bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical Evidence of PM2.5 Critical Components in the Induction of Myocardial Fibrosis in Mice
Authors: Xing Qisong , Wu Meiqiong , Xue Zhen , Nan Nan , Yan Zhipeng , Li Shuyue , Qin Guohua , Sang Nan 
Published: February 2022

Abstract
Background:PM2.5 components are tightly linked to the initiation of a multitude of cardiovascular diseases (CVD). However, it is unclear that whether critical components of PM2.5 can induce myocardial fibrosis.Methods:We exposed female C57BL/6 mice to PM2.5 (3 mg/kg b.w.) from four different cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) by oropharyngeal aspiration every other day. Thevarying degreesofmyocardial fibrosismarkers (Col1a1, Col3a1)and thepossible relevantindicators, including(E/E¢),NADPH oxidase 4 (NOX4), andtransforming growth factor β1 (TGFβ1)were detected by echocardiographyand / orqPCR and/ or Western blotinvivo.Pb, Cr, Mn, Zn, and most of thepolycyclic aromatic hydrocarbons (PAHs)were positive associated withdiastolic cardiac function andmyocardialfibrosisbyusingPearson correlation. BEAS-2b cells were treated with one or more of five candidate components with or without Guangzhou PM2.5, and the conditioned medium was used to culture AC16 cells. MTT assays were performed to evaluate the cytotoxicity of the treatments.ROS generation was detected by photocatalysis using 2¢,7¢-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of Col1a1, TGFβ1 were detected by qPCRinvitro.Results:The effects of PM2.5 from Taiyuan are the most serious, while Guangzhou group caused minor effects. Zn + Pb + Mn + BaPwith PM2.5 from Guangzhou exposure significantly increased ROS production of BEAS-2b cells, and induced a dramatic increase of myocardial fiber-related gene expression (Col1a1 and TGF-β) in AC16 cells. Conclusion：It indicated that the different mass concentrations of Zn, Pb, Mn, and ΣPAHs in PM2.5mightbe the critical factor thatmodulated myocardial fibrosis induction by targeted. Our study provided anovel avenue for further elucidation of molecular mechanisms of PM2.5 components-induced myocardial fibrosis.
Metformin Combined with Alendronate Ameliorates Osteoarthritis by Attenuating RANKL-Induced Bone Resorption and Protecting Cartilage Against Degradation
Authors: Guo Yanjing , Yang Ruijia , Zong Sujing , Wang Zhenyu , Zhao Jiyu , Chen Chongwei , Wang Chunfang , Wang Shaowei 
Published: February 2022

Abstract
BackgroundThe purpose of the present study was to investigate the effect of metformin combined with alendronate on subchondral bone and cartilage degeneration in a destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mouse model.MethodThe effect of metformin on OA was assessed by H&E, safranin O/fast green, immunohistochemical and tartrate-resistant acid phosphatase (TRAP) staining. The Osteoarthritis Research Society International (OARSI) criteria were used to grade the degeneration of articular cartilage. ATDC5 cells were stimulated with 10 ng/mL IL-1β to establish an in vitro model of OA. Bone marrow macrophages were isolated. Cell proliferation was examined using CCK-8 assays. Cartilage extracellular matrix degradation was analyzed using Alcian Blue staining and high-density culture. Osteoclastogenesis was analyzed using TRAP staining. The mitochondrial membrane potential of ATDC5 cells and osteoclasts was determined by JC-1 fluorescent staining. Immunostaining, RT–PCR, and western blot analyses were carried out to examine protein and RNA expression levels.ResultThere were lower OARSI scores and fewer TRAP-positive cells in DMM mice after treatment with metformin combined with alendronate. In cartilage, metformin inhibited the expression of MMP3 and MMP13 in IL-1β-stimulated OA chondrocytes and increased the expression of Sox9 and aggrecan. In parallel, metformin also inhibited cartilage matrix degradation, as shown by Alcian blue staining and SO/FG staining in ATDC5 cells and cartilage tissues. Moreover, metformin and alendronate downregulated the levels of specific genes and proteins (NFATc1, c-Fos, DC-STAMP, TNFRSF11, CTSK), thereby inhibiting osteoclast differentiation in vitro. Mechanistically, metformin increased the expression of phospho-AMPK alpha1, attenuated the phosphorylation of NF-κB, and reduced reactive oxygen species (ROS) levels.ConclusionMetformin combined with alendronate may be a useful candidate for attenuating early-stage OA. This would be an ideal drug/drug combination for treating osteoarthritis in the presence of osteoporosis combined with T2D.
Intratumoral LAG-3 + cells infiltration determines poor prognosis in patients with castration-naïve prostate cancer
Authors: Dai Bo , Lin Nan , Li Jun-hong , Yang Yun-jie , Zhang Jun-Yu , Zhang Xuan-zhi , Liu Zheng 
Published: February 2022

