bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraoxonase 1 gene (PON1) variants concerning hepatitis C virus (HCV) spontaneous clearance in hemodialysis individuals: a case–control study
Authors: Grzegorzewska Alicja E. , Mostowska Adrianna , Warchoł Wojciech , Jagodziński Paweł P. 
Published: August 2021

Abstract
Background
To explore associations between PON1 rs854560, rs662, 705,379, HCV clearance, and interactions between tested PON1 single nucleotide variants (SNVs) and interferon-λ4 gene (IFNL4) rs368234815 variant in hemodialyzed individuals.

Methods
The study included 83 HD individuals who spontaneously resolved HCV infection (all had known IFNL4 rs368234815 variant) and 104 individuals with persistently positive blood tests for HCV RNA (102 were IFNL4 rs368234815 variant successfully genotyped). We genotyped PON1 by high-resolution melt analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). We used a logistic regression model to assess the association between genetic data and HCV outcome while adjusting for clinical confounding variables. Epistatic interactions between tested PON1 SNVs and IFNL4 rs368234815 were analyzed by the multifactor dimensionality reduction method.

Results
In the recessive inheritance model, PON1 rs662 GG (OR 9.94, 95% CI 1.20–82.7, P = 0.022) and rs854560 TT (OR 4.31, 95% CI 1.62–11.5, P = 0.003) genotypes were associated with a higher probability for HCV clearance. The haplotype composed of rs662A_rs854560A_rs705379 was not associated with spontaneous HCV clearance. The IFNL4 rs368234815 TT/TT variant was equally distributed among individuals bearing different PON1 SNVs. The epistatic gene–gene analysis did not reveal the interaction between tested PON1 SNVs and IFNL4 rs368234815 (P = 0.094). Regression model, including the PON1 rs662 GG genotype, the PON1 rs854560 genotype, the IFNL4 rs368234815 TT/TT genotype, age at RRT onset, RRT duration, and chronic glomerulonephritis as possible explanatory variables for spontaneous HCV clearance, showed that significant predictors of spontaneous HCV clearance were the IFNL4 rs368234815 TT/TT genotype (OR 2.607, 95% CI 1.298—5.235, P = 0.007), PON1 rs854560 TT (OR 6.208, 1.962–19.644, P = 0.002), PON1 rs662 GG (OR 10.762, 1.222–94.796, P = 0.032), and RRT duration (OR 0.930, 95% CI 0.879–0.984, P = 0.011).

Conclusion
In HD individuals, PON1 rs662 GG and rs854560 TT are associated with a higher frequency of spontaneous HCV clearance.
Genome-wide profiling of alternative splicing in glioblastoma and their clinical value
Authors: Li Youwei , Guo Dongsheng 
Published: August 2021

Abstract
Background
Alternative splicing (AS), one of the main post-transcriptional biological regulation mechanisms, plays a key role in the progression of glioblastoma (GBM). Systematic AS profiling in GBM is limited and urgently needed.

Methods
TCGA SpliceSeq data and the corresponding clinical data were downloaded from the TCGA data portal. Survival-related AS events were identified through Kaplan–Meier survival analysis and univariate Cox analysis. Then, splicing correlation network was constructed based on these AS events and associated splicing factors. LASSO regression followed by multivariate Cox analysis was performed to validate independent AS biomarkers and to construct a risk prediction model. Enrichment analysis was subsequently conducted to explore potential signaling pathways of these AS events.

Results
A total of 132 TCGA GBM samples and 45,610 AS events were included in our study, among which 416 survival-related AS events were identified. An AS correlation network, including 54 AS events and 94 splicing factors, was constructed, and further functional enrichment was performed. Moreover, the novel risk prediction model we constructed displayed moderate performance (the area under the curves were > 0.7) at both one, two and three years.

