bluuebunny/crossref_metadata_2025_split huggingface dataset:
CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses
Authors: Bi Xiaowen , Jiang Baolin , Zhou Jinyi , Fan Xirui , Yan Xintong , Liang Juanjuan , Luo Lan , Yin Zhimin 
Published: February 2021

CREB binding protein (CBP), a transcriptional coactivator and acetyltransferase, is involved in the pathogenesis of inflammation-related diseases. High mobility group box-1 protein (HMGB1) is a critical mediator of lethal sepsis, which has prompted investigation for the development of new treatment for inflammation. Here, we report that the potent and selective inhibition of CBP bromodomain by SGC-CBP30 blocks HMGB1-mediated inflammatory responses in vitro and in vivo. Our data suggest that CBP bromodomain inhibition suppresses LPS-induced expression and release of HMGB1, when the inhibitor was given 8 h post LPS stimulation; moreover, CBP bromodomain inhibition attenuated pro-inflammatory activity of HMGB1. Furthermore, our findings provide evidence that SGC-CBP30 down-regulated rhHMGB1-induced activation of MAPKs and NF-κB signaling by triggering the reactivation of protein phosphatase 2A (PP2A) and the stabilization of MAPK phosphatase 1 (MKP-1). Collectively, these results suggest that CBP bromodomain could serve as a candidate therapeutic target for the treatment of lethal sepsis via inhibiting LPS-induced expression and release of HMGB1 and suppressing the pro-inflammatory activity of HMGB1.
The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
Authors: Liu Weixi , Yang Zhicheng , Chen Yan , Yang Haoyu , Wan Xiaoxian , Zhou Xindie , Liu Ruiping , Zhang Yunkun 
Published: February 2021

Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial.Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility.Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the CTLA-4 genes and RA for more robust conclusions.Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms.Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.
Oxidative Imbalance in Candida tropicalis Biofilms and Its Relation With Persister Cells
Authors: da Silva María A. , Baronetti José L. , Páez Paulina L. , Paraje María G. 
Published: February 2021

BackgroundPersister cells (PCs) make up a small fraction of microbial population, can survive lethal concentrations of antimicrobial agents. In recent years, Candida tropicalis has emerged as being a frequent fungal agent of medical devices subject to biofilm infections. However, PCs are still poorly understood.ObjectivesThis study aimed to investigate the relation of PCs on the redox status in C. tropicalis biofilms exposed to high doses of Amphotericin B (AmB), and alterations in surface topography and the architecture of biofilms.MethodsWe used an experimental model of two different C. tropicalis biofilms exposed to AmB at supra minimum inhibitory concentration (SMIC80), and the intra- and extracellular reactive oxygen species (iROS and eROS), reactive nitrogen species (RNS) and oxidative stress response were studied. Light microscopy (LM) and confocal laser scanning microscopy (CLSM) were also used in conjunction with the image analysis software COMSTAT.ResultsWe demonstrated that biofilms derived from the PC fraction (B2) showed a higher capacity to respond to the stress generated upon AmB treatment, compared with biofilms obtained from planktonic cells. In B2, a lower ROS and RNS accumulation was observed in concordance with higher activation of the antioxidant systems, resulting in an oxidative imbalance of a smaller magnitude compared to B1. LM analysis revealed that the AmB treatment provoked a marked decrease of biomass, showing a loss of cellular aggrupation, with the presence of mostly yeast cells. Moreover, significant structural changes in the biofilm architecture were noted between both biofilms by CLSM—COMSTAT analysis. For B1, the quantitative parameters bio-volume, average micro-colony volume, surface to bio-volume ratio and surface coverage showed reductions upon AmB treatment, whereas increases were observed in roughness coefficient and average diffusion distance. In addition, untreated B2 was substantially smaller than B1, with less biomass and thickness values. The analysis of the above-mentioned parameters also showed changes in B2 upon AmB exposure.ConclusionTo our knowledge, this is the first study that has attempted to correlate PCs of Candida biofilms with alterations in the prooxidant-antioxidant balance and the architecture of the biofilms. The finding of regular and PCs with different cellular stress status may help to solve the puzzle of biofilm resistance, with redox imbalance possibly being an important factor.
Outcomes of Non-anesthesiologist-Administered Propofol in Pediatric Gastroenterology Procedures
Authors: Lee Frances C. , Queliza Karen , Chumpitazi Bruno P. , Rogers Amber P. , Seipel Catherine , Fishman Douglas S. 
Published: February 2021

