bluuebunny/crossref_metadata_2025_split huggingface dataset:
A research-driven approach to the identification of novel natural killer cell deficiencies affecting cytotoxic function
Authors: Lam Michael T. , Mace Emily M. , Orange Jordan S. 
Published: January 2020

AbstractNatural killer cell deficiencies (NKDs) are an emerging phenotypic subtype of primary immune deficiency. NK cells provide a defense against virally infected cells using a variety of cytotoxic mechanisms, and patients who have defective NK cell development or function can present with atypical, recurrent, or severe herpesviral infections. The current pipeline for investigating NKDs involves the acquisition and clinical assessment of patients with a suspected NKD followed by subsequent in silico, in vitro, and in vivo laboratory research. Evaluation involves initially quantifying NK cells and measuring NK cell cytotoxicity and expression of certain NK cell receptors involved in NK cell development and function. Subsequent studies using genomic methods to identify the potential causative variant are conducted along with variant impact testing to make genotype-phenotype connections. Identification of novel genes contributing to the NKD phenotype can also be facilitated by applying the expanding knowledge of NK cell biology. In this review, we discuss how NKDs that affect NK cell cytotoxicity can be approached in the clinic and laboratory for the discovery of novel gene variants.
Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort
Authors: Wijker Naomi E. , Vidmar Suzanna , Grimwood Keith , Sly Peter D. , Byrnes Catherine A. , Carlin John B. , Cooper Peter J. , Robertson Colin F. , Massie R. John , Kemner van de Corput Mariette P.C. , Cheney Joyce , Tiddens Harm A.W.M. , Wainwright Claire E. 
Published: January 2020

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sdage 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4–22; p≤ 0.001), bronchoalveolar lavage (BAL) log2interleukin (IL)-8 (OR 1.2, 95% CI 1.05–1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24–1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2IL-8 (coefficient 1.3, 95% CI 0.57–2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.
Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme
Authors: Nwaru Bright I. , Ekström Magnus , Hasvold Pål , Wiklund Fredrik , Telg Gunilla , Janson Christer 
Published: January 2020

BackgroundOveruse of short-acting β2-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme.MethodsBy linking data from Swedish national registries, asthma patients aged 12–45 years with two or more collections of drugs for obstructive lung disease during 2006–2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3–5, 6–10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality.ResultsThe analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3–5 canisters per year, 7% collecting 6–10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3–5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24–1.28); 6–10 canisters: 1.44 (1.41–1.46); and ≥11 canisters: 1.77 (1.72–1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3–5 canisters: HR 1.26 (95% CI 1.14–1.39); 6–10 canisters 1.67 (1.49–1.87); and ≥11 canisters: 2.35 (2.02–2.72) compared to two or fewer canisters per year.ConclusionOne-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.
Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis
Authors: Wasik Urszula , Kempinska-Podhorodecka Agnieszka , Bogdanos Dimitrios P. , Milkiewicz Piotr , Milkiewicz Malgorzata 
Published: January 2020

AbstractBackground & AimsAnti-mitochondrial-autoantibodies (AMA) remain a hallmark of Primary Biliary Cholangitis (PBC) however approximately 10% of patients test negative for these antibodies. They do not differ in terms of biochemistry or clinical presentation from AMA positive ones. Epigenetics play a key role in immune signalling. Two microRNAs (miRs), namely, miR-21 and miR-150 are known to be involved in liver inflammation and fibrosis. The expression of those two microRNAs and their downstream targets were analyze in the context of AMA-status and the stage of liver fibrosis.MethodsThe relative levels of miR-21 and miR-150 and their target genes: cMyb, RAS-guanyl-releasing protein-1(RASGRP1), and DNA-methyltransferase-1(DNMT1) were determined by Real-Time PCR in serum, liver tissue and peripheral blood mononuclear cells (PBMCs) of patients with PBC.ResultsSerum expressions of miR-21 and miR-150 were significantly enhanced in AMA-negative patients, and they inversely correlated with disease-specific AMA titers in PBS patients. In PBMCs, an increased expression of miR-21 correlated with decreased levels of RASGRP1 and DNMT1 mRNAs whereas, the level of miR-150 remained comparable to controls; and cMyb mRNA was downregulated. In cirrhotic livers, the level of miR-21 was unchanged while miR-150 expression was increased.ConclusionThis study convincingly report, that AMA-negative PBC is characterized by notable alternations of miR-21 and miR-150 and their downstream targets compared to AMA-positive patients underlining their possible importance in the induction of the disease and its progression to fibrosis.
The ubiquitin system: orchestrating cellular signals in non-small-cell lung cancer
Authors: Fan Qiang , Wang Qian , Cai Renjie , Yuan Haihua , Xu Ming 
Published: January 2020

