bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing effects of personal behaviors and environmental exposure on asthma episodes: a diary-based approach
Authors: Chan Ta-Chien , Hu Tsuey-Hwa , Chu Yen-Hua , Hwang Jing-Shiang 
Published: December 2019

Abstract
Background
Quantifying the effects of personal health behaviors and environmental exposure on asthma flare-ups is a challenge. Most studies have focused on monitoring the symptoms and drug usage for relieving symptoms. In this study, we emphasize the need to understand how personal and environmental conditions are related to the occurrence of asthma symptoms.

Methods
We designed an online health diary platform to collect personal health behaviors from children, their parents and other adults with any allergic diseases including asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis. The participants used mobile devices or computers to record their daily health-related activities such as sleep, exercise, diet, perception of air quality and temperature, and asthma symptoms. The participants also recorded secondhand smoke exposure and the time of activities, which were combined with ambient air quality measurements for calculating personal air pollution exposure. A generalized linear mixed model was used to estimate the effects of the factors.

Results
During the study period (January 2017–June 2017, and October 2017–September 2018), 132 participants provided 25,016 diary entries, and 84 participants had experienced asthma symptoms in 1458 diary entries. The results showed some different risk factors for the minors and adults. For minors, high-intensity exercise, contact with persons with influenza-like illness (ILI) and the perception of hot temperature and bad indoor air quality were associated with the occurrence of asthma episodes. The identified risk factors for the adult participants included having dehumidifiers at home, exposure to secondhand smoke, having bad sleep quality, contact with persons with ILI, not eating fruit and seafood, perceiving cold temperature, bad quality of indoor and outdoor air, and exposure to high concentration of ozone.

Conclusions
The revealed personal risk factors and perceptions of air quality and temperature may provide guidance on behavioral change for people susceptible to asthma to help control acute onset and severe exacerbation of asthma flare-ups.
Substantive molecular and histological changes within the meniscus with tears
Authors: Long Yi , Xie Jingping , Zhang Zhi-Qi , Zhang Ziji , Meng Fangang , He Aishan 
Published: December 2019

Abstract
Background
The meniscus plays a vital role in the normal biomechanics of the knee. However, it is not well studied at the molecular level. The purpose of this study was to determine whether molecular and pathological changes in the meniscal tissue vary depending on the presence or absence of meniscal and/or anterior cruciate ligament tear (ACL).

Methods
Six normal menisci (group A), seven simple torn menisci (group B) and seven torn menisci with concomitant anterior cruciate ligament tears (group C) were collected. We observed the pathological changes in the menisci and used real-time polymerase chain reaction along with immunohistochemistry and in situ hybridisation to examine the levels of ACAN, ADAMTS5, COL10A1, CEBPβ, MMP13 and miR-381-3p, miR-455-3p, miR-193b-3p, miR-92a-3p, respectively. Patients were scored preoperatively and postoperatively using the Lysholm Knee Scoring Scale and International Knee Documentation Committee Subjective Knee Evaluation Form.

Results
Compared with group A, the expression levels of ADAMTS5, COL10A1, CEBPβ, and MMP13 and all the miRNAs were increased while ACAN was down-regulated in groups B and C. Additionally, the gene expression and miRNA levels were higher in group C than that in group B, except for ACAN, which was lower. Several fibrochondrocytes strongly expressed ADAMTS5, CEBPβ, and MMP13 in groups B and C and had high levels of miR-381-3p and miR-455-3p than that in group A. Postoperative Lysholm and IKDC scores were higher in group B than in group C.

Conclusions
Our findings suggest that the meniscus tended to degenerate after it was injured, especially when combined with a torn ACL. The miRNAs investigated in this study might also contribute to meniscus degeneration. Patients with a combined injury patterns might have relatively worse joint function.
Dynamic viscoelastic characterisation of human osteochondral tissue: understanding the effect of the cartilage-bone interface
Authors: Mountcastle Sophie E. , Allen Piers , Mellors Ben O. L. , Lawless Bernard M. , Cooke Megan E. , Lavecchia Carolina E. , Fell Natasha L. A. , Espino Daniel M. , Jones Simon W. , Cox Sophie C. 
Published: December 2019

Abstract
Background
Despite it being known that subchondral bone affects the viscoelasticity of cartilage, there has been little research into the mechanical properties of osteochondral tissue as a whole system. This study aims to unearth new knowledge concerning the dynamic behaviour of human subchondral bone and how energy is transferred through the cartilage-bone interface.

Methods
Dynamic mechanical analysis was used to determine the frequency-dependent (1–90 Hz) viscoelastic properties of the osteochondral unit (cartilage-bone system) as well as isolated cartilage and bone specimens extracted from human femoral heads obtained from patients undergoing total hip replacement surgery, with a mean age of 78 years (N = 5, n = 22). Bone mineral density (BMD) was also determined for samples using micro-computed tomography as a marker of tissue health.

