bluuebunny/crossref_metadata_2025 huggingface dataset:
Karbon Salınımının, Ekonomik Büyüme ve Finansal Gelişme ile İlişkisi: Türkiye Örneği
Authors: ŞAHİN Cumhur , ÜNAL Seyfettin
Published: November 2023

Amaç: Bu araştırma, Türkiye’de 1990-2020 dönemine ilişkin karbondioksit emisyonu, ekonomik büyüme ve finansal gelişme arasındaki ilişkiyi ortaya koymayı amaçlamaktadır.

Tasarım/Yöntem: Araştırmada birim kök testi için Augmented Dickey Fuller (ADF) ve Phillipp-Perron (PP) birim testlerine başvurulurken; zaman serilerinde Zivot-Andrews birim kök testleri, eş bütünleşme için Gregory-Hansen eşbütünleşme testi kullanılmıştır. Nedensellik analizlerinde, Toda-Yamamoto ve Granger nedensellik testinin bootsrap üzerinden yapıldığı Hacker ve Hatemi-J Bootsrap nedensellik testi kullanılmıştır. Analizler E-views 7.0 programında yürütülmüştür.

Bulgular: Analizlerin sonuçları, karbon dioksit salınımının Türkiye’de makroekonomik ve finansal gelişme bağlamında bir etkiye sahip olmadığını göstermektedir.

Sınırlılıklar: Örneklem, Türkiye için 1990-2020 periyoduna ilişkin karbon dioksit emisyonu, ekonomik büyüme ve finansal gelişme endeksi değişkenlerini kapsamaktadır.

Özgünlük/Değer: Konu, pek çok çalışmada farklı yönleriyle yoğun bir biçimde ele alınmasına karşın, özellike Türkiye açısından sınırlı bir literatür söz konusudur. Dolayısıyla, çalışma bu alandaki boşluğun doldurulmasına katkı sunacaktır.
Dış Ticaret İktisadi Büyüme Etkileşimine İlişkin Hipotezlerin Geçerliliği: Türkiye Örneği
Authors: ALANCIOĞLU Erdal , BAYRAKTUTAN Yusuf
Published: November 2023

Amaç: Türkiye büyüme performansında ihracat ve ithalatın etki kanalı olarak konumunu saptamak üzere bu çalışmada, 1980-2021 dönemi için iktisadi büyüme, ihracat ve ithalat arasındaki dinamik ilişkilerin araştırılması amaçlanmaktadır.

Tasarım/Yöntem: Teorik bilgiler, lietarür ve VAR yöntemi ile analiz.

Bulgular: Analiz bulguları, ihracattan iktisadi büyümeye tek yönlü ilişkiye karşın, ithalat ile büyüme arasında çift yönlü nedensellik ortaya koymaktadır. Bulgulardan hareketle, analiz döneminde hem ihracata hem de ithalata dayalı büyüme hipotezinin geçerli olduğu belirlenmiş olmaktadır.

Sınırlılıklar: Hipotezler, sadece Türkiye için test edilmiştir. Yeni çalışmalarda farklı ülkelerle örneklem genişletilerek hipotezlerin geçerliliği araştırılabilir.

Özgünlük/Değer: Bu çalışma hem ihracatın hem de ithalatın büyüme üzerindeki etkisini, ortodox politikalardan farklı bir ekonomi modeli deneyen Türkiye için araştırarak mevcut literatüre katkı sağlamayı amaçlanmıştır.
EXERIMENTAL ESTIMATION OF HARD TURNING CONTACT CHARACTERISTICS
Authors: Manokhin Andrey , Melniychuk Yuriy , Klimenko Sergey , Klimenko Sergey , Chumak Anatoliy , Ryzhov Yuriy , Kamchatna-Stepanova Kateryna
Published: November 2023

When processing hardened steel with a PcBN cutting tool in conditions close to orthogonal cutting, the cutting forces are determined depending on the amount of feed and cutting speed. The value of contact stresses, friction coefficient and the length of contact of the chip with the front surface of the cutter for a cutting speed of 100 m/min were determined, and the sections of the chip were obtained, which demonstrate the morphology of the chip. It was experimentally established that when processing hardened bearing steel, the magnitude of the tangential and radial components of the cutting force acting on the front surface of the tool at a feed of 0.05 mm/rev and a cutting speed of 100 m/min is 125 N/mm and 42 N/mm, respectively. The average coefficient of friction is 0.33. It is shown that to measure the contact length of the chip with the front surface of the cutter, it is advisable to use thin metal PVD coatings with a thickness of ~ 0.1 μm, which allows to increase the accuracy of determining this parameter. Chip samples obtained in the investigated range of processing conditions indicate a segmental type of chip formation. Chip thickness measurements obtained at a feed of 0.05 mm/rev and a cutting speed of 100 m/min range from 40 to 80 µm in thickness.
AN EFFECTIVE MODEL FOR CALCULATING THE NONLINEAR RIGIDITY OF BALL BEARINGS
Authors: Havin Valerij , Kyrkach Borys , Pogorilov Sergij , Sherhin Sergij
Published: November 2023

