bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabotropic Glutamate Receptor 5 in Natural Killer Cells Attenuates Liver Fibrosis by Exerting Cytotoxicity to Activated Stellate Cells
Authors: Choi Won‐Mook , Ryu Tom , Lee Jun‐Hee , Shim Young‐Ri , Kim Myung‐Ho , Kim Hee‐Hoon , Kim Ye Eun , Yang Keungmo , Kim Kyurae , Choi Sung Eun , Kim Won , Kim Seok‐Hwan , Eun Hyuk Soo , Jeong Won‐Il 
Published: May 2021

Background and Aims
The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon‐γ (IFN‐γ) production in both mice and humans.

Approach and Results
Following 2‐week injection of carbon tetrachloride (CCl4) or 5‐week methionine‐deficient and choline‐deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild‐type mice. Consistently, NK cell–specific mGluR5 knockout mice had aggravated CCl4‐induced liver fibrosis with decreased production of IFN‐γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti‐fibrosis‐related genes including Ifng, Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN‐γ through the mitogen‐activated extracellular signal‐regulated kinase/extracellular signal‐related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo, pharmacologic activation of mGluR5 accelerated CCl4‐induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells.

Conclusions
mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.
The impact of reclassifying cancers of unspecified histology on international differences in survival for small cell and non‐small cell lung cancer (ICBP SurvMark‐2 project)
Authors: Morgan Eileen , Arnold Melina , Rutherford Mark J. , Bardot Aude , Ferlay Jacques , De Prithwish , Engholm Gerda , Jackson Christopher , Little Alana , Saint‐Jacques Nathalie , Walsh Paul , Woods Ryan R. , O'Connell Dianne L. , Bray Freddie , Parkin D. Max , Soerjomataram Isabelle 
Published: May 2021

AbstractSurvival from lung cancer remains low, yet is the most common cancer diagnosed worldwide. With survival contrasting between the main histological groupings, small‐cell lung cancer (SCLC) and non‐small cell lung cancer (NSCLC), it is important to assess the extent that geographical differences could be from varying proportions of cancers with unspecified histology across countries. Lung cancer cases diagnosed 2010‐2014, followed until 31 December 2015 were provided by cancer registries from seven countries for the ICBP SURVMARK‐2 project. Multiple imputation was used to reassign cases with unspecified histology into SCLC, NSCLC and other. One‐year and three‐year age‐standardised net survival were estimated by histology, sex, age group and country. In all, 404 617 lung cancer cases were included, of which 47 533 (11.7%) and 262 040 (64.8%) were SCLC and NSCLC. The proportion of unspecified cases varied, from 11.2% (Denmark) to 29.0% (The United Kingdom). After imputation with unspecified histology, survival variations remained: 1‐year SCLC survival ranged from 28.0% (New Zealand) to 35.6% (Australia) NSCLC survival from 39.4% (The United Kingdom) to 49.5% (Australia). The largest survival change after imputation was for 1‐year NSCLC (4.9 percentage point decrease). Similar variations were observed for 3‐year survival. The oldest age group had lowest survival and largest decline after imputation. International variations in SCLC and NSCLC survival are only partially attributable to differences in the distribution of unspecified histology. While it is important that registries and clinicians aim to improve completeness in classifying cancers, it is likely that other factors play a larger role, including underlying risk factors, stage, comorbidity and care management which warrants investigation.
A retrospective review of clinical and non‐clinical factors associated with unscheduled cesarean deliveries at one urban medical center
Authors: Hamilton A. Rebecca L. , Drzymalski Dan M. 
Published: May 2021

