bluuebunny/crossref_metadata_2025 huggingface dataset:
Penerapan SDLC Model Waterfall pada Rancang Bangun SI-PKP Direktorat Jenderal ILMATE Kementrian Perindustrian Jakarta
Authors: Hartati Tri , Anastia Nada , Widyastuti Reni
Published: November 2021

Direktorat Jenderal (Ditjen) ILMATE merupakan unit kerja di Kementerian Perindustrian yang mengelola bidang industri logam, mesin, alat transportasi dan elektronika. Pegawai Negeri Sipil (PNS) yang bekerja pada Direktorat Jenderal ILMATE merupakan pegawai yang diterima berdasarkan hasil seleksi ketat dari beberapa kandidat dan setelah diterima masih diperlukan pembinaan pegawai sehingga proses monitoring dan evaluasi menggunakan sistem penilaian yang objektif dan kuantitatif. Penelitian kali ini berpusat pada penilaian kinerja pegawai yang dianggap belum maksimal karena masih bersifat subjektif dimana penilaian diambil berdasarkan penilai interpersonal pejabat penilai dan hasil dari penilaian ini akan berpengaruh bagi PNS dari segi promosi kenaikan jabatan dan kenaikan gaji secara berkala. Penelitian ini bertujuan untuk merancang aplikasi SI-PKP (Sistem Informasi-Penilaian Kinerja Pegawai) yang memudahkan dalam sistem penilaian PNS pada Ditjen ILMATE dimana penilai dapat bersikap secara objektif dalam pengambilan keputusan sehingga diharapkan tidak merugikan PNS dalam hal penilaian kinerja personal. Dalam rancang bangun aplikasi SI-PKP ini, peneliti menggunakan model waterfall yang terdiri dari System Requirements Analysis, Design, Code Generation, Testing, Support And Maintenance.
Analisis dan Perancangan Sistem Informasi Pembelian, Penjualan dan Persediaan pada UD. Parjuma Sonari
Authors: Turnip Raelida , Salim Rin Rin Meilani , Handoko Handoko
Published: November 2021

Perkembangan teknologi yang begitu pesat dan persaingan bisnis yang semakin ketat memaksa suatu perusahaan menggunakan teknologi yang mampu mendukung kegiatan aktivitas kerja dengan cepat dan tepat. UD. Parjuma Sonari adalah salah satu perusahaan dagang yang melakukan pembelian, penjualan, dan pencatatan persediaan obat-obatan tani. Pada saat ini, proses bisnis yang berjalan pada UD. Parjuma Sonari masih melakukan pencatatan berbasis kertas yang menghambat proses bisnis yang berjalan. Penelitian ini bertujuan menganalisis dan merancang sistem informasi pembelian, penjualan, persediaan barang yang dapat mendukung proses operasional perusahaan. Metodologi yang digunakan dalam analisis dan perancangan ini adalah metodologi SDLC (System Development Life Cycle). Sistem informasi yang dirancang berbasis desktop menggunakan Microsoft Visual Studio 2015 dan SQL Server 2014. Rancangan proses menggunakan DFD (Data Flow Diagram). Hasil dari penelitian ini dapat disimpulkan bahwa analisis dan perancangan sistem informasi UD. Parjuma Sonari berguna sebagai rekomendasi terhadap sistem kedepannya yang dapat dijadikan sebagai landasan untuk pengembangan sistem usulan.
Aplikasi Mandarin Scrabble Game bagi Pemula dengan Algoritma Directed Acyclic Word Graph
Authors: Benny Leo , Monti Cico Valangi
Published: November 2021

Scrabble merupakan permainan papan dan permainan menyusun kata yang dimainkan 2 atau 4 orang yang mengumpulkan poin berdasarkan nilai kata yang dibentuk dari keping huruf di atas papan permainan berkotak-kotak (15 kolom dan 15 baris). Kebanyakan permainan scrabble menggunakan bahasa Indonesia ataupun bahasa Inggris. Namun, belum ada permainan scrabble yang menggunakan bahasa Mandarin. Metode yang digunakan untuk penyusunan kata dalam permainan Mandarin Scrabble ini adalah algoritma Directed Acyclic Word Graph (DAWG). Penelusuran kata pada DAWG seperti pada sebuah tree atau pohon data dimana setiap awalan dan akhiran digunakan bersama-sama untuk memperkecil jumlah ruang yang diperlukan untuk menyimpan kosa kata dan juga memperkecil waktu yang diperlukan untuk me-retrieve kata. Metode pengembangan sistem yang digunakan penelitian ini adalah metode waterfall dengan perangkat bantu yang digunakan untuk memodelkan sistem adalah flowchart diagram, activity diagram dan use case diagram. Aplikasi permainan Scrabble berbahasa Mandarin ini dapat digunakan untuk membantu pemakai dalam mempelajari mengenai cara pelafalan (pembacaan) dan mengenal intonasi dari karakter dalam bahasa Mandarin. Aplikasi permainan Mandarin Scrabble ini akan terdiri dari beberapa bagian, yaitu proses pengenalan karakter Mandarin, dimana pemain akan diberikan sebuah karakter Mandarin dan pemain harus menyusun pelafalan atau intonasi yang tepat dalam pinyin dari karakter Mandarin tersebut.
Prediksi Customer Churn Pada Bisnis Retail Menggunakan Algoritma Naïve Bayes
Authors: Yulianto Agus , Firmansyah Firmansyah
Published: November 2021