An analysis of the features of the static calculation of the spindle assembly for stiffness, taking into account the stiffness of the supports, was carried out. It is noted that during the static analysis of spindle shafts, approximate reference values of the rigidity of supports - rolling bearings are usually used. which can give an error in estimating the stiffness of the support up to 50%. The paper presents an analysis of the modified Jones-Harris method for calculating the stiffness of bearings, which provides an increase in accuracy due to new constants in the dependencies for the radial stiffnesses of support and support-thrust ball bearings. The finite element models used instead of the Hertzian contact model in the modified Jones-Harris model in the contact problem "rolling element - bearing rings" more accurately reflect the geometry and stiffness of the bearing raceways, which allow obtaining more accurate constants for the nonlinear stiffness model of ball bearings. The advantage of the modified model is the possibility of automatic calculation of the technological gap in the bearing and the speed of rotation of the shaft. The calculation of the stiffness of SKF bearings showed greater accuracy, which is confirmed by comparison with the experiment. The results of the stiffness calculation obtained for a number of SKF bearings can be successfully used for practical stiffness calculations of radial and radial thrust ball bearings of other firms, the structural and technological characteristics of which correspond to the characteristics of the SKF bearings considered in the work.
Sejuta Potensi dan Inspirasi
Authors:   Universitas Muhammadiyah Sidoarjo, Eko Agus Suprayitno Eko Agus Suprayitno
Published: November 2023

Segala puji dan syukur penulis panjatkan ke hadirat Tuhan Yang Maha Esa, yang telah memberikan berkat dan karuniannya sehingga penulis dapat menyelesaikan Sebuah Buku hasil Karya kegiatan Kuliah Kerja Nyata (KKN) Terpadu Universitas dengan judul “SEJUTA POTENSI DAN INSPIRASI DI DESA ENTALSEWU”. KKN bukanlah hanya pengabdian kepada masyarakat, akan tetapi merupakan kegiatan yang memadukan unsur Pendidikan, Penelitian, dan Pengabdian Kepada Masyarakat, Dimana tiga hal tersebut terkemas dalam istilah “Tri Dharma Perguruan Tinggi”.
The Potential Bryophyta Diversity On Riverside Susup As Science Teaching Materials For SMP
Authors: Ronggo Waskito Jefri , Karyadi Bakti , Sutarno Sutarno , Parlindungan Deni , Ekaputri Rendi Zulni , Sakti Indra , Uliandari Mellyta
Published: November 2023

The purpose of this study was to determine the diversity of bryophyta on the riverside Susup as learning material in the form of Learning Unit Books (BUP). The research method used is Research and Development which is limited to needs analysis and BUP design. Moss plant diversity samples were obtained using a purposive sampling technique. Found 10 families, 13 types of species and 80 total bryophyta colonies on the banks of the river. The diversity index (H') ranges from 1.474 - 1.911 which includes the medium category, the evenness index (E) ranges from 0.822 - 0.940 which includes the high category and the dominance index (C) ranges from 0.1550 - 0.3056 which includes the low category. These findings are then used as teaching materials for designing BUP for SMP.
Profile of Basic and Integrated Science Process Skills in Science Learning at Madrasah Ibtidaiyah Negeri
Authors: Farida Laila , Suryajaya Suryajaya , Suyidno Suyidno
Published: November 2023

Science process skills underlie every student's activity in learning science at school and its application in technology and problem-solving. However, these skills are not trained enough in the Madrasah Ibtidaiyah Negeri (MIN). Therefore, the purpose of this study was to describe the profile of basic and integrated science process skills in MIN students. This research is a quantitative and qualitative descriptive study, where 79 students from 4 MINs in Hulu Sungai Utara were involved in working on a science process skills test instrument adapted from Suja (2010). The results showed the achievement of students' basic science process skills including measuring, questioning, communication, predicting, classifying, inferring, and observation; as well as the achievement of integrated science process skills including formulating hypotheses, planning experiments, interpreting data, and applying concepts with the lowest being 5.3% (hypothesizing) and the highest being 51.8% (measuring). Therefore; The profile of students' basic and integrated science process skills is still not good. Considering scientific process skills as the basic foundation in learning science, educators need to cultivate these skills in learning scientific concepts and their application in solving real life problems.
The Analysis of Misconceptions in Simple Airplane Material for 8th Grade Students in SMP Muhammadiyah 3 Gorontalo
Authors: Fahrunissa Putri , Buhungo Trisnawaty Junus , Pikoli Masrid
Published: November 2023

This study aims to (1) determine students' conception maps in simple machine material (2) analyze students' misconceptions in simple machine material. This research is a descriptive research. The research subjects were class VIII of SMP Muhamadiyah 3 Gorontalo City with a sample size of 25 students. The/research data were obtained from students' answers through a three-level multiple-choice diagnostic test (Three Tier Multiple Choice) and processed based on the pattern of student answers grouped into categories of understanding the concept, misconception 1, misconception 2, misconception 3 and not understanding the concept. The results showed that category 1 misconception had a percentage of 23%, misconception 2 had a percentage of 17%, and misconception 3 had a percentage of 25%.
Salafist Preachers Struggle to Affirm Allah Attributes in Anthropomorphism Verses on YouTube
Authors: Romadlon Dzulfikar Akbar , Biyanto Biyanto
Published: November 2023