AbstractThe ubiquitin system, known as a common feature in eukaryotes, participates in multiple cellular processes, such as signal transduction, cell-cycle progression, receptor trafficking and endocytosis, and even the immune response. In lung cancer, evidence has revealed that aberrant events in ubiquitin-mediated processes can cause a variety of pathological outcomes including tumorigenesis and metastasis. Likewise, ubiquitination on the core components contributing to the activity of cell signaling controls bio-signal turnover and cell final destination. Given this, inhibitors targeting the ubiquitin system have been developed for lung cancer therapies and have shown great prospects for clinical application. However, the exact biological effects and physiological role of the drugs used in lung cancer therapies are still not clearly elucidated, which might seriously impede the progress of treatment. In this work, we summarize current research advances in cell signal regulation processes mediated through the ubiquitin system during the development of lung cancer, with the hope of improving the therapeutic effects by means of aiming at efficient targets.
Advances of Nano-Structured Extended-Release Local Anesthetics
Authors: He Yumiao , Qin Linan , Huang Yuguang , Ma Chao 
Published: January 2020

AbstractExtended-release local anesthetics (LAs) have drawn increasing attention with their promising role in improving analgesia and reducing adverse events of LAs. Nano-structured carriers such as liposomes and polymersomes optimally meet the demands of/for extended-release, and have been utilized in drug delivery over decades and showed satisfactory results with extended-release. Based on mature technology of liposomes, EXPAREL, the first approved liposomal LA loaded with bupivacaine, has seen its success in an extended-release form. At the same time, polymersomes has advances over liposomes with complementary profiles, which inspires the emergence of hybrid carriers. This article summarized the recent research successes on nano-structured extended-release LAs, of which liposomal and polymeric are mainstream systems. Furthermore, with continual optimization, drug delivery systems carry properties beyond simple transportation, such as specificity and responsiveness. In the near future, we may achieve targeted delivery and controlled-release properties to satisfy various analgesic requirements.
Biosynthesis and Antibacterial Activity of Silver Nanoparticles Using Yeast Extract as Reducing and Capping Agents
Authors: Shu Mengjun , He Fengjiao , Li Zhaohui , Zhu Xingzhong , Ma Yujie , Zhou Zhihua , Yang Zhi , Gao Feng , Zeng Min 
Published: January 2020

AbstractBiosynthesis for the preparation of antimicrobial silver nanoparticles (Ag NPs) is a green method without the use of cytotoxic reducing and surfactant agents. Herein, shape-controlled and well-dispersed Ag NPs were biosynthesized using yeast extract as reducing and capping agents. The synthesized Ag NPs exhibited a uniform spherical shape and fine size, with an average size of 13.8 nm. The biomolecules of reductive amino acids, alpha-linolenic acid, and carbohydrates in yeast extract have a significant role in the formation of Ag NPs, which was proved by the Fourier transform infrared spectroscopy analysis. In addition, amino acids on the surface of Ag NPs carry net negative charges which maximize the electrostatic repulsion interactions in alkaline solution, providing favorable stability for more than a year without precipitation. The Ag NPs in combination treatment with ampicillin reversed the resistance in ampicillin-resistant E. coli cells. These monodispersed Ag NPs could be a promising alternative for the disinfection of multidrug-resistant bacterial strains, and they showed negligible cytotoxicity and good biocompatibility toward Cos-7 cells.
Combined Use of Anisotropic Silver Nanoprisms with Different Aspect Ratios for Multi-Mode Plasmon-Exciton Coupling
Authors: Takeshima Naoto , Sugawa Kosuke , Tahara Hironobu , Jin Shota , Noguchi Masaki , Hayakawa Yutaro , Yamakawa Yuhei , Otsuki Joe 
Published: January 2020

AbstractAbsorption enhancement based on interaction between the localized surface plasmon (LSP) and molecular exciton is one of the most important phenomena for the development of high-performance solar devices. In this study, hybrids of plasmonic metal nanoparticles and dye molecules have been developed, which exhibit enhanced absorption at precisely tuned wavelengths in a visible region. The hybrids consist of a porphyrin derivative, which has four absorption peaks (Q-bands) in a range of 500–700 nm, and triangular silver nanoprisms (AgPRs), which are developed by us to exhibit precisely tuned LSP resonance wavelengths. Absorption enhancement over the whole Q-band range is induced by the combined use of three kinds of AgPRs of different aspect ratios. Furthermore, the quantitative evaluation of absorption enhancement based on the LSP-based fluorescence enhancement phenomenon has demonstrated that efficient absorption enhancement can be effected at multiple wavelengths.
Evaluation of androgen receptor status in urothelial carcinoma of the urinary bladder in Egyptian patients: an immunohistochemical study
Authors: Wagih Mohamed , Kamel Marwa 
Published: January 2020

Abstract
Background
The roles of androgen and androgen receptor (AR) signaling in the oncogenesis of prostate cancer are very well established. What is more poorly understood is the role of AR in other human malignancies including bladder cancer. The incidence of bladder cancer is much higher in males than females, but the exact etiology has not been fully elucidated. This gender disparity has raised the possibility of the AR pathway being involved in the genesis of this disease. Thereby, the aim of this work was to evaluate the expression of AR in a group of Egyptian patients with urothelial bladder carcinoma and to assess whether its expression was correlated with other pathological tumor features. Urothelial bladder carcinoma tissue samples from 50 patients were studied by immunostaining for AR expression in tumor cells.

