bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lack of association between PADI4_94 or PADI4_104 polymorphisms and RF, ACPA and anti-PAD4 in patients with rheumatoid arthritis
Authors: Ciesla Marek , Kolarz Bogdan , Darmochwal-Kolarz Dorota 
Published: July 2022

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease that leads to chronic inflammation of synovial tissue, ultimately causing joint damage, disability, and premature mortality. The peptidylarginine deiminase (PAD) family of proteins is involved in the production of anticitrullinated peptide antibodies (ACPA), which are clinically relevant markers of RA. ACPA recognizes citrullinated proteins generated mainly by PAD4. Polymorphisms of the PADI4 gene have been associated with RA in Asian populations, but in Europeans these associations are still difficult to estimate. A total of 147 subjects, 122 patients with RA, 52 ± 12.3 aged, 84.4% women and 25 healthy controls, 53 ± 8.4 aged, 72% women were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of the PADI4 gene (PADI4_94, rs2240340 and PADI4_104, rs1748033) were genotyped using a real-time polymerase chain reaction. Genetic models (co-dominant-1 and 2, dominant, over-dominant, and recessive) were applied to find the associations between genotypes and ACPA as well as PAD4 antibodies (anti-PAD4) levels. We found no relationship between the distribution of genotypes in different genetic models and the levels of anti-PAD4, ACPA and RF antibodies. There were also no differences with respect to the haplotypes. Genetic variants PADI4_94 and PADI4_104 may not be clinically relevant as prognostic factors in patients with established RA.
Efficacy of auranofin as an inhibitor of desmoid progression
Authors: Ito Kan , Nishida Yoshihiro , Hamada Shunsuke , Shimizu Koki , Sakai Tomohisa , Ohkawara Bisei , Alman Benjamin A. , Enomoto Atsushi , Ikuta Kunihiro , Koike Hiroshi , Zhang Jiarui , Ohno Kinji , Imagama Shiro 
Published: July 2022

AbstractAnticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were screened. An identified drug was subjected to the investigation of apoptotic effects on DF cells with analysis of Caspase 3/7 activity. Expression of β-catenin was evaluated with western blot analysis, and immunofluorescence staining. Effects of the identified drug on in vivo DF were analyzed using Apc1638N mice. Auranofin was identified as a drug that effectively inhibits the proliferation of DF cells. Auranofin did not affect Caspase 3/7 activity compared to control. The expression level of β-catenin protein was not changed regardless of auranofin concentration. Auranofin effectively inhibited the development of tumorous tissues by both oral and intraperitoneal administration, particularly in male mice. Auranofin, an anti-rheumatic drug, was identified to have repositioning effects on DF. Since auranofin has been used for many years as an FDA-approved drug, it could be a promising drug with fewer side effects for DF.
Varus stress MRI in the refined assessment of the posterolateral corner of the knee joint
Authors: Ciba Malin , Winkelmeyer Eva-Maria , Schock Justus , Westfechtel Simon , Nolte Teresa , Knobe Matthias , Prescher Andreas , Kuhl Christiane , Truhn Daniel , Nebelung Sven 
Published: July 2022

AbstractMagnetic resonance imaging (MRI) is commonly used to assess traumatic and non-traumatic conditions of the knee. Due to its complex and variable anatomy, the posterolateral corner (PLC)—often referred to as the joint’s dark side—remains diagnostically challenging. We aimed to render the diagnostic evaluation of the PLC more functional by combining MRI, varus loading, and image post-processing in a model of graded PLC injury that used sequential transections of the lateral collateral ligament, popliteus tendon, popliteofibular ligament, and anterior cruciate ligament. Ten human cadaveric knee joint specimens underwent imaging in each condition as above, and both unloaded and loaded using an MR-compatible device that standardized loading (of 147 N) and position (at 30° flexion). Following manual segmentation, 3D joint models were used to computationally measure lateral joint space opening for each specimen, configuration, and condition, while manual measurements provided the reference standard. With more extensive ligament deficiency and loading, lateral joint spaces increased significantly. In conclusion, varus stress MRI allows comprehensive PLC evaluation concerning structural integrity and associated functional capacity. Beyond providing normative values of lateral compartment opening, this study has potential implications for diagnostic and surgical decision-making and treatment monitoring in PLC injuries.
Association between time in range of relative normoglycemia and in-hospital mortality in critically ill patients: a single-center retrospective study
Authors: Okazaki Tomoya , Inoue Akihiko , Taira Takuya , Nakagawa Shun , Kawakita Kenya , Kuroda Yasuhiro 
Published: July 2022