The issue of anthropomorphic verses that describe God with human characteristics has been the subject of a long debate between the Ash'arism and Salafist groups. Ash'arism interprets these verses using ta'wil, but the Salafis reject this opinion because Allah can explain Himself, so ta'wil is prohibited. This kind of debate has become public consumption in this era because it spreads through social media, including YouTube. In this article, the author will discuss Salafist preachers' efforts in confirming Allah's attributes in anthropomorphic verses on YouTube, using a three-dimensional Critical Discourse Analysis (CDA) from Fairclough's perspective: micro-level, meso-level, and macro-level. In a micro-level analysis, the author concludes that Salafist affirm Allah's attributes in anthropomorphic verses without takyif and tahrif. In the meso-level analysis, Salafist preachers have an audience mainly Salafist followers. However, some viewers disagreed with the Salafism of NU followers and wrote criticism in the comments column. In macro-level analysis, the Salafist rejection of ta'wil is part of the spirit to secure the authority of Islamic texts, based on the understanding of the salaf. Many people follow the Salafi ideology because The Kingdom of Saudi Arabia supports the Salafists by creating cadres from each country through education so that their ideology spreads throughout the world.
Loss of macrophage TSC1 exacerbates sterile inflammatory liver injury through inhibiting the AKT/MST1/NRF2 signaling pathway
Authors: zhu qiang , Ni Ming , qiu jiannan , liu Guoqing , Sun Xiaohu , Zhu Wenjie , Wu Peng , Chen Zheng , Qiu Jiajing , Wu Ziming , Zhang Yang , Zhang Feng , Li Changyong , Gao Yuan , Zhou Jun
Published: November 2023

Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficientmacrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors.
Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients.
Comparative Metagenomics to Study the Impact of Soil Salinity on Microbial Diversity in Al-Madinah, KSA
Authors: Waznah Moayad S , Albasri Hibah M , Albahri Hassan A
Published: November 2023

The chemical properties and fertility of soil are greatly influenced by soil microbes, which are essential to the biogeochemical cycle. Analyzing the microbial structure of soil is important for efficient use of the soil, whether it be for agricultural purposes or other uses. Sabkhat Al-Madinah in Saudi Arabia has soil with high salinity and plants that thrive in that environment. The microbial makeup of the soil in this area has not been extensively researched. This study aimed to analyze the microbial structure of two locations in Sabkhat Al-Madinah's soil and examine the correlation with soil properties. The 16S rRNA gene's V3-V4 region was targeted for metagenomic analysis using Illumina MiSeq. The soil chemical properties including EC, pH as well the concentration of some soil elements were determined. The microbial composition of both sites were investigated at different taxonomic levels using MG-RAST and QIIME2 pipelines. There was a significant difference in salt concentration between the two sites that were derived from the same sabkha. The second sample had higher sodium content, leading to increased E.C measures. Moreover, The two samples had different microbial compositions. The first sample was dominated by Bacteroidetes (18.37%), Firmicutes (13.57%) and Proteobacteria (13.57%), while the second one contained Proteobacteria (25.01%), Actinobacteria (12.03%) and Firmicutes (11.36%). Firmicutes were newly recorded and found only in saline habitats in KSA. Acidobacteria, Thermodesulfobacteria and Streptophyta were present only in the first sample, while Verrucomicrobia sequences were identified only in the second sample which had higher salt content. On the genus level, 16 genera were found across both samples withBacillusbeing the most prevalent at 5.17% followed byMarinoscillum(4%),Fibrobacter(3.57%) andRubrobacter(3.45%) in the first sample. The second soil sample had a dominant genus,Halomonas, making up 10.64% of the total sequences. Other genera present included Fibrobacter (3.96%),Nitrospira(3.92%),Rubrobacter(3.36%) andMethylophaga(3%). In conclusion, the analysis of bacteria in the two sites revealed notable differences in soil properties and bacterial diversity.
The impact of FFP2 masking on medical wards for allogeneic hematopoietic stem cell transplantation: Retrospective analysis for future guidance
Authors: Richardson Tim , Holtick Udo , Scheid Christoph , Schuette Daniel , Feyer Kim , Grass Lea , Simon Florian , Goedel Philipp , Hallek Michael , Braun Till , Fuerstenau Moritz
Published: November 2023

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the covid-19 pandemic.
We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 2018 – 2020 to the era of FFP2 masking between 2021 – 2023 covering similar seasons of the year. Each group consisted of 150 matched patients.
The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22,1% to 2,1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23,5 days (p = 0,002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0,057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0,78).
Our retrospective results indicate that FFP2 masks worn by patients and hospital staff significantly reduce the incidence of viral respiratory infections, including covid-19, shorten the time spent in hospital and reduce costs without affecting survival.
Extracellular vesicles from Nurse-Like Cells and THP1-derived Type-2 macrophages transfer aggressiveness to chronic lymphocytic leukemia cells
Authors: Gallet Paul-Francois , Ikhlef Lea , Ratti Nina , Durand Stephanie , Formento Remy , Guillou Clement , Daverat Heloise , Boutaud Marie , Dmytruk Natalya , Gachard Nathalie , Cosette Pascal , Jauberteau Marie-Odile
Published: November 2023

