bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum proteomics of severe fever with thrombocytopenia syndrome patients
Authors: Lee Sang-Yeop , Yun Sung Ho , Lee Hayoung , Lee Yun Gyeong , Seo Giwan , Kim Nam Hoon , Park Edmond Changkyun , Lee Chang-Seop , Kim Seung Il 
Published: August 2022

AbstractBackgroundDabie bandavirus, also termed as severe fever with thrombocytopenia syndrome virus (SFTSV), was first isolated in China in 2010. At this time, the virus was found to have spread to South Korea, Japan, and other countries. A high case fatality rate is reported for SFTS, ranging from 12–50% within various sources. Several omics for clinical studies among SFTS patients as well as studies of cultured SFTSV have attempted to characterize the relevant molecular biology and epidemiology of the disease. However, a global serum proteomics analysis among SFTS patients has not yet been reported to date.MethodsIn the current study, we evaluated comparative serum proteomics among SFTS patients (eight recovered patients and three deceased patients) with the goal of identifying the protein expression patterns associated with the clinical manifestations of SFTS.ResultsThe proteomic results in the current study showed that the coagulation factor proteins, protein S and protein C, were statistically significantly downregulated among the deceased patients. Downregulation of the complement system as well as prolonged neutrophil activation were also observed. Additionally, the downstream proteins of tumour necrosis factor alpha, neutrophil-activating cytokine, and interleukin-1β, an inflammatory cytokine, were overexpressed.ConclusionsThrombocytopenia and multiple organ failure are the major immediate causes of death among SFTS patients. In this study, serum proteomic changes related to thrombocytopenia, abnormal immune response, and inflammatory activation were documented in SFTS patients. These findings provide useful information for understanding the clinical manifestations of SFTS.
A composite strategy of genome-wide association study and copy number variation analysis for carcass traits in a Duroc pig population
Authors: Ding Rongrong , Zhuang Zhanwei , Qiu Yibin , Wang Xingwang , Wu Jie , Zhou Shenping , Ruan Donglin , Xu Cineng , Hong Linjun , Gu Ting , Zheng Enqin , Cai Gengyuan , Huang Wen , Wu Zhenfang , Yang Jie 
Published: August 2022

Abstract
Background
Carcass traits are important in pig breeding programs for improving pork production. Understanding the genetic variants underlies complex phenotypes can help explain trait variation in pigs. In this study, we integrated a weighted single-step genome-wide association study (wssGWAS) and copy number variation (CNV) analyses to map genetic variations and genes associated with loin muscle area (LMA), loin muscle depth (LMD) and lean meat percentage (LMP) in Duroc pigs.

Results
Firstly, we performed a genome-wide analysis for CNV detection using GeneSeek Porcine SNP50 Bead chip data of 3770 pigs. A total of 11,100 CNVs were detected, which were aggregated by overlapping 695 CNV regions (CNVRs). Next, we investigated CNVs of pigs from the same population by whole-genome resequencing. A genome-wide analysis of 21 pigs revealed 23,856 CNVRs that were further divided into three categories (851 gain, 22,279 loss, and 726 mixed), which covered 190.8 Mb (~ 8.42%) of the pig autosomal genome. Further, the identified CNVRs were used to determine an overall validation rate of 68.5% for the CNV detection accuracy of chip data. CNVR association analyses identified one CNVR associated with LMA, one with LMD and eight with LMP after applying stringent Bonferroni correction. The wssGWAS identified eight, six and five regions explaining more than 1% of the additive genetic variance for LMA, LMD and LMP, respectively. The CNVR analyses and wssGWAS identified five common regions, of which three regions were associated with LMA and two with LMP. Four genes (DOK7, ARAP1, ELMO2 and SLC13A3) were highlighted as promising candidates according to their function.