AbstractThe aim of this single-center retrospective study was to investigate the association between the time in range (TIR) of relative normoglycemia (RN) and in-hospital mortality. We defined RN as measured blood glucose in the range of 70–140% of A1C-derived average glucose and absolute normoglycemia (AN) as 70–140 mg/dL. We conducted multivariate logistic regression analyses to examine the association between TIR of RN > 80% or TIR of AN > 80% up to 72 h after ICU admission and in-hospital mortality (Model 1 and Model 2, respectively). The discrimination of the models was assessed using the area under the receiver operating characteristic curve (AUROC). Among 328 patients, 35 died in hospital (11%). Model 1 showed that TIR of RN > 80% was associated with reduced in-hospital mortality (adjusted OR 0.16; 95% CI 0.06–0.43; P < 0. 001); however, Model 2 showed that the TIR of AN > 80% was not. The AUROC of Model 1 was significantly higher than that of Model 2 (0.84 [95% CI 0.77–0.90] vs. 0.79 [0.70–0.87], P = 0.008).Our findings provide a foundation for further studies exploring individualized glycemic management in ICUs.
Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia
Authors: Sha Hong Xi , Veerapen Kumar , Chow Sook Khuan , Gun Suk Chyn , Lau Ing Soo , Lim Renee Lay Hong , Zulkifli Zaliha , Yow Yoon-Yen , Peh Suat Cheng , Hwang Jung Shan 
Published: July 2022

AbstractMethotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR 0.5478, 95% CI 0.3396–0.8835, p = 0.01321) and ATIC T675C (rs4673993) (OR 0.5247, 95% CI 0.3248–0.8478, p = 0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene–gene and gene–environment interactions.
A first-principles-based high fidelity, high throughput approach for the design of high entropy alloys
Authors: Sorkin V. , Yu Z. G. , Chen S. , Tan Teck L. , Aitken Z. H. , Zhang Y. W. 
Published: July 2022

AbstractHere, we present a preselected small set of ordered structures (PSSOS) method, a first principles-based high fidelity (HF), high throughput (HT) approach, for fast screening of the large composition space of high entropy alloys (HEAs) to select the most energetically stable, single-phase HEAs. Taking quinary AlCoCrFeNi HEA as an example system, we performed PSSOS calculations on the formation energies and mass densities of 8801 compositions in both FCC and BCC lattices and selected five most stable FCC and BCC HEAs for detailed analysis. The calculation results from the PSSOS approach were compared with existing experimental and first-principles data, and the good agreement was achieved. We also compared the PSSOS with the special quasi-random structures (SQS) method, and found that with a comparable accuracy, the PSSOS significantly outperforms the SQS in efficiency, making it ideal for HF, HT calculations of HEAs.
Deficiency of protocadherin 9 leads to reduction in positive emotional behaviour
Authors: Uemura Masato , Furuse Tamio , Yamada Ikuko , Kushida Tomoko , Abe Takaya , Imai Keiko , Nagao Soichi , Kudoh Moeko , Yoshizawa Katsuhiko , Tamura Masaru , Kiyonari Hiroshi , Wakana Shigeharu , Hirano Shinji 
Published: July 2022