Results
AR was positively expressed in 29 (58%) patients, while negative expression was observed in 21 (42%) patients. No statistically significant difference in AR expression with respect to tumor grade (P = 0.07) and pT stage (P = 0.09) was observed.

Conclusions
The results obtained in this study indicates a clinical value of the AR expression in Egyptian patients with urothelial bladder carcinoma, providing the basis for further studies to evaluate its role and the possibility of new target-based therapies for urothelial bladder carcinoma.
The activation of antioxidant and apoptosis pathways involved in damage of human proximal tubule epithelial cells by PM2.5 exposure
Authors: Huang Xiaoliu , Shi Xiujuan , Zhou Ji , Li Sen , Zhang Lijuan , Zhao Huijun , Kuang Xingya , Li Jue 
Published: January 2020

Abstract
Background
Exposure to airborne fine particulate matter (PM2.5) has been reported to be harmful to the human kidney. However, whether the activation of oxidative stress and cell apoptosis plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of cytotoxicity after PM2.5 exposure in human proximal tubule epithelial cells (HK-2 cells).

Results
PM2.5 exposure resulted in a significant decrease in cell viability, with an increase in LDH release and the early kidney damage marker kidney injury molecule-1 (KIM-1) expression in a dose-dependent manner and time-dependent manner. PM2.5 exposure induced reactive oxygen species (ROS) generation and markedly elevated apoptosis in HK-2 cells. In addition, PM2.5 exposure resulted in the activation of antioxidant pathway, as evidenced by the increased expressions of Nrf2, HO-1 and NQO1 and decreased expression of Keap1. Moreover, PM2.5 exposure also induced the activation of apoptotic pathway, as evidenced by the increased expressions of pro-apoptotic proteins Bax, caspase-3 and caspase-8 and decreased expression of antiapoptotic protein Bcl-2.

Conclusions
Our results demonstrated that both antioxidant pathway and apoptotic pathway played critical roles in the damage mediated by PM2.5 in HK-2 cells. This study would give us a strategy to prevent the impairment of renal function by PM2.5 induced through repression of oxidative stress and apoptosis.
Comparative transcriptomics reveals candidate carotenoid color genes in an East African cichlid fish
Authors: Ahi Ehsan Pashay , Lecaudey Laurène A. , Ziegelbecker Angelika , Steiner Oliver , Glabonjat Ronald , Goessler Walter , Hois Victoria , Wagner Carina , Lass Achim , Sefc Kristina M. 
Published: January 2020

AbstractBackgroundCarotenoids contribute significantly to animal body coloration, including the spectacular color pattern diversity among fishes. Fish, as other animals, derive carotenoids from their diet. Following uptake, transport and metabolic conversion, carotenoids allocated to body coloration are deposited in the chromatophore cells of the integument. The genes involved in these processes are largely unknown. Using RNA-Sequencing, we tested for differential gene expression between carotenoid-colored and white skin regions of a cichlid fish,Tropheus duboisi“Maswa”, to identify genes associated with carotenoid-based integumentary coloration. To control for positional gene expression differences that were independent of the presence/absence of carotenoid coloration, we conducted the same analyses in a closely related population, in which both body regions are white.ResultsA larger number of genes (n = 50) showed higher expression in the yellow compared to the white skin tissue than vice versa (n = 9). Of particular interest was the elevated expression level ofbco2ain the white skin samples, as the enzyme encoded by this gene catalyzes the cleavage of carotenoids into colorless derivatives. The set of genes with higher expression levels in the yellow region included genes involved in xanthophore formation (e.g.,pax7andsox10), intracellular pigment mobilization (e.g.,tubb,vim,kif5b), as well as uptake (e.g.,scarb1) and storage (e.g.,plin6) of carotenoids, and metabolic conversion of lipids and retinoids (e.g.,dgat2, pnpla2, akr1b1,dhrs). Triglyceride concentrations were similar in the yellow and white skin regions. Extracts of integumentary carotenoids contained zeaxanthin, lutein and beta-cryptoxanthin as well as unidentified carotenoid structures.ConclusionOur results suggest a role of carotenoid cleavage by Bco2 in fish integumentary coloration, analogous to previous findings in birds. The elevated expression of genes in carotenoid-rich skin regions with functions in retinol and lipid metabolism supports hypotheses concerning analogies and shared mechanisms between these metabolic pathways. Overlaps in the sets of differentially expressed genes (includingdgat2,bscl2,faxdc2andretsatl) between the present study and previous, comparable studies in other fish species provide useful hints to potential carotenoid color candidate genes.
Incidence of common opportunistic infections among HIV-infected children on ART at Debre Markos referral hospital, Northwest Ethiopia: a retrospective cohort study
Authors: Melkamu Mamaru Wubale , Gebeyehu Mulugeta Tesfa , Afenigus Abebe Dilie , Hibstie Yitbarek Tenaw , Temesgen Belisty , Petrucka Pammla , Alebel Animut 
Published: January 2020