Results
Cartilage storage and loss moduli along with bone storage modulus were found to increase logarithmically (p < 0.05) with frequency. The mean cartilage storage modulus was 34.4 ± 3.35 MPa and loss modulus was 6.17 ± 0.48 MPa (mean ± standard deviation). In contrast, bone loss modulus decreased logarithmically between 1 and 90 Hz (p < 0.05). The storage stiffness of the cartilage-bone-core was found to be frequency-dependent with a mean value of 1016 ± 54.0 N.mm− 1, while the loss stiffness was determined to be frequency-independent at 78.84 ± 2.48 N.mm− 1. Notably, a statistically significant (p < 0.05) linear correlation was found between the total energy dissipated from the isolated cartilage specimens, and the BMD of the isolated bone specimens at all frequencies except at 90 Hz (p = 0.09).

Conclusions
The viscoelastic properties of the cartilage-bone core were significantly different to the tissues in isolation (p < 0.05). Results from this study demonstrate that the functionality of these tissues arises because they operate as a unit. This is evidenced through the link between cartilage energy dissipated and bone BMD. The results may provide insights into the functionality of the osteochondral unit, which may offer further understanding of disease progression, such as osteoarthritis (OA). Furthermore, the results emphasise the importance of studying human tissue, as bovine models do not always display the same trends.
Perioperative fluid dynamics evaluated by bioelectrical impedance analysis predict infectious surgical complications after esophagectomy
Authors: Oya Shuichiro , Yamashita Hiroharu , Iwata Ryohei , Kawasaki Koichiro , Tanabe Asami , Yagi Koichi , Aikou Susumu , Seto Yasuyuki 
Published: December 2019

Abstract
Background
Transthoracic esophagectomy, among the most invasive surgeries, is highly associated with postoperative infectious complications which adversely affect postoperative management including fluid dynamics. The aim of the study is to evaluate the utility of perioperative bioelectrical impedance analysis (BIA) measurements for the patients after transthoracic esophagectomy.

Method
Multi-frequency BIA measurements were conducted in 24 patients undergoing transthoracic esophagectomy preoperatively, at 1 h after surgery, and twice daily for the following 7 days. The amounts of extracellular water (ECW), internal cellular water (ICW), total body water (TBW), and fat-free mass (FFM) were calculated. Changing trends in variables were analyzed, and the patients were subdivided according to the presence of infectious surgical adverse events to identify differences in fluid dynamics.

Results
ECW was the major body fluid compartment showing an increase after surgery, and peaked on postoperative day (POD) 2. Twelve patients experienced infectious complications. The peaks of changes in ECW and ECW/TBW appeared earlier and their values at the highest peak were significantly lower in the group without infectious complications on POD 2. The ICW/FFM value showed a mild decrease as compared to POD1 and then gradually recovered. It was significantly lower even before surgery and showed the most significant stratification on POD2. ECW/TBW of 48% and ICW/FFM of 37% on POD2 were predictive cut-off values for infectious adverse events with high area-under receiver operating characteristic (ROC) curves: 0.80 or higher.

Conclusion
BIA measurements are useful for monitoring fluid retention and may predict infectious complications in the early phase after transthoracic esophagectomy.

Trial registration
Registry name: UMIN-CTR, ID: UMIN000030734, Registered on January 9, 2018, retrospectively registered.
Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis
Authors: Wang Huitao , Liu Jianhe , Fang Kewei , Ke Changxing , Jiang Yongming , Wang Guang , Yang Tongxin , Chen Tao , Shi Xin 
Published: December 2019

Abstract
Background
Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients.

Methods
The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Results
Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator’s choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis.

Conclusions
This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.
The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro
Authors: Benson Kathleen F. , Stamets Paul , Davis Renee , Nally Regan , Taylor Alex , Slater Sonya , Jensen Gitte S. 
Published: December 2019

AbstractBackgroundThe medicinal mushroomTrametes versicolor(Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate.MethodsTv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and theTrametes versicolormycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays.ResultsBoth aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells.Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors.ConclusionThe results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.
Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos
Authors: Mehrbod Parvaneh , Ebrahimi Samad Nejad , Fotouhi Fatemeh , Eskandari Fatemeh , Eloff Jacobus N. , McGaw Lyndy J. , Fasina Folorunso O. 
Published: December 2019

Abstract
Background
Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking.

Methods
MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R.

Results
The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively.

Conclusions
Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.
Operating room first case start times: a metric to assess systems-based practice milestones?
Authors: Hoffman Christopher Ryan , Horrow Jay , Ranganna Shreyas , Green Michael Stuart 
Published: December 2019

Abstract
Background
Resident competence in peri-operative care is a reflection on education and cost-efficiency. Inspecting pre-existing operating room metrics for performance outliers may be a potential solution for assessing competence. Statistical correlation of problematic benchmarks may reveal future opportunities for educational intervention.