AbstractObjectiveTo investigate factors associated with unscheduled cesarean delivery at one urban tertiary medical center.MethodsA retrospective chart review was performed on 11 162 deliveries between 2009 and 2019. The dependent variable was unscheduled cesarean delivery. Covariates examined included time of delivery, as well as several maternal and pregnancy‐related factors.ResultsThere were a total of 7037 (63.1%) vaginal, 1133 (10.1%) elective cesarean, and 2992 (26.8%) unscheduled cesarean deliveries. Independent factors associated with increased odds for unscheduled cesarean delivery included daytime delivery (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.18–1.42, P < 0.001); advanced maternal age (OR 1.40, 95% CI 1.26–1.56, P < 0.001); obesity (OR 1.04, 95% CI 1.03–1.05, P < 0.001); history of previous cesarean delivery (OR 2.77, 95% CI 1.91–4.01, P < 0.001); hypertension (OR 1.72, 95% CI 1.27–2.32, P < 0.001); multiparity (OR 3.99, 95% CI 2.82–5.64, P < 0.001); pre‐eclampsia (OR 1.96, 95% CI 1.33–2.89, P = 0.001); and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome (OR 5.45, 95% CI 1.13–26.28, P = 0.035).ConclusionFactors associated with unscheduled cesarean delivery in this study cohort included daytime delivery, advanced maternal age, obesity, hypertension, previous cesarean delivery, multiparity, preterm labor, pre‐eclampsia, and HELLP syndrome.
Fibronectin grafting to enhance skin sealing around transcutaneous titanium implant
Authors: Ghadhab Souhaila , Bilem Ibrahim , Guay‐Bégin Andrée‐Anne , Chevallier Pascale , Auger François A. , Ruel Jean , Pauthe Emmanuel , Laroche Gaétan 
Published: May 2021

AbstractIntraosseous transcutaneous amputation prosthesis is a new approach in orthopedic implants that overcomes socket prosthesis problems. Its long‐term performance requires a tight skin‐implant seal to prevent infections. In this study, fibronectin (Fn), a widely used adhesion protein, was adsorbed or grafted onto titanium alloy. Fn grafting was performed using two different linking arms, dopamine/glutaric anhydride or phosphonate. The characterization of Fn‐modified surfaces showed that Fn grating via phosphonate has led to the highest amount of Fn cell‐binding site (RGD, arginine, glycine, and aspartate) available on the surface. Interestingly, cell culture studies revealed a strong correlation between the amount of available RGD ligands and cellular behavior, since enhanced proliferation and spreading of fibroblasts were noticed on Fn‐grafted surfaces via phosphonate. In addition, an original in vitro mechanical test, inspired from the real situation, to better predict clinical outcomes after implant insertion, has been developed. Tensile test data showed that the adhesion strength of a bio‐engineered dermal tissue was significantly higher around Fn‐grafted surfaces via phosphonate, as compared to untreated surfaces. This study sheds light on the importance of an appropriate selection of the linking arm to tightly control the spatial conformation of biomolecules on the material surface, and consequently cell interactions at the interface tissue/implant.
The best density functional theory functional for the prediction of 1H and 13C chemical shifts of protonated alkylpyrroles
Authors: Zahn Sarah L. V. , Hammerich Ole , Hansen Poul Erik , Sauer Stephan P. A. 
Published: May 2021

AbstractThe prediction of 13C chemical shifts can be challenging with density functional theory (DFT). In this study 39 different functionals and three different basis sets were tested on three neutral alkylpyrroles and their corresponding protonated species. The calculated shielding constants were compared to experimental data and results from previous calculations at the MP2. We find that the meta‐hybrid functional TPSSh with either the Pople style basis set 6‐311++G(2d,p) or the polarization consistent basis set pcSseg‐1 gives the best results for the 13C chemical shifts, whereas for the 1H chemical shifts it is the TPSSh functional with either the 6‐311++G(2d,p) or pcSseg‐2 basis set. Including an explicit solvent molecule hydrogen bonded to NH in the alkylpyrroles improves the results slightly for the 13C chemical shifts. On the other hand, for 1H chemical shifts the opposite is true. Compared to calculations at the MP2 level none of the DFT functionals can compete with MP2 for the 13C chemical shifts but for the 1H chemical shifts the investigated DFT functionals are shown to give better agreement with experiment than MP2 calculations.
MoSDeF Cassandra: A complete Python interface for the Cassandra Monte Carlo software
Authors: DeFever Ryan S. , Matsumoto Ray A. , Dowling Alexander W. , Cummings Peter T. , Maginn Edward J. 
Published: May 2021

AbstractWe introduce a new Python interface for the Cassandra Monte Carlo software, molecular simulation design framework (MoSDeF) Cassandra. MoSDeF Cassandra provides a simplified user interface, offers broader interoperability with other molecular simulation codes, enables the construction of programmatic and reproducible molecular simulation workflows, and builds the infrastructure necessary for high‐throughput Monte Carlo studies. Many of the capabilities of MoSDeF Cassandra are enabled via tight integration with MoSDeF. We discuss the motivation and design of MoSDeF Cassandra and proceed to demonstrate both simple use‐cases and more complex workflows, including adsorption in porous media and a combined molecular dynamics – Monte Carlo workflow for computing lateral diffusivity in graphene slit pores. The examples presented herein demonstrate how even relatively complex simulation workflows can be reduced to, at most, a few files of Python code that can be version‐controlled and shared with other researchers. We believe this paradigm will enable more rapid research advances and represents the future of molecular simulations.
A computational investigation of the selectivity and mechanism of the Lewis acid catalyzed oxa‐Diels–Alder cycloaddition of substituted diene with benzaldehyde
Authors: Khorief Nacereddine Abdelmalek , Merzoud Lynda , Morell Christophe , Chermette Henry 
Published: May 2021

