bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection
Authors: Garg Himanshu , Yeh Rose , Watts Douglas M. , Mehmetoglu-Gurbuz Tugba , Resendes Robert , Parsons Bruce , Gonzales Fernando , Joshi Anjali 
Published: January 2021

Abstract
Background
Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown.

Results
Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies.

Conclusions
Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.
Highly abundant core taxa in the blow within and across captive bottlenose dolphins provide evidence for a temporally stable airway microbiota
Authors: Vendl Catharina , Nelson Tiffanie , Ferrari Belinda , Thomas Torsten , Rogers Tracey 
Published: January 2021

AbstractBackgroundThe analysis of blow microbiota has been proposed as a biomarker for respiratory health analysis in cetaceans. Yet, we lack crucial knowledge on the long-term stability of the blow microbiota and its potential changes during disease. Research in humans and mice have provided evidence that respiratory disease is accompanied by a shift in microbial communities of the airways. We investigate here the stability of the community composition of the blow microbiota for 13 captive bottlenose dolphins over eight months including both sick and healthy individuals. We used barcoded tag sequencing of the bacterial 16S rRNA gene. Four of the dolphins experienced distinct medical conditions and received systemic antimicrobial treatment during the study.ResultsWe showed that each dolphin harboured a unique community of zero-radius operational taxonomic units (zOTUs) that was present throughout the entire sampling period (‘intra-core’). Although for most dolphins there was significant variation over time, overall the intra-core accounted for an average of 73% of relative abundance of the blow microbiota. In addition, the dolphins shared between 8 and 66 zOTUs on any of the sampling occasions (‘inter-core’), accounting for a relative abundance between 17 and 41% of any dolphin’s airway microbiota. The majority of the intra-core and all of the inter-core zOTUs in this study are commonly found in captive and free-ranging dolphins and have previously been reported from several different body sites. While we did not find a clear effect of microbial treatment on blow microbiota, age and sex of the dolphins did have such an effect.ConclusionsThe airways of dolphins were colonized by an individual intra-core ‘signature’ that varied in abundance relative to more temporary bacteria. We speculate that the intra-core bacteria interact with the immune response of the respiratory tract and support its function. This study provides the first evidence of individual-specific airway microbiota in cetaceans that is stable over eight months.
Comparative proteomic analysis reveals that the Heterosis of two maize hybrids is related to enhancement of stress response and photosynthesis respectively
Authors: Wang Daoping , Mu Yongying , Hu Xiaojiao , Ma Bo , Wang Zhibo , Zhu Li , Xu Jiang , Huang Changling , Pan Yinghong 
Published: January 2021

AbstractBackgroundHeterosis refers to superior traits exhibiting in a hybrid when compared with both parents. Generally, the hybridization between parents can change the expression pattern of some proteins such as non-additive proteins (NAPs) which might lead to heterosis. ‘Zhongdan808’ (ZD808) and ‘Zhongdan909’ (ZD909) are excellent maize hybrids in China, however, the heterosis mechanism of them are not clear. Proteomics has been wildly used in many filed, and comparative proteomic analysis of hybrid and its parents is helpful for understanding the mechanism of heterosis in the two maize hybrids.ResultsOver 2000 protein groups were quantitatively identified from second seedling leaves of two hybrids and their parents by label-free quantification. Statistical analysis of total identified proteins, differentially accumulated proteins (DAPs) and NAPs of the two hybrids revealed that both of them were more similar to their female parents. In addition, most of DAPs were up-regulated and most of NAPs were high parent abundance or above-high parent abundance in ZD808, while in ZD909, most of DAPs were down-regulated and most of NAPs were low parent abundance or below-low parent abundance. Pathway enrichment analysis showed that more of stress response-related NAPs in ZD808 were high parent abundance or above-high parent abundance, and most of PS related NAPs in ZD909 were high parent abundance or above-high parent abundance. Finally, four stress response-related proteins and eight proteins related to PS were verified by PRM, ten of them had significant differences between hybrid and midparent value.ConclusionsEven though every one of the two hybrids were more similar to its female parent at proteome level, the biological basis of heterosis is different in the two maize hybrids. In comparison with their parents, the excellent agronomic traits of hybrid ZD808 is mainly correlated with the high expression levels of some proteins related to stress responses and metabolic functions, while traits of ZD909 is mainly correlated with high expressed proteins related to photosynthesis. Our proteomics results support previous physiological and morphological research and have provided useful information in understanding the reason of valuable agronomic traits.
GmbZIP1 negatively regulates ABA-induced inhibition of nodulation by targeting GmENOD40–1 in soybean
Authors: Xu Shimin , Song Shanshan , Dong Xiaoxu , Wang Xinyue , Wu Jun , Ren Ziyin , Wu Xuesong , Lu Jingjing , Yuan Huifang , Wu Xinying , Li Xia , Wang Zhijuan 
Published: January 2021

AbstractBackgroundAbscisic acid (ABA) plays an important role in plant growth and adaptation through the ABA signaling pathway. The ABA-responsive element binding (AREB/ABF) family transcriptional factors are central regulators that integrate ABA signaling with various signaling pathways. It has long been known that ABA inhibits rhizobial infection and nodule formation in legumes, but the underlying molecular mechanisms remain elusive.ResultsHere, we show that nodulation is very sensitive to ABA and exogenous ABA dramatically inhibits rhizobial infection and nodule formation in soybean. In addition, we proved that GmbZIP1, an AREB/ABF transcription factor, is a major regulator in both nodulation and plant response to ABA in soybean.GmbZIP1was specifically expressed during nodule formation and development. Overexpression ofGmbZIP1resulted in reduced rhizobial infection and decreased nodule number. Furthermore,GmbZIP1is responsive to ABA, and ectopic overexpression ofGmbZIP1increased sensitivity of Arabidopsis plants to ABA during seed germination and postgerminative growth, and conferred enhanced drought tolerance of plants. Remarkably, we found that GmbZIP1 directly binds to the promoter ofGmENOD40–1, a marker gene for nodule formation, to repress its expression.ConclusionOur results identified GmbZIP1 as a node regulator that integrates ABA signaling with nodulation signaling to negatively regulate nodule formation.
Identification and fine mapping of qGR6.2, a novel locus controlling rice seed germination under salt stress
Authors: Zeng Peng , Zhu Peiwen , Qian Luofeng , Qian Xumei , Mi Yuxin , Lin Zefeng , Dong Shinan , Aronsson Henrik , Zhang Hongsheng , Cheng Jinping 
Published: January 2021

AbstractBackgroundRice growth is frequently affected by salinity. When exposed to high salinity, rice seed germination and seedling establishment are significantly inhibited. With the promotion of direct-seeding in Asia, improving rice seed germination under salt stress is crucial for breeding.ResultsIn this study, anindicalandrace Wujiaozhan (WJZ) was identified with high germinability under salt stress. A BC1F2population derived from the crossing WJZ/Nip (japonica, Nipponbare)//Nip, was used to quantitative trait loci (QTL) mapping for the seed germination rate (GR) and germination index (GI) under H2O and 300 mM NaCl conditions. A total of 13 QTLs were identified, i.e. ten QTLs under H2O conditions and nine QTLs under salt conditions. Six QTLs,qGR6.1,qGR8.1,qGR8.2,qGR10.1,qGR10.2andqGI10.1were simultaneously identified under two conditions. Under salt conditions, three QTLs,qGR6.2,qGR10.1andqGR10.2for GR were identified at different time points during seed germination, which shared the same chromosomal region withqGI6.2,qGI10.1andqGI10.2for GI respectively. TheqGR6.2accounted for more than 20% of phenotypic variation under salt stress, as the major effective QTL. Furthermore,qGR6.2was verified via the BC2F2population and narrowed to a 65.9-kb region with eleven candidate genes predicted. Based on the microarray database, five candidate genes were found with high transcript abundances at the seed germination stage, of whichLOC_Os06g10650andLOC_Os06g10710were differentially expressed after seed imbibition. RT-qPCR results showed the expression ofLOC_Os06g10650was significantly up-regulated in two parents with higher levels in WJZ than Nip during seed germination under salt conditions. Taken together, it suggests thatLOC_Os06g10650, encoding tyrosine phosphatase family protein, might be the causal candidate gene forqGR6.2.ConclusionsIn this study, we identified 13 QTLs from a landrace WJZ that confer seed germination traits under H2O and salt conditions. A major salt-tolerance-specific QTLqGR6.2was fine mapped to a 65.9-kb region. Our results provide information on the genetic basis of improving rice seed germination under salt stress by marker-assisted selection (MAS).
The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-β pathway
Authors: Gao Yuanfeng , Liu Ye , Fu Yuan , Wang Qianhui , Liu Zheng , Hu Roumu , Yang Xinchun , Chen Mulei 
Published: January 2021