Abstract
Background: As a transmembrane immune checkpoint protein, lymphocyte-activation gene 3 (LAG-3) is expressed on activated T cells and natural killer cells, could negatively regulate CD8 + T cells activation and reshaped the phenotype of CD4 + T cells to trigger an immunosuppressive function. Previous studies had demonstrated the prognostic value of LAG-3 in different cancers. However, its value in evaluating prognosis and predicting ADT resistance in patients with prostate cancer is still unclear. Method and Materials: The mRNA sequencing data of 498 and 140 prostate cancer specimens were respectively from TCGA and MSKCC. 175 patients with castration-naïve prostate cancer between June 2012 and December 2014 from Fudan University Shanghai Cancer Center at first visit were retrospective analyzed to evaluate the prognostic value of LAG-3 + cells through immunohistochemistry. All patients were treated with androgen deprivation therapy after initial diagnosis. Fresh tumor tissue samples from 18 patients with prostate cancer were examined to discover the phenotype of the immune cells by flow cytometry. Results: High infiltration of intratumoral LAG-3 + cells predicted poor castration-resistant prostate cancer-free survival (CRPC-FS, P = 0.0006) and overall survival (OS, P < 0.0001) in castration-naïve prostate cancer. Multivariate Cox regression model indicated that high infiltration of intratumoral LAG-3 + cells was an independent risk factor for shorter CRPC-FS (hazard ratio [HR], 1.90; 95%confidence interval [CI], 1.30-2.77; P = 0.001) as well as shorter OS (hazard ratio [HR], 2.82; 95%confidence interval [CI],1.65-4.80; P < 0.001). Intratumoral LAG-3 + cell abundance correlated with exhausted CD8 + T-cells in castration-naïve prostate cancer, marking dampened CD8 + T-cell antitumor immunity. Conclusion: This study demonstrated that intratumoral LAG-3 + cell abundance in patients with castration-naïve prostate cancer was associated with earlier resistance to ADT and shorter overall survival. Intratumoral LAG-3 + cell abundance impairs CD8 + T-cell antitumor immunity in patients with castration-naïve prostate cancer.
On the Origins of Conductive-Pulse Sensing Inside a Nanopore
Authors: Lastra Lauren , Nguyen Michelle , Farajpour Nasim , Freedman Kevin 
Published: February 2022

Abstract
Nanopore sensing is nearly synonymous with resistive pulse sensing due to the characteristic reduction of ionic flux during molecular occupancy of a pore, particularly at high salt concentrations. However, conductive pulses are widely reported at low salt conditions wherein electroosmotic flow can be quite significant. Aside from transporting molecules like DNA, we investigated whether electroosmotic flow has other potential impacts on sensing attributes such current enhancements due to the analyte molecule. The overwhelming majority of literature reports counterions as the dominant mechanism of conductive events (a molecule-centric theory for conductive events). Conductive events are not well understood due to the complex interplay between (charged) nanopore walls, DNA grooves, ion mobility, and counterion clouds. Yet, the prevailing consensus of counterions being introduced into the pore by the molecule does not fit well with a growing number of experiments including the fact that proteins can generate conductive events despite having a heterogeneous surface charge. Herein, we demonstrate theory and experiments underpinning the translocation mechanism (i.e., electroosmosis or electrophoresis), pulse direction (i.e., conductive or resistive) and shape (e.g., monophasic or biphasic) through fine control of chemical, physical, and electronic parameters. Results from these studies predict strong electroosmosis plays a role in driving DNA events and generating conductive events due to polarization effects (i.e. a pore-centric theory). We believe these findings will stimulate a useful discussion on the nature of conductive events and their impact on molecular sensing in nanoscale pores.
Six-Week Actual Use Study to Evaluate the Impact of Oral Tobacco-Derived Nicotine Pouches on Cigarette Smoking and Smokeless Tobacco Product Use Behaviors
Authors: McCaffrey Stacey , Lewis Jennifer , Becker Elizabeth , Vansickel Andrea , Larson Elsa , Sarkar Mohamadi 
Published: February 2022