AbstractThe selectivity and the mechanism of the uncatalyzed and AlCl3 catalyzed hetero‐Diels–Alder reaction (HDR) between ([E]‐4‐methylpenta‐2,4‐dienyloxy)(tert‐butyl)dimethylsilane 1 and benzaldehyde 2 have been studied using density functional theory at the MPWB1K/6‐31G(d) level of theory. The uncatalyzed HDR between diene 1 and alkene 2 is characterized by a polar character and proceeds via an asynchronous one‐step mechanism for the meta paths and synchronous for the ortho ones. In the presence of AlCl3 catalyst, the mechanism changes to be stepwise, while the first step is the rate‐determining step. The activation energies widely decrease, and the polar character increases dramatically. A large analysis of the mechanism is performed using the activation strain model/energy decomposition analysis (ASM/EDA) model, the natural bond orbital (NBO) and state specific dual descriptors (SSDDs). The obtained results indicate that the combined interaction energy associated with the distortion of the reactants in these HDR are at the origin of the observed kinetics. NBO analyses were applied to estimate the Lewis‐acid catalyst donor‐acceptor interaction with the molecular system. The SSDD analysis shed light into the orientation effects on the reaction kinetics by providing important information about charge transfer interactions during the chemical reaction. It indicates that the more favorable HDR pathway have the lowest excitation energies, facilitating the interaction between diene 1 and benzaldehyde 2 moieties. Non‐covalent interaction (NCI) and QTAIM analyses of the meta‐endo structure indicate that the presence of several weak NCIs formed at this approach is at the origin of the meta‐endo selectivity.
Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk
Authors: Gouda Nawal S. , Fawzy Manal S. , Toraih Eman A. 
Published: May 2021

AbstractBackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.MethodsThe CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.ResultsA higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed.ConclusionThe CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.
Mycobacterium tuberculosis causes a leaky blood‐brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring
Authors: Manjeese Wadzanai , Mvubu Nontobeko E. , Steyn Adrie J. C. , Mpofana Thabisile 
Published: May 2021

AbstractThe maternal system's exposure to pathogens influences foetal brain development through the influx of maternal cytokines and activation of the foetal immune status to a persistent inflammatory state characterised by glia cell activation. Neuroinflammation influences the blood‐brain barrier's (BBB) permeability allowing peripheral immune cell trafficking into the brain. Mycobacterium tuberculosis (Mtb) is a pathogen that causes Tuberculosis (TB), a global pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of Autism spectrum disorder (ASD), it is not known whether gestational Mtb infections also contribute to impaired foetal neurodevelopment. Here we infect pregnant Balb/c mice with Mtb H37Rv and Valproic acid (VPA) individually and in combination. Neuroinflammation was measured by assessing microglia and astrocyte population in the prefrontal cortex (PFC) and cerebellum (CER) of pups. Mtb infection increased the microglia population and caused morphological changes to a reactive phenotype in the PFC. Also, the astrocyte population was significantly increased in the PFC of Mtb pups. The BBB permeability was determined by measuring the Evans Blue (EB) dye concentration in the PFC and CER 1 hr post receiving intravenous EB‐dye injection. We found that prenatal Mtb exposure significantly increased the BBB's permeability in the PFC and CER of pups versus saline. Overall, our data demonstrate that prenatal exposure to Mtb predisposes offspring to a higher risk of BBB damage while inducing persistent neuroinflammation, which could lead to impaired neuronal development and function. These findings implicate a potential role of gestational Mtb infections in the aetiology of ASD.
Detection of the hybrid layer biodegradation initiation factor with a scanning electron microscope
Authors: Paken Gamze , Çömlekoğlu Muharrem Erhan , Sonugelen Mehmet 
Published: May 2021

