bluuebunny/crossref_metadata_2025 huggingface dataset:
FAKTOR-FAKTOR YANG MEMENGARUHI KEBERLANGSUNGAN UMKM DI KABUPATEN BANYUMAS PADA MASA PANDEMI COVID-19
Authors: Azhar Ade Novianti , Arofah Triani
Published: December 2021

Penelitian ini bertujuan untuk mengetahui pengaruh literasi keuangan, penggunaan ecommerce, inovasi produk, dan kesiapan berubah terhadap keberlangsungan UMKM di masa pandemic Covid-19. Teknik pengambilan sampel menggunakan purposive sampling dengan jumlah sampel sebanyak 100 pelaku UMKM di Kabupaten Banyumas. Teknik analisis data yang digunakan dalam penelitian adalah analisis regresi berganda. Hasil penelitian ini menunjukkan bahwa: (1) literasi keuangan berpengaruh secara signifikan terhadap keberlangsungan UMKM di masa pandemi Covid-19; (2) penggunaan e-commerce berpengaruh secara signifikan terhadap keberlangsungan UMKM di masa pandemi Covid-19; (3) inovasi produk tidak berpengaruh terhadap keberlangsungan UMKM di masa pandemi Covid-19; (4) kesiapan berubah tidak berpengaruh terhadap keberlangsungan UMKM di masa pandemi Covid-19. Implikasi dari penelitian ini adalah pemahaman terkait literasi keuangan akan membantu pelaku usaha dalam melihat kondisi keuanganya dan membantu dalam mengambil keputusan yang tepat khususnya pada masa pandemi ini, sehingga akan membantu pelaku usaha dalam menjaga kelangsungan usahanya. Penggunaan e-commerce membantu pelaku usaha dalam menjangkau pasar yang lebih luas, khususnya pada masa pandemi ini dimana kegiatan belanja banyak dilakukan secara online, sehingga penggunaan e-commerce akan menjaga stabilitas usaha dan menjaga kelangsungan usaha.
Renovação educacional
Authors: Rabello Maciel de Barros Tamberlini Angela
Published: December 2021

Este texto aborda o Ensino Vocacional do Estado de São Paulo, valendo-se de fontes documentais, orais e bibliográficas, buscando compreendê-lo em conexão com o rico contexto da época, marcado pela pujança dos movimentos sociais e políticos em um período democrático, caracterizado por iniciativas voltadas à modernização do país, à difusão da cultura urbana e à aposta na renovação educacional como fator de desenvolvimento nacional, visando reinventar o Brasil. Logramos, a partir do histórico da renovação, estabelecer os pontos de contato entre esta experiência e o ímpeto renovador presente nos trabalhos do Centro Regional de Pesquisas Educacionais de São Paulo e na criação da Faculdade de Educação da USP, iniciativas estas que seriam ceifadas pelo golpe militar, tidas como subversivas.
Analiza gornjih domova izbornih demokracija
Authors: Zrile Ante
Published: December 2021

Dvodomna zakonodavna tijela dio su institucionalnog uređenja u sedamdeset devet država. Bikameralizam predstavlja jednu od najsnažnijih institucionalnih protuteža izvršnoj vlasti. Zbog svoje specifičnosti gornji su domovi zanimljivi za politologe, stoga se postavlja pitanje zašto su rijetko predmetom istraživanja. Rad nastoji popuniti istraživačku prazninu proučavanjem institucionalnih uređenja sedamnaest izbornih demokracija, koje imaju dvodomna zakonodavna tijela. Prvi dio rada donosi pregled povijesnog razvoja bikameralizma. Drugi dio rada prikazuje suvremeni bikameralizam i detaljno prikazuje četiri idealtipska primjera gornjih domova – Ujedinjenog Kraljevstva, Sjedinjenih Američkih Država, Francuske i Poljske. Treći dio donosi osnovne značajke ostalih gornjih domova koji su predmet istraživanja. U četvrtom dijelu rada provodi se komparacija sedamnaest gornjih domova kako bi se dao odgovor na istraživačko pitanje što čini gornji dom snažnim prema njegovim formalnim ovlastima. Povodom dvadesete godišnjice njegova ukidanja, u posljednjem odlomku analiziraju se formalne ovlasti i demokratičnost izbora hrvatskog Županijskog doma Sabora Republike Hrvatske (1993-2001).
Technology, Development, and the Competition for Supremacy
Authors: Balaban Delia Cristina
Published: December 2021

From its very first pages, Paul Dobrescu’s new book The Dragons of Development makes its roots visible: it is built on a comprehensive literature review, and on a reflection upon progress and supremacy in contemporary societies. The author sees the development of a society as “a way to get to know ourselves” (p.10), and the ideas elaborated in the volume are based on historical and societal knowledge. To understand the development of a nation, its cultural roots and the following integration of culture in the norms of that society are a relevant object of study.
An introduction of the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) Project
Authors: Jeong Na-Young , Lee Hae-In , Kim Min-Ju , Kim Hee-Jin , Choi Nam-Kyong
Published: December 2021