AbstractProtocadherin 9 (Pcdh9) is a member of the cadherin superfamily and is uniquely expressed in the vestibular and limbic systems; however, its physiological role remains unclear. Here, we studied the expression of Pcdh9 in the limbic system and phenotypes of Pcdh9-knock-out mice (Pcdh9 KO mice). Pcdh9 mRNA was expressed in the fear extinction neurons that express protein phosphatase 1 regulatory subunit 1 B (Ppp1r1b) in the posterior part of the basolateral amygdala (pBLA), as well as in the Cornu Ammonis (CA) and Dentate Gyrus (DG) neurons of the hippocampus. We show that the Pcdh9 protein was often localised at synapses. Phenotypic analysis of Pcdh9 KO mice revealed no apparent morphological abnormalities in the pBLA but a decrease in the spine number of CA neurons. Further, the Pcdh9 KO mice were related to features such as the abnormal optokinetic response, less approach to novel objects, and reduced fear extinction during recovery from the fear. These results suggest that Pcdh9 is involved in eliciting positive emotional behaviours, possibly via fear extinction neurons in the pBLA and/or synaptic activity in the hippocampal neurons, and normal optokinetic eye movement in brainstem optokinetic system-related neurons.
An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics
Authors: Spick Matt , Lewis Holly-May , Frampas Cecile F. , Longman Katie , Costa Catia , Stewart Alexander , Dunn-Walters Deborah , Greener Danni , Evetts George , Wilde Michael J. , Sinclair Eleanor , Barran Perdita E. , Skene Debra J. , Bailey Melanie J. 
Published: July 2022

AbstractThe majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions.
Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity
Authors: Mao Yiping , Schoenborn Jacob , Wang Zhihong , Chen Xinqian , Matson Katy , Mohan Ramkumar , Zhang Shungang , Tang Xiaohu , Arunagiri Anoop , Arvan Peter , Tang Xiaoqing 
Published: July 2022

AbstractAbnormal microRNA functions are closely associated with pancreatic β-cell loss and dysfunction in type 2 diabetes. Dysregulation of miR-30d has been reported in the individuals with diabetes. To study how miR-30d affects pancreatic β-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in β-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected β-cell function. Elevated miR-30d at low-level (TgL, 2-fold) had mild effects on signaling pathways and displayed no significant changes to metabolic homeostasis. In contrast, transgenic mice with high-level of miR-30d expression (TgH, 12-fold) exhibited significant diet-induced hyperglycemia and β-cell dysfunction. In addition, loss of β-cell identity was invariably accompanied with increased insulin/glucagon-double positive bihormonal cells and excess plasma glucagon levels. The transcriptomic analysis revealed that miR-30d overexpression inhibited β-cell-enriched gene expression and induced α-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal β-cell identity and function.
Integrated transcriptomic and regulatory network analyses uncovers the role of let-7b-5p, SPIB, and HLA-DPB1 in sepsis
Authors: Mohsin Mohd , Singh Prithvi , Khan Salman , Verma Amit Kumar , Jha Rishabh , Alsahli Mohammed A. , Rahmani Arshad Husain , Almatroodi Saleh A. , Alrumaihi Faris , Kaprwan Nisha , Dev Kapil , Dohare Ravins , Syed Mansoor Ali 
Published: July 2022

AbstractSepsis has affected millions of populations of all age groups, locations, and sexes worldwide. Immune systems, either innate or adaptive are dysregulated due to the infection. Various biomarkers are present to date, still sepsis is a primary cause of mortality. Globally, post-operative body infections can cause sepsis and septic shock in ICU. Abnormal antigen presentation to T-cells leads to a dysregulated immune system. miRNAs are sparkly evolved as biomarkers due to their high sensitivity and efficiency. In this work, we analyzed high-throughput mRNA data collected from Gene Expression Omnibus (GEO) and linked it to significant miRNAs and TFs using a network-based approach. Protein–protein interaction (PPI) network was constructed using sepsis-specific differentially expressed genes (DEGs) followed by enrichment analyses and hub module detection. Sepsis-linked decrease transcription of the classical HLA gene such as HLA-DPB1 and its interplay with miR-let-7b-5p and transcription factor SPIB was observed. This study helped to provide innovative targets for sepsis.
Improved inpatient deterioration detection in general wards by using time-series vital signs
Authors: Su Chang-Fu , Chiu Shu-I , Jang Jyh-Shing Roger , Lai Feipei 
Published: July 2022