Abstract
Introduction
The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression.

Materials and methods
6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis.

Results
PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = − 0.797, p < 0.001).

Conclusion
CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.
Missing not at random in end of life care studies: multiple imputation and sensitivity analysis on data from the ACTION study
Authors:   ACTION consortium, Carreras Giulia , Miccinesi Guido , Wilcock Andrew , Preston Nancy , Nieboer Daan , Deliens Luc , Groenvold Mogensm , Lunder Urska , van der Heide Agnes , Baccini Michela 
Published: January 2021

Abstract
Background
Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer.

Methods
Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations.

Results
Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption.

Conclusions
The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies.
Impact of time-varying cumulative bevacizumab exposures on survival: re-analysis of data from randomized clinical trial in patients with metastatic colo-rectal cancer
Authors: Guilloteau Adrien , Abrahamowicz Michal , Boussari Olayide , Jooste Valérie , Aparicio Thomas , Quantin Catherine , Le Malicot Karine , Binquet Christine 
Published: January 2021

AbstractBackgroundAs cancer treatment, biotherapies can be as effective as chemotherapy while reducing the risk of secondary effects, so that they can be taken over longer periods than conventional chemotherapy. Thus, some trials aimed at assessing the benefit of maintaining biotherapies during chemotherapy-free intervals (CFI). For example, the recent PRODIGE9 trial assessed the effect of maintaining bevacizumab during CFI in metastatic colorectal cancer (mCRC) patients. However, its analysis was hindered by a small difference of exposure to the treatment between the randomized groups and by a large proportion of early drop outs, leading to a potentially unbalanced distribution of confounding factors among the trial completers. To address these limitations, we re-analyzed the PRODIGE9 data to assess the effects of different exposure metrics on all-cause mortality of patients with mCRC using methods originally developed for observational studies.MethodsTo account for the actual patterns of drug use by individual patients and for possible cumulative effects, we used five alternative time-varying exposure metrics: (i) cumulative dose, (ii) quantiles of the cumulative dose, (iii) standardized cumulative dose, (iv) Theoretical Blood Concentration (TBC), and (v) Weighted Cumulative Exposure (WCE). The last two metrics account for the timing of drug use. Treatment effects were estimated using adjusted Hazard Ratio from multivariable Cox proportional hazards models.ResultsAfter excluding 112 patients who died during the induction period, we analyzed data on 382 patients, among whom 320 (83.8%) died. All time-varying exposures improved substantially the model’s fit to data, relative to using only the time-invariant randomization group. All exposures indicated a protective effect for higher cumulative bevacizumab doses. The best-fitting WCE and TBC models accounted for both the cumulative effects and the different impact of doses taken at different times.ConclusionsAll time-varying analyses, regardless of the exposure metric used, consistently suggested protective effects of higher cumulative bevacizumab doses. However, the results may partly reflect the presence of a confusion bias. Complementing the main ITT analysis of maintenance trials with an analysis of potential cumulative effects of treatment actually taken can provide new insights, but the results must be interpreted with caution because they do not benefit from the randomization.Trial registrationclinicaltrials.gov,NCT00