The vaccine benefit-risk assessment entails comprehensive and systematic evaluation of the major benefits and risks of vaccine based on information after a marketing authorization. In 2009, the influenza A (H1N1) pandemic led to the licensing of new H1N1 vaccines in many countries including Europe. The post-marketing evaluation and monitoring of H1N1 vaccines was carried out based on a project previously conducted in Europe. In 2013, the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) project was launched with the support of Innovative Medicines Initiative (IMI) to address the limitations reported in the previous project. ADVANCE consisted of seven Work Packages (WPs), each indicating the vaccine benefitrisk monitoring readiness across four areas: Governance, Data source, Methods, and Study. First, a model for vaccine surveillance and governance with various functions such as decision making, quality management, execution, and financial administration was established. Also, the project developed a tool to identify, collect, and link the data sources available for vaccine surveillance. In addition, various methodologies were reviewed to assess the infectious disease burden, vaccine coverage, and benefit-risk based on linked data sources in Europe. Guidelines were proposed for real-world vaccine surveillance studies. Accordingly, a variety of tools and programs were developed, including a code of conduct related to the benefit-risk assessment of vaccines, ADVANCE International Research Readiness (AIRR), CodeMapper, and VaccO. Since the end of the ADVANCE project in 2019, the Vaccine Monitoring Collaboration for Europe (VAC4EU) has been conducting effective and sustainable vaccine benefit-risk monitoring programs based on the vision and ideology of ADVANCE. This study explains the contents and findings of ADVANCE with emphasis on WPs and proposes directions for establishing a vaccine benefit-risk assessment system in Korea.
The Effect of Zakat Institution System and Government Support on Intention to Pay Zakat: Knowledge as A Moderating Variable
Authors: Sudarsono Heri , Nugrohowati Rindang Nuri Isnaini , Tumewang Yunice Karina
Published: December 2021

This study aims to determine the effect of attitudes, subjective norms, zakat institution system and government support in influencing the interest of the government and private officers to pay zakat. This study also aims to determine the extent of muzakki’s knowledge of zakat in improving attitudes, subjective norms, zakat institutional systems and government support in the interest of the government and private officers to pay zakat. Respondents in this study are 402 respondents consisting of 154 government officers and 248 private officers who live in 6 big cities in Java, such as Jakarta, Serang, Bandung, Semarang, Yogyakarta and Surabaya. This research uses the Partial-Least-Square Structural Equation Modeling (PLS-SEM) analysis technique with the Theory of Reasoned Action (TRA) model. The finding reveals that attitudes, subjective norms, zakat institutional system, and government support affect the government and private officers' interest in paying zakat. Meanwhile, knowledge as a moderating variable does not strengthen the influence of attitudes, zakat institutional systems and government support. Still, it reinforces the subjective norms of government and private officers in influencing intention to pay zakat. BAZNAS can collaborate with educational institutions, professional institutions, community institutions and utilize social networks to increase public knowledge about zakat. Hence, knowledge about zakat supports subjective norms and attitudes, zakat institutional system, and government support.
Sharia Value-Based Learning Environment and Students’ Career Choice
Authors: 'Imari Iqbal , Wafaretta Vega
Published: December 2021

The purpose of this study is to find out whether the sharia value-based learning environment influences the career choice of sharia economics students at Islamic Financial Industries (IFIs). Learning is one of the crucial factors that could shape career choices referring to Social Cognitive Career Theory (SCCT). A quantitative approach is employed. Questionnaires totaling 378 were filled by students from three (3) types of universities in East Java, Indonesia. Path analysis and different tests using Partial Least Square (PLS) 3.0 and SPSS ver. Twenty-three were conducted. The weight of courses, learning, and lecturers' motivation positively affected career intention at IFIs. Students from the public–non-Islamic universities perceived the highest learning and motivation, and the lowest was public–Islamic universities. It might be because the Islamic culture at public-Islamic universities might form an ideal perspective for the contemporary IFIs. Besides, students who completed an internship at IFIs had the highest intention; meanwhile, students who have interned at non-IFIs showed the lowest career intention at IFIs. The implications of this study are learning environment should more involve sharia values. Besides, students should intern at IFIs to choose a career at IFIs to contribute to developing sharia economics.
CAUSES OF CONFLICTS IN DENTAL PRACTICE, WAYS TO PREVENT AND RESOLVE THEM
Authors:   Northern State Medical University of the Ministry of Health of the Russian Federation, Luzgina T.A. , Tsyganova O.A. ,   Northern State Medical University of the Ministry of Health of the Russian Federation
Published: December 2021

Significance: the number of conflicts related to realization of the right to health and medical care especially in such specific branch of medicine as dentistry has recently been on the rise in Russia. Furthermore, among the main fields of social interaction, a large number of interpersonal conflicts does relate to professional activity. Subject of research: conflicts and conflict situations in dental practice. Purpose of work: to identify main groups of causes of conflict situations and conflicts in dental practice and suggest ways to prevent and resolve them. Material and methods: questionnaire survey of dentists with additional interview of the respondents, mathematical and statistical data analysis using the SPSS Statistics software (Pearson chi-square tests, Kruskal-Wallis tests). Results: The majority of the respondents (59.0%) say that they have never had any conflicts with the administration. The leading cause of disagreement is dissatisfaction with the material base and supplies (35%). The prevailing share of the dentists (61.5%) indicate that conflicts between them and a colleague / nurse have never occurred. The main cause of the conflict communication is insubordination or lack of subordination, especially in rural areas and public facilities. Doctors of public healthcare facilities and dentists working in rural areas were more often in conflict with a colleague or manager. Almost all health workers (98%) note that they have encountered conflict patients. The main cause of the conflict communication is long waiting for a dental appointment (33.3%). Out of all factors influencing the relationship, about half of the respondents (53.0%) mentioned the emotional state of the patient. Out of all behavior strategies in conflicts, the majority of dentists (44%) prefer cooperation. Conclusion: Almost all (98%) dentists came into conflict with the patient. The main causes of these conflicts included: long waiting times for admission (33.3%), irrational work of the registry, the administrator (23.1%) and complaints about the quality of services (22.2%). Medical workers with average work experience (10-29 years) were more likely to conflict with the patient about claims to the quality of treatment (31.3%).
Evidence that abrasion can govern snow kinetic friction
Authors: Lever James , Taylor Susan , Hoch Garrett , Daghlian Charles
Published: December 2021