Abstract
Background: Oral tobacco-derived nicotine (OTDN) products are a rapidly emerging, innovative category of noncombustible tobacco products. These products are tobacco-leaf free and do not contain or generate many of the harmful and potentially harmful constituents (HPHCs) found in combustible cigarettes or smokeless tobacco (ST) products. OTDN products may therefore offer adult tobacco consumers a potentially reduced harm alternative. However, little is known about OTDN product use patterns or their ability to substitute for more harmful tobacco products.Methods: We conducted an open-label, 2-phase, actual use study designed to characterize OTDN pouch product (on!® nicotine pouches - NP) use patterns, including impact on other tobacco use behaviors among adult tobacco consumers interested in using NP. Adult current cigarette smokers (AS) and/or adult ST users (ASTU) (n = 1,147 complete) who were not planning to quit were offered free choice of a portfolio of NP (seven flavors at five nicotine levels) to use at-home, ad-libitum, for 6-weeks following an initial 5-day trial. Participants responded to daily electronic surveys that captured the amount, frequency, and topography (e.g., time in mouth, placement in mouth) of NP and other tobacco product use. Results: The majority (99 to 100%) of study participants used NP throughout the 6-week period. Participants used ~5-6 pouches/day of a variety of flavors and nicotine levels. At the end of 6 weeks, a modest proportion of AS (27%) and a substantial proportion of ASTU (71%) reported no use of cigarettes or ST respectively, while reporting continued use of NPs. Additionally, 39% of AS and 14% of ASTU reduced daily consumption of cigarettes or ST products, respectively by 50-99%. Conclusions: Participants found NPs acceptable with a sizeable proportion completely switching away from or substantially reducing (50-99%) their cigarette or ST consumption by week 6. Availability of a variety of flavors and nicotine levels appeared to facilitate the conversion to NP. These data suggest that, under the conditions of the study, NP can be a potential substitute for cigarettes or ST products and may offer harm reduction potential for adult smokers and smokeless tobacco users not interested in quitting.Trial Registration: Note: This study is an observational study with tobacco products currently available in the marketplace for adult tobacco consumers. Since there is no intervention per se and we did not collect any biosamples this is not a “clinical study” and there is no appropriate registry for such behavioral observational studies, we do not believe that this requirement is applicable.
Association of Early-Onset Constipation and Diarrhea with Patient Outcomes in Critically Ill Ventilated Patients: A Retrospective Observational Cohort Study
Authors: Aikawa Gen , Ouchi Akira , Sakuramoto Hideaki , Hoshino Tetsuya , Enomoto Yuki , Shimojo Nobutake , Inoue Yoshiaki 
Published: February 2022

Abstract
Background
Constipation and diarrhea are closely related, but few studies have examined them simultaneously. The purpose of this study was to describe patient defecation status after ICU admission and determine the association of constipation and diarrhea in the early stage of ICU admission with outcomes for critically ill ventilated patients.
Methods
Patients ventilated for ≥ 48 hours in an ICU were retrospectively investigated and their defecation status was assessed during the first week after admission. The patients were divided into three groups: normal defecation, constipation, and diarrhea, and multiple comparison tests were performed. Additionally, multivariable analysis was performed for mortality and length of stay.
Results
Of the 85 critically ill ventilated patients, 47 (55%) experienced constipation, and 12 (14%) experienced diarrhea during the first week of ICU admission. Patients with normal defecation and diarrhea increased from the fourth and fifth day of ICU admission. Diarrhea was significantly associated with the length of ICU stay (B = 7.534, 95% confidence interval: 0.116–14.951).
Conclusions
Early-onset constipation and diarrhea were common in critically ill ventilated patients, and early-onset diarrhea was associated with the length of ICU stay. Thus, prevention of constipation and diarrhea before the fifth day of ICU admission is essential.
Dominasi Patriarki dalam Budaya Merariq Kodeq di Lombok Timur
Authors: Suhastini Novia 
Published: February 2022

Youth marriage had been the problem in all over regionals in Indonesia, without exception what had occurred in Sasak ethnic in Lombok. Merariq culture is a culture to kidnap a girl without knowing by parents in the night. Merariq kodeq is a marriage conducted by kidnapping a girl in young age. The culture of merariq is regarded as the highest contributor of youth marriage number in Lombok. Data BPPKB (Agency for Women Protection and Family Planning) stated that East Lombok had been included in red zone for youth marriage. Besides, the high number of divorce and women as the head of household is because of the ease to get married and divorce in Sasak ethnic Lombok.
This study is aimed to know the domination of patriarchy in merariq kodeq culture and the effect caused by merariq kodeq culture by using qualitative approach case study method. Data collection was conducted by in-depth interview, observation and documentation. Post-feminist theory of Luce Irigaray used as reference to discuss patriarchy domination in merariq kodeq culture. Domination occurs because of the difference of men and women in symbolic norms, in masculine and patriarchal. Patriarchal position arranged by conformation a genealogy by others.
Domination of patriarchy in merariq kodeq culture occurs in pre-marriage, household and divorce and children custody. The form of patriarchy domination in pre-marriage visible on merariq values, when a young man who protected by custom rules allowed to kidnap a girl if they get married. The form of domination in household can be seen from domestic sphere, even the girl has her function as a wife but she still have pressure and physical or psychological abuses. The form of domination in divorce is children custody visible during divorce decision, husband as superior decision maker because he has no marriage letter. Besides, post-divorce, their children would be the wife and entrusted to grandparents. The effect of merariq kodeq marriage is 1) the ease of marriage-divorce and physical abuse in household, 2) unreadiness in reproduction and wrong parenting.
VISUAL AXIOLOGY OF THE POST-KIEV URBAN MODEL
Authors: Аванесов Сергей Сергеевич 
Published: February 2022

Исследуется аксиологическая трансформация ведущей градостроительной модели русского Средневековья во второй половине XII века. Показано, что строительная программа Андрея Боголюбского, призванная решить задачу архитектурного оформления идеи приоритета Владимира над Киевом, обусловила ориентацию на западные архитектурные образцы, претерпевшие тем не менее очевидную адаптацию к сложившейся русско-византийской художественной традиции. Выражая вполне определённые идеологические приоритеты князя и княжества, городская среда Владимира приобрела визуально фиксированную аксиологическую окраску. Эта новая для Руси аксиология свидетельствует о начавшейся трансформации исходной русской градостроительной модели: перенос святости постепенно теряет свой исключительный культурно-семиотический смысл, приобретая подчёркнутый политический акцент. Именно поэтому город-прототип, потеряв свой сакральный характер, утрачивает и свою прежнюю ценность, а следовательно, подлежит безжалостному уничтожению. Целенаправленная, осмысленная попытка князя Андрея отнять у Киева характер и функцию «Иерусалима», построить новый город как альтернативу старому сакральному центру демонстрирует начавшуюся деструкцию иерусалимской урбанистической матрицы и закладывает первоначальное основание под будущую теорию «третьего Рима».
The article is dedicated to the study of the axiological transformation of the leading urban planning model of the Russian Middle Ages in the second half of the 12th century. The article shows that the construction program of Andrei Bogolyubsky, which was supposed to solve the problem of architectural design of the idea of Vladimir’s priority over Kiev, led to an ori-entation towards Western architectural samples, which, nevertheless, underwent an obvious adaptation to the established Russian-Byzantine artistic tradition. Expressing quite clear ideo-logical priorities of the duke and dukedom, the urban environment of Vladimir acquired a visually fixed axiological peculiarity. This axiology, new for Russia, indicates the start of the original Russian urban planning model transformation: the transformation of sacredness is gradually losing its exclusive cultural and semiotic meaning, and acquiring a vivid political emphasis. That is why the prototype-city, having lost its sacred character, loses its former value and therefore becomes a subject to cruel destruction. The purposeful and meaningful attempt of Duke Andrei to deprive Kiev of the character and function of “Jerusalem” and to build a new city as an alternative to the old sacred center demonstrates the beginning of de-struction of the Jerusalem urban matrix and lays the initial foundation for the future theory of the “third Rome”.
Availability And Utilization of Physical Facilities as Correlates of Students’ Academic Performance in Electrical Installation and Maintenance Work Practice in Technical Colleges in Ekiti State
Authors: Adameji James Olusola , Kelechi Reko E. Prof. Okoye, 
Published: February 2022

This study determined the availability and utilization of physical facilities as correlates of students’ academic performance in electrical installation and maintenance work practice in technical colleges in Ekiti State. Four research questions and three null hypotheses guided the study. Descriptive survey and correlational research designs was used for the study. Eight hundred and fifty-three (818 students and 35 teachers) of electrical installation in the six government-owned technical colleges in Ekiti State were studied without sampling. The Instruments for data collection included checklist, structured questionnaire and performance test. The reliability of the performance test was determined through split-half technique. Spearman-Brown formula was employed for reliability coefficient computation which yielded a reliability coefficient of 0.905. Percentage, mean, standard deviation and Pearson Product Moment Correlation coefficient were used to answer research questions. The t-test statistical tool was used to test the null hypotheses relating to utilization of instructional facilities while Pearson Product Moment Correlation coefficient was used to test the null hypotheses relating to physical facilities and students’ academic performance. Findings revealed that majority of physical facilities are available for electrical installation and maintenance work practice in technical colleges in technical colleges in Ekiti State. The study also revealed that there is high positive relationship of 0.61 existing between students’ utilization of physical resources and their academic performances in electrical installation and maintenance work practice in technical colleges in Ekiti State. The study concluded that the level of availability and utilization of physical facilities for electrical installation and maintenance work practice in technical colleges in technical colleges in Ekiti State is not adequate for equipping students with practical skills for self-reliance. The study recommended among others that owners of technical colleges in Ekiti State should adequately provide relevant physical facilities for effective teaching of electrical installation and maintenance workshop practices.
AVALIAÇÃO DE ANSIEDADE NO PRÉ-OPERATÓRIO DE TRATAMENTO ENDODÔNTICO
Authors: Dias Michelle Cristina Capatina , Araújo Izabella Pereira , Craveiro Marco André 
Published: February 2022

A ansiedade é um fenômeno que pode ser caracterizado por sentimentos subjetivos de tensão, apreensão, nervosismo e preocupação que são experimentados por um indivíduo em um momento particular. O tratamento odontológico é considerado um dos que mais geram estado de ansiedade nos pacientes, por medo e por pensamentos preocupantes em relação aos procedimentos. A terapia endodôntica é uma das especialidades que mais causam temor e ansiedade. Foram entrevistados um total de 75 pacientes que se apresentaram na Clínica de Odontologia da Universidade São Francisco, para tratamento endodôntico, entre setembro e outubro de 2019, sendo 45 do sexo feminino e 30 do sexo masculino. O paciente foi caracterizado quanto ao gênero, idade, grau de escolaridade e renda familiar. Foram feitas perguntas quanto ao tempo decorrido desde sua última consulta ao dentista e sobre seu maior anseio em relação aos procedimentos odontológicos. Foram categorizados através de um questionário de ansiedade. O grupo do sexo feminino foi o que apresentou maior prevalência de ansiedade. Paciente considerados moderadamente e extremamente ansiosos somaram 24% da amostra, o procedimento que mais causou medo e ansiedade foi a anestesia (40%) e grande parte dos pacientes procuram tratamento odontológicos a cada 6 meses (53,33%) . Com base nesses resultados podemos concluir que dentro da população estudada o nível de ansiedade entre mulheres se mostrou mais alto que em homens, e que a ansiedade ainda se mostra muito prevalente e deve ser sempre um fator a ser considerado e, desde que possível, minimizada no planejamento e pré-operatório do tratamento.
Nilai-Nilai Moral dalam Novel Ayat-Ayat Cinta Karya Habiburrahman El Shirazy
Authors: Wibowo Aris , Wuryantoro Aris , Ricahyono Sigit 
Published: February 2022

<div><p>Penelitian ini menggunakan metode deskriptif analisis. Sedangkan tujuan yang hendak dicapai adalah mendekripsilan dan menganalisis nilai-nilai moral dalam novel Ayat-Ayat Cinta<em> </em>karya Habiburrahman El Shirazy. Hasil análisis data menunjukkan nilai moral dalam Novel Ayat-Ayat Cinta meliputi nilai kejujuran, menjadi diri sendiri, sikap bertanggung jawab, nilai kemandirian, nilai kerendahan hati, dan nilai atau sikap kritis. Nilai-nilai tersbut menunjukkan adanya pesan moral yang sangat tinggi sehingga menjadikan novel tersebut menjadi novel yang sangat dinikmati pembacanya. Selain itu, masih ada beberapa nilai moral yang ada dalam novel AAC karya Habiburrahman El Shirasy tersebut. Nilai-nilai moral tersebut (1)) bermunajad (berdoa), (2) sikap berhati-hati, (3) ketentuan allah (takdir), (4) bertasbih, (5) bersyukur kepada allah, (6) bersikap sabar, (7) taqdir. Nilai nilai dalam novel AAC dalam bahasan ini mengacu pada baik-buruknya sebagai manusia.</p></div>