Abstract
Background
Opportunistic infections (OIs) are the leading cause of morbidity and mortality among children living with human immunodeficiency virus (HIV). For better treatments and interventions, current and up-to-date information concerning occurrence of opportunistic infections in HIV-infected children is crucial. However, studies regarding the incidence of common opportunistic infections in HIV-infected children in Ethiopia are very limited. Hence, this study aimed to determine the incidence of opportunistic infections among HIV-infected children on antiretroviral therapy (ART) at Debre Markos Referral Hospital.

Methods
A facility-based retrospective cohort study was undertaken at Debre Markos Referral Hospital for the period of January 1, 2005 to March 31, 2019. A total of 408 HIV-infected children receiving ART were included. Data from HIV-infected children charts were extracted using a data extraction form adapted from ART entry and follow-up forms. Data were entered using Epi-data™ Version 3.1 and analyzed using Stata™ Version 14. The Kaplan Meier survival curve was used to estimate the opportunistic infections free survival time. Both bi-variable and multivariable Cox proportional hazard models were fitted to identify the predictors of opportunistic infections.

Results
This study included the records of 408 HIV-infected children-initiated ART between the periods of January 1, 2005 to March 31, 2019. The overall incidence rate of opportunistic infections during the follow-up time was 9.7 (95% CI: 8.13, 11.48) per 100 child-years of observation. Tuberculosis at 29.8% was the most commonly encountered OI at follow-up. Children presenting with advanced disease stage (III and IV) (AHR: 1.8, 95% CI: 1.2, 2.7), having “fair” or “poor” ART adherence (AHR: 2.6, 95% CI: 1.8, 3.8), not taking OI prophylaxis (AHR:1.6, 95% CI: 1.1, 2.4), and CD4 count or % below the threshold (AHR:1.7, 95% CI: 1.1, 2.6) were at a higher risk of developing opportunistic infections.

Conclusions
In this study, the incidence rate of opportunistic infections among HIV-infected children remained high. Concerning predictors, such as advanced disease stage (III and IV), CD4 count or % below the threshold, “fair” or “poor” ART adherence, and not taking past OI prophylaxis were found to be significantly associated with OIs.
Chlamydia trachomatis isolated from cervicovaginal samples in Sapporo, Japan, reveals the circulation of genetically diverse strains
Authors: Thapa Jeewan , Watanabe Takanori , Isoba Mana , Okubo Torahiko , Abe Kiyotake , Minami Kunihiro , Yamaguchi Hiroyuki 
Published: January 2020

Abstract
Background
This study was conducted to understand the molecular epidemiology of circulating Chlamydia trachomatis (Ct) strains in Sapporo, Japan.

Methods
A total of 713 endocervical samples collected from April 2016 to March 2019 were screened for Ct. The obtained Ct positive samples were analyzed by ompA genotyping and multilocus sequence analysis (MLSA).

Results
Eighty-three (11.6%) samples were positive for Ct plasmid DNA. Sequence analysis of the ompA gene from the 61 positive cases revealed eight genotypes: F (40.9%), E (19.6%), D (14.7%), G (9.8%), H (6.5%), I (3.2%), K (3.2%), and J (1.6%). The globally dominant genotype E and F strains were highly conserved with 13 ompA genetic variants being detected, whereas genotype D strains were the most diverse. Genetic characterization of D strains revealed that D1 genetic variants may be potentially specific to Sapporo. MLSA revealed 13 unique sequence types (STs) including four novel STs from 53 positive samples, with the globally dominant STs 39 and 19 being predominant. STs 39, 34, and 21 were exclusively associated with genotypes E and F indicating their global dominance. Novel ST70 and ST30 were specifically associated with genotype D.

Conclusion
Our study has revealed the circulation of genetically diverse Ct strains in the women population of Sapporo, Japan. We suggest identifying a transmission network of those successful strains and implementing public health prevention strategies to control the spread of Ct in Sapporo.