Perusahaan retail seperti toko dan sejenisnya pada umumnya memiliki data customer yang menjadi anggota belanja dengan tujuan untuk menjalin hubungan yang saling menguntungkan antara customer dan toko, namun data customer seringkali tidak dikelola dan dianalisa dengan baik sehingga menyebabkan customer retail berhenti belanja di toko tersebut atau berpindah ke toko lain. Untuk dapat memprediksi kehilangan pelanggan, dibutuhkan model algoritma yang dapat memprediksi customer churn dengan akurat dan presisi. Untuk melakukan prediksi, maka dibuat model algoritma dengan naïve bayes dengan tujuan untuk memprediksi kemungkinan customer churn sehingga toko dapat melakukan tindakan preventif. Data customer diambil dengan klasifikasi yaitu jenis kelamin, grade point, kepemilikan kartu kredit, rentang usia, nilai rata-rata transaksi dan lama menjadi anggota. Data training dan testing dimasukkan ke dalam pemodelan naïve bayes dengan menghasilkan akurasi 80%. Naïve bayes terbukti dapat memprediksi kemungkinan customer churn berdasarkan data dan klasifikasi sehingga hasilnya dapat menjadi pendukung keputusan bisnis.
Pengaruh Disiplin Kerja dan Kompetensi terhadap Kinerja Dosen AMIK Medicom
Authors: Br Sembiring Dinaria
Published: November 2021

Penelitian ini dilakukan untuk mengetahui bagaimana pengaruh disiplin kerja (X1) dan kompetensi (X2) terhadap kinerja dosen (Y) pada Akademi  Manajemen Informatika Komputer  Medicom. Jenis penelitian yang digunakan adalah explanatory research melalui penelitian asosiatif, yaitu penelitian yang bertujuan  untuk menjelaskan pengaruh  antara dua variabel atau lebih. Populasi dalam penelitian ini adalah seluruh dosen Akademi Manajemen Informatika dan Komputer Medicom Medan  berjumlah 35 orang. Metode  pengumpulan data dilakukan  dengan kuesioner . studi kepustakaan, dan observasi. Analisis data dilakukan  dalam penelitian ini adalah uji hipotesis dengan uji t (uji parsial) dan uji F (uji simultan). Hasil penelitian ini diperoleh bahwa : (1) berdasarkan uji parsial disiplin kerja Berpengaruh terhadap kinerja Dosen pada Akademi Manajemen Informatika  Komputer Medicom dengan uji t sebesar 3.724. (2) Berdasarkan uji parsial Kompetensi berpengaruh terhadap kinerja Dosen Akademi Manajemen Informatika Komputer Medicom  dengan uji t sebesar 4.065 (3) Berdasarkan uji Simultan  bengaruh disiplin kerja dan kompetensi terhadap kinerja Dosen AMIK Medicom dengan uji F sebesar 54.416.
Biological effects of two successive shock-waves focused on liver tissue and melanoma cells
Authors: Beneš J , Šunka P , Králová J , Kašpar J , Poučková P
Published: November 2021

A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes.
Mechanical response of porous scaffolds for cartilage engineering
Authors: Jančář J , Slovíková A , Amler E , Krupa P , Kecová H , Planka L , Gal P , Nečas A
Published: November 2021