The resistance of leukemic B cells to cell death is mainly associated with interactions within the tumor microenvironment, where they interact with various types of cells. Within this microenvironment, CLL B cells produce and bind cytokines, growth factors, and microvesicles. In the present study, extracellular vesicles (EVs) purified from nurse-like cells and M2-polarized THP1 cell (M2-THP1) cultures were added to CLL B cell cultures. The vesicles were rapidly internalized by B cells, leading to a decrease in spontaneous apoptosis and an increase in proliferation. Additionally, the vesicles induced an increase in the resistance of CLL B cells to Bruton kinase inhibitor Ibrutinib. A transcriptomic analysis showed an increase in the expression of anti-apoptotic gene Bcl-2 but not Mcl-1 and an increase in the expression of proliferation-inducing gene APRIL following treatment of CLL B cells with EVs derived from both NLCs and M2-THP1 cells. Meanwhile, an analysis of apoptotic protein markers revealed increased amounts of IGFBP-2, CD40, p53 and Bcl-2 following EVs treatment. Finally, exploration of EVs protein content by mass spectrometry revealed they carry various proteins involved in known oncogenic pathways and the RNAseq analysis of B CLL cells treated or not with NLCs EVs show various differentially expressed genes.
How Scientist Identity Shapes Engagement with Environmental Activism: Findings from a Multinational Survey
Authors: Finnerty Samuel , Levine Mark , Piazza Jared
Published: November 2023

Scientists are increasingly joining environmental movements. As knowledge producers and influential figures in society, scientists are uniquely positioned to drive change. The present study explored how “scientist identity” shapes engagement in environmental activism. Participants were 329 scientists from 41 countries. Scientist identity content, specifically perception of the science-activism relationship, was a more significant predictor than mere strength of identification as a “scientist”. Perceiving a harmonious relationship between science and activism, endorsing environmental stewardship as a scientist’s duty, and believing objectivity and impartiality remained uncompromised by activism, each had significant correlations with engagement. These components formed a composite variable, which remained a strong predictor of engagement even when accounting for the influence of activist identity. Scientists embracing this scientist-activist compatibilism were also less inclined to view new technologies as a panacea for the climate crisis. This research underscores the vital role of scientist identity content in shaping climate actions and perspectives.
Projection of Diabetes Morbidity and Mortality till 2045 in Indonesia: A Dynamic Modeling Based on Risk Factors and National NCD Prevention and Control Programs
Authors: Wahidin Mugi , Achadi Anhari , Besral Besral , Kosen Soewarta , Nadjib Mardiati , Nurwahyuni Atik , Ronoatmodjo Sudarto , Rahajeng Ekowati , Pane Masdalina , Kusuma Dian
Published: November 2023

Background: Diabetes Mellitus is one of the biggest health problems in Indonesia but the research on the disease’s projection is still limited. This study aimed to make a projection model of prevalence and mortality of diabetes in Indonesia based on risk factors and NCD programs.
Method: The study was a quantitative non-experimental study through multiple linear regression models and system dynamics. The baseline projection was created by 2018 data and projections until 2045 involved the dynamization of risk factors and programs, population, and case fatality rate. The model was created from 205 districts data. This study used secondary data from Basic Health Research, BPJS Kesehatan, NCD programs, and Ministry of Health.
Results: The prevalence of diabetes in Indonesia is estimated to increase from 9.19% in 2020 (18.69 million cases) to 16.09% in 2045 (40.7 million cases). The prevalence will be lower to 15.68% (39.6 million) if interventions of programs were carried out, and to 9.22% (23.2 million) if the programs were added with prevention of risk factors. The projected number of deaths due to diabetes increases from 433,752 in 2020 to 944,468 in 2045. Deaths due to stroke among diabetes increases from 52,397 to 114,092 in the same period. Deaths from IHD among diabetes increase from 35,351 to 76,974, and deaths from chronic kidney disease among diabetes increase from 29,061 to 63,279.
Conclusion: Diabetes prevalence and mortality in Indonesia rise significantly in Indonesia and can be reduced by intervention of several programs and risk factors.
Impact of late winter sea surface temperature seesaw between equatorial central Pacific and Philippine Sea on early spring vegetation over the low-latitude highlands of China
Authors: Pan Wei , Zhao Jingchuan , Chen Bing , Wu Jian , Li Hudie , Zhang Ziyu , Song Yanfang
Published: November 2023

In this study, the impact of late winter (January-February) sea surface temperature (SST) seesaw between equatorial central Pacific and Philippine Sea on early spring (March-April) vegetation interannual variation over the low-latitude highlands of China (CLLH) is investigated. The positive phase of late winter seesaw SST pattern, characterized by warmer(colder)-than-normal SSTs in the equatorial central Pacific (Philippine Sea), favors early spring CLLH vegetation growth. From the local perspective, the positive phase of late winter SST seesaw results in stronger(higher)-than-normal precipitation (surface air temperature) in the west (east) of the CLLH, these abnormal signals may be recorded by land surface and may persist to early spring, and this wetter(warmer)-than-normal land surface condition in the west (east) of the CLLH favors local vegetation growth. For the atmospheric circulation anomalies, the positive phase of late winter seesaw SST pattern contributes to an anomalous anticyclone over Philippine Sea in lower troposphere. On one hand, anomalous northerly winds on the eastern flank of this anomalous cyclone advect off-equatorial dry and cold air to the Maritime Continent and cause precipitation reduction there, consequently an anomalous anticyclone over the tropical north Indian Ocean in lower troposphere is excited via a Gill-type Rossby wave atmospheric response. This anomalous anticyclone leads to enhanced water vapor transport and increased precipitation in the west of the CLLH resultantly. On the other hand, southerly wind anomalies being the western flank of the anomalous anticyclone advect warm air to the east of the CLLH, result in increased surface air temperature there.
Optimization of the process conditions for methane yield from co-digestion of mixed vegetable residues and pig manure using response surface methodology
Authors: Meng Yan , Li Yi , Han Rui , Du zhongping
Published: November 2023