Methods
Case-log database review yielded 3071 surgical cases involving residents over the course of 5 years. Surgery anticipated and actual start times were evaluated for delays and residents were assessed using the days of resident training performed at the time of each corresponding case. Other variables recorded included day of week, attending anesthesiologist name, attending surgeon name, patient age, sex, American Society of Anesthesiologists physical status classification (ASA PS), and in-patient versus day surgery status. Mixed-effect, multi-variable, linear regression determined independent determinants of delay time.

Results
The analysis identified day of the week (F = 25.65, P < 0.0001), days of training (F = 8.39, P = 0.0038), attending surgeon (F = 2.67, P < 0.0001), and anesthesiology resident (F = 1.67, P = 0.0012) as independent predictors of delay time for first-start cases, with an overall regression model F = 3.09, r2 = 0.186, and P < 0.0001.

Conclusions
The day of the week and attending surgeon demonstrated significant impact of case delay compared to resident days trained. If a learning curve for first-case start punctuality exists for anesthesiology residents, it is subtle and irrelevant to operating room efficiency. The regression model accounted for only 19% of the variability in the outcome of delay time, indicating a multitude of additional unidentified factors contributing to operating room efficiency.
DNA methylation is associated with lung function in never smokers
Authors:   BIOS Consortium, de Vries Maaike , Nedeljkovic Ivana , van der Plaat Diana A. , Zhernakova Alexandra , Lahousse Lies , Brusselle Guy G. , Amin Najaf , van Duijn Cornelia M. , Vonk Judith M. , Boezen H. Marike 
Published: December 2019

Abstract
Background
Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers.

Methods
We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Illumina 450 K) in blood of never smokers in four independent cohorts, LifeLines COPD&C (N = 903), LifeLines DEEP (N = 166), Rotterdam Study (RS)-III (N = 150) and RS-BIOS (N = 206). We meta-analyzed the cohort-specific methylation results to identify differentially methylated CpG-sites with FEV1/FVC. Expression Quantitative Trait Methylation (eQTM) analysis was performed in the Biobank-based Integrative Omics Studies (BIOS).

Results
A total of 36 CpG-sites were associated with FEV1/FVC in never smokers at p-value< 0.0001, but the meta-analysis did not reveal any epigenome-wide significant CpG-sites. Of interest, 35 of these 36 CpG-sites have not been associated with lung function before in studies including subjects irrespective of smoking history. Among the top hits were cg10012512, cg02885771, annotated to the gene LTV1 Ribosome Biogenesis factor (LTV1), and cg25105536, annotated to Kelch Like Family Member 32 (KLHL32). Moreover, a total of 11 eQTMS were identified.

Conclusions
With the identification of 35 CpG-sites that are unique for never smokers, our study shows that DNA methylation is also associated with FEV1/FVC in subjects that never smoked and therefore not merely related to smoking.
Relationship between diffusion capacity and small airway abnormality in COPDGene
Authors: Criner Rachel N. , Hatt Charles R. , Galbán Craig J. , Kazerooni Ella A. , Lynch David A. , McCormack Meredith C. , Casaburi Richard , MacIntyre Neil R. , Make Barry J. , Martinez Fernando J. , Labaki Wassim W. , Curtis Jeffrey L. , Han Mei Lan K. 
Published: December 2019

Abstract
Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1–2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease.

Trial registration
NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.
The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells
Authors: Zou Dongling , Dong Lei , Li Chenying , Yin Zhe , Rao Shuan , Zhou Qi 
Published: December 2019

Abstract
Background
Since FTO was recognized as the first m6A demethylase, the understanding of its biological function has been widely expanded. However, the role of FTO in cervical cancer tumorigenesis remains unclear.

Methods
In this study, we first analyzed the expression of FTO in two independent human cancer datasets and evaluated the correlation between FTO level and cervical cancer progression. Using small hairpin RNA technology, we explored the function of FTO in cervical cancer cell line Hela and SiHa cells, respectively. We then determined the FTO targets by performing transcriptional profile with FTO deficient and competent Hela cells, and finally validated these targets with ribosome profiling and functional rescue experiments.

Results
Our data suggested that FTO was frequently overexpressed in human cervical cancer tissues and highly correlated with cervical cancer progression. FTO serves as an oncogenic regulator for cervical cancer cells’ proliferation and migration which is vastly depended on its demethylase activity. Mechanistically, FTO interacts with transcripts of E2F1 and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc, however, either overexpress E2F1 or Myc sufficiently compensates the FTO deficiency which decreases cell proliferation and migration.

Conclusions
Our study indicates that FTO plays important oncogenic role in regulating cervical cancer cells’ proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts. FTO represents a potential drug candidate for cervical cancer therapy.