Conclusions
We determined an overall validation rate for the CNV detection accuracy of low-density chip data and constructed a genomic CNV map for Duroc pigs using resequencing, thereby proving a value genetic variation resource for pig genome research. Furthermore, our study utilized a composite genetic strategy for complex traits in pigs, which will contribute to the study for elucidating the genetic architecture that may be influenced and regulated by multiple forms of variations.
Mendelian randomization of circulating proteome identifies actionable targets in heart failure
Authors: Moncla Louis-Hippolyte Minvielle , Mathieu Samuel , Sylla Mame Sokhna , Bossé Yohan , Thériault Sébastien , Arsenault Benoit J. , Mathieu Patrick 
Published: August 2022

Abstract
Background
Heart failure (HF) is a prevalent cause of mortality and morbidity. The molecular drivers of HF are still largely unknown.

Results
We aimed to identify circulating proteins causally associated with HF by leveraging genome-wide genetic association data for HF including 47,309 cases and 930,014 controls. We performed two-sample Mendelian randomization (MR) with multiple cis instruments as well as network and enrichment analysis using data from blood protein quantitative trait loci (pQTL) (2,965 blood proteins) measured in 3,301 individuals. Nineteen blood proteins were causally associated with HF, were not subject to reverse causality and were enriched in ligand-receptor and glycosylation molecules. Network pathway analysis of the blood proteins showed enrichment in NF-kappa B, TGF beta, lipid in atherosclerosis and fluid shear stress. Cross-phenotype analysis of HF identified genetic overlap with cardiovascular drugs, myocardial infarction, parental longevity and low-density cholesterol. Multi-trait MR identified causal associations between HF-associated blood proteins and cardiovascular outcomes. Multivariable MR showed that association of BAG3, MIF and APOA5 with HF were mediated by the blood pressure and coronary artery disease. According to the directional effect and biological action, 7 blood proteins are targets of existing drugs or are tractable for the development of novel therapeutics. Among the pathways, sialyl Lewis x and the activin type II receptor are potential druggable candidates.

Conclusions
Integrative MR analyses of the blood proteins identified causally-associated proteins with HF and revealed pleiotropy of the blood proteome with cardiovascular risk factors. Some of the proteins or pathway related mechanisms could be targeted as novel treatment approach in HF.
Effects of N and P enrichment on plant photosynthetic traits in alpine steppe of the Qinghai-Tibetan Plateau
Authors: Shen Hao , Dong Shikui , Xiao Jiannan , Zhi Yangliu 
Published: August 2022

Abstract
Background
N (nitrogen) and P (phosphorus) play important roles in plant growth and fitness, and both are the most important limiting factors that affect grassland structure and function. However, we still know little about plant physiological responses to N and P enrichment in alpine grassland of the Qinghai-Tibetan Plateau. In our experiment, five dominant common herbaceous species were selected and their photosynthetic parameters, leaf N content, and aboveground biomass were measured.

Results
We found that species-specific responses to N and P enrichment were obvious at individual level. N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1, simultaneously) significantly promoted net photosynthetic rate of Leymus secalinus. Differential responses also existed in the same functional groups. Responses of forb species to the nutrients addition varied, Aconitum carmichaeli was more sensitive to nutrients addition including N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1). Responses of plant community photosynthetic traits were not so sensitive as those of plant individuals under N and P enrichment.

Conclusions
Our findings highlighted that photosynthetic responses of alpine plants to N and P enrichment were species-specific. Grass species Leymus secalinus had a higher competitive advantage compared with other species under nutrient enrichment. Additionally, soil pH variation and nutrients imbalance induced by N and P enrichment is the main cause that affect photosynthetic traits of plant in alpine steppe of the Qinghai-Tibetan Plateau.
Cortical symptoms described in emergency calls for patients with suspected large vessel occlusion: a descriptive analysis of 157 emergency calls
Authors: Vuorinen Pauli , Kiili Joonas , Alanko Essi , Huhtala Heini , Ollikainen Jyrki , Setälä Piritta , Hoppu Sanna 
Published: August 2022

