remember doctor’s instructions on keeping healthy lifestyle, but they had very little impression about doctors’ reminding about regular liver function test. Failure of regular follow-up to liver function test brought irreversible loss for certain patients.Conclusions: Most of the patients were found hepatitis B passively. The patients need professional mental help after the diagnosis to overcome the negative emotion. The doctors’ instruction should emphasize more on the importance of regular follow-up to liver function test besides health lifestyle.
A Bibliometric Analysis of Researches on Flap Endonuclease 1 From 2005 to 2019
Authors: Wei Qiaochu , Shen Jiming , Wang Dongni , Han Xu , Shi Jing , Zhao Lei , Teng Yuee
Published: January 2021

Background: Flap endonuclease 1 (FEN1) is a structure-specific nuclease that plays a role in a variety of DNA metabolism processes. FEN1 is important for maintaining genomic stability and regulating cell growth and development. It is associated with the occurrence and development of several diseases, especially cancers. There is a lack of systematic bibliometric analyses focusing on research trends and knowledge structures related to FEN1.Purpose: To analyze hotspots, the current state and research frontiers performed for FEN1 over the past 15 years. Methods: Publications were retrieved from the Web of Science Core Collection (WoSCC) database, analyzing publication dates ranging from 2005 to 2019. VOSviewer1.6.15 and Citespace5.7 R1 were used to perform a bibliometric analysis in terms of countries, institutions, authors, journals and research areas related to FEN1. A total of 421 publications were included in this analysis. Results: Our findings indicated that FEN1 has received more attention and interest from researchers in the past 15 years. Institutes in the United States, specifically the Beckman Research Institute of City of Hope published the most research related to FEN1. SHEN BH，ZHENG L and BAMBARA RA were the most active researchers investigating this endonuclease and most of this research was published in the Journal of Biological Chemistry. The main scientific areas of FEN1 were related to biochemistry, molecular biology，cell biology，genetics and oncology. Research hotspots included biological activities, DNA metabolism mechanisms, protein-protein interactions and gene mutations. Research frontiers included oxidative stress, phosphorylation and tumor progression and treatment. Conclusion: This bibliometric study may aid researchers in the understanding of the knowledge base and research frontiers associated with FEN1. In addition, emerging hotspots for research can be used as the subjects of future studies.
Treatment of Atrophic Rhinitis with Manuka Honey–a non-randomized control trial, and a new theory of etiopathogenesis for the disease.
Authors: Sarkar Saurav , Purkait Suvendu , Maiti Rituparna , Sharma Prity , Venugopal Giriprasad , Mutha Naresh , Ramadass Balamurugan
Published: January 2021

Exact etiology of Atrophic rhinitis (AtR) is yet unknown. Polygenic and polybacterial causes have been implicated in the onset and progression of this disease. AtR doesn’t respond to any particular modality of treatment that targets specific etiology, this describes its multifactorial nature. In this study, we report on a non-randomized control trial on the use of a nasal spray of 10% Manuka honey in patients with AtR attending the out-patient unit of the Department of Otorhinolaryngology and Head Neck Surgery. In this study, we show significant observations: 1. Decreased fetid smell, 2. Thickening of the mucosa, 3. Decreased inflammation with healed mucosal ulcers, 4. Increased concentration of the mucosal glands, 5. Alteration in Nasal microbiome, and 6. Increased expression of SCFA receptors. These changes occurred in response to honey therapy, and are consequent to the resetting of the Nasal microbiome.
Predicting High Energy Density Materials using Abinitio Evolutionary Algorithms: The Results for N5AsF6
Authors: Benchafia El Mostafa , Wang Xianqin , Iqbal Zafar , Abedrabbo Sufian
Published: January 2021