AbstractAlthough in-hospital cardiac arrest is uncommon, it has a high mortality rate. Risk identification of at-risk patients is critical for post-cardiac arrest survival rates. Early warning scoring systems are generally used to identify hospitalized patients at risk of deterioration. However, these systems often require clinical data that are not always regularly measured. We developed a more accurate, machine learning-based model to predict clinical deterioration. The time series early warning score (TEWS) used only heart rate, systolic blood pressure, and respiratory data, which are regularly measured in general wards. We tested the performance of the TEWS in two tasks performed with data from the electronic medical records of 16,865 adult admissions and compared the results with those of other classifications. The TEWS detected more deteriorations with the same level of specificity as the different algorithms did when inputting vital signs data from 48 h before an event. Our framework improved in-hospital cardiac arrest prediction and demonstrated that previously obtained vital signs data can be used to identify at-risk patients in real-time. This model may be an alternative method for detecting patient deterioration.
Failure modes and mechanisms of layered h-BN under local energy injection
Authors: Liu Ping , Pei Qing-Xiang , Zhang Yong-Wei 
Published: July 2022

AbstractLayered h-BN may serve as an important dielectric and thermal management material in the next-generation nanoelectronics, in which its interactions with electron beam play an important role in device performance and reliability. Previous studies report variations in the failure strength and mode. In this study, using molecular dynamics simulations, we study the effect of local heat injection due to the electron beam and h-BN interaction on the failure start time and failure mode. It is found that at the same heat injection rate, the failure start time decreases with the increase in the layer number. With the introduction of point defects in the heating zone, the failure always starts from the defect site, and the start time can be significantly shortened. For monolayer h-BN, failure always starts within the layer, and once failure starts, its propagation is through melting or vaporization of the h-BN atoms, and no swelling occurs. For multiple layers, once failure starts within the h-BN film, swelling occurs first. With continued heating, the large pressure induced by melting and vaporization can cause the burst of the layers above, leading to the formation of a pit. In the presence of multiple defects within the heating zone, these defects can interact, causing a further reduction in the failure start time. We also reveal the relation of beam power with layer-by-layer failure mode and swelling/pit formation mode. The present work not only reproduces many interesting experimental observations, but also reveal several interesting mechanisms responsible for the failure processes and modes. It is expected that the findings revealed here may provide useful references for the design and engineering of h-BN for device applications.
Effect of polyglycerol polyricinoleate on the inhibitory mechanism of sesamol during bulk oil oxidation
Authors: Keramat Malihe , Golmakani Mohammad-Taghi , Niakousari Mehrdad 
Published: July 2022