Abstract
Background
Emergency medical dispatchers typically use the dispatch code for suspected stroke when the caller brings up one or more symptoms from the face-arm-speech triad. Paramedics and emergency department physicians are trained to suspect large vessel occlusion stroke when the stroke patient presents with hemiparesis and cortical symptoms: neglect, aphasia, and conjugate eye deviation (CED). We hypothesized that these symptoms could be evident in the emergency call.
In this study, we aimed to describe common symptoms mentioned in the emergency calls for paramedic-suspected thrombectomy candidates. Secondly, we wanted to explore how the question about CED arises in the Finnish suspected stroke dispatch protocol. Our third aim was to find out if the symptoms brought up in suspected stroke and non-stroke dispatches differed from each other.

Methods
This was a retrospective study with a descriptive analysis of emergency calls for patients with paramedic-suspected large vessel occlusion stroke. We listened to the emergency calls for 157 patients transported to Tampere University Hospital, a Finnish comprehensive stroke centre. Two researchers listened for symptoms brought up in these calls and filled out a pre-planned case report form.

Results
Speech disturbance was the most common symptom brought up in 125 (80%) calls. This was typically described as an inability to speak any words (n = 65, 52% of calls with speech disturbance). Other common symptoms were falling down (n = 63, 40%) and facial asymmetry (n = 41, 26%). Suspicion of stroke was mentioned by 44 (28%) callers. When the caller mentioned unconsciousness the emergency dispatcher tended to use a non-stroke dispatch code. The dispatchers adhered poorly to the protocol and asked about CED in only 57% of suspected stroke dispatches. We found CED in 12 emergency calls and ten of these patients were diagnosed with large vessel occlusion.

Conclusion
In cases where paramedics suspected large vessel occlusion stroke, typical stroke symptoms were described during the emergency call. Speech disturbance was typically described as inability to say anything. It is possible to further develop suspected stroke dispatch protocols to recognize thrombectomy candidates from ischemic cortical signs such as global aphasia and CED.
Feasibility of quantification based on novel evaluation with stool DNA and fecal immunochemical test for colorectal cancer detection
Authors: Xu Hongli , Chen Huixin , Hu Junjie , Xiong Zhiguo , Li Dongqing , Wang Shun , Yu Jing 
Published: August 2022

Abstract
Background
Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China.

Methods
Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring.

Results
The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (< 165) at after surgery.

Discussion
The novel evaluation with sDNA test and FIT has increased sensitivity for screening of CRC and AA. The novel evaluation may have potential importance as an indicator of early CRC. Additionally, the dynamic changes of the comprehensive value after surgery were correlated with CRC treatment.
Systematic transcriptome profiling of pyroptosis related signature for predicting prognosis and immune landscape in lower grade glioma
Authors: Yu Huihan , Gong Meiting , Qi Jian , Zhao Chenggang , Niu Wanxiang , Sun Suling , Li Shuyang , Hong Bo , Qian Junchao , Wang Hongzhi , Chen Xueran , Fang Zhiyou 
Published: August 2022

Abstract
Background
Pyroptosis is a programmed cell death mediated by the gasdermin superfamily, accompanied by inflammatory and immune responses. Exogenously activated pyroptosis is still not well characterized in the tumor microenvironment. Furthermore, whether pyroptosis-related genes (PRGs) in lower-grade glioma (LGG) may be used as a biomarker remains unknown.

Methods
The RNA-Sequencing and clinical data of LGG patients were downloaded from publicly available databases. Bioinformatics approaches were used to analyze the relationship between PRGs and LGG patients’ prognosis, clinicopathological features, and immune status. The NMF algorithm was used to differentiate phenotypes, the LASSO regression model was used to construct prognostic signature, and GSEA was used to analyze biological functions and pathways. The expression of the signature genes was verified using qRT-PCR. In addition, the L1000FWD and CMap tools were utilized to screen potential therapeutic drugs or small molecule compounds and validate their effects in glioma cell lines using CCK-8 and colony formation assays.