Background and Aims: Non-anesthesiologist-administered propofol (NAAP) has been found to have an acceptable safety profile in adult endoscopy, but its use remains controversial and pediatric data is limited. Our aim was to examine the safety and efficacy of NAAP provided by pediatric hospitalists in pediatric endoscopy.Methods: We retrospectively reviewed 929 esophagogastroduodenoscopy (EGD), colonoscopy, and combined EGD/colonoscopy cases in children aged 5–20 years between April 2015 and December 2016 at a large children's hospital. We analyzed the data for adverse events in relation to demographics and anthropometrics, American Society of Anesthesiologists physical classification score, presence of a trainee, comorbid conditions, and procedure time.Results: A total of 929 cases were included of which 496 (53%) were completed with NAAP. Seventeen (3.4%) of NAAP cases had an adverse event including the following: 12 cases of hypoxia, 2 cardiac, and 3 gastrointestinal adverse events. General anesthesia cases had 62 (14.3%) adverse events including the following: 54 cases of hypoxia, 1 cardiac, 7 gastrointestinal, and 1 urologic adverse event. No adverse events in either group required major resuscitation. NAAP vs. general anesthesia had a lower overall adverse event rate (3.4 vs. 14.3%, p &lt; 0.0004) and respiratory adverse event rate (2.4% vs. 12.5%, p &lt; 0.0004). Overall, cardiac and gastrointestinal adverse event rates between the two groups were comparable. When accounting for all captured factors via logistic regression, both younger age (P &lt; 0.001) and general anesthesia (P &lt; 0.0001) remained risk factors for an adverse event.Conclusion: The overall adverse event rate of NAAP was low (3.4%) with none requiring major resuscitation or hospitalization. This is comparable to studies of NAAP in adult endoscopy and suggests that NAAP provided by pediatric hospitalists has an acceptable safety profile.
Glycyrrhetinic Acid Protects Renal Tubular Cells against Oxidative Injury via Reciprocal Regulation of JNK-Connexin 43-Thioredoxin 1 Signaling
Authors: Zhou Yao , Gao Leiping , Xia Ping , Zhao Jing , Li Wei , Zhou Yufeng , Wei Qingxue , Wu Qijing , Wu Qi , Sun Dongdong , Gao Kun 
Published: February 2021