The long-accepted theory to explain why snow is slippery postulates self-lubrication: frictional heat from sliding melts and thereby lubricates the contacting snow grains. We recently published micro-scale interface observations that contradicted this explanation: contacting snow grains abraded and did not melt under a polyethylene slider, despite low friction values. Here we provide additional observational and theoretical evidence that abrasion can govern snow kinetic friction. We obtained coordinated infrared, visible-light and scanning-electron micrographs that confirm that the evolving shapes observed during our tribometer tests are contacting snow grains polished by abrasion, and that the wear particles can sinter together and fill the adjacent pore spaces. Furthermore, dry-contact abrasive wear reasonably predicts the evolution of snow-slider contact area and sliding-heat-source theory confirms that contact temperatures would not reach 0°C during our tribometer tests. Importantly, published measurements of interface temperatures also indicate that melting did not occur during field tests on sleds and skis. Although prevailing theory anticipates a transition from dry to lubricated contact along a slider, we suggest that dry-contact abrasion and heat flow can prevent this transition from occurring for snow-friction scenarios of practical interest.
Decision Support System For Energy Source Selection Based On Credibility Fuzzy Information.
Authors: Abdullah Saleem , Yahya Muhammad
Published: December 2021

This main objective of this work is to define some new operations of credibility fuzzy numbers using Hamacher t-norm and t-conorm. These operation are more generalized operation for credibility fuzzy numnbers, we apply these operations to aggregation operators for credibility fuzzy numbers. Furthermore, using the basic operational laws of Hamacher t-norm and t-conorm, we develop a series of credibility fuzzy Hamacher aggregation operators like credibility fuzzy Hamacher weighted averaging (CFHWA) and credibility fuzzy Hamacher geometric (CFHWG) aggregation operators. we also explained some of the proposed Hamacher aggregation operators properties like commutativity, idempotency and monotonicity. In order to validate the proposed Hamacher aggregation operators for credibility fuzzy numbers, we develop general algorithm for decision making technique under credibility fuzzy numbers and using these operators. The proposed algorithm is apply to electricity crises in Pakistan problems. Finally a comparison with other existing methods is done to check the accuracy and validation of the proposed methods. At rest the proposed method is verified by other well known methods.
Invasion in An Omnivorous Food Web: The Impact of Roles and Different Trophic Levels
Authors: Jiabu Duojie , Li Weide
Published: December 2021

In the field of ecology, habitat loss and fragmentation are the two main characteristic forms of habitat destruction and the main drivers of species extinction, resulting in the gradual loss of biodiversity. So far, many scholars have made some progress in the theoretical research of the spatial food web, but research on the effect of introducing an invasive species in an omnivorous food web is very rare. In order to explore the impact of invader on the persistence of species in omnivorous food webs, we constructed a model framework to describe the patch occupation of each species in omnivorous systems. Our model results show that invasive species is a prey of species in omnivorous food webs is easier to invade than invasive species is a predator of species in original omnivorous food webs on habitat loss and fragmentation. One conclusion also can be drawn is that when an invasive species is a prey of species in omnivorous food webs, no matter what trophic level the invasive species is invade, it is more successful. But when invasive species is a predator of species in different trophic levels on omnivorous food webs, they show different coexistence patterns. The invasion of a species has little effect upon the stability of original omnivorous food web for habitat loss and fragmentation, and will only make the original omnivorous food web more stable and more complicated. Therefore, we have proved that the omnivorous food web is stable and is not easy to destroy this ecological fact. Some examples to illustrate the reliability of our model results are discussed.
Reduced rice paddy methane emission through dual compound mechanism in novel cultivars
Authors: Jin Yunkai , Liu Tong , Hu Jia , Sun Kai , Xue Lihong , Bettembourg Mathilde , Hou Pengfu , Hao Peiyinh , Tang Jintian , Ye Zihoung , Liu Chunlin , Li Peng , Pan Aihu , Wang Lushui Wang , Xiao Guoying , Moazzami Ali , Yu Xiaoping , Schnürer Anna , Sun Chunaxin
Published: December 2021