Results
Based on PRGs, we defined two phenotypes with different prognoses. Stepwise regression analysis was carried out to identify the 3 signature genes to construct a pyroptosis-related signature. After that, samples from the training and test cohorts were incorporated into the signature and divided by the median RiskScore value (namely, Risk-H and Risk-L). The signature shows excellent predictive LGG prognostic power in the training and validation cohorts. The prognostic signature accurately stratifies patients according to prognostic differences and has predictive value for immune cell infiltration and immune checkpoint expression. Finally, the inhibitory effect of the small molecule inhibitor fedratinib on the viability and proliferation of various glioma cells was verified using cell biology-related experiments.

Conclusion
This study developed and validated a novel pyroptosis-related signature, which may assist instruct clinicians to predict the prognosis and immunological status of LGG patients more precisely. Fedratinib was found to be a small molecule inhibitor that significantly inhibits glioma cell viability and proliferation, which provides a new therapeutic strategy for gliomas.
Normal gastrointestinal mucosa at biopsy and subsequent cancer risk: nationwide population-based, sibling-controlled cohort study
Authors: Sun Jiangwei , Fang Fang , Olén Ola , Song Mingyang , Halfvarson Jonas , Roelstraete Bjorn , Khalili Hamed , Ludvigsson Jonas F. 
Published: August 2022

Abstract
Background
While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored.

Methods
Through Sweden’s 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965–2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group.

Results
During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06–1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05–1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings.

Conclusion
Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small.
Psychometric property and measurement invariance of internet addiction test: the effect of socio-demographic and internet use variables
Authors: Lu Xi , Yeo Kee Jiar , Guo Fang , Zhao Zhenqing , Wu Ou 
Published: August 2022

Abstract
Background
According to the validation literature on items of Young’s Internet Addiction Test (IAT), this study rephrased disputable items to improve the psychometric properties of this Chinese version of IAT and identify the presence of differential item function (DIF) among demographic and Internet use factors; detect the effect of demographic and Internet use factors on IAT after adjusting for DIF.

Methods
An online questionnaire was distributed to college students in Zhe Jiang province in two stage. The 1st phase study collected 384 valid responses to examine the quality of IAT items by using Rasch Model analysis and exploring factor analysis (EFA). The online questionnaire was modified according to the 1st phase study and distributed online for the 2nd phase study which collected a total of 1131 valid responses. The 2nd phase study applied confirmatory factor analysis (CFA) and a multiple indicator multiple causes (MIMIC) model to verify the construct of IAT, potential effect of covariates on IAT latent factors, as well as the effect of differential item functioning (DIF).

Results
Rasch model analysis in the 1st phase study indicated a 5-point rating scale was performed better, no sever misfit was found on item. The overall property of Chinese version IAT with the 5-point scale was good to excellent person and item separation (2.66 and 6.86). A three-factor model was identified by EFA. In the 2nd phase study, IAT 13 were detected with DIF for gender in MIMIC model. After correcting DIF effect, the significant demographic and Internet use factors on IAT were time spent online per day, year 3, year 2, general users.

Conclusion
Item improvement was efficient that the problematic items found in literature was performed good in this study. The overall psychometric property of this Chinese version IAT was good with limited DIF effect in one item. Item improvement on IAT13 was encouraged in the future study to avoid gender bias and benefit for epidemiology on PIU.
Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season
Authors: Ramay Brooke M. , Jara Jorge , Moreno Maria Purificación , Lupo Patrizia , Serrano Carlos , Alvis Juan P. , Arriola C. Sofia , Veguilla Vic , Kaydos-Daniels S. Cornelia 
Published: August 2022

Abstract
Objectives
We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices.

Methods
A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants’ ILI-associated self-medication practices were documented using a questionnaire.

Results
Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased.

Conclusions
During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens.