bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ECHO of Cartilage: In Silico Prediction of Combinatorial Treatments to Switch Between Transient and Permanent Cartilage Phenotypes With Ex Vivo Validation
Authors: Khurana Sakshi , Schivo Stefano , Plass Jacqueline R. M. , Mersinis Nikolas , Scholma Jetse , Kerkhofs Johan , Zhong Leilei , van de Pol Jaco , Langerak Rom , Geris Liesbet , Karperien Marcel , Post Janine N. 
Published: November 2021

A fundamental question in cartilage biology is: what determines the switch between permanent cartilage found in the articular joints and transient hypertrophic cartilage that functions as a template for bone? This switch is observed both in a subset of OA patients that develop osteophytes, as well as in cell-based tissue engineering strategies for joint repair. A thorough understanding of the mechanisms regulating cell fate provides opportunities for treatment of cartilage disease and tissue engineering strategies. The objective of this study was to understand the mechanisms that regulate the switch between permanent and transient cartilage using a computational model of chondrocytes, ECHO. To investigate large signaling networks that regulate cell fate decisions, we developed the software tool ANIMO, Analysis of Networks with interactive Modeling. In ANIMO, we generated an activity network integrating 7 signal transduction pathways resulting in a network containing over 50 proteins with 200 interactions. We called this model ECHO, for executable chondrocyte. Previously, we showed that ECHO could be used to characterize mechanisms of cell fate decisions. ECHO was first developed based on a Boolean model of growth plate. Here, we show how the growth plate Boolean model was translated to ANIMO and how we adapted the topology and parameters to generate an articular cartilage model. In ANIMO, many combinations of overactivation/knockout were tested that result in a switch between permanent cartilage (SOX9+) and transient, hypertrophic cartilage (RUNX2+). We used model checking to prioritize combination treatments for wet-lab validation. Three combinatorial treatments were chosen and tested on metatarsals from 1-day old rat pups that were treated for 6 days. We found that a combination of IGF1 with inhibition of ERK1/2 had a positive effect on cartilage formation and growth, whereas activation of DLX5 combined with inhibition of PKA had a negative effect on cartilage formation and growth and resulted in increased cartilage hypertrophy. We show that our model describes cartilage formation, and that model checking can aid in choosing and prioritizing combinatorial treatments that interfere with normal cartilage development. Here we show that combinatorial treatments induce changes in the zonal distribution of cartilage, indication possible switches in cell fate. This indicates that simulations in ECHO aid in describing pathologies in which switches between cell fates are observed, such as OA.
A Myo-Inositol-Inducible Expression System for Corynebacterium glutamicum and Its Application
Authors: Lu Nan , Zhang Chenglin , Zhang Wenjie , Xu Haoran , Li Yuhong , Wei Minhua , Meng Jing , Meng Yan , Wang Junzhe , Chen Ning 
Published: November 2021

Corynebacterium glutamicum is one of the important industrial microorganisms for production of amino acids and other value-added compounds. Most expression vectors used in C. glutamicum are based on inducible promoter (Ptac or Ptrc) activated by isopropyl-β-D-thiogalactopyranoside (IPTG). However, these vectors seem unsuitable for large-scale industrial production due to the high cost and toxicity of IPTG. Myo-inositol is an ideal inducer because of its non-toxicity and lower price. In this study, a myo-inositol-inducible expression vector pMI-4, derived from the expression vector pXMJ19, was constructed. Besides the original chloramphenicol resistance gene cat, multiple cloning sites, and rrnB terminator, the pMI-4 (6,643 bp) contains the iolRq cassette and the myo-inositol-inducible promoter PiolT1. The pMI-4 could stably replicate in the C. glutamicum host. Meanwhile, the non-myo-inositol degradation host strain C. glutamicumΔiolGΔoxiCΔoxiDΔoxiE for maintaining the pMI-4 was developed. Overexpression of hemAM and hemL using pMI-4 resulted in a significant accumulation of 5-aminolevulinic acid, indicating its potential application in metabolic engineering and industrial fermentation.
Macros to Quantify Exosome Release and Autophagy at the Neuromuscular Junction of Drosophila Melanogaster
Authors: Sanchez-Mirasierra Irene , Hernandez-Diaz Sergio , Ghimire Saurav , Montecinos-Oliva Carla , Soukup Sandra-Fausia 
Published: November 2021

Automatic quantification of image parameters is a powerful and necessary tool to explore and analyze crucial cell biological processes. This article describes two ImageJ/Fiji automated macros to approach the analysis of synaptic autophagy and exosome release from 2D confocal images. Emerging studies point out that exosome biogenesis and autophagy share molecular and organelle components. Indeed, the crosstalk between these two processes may be relevant for brain physiology, neuronal development, and the onset/progression of neurodegenerative disorders. In this context, we describe here the macros “Autophagoquant” and “Exoquant” to assess the quantification of autophagosomes and exosomes at the neuronal presynapse of the Neuromuscular Junction (NMJ) in Drosophila melanogaster using confocal microscopy images. The Drosophila NMJ is a valuable model for the study of synapse biology, autophagy, and exosome release. By use of Autophagoquant and Exoquant, researchers can have an unbiased, standardized, and rapid tool to analyze autophagy and exosomal release in Drosophila NMJ.Code available at: https://github.com/IreneSaMi/Exoquant-Autophagoquant
Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]-pyrazole–Based RalA Inhibitors Against Hepatocellular Carcinoma
Authors: Wang Yuting , He Mingyao , Li Xiang , Chai Jinlong , Jiang Qinglin , Peng Cheng , He Gu , Huang Wei 
Published: November 2021

The activation of Ras small GTPases, including RalA and RalB, plays an important role in carcinogenesis, tumor progress, and metastasis. In the current study, we report the discovery of a series of 6-sulfonylamide-pyrano [2,3-c]-pyrazole derivatives as novel RalA inhibitors. ELISA-based biochemical assay results indicated that compounds 4k–4r suppressed RalA/B binding capacities to their substrates. Cellular proliferation assays indicated that these RalA inhibitors potently inhibited the proliferation of HCC cell lines, including HepG2, SMMC-7721, Hep3B, and Huh-7 cells. Among the evaluated compounds, 4p displayed good inhibitory capacities on RalA (IC50 = 0.22 μM) and HepG2 cells (IC50 = 2.28 μM). Overall, our results suggested that a novel small-molecule RalA inhibitor with a 6-sulfonylamide-pyrano [2, 3-c]-pyrazole scaffold suppressed autophagy and cell proliferation in hepatocellular carcinoma, and that it has potential for HCC-targeted therapy.
Unveiling the Enzymatic Degradation Process of Biobased Thiophene Polyesters
Authors: Bertolini Federico A. , Soccio Michelina , Weinberger Simone , Guidotti Giulia , Gazzano Massimo , Guebitz Georg M. , Lotti Nadia , Pellis Alessandro 
Published: November 2021

In the past 20 years, scientific research focused on the identification of valid alternatives to materials of fossil origin, in particular, related to biobased polymers. Recently, the efforts led to the synthesis of thiophene-based polymers (TBPs), a new class of polyesters based on 2,5-thiophenedicarboxylic acid (TPCA) that can be industrially produced using biomass-derived molecules. In this study, TBPs were synthesized using diols with different chain length (from C4 to C6) leading to poly(butylene 2,5-thiophenedicarboxylate) (PBTF), poly(pentamethylene 2,5-thiophenedicarboxylate) (PPeTF), and poly(hexamethylene 2,5-thiophenedicarboxylate) (PHTF), respectively, that were processed to thin films. To investigate enzymatic hydrolysis of these polymer films, cutinase 1 (Thc_cut1) and cutinase 2 (Thc_cut2) from Thermobifida cellulosilytica were recombinantly expressed in the host E. coli and purified. After 72 h of incubation at 65°C with 5 µM Thc_cut1, weight loss and HPLC analysis indicated 9, 100, and 80% degradation of PBTF, PPeTF, and PHTG with a concomitant release of 0.12, 2.70, and 0.67 mM of TPCA. The SEM analysis showed that tiny holes were formed on the surface of the films and after 72 h PPeTF was completely degraded. The LC-TOF/MS analysis indicated that Thc_cut2 in particular released various oligomers from the polymer during the reaction. In addition, the FTIR analysis showed the formation of novel acid and hydroxyl groups on the polymer surfaces. The results showed that the two used thermostable cutinases are promising biocatalysts for the environmentally friendly degradation of TPCA-based polyesters, in view of a possible sustainable recycling of plastic waste through resynthesis processes.
Influence of Direct Current–Voltage Accompanied by Charge Flow on CO2 Hydrate Formation
Authors: Zhao Qi , Xia Zhi-Ming , Xu Chun-Gang , Chen Zhao-Yang , Li Xiao-Sen 
Published: November 2021

The capture and storage of carbon dioxide (CO2) are urgent and crucial to achieve the goal of carbon neutrality. Hydrate-based CO2 capture technology is one of the promising technologies for capturing and storing CO2. This work studied the nucleation and growth of CO2 hydrate provoked by direct current–voltage accompanied by charge flow with the agitation of 450 rpm at an initial pressure of 3.5 MPa and a temperature of 274.15 K. The results show that the physical bubble behavior and electrochemistry mechanisms could influence CO2 hydrate formation process in the application of voltage. The induction time and semi-completion time of CO2 hydrate formation were decreased by 51% and 27.8% in the presence of 15 V, respectively. However, more product of electrolysis, Joule heat and ions, could inhibit the CO2 hydrate formation process in the application of a high voltage (60 V). In addition, a high voltage (60 V) could change the morphology characteristics of CO2 hydrate from gel-like to whisker-like. This study provides valuable information on the formation of CO2 hydrate under the action of charge flow.
Role of BMI in the Relationship Between Dietary Inflammatory Index and Depression: An Intermediary Analysis
Authors: Ma Yuxia , Li Ruiqiang , Zhan Wenqiang , Huang Xin , Zhang Zechen , Lv Shuaishuai , Wang Jiaqi , Liang Luyao , Jia Xiaofang 
Published: November 2021

Introduction: This study investigated this association and the role of BMI in the inflammatory process in a large population-based observational study.Methods: A total of 1,865 elderly people (≥55 years) were followed from the Community Cohort Study of Nervous System Diseases (CCSNSD) cohort study from 2018 to 2019 (Mean [SD] age, 66.31 [0.32] years; 716 [38.4%] males). The semi-quantitative FFQ and geriatric depression scale (GDS) were used to evaluate the diet and depressive symptoms of the elderly, respectively. The multivariable logistic regression model estimated the OR and 95% CI between Empirical Dietary Inflammatory Index (E-DII) and depression. The interaction of E-DII and BMI on depressive events was tested, and the mediation analysis of BMI was performed.Results: As measured by E-DII, the mean (SE) value of the inflammatory potential of the diet in our study was 1.56 (0.12). E-DII ranged from 5.23 to 5.58. In comparison with the first quartile, the elderly from the second quartile (OR: 1.15 [95% CI: 1.09, 1.28]) to the fourth quartile (OR: 1.31 [95% CI: 1.16, 1.42]) have a higher risk of depression before adjustment for BMI. An interaction was observed between E-DII and BMI in terms of the risk of depression (PInteraction &lt; 0.001). The whole related part is mediated by BMI (31.06%).Conclusion: Our findings indicate that the higher pro-inflammatory potential of diet is associated with a higher risk of depression, and this association may be mediated by BMI. Further research is needed to verify our findings and clarify the latent mechanism.
A Systematic Review and Meta-Analysis Protocol of Chemoablation vs. Transurethral Resection of Bladder Tumor in Patients With Non-Muscle-Invasive Bladder Cancer
Authors: Shi Xu , Feng Dechao , Wei Wuran 
Published: November 2021

Background: Bladder cancer is the second-ranked tumor of the genitourinary system. Transurethral resection of bladder tumor (TURBT) is currently the most important diagnosis and treatment method for non-muscular invasive bladder cancer (NMIBC). However, due to its high recurrence and progression rate, as well as high cost and inapplicability to some patients, intravesical chemoablation as an alternative to TURBT may be promising for NMIBC patients. However, there are very little data comparing its effectiveness, safety, best effective drug type, dosage selection, and cost with TURBT at present, which deserves further evaluation. The present study was designed in order to discuss which treatment is superior to another between chemoablation and TURBT in patients with NMIBC.Methods and Analysis: Databases including PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as Chinese databases including CNKI (China national knowledge infrastructure), Wan Fang database, and Chinese Clinical Trial Registry, from August 1994 to the time when the official submission of this review was published was included in this review and screened by two reviewers (XS and DCF) independently. There were no language limitations. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data was analyzed using RevMan and Stata software. The primary aims were the clinical effectiveness, including response rate, complete response OS, CSM, recurrence rate, time to recurrent, progression rate, and time to progression, among others. The secondary aims mainly included safety and tolerability, including costs, operation time, hospital stay, bleeding volume, and complications, among others.Study Registration: This study is registered as PROSPERO CRD42021271124.
Peran Serta Dalam Melaksanakan Pembagian Makanan Di Wilayah Bsd City
Authors: Salam Rahmat , Nusantoro Hardjanto , Ayuninggati Tsara , Devana Viola Tashya , Candra Ariya Pannadhitthana 
Published: November 2021

Tujuan kegiatan ini adalah sebagai bentuk perhatian dalam membantu mengurangi berat badan pada manusia dan memberi mereka sedikit kegembiraan dan senyuman dengan membantu mereka dengan murah hati di tengah wabah COVID-19 dengan pemberlakuan Pembatasan Sosial Berskala Besar (PSBB) di BSD, terutama di dalam lingkungan perumahan BSD ini. Ketertarikan ini dituntaskan melalui penggabungan dari uang yang telah dikumpulkan dari beberapa orang dengan mengaplikasikan dalam bentuk makanan kotak dengan minimal konversi Rp 250.000. Hasil dari pengumpulan kisaran harga memperoleh 50 Makanan Kotak. Tahapan dalam kegiatan adalah dimulai dari pencarian penerima makanan. Tahap kedua adalah dengan membagikan pada sasaran penerima makanan terdiri dari ojek online, pemulung, dan pengemis. Kegiatan ini dimulai pada bulan Mei 2021.
Suplementasi Vitamin D pada Wanita dengan Polycystic Ovarian Syndrome (PCOS)
Authors: Aziza Dian octaviana , Kurniati Karin Indah 
Published: November 2021

Polycyctic Ovarian Syndrome (PCOS) adalah penyebab paling sering terjadinya anovulasi dan infertilitas anovulasi. PCOS dapat dikatakan endokrinopati yang sering terjadi pada wanita dengan usia subur dan berkaitan dengan kelainan metabolik dan disfungsi reproduksi. Apabila tidak dilakukan manajemen terapi pada wanita dengan PCOS dapat terjadi komplikasi. Beberapa studi percontohan menilai efikasi terapeutik vitamin D dalam parameter metabolik terkait PCOS. Vitamin D adalah hormon steroid esensial yang berperan dalam menjaga hemostasis kalsium dan fosfat. Konsentrasi vitamin D dalam serum dinyatakan kurang jika kadar 25(OH)D 21-29 ng/mL dan dinyatakan defisiensi vitamin D jika kadar 25(OH)D <20 ng/mL. Efek defisiensi vitamin D yang dapat terjadi gangguan fertilitas dan menstruasi serta efek negatif pada sistem kardiovaskuler. Vitamin D memiliki efek langsung pada proses folikulogenesis dan maturasi oosit. Steroidogenesis dalam ovarium yang menghasilkan progesteron, estradiol dan estron dibantu calcitriol (vitamin D). Suplementasi vitamin D pada wanita dengan PCOS menunjukkan peningkatan kerja sel granulosa yakni sekresi progesteron meningkat.
Perbandingan Efek Antara Mobilization of the Nervous as System Active Exercise Terhadap Perubahan Nyeri dan Fleksibilitas Penderita Low Back Pain
Authors: Aras Djohan 
Published: November 2021

Low Back Pain merupakan gangguan yang dirasakan di punggung bagian bawah yang disebabkan oleh berbagai gangguan musculoskeletal maupun mobilisasi yang salah. LBP dapat menyebabkan timbulnya nyeri dan penurunan fleksibilitas lumbal sehingga mengganggu aktivitas penderitanya. Mobilization of the Nervous as System (MONAS) dan Active Exercise merupakan latihan yang dapat digunakan untuk menurunkan nyeri dan meningkatkan fleksibilitas pada penderita LBP.
Penelitian ini bertujuan untuk mengetahui perbandingan antara Mobilization of the Nervous as System dan Active Exercise Terhadap Perubahan Nyeri dan Fleksibilitas pada Penderita Low Back Pain (LBP).
Penelitian ini merupakan penelitian eksperimental dengan desain penelitian pre test-post test two group design. Teknik pengambilan sampel yaitu purposive sampling dengan jumlah sampel sebanyak 22 orang dibagi dalam 2 kelompok, yaitu kelompok MONAS dan Active Exercise. Masing-masing kelompok beranggotakan 11 responden. Alat ukur yang digunakan adalah Visual Analogue Scale (VAS) untuk mengukur nyeri dan Modified Schober Test (MST) untuk fleksibilitas. Penelitian ini menggunakan uji paired sampel T test sebagai uji pengaruh dan uji perbandingan menggunakan uji Independent sampel T test.
Hasil penelitan dengan uji paired sample t-test menunjukkan terdapat perubahan nyeri dan fleksibilitas pada penderita LBP setelah pemberian MONAS dengan nilai p=0,000 dan Active Exercise dengan nilai p=0,000. Sedangkan hasil uji independent sample t-test pada nyeri diperoleh nilai p=0,658 sedangkan fleksibilitas p=0,729 yang artinya tidak ada perbedaan yang signifikan antara MONAS dan Active Exercise baik terhadap nyeri maupun fleksibilitas.
Costos ambulatorios y hospitalarios de la falla cardíaca en dos hospitales de Bogotá
Authors: Tamayo Fuquen Diana Carolina , Rodríguez Viviana Alejandra , Rojas Reyes María Ximena , Rincón Roncancio Mónica , Franco Camilo , Ibarra María Teresa , Dennis Verano Rodolfo José 
Published: November 2021