AbstractIn this study, effects of sesamol on improving the oxidative stability of sunflower oil and its oil-in-water emulsion was investigated. To investigate the kinetic parameters related to the initiation and propagation stages of oxidation, a sigmoidal-model was used. Sesamol exhibited higher antioxidant activity in sunflower oil-in-water emulsion than that of sunflower oil. In both sunflower oil and sunflower oil-in-water emulsion, the inhibitory effect of sesamol against lipid oxidation continued even after the induction period. To improve the efficiency of sesamol in sunflower oil, polyglycerol polyricinoleate (PGPR) was incorporated into the functional environment of the sesamol. Sesamol exhibited a synergistic effect with PGPR during both initiation (synergistic effect of 68.87%) and propagation (synergistic effect of 36.84%) stages. Comparison of the size of reverse micelles in samples containing PGPR with those without PGPR revealed that PGPR can enhance the efficiency of sesamol by increasing the acceptance capacity of lipid hydroperoxides in reveres micelles structures. This can result in enhancing the effective collisions between sesamol and lipid hydroperoxides in the presence of PGPR. The water produced as a major byproduct of oxidation played a key role on the antioxidant activity of sesamol alone or in combination with PGPR during oxidation process.
Comparison of NUCLEOCOUNTER, ANDROVISION with Leja chambers and the newly developed ANDROVISION eFlow for sperm concentration analysis in boars
Authors: Grossfeld Rudolf , Pable Julia , Jakop Ulrike , Simmet Christian , Schulze Martin 
Published: July 2022

AbstractExact analysis of sperm concentration in raw and diluted semen is of major importance in swine artificial insemination, as sperm concentration is one of the most important characteristics of an ejaculate determining the value of the ejaculate and the productive life of the boar. The study compares different methods for sperm concentration analysis in raw and diluted boar semen: NUCLEOCOUNTER SP-100, the ANDROVISION with Leja chambers and the new ANDROVISION eFlow system. The Concordance Correlation Coefficient (CCC) between NUCLEOCOUNTER and ANDROVISION eFlow was 0.955 for raw (n = 185 ejaculates) and 0.94 for diluted semen (n = 109 ejaculates). The CCC between NUCLEOCOUNTER and ANDROVISION with Leja chambers was 0.66. A Bland–Altman plot of split-sample measurements of sperm concentration with NUCLEOCOUNTER and ANDROVISION eFlow showed that 95.1% of all measurements lay within ± 1.96 standard deviation. The coefficients of variance were 1.6 ± 1.3%, 3.6 ± 3.6% and 7.3 ± 6.3% for NUCLEOCOUNTER, ANDROVISION eFlow and ANDROVISION with Leja chambers in diluted semen, respectively. NUCLEOCOUNTER and ANDROVISION eFlow are comparable tools to measure the concentration of raw and diluted boar semen. In comparison to ANDROVISION with Leja chambers, concentration analyses of diluted semen using NUCLEOCOUNTER or ANDROVISION eFlow show a higher repeatability within and a higher concordance between the methods.
Proteomic profiling of plasma exosomes from patients with B-cell acute lymphoblastic leukemia
Authors: Zhu Shicong , Xing Cheng , Li Ruijuan , Cheng Zhao , Deng Mingyang , Luo Yunya , Li Heng , Zhang Guangsen , Sheng Yue , Peng Hongling , Wang Zhihua 
Published: July 2022

AbstractWe aimed to comprehensively investigate the proteomic profile and underlying biological function of exosomal proteins associated with B-cell acute lymphoblastic leukemia. Exosomes were isolated from plasma samples collected from five patients with B-ALL and five healthy individuals, and their protein content was quantitatively analyzed by liquid chromatography with tandem mass spectrometry. A total of 342 differentially expressed proteins were identified in patients with B-ALL. The DEPs were mainly associated with protein metabolic processes and protein activity regulation and were significantly enriched in the Notch and autophagy pathways. Furthermore, we found that ADAM17 and ATG3 were upregulated in patients with B-ALL and enriched in the Notch and autophagy pathways, respectively. Further western blot analysis of exosomes collected from additional 18 patients with B-ALL and 10 healthy controls confirmed that both ADAM17 and ATG3 were overexpressed in exosomes derived from patients with B-ALL (p < 0.001). The areas under the curves of ADAM17 and ATG3 were 0.989 and 0.956, respectively, demonstrating their diagnostic potential. In conclusion, ADAM17 and ATG3 in plasma-derived exosomes may contribute to the progression of B-ALL by regulating the Notch and autophagy pathways. Hence, these proteins may represent valuable diagnostic biomarkers and therapeutic targets for B-ALL.