Mechanical properties of scaffolds seeded with mesenchymal stem cells used for cartilage repair seem to be one of the critical factors in possible joint resurfacing. In this paper, the effect of adding hyaluronic acid, hydroxyapatite nanoparticles or chitosan nanofibers into the cross-linked collagen I on the mechanical response of the lyophilized porous scaffold has been investigated in the dry state at 37 oC under tensile loading. Statistical significance of the results was evaluated using ANOVA analysis. The results showed that the addition of hyaluronic acid significantly (p<<0.05) reduced the tensile elastic modulus and enhanced the strength and deformation to failure of the modified cross-linked collagen I under the used test conditions. On the other hand, addition of hydroxyapatite nanoparticles and chitosan nanofibers, respectively, increased the elastic modulus of the modified collagen ten-fold and four-fold, respectively. Hydroxyapatite caused significant reduction in the ultimate deformation at break while chitosan nanofibers enhanced the ultimate deformation under tensile loading substantially (p<<0.05). The ultimate tensile deformation was significantly (p<<0.05) increased by addition of the chitosan nanofibers. The enhanced elastic modulus of the scaffold was translated into enhanced resistance of the porous scaffolds against mechanical load compared to scaffolds based on cross-linked neat collagen or collagen with hyaluronic acid with similar porosity. It can be concluded that enhancing the rigidity of the compact scaffold material by adding rigid chitosan nanofibers can improve the resistance of the porous scaffolds against compressive loading, which can provide more structural protection to the seeded mesenchymal stem cells when the construct is implanted into a lesion. Moreover, scaffolds with chitosan nanofibers seemed to enhance cell growth compared to the neat collagen I when tested in vitro as well as the scaffold stability, extending its resorption to more than 10 weeks.
In vitro study of reactive oxygen species production during photodynamic therapy in ultrasound-
pretreated cancer cells
Authors: Kolářová H , Bajgár R , Tománková K , Krestyn E , Doležal L , Hálek J
Published: November 2021

Several recent studies bring evidence of cell death enhancement in photodynamic compound loaded cells by ultrasonic treatment. There are a number of hypotheses suggesting the mechanism of the harmful ultrasonic effect. One of them considers a process in the activation of photosensitizers by ultrasonic energy. Because the basis of the photodynamic damaging effect on cells consists in the production of reactive oxygen species (ROS), we focused our study on whether the ultrasound can increase ROS production within cancer cells. Particularly, we studied ROS formation in ultrasound pretreated breast adenocarcinoma cells during photodynamic therapy in the presence of chloroaluminum phthalocyanine disulfonate (ClAlPcS2). Production of ROS was investigated by the molecular probe CM-H2DCFDA. Our results show that ClAlPcS2 induces higher ROS production in the ultrasound pretreated cell lines at a concentration of 100 microM and light intensity of 2 mW/cm2. We also observed a dependence of ROS production on photosensitizer concentration and light dose. These results demonstrate that the photodynamic effect on breast cancer cells can be enhanced by ultrasound pretreatment.
Biological effects of noble gases
Authors: Růžička J , Beneš J , Bolek L , Markvartová V
Published: November 2021

Noble gases are known for their inertness. They do not react chemically with any element at normal temperature and pressure. Through that, some of them are known to be biologically active by their sedative, hypnotic and analgesic properties. Common inhalation anesthetics are characterized by some disadvantages (toxicity, decreased cardiac output, etc). Inhalation of xenon introduces anesthesia and has none of the above disadvantages, hence xenon seems to be the anesthetic gas of the future (with just one disadvantage - its cost). It is known that argon has similar anesthetic properties (under hyperbaric conditions), which is much cheaper and easily accessible. The question is if this could be used in clinical practice, in anesthesia of patients who undergo treatment in the hyperbaric chamber. Xenon was found to be organ-protective. Recent animal experiments indicated that xenon decreases infarction size after ischemic attack on brain or heart. The goal of our study is to check if hyperbaric argon has properties similar to those of xenon.
Biochemical and biophysical aspects of collagen nanostructure in the extracellular matrix
Authors: Koláčná L , Bakešová J , Varga F , Košťáková E , Lukáš D , Amler E , Pelouch V
Published: November 2021

ECM is composed of different collagenous and non-collagenous proteins. Collagen nanofibers play a dominant role in maintaining the biological and structural integrity of various tissues and organs, including bone, skin, tendon, blood vessels, and cartilage. Artificial collagen nanofibers are increasingly significant in numerous tissue engineering applications and seem to be ideal scaffolds for cell growth and proliferation. The modern tissue engineering task is to develop three-dimensional scaffolds of appropriate biological and biomechanical properties, at the same time mimicking the natural extracellular matrix and promoting tissue regeneration. Furthermore, it should be biodegradable, bioresorbable and non-inflammatory, should provide sufficient nutrient supply and have appropriate viscoelasticity and strength. Attributed to collagen features mentioned above, collagen fibers represent an obvious appropriate material for tissue engineering scaffolds. The aim of this minireview is, besides encapsulation of the basic biochemical and biophysical properties of collagen, to summarize the most promising modern methods and technologies for production of collagen nanofibers and scaffolds for artificial tissue development.
Derivation of sonograph quality parameters by the use of Point Spread Function analysis
Authors: Doležal L , Mazura J , Tesařík J , Kolářová H , Korpas D , Binder S , Hálek J
Published: November 2021