Conclusions
Survival-related AS events may be vital factors of both biological function and prognosis. Our findings in this study can deepen the understanding of the complicated mechanisms of AS in GBM and provide novel insights for further study. Moreover, our risk prediction model is ready for preliminary clinical applications. Further verification is required.
Fine particulate matter constituents associated with emergency room visits for pediatric asthma: a time-stratified case–crossover study in an urban area
Authors: Ho Yu-Ni , Cheng Fu-Jen , Tsai Ming-Ta , Tsai Chih-Min , Chuang Po-Chun , Cheng Chi-Yung 
Published: August 2021

Abstract
Background
Global asthma-related mortality tallies at around 2.5 million annually. Although asthma may be triggered or exacerbated by particulate matter (PM) exposure, studies investigating the relationship of PM and its components with emergency department (ED) visits for pediatric asthma are limited. This study aimed to estimate the impact of short-term exposure to PM constituents on ED visits for pediatric asthma.

Methods
We retrospectively evaluated non-trauma patients aged younger than 17 years who visited the ED with a primary diagnosis of asthma. Further, measurements of PM with aerodynamic diameter of < 10 μm (PM10), PM with aerodynamic diameter of < 10 μm (PM2.5), and four PM2.5 components (i.e., nitrate (NO3−), sulfate (SO42−), organic carbon (OC), and elemental carbon (EC)) were collected between 2007 and 2010 from southern particulate matter supersites. These included one core station and two satellite stations in Kaohsiung City, Taiwan. A time-stratified case-crossover study was conducted to analyze the hazard effect of PM.

Results
Overall, 1597 patients were enrolled in our study. In the single-pollutant model, the estimated risk increase for pediatric asthma incidence on lag 3 were 14.7% [95% confidence interval (CI), 3.2–27.4%], 13.5% (95% CI, 3.3–24.6%), 14.8% (95% CI, 2.5–28.6%), and 19.8% (95% CI, 7.6–33.3%) per interquartile range increments in PM2.5, PM10, nitrate, and OC, respectively. In the two-pollutant models, OC remained significant after adjusting for PM2.5, PM10, and nitrate. During subgroup analysis, children were more vulnerable to PM2.5 and OC during cold days (< 26 °C, interaction p = 0.008 and 0.012, respectively).

Conclusions
Both PM2.5 concentrations and its chemical constituents OC and nitrate are associated with ED visits for pediatric asthma. Among PM2.5 constituents, OC was most closely related to ED visits for pediatric asthma, and children are more vulnerable to PM2.5 and OC during cold days.
Evaluation of the “safe multidisciplinary app-assisted remote patient-self-testing (SMART) model” for warfarin home management during the COVID-19 pandemic: study protocol of a multi-center randomized controlled trial
Authors: Chen Lei , Zhou Yang-Zhao , Zhou Xin-Min , Liu Li-Ming , Xu Ping , Zhang Xia , Tan Sheng-Lan 
Published: August 2021

Abstract
Background
Warfarin treatment requires frequent monitoring of INR (international normalized ratio) to adjust dosage in a therapeutic range. In China, patients living in small towns usually go to tertiary hospitals to get warfarin monitoring and dosing, resulting in low frequencies of follow-ups and high incidence of complications. Influenced by the COVID-19 pandemic, patients on warfarin have further reduced their visits to healthcare institutions. While patient self-testing (PST) via using a point-of-care testing device for INR measuring at home has been widely used in developed countries and demonstrated improved clinical outcomes compared to usual care in clinics, it is rarely applied in developing countries, including China. This proposed study will develop and assess the “Safe Multidisciplinary App-assisted Remote patient-self-Testing (SMART) model” for warfarin home management in China during the COVID-19 pandemic.

Methods
This is a multi-center randomized controlled trial. We will carry out the study in three county hospitals, three small tertiary hospitals and three large tertiary hospitals with anticoagulation clinics in Hunan province of China. Eligible patients will be randomly assigned to the SMART model group (n = 360) or the control group (usual care clinic group, n = 360; anticoagulation clinic group, n = 120). Patients in the SMART model group do PST at home once every two to 4 weeks. Controls receive usual care in the clinics. All the patients will be followed up through outpatient clinics, phone call or online interviews at the 3rd, 6th, 9th and 12th month. The percentage of time in therapeutic range (TTR), incidence of warfarin associated major bleeding and thromboembolic events and costs will be compared between the SMART model group and control groups.