AbstractThe purpose of this study was to elucidate the origin of initiation of hybrid layer biodegradation. Ninety caries‐free human third molars were divided into three surface groups: enamel, dentin, and NaOCl‐treated dentin. (n = 30/group) Each group was divided into three subgroups (n = 10/group) of luting resin materials with etch‐and‐rinse; self‐etch and self‐adhesive systems. Resin composite blocks and sticks were fabricated and adhered onto dentin and enamel surfaces. The bond strength values were evaluated with micro shear test and statistical analysis were made. On the other hand, teeth were sectioned with a slow‐speed saw into multiple beams. After thermocycling, samples were kept in 50% silver nitrate solution. Samples were analyzed with SEM in back‐scattered mode. According to the micro‐shear bond tests, higher bond strength values were observed in etch‐and‐rinse system. Bond strength values in self‐adhesive and etch‐and‐rinse groups were significantly higher than self‐etch groups in dentin surface and dentin surface treatment with NaOCl. Back‐scattered scanning electron microscope results showed that, different degradation mechanism was observed. The present study indicates that, due to the acid etching in dentin, collagen biodegradation was observed within the hybrid layer. On the enamel surfaces, resin degradation was related with resin monomers in adhesive systems.
Morphometric analysis of nuclear symmetry in urothelial carcinoma for predicting tumor recurrence
Authors: Klorin Geula , Halachmi Sarel , Nativ Ofer , Massalha Yamen , Stroller Leah , Amit Amnon , Sabo Edmond 
Published: May 2021

AbstractUrothelial carcinoma is the ninth most common cancer in the world. Cytological analysis of the urine is used for screening, as well as for cases suspected for neoplasia of the urinary tract. However, the sensitivity of urine cytology examination is low. The golden standard for diagnosing bladder cancer relies upon cystoscopy followed by a biopsy, which is microscopically assessed by the pathologist. Treatment decisions are based on the histological grade and stage of the tumor. Posttreatment tumor recurrence is 50%. The purpose of this study is to predict recurrence of urothelial carcinoma using a novel morphometric method of nuclear symmetry analysis. This method may help tailor the appropriate treatment and may reduce the need of invasive surgical procedures in patients. Computerized morphometry was applied to develop multiple symmetry indices of the nuclei of the tumor cells as follows: each nucleus was physically divided along its digital axis in two segments that were separately analyzed for their shape, size, optical density, and texture. Subsequently, ratios were obtained by mathematically dividing between the morphometric values of the two nuclear segments where the denominator contained the largest value of the two. These ratios were named symmetry indices and were included as variables to predict the recurrence time of the tumors. The change in the symmetry indices (loss of symmetry) of the nuclear roundness, fractal dimension and margination were the only independent predictors of recurrence time. Computerized morphometry of nuclear symmetry indices may help to predict tumor recurrence in urothelial carcinomas.
Anatomical, histological, and surface ultrastructural evaluation of the palatal mucosa of domestic rabbit (Oryctolagus cuniculus)
Authors: Mahdy Mohamed A. A. , Mohammed Elsayed S. I. 
Published: May 2021

AbstractThe present study investigated the morphology of the palate of rabbit (Oryctolagus cuniculus). Samples from 12 healthy adult rabbits were examined by gross observation, morphometry, scanning electron and light microscopy. The hard palate was elongated and narrowed rostrally. The incisive papilla appeared as a diamond‐shaped prominence flanked on both sides by a groove on which a slit‐like opening of the nasopalatine duct opened. The palatine raphe was in the form of a groove. On either side of the raphe, 14–16 palatine ridges were present. The direction of these ridges differed according to their position. An incomplete (short) palatine ridge was occasionally present at the caudal part of the hard palate. Several gland openings were scattered on the surface of the palatine ridges. The soft palate extended to about the middle of epiglottis caudally. Its ventral surface had numerous thin transverse mucosal folds separated by furrows, and several openings of glands. Histologically, the incisive papilla, palatine ridges, and soft palate were lined by a parakeratinized stratified squamous epithelium resting on a dense connective layer of lamina propria. The degree of keratinization and the thickness of the lamina propria decreased caudally. Seromucoid glands were present in the rostral and caudal parts of the hard palate, as well as in the soft palate. In conclusion, the palate of rabbit presented characteristic features suggesting functional adaptations for their herbivores diet. Studying the morphological characteristics of the hard and soft palate of rabbits will help veterinary practitioners to investigate pathology malformations and diseases of the oral cavity.