bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiopathic pulmonary fibrosis cluster analysis highlights diagnostic delay and cardiovascular comorbidity association with outcome
Authors: Bordas-Martínez Jaume , Gavaldà Ricard , Shull Jessica G. , Vicens-Zygmunt Vanesa , Planas-Cerezales Lurdes , Bermudo-Peloche Guadalupe , Santos Salud , Salord Neus , Monasterio Carmen , Molina-Molina Maria , Suarez-Cuartin Guillermo 
Published: March 2021

IntroductionIdiopathic pulmonary fibrosis (IPF) prognosis is heterogeneous despite antifibrotic treatment. Cluster analysis has proven to be a useful tool in identifying interstitial lung disease phenotypes, which has yet to be performed in IPF. The aim of this study is to identify phenotypes of IPF with different prognoses and requirements.MethodsObservational retrospective study including 136 IPF patients receiving antifibrotic treatment between 2012 and 2018. Six patients were excluded due to follow-up in other centres. Cluster analysis of 30 variables was performed using approximate singular value-based tensor decomposition method and comparative statistical analysis.ResultsThe cluster analysis identified three different groups of patients according to disease behaviour and clinical features, including mortality, lung transplant and progression-free survival time after 3-year follow-up. Cluster 1 (n=60) was significantly associated (p=0.02) with higher mortality. Diagnostic delay was the most relevant characteristic of this cluster, as 48% of patients had ≥2 years from first respiratory symptoms to antifibrotic treatment initiation. Cluster 2 (n=22) had the longest progression-free survival time and was correlated to subclinical patients evaluated in the context of incidental findings or familial screening. Cluster 3 (n=48) showed the highest percentage of disease progression without cluster 1 mortality, with metabolic syndrome and cardiovascular comorbidities as the main characteristics.ConclusionThis cluster analysis of IPF patients suggests that diagnostic and treatment delay are the most significant factors associated with mortality, while IPF progression was more related to metabolic syndrome and cardiovascular comorbidities.
In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of a possible putative protective effect
Authors: Haddad-Boubaker Sondes , Othman Houcemeddine , Touati Rabeb , Ayouni Kaouther , Lakhal Marwa , Ben Mustapha Imen , Ghedira Kais , Kharrat Maher , Triki Henda 
Published: March 2021

Abstract
Background
Coronavirus Disease 2019 (COVID-19) is a viral pandemic disease that may induce severe pneumonia in humans. In this paper, we investigated the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. Sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins were compared to identify similar patterns. The immunogenic effect of identified segments was, then, assessed using a combination of structural and antigenicity prediction tools.

Results
A total of 14 highly similar segments were identified in the investigated vaccines. Structural and antigenicity prediction analysis showed that, among the identified patterns, three segments in Hepatitis B, Tetanus, and Measles proteins presented antigenic properties that can induce putative protective effect against COVID-19.

Conclusions
Our results suggest a possible protective effect of HBV, Tetanus and Measles vaccines against COVID-19, which may explain the variation of the disease severity among regions.
A new algorithm to train hidden Markov models for biological sequences with partial labels
Authors: Li Jiefu , Lee Jung-Youn , Liao Li 
Published: March 2021

Abstract
Background
Hidden Markov models (HMM) are a powerful tool for analyzing biological sequences in a wide variety of applications, from profiling functional protein families to identifying functional domains. The standard method used for HMM training is either by maximum likelihood using counting when sequences are labelled or by expectation maximization, such as the Baum–Welch algorithm, when sequences are unlabelled. However, increasingly there are situations where sequences are just partially labelled. In this paper, we designed a new training method based on the Baum–Welch algorithm to train HMMs for situations in which only partial labeling is available for certain biological problems.

Results
Compared with a similar method previously reported that is designed for the purpose of active learning in text mining, our method achieves significant improvements in model training, as demonstrated by higher accuracy when the trained models are tested for decoding with both synthetic data and real data.