Discussion
Patients in the SMART model group would show improved TTR, lower incidence of complications and better quality of life compared to the control groups. Our design, implementation and usage of the SMART model will provide experience and evidence in developing a novel model for chronic disease management to solve the problem of healthcare service maldistribution, an issue particularly obvious in developing countries during the COVID-19 pandemic.

Trial registration
ChiCTR, ChiCTR 2000038984. Registered 11 October, 2020.
Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study
Authors: Zarei Ghobadi Mohadeseh , Emamzadeh Rahman , Teymoori-Rad Majid , Mozhgani Sayed-Hamidreza 
Published: August 2021

Abstract
Background
Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymptomatic carrier (AC). There are no obvious explanations about how each of the mentioned diseases develops in the AC carriers. Finding the discriminative molecular factors and pathways may clarify the destiny of the infection.

Methods
To shed light on the involved molecular players and activated pathways in each state, differentially co-expressed modules (DiffCoEx) algorithm was employed to identify the highly correlated genes which were co-expressed differently between normal and ACs, ACs and ATLL, as well as ACs and HAM/TSP samples. Through differential pathway analysis, the dysregulated pathways and the specific disease-genes-pathways were figured out. Moreover, the common genes between the member of DiffCoEx and differentially expressed genes were found and the specific genes in ATLL and HAM/TSP were introduced as possible biomarkers.

Results
The dysregulated genes in the ATLL were mostly enriched in immune and cancer-related pathways while the ones in the HAM/TSP were enriched in immune, inflammation, and neurological pathways. The differential pathway analysis clarified the differences between the gene players in the common activated pathways. Eventually, the final analysis revealed the involvement of specific dysregulated genes including KIRREL2, RAB36, and KANK1 in HAM/TSP as well as LTB4R2, HCN4, FZD9, GRIK5, CREB3L4, TACR2, FRMD1, LHB, FGF3, TEAD3, GRIN2D, GNRH2, PRLH, GPR156, and CRHR2 in ATLL.

Conclusion
The identified potential prognostic biomarkers and therapeutic targets are proposed as the most important platers in developing ATLL or HAM/TSP. Moreover, the proposed signaling network clarifies the differences between the functional players in the activated pathways in ACs, ATLL, and HAM/TSP.
The CXCL13/CXCR5-chemokine axis in neuroinflammation: evidence of CXCR5+CD4 T cell recruitment to CSF
Authors: Harrer Christine , Otto Ferdinand , Pilz Georg , Haschke-Becher Elisabeth , Trinka Eugen , Hitzl Wolfgang , Wipfler Peter , Harrer Andrea 
Published: August 2021

Abstract
Background
C-X-C chemokine ligand 13 (CXCL13) is frequently elevated in cerebrospinal fluid (CSF) in a variety of inflammatory central nervous system (CNS) diseases, has been detected in meningeal B cell aggregates in brain tissues of multiple sclerosis patients, and proposedly recruits B cells into the inflamed CNS. Besides B cells also follicular helper T (Tfh) cells express the cognate receptor C-X-C chemokine receptor type 5 (CXCR5) and follow CXCL13 gradients in lymphoid tissues. These highly specialized B cell helper T cells are indispensable for B cell responses to infection and vaccination and involved in autoimmune diseases. Phenotypically and functionally related circulating CXCR5+CD4 T cells occur in blood. Their co-recruitment to the inflamed CSF is feasible but unresolved.