Methane is the second most abundant greenhouse gas after carbon dioxide and its concentrations have risen tenfold in the past decade due to agricultural activity1. Rice paddies are considered a major source of anthropogenic methane, however strategies to mitigate methane emission in rice paddies is not yet successful despite considerable efforts being made. Methane production is caused by microbial communities feeding on organic exudates from the rice root, and regulation of the dominant secretions has been suggested as leading way to put an end to the methane emission from rice paddies. Here, we introduced a new system to reduce methane emission in rice paddies based on the discovery that fumarate and ethanol are two specific rice-orchestrated compounds that determine the levels of methane emission from rice paddies. Moreover, stable low-fumarate high-ethanol secretion lines have been successively bred through hybrid breeding and shown to cut around 70% of methane emission in paddies as compared to control. Approaches to block fumarate reductase or increase ethanol level, were furthermore employed as cultivation managements and resulted in a reduction in methane emissions of around 60%, calculated from two-year four-site field work. All results highlight the application of our findings to largely mitigate influences of rice cultivation on global climate.
Many-body localization enables iterative quantum optimization
Authors: Wang Hanteng , Yeh Hsiu-Chung , Kamenev Alex
Published: December 2021

We suggest an iterative quantum protocol, allowing to solve optimization problems with a glassy energy landscape. It is based on a periodic cycling around the tricritical point of the many-body localization transition. This ensures that each iteration leads to a non-exponentially small probability to find a lower local energy minimum. The other key ingredient is to tailor the cycle parameters to a currently achieved optimal state (the "reference" state) and to reset them once a deeper minimum is found. We show that, if the position of the tricritical point is known, the algorithm allows to approach the absolute minimum with any given precision in a polynomial time.
The Effect of IL-6-Primed Platelets on ADAMTS13-Mediated Clearance of Platelet-Bearing ULVWF and Its Mechanism
Authors: Kim Hyun-Jeong , Dong Jing-fei , Song Yejin , Jung Hyo-Il , Song Jaewoo
Published: December 2021

Inflammation is an essential contributing factor in the development of thrombosis. Using a microfluidic flow chamber, we investigated how the proinflammatory cytokine interleukin 6 (IL-6) affects the cleavage of platelet-bearing ultra-large VWF (ULVWF) by plasma ADAMTS13. We found that IL-6-treated platelets perfused at arteriolar shear stress significantly enhanced the ULVWF-platelet complex formation on activated endothelial cells and suppressed their clearance by ADAMTS13 under flow conditions. We also detected the phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in platelets treated with IL-6. Treatment of IL-6-primed platelets with either the phosphoinositol-3 kinase (PI3K) inhibitor LY294002 or the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 reduced the ULVWF-platelet complex formation and restored the clearance of the complex by plasma ADAMTS13, compared to IL-6-primed platelets. Furthermore, IL-6 enhanced the phosphorylation of the intracellular adaptor molecule 14-3-3ζ, which regulates VWF binding to the glycoprotein (GP) Ib-IX complex. The 14-3-3 antagonist R18 significantly increased ADAMTS-13 cleavage of ULVWF strings with adherent IL-6-treated platelets. These findings indicate that IL-6 related intracellular signals of platelet is involved in regulating ULVWF-platelet binding and ULVWF cleavage by ADAMTS13.
miR-199b-3p Promotes Radiation-induced Oral Mucositis via DDIT4-mediated mTOR Signal Pathway
Authors: Yang Jiantang , Fu Lili , Zeng Yi , Yuan Chen
Published: December 2021

Background: Radiation-induced oral mucositis (RIOM) is an adverse reaction in patients of head and neck cancer after radiotherapy. However, the key regulatory factors in the pathogenesis of RIOM remain largely unclear. In this article, we discover a novel role of DNA damage-inducible transcript 4 (DDIT4) in regulating RIOM pathogenesis.Methods: We established RIOM in vitro and in vivo models to mimic the biological processes of RIOM. The level of DDIT4 in RIOM was analyzed by real-time PCR and Western blot. Through the bioinformatics analysis and luciferase assay, the relationship between miR-199b-3p and DDIT4 was performed. The level of mTOR signaling were explored by Western blot. Besides, Clone Formation and EDU assay were performed to investigate the effects of miR-199b-3p/DDIT4 on cell proliferation. H&E and immunohistochemistry experiments examined the effects of miR-199b-3p/DDIT4 on RIOM in vivo. Results: We found that the level of DDIT4 was significantly reduced during the RIOM formation, and up-regulated of DDIT4 suppressed the progression of RIOM in vitro and in vivo. Besides, we found DDIT4 was a direct target of miR-199b-3p. Ectopic expression of miR-199b-3p repressed the level of DDIT4 and activated mTOR signal conduction to promote RIOM progress, whereas the silencing of miR-199b-3p promoted the DDIT4-mediated RIOM regulation both in vitro and in vivo. Conclusion: Collectively, our studies not only identified the novel functional role of DDIT4 in modulating pathogenic processes of RIOM but also provided new directions and ideas for the future treatment of radiotherapy oral mucositis.
Effect of Solid-State Fermentation on the essential oil yield of Curcuma longa residues
Authors: Boum Alexandre Teplaira , Kwanga Sylvie Nguikwie , Tegoundio Doriane , Anoh Felix Adje
Published: December 2021