To determine optimized conditions for co-digestion for a mixture of four kinds of mixed vegetable crop residues consisting of cucumber, tomato, eggplant, and pepper mixed in equal parts on a mass basis, co-digestion experiments were carried out with pig manure. The interaction effects of parameters such as manure-to-mixed vegetable residues ratios (M/S), initial pH, and organic load (OL) were investigated with respect to cumulative methane yield using response surface methodology (RSM). The highest cumulative methane yield was calculated to be 380.50 mL/g VS at an initial pH of 7.3, OL of 18.8 g VS/L, and M/S of 3.9:1. Comparison and verification experiments showed that under optimized conditions the co-digestion process showed increased the methane yield and had practical application value. The microbial analysis showed that the relative abundances of bacterial taxa, such as Clostridium_sensu_stricto_1, Fastidiosipila, and Terrisporobacter, were all highest in the co-digestion samples under optimized process conditions (PV). Different types of methanogenic archaea taxa in PV samples were richer than other samples, which showed higher relative abundances of Methanogenium, Methanobrevibacter, Methanoplanus, Methanospirillum, and Methanobrevibacter. Thus, the co-digestion system of a mixture of vegetable residues and pig manure can enrich different types of methanogenic archaea taxa, which leads to increased digestion performance, and may strengthen process stability. Importantly, pig manure, mixed vegetable residues can be included into anaerobic digestion applications through co-digestion, thus enabling valorization of these substantial residues and can be engineered for applications.
The ratio of corpus luteum and coexistent follicle was notably high before embryo transfer in Hanwoo cows (Bos taurus coreanae)
Authors: Lim Su-Geun , Yi Junkoo , Ha Jaejung , Park Jinyeon , Kwon Woo-Sung , Yu Daejung , Ryoo Zaeyoung , Kim Daehyun
Published: November 2023

The authors have requested that this preprint be removed from Research Square.
Nanocrystals and nanosuspensions: an exploration from classic formulations to advanced drug delivery systems
Authors: Rossier Benjamin , Jordan Olivier , Allémann Eric , Rodriguez-Nogales Carlos
Published: November 2023

Nanocrystals and nanosuspensions have become realistic approaches to overcome the formulation challenges of poorly water-soluble drugs. They also represent a less-known but versatile platform for multiple therapeutic applications. They can be integrated into a broad spectrum of drug delivery systems including tablets, hydrogels, microneedles, microparticles, or even functionalized liposomes. The recent progresses, challenges, and opportunities in this field are gathered originally together with an informative case study concerning an itraconazole nanosuspension-in-hydrogel formulation. The translational aspects, historical and current clinical perspectives are also critically reviewed here to shed light on the incoming generation of nanocrystal formulations.
Change characteristics and source apportionment of ozone pollution in Sanya City in 2019
Authors: Huang Ding , wang ping , Lu Fang , Zhao Youzhi , Ding Wenci , Du Jiaxin
Published: November 2023

This article is based on the hourly data of O3 and NO2 in Sanya City in 2019, various collected meteorological data, and online monitoring of VOCS major species data to analyze the characteristics of ozone pollution changes and source apportionment in Sanya City. The results indicate that 1) the daily variation characteristics of ozone pollution in Sanya City conform to the typical characteristics of ozone photochemical pollution events and 2) the EKMA curve indicates that Sanya City as a whole belongs to a NOX-sensitive area. The OH consumption rate (LOH) and ozone generation potential (OFP) indicate that the key active components of VOCS are mainly isoprene, ethylene, n-butane, propane, etc. The corresponding main potential sources of emissions include combustion emissions, solvent volatilization, and automotive exhaust emissions. 3) The O3 emission reduction plan is to reduce the ozone concentration from 180 µg·m− 3 to 158 µg·m− 3, corresponding to a 25% and 20% reduction in the concentrations of the two main precursors, NOX and VOCS, respectively. This article provides scientific support for the problem of ozone photochemical pollution in Sanya City.
Pathological Changes and Immunohistochemical Detection of Encephalitozoon cuniculi of Fox Origin
Authors: Gao Yan , Liu Li-fan , Hu Yi-shu , Wang Hao
Published: November 2023