Methods
We approached this question with a retrospective study including data of all patients between 2017 and 2019 of whom immune phenotyping data of CXCR5 expression and CSF CXCL13 concentrations were available. Discharge diagnoses and CSF laboratory parameters were retrieved from records. Patients were categorized as pyogenic/aseptic meningoencephalitis (ME, n = 29), neuroimmunological diseases (NIMM, n = 22), and non-inflammatory neurological diseases (NIND, n = 6). ANOVA models and Spearman’s Rank-Order correlation were used for group comparisons and associations of CXCL13 levels with immune phenotyping data.

Results
In fact, intrathecal CXCL13 elevations strongly correlated with CXCR5+CD4 T cell frequencies in the total cohort (p < 0.0001, r = 0.59), and ME (p = 0.003, r = 0.54) and NIMM (p = 0.043, r = 0.44) patients. Moreover, the ratio of CSF-to-peripheral blood (CSF/PB) frequencies of CXCR5+CD4 T cells strongly correlated with CXCL13 levels both in the total cohort (p = 0.001, r = 0.45) and ME subgroup (p = 0.005, r = 0.50), indicating selective accumulation. ME, NIMM and NIND groups differed with regard to CSF cell counts, albumin quotient, intrathecal IgG, CXCL13 elevations and CXCR5+CD4 T cells, which were higher in inflammatory subgroups.

Conclusion
The observed link between intrathecal CXCL13 elevations and CXCR5+CD4 T cell frequencies does not prove but suggests recruitment of possible professional B cell helpers to the inflamed CSF. This highlights CSF CXCR5+CD4 T cells a key target and potential missing link to the poorly understood phenomenon of intrathecal B cell and antibody responses with relevance for infection control, chronic inflammation and CNS autoimmunity.
RETRACTED ARTICLE: Forecasting algorithm of tourism service trade based on PSO-optimized hybrid RVM model
Authors: Dong Xiaoying , Chen Xuanjun 
Published: August 2021

AbstractAs a comprehensive form of trade, tourism service trade has had a profound impact on the economies of various countries. This research mainly discusses the tourism service trade forecasting algorithm based on the PSO-optimized hybrid RVM model. This study extracts 8 indicators including gross national product, total fixed asset investment, total import and export, China's import and export tariff rate, the exchange rate of renminbi to the US dollar, and the global economic growth rate. The same as the impact indicators of tourism service trade, but there is a certain degree of redundancy and correlation in these indicators. In order to measure the correlation between the evaluation indicators, the autocorrelation evaluation function in MATLAB is used, and the principal component analysis method is used to extract the principal components that can represent the indicators in a larger percentage. In order to improve the prediction accuracy of the RVM model, based on the adaptive construction model structure and initial model weights, the PSO algorithm is used to optimize the RVM model weights. The optimization process takes the minimum error of the RVM model as the algorithm search target, and each represents the RVM model. The algorithm finds the value and threshold of the optimal RVM model through the particle swarm tracking search algorithm and then uses the original RVM model and the optimized RVM prediction respectively total amount of tourism service trade in City A, and compares the prediction errors of the single RVM method and the PSO-optimized RVM method, and analyzes the degree of model prediction error reduction after the PSO model optimizes the RVM model. According to the forecast result, the relative average error of 2020 is 5.7%, and the forecast result is relatively accurate. This research is helpful to provide scientific reference for my country's tourism service trade.
Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS
Authors: Waters Sarah , Swanson Molly E. V. , Dieriks Birger V. , Zhang Yibin B. , Grimsey Natasha L. , Murray Helen C. , Turner Clinton , Waldvogel Henry J. , Faull Richard L. M. , An Jiyan , Bowser Robert , Curtis Maurice A. , Dragunow Mike , Scotter Emma 
Published: August 2021