A measuring system evaluating a Point Spread Function generated in an ultrasonographic image by scanning a spherical target was developed. The target is moved in measuring bath filled by water over scanned volume via 3D computer controlled positioning system. A video signal obtained is converted to digital form and analyzed by original software to derive various objective parameters of the imager as follows: Focal areas in both the azimuth and the elevation directions, Ultrasound scanning lines visualisation, Manufacturer preloaded TGC, Width of the scanning plane, Side lobe levels and Amplification uniformity in the azimuth direction. The method was verified by testing 18 different equipments in 282 measurements. Samples of particular measurement results in form of graphical outputs are included. Medical and physiological impacts of this approach are discussed.
Impedance spectroscopy of bilayer lipid membranes self-assembled on agar support – interaction with HDL
Authors: Legiň M , Laputková G , Sabo J , Vojčíková L
Published: November 2021

The electrical properties of the supported lipid bilayer membrane (s-BLM) of egg phosphatidylcholine (PC) self-assembled on agar surface were examined. To characterize the insulating properties of s-BLMs, electrochemical impedance spectroscopy (EIS) was used. The analysis of impedance spectra in terms of an equivalent circuit of agar/electrolyte and agar/s-BLM/electrolyte in the frequency range of 0.1 Hz-10 kHz was performed. The high-density lipoproteins (HDL)/s-BLM interaction in the concentration range from 20 microg/ml to 80 microg/ml of HDL was investigated. It is evident that treatment of s-BLM with HDL resulted in an increase of the lipid film resistance and a decrease of membrane capacitance.
Use of 3D geometry modelling of osteochondrosis-like iatrogenic lesions as a template for press-and-fit scaffold seeded with mesenchymal stem cells
Authors: Krupa P , Kršek P , Javorník M , Dostál O , Srnec R , Usvald D , Prokš P , Kecová H , Amler E , Jančář J , Gal P , Planka L , Nečas A
Published: November 2021

Computed tomography (CT) is an effective diagnostic modality for three-dimensional imaging of bone structures, including the geometry of their defects. The aim of the study was to create and optimize 3D geometrical and real plastic models of the distal femoral component of the knee with joint surface defects. Input data included CT images of stifle joints in twenty miniature pigs with iatrogenic osteochondrosis-like lesions in medial femoral condyle of the left knee. The animals were examined eight and sixteen weeks after surgery. Philips MX 8000 MX and View workstation were used for scanning parallel plane cross section slices and Cartesian discrete volume creation. On the average, 100 slices were performed in each stifle joint. Slice matrices size was 512 x 512 with slice thickness of 1 mm. Pixel (voxel) size in the slice plane was 0.5 mm (with average accuracy of +/-0.5 mm and typical volume size 512 x 512 x 100 voxels). Three-dimensional processing of CT data and 3D geometrical modelling, using interactive computer graphic system MediTools formerly developed here, consisted of tissue segmentation (raster based method combination and 5 % of manual correction), vectorization by the marching-cubes method, smoothing and decimation. Stifle- joint CT images of three individuals of different body size (small, medium and large) were selected to make the real plastic models of their distal femurs from plaster composite using rapid prototyping technology of Zcorporation. Accuracy of the modeling was +/- 0.5 mm. The real plastic models of distal femurs can be used as a template for developing custom made press and fit scaffold implants seeded with mesenchymal stem cells that might be subsequently implanted into iatrogenic joint surface defects for articular cartilage-repair enhancement.
Dependence of the vulnerability index on the heart cycle length
Authors: Martinka J , Kozlíková K
Published: November 2021

Index of vulnerability is a parameter based on ventricular gradient evaluating the risk of arrhythmia development. The index is derived from isointegral maps of the QT interval. Individual characteristics of isointegral maps are influenced by different factors, which contribute to the relatively high variability among measured parameters of maps in measured subjects. While several electrocardiographic indexes have been introduced, there are only few studies of their dependence on heart rate. In this study we set out to establish the dependence of vulnerability index on the RR interval or heart rate in healthy population. A positive linear correlation between RR intervals and mean and minimum values of vulnerability indexes was found.
Noninvasive assessment of local myocardium repolarization changes using high-resolution surface ECG mapping
Authors: Tyšler M , Kneppo P , Turzová M , Švehlíková J , Karas S , Hebláková E , Hána K , Filipová S
Published: November 2021

A method using body surface potential maps for assessment of myocardium lesions with changed repolarization is presented and suitable mapping system is introduced. Differences between normal and altered QRST integral maps together with torso volume conductor model were used to determine the equivalent dipole representing the lesion. Performance of the method was studied on simulated data. Changed repolarization was modeled by shortening of myocyte action potentials in regions typical for stenosis of the main coronary arteries. The equivalent dipole estimated the positions of small lesions with a mean error of 9+/-4 mm (17+/-14 mm for larger transmural lesions). The subepicardial or subendocardial character of the lesions was reflected in the dipole orientation. Tests of the method on patients after myocardial infarction that underwent coronary intervention on a single coronary vessel showed that in 7 of 8 successfully treated patients the dipole position matched well with the treated vessel. A small dipole moment in another patient indicated unsuccessful treatment. The method was implemented in a new 128-channel mapping system. Its active electrodes, battery powered measuring unit and optical computer interface help to minimize noise in ECG and guarantee patient's safety. The results suggest that the method and mapping system offer useful tools for noninvasive identification of local repolarization changes in the myocardium.
Comparative modeling of the H4-H5 loop of the α2-isoform of Na+/K+-ATPase α-subunit in the
E1 conformation
Authors: Tejral G , Koláčná L , Kotyk A , Amler E
Published: November 2021

Restraint-based comparative modeling was used for calculation and visualization of the H4-H5-loop of Na+/K+-ATPase from mouse brain (Mus musculus, adult male brain, alpha2-isoform) between the amino acid residues Cys 336 and Arg 758 in the E1 conformation The structure consists of two well separated parts. The N-domain is formed by a seven-stranded antiparallel beta-sheet with two additional beta-strands and five alpha-helices sandwiching it, the P-domain is composed of a typical Rossman fold. The ATP-binding site was found on the N-domain to be identical in both alpha2- and alpha1-isoforms. The phosphorylation Asp 369 residue was found in the central part of the P-domain, located at the C-terminal end of the central beta-sheet. The distance between the alpha-carbon of Phe 475 at the ATP-binding site and the alpha-carbon of Asp 369 at the phosphorylation site is 3.22 nm. A hydrogen bond between the oxygen atom of Asp 369 and the nitrogen atom of Lys 690 was clearly detected and assumed to play a key role in maintaining the proper structure of the phosphorylaton site in E1 conformation.
O FUTURO DO EMPREGO E O PROFISSIONAL DO FUTURO
Authors: Ramos Mota Junior José Dimas , Maria Andrade Brisola Elisa
Published: November 2021

P

Pensar no profissional do futuro tem sido uma das principais preocupações individuais e coletivas nos últimos anos. A indústria que até então era fonte dos “melhores” empregos, com o advento da 4ª Revolução Industrial, parece precisar cada vez menos da mão de obra humana. Nesse contexto, o Fórum Econômico Mundial publicou, em 2018, o relatório intitulado “O Futuro dos Empregos”, no qual compila dados e opiniões dos maiores empregadores mundiais acerca do futuro dos empregos, as exigências e adaptações necessárias para atender aos requisitos da 4ª Revolução Industrial. As análises e cenários traçados tinham um horizonte temporal de 5 anos (2018-2022), porém após o início da crise, em decorrência da pandemia de COVID-19, um novo relatório foi publicado com o mesmo nome, formato e horizonte de tempo (2020-2025). Esse artigo utiliza a metodologia de pesquisa bibliográfica para trazer uma leitura crítica do relatório de 2018, bem como sua comparação com o relatório de 2020. Os dados contidos nos relatórios com relação ao Brasil são colocados para um recorte local e identificação da situação nacional.  Conclui-se que os dados dos dois relatórios são uteis para as análises, contudo em uma análise crítica questiona-se a abrangência dos grupos pesquisados, assim como a perspectiva positiva do relatório de 2018, reduzida em 2020 ainda que mantido o viés positivo. Por fim, ponderamos que os problemas que a 4ª Revolução Industrial já vem causando pelo mundo podem se agravar, principalmente em países como o Brasil que tem historicamente questões como por exemplo a desigualdade social que pode se aprofundar no contexto estudado.
ENFERMEIRO AUDITOR: O PROCESSO DE SOCIALIZAÇÃO NA ESCOLHA PROFISSIONAL
Authors: Da Silva Monteiro Magali Beatris , Boccara De Paula Maria Angela
Published: November 2021

A escolha profissional consiste em um momento de grande responsabilidade, na qual muitos jovens podem vivenciar este processo com grande dificuldade e incerteza. Lembrar momentos vividos pode promover segurança no momento da decisão final, por isso objetivou-se conhecer as influências dos processos de socialização, primária e secundária na trajetória profissional de uma enfermeira auditora (EA). Foi realizado um estudo de caso, a partir de uma pesquisa biográfica-narrativa, aprovada pelo CEP-UNITAU sob o número 2.975.245, com abordagem qualitativa, no vale do Paraíba paulista. Para a construção dos dados (auto)biográficos utilizou-se um formulário sociodemográfico e de formação da EA, e a entrevista biográfica, realizada em três momentos, a partir da seguinte questão desencadeadora: “Considerando que o processo de formação do enfermeiro constitui-se essencialmente para a prática assistencialista, conte-me como aconteceu sua trajetória profissional na AE?”. A análise da narrativa permitiu verificar que a escolha da profissão foi um incidente crítico na trajetória profissional da EA, que ocorreu aos 20 anos de idade e foi caracterizada como período de desenvolvimento pessoal e profissional em sua vida. Assim, os grupos de socialização, primária e secundária, não só influenciaram como definiram sua escolha pela carreira, na qual acontecimentos e pessoas marcantes se mostraram especialmente importantes ao longo de sua trajetória profissional.
Ry/Rk-Lex: A Computational Lexicon for Runyankore and Rukiga Languages
Authors: Sabiiti Bamutura David
Published: November 2021

Current research in computational linguistics and NLP requires the existence of language resources. Whereas these resources are available for only a few well-resourced languages, there are many languages that have been neglected. Among the neglected and / or under-resourced languages are Runyankore and Rukiga (henceforth referred to as Ry/Rk). In this paper, we report on Ry/Rk-Lex, a moderately large computational lexicon for Ry/Rk that we constructed from various existing data sources. Ry/Rk are two under-resourced Bantu languages with virtually no computational resources. About 9,400 lemmata have been entered so far. Ry/Rk-Lex has been enriched with syntactic and lexical semantic features, with the intent of providing a reference computational lexicon for Ry/Rk in other NLP (1) tasks such as: morphological analysis and generation; part of speech (POS) tagging; named entity recognition (NER); and (2) applications such as: spell and grammar checking; and cross-lingual information retrieval (CLIR). We have used Ry/Rk-Lex to dramatically increase the lexical coverage of previously developed computational resource grammars for Ry/Rk.
Very Necessary: The Meaning of Non-gradable Modal Adjectives in Discourse Contexts
Authors: Rajestari Maryam , Dobnik Simon , Cooper Robin , Karimi Aram
Published: November 2021

In this paper we provide a quantitative and qualitative analysis of meaning of allegedly non-gradable modal adjectives in different discourse contexts. The adjectives studied are essential, necessary, crucial and vital which are compared with a gradable modal adjective important. In our study sentences containing these adjectives were chosen from a large corpus together with their contexts. Then 120 English native speakers evaluated the meaning of these adjectives in a crowd-sourced study. Different types of contexts were chosen for this purpose. In some the adjectives were used as gradable with a modifier very while in others as non-gradable, without a modifier. We also modified the contexts by adding or removing the modifier very. The task for evaluators was to provide a replacement for adjectives for all the resulting contexts. From the replacements we are able to quantitatively evaluate the semantic potential of these contexts and what kind of adjectives they license.
Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer
Authors: Liu Taisheng , Guo Liyi , Liu Guihong , Hu Xiaoshan , Li Xiaoning , Zhang Jinye , Dai Zili , Yu Peng , Jiang Ming , Wang Jian , Zhang Jian
Published: November 2021

Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear.

Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors.

Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit.

Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.
Lanthanum Oxide Nickel Hydroxide Composite Triangle Nanosheets for Energy Density Asymmetric Supercapacitors
Authors: Duan Huiyu , Shi Mei , Zhang Mengfei , Feng Geyu , Liu Suli , Chen Changyun
Published: November 2021

Transition metal hydroxides are a kind of promising electrode material in electrochemical energy storage, but the poor conductivity limits their application. Lanthanides are good proton conductors and can usually improve the intrinsic conductivity of other materials. By integrating the merits of lanthanide elements and transition metal hydroxide, we designed lanthanum oxide nickel hydroxide composites (LONH) with unique ultrathin triangle nanosheet morphology via a controllable synthetic strategy for high-performance supercapacitors. When the LONH is used as positive electrode material in aqueous asymmetric supercapacitor, it reveals an energy density (107.8 W h kg−1 at 800 W kg−1), rate performance (86.9% retention at 4 kW kg−1) and outstanding cycle stability (more than 90% retention after 3,000 cycles). This work confirms that compositing La2O3 and Ni(OH)2 can significantly improve the supercapacitor performance of both pristine La2O3 and transition metal hydroxide composites. We hope this work would offer a good prospect for developing other lanthanide-transition metal hydroxide composites as an attractive class of electrode materials in electrochemical energy storage.
Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach
Authors: Chen Yuying , Zhang Mingming , Ding Xin , Yang Yougui , Chen Yujia , Zhang Qiang , Fan Yinwen , Dai Yang , Wang Junhong
Published: November 2021

Hookworm is one type of soil-transmitted helminth, which could exert an anti-inflammatory effect in human or animal host, which provides a beneficial possibility for the discovery of inflammatory-related disease interventions. The identification of hookworm-derived anti-inflammatory molecules is urgently needed for future translational research. The emergence of metabolomics has become a powerful approach to comprehensively characterize metabolic alterations in recent times. Herein, excretory and secretory products (ESPs) were collected from cultured adult worm, while small intestinal contents were obtained from Nippostrongylus brasiliensis (N. brasiliensis, Nb)-infected mice. Through ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) platform, metabolomics analysis was used to explore the identification of anti-inflammatory molecules. Out of 45 differential metabolites that were discovered from ESPs, 10 of them showed potential anti-inflammatory properties, which could be subclassed into amino acids, furanocoumarins, linear diarylheptanoids, gamma butyrolactones, and alpha-keto acids. In terms of intestinal contents that were derived from N. brasiliensis-infected mice, 14 out of 301 differential metabolites were discovered to demonstrate anti-inflammatory effects, with possible subclassification into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. Furthermore, nine of the differential metabolites appeared both in ESPs and infected intestinal contents, wherein four were proven to show anti-inflammation properties, namely, L-glutamine, glutamine (Gln), pyruvate, and alanine-Gln (Ala-Gln). In summary, we have provided a method for the identification and analysis of parasite-derived molecules with potential anti-inflammatory properties in the present study. This array of anti-inflammatory metabolites could provide clues for future evaluation and translational study of these anti-inflammatory molecules.
Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
Authors: Zhang Fuquan , Cao Hongbao , Baranova Ancha
Published: November 2021

Major depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze shared genetic variations between MDD and seven cardiovascular outcomes (coronary artery disease (CAD), heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, and pulse pressure measurement). Mendelian randomization analysis was used to uncover causal relationships between MDD and cardiovascular traits. By cross-trait meta-analysis, we identified a set of genomic loci shared between the traits of MDD and stroke. Putative causal genes for MDD and stroke were prioritized by fine-mapping of transcriptome-wide associations. Polygenic overlap analysis pointed toward substantial genetic variation overlap between MDD and CVD. Mendelian randomization analysis indicated that genetic liability to MDD has a causal effect on CAD and stroke. Comparison of genome-wide genes shared by MDD and CVD suggests 20q12 as a pleiotropic region conferring risk for both MDD and CVD. Cross-trait meta-analyses and fine-mapping of transcriptome-wide association signals identified novel risk genes for MDD and stroke, including RPL31P12, BORSC7, PNPT11, and PGF. Many genetic variations associated with MDD and CVD outcomes are shared, thus, pointing that genetic liability to MDD may also confer risk for stroke and CAD. Presented results shed light on mechanistic connections between MDD and CVD phenotypes.
Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study
Authors: Zhang Qiaoyun , Zhang Xiaoyu , Zhang Jie , Wang Biyan , Meng Xiaoni , Tian Qiuyue , Zhang Jinxia , Jiang Mengyang , Zhang Yiqiang , Zheng Deqiang , Wu Lijuan , Wang Wei , Wang Baoguo , Wang Youxin
Published: November 2021

Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality.

Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF.

Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909–1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834–1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966–1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966–1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965–1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973–1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178–1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = −0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445–5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056–4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288–13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data.

Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.
Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
Authors: Yang Shuheng , Zheng Wei , Yang Chen , Zu Ruowen , Ran Shiyu , Wu Huan , Mu Mingkun , Sun Simin , Zhang Nana , Thorne Rick F. , Guan Yichun
Published: November 2021

Objective

Supraphysiological hormone exposure, in vitro culture and embryo transfer throughout the in vitro fertilization-embryo transfer (IVF-ET) procedures may affect placental development. The present study aimed to identify differences in genomic expression profiles between IVF-ET and naturally conceived placentals and to use this as a basis for understanding the underlying effects of IVF-ET on placental function.