Background and Objective: The incidence of chronic kidney disease (CKD) is steadily increasing. Although renal tubular epithelium injury is closely correlated with the prognosis of CKD, the underlying mechanism is not fully understood and therapeutic strategies are limited. The main bioactive component of the Chinese medicine herb, glycyrrhiza, is 18α-glycyrrhetinic acid (Ga), which is also a pharmacological inhibitor of gap junctions. Our previous studies indicated that Ga is able to ameliorate renal cell injury. The present study explored the regulatory role of Ga in redox signaling in renal tubular epithelial cells with oxidative injury.Methods: Rat renal tubular epithelial cells, NRK-52E, were incubated with Px-12, a thioredoxin inhibitor, to mimic thioredoxin deficiency and induce oxidative injury in vitro. A Cell Counting Kit-8 was used to analyze cell viability while a reactive oxygen species (ROS)/superoxide (O2−) fluorescence probe was employed to determine oxidative stress. Apoptosis was evaluated using DT-mediated dUTP nick end labeling/4,6-diamidino-2-phenylindole staining and cleaved caspase 3 protein analysis. Western blot analysis was used to analyze the expression of specific proteins while siRNA transfection was performed to downregulate targeted proteins.Results: Inhibition of thioredoxin 1 by Px-12 triggered renal tubular cell oxidative injury as evidenced by morphological change, loss of cellular viability, over production of ROS and O2−, and appearance of cleaved caspase-3. Ga significantly attenuated cell oxidative injury, as indicated by the parameters mentioned above. Px-12 induced phosphorylation of c-Jun N-terminal kinase (JNK) and subsequently the expression of connexin 43 (Cx43) in NRK-52E cells. Ga and the JNK inhibitor, sp600125, markedly suppressed Px-12-induced generation of intracellular ROS and O2−. Inhibition of JNK improved Px-12-elicited NRK-52E cell injury. Moreover, sp600125 inhibited Cx43 expression. After downregulation of Cx43 via Cx43 siRNA transfection, the phosphorylation of JNK was markedly reduced. Furthermore, Ga restored the expression of thioredoxin 1 inhibited by Px-12.Conclusion: ROS-JNK-Cx43-thioredoxin 1 signaling plays a crucial role in renal tubular cell injury. JNK is involved in the regulation of thioredoxin 1 and Cx43, and Cx43 reciprocally regulates thioredoxin 1. Inhibition of gap junctions by Ga alleviated renal tubular oxidative injury via improvement of thioredoxin 1-mediated redox signaling.
“Test Your Spirituality in One Minute or Less” Structural Validity of the Multidimensional Inventory for Religious/Spiritual Well-Being Short Version (MI-RSWB 12)
Authors: Fuchshuber Jürgen , Unterrainer Human F. 
Published: February 2021

Background: The Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB 48) was developed in order to address a religious/spiritual dimension as being an important part of psychological well-being. In the meantime, the instrument has been successfully applied in numerous studies. Subsequently, a short version, the MI-RSWB 12 was constructed, especially for the use in clinical assessment. Here it is intended to contribute to the further development of the MI-RSWB 12 by investigating its structural validity through structural equation modeling.Materials and Methods: A total sample of 1,097 German-speaking adults (744 females; 67.8%; Age range: 18–69 years) from the normal population filled in the MI-RSWB 12 via an online-survey. In line with theoretical assumptions 5 different factor structure models for the MI-RSWB 12 were tested: (1) a single-factor model, (2) a model with four correlated RSWB dimensions, (3) a single higher-order model with four lower order factors, (4) a two higher-order model with four lower order factors, (5) a bifactor model, which includes four specific RSWB dimensions.Results: The single-factor model provided the poorest model fit, with no indices falling within the acceptable range. The four-factor, two higher-order factors and the bifactor models showed overall acceptable fit indices. With regard to the Akaike information criterion (AIC), the four-factor model demonstrated superiority compared to both the two higher-order factor model and the bifactor model, which in turn showed did not differ from each other.Conclusion: Four different MI-RSWB 12 sub-scales should be calculated in future studies, while a general factor and two higher order factors are statistically valid as well. Further applications of the MI-RSWB 12, especially in the clinical patient groups, are encouraged.
Reduced Activity in an Inpatient Liaison Psychiatry Service During the First Wave of the COVID-19 Pandemic: Comparison With 2019 Data and Characterization of the SARS-CoV-2 Positive Cohort
Authors: Butler Matthew , Delvi Afraa , Mujic Fedza , Broad Sophie , Pauli Lucy , Pollak Thomas A. , Gibbs Soraya , Fai Lam Chun Chiang Sin , Calcia Marilia A. , Posporelis Sotirios 
Published: February 2021

Background: The COVID-19 pandemic led to changes in the way that healthcare was accessed and delivered in the United Kingdom (UK), particularly during the peak of the first lockdown period (the “first wave”) beginning in March 2020. In some patients, COVID-19 is associated with acute neuropsychiatric manifestations, and there is suggestion that there may also be longer term neuropsychiatric complications. Despite this, at the time of writing there are only emerging data on the direct effects of the COVID-19 pandemic on psychiatric care.Methods: In this retrospective study we analyzed referrals to an inpatient liaison psychiatry department of a large acute teaching hospital during the first wave of covid-19 in the UK and compared this data to the same period in 2019.Results: We saw a 40% reduction in the number of referrals in 2020, with an increase in the proportion of referrals for both psychosis or mania and delirium. Almost one third (28%) of referred patients tested positive for COVID-19 at some point during their admission, with 40% of these presenting with delirium as a consequence of their COVID-19 illness. Save delirium, we did not find evidence for high prevalence of new-onset acute mental illness in COVID-19 positive patients.Conclusion: Our data indicate decreased clinical activity in our inpatient psychiatry liaison department during the first wave of the COVID-19 pandemic, although a relative increase in relative increase in referrals for psychosis or mania, suggesting less of a relative decrease in more severe cases of mental illness. The reasons for this are likely multifactorial, including structural changes in the NHS and patient reluctance to present to emergency departments (ED) due to infection fears and Government advice. Our data also supports the literature suggesting the high relative prevalence of delirium in COVID-19, and we support integration of psychiatry liaison teams in acute general hospital wards to optimize delirium management. Finally, consideration should be given to adequate staffing of community and crisis mental health teams to safely manage the mental health of people reluctant to visit EDs.
Decentralised Electricity Markets and Proactive Customer Behaviour
Authors: Maiwald Jens , Schuette Tino 
Published: February 2021

The energy transition in Germany takes part in decentral structures. With the ongoing integration of Renewable Energy Sources (RES) into the electricity supply system, supply-side is therefore becoming increasingly decentral and volatile due to the specific generation characteristics. A rather inflexible demand-side, on the other hand, increases the effort to gain the necessary equilibrium between generation and consumption. This paper discusses how consumer behaviour can be influenced by real-time pricing to align demand with generation. Therefore, a combination of two different approaches is used, (I) The Cellular Approach (CA) and (II) Agent Based Modelling (ABM). A model is set up considering a regional energy market, where regional electricity products can be traded peer-to-peer regarding each consumer’s preferences. The observation is made for a whole distribution grid including all types of consumers. The investigations show that energy purchases can be stimulated individually by a flexible pricing mechanism and met preferences. Moreover, benefits occur for the whole region and potentials arise to smooth the exchange balance to the superordinate grid level. Running the model for one entire year in a conservative generation scenario, hours of oversupply could be reduced by 18% and the consumption of green electricity generated regionally could be increased by over 125 MWh within the region itself, in comparison to a base scenario.
Les rapports d’affinité de Geoffroy, ou la clé d’un mariage réussi sous les lois de la thermodynamique
Authors: Bourzat Jean-Dominique 
Published: February 2021

Geoffroy’s affinity ratios or the key to a successful blending under the laws of thermodynamic –
On the 27th of August 1718, Geoffroy issued a communication to the French Royal Academy of Sciences entitled : «Table des différents rapports observés en chimie entre différentes substances.».
This table is a major step to the understanding of the chemical reaction ; it creates a classification by affinity between chemical substances according to their tendency towards preferential union. These selective affinities lead for example to define a scale of values in according to the acid’s strength, or the more or less ease for metals to give amalgam.
Combination of platelet-rich plasma and hyaluronic acid in the treatment of moderate and severe osteoarthritis of the knee joint
Authors: Razaq Muthanna Abdul , Qasim Anmar Ahmed , Assim Thamer Mohammed , Ramzi Ramzi 
Published: February 2021

The study aimed to determine the effectiveness of monthly intra-articular injection of combination of PRP and hyaluronic acid in improvement of outcome of knee OA. It was conducted as open clinical trial on a convenient sample of 17 patients with unilateral or bilateral symptomatic knee OA in rheumatology and orthopedic clinics at Al-Jumhoori Teaching Hospital in Mosul, Iraq during 1st of Jan to 30th Jun, 2018. The patients received intra-articular injection of combination of plate rich plasma (PRP) and hyaluronic acid (HA) monthly for three months. The outcome assessment was carried out 4 weeks after the last injection using WOMAC index. The results revealed that WOMAC index subscales was reduced significantly (p <0.001) after treatment by followings mean differences: 3.88 in pain (95% CI: 3.18-4.58); 1.29 in stiffness (95% CI: 0.85-1.73); 9.29 in physical function (95% CI: 6.70-11.88); and 14.47 in total score (95% CI: 11.20-17.73). The intervention effect size were as follows: 1.23 in pain; 1.49 in stiffness; 1.11 in physical function, and 1.20 in total WOMAC score. Overall, effect size of combination of PRP and HA intra-articular injection is classified as large effect size (> 0.8) in improving outcome of knee OA. A combination of PRP and HA has large synergistic effect size in improving outcome of moderate and severe OA of knee.
PERDAMAIAN DALAM PERSPEKTIF ISLAM DAN KRISTEN
Authors: Asy'ari Asy’ari 
Published: February 2021

The existence of Religion is a correction of behavioral problems that substantively cause tension, violence and even damage to the social fabric, or better known as tyranny. There is no religion established itself as a rel igion of violence and it is certain that all religions claim to be a religion of peace. But on the other hand, religion can lead to damage and even mass murder. Therefore, religious messages are ambivalent, whether religion is to solve problems or it is the source of problems. This ambivalence is emphasized with the rise of religious adherents by showing complex faces to interpret. The complex face is inseparable from the adherents of the r eligion itself, both Islam and Christian. Because the realizat ion of religious adherents have the legitimacy of the text (the source of their religious teachings).
PERAN AKTIF HAKIM DALAM PEMERIKSAAN KETERANGAN SAKSI DALAM PERSIDANGAN MENUJU HAKIM YANG PROFESIONAL DI ERA KEMAJUAN TEKHNOLOGI INFORMASI
Authors: Fikriyah Uswatul 
Published: February 2021

Dalam perkara perdata di Pengadilan Agama khususnya perceraian alat bukti saksi adalah hal yang banyak dihadirkan oleh para pihak. Hakim harus mempunyai metode dan kemampuan professional untuk menggali fakta hukum dan menghasilkan putusan yang berkualitas, adanya perkembangan tekhnologi informasi yang direspon oleh Mahkamah Agung menjadikan semua proses persidangan dilaksanakan melalui media elektronik. Dalam tulisan ini penulis membahas bagaimana tugas dan peran aktif Hakim dalam memeriksa Keterangan Saksi menuju Hakim yang Profesional di era kemajuan tekhnologi informasi. Hasil dari penelitian ini: seorang hakim dalam menyelesaikan perkara melalui beberapa tahapan yang terdiri dari Konstantir, Kualifisir, dan Konstituir. Dalam setiap tahapan yang dilakukan Hakim harus memunyai kepekaan nurani, mempunyai kecerdasan moral dan mengasah profesionalisme. Profesionalisme seorang hakim harus mengacu pada Poin 10 kode etik dan pedoman perilaku hakim. terkait professional, hakim dimaknai sebagai suatu sikap moral yang dilandasi oleh tekad untuk melaksanakan tugasnya dengan kesungguhan yang didukung oleh keahlian, ketrampilan, dan wawasan luas. Selain itu Hakim juga harus berpedoman pada konsep profesionalitas dalam Islam lebih dilihat sebagai sinkronisasi antara gerak manusia dalam dua wujud, yaitu rohaniah dan jasmani.
In civil cases in the Religious Courts, especially divorce cases, the witnesses evidence is a matter that is always presented by the parties. Judges must have professional methods and abilities to explore legal facts and produce quality decisions, the development of information technology that was responded by the Supreme Court made all proceedings carried out through electronic media. In this paper discusses how the duties and the roles of Judges in examining the Witness' statements to become Professional Judges in the era of advancement in information technology. The results of this study: a judge in deciding a case through several stages consisting of Constantine, Qualifiers, and Constituencies. In each stage, the Judge must have a sensitivity of conscience, moral intelligence and hone professionalism. Professionalism of judges must refer to Point 10 of the ethics code and guidelines for judge behavior. Professionalism of judge is interpreted as a moral attitude based on a determination to carry out the task seriously supported by expertise, skills, and broad insight. In addition, the Judge must be guided by the concept of islamic professionalism, which is seen as a synchronization between human movements in two forms, namely spiritual and physical.