Encephalitozoon cuniculi is an obligate intracellular parasitic eukaryotic pathogen.The blue fox (Alopex lagopus) is one of the most susceptible species of microsporidian in rabbit encephalitis. In this study, the kidney, brain, heart, liver, spleen and intestine tissues of diseased and healthy blue foxes were collected, and paraffin sections were prepared by H&E staining. The pathological changes of each tissue were observed under a microscope, photographed and pathological analysis was performed, and the results were found by comparison The fox’s kidney and brain are susceptible tissues of microsporidian rabbit encephalitis. The typical pathological changes are chronic interstitial nephritis and diffuse non-suppurative meningoencephalitis. Heart and liver tissues occasionally have inflammatory lesions, while the spleen and There is no obvious lesion in the intestinal tissue. The kidney and brain tissues, which are susceptible to the disease, were selected for immunohistochemical tests. The fox serum was purified by affinity chromatography to prepare fox IgG, fox IgG was used as the primary antibody, rabbit anti-fox IgG was used as the secondary antibody, DAB was used as the developer, and hematoxylin staining was used to establish an immunohistochemical detection method to locate rabbit encephalitis microbes. Sporozoite antigen. The spores of Microsporidium encephalitis were observed in the kidney and brain tissues of sick foxes by immunohistochemistry. The spores of rabbit encephalitis were brown and granular. In the kidney tissue, the spores were mostly located in the renal capsule and tubule, while in the brain tissue only A few spores were found. Through the preparation of paraffin sections, the histopathological changes of the blue fox infected with Microsporidium encephalitis in rabbits were analyzed specifically to provide guidance for the diagnosis of the disease. The immunohistochemical method established in this study shows that it is more specific than histopathological diagnosis, can accurately locate the location of microsporidium, and is suitable for the detection of fox-derived rabbit encephalitis microsporidia.
Evaluating Bovine Umbilical Cord Stem Cells and Glutamine for Hepatic Injury in Acute Pancreatitis
Authors: Guan Weijun
Published: November 2023

Acute pancreatitis (AP) is a localized-to-systemic inflammatory disorder that triggers the release of various proinflammatory mediators. Unfortunately, effective treatments for this condition are currently lacking, and a substantial portion of AP patients succumb to liver failure due to the intricate physiological and pathological interplay between the liver and pancreas.Umbilical cord mesenchymal stem cells (UCMSCs) exhibit notable attributes, including multipotent differentiation capacity, colony-forming potential, and robust migratory responses to injury. Glutamine, an essential amino acid in cell culture and a source of immune cells, is used in early nutritional interventions to help with pancreatitis.In this study, our objective was to evaluate the therapeutic efficacy of a combinatorial approach involving UCMSCs and glutamine in the management of hepatic injury associated with pancreatitis.
To accomplish this objective, we established an acute pancreatitis murine model and administered UCMSCs via tail vein njections while concurrently providing oral glutamine supplementation. The homing of these cells was observed in rats through fluorescence microscopy. A comprehensive array of techniques was employed to assess treatment outcomes.Histopathological examination, as revealed by HE staining, demonstrated a significantly reduced extent of pancreatic tissue damage in both the UCMSC-treated and combined therapy groups compared to the AP control group. Serum amylase and lipase activities were markedly diminished in the UCMSC and combined therapy groups in comparison to the untreated AP group (P<0.05).
Furthermore, the expression levels of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α were significantly attenuated, while those of the anti-inflammatory IL-10 and SOD were notably elevated in the UCMSC-treated and combined therapy groups (P<0.05).The assessment of apoptosis, a pivotal aspect of tissue damage in pancreatitis, demonstrated a significantly higher apoptotic index in the untreated AP group (P<0.05), whereas it was significantly lower in the UCMSC-treated and combined therapy groups (P<0.05).
Our findings indicate that the combined therapeutic approach involving UCMSCs and glutamine substantially mitigates hepatocyte apoptosis induced by acute pancreatitis (AP). However, there was no statistically significant difference in efficacy between combination therapy and direct mesenchymal stem cell (MSC) therapy in ameliorating liver injury in the context of pancreatitis(P>0.05). While combination glutamine therapy presents a promising and novel therapeutic avenue, its efficacy not diverges from that of direct cell-based regimens.
Gefitinib effectively treated advanced lung cancer with a rare EGFR L747P mutation in a kidney transplant recipient: the first case report
Authors: Xie Wenxiu , Chen Feng , Zhang Lei , Lin Baoquan , Ye Jia , Yu Zongyang , Liu Wei
Published: November 2023

Allograft kidney transplantation is considered to be the best treatment for end-stage renal disease, which can both improve the quality of life and prolong the life of patients. The inevitable use of immunosuppressants after kidney transplantation is highly associated with De Novo malignancies, which are currently the second cause of death among kidney transplant recipients (KTRs). Previous studies have shown that lung cancer accounts for 3–7% of new malignancies after kidney transplantation. It is well known that the first-line treatment for epidermal growth factor receptor (EGFR) positive advanced non-small cell lung cancer (NSCLC) in the general population is tyrosine kinase inhibitors (TKIs), and this principle also applies to KTRs. But L747P is a rare EGFR mutation in EGFR Exon 19 and the response of patients with EGFR L747P to TKIs remains controversial. Here we report a kidney transplant recipient with advanced lung adenocarcinoma harboring EGFR L747P mutation who benefited from the first-line treatment of gefitinib.
Toward digital ionization: Wide-energy programmable microwave plasma for high coverage mass spectrometry analysis of trace biosamples
Authors: Wang Xiaozhi , Chu Fengjian , Zhao Gaosheng , Wei Wei , Feng Hongru , Pan Yuan-Jiang
Published: November 2023