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern of lower motor neuron loss along the spinal cord follows the pattern of deposition of phosphorylated TDP-43 aggregates. The blood-spinal cord barrier (BSCB) restricts entry into the spinal cord parenchyma of blood components that can promote motor neuron degeneration, but in ALS there is evidence for barrier breakdown. Here we sought to quantify BSCB breakdown along the spinal cord axis, to determine whether BSCB breakdown displays the same patterning as motor neuron loss and TDP-43 proteinopathy. Cerebrospinal fluid hemoglobin was measured in living ALS patients (n = 87 control, n = 236 ALS) as a potential biomarker of BSCB and blood–brain barrier leakage. Cervical, thoracic, and lumbar post-mortem spinal cord tissue (n = 5 control, n = 13 ALS) were then immunolabelled and semi-automated imaging and analysis performed to quantify hemoglobin leakage, lower motor neuron loss, and phosphorylated TDP-43 inclusion load. Hemoglobin leakage was observed along the whole ALS spinal cord axis and was most severe in the dorsal gray and white matter in the thoracic spinal cord. In contrast, motor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the anterior gray matter of the cervical and lumbar cord. Our data show that leakage of the BSCB occurs during life, but at end-stage disease the regions with most severe BSCB damage are not those where TDP-43 accumulation is most abundant. This suggests BSCB leakage and TDP-43 pathology are independent pathologies in ALS.
Celebrity profiling through linguistic analysis of digital social networks
Authors: Moreno-Sandoval Luis G. , Pomares-Quimbaya Alexandra , Alvarado-Valencia Jorge A. 
Published: August 2021

AbstractDigital social networks have become an essential source of information because celebrities use them to share their opinions, ideas, thoughts, and feelings. This makes digital social networks one of the preferred means for celebrities to promote themselves and attract new followers. This paper proposes a model of feature selection for the classification of celebrities profiles based on their use of a digital social network Twitter. The model includes the analysis of lexical, syntactic, symbolic, participation, and complementary information features of the posts of celebrities to estimate, based on these, their demographic and influence characteristics. The classification with these new features has an F1-score of 0.65 in Fame, 0.88 in Gender, 0.37 in Birth year, and 0.57 in Occupation. With these new features, the average accuracy improve up to 0.14 more. As a result, extracted features from linguistic cues improved the performance of predictive models of Fame and Gender and facilitate explanations of the model results. Particularly, the use of the third person singular was highly predictive in the model of Fame.
Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study
Authors: Ramalingam Suresh S. , Novello Silvia , Guclu Salih Zeki , Bentsion Dmitry , Zvirbule Zanete , Szilasi Maria , Bernabe Reyes , Syrigos Konstantinos , Byers Lauren Averett , Clingan Philip , Bar Jair , Vokes Everett E. , Govindan Ramaswamy , Dunbar Martin , Ansell Peter , He Lei , Huang Xin , Sehgal Vasudha , Glasgow Jaimee , Bach Bruce A. , Mazieres Julien 
Published: August 2021

PURPOSE Squamous non–small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC ( NCT02106546 ). PATIENTS AND METHODS Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52). RESULTS Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; P = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm. CONCLUSION In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.
“My Unwritten Novel”: The Long Poems of Gajanan Madhav Muktibodh between Genre and Form
Authors: Goulding Gregory 
Published: August 2021

AbstractThe long poems of the Hindi poet Gajanan Madhav Muktibodh (1917–64) present a series of fantastic narratives, in which a nameless speaker journeys through a fantastic landscape. These works, often analyzed solely in terms of a supposed mythic, romantic structure, should be considered as a response to formal problems of the novel and the lyric in midcentury Hindi literature. Despite acknowledging these long poems as his most important contribution, literary critics display a marked discomfort with what they see as their excesses. Muktibodh’s writings, however, reflect his substantive consideration of the problems of narrative poetry. In Muktibodh’s most famous work, “Aṁdhere meṁ” (“In the Dark”), the long poem’s distinct formal structure is deployed to produce the disjointed paratactic narratives that typify Muktibodh’s work. Furthermore, this poetic structure is crucially influenced by free verse poetics in Marathi, making clear that any consideration of modern Hindi literature must take into account the complex interrelationships of literary cultures in South Asia. Thus, Muktibodh’s long poem prompts a reconsideration of the role of genre and form in our understanding of South Asian literary cultures and their engagements with the world.