N5AsF6 is the first successfully synthesized salt that has a polymeric nitrogen moeity (N5+). Although 12 other N5+ salts followed, with N5SbF6 and N5Sb2F11 being the most stable, the crystal structure of N5AsF6 remains unknown. Currently, it is impossible to experimentally determine the structures of N5AsF6 due to its marginal stability and explosive nature. Here, following an ab initio evolutionary prediction and using only the stoichiometry of N5AsF6 as a starting point, we were able to reveal the crystal structure of this high energy density material (HEDM). The C2V symmetry of the N5+ cation, as suggested from earlier investigations, is confirmed to be the symmetry adopted by this polymeric nitrogen within the crystal. This result gave full confidence in the validity of this crystal prediction approach. While stability of the N5+ within the crystal is found to be driven by electronic considerations, the marginal stability of this HEDM is found to be related to a partial softening of its phonon modes.
Cholinesterase activity in serum during general anesthesia in health and disease
Authors: Sinai Yitzhak Brzezinski , Zwang Ester , Plotnikova Elena , Halizov Esti , Shapira Itzhak , Zeltser David , Rogowski Ori , Berliner Shlomo , Matot Idit , Shenhar-Tsarfaty Shani
Published: January 2021

Atherosclerotic patients challenge the anesthesiologist as they display a significant instability between the two parts of the autonomic nervous system. We aimed to assess the effect of general anesthesia (GA) and surgery on serum cholinesterase activity. Prospective study of 57 patients undergoing ambulatory or vascular surgery under GA. Cholinesterase levels were measured before induction of anesthesia, 15 minutes thereafter and at the end of surgery by measuring the capacity of serum Acetylcholinesterase (AChE) and Butyrylcholinesterase to hydrolyze AcetylThioCholine. Data of atherosclerotic disease, anesthesia management were analyzed.Both AChE and total Cholinergic Status (CS) decreased significantly after GA induction at 15 minutes and furthermore by the end of surgery. Vascular surgery patients, presented lower baseline cholinesterase activity compared to patients for ambulatory surgery. In patients requiring intraoperative administration of phenylephrine for hemodynamic support (21.1%), a significant lower level of AChE and CS was observed compared to untreated patients. A positive correlation was found between the lowest temperatures measured and the AChE and CS change from the baseline values. Our findings serve as a mirror to the sympathetic/parasympathetic disbalance during GA with a marked decrease in the parasympathetic tone. Our data show that low cholinesterase activity increase the need for hemodynamic support.
A Novel External Fixator to Facilitate Accurate and Efficient Fracture Treatment
Authors: Shen Mingkui , Ai Zizheng , Li Jingna , Liang Huaping , Dong Xieping
Published: January 2021

Background: The rapid popularization and application of bone external fixation technology has led to external fixators emerging as remarkable methods to treat various complex fractures. Because of their instability, assembly complexity and poor controllability, however, new external fixators are challenging to design in terms of facilitating accurate and efficient fracture treatment.Methods: We designed a novel external fixator that could feasibly treat clinical complex fractures. A prospective study was conducted on patients with various complex fractures from September 2017 to September 2019. During this period, we treated 24 patients with a universal joint external fixator and then evaluated its therapeutic effects. In this study, adult cadaver femur fracture fixations were modelled by using universal joint (UJ) and AO external fixators, and the mechanical stability was assessed by applying a biomechanical testing device.Results: The designed device not only fits the repair site but could also be conveniently installed and implanted. All patients achieved good fixation and fracture healing with the universal joint fracture external fixators. In in vitro biomechanical testing, constructs were loaded under axial compression, lateral compression and torsion. Overall axial stiffness showed no significant differences between the two groups. The lateral stiffness was 1.554 ± 0.017 mm for the UJ group and 1.342 ± 0.020 mm for the AO group (p<0.001) under a 600 N load, while the torsional stiffness was 15.727 ± 0.141° for the UJ group and 14.472 ± 0.292° for the AO group under a 40 Nm load.Conclusion: In this small and preliminary study, the universal joint external fixator, which achieved a stable mechanical structure, was capable of intensive and efficient treatment for comprehensive fractures. If these findings can be confirmed in a larger study, this external fixator may be widely used in certain situations where traditional external fixators are not a convenient option.