Although numerous ambient mass spectroscopy (AMS) technologies have been developed over the past 20 years to address diverse analytical circumstances, a single ion source technique that can handle all analyte types is still lacking. In this study, a novel wide-energy programmable microwave plasma ionization mass spectrometry system (WPMPI-MS) is presented, through which MS analysis can achieve high coverage of substances with various characteristics by digitally regulating the microwave energy. In addition, ionizing energy can be rapidly scanned using programmable waveforms, enabling the simultaneous detection of biomolecules, heavy metals, molecular structure, etc., in seconds. WPMPI-MS performed well in the analysis of real samples, rapidly analyzed 9 toxicological standards in one drop of serum, and demonstrated good quantification and LC coupling capability. The prospective uses of the technology in biological and chemical analysis are extensive, and it is anticipated to emerge as a viable alternative to commercially available ion sources.
Integrating Core Physics and Machine Learning for Improved Parameter Prediction in Boiling Water Reactor Operations
Authors: Oktavian M. Rizki , Nistor Jonathan , Gruenwald J. Thomas , Xu Yunlin
Published: November 2023

This study introduces a novel method for enhancing Boiling Water Reactor (BWR) operation simulations by integrating machine learning (ML) models with conventional simulation techniques. The ML model is trained to identify and correct errors in low-fidelity simulation outcomes, traditionally derived from core physics computations. These corrections aim to align the low-fidelity results closely with high-fidelity data. Precise predictions of nuclear reactor parameters like core eigenvalue and power distribution are crucial for efficient fuel management and adherence to technical specifications. Current high-fidelity transport calculations, while accurate, are impractical for real-time predictions due to extensive computational demands. Our approach, therefore, utilizes the standard two-step simulation process—assembly-level lattice physics calculations followed by whole-core nodal diffusion computations—to generate initial results, which are then refined using the ML-based error correction model. The methodology focuses on improving simulation accuracy in regular BWR operations rather than developing a universal ML predictor for reactor physics. This work suggests a promising approach for achieving more accurate, computationally feasible simulation solutions in nuclear reactor operation and management.
A novel IN718 superalloy of superior mechanical properties designed by the first principle and D-electron theory
Authors: Li Rui , Chen Mingzhi , wang Zhandong , Bi Kedong , Sun Guifang
Published: November 2023

A novel IN718 superalloy has been designed based on the commercial IN718 alloy to improve its service performance in the aerospace field. Firstly, first principle calculations were performed to determine the total energy, formation enthalpy, and binding energy of the γ-Ni phase, Laves-Fe2Nb phase, and γ-Ni/Fe2Nb interface model doped with Co, Cr, Mo, V, and Zr atoms in IN718 superalloy. The calculation results reveal the influence of various atoms doping on the typical phases of the IN718 superalloy. Secondly, 8488 group’s suitable alloy composition data were selected from 831600 group’s datasets by D-electron theory and Python programs. Subsequently, the optimal alloy components were determined by thermodynamic calculations using the control variable. Finally, molecular dynamics tensile simulations and mechanical properties tests were conducted to validate the mechanical properties of the optimized superalloy. This entire calculation process serves as a reference for designing other alloy compositions.
Temporal variation in phenoloxidase enzyme activity in haemocyte lysate supernatant (HLS) of grubs of Oryctes rhinoceros
Authors: Marieshwari Balashanmuga Nehru , Keerthana Chitti Babu , Janarthanan Sundaram
Published: November 2023

The phenoloxidase (PO) cascade is a significant component of the innate immune mechanism of insects, involved in melanization, sclerotization, wound healing and melanotic encapsulation. In this paper, we examined the nature of PO activity released from the haemocytes of the grub of Oryctes rhinoceros, by preparing haemocyte lysate supernatant (HLS) without any anticoagulant, as most of it contains EDTA which is reported as one of the inhibitors of the PO enzyme. The empirical analysis performed using different phenolic substrates in order to characterize the appropriate substrate of HLS PO revealed that phenoloxidase from HLS maximally oxidized an o-diphenolic substrate, dopamine followed by a monophenolic substrate tyramine, indicating that PO from HLS belongs to tyrosinase like phenoloxidase type as they possess the properties of catalyzing both monophenolic and diphenolic substrates. Furthermore, maximum PO activity was observed at 5 min of incubation for all the tested substrates at various concentrations. The ideal pH and temperature for HLS PO activity developed using 10 mM dopamine was observed to be 9 and 20°C, respectively. Among the various chemical inhibitors tested, HLS PO activity was significantly reduced in the case of PTU followed by EDTA. Further, PO activity in HLS was found to be increased in vitro by exogenous proteases viz., trypsin and a-chymotrypsin and detergents such as SDS and CPC. In addition, the selective response of HLS PO to activation by different types of bacterial LPS tested, suggested that haemocytes PO serve an important function in non-self recognition and host immune reactions.
Projected changes in the frequency of compound events over tropical Brazil in CORDEX-CORE simulations
Authors: Alves Lincoln Muniz , Firpo Mári Ândrea Feldman , Bettolli Maria Laura , Hasson Shabeh ul , Guerron Oscar , Añazco Alex Avilés , Llopart Marta
Published: November 2023

Under global warming, extreme events have been increasing in the last decade and are projected to increase in the future with every increment of global warming. The potential increase in compound drought and hot events may induce a complex web of impacts on societies, ecosystems, and economies, including crop failure, wildfires, and water scarcity. This is particularly concerning for Brazil, where it has been demonstrated to be vulnerable to recent extreme climate events. Using an ensemble of CORDEX-CORE simulations over Tropical Brazil, we investigate changes in compound events in response to changes in radiative forcing and their impact on climate extreme events, including drought and extreme heat. The simulations are conducted at a 25 km horizontal grid spacing using lateral and lower boundary forcing from three Coupled Model Intercomparison Project Phase 5 (CMIP5) climate models. Each model covers the period from 1980 to 2100 under two Radiative Concentration Pathways (RCP2.6 and RCP8.5) in the 21st-century projection period. We used observed data from the Brazilian Daily Weather Gridded Data (BR-DWGD) to evaluate the simulations and perform a quantitative assessment of areas affected by these compound events during the present day. The study finds a strong agreement between RCM simulations and observed data, particularly in terms of precipitation, with high correlation coefficients. The analysis emphasizes the prevalence of compound climate events during the Austral summer season and projects a significant increase in both extreme heat and drought events in the coming decades. These findings underscore Brazil's vulnerability to compound climate events, highlighting the need for adaptive strategies and policy interventions to mitigate the socio-economic and environmental impacts across various sectors.
OPN promotes pro-inflammatory cytokine expression via ERK/JNK pathway and M1 macrophage polarization in Rosacea
Authors: Tang Siyi , Hu Hao , Li Manhui , Zhang Kaoyuan , liu Xiaojuan , Wu Lin , Yu Bo , Chen Xiaofan
Published: November 2023

Objective: Rosacea is a chronic inflammatory dermatosis that involves dysregulation of innate and adaptive immune systems. Osteopontin (OPN) is a phosphorylated glycoprotein produced by a broad range of immune cells such as macrophages, keratinocytes, and T cells. OPN is significantly elevated in the epidermis of rosacea patients. However, the role of OPN in rosacea remains to be elucidated.
Methods: OPN knockout mice and WT mice were used to establish LL37-induced rosacea-like skin inflammation models. Histological analyses were performed to detect immune cell infiltration and angiogenesis. In addition, we study the mechanism of OPN in keratinocytes by OPN overexpression or deficiency. The co-culture assay was conducted to investigate keratinocyte-macrophage crosstalk in rosacea inflammation.
Results: In this study, it was found that OPN expression was significantly upregulated in rosacea patients and LL37-induced rosacea-like skin inflammation. OPN regulated pro-inflammatorycytokine IL1B and contributed macrophage polarizationtowards M1 phenotype in rosacea-like skin inflammation. In vitro, it was demonstrated that intracellular OPN (iOPN) promoted LL-37-induced IL1B productionthrough ERK1/2 and JNK pathways in keratinocytes . Moreover, secreted OPN (sOPN) played an important role in keratinocyte-macrophage crosstalk.
Conclusions: Our findings identified the different roles of sOPN and iOPN in the pathogenesis of rosacea, suggesting that OPN might be a promising therapeutic target in rosacea treatment.
Clinical Characteristics of Neuro-Behçet's Disease: A Retrospective Study in a Tertiary Care Center in a Third World Country
Authors: Chamoun Nadia , Bejjani Martine El , Ayoubi Nabil El , Hatab Taha , Hazimeh Dana , Ibrahem Michael , Merashli Mira
Published: November 2023

Background
Behçet Disease (BD) is a complex, multi-systemic vasculitis characterized by inflammatory processes in blood vessels. Neuro-Behçet's Disease (NBD) represents a rare yet debilitating manifestation of BD, demanding a comprehensive understanding of its clinical features, prevalence, and distinction between parenchymal and non-parenchymal involvement.
Methods and Results
A retrospective observational study was conducted, spanning the years 2000 to 2022, involving 262 patients diagnosed with BD at a tertiary medical center in Lebanon. Neurological involvement was diagnosed based on International Consensus Recommendation criteria. Patients were stratified into groups based on NBD severity and subtypes, and clinical data, including demographics, manifestations, and genetic factors collected. The modified Rankin Scale (mRS) was used to assess NBD severity. Among the BD cohort, 10.3% were diagnosed with NBD. Clinical manifestations in NBD included prevalent neurological symptoms, with headaches, weakness, and dizziness being most frequent. The study found a similar prevalence of NBD between genders, contrary to some regional studies. Interestingly, HLA B51 positivity was observed in 83.3% of patients tested which were only sixty. Further stratification revealed a higher proportion of severe disease in parenchymal NBD compared to non-parenchymal cases.
Conclusion
This study provides valuable insights into the prevalence and clinical characteristics of NBD in a Middle Eastern population. Despite challenges in diagnosis and limited prevalence, the findings underscore the need for ongoing research to enhance the understanding, diagnosis, and management of NBD. These insights contribute to the broader comprehension of BD, particularly in the context of the Middle East, emphasizing the significance of tailored approaches for effective patient care.