The solid waste of Curcuma longa rhizomes generated after its cold juice process making is mostly unused and discarded even though they can contain essential oil. Conventional techniques such as hydrodistillation can be used to extract essential oil, but this generally results in low essential oil yield and inefficient extraction time. Solid-state fermentation as a pretreatment of distillation could improve the yield of essential oil. In this study, we evaluated the effect of solid state fermentation on the yield of extraction of Curcuma longa solid wastes essential oil. The solid-state fermentation was carried out naturally without any addition of inoculum and the extraction was performed by hydrodistillation. Under experimental conditions at room temperature and anaerobically in the dark, the treatment of 7 days of solid state fermentation followed by 2h of hydrodistillation provided the highest yield of 1.21% as compared to non-fermented of 0.35% and of 0.96% relative to the raw plant material representing an increase of 71% and 21% respectively. A
Regional Parameters for Human Health Impact Assessment
Authors: Belyanovskaya Alexandra , Soktoev Bulat , Laratte Bertrand , Ageeva Elena , Baranovksaya Natalia , Korogod Natalia
Published: December 2021

The research paper is aimed to modify the human health impact assessment of Cr in soils. The current article presents the input of several critical parameters for the human health Impact Score (IShum) assessment in soils. The modification of the IShum is derived using geological data (results of neutron activation analysis of soils are used in the IShum calculation; research area is divided using the watersheds) and population size and density. Watersheds reflect the local environmental conditions of the territory unlike the administrative units due to their geological independence. The calculations of the Characterization factor value underestimate the influence of the population size and density on the final result. Default regional values cannot be considered during the assessment of the potential human health impact for the big sparsely inhabited areas. In case of very low population density the result will be overrated and underestimated in the opposite case. The current approach demonstrates the generosity of the geographical separation in the USEtox model. The same approach can be utilized for other geo zones due to the accessibility of this information (area size, population size and density, geological and landscape features).
Chemical and Behavioural Strategies along The Spectrum of Host Specificity in Ant-Associated Silverfish
Authors: Parmentier Thomas , Gaju-Ricart Miquel , Wenseleers Tom , Molero-Baltanás Rafael
Published: December 2021

Background
Host range is a fundamental trait to understand the ecological and evolutionary dynamics of symbionts. Increasing host specificity is expected to be accompanied with specialization in different symbiont traits. We tested this specificity-specialization association in a large group of 16 ant-associated silverfish species by linking their level of host specificity with their degree of behavioural integration into the colony and their accuracy of chemically deceiving the host’s recognition system, i.e. the cuticular hydrocarbon (CHC) profile.
Results
As expected, facultative associates and host generalists (targeting multiple unrelated ants) tend to avoid the host, whereas host-specialists (typically restricted to Messor ants) were bolder, approached the host and allowed inspection. Generalists and host specialists regularly followed a host worker, unlike the other silverfish. Host aggression was extremely high toward non-ant-associated silverfish and modest to low in ant-associated groups. Surprisingly, the degree of chemical deception was not linked with host specificity as most silverfish, including facultative ant associates, imitated the host’s CHC profile. Messor specialists retained the same CHC profile as the host after moulting, in contrast to a host generalist, suggesting an active production of the cues (chemical mimicry). Host generalist and facultative associates flexibly copied the highly different CHC profiles of alternative host species, pointing at passive acquisition (chemical camouflage) of the host’s odour.
Conclusions
Overall, we found that behaviour that seems to facilitate the integration in the host colony was more pronounced in host specialist silverfish. Chemical deception, however, was employed by all ant-associated species, irrespective of their degree of host specificity.
Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity
Authors: Reis Raphael Dos , Kornobis Etienne , Pereira Alyssa , Tores Frédéric , Carrasco Judit , Jahannault-Talignani Céline , Nitschké Patrick , Muchardt Christian , Schlosser Andreas , Maric Hans , Ango Fabrice , Allemand Eric
Published: December 2021

Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and GABA-A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
Evaluation of Biological Effect in Breast Cell Irradiated with Dose 2 Gy in Radiotherapy
Authors: Pereira Leslie , Lima Antonio Gilcler F. , Ferreira Marcella T. , Salata Camila , Ferreira-Machado Samara C , Morandi Veronica , Magalhães Luis Alexandre Gonçalves
Published: December 2021

Introduction: Breast cancer (BC) is the most common female malignancy worldwide. For the definitive treatment of MC, radiotherapy can be used, as an important component, and uses ionizing radiation (IR). Studies reveal the potential capacity of IR to promote metastasis. The clinical response of BC to radiotherapy is related to radiosensitivity and resistance of irradiated cells, which is associated with clonogenic activity and sensitivity to radiation. Unsuccessful treatment increases the risk of local and distant recurrence.Methodology: Three breast cell lines (MCF-10A, MCF-7, and MDA-MB-231) were irradiated with 2 Gy and after 72 hours following markers were evaluated: E-cadherin, fibronectin, vimentin, and Snail. The processes of invasion, degradation of MMP2 and MMP9, and transendothelial migration were then assessed. Double-strand DNA breaks (DSBs), apoptosis, and colony formation were quantified. Result: The detection of γH2AX histone of irradiated cells showed that MCF-10A non-tumor cell is more radiosensitive while the MDA-MB-231 tumor cell is more radioresistant. The dose 2 Gy altered the formation of colonies to any of the cell lines. Tumorigenic cells exhibited a markedly increase in apoptosis, 24 h after irradiation while MCF-10A cells only after 72 h. A single dose of 2 Gy does not induce changes in the cellular microenvironment that lead to changes in the mesenchymal epithelium in breast BC.Conclusion: A dose of 2 Gy induces apoptosis and consequently an alteration in cell survival. However, a single dose of 2 Gy does not induce changes in the cellular microenvironment that lead to changes in the mesenchymal epithelium.
Instant diagnosis of gastroscopic biopsy via deep-learned single-shot femtosecond stimulated Raman histology
Authors: Liu Zhijie , Su Wei , Ao Jianpeng , Wang Min , Jiang Qiuli , He Jie , Gao Hua , Lei Shu , Nie Jinshan , Yan Xuefeng , Guo Xiaojing , Zhou Pinghong , Hu Hao , Ji Minbiao
Published: December 2021