Methods

Full-term human placental tissues were subjected to next-generation sequencing to determine differentially expressed miRNAs (DEmiRs) and genes (DEGs) between uncomplicated IVF-ET assisted and naturally conceived pregnancies. Gene ontology (GO) enrichment analysis and transcription factor enrichment analysis were used for DEmiRs. MiRNA-mRNA interaction and protein-protein interaction (PPI) networks were constructed. In addition, hub genes were obtained by using the STRING database and Cytoscape. DEGs were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed miRNAs were validated through qRT-PCR.

Results

Compared against natural pregnancies, 12 DEmiRs and 258 DEGs were identified in IVF-ET placental tissues. In a validation cohort, it was confirmed that hsa-miR-204-5p, hsa-miR-1269a, and hsa-miR-941 were downregulation, while hsa-miR-4286, hsa-miR-31-5p and hsa-miR-125b-5p were upregulation in IVF-ET placentas. Functional analysis suggested that these differentially expressed genes were significantly enriched in angiogenesis, pregnancy, PI3K-Akt and Ras signaling pathways. The miRNA-mRNA regulatory network revealed the contribution of 10 miRNAs and 109 mRNAs while EGFR was the most highly connected gene among ten hub genes in the PPI network.

Conclusion

Even in uncomplicated IVF-ET pregnancies, differences exist in the placental transcriptome relative to natural pregnancies. Many of the differentially expressed genes in IVF-ET are involved in essential placental functions, and moreover, they provide a ready resource of molecular markers to assess the association between placental function and safety in IVF-ET offspring.
Comprehensive Analysis of N6-Methyladenosine (m6A) Methylation in Neuromyelitis Optica Spectrum Disorders
Authors: Yang Hong , Wu Yi-Fan , Ding Jie , Liu Wei , Zhu De-Sheng , Shen Xia-Feng , Guan Yang-Tai
Published: November 2021

Background: N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known.

Aims: To explore the mechanism of m6A in NMOSD patients.

Methods: This study assessed the m6A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m6A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m6A level. Differential m6A methylation genes were validated by MeRIP-qPCR.

Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling.

Conclusion: These findings demonstrate that differential m6A methylation may act on functional genes to regulate immune homeostasis in NMOSD.
PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer
Authors: Deng Mingxia , Peng Long , Li Jiamin , Liu Xiong , Xia Xichun , Li Guangqiang
Published: November 2021

Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.
Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy
Authors: Nunes João Paulo Silva , Andrieux Pauline , Brochet Pauline , Almeida Rafael Ribeiro , Kitano Eduardo , Honda André Kenji , Iwai Leo Kei , Andrade-Silva Débora , Goudenège David , Alcântara Silva Karla Deysiree , Vieira Raquel de Souza , Levy Débora , Bydlowski Sergio Paulo , Gallardo Frédéric , Torres Magali , Bocchi Edimar Alcides , Mano Miguel , Santos Ronaldo Honorato Barros , Bacal Fernando , Pomerantzeff Pablo , Laurindo Francisco Rafael Martins , Teixeira Priscila Camillo , Nakaya Helder I. , Kalil Jorge , Procaccio Vincent , Chevillard Christophe , Cunha-Neto Edecio
Published: November 2021

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes’ mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.
Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
Authors: Zhang Kexiong , Xu Lu , Cong Yu-Sheng
Published: November 2021

Idiopathic pulmonary fibrosis is an age-dependent progressive and fatal lung disease of unknown etiology, which is characterized by the excessive accumulation of extracellular matrix inside the interstitial layer of the lung parenchyma that leads to abnormal scar architecture and compromised lung function capacity. Recent genetic studies have attributed the pathological genes or genetic mutations associated with familial idiopathic pulmonary fibrosis (IPF) and sporadic IPF to telomere-related components, suggesting that telomere dysfunction is an important determinant of this disease. In this study, we summarized recent advances in our understanding of how telomere dysfunction drives IPF genesis. We highlighted the key role of alveolar stem cell dysfunction caused by telomere shortening or telomere uncapping, which bridged the gap between telomere abnormalities and fibrotic lung pathology. We emphasized that senescence-associated secretory phenotypes, innate immune cell infiltration, and/or inflammation downstream of lung stem cell dysfunction influenced the native microenvironment and local cell signals, including increased transforming growth factor-beta (TGF-β) signaling in the lung, to induce pro-fibrotic conditions. In addition, the failed regeneration of new alveoli due to alveolar stem cell dysfunction might expose lung cells to elevated mechanical tension, which could activate the TGF-β signaling loop to promote the fibrotic process, especially in a periphery-to-center pattern as seen in IPF patients. Understanding the telomere-related molecular and pathophysiological mechanisms of IPF would provide new insights into IPF etiology and therapeutic strategies for this fatal disease.