Conclusions
A novel training method is developed to improve the training of hidden Markov models by utilizing partial labelled data. The method will impact on detecting de novo motifs and signals in biological sequence data. In particular, the method will be deployed in active learning mode to the ongoing research in detecting plasmodesmata targeting signals and assess the performance with validations from wet-lab experiments.
Development of genic KASP SNP markers from RNA-Seq data for map-based cloning and marker-assisted selection in maize
Authors: Chen Zhengjie , Tang Dengguo , Ni Jixing , Li Peng , Wang Le , Zhou Jinhong , Li Chenyang , Lan Hai , Li Lujiang , Liu Jian 
Published: March 2021

Abstract
Background
Maize is one of the most important field crops in the world. Most of the key agronomic traits, including yield traits and plant architecture traits, are quantitative. Fine mapping of genes/ quantitative trait loci (QTL) influencing a key trait is essential for marker-assisted selection (MAS) in maize breeding. However, the SNP markers with high density and high polymorphism are lacking, especially kompetitive allele specific PCR (KASP) SNP markers that can be used for automatic genotyping. To date, a large volume of sequencing data has been produced by the next generation sequencing technology, which provides a good pool of SNP loci for development of SNP markers. In this study, we carried out a multi-step screening method to identify kompetitive allele specific PCR (KASP) SNP markers based on the RNA-Seq data sets of 368 maize inbred lines.

Results
A total of 2,948,985 SNPs were identified in the high-throughput RNA-Seq data sets with the average density of 1.4 SNP/kb. Of these, 71,311 KASP SNP markers (the average density of 34 KASP SNP/Mb) were developed based on the strict criteria: unique genomic region, bi-allelic, polymorphism information content (PIC) value ≥0.4, and conserved primer sequences, and were mapped on 16,161 genes. These 16,161 genes were annotated to 52 gene ontology (GO) terms, including most of primary and secondary metabolic pathways. Subsequently, the 50 KASP SNP markers with the PIC values ranging from 0.14 to 0.5 in 368 RNA-Seq data sets and with polymorphism between the maize inbred lines 1212 and B73 in in silico analysis were selected to experimentally validate the accuracy and polymorphism of SNPs, resulted in 46 SNPs (92.00%) showed polymorphism between the maize inbred lines 1212 and B73. Moreover, these 46 polymorphic SNPs were utilized to genotype the other 20 maize inbred lines, with all 46 SNPs showing polymorphism in the 20 maize inbred lines, and the PIC value of each SNP was 0.11 to 0.50 with an average of 0.35. The results suggested that the KASP SNP markers developed in this study were accurate and polymorphic.

Conclusions
These high-density polymorphic KASP SNP markers will be a valuable resource for map-based cloning of QTL/genes and marker-assisted selection in maize. Furthermore, the method used to develop SNP markers in maize can also be applied in other species.
Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017
Authors: Lei Cheng , Yang Lisong , Lou Cheong Tat , Yang Fan , SiTou Kin Ian , Hu Hao , Io King , Cheok Kun Tat , Pan Baoquan , Ung Carolina Oi Lam 
Published: March 2021

Abstract
Background
Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao.

Methods
A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality.

Results
Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup.

Conclusions
This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.
Optimal empiric treatment for KPC-2-producing Klebsiella pneumoniae infections in critically ill patients with normal or decreased renal function using Monte Carlo simulation
Authors: Wang Guoan , Yu Wei , Cui Yushan , Shi Qingyi , Huang Chen , Xiao Yonghong 
Published: March 2021

Abstract
Background
Limited clinical studies describe the pharmacodynamics of fosfomycin (FOS), tigecycline (TGC) and colistin methanesulfonate (CMS) in combination against KPC-producing Klebsiella pneumoniae (KPC-Kp). Population pharmacokinetic models were used in our study. Monte Carlo simulation was conducted to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR) of each agent alone and in combination against KPC-Kp in patients with normal or decreased renal function.

Results
The simulated regimen of FOS 6 g q8h reached ≥90% PTA against a MIC of 64 mg/L in patients with normal renal function. For patients with renal impairment, FOS 4 g q8h could provide sufficient antimicrobial coverage against a MIC of 128 mg/L. And increasing the daily dose could result to the cut-off value to 256 mg/L in decreased renal function. For TGC, conventional dosing regimens failed to reach 90% PTA against a MIC of 2 mg/L. Higher loading and daily doses (TGC 200/400 mg loading doses followed by 100 mg q12h/200 mg q24h) were needed. For CMS, none achieved 90% PTA against a MIC of 2 mg/L in normal renal function. Against KPC-Kp, the regimens of 200/400 mg loading dose followed by 100 q12h /200 mg q24h achieved > 80% CFRs regardless of renal function, followed by CMS 9 million IU loading dose followed by 4.5/3 million IU q12h in combination with FOS 8 g q8h (CFR 75–91%).

Conclusions
The use of a loading dose and high daily dose of TGC and CMS in combination with FOS can provide sufficient antimicrobial coverage against critically ill patients infected with KPC-Kp.
Health outcomes of smoking during pregnancy and the postpartum period: an umbrella review
Authors: Avşar Tuba Saygın , McLeod Hugh , Jackson Louise 
Published: March 2021

Abstract
Background
Smoking during pregnancy (SDP) and the postpartum period has serious health outcomes for the mother and infant. Although some systematic reviews have shown the impact of maternal SDP on particular conditions, a systematic review examining the overall health outcomes has not been published. Hence, this paper aimed to conduct an umbrella review on this issue.

Methods
A systematic review of systematic reviews (umbrella review) was conducted according to a protocol submitted to PROSPERO (CRD42018086350). CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, CRD Database and HMIC databases were searched to include all studies published in English by 31 December 2017, except those focusing exclusively on low-income countries. Two researchers conducted the study selection and quality assessment independently.

Results
The review included 64 studies analysing the relationship between maternal SDP and 46 health conditions. The highest increase in risks was found for sudden infant death syndrome, asthma, stillbirth, low birth weight and obesity amongst infants. The impact of SDP was associated with the number of cigarettes consumed. According to the causal link analysis, five mother-related and ten infant-related conditions had a causal link with SDP. In addition, some studies reported protective impacts of SDP on pre-eclampsia, hyperemesis gravidarum and skin defects on infants. The review identified important gaps in the literature regarding the dose-response association, exposure window, postnatal smoking.

Conclusions
The review shows that maternal SDP is not only associated with short-term health conditions (e.g. preterm birth, oral clefts) but also some which can have life-long detrimental impacts (e.g. obesity, intellectual impairment).

Implications
This umbrella review provides a comprehensive analysis of the overall health impacts of SDP. The study findings indicate that while estimating health and cost outcomes of SDP, long-term health impacts should be considered as well as short-term effects since studies not including the long-term outcomes would underestimate the magnitude of the issue. Also, interventions for pregnant women who smoke should consider the impact of reducing smoking due to health benefits on mothers and infants, and not solely cessation.
Drug-drug interactions in subjects enrolled in SWOG trials of oral chemotherapy
Authors: Marcath Lauren A. , Finley Colin M. , Wong Siu Fun , Hertz Daniel L. 
Published: March 2021

Abstract
Background
Patients with cancer are at increased risk of drug-drug interactions (DDI), which can increase treatment toxicity or decrease efficacy. It is especially important to thoroughly screen DDI in oncology clinical trial subjects to ensure trial subject safety and data accuracy. This study determined the prevalence of potential DDI involving oral anti-cancer trial agents in subjects enrolled in two SWOG clinical trials.

Methods
Completed SWOG clinical trials of commercially available agents with possible DDI that had complete concomitant medication information available at enrollment were included. Screening for DDI was conducted through three methods: protocol-guided screening, Lexicomp® screening, and pharmacist determination of clinical relevance. Descriptive statistics were calculated.

Results
SWOG trials S0711 (dasatinib, n = 83) and S0528 (everolimus/lapatinib, n = 84) were included. Subjects received an average of 6.6 medications (standard deviation = 4.9, range 0–29) at enrollment. Based on the clinical trial protocols, at enrollment 18.6% (31/167) of subjects had a DDI and 12.0% (20/167) had a DDI that violated a protocol exclusion criterion. According to Lexicomp®, 28.7% of subjects (48/167) had a DDI classified as moderate or worse, whereas pharmacist review indicated that 7.2% of subjects (12/167) had a clinically relevant interaction. The majority of clinically relevant DDI identified were due to the coadministration of acid suppression therapies with dasatinib (83.3%, 10/12).

Conclusions
The high DDI prevalence in subjects enrolled on SWOG clinical trials, including a high prevalence that violate trial exclusion criteria, support the need for improved processes for DDI screening to ensure trial subject safety and trial data accuracy.
Examining the mediating role of resources in the temporal relationship between proactive burnout prevention and burnout
Authors: Otto Madelon C. B. , Van Ruysseveldt Joris , Hoefsmit Nicole , Van Dam Karen 
Published: March 2021

Abstract
Background
Employees who engage in proactive burnout prevention can prevent burnout by changing aspects of the work, home, and personal domain. However, these proactive behaviors may be impeded by high initial levels of burnout. Based on the conservation of resources theory and the dual-pathway proactivity model, resources were expected to play a vital role in the relationship between proactive burnout prevention and burnout through two distinct processes: a resource-generation process in which proactive burnout prevention negatively affects burnout through an increase in resources, and a resource-depletion process in which proactive burnout prevention is hindered because high initial levels of burnout negatively affected resources.

Methods
A two-wave longitudinal panel design was used in which 617 employees, mainly employed in government agencies, healthcare and education, were asked to complete an online survey twice with an interval of 1 month.

Results
Results of structural equation modelling showed clear evidence for the resource-generation process in the work, home, and personal domain, and only limited evidence for the resource-depletion process. Solely in the personal domain a small negative indirect effect of burnout on proactive burnout prevention through personal resources was found.

Conclusions
The findings of this study confirm that employees can proactively prevent burnout by investing in resources, yet proactive actions should be taken before increased burnout-complaints impede employees to do so. This study contributes to scientific knowledge on proactive behaviors and burnout prevention by investigating the mechanism underlying the temporal relationship between proactive burnout prevention and burnout. An important practical implication of this study is that it highlights that more attention should be given to employees’ self-initiated actions to prevent burnout, as proactive burnout prevention can effectively reduce levels of burnout.
A novel integrated global coronal aligner helps prevent post-operative standing coronal imbalance in adult spinal deformity patients fused to pelvis: technical notes and preliminary results
Authors: Zhang Jiandang , Chi Pengfei , Cheng Junyao , Wang Zheng 
Published: March 2021

Abstract
Background
Chieving postoperative coronal balance in adult spinal deformity correction surgeries can be challenging. Even with T square rod technique, there were still some cases with good intraoperative coronal alignment but unsatisfactory post-operative standing coronal imbalance. Thus, the novel techniques to obtain global coronal balance are still in great needs. The purpose of this study was to describe a novel integrated global coronal aligner (IGCA) and evaluate its efficacy on avoidance of post-operative coronal imbalance in adult spinal deformity patients fused to pelvis.

Methods
A detailed description of IGCA technique was presented. 52 ASD patients fused to pelvis were divided into two groups (IGCA group, n = 27; and non-IGCA group, n = 25) according to whether intraoperative IGCA was used or not. Preoperative demographics and postoperative outcomes were compared.

Results
There were no significant differences regarding coronal balance difference (CBD) and imbalance/balance ratio between IGCA and non-IGCA groups preoperatively. After surgery, CBD in IGCA group was significantly improved from 24.7 ± 20.3 mm preoperatively to 12.6 ± 6.4 mm postoperatively (t = 3.185 p = 0.004), and imbalance/balance ratio decreased significantly from 55.6% (15/27) preoperatively to 11.1% (3/27) postoperatively (χ2 = 12.000, p = 0.001), while CBD and imbalance/balance ratio in non-IGCA group were not significantly improved. Compared to non-IGCA group, the amount of correction in CBD was significantly larger in IGCA group (t = 3.274, P = 0.002), and imbalance/balance ratio in IGCA group was significantly lowered (χ2 = 8.606 p = 0.003). Further logistic regression analysis revealed IGCA technique was associated with increased odds ratio for postoperative coronal balance (odds ratio: 7.385; 95% confidence interval 1.760–30.980; P = 0.006).

Conclusions
The novel intraoperative IGCA technique could help improve CBD and reduce imbalance/balance ratio. It could help prevent post-operative coronal imbalance in adult spinal deformity patients fused to pelvis.

Level of evidence
3
Do organic substances act as a degradable binding matrix in calcium oxalate kidney stones?
Authors: Adelman Adi , Shilo Yaniv , Modai Jonathan , Leibovici Dan , Dror Ishai , Berkowitz Brian 
Published: March 2021

Abstract
Background
Calcium oxalate (CaOx) stones are considered to be highly resistant to chemolysis. While significant organic matter has been identified within these stones, which is presumed to bind (inorganic) CaOx particles and aggregates, most chemolysis efforts have focused on methods to attack the CaOx components of a stone. We examine the feasibility of inducing chemolysis of CaOx kidney stones, within hours, by specifically attacking the organic matrix present in these stones.

Methods
In contrast to previous studies, we focused on the possible “brick and mortar” stone configuration. We systematically tested, via in vitro experiments, the ability of an extensive range of 26 potential chemolysis agents to induce relatively fast disintegration (and/or dissolution) of a large set of natural CaOx stone fragments, extracted during endourological procedures, without regard to immediate clinical application. Each stone fragment was monitored for reduction in weight and other changes over 72 h.

Results
We find that agents known to attack organic material have little, if any, effect on stone chemolysis. Similarly, protein and enzymatic agents, and oral additive medical treatments, have little immediate effect.

Conclusions
These findings suggest that the organic and inorganic constituents present in CaOx stones are not structured as “brick and mortar” configurations in terms of inorganic and organic components.