Gastroscopic biopsy provides the only effective way for gastric cancer diagnosis, but the gold standard histopathology is time-consuming and incompatible with gastroscopy. Conventional stimulated Raman scattering (SRS) microscopy has shown promise in label-free diagnosis on human tissues, yet it requires the tuning of picosecond lasers to achieve chemical specificity at the cost of time and complexity. Here, we demonstrated single-shot femtosecond SRS (femto-SRS) could reach the maximum speed and sensitivity with preserved chemical resolution by integrating with U-Net. Fresh gastroscopic biopsy was imaged in < 60 seconds, revealing essential histoarchitectural hallmarks perfectly agreed with standard histopathology. Moreover, a diagnostic neural network (CNN) was constructed based on images from 279 patients that predicts gastric cancer with accuracy > 96%. We further demonstrated semantic segmentation of intratumor heterogeneity and evaluation of resection margins of endoscopic submucosal dissection (ESD) tissues to simulate rapid and automated intraoperative diagnosis. Our method holds potential for synchronizing gastroscopy and histopathological diagnosis.
Alterations in Co-abundant Bacteriome in Colorectal Cancer and Persistent Microbial Dysbiosis After Surgery
Authors: Png Chin-Wen , Chua Yong-Kang , Law Jia-Hao , Zhang Yongliang , Tan Ker-Kan
Published: December 2021

ObjectiveThere is growing interest in the role of gut microbiome in colorectal cancer (CRC), ranging from screening to disease recurrence. Our study aims to identify microbial markers characteristic of CRC and to examine if changes in bacteriome persist after surgery. Design49 fecal samples from non-cancer (NC) individuals and CRC patients, before and after surgery, were collected for analysis by bacterial 16S rRNA gene sequencing. ResultsBacterial richness and diversity were reduced in the CRC patients compared to NC individuals. Pro-carcinogenic bacteria such as Bacteroides fragilis and Odoribacter splanchnicus were increased in pre-op CRC compared to NC group. These differences were no longer observed after surgery. Comparison between post- and pre-op CRC showed increased abundance of probiotic bacteria after surgery. Concomitantly, bacteria associated with CRC progression were observed to have increased after surgery, implying persistent dysbiosis. ConclusionMicrobiome signatures characteristic of CRC likely comprise a set of significant alteration in specific bacterial strains. Elements of these dysbiotic signatures persists even after surgery, suggesting possible field-change in remnant non-diseased colon. Future studies should seek to examine if these signatures are also associated with pre-malignant colonic polyps and, explore if these profiles can be used to guide CRC screening and surveillance.
Selecting Essential Factors for Predicting Reference Crop Evapotranspiration Through Tree-based Machine Learning and Bayesian Optimisation
Authors: Zhao Long , Zhao Xinbo , Shi Yi , Wang Yuhang , Cui Ningbo , Zhang Shuo
Published: December 2021

Reference crop evapotranspiration (ETO) is a basic component of the hydrological cycle, and its estimation is critical for agricultural water resource management and scheduling. In this study, three tree-based machine learning algorithms (random forest [RF], gradient boosting decision tree [GBDT], and extreme gradient boosting [XGBoost]) were adopted to determine the essential factors for ETO prediction. The tree-based models were optimised using the Bayesian optimisation (BO) algorithm, and they were compared with three standalone models in terms of daily ETO and monthly mean ETO estimation in North China, with different input combinations of essential variables. The results indicated that solar radiation (Rs) and air temperature (Ts), including the maximum, minimum, and average temperature, in daily ETO were the key parameters affecting model prediction accuracy. Rs was the most influential factor in the monthly average ETO model, followed by Ts. Both relative humidity (RH) and wind speed at 2 m (U2) had little impact on ETO prediction at different scales, although their importance differed. Compared with the GBDT and RF models, the XGBoost model exhibited the highest performance for daily ETO and monthly mean ETO estimation. The hybrid tree-based models with the BO algorithm outperformed the standalone tree-based models. Overall, compared with other inputs, the model with three inputs (Rs, Ts, and RH/U2) had the highest accuracy. The BO-XGBoost model exhibited superior performance in terms of the global performance index (GPI) for daily ETO and monthly mean ETO prediction and it is recommended as a more accurate model predicting daily ETO and monthly mean ETO in North China or areas with a similar climate.
Higher Expectancy of Acupuncture Treatment is Associated with Significant Higher Ovulation, Less Bruising and Lower Dropout in Infertile Women with PCOS Receiving Acupuncture
Authors: Gong Yi , Li Jian , Ma Hong-Li , He Hui , Wu Xiao-Ke
Published: December 2021

Object: To study the expectancy of acupuncture treatment on fertility outcomes and adverse events in infertile women with polycystic ovary syndrome (PCOS) receiving acupuncture. Method: This analysis including 1000 infertile women with PCOS. Women with available expectancy of acupuncture treatment were included in analysis, of whom were subdivided into low and high expectancy groups. The anthropometric and endocrinal parameters, fertility outcomes as well as adverse events and dropout were compared. The risk of low expectancy of acupuncture treatment on ovulation and correspondent 95% confidence interval was computed by multivariable logistic regression model. The Kaplan Meier survival curve was employed to plot the time to ovulation and Cox regression model was used to compare the difference of time to ovulation between groups, adjusting by interventions. Results: 827 women were included in analysis, of whom 373 and 454 women were identified as low and high expectancy, respectively. Compared with low expectancy, women with high expectancy had higher BMI (24.56 vs 23.77 kg/m2, p = 0.03), shorter time to attempt to conception (22.97 vs. 25.00 months, p = 0.03), earlier menarche (13.61vs.13.68 years, p = 0.03) and lower estradiol (256.68 vs. 284.13 pmol/L, p = 0.03). There was not interaction between acupuncture treatment and expectancy of acupuncture treatment regarding ovulation (p = 0.07). High expectancy was associated with significant higher ovulation (adjusted odds ratio (OR) 2.33, 95% CI 1.31 to 4.16, p = 0.004) and lower dropout (adjusted OR 0.13, 95%CI 0.03 to 0.57) in women receiving control acupuncture, even after adjustment by BMI, estradiol, and clomiphene, while it was associated with significant less bruising (adjusted OR 0.28, 95%CI 0.13-0.61) and lower dropout (adjusted OR 0.42, 95%CI 0.18-0.96) in those receiving active acupuncture. High expectancy was associated with significant shorter time to ovulation (median 28 vs 49 days, P < 0.001) in women received control acupuncture, yet it was no longer significant after adjustment for clomiphene. Conclusion: High expectancy of acupuncture treatment was associated with significant higher ovulation, less bruising and lower dropout, but not other fertility outcome in infertile women with PCOS receiving acupuncture. Trial Registration:ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081.
Assessing The Performance of Physician’s Prescribing Preference As An Instrumental Variable in Comparative Effectiveness Research With Moderate and Small Sample Sizes: A Simulation Study
Authors: Zhang Lisong , Lewsey Jim , McAllister David
Published: December 2021

BackgroundInstrumental variable (IV) analyses are used to account for unmeasured confounding in Comparative Effectiveness Research (CER) in pharmacoepidemiology. To date, simulation studies assessing the performance of IV analyses have been based on large samples. However, in many settings, sample sizes are not large.Objective In this simulation study, we assess the utility of Physician’s Prescribing Preference (PPP) as an IV for moderate and smaller sample sizes.MethodsWe designed a simulation study in a CER setting with moderate (around 2500) and small (around 600) sample sizes. The outcome and treatment variables were binary and three variables were used to represent confounding (a binary and a continuous variable representing measured confounding, and a further continuous variable representing unmeasured confounding). We compare the performance of IV and non-IV approaches using two-stage least squares (2SLS) and ordinary least squares (OLS) methods, respectively. Further, we test the performance of different forms of proxies for PPP as an IV.ResultsThe PPP IV approach results in a percent bias of approximately 20%, while the percent bias of OLS is close to 60%. The sample size is not associated with the level of bias for the PPP IV approach. However, smaller sample sizes led to lower statistical power for the PPP IV. Using proxies for PPP based on longer prescription histories result in stronger IVs, partly offsetting the effect on power of smaller sample sizes.Conclusion Irrespective of sample size, the PPP IV approach leads to less biased estimates of treatment effectiveness than conventional multivariable regression adjusting for known confounding only. Particularly for smaller sample sizes, we recommend constructing PPP from long prescribing histories to improve statistical power.
Atomistic Mechanisms of Human TRPA1 Activation By Electrophile Irritants Through Molecular Dynamics Simulation and Mutual Information Analysis
Authors: Habgood Matthew , Seiferth David , Zaki Afroditi-Maria , Alibay Irfan , Biggin Philip
Published: December 2021

The ion channel TRPA1 is a promiscuous chemosensor, with reported response to a wide spectrum of noxious electrophilic irritants, as well as cold, heat, and mechanosensation. It is also implicated in the inception of itch and pain and has hence been investigated as a drug target for novel analgesics. The mechanism of electrophilic activation for TRPA1 is therefore of broad interest. TRPA1 structures with the pore in both open and closed states have recently been published as well as covalent binding modes for electrophile agonists. However, the detailed mechanism of coupling between electrophile binding sites and the pore remains speculative. In addition, while two different cysteine residues (C621 and C665) have been identified as critical for electrophile bonding and activation, the bound geometry has only been resolved at C621. Here, we use molecular dynamics simulations of TRPA1 in both pore-open and pore-closed states to explore the allosteric link between the electrophile binding sites and pore stability. Our simulations reveal that an open pore is structurally stable in the presence of open ‘pockets’ in the C621 / C665 region, but rapidly collapses and closes when these pockets are shut. Binding of electrophiles at either C621 or C665 provides stabilisation of the pore-open state, but molecules bound at C665 are shown to be able to rotate in and out of the pocket, allowing for immediate stabilisation of transient open states. Finally, mutual information analysis of trajectories reveals an informational path linking the electrophile binding site pocket to the pore via the voltage-sensing-like domain, giving a detailed insight into the how the pore is stabilized in the open state.
Identification of Novel Chemical Entities for Mirk/Dyrk1B Receptor Using Molecular Modeling and Molecular Dynamic Approaches
Authors: Vanajothi Ramar , Bhavaniramya Sundaresan , Umadevi Muthu , Vijayakumar Rajendran , Alqurashi Yaser E. , Premkumar Kumpati
Published: December 2021

Cancer is a major health problem worldwide and one of the leading death-causing diseases. Mirk (Minibrain-related kinase is a member of the dual-specificity tyrosine-phosphorylation-regulated kinase (Dyrk) family that is highly upregulated in various solid tumors and mediates cell survival including lung cancer. Mirk effectively increases the expression of a series of antioxidant genes, which scavenge the reactive oxygen species and stabilize the p27kip1 that maintain the viability of the quiescent cancer cell and also mediates the cell cycle and survival of cancer cells by influencing the MAPK/ERK signaling pathway. Hence, Mirk acts as a novel therapeutic target for cancer prevention. Owing to the unavailability of the three-dimensional structure of Mirk, in the present study, we have modeled the 3D structure of Mirk, based on the crystal structure of Dyrk1a as a template, and subsequently used it as a target for virtual screening and molecular docking against a small molecule database. Based on the visual inspection, four best hits such as Chembridge_ID 7768949, 7771055, 7758866, and 7764195 have high binding affinity, good docking score, and pharmacokinetic properties were shortlisted. Further, the dynamic stability of lead molecules with modeled Mirk/Dyrk1B was evaluated using 10 ns molecular dynamics simulation approach. The four hit molecules exhibited good and stable binding complex in the binding pocket of the target protein. Collectively the finding of this study suggested that the identified molecules may serve as potential effective anti-cancer inhibitors for cancer prevention.
Ultrasound-guided Serratus Anterior Plane Block Versus Thoracic Paravertebral Block on Alleviating the Acute and Chronic Pain Following the Video-assisted Thoracic Surgery: a Prospective, Randomized, Double-blinded Non-inferiority Clinical Trial
Authors: Wang Yan , Hao Jing , Huang Simin , Gu Xiaoping , Ma Zhengliang
Published: December 2021

The authors have requested that this preprint be removed from Research Square.
Design, Synthesis and Biological Evaluation of Indoline Derivatives as Multifunctional Agents for the Treatment of Ischemic Stroke
Authors: Du Shuaishuai , Jin Fan , Li Jiaming , Ma Xiaodong , Wang Hongwei , Qian Shihu
Published: December 2021

In this work, a series of indoline derivatives as multifunctional neuroprotective agents for battling ischemic stroke were designed, synthesized, and biologically evaluated. In antioxidant assay, all compounds showed significant protective effects against H2O2-induced death of RAW 264.7 cells. In oxygen glucose deprivation/reperfusion (OGD/R)-induced neuronal damage, some compounds significantly elevated the cell survival rate. Among them, 7i, 7j and 7r exerted comparable neuroprotective effects to Ifenprodil, and exhibited binding affinity to N-methyl-D-aspartic acid receptors 2B (NMDA-GluN2B). At the concentrations of 0.1, 1 and 10 μM, 7i, 7j and 7r dose-dependently lowered the LPS-induced secretion of inflammatory cytokines, including TNF-α, IL-6 and NO, by BV-2 cells. Importantly, 7i and 7j can dramatically reduce the cerebral infarction rate and improve neurological deficit scores in middle cerebral artery occlusion (MCAO) rat model. As demonstrated by the above results, 7i and 7j are potential neuroprotective agents for the treatment of ischemic stroke.
Hyperbaric Oxygen Combined with Alginate Oligosaccharide Delay D-gal-induced Liver, Kidney and Spleen Senescence in Mice by Attenuating Oxidative Stress
Authors: Wang Gui-Mei , Zheng Xiao-yue , Wang Pei-Song , Wan Jin-E , Gu Jian , Chen Ming , Long Ying , Mao Yongjun
Published: December 2021

Objectives Hyperbaric oxygen treatment (HBOT) is an adjuvant therapy progressively applied in the treatment of clinical diseases, and alginate oligosaccharide (AOS) is a natural polysaccharide with excellent antioxidant property. In this study, the effects of HBOT combined with AOS on the senescence on liver, kidney and spleen were investigated in a D-galactose (D-gal) -induced senescent mice model. Results The findings indicated that HBOT combined with AOS could delay D-gal-induced aging of liver, kidney and spleen in mice. Specifically, HBOT combined with AOS improved the daily behavior and organ indices of mice. Biochemical and morphological analyses of all tissues indicated that HBOT combined with AOS markedly decreased the unusual elevation of ALT, AST and CREA induced by D-gal, alleviated pathological injury, and significantly enhanced the capacity of antioxidant defense system of mice, including increaing T-SOD, CAT AND GSH-Px activities and decreasing MDA content . In addition, Western Blot results indicated that HBOT combined with AOS also inhibited the overexpression of aging-related proteins p53 and p16. Conclusions To some extent, these findings suggest that HBOT combined with AOS has significant anti-senescence potential in D-gal-induced senescent mice, and the underlying factors may be correlated with the enhancement of antioxidant defense capacity.