Objetivo: realizar una aproximación a la determinación de costos directos de la falla cardíaca (FC) en el país, a través de la evaluación de costos asociados con el cuidado de pacientes atendidos en dos instituciones prestadoras de salud de Bogotá.
Métodos: estudio de costos bajo la perspectiva del tercer pagador. La identificación de eventos generadores de costos en atención ambulatoria se realizó mediante revisión de historias clínicas de pacientes atendidos durante 2011 en la consulta externa especializada de una institución. Los costos de interconsultas y paraclínicos se determinaron según los valores del Acuerdo 256 de 2001, con adición del 30%. Los costos de la medicación se determinaron a partir del registro SISMED. La identificación de eventos generadores de costos en hospitalización se realizó mediante revisión de listados y facturas de pacientes atendidos entre 2009 y 2010 en dos instituciones. Los resultados se presentan resumidos por medidas de tendencia central y de dispersión, en pesos colombianos (COP) de 2011.
Resultados: el costo mensual promedio del tratamiento ambulatorio de FC fue de 304.318 COP (D.E. 760.876), con una mediana de 45.280 COP (RIC 25.539 - 109.715); los medicamentos representaron la fuente principal de consumo de recursos (55,2%). El costo promedio de la hospitalización por descompensación de FC fue de 6.427.887 COP (D.E. 9.663.176); la estancia hospitalaria representó la mayor proporción del costo (29,1%).
Conclusiones: los costos ambulatorios, y especialmente los hospitalarios, asociados con la FC en Colombia son sustanciales. La fuente principal de costos difiere dependiendo de si el manejo es hospitalario (estancia) o ambulatorio (medicamentos).
Retrospective of normative application of the concept of bribery to describe corruption criminal offenses
Authors: Mykhailov Mykhailo 
Published: November 2021

The article presents the chronology of the introduction of the concept of bribery into the national criminal legislation as the mainelement of the legislative description of corruption. The concept of corrupt bribery is crucial for research on criminal liability for corruption.A retrospective analysis of the application of the concept of bribery to the legislative description of corruption criminal offenseswill help to determine the etymology of the concept of corruption bribery.Based on the results of the retrospective review of the normative application of the concept of bribery, a number of conclusionshave been made, in particular, that this concept is not completely new in modern national legislation. Its use in the formulation of crimi -nal law has usually been associated with the description of how to commit a non-corruption crime, and since 2001, in connection withthe adoption of the new Criminal Code of Ukraine, and with the description of one of the methods of incitement as complicity.Beginning in 2009, the concept of bribery was gradually introduced into criminal law precisely to denote the form of action inthe formulation of dispositions of articles that provided for liability for corruption offenses. This concept became widespread in thenorms of the Criminal Code of Ukraine in 2011 with the adoption of the Law of Ukraine “On Amendments to Certain Legislative Actsof Ukraine on Liability for Corruption Offenses.” Later, its use by the legislator to describe acts of corruption only increased and todayit is more associated with corruption offenses, although it is used in the Code and in other cases.
Thus, at present, the Criminal Code, using the concept of bribery, uses it in two guises: the first does not etymologically link thisconcept with corruption; the second variant of using the concept of bribery is substantively related to the concept of corruption and isin fact its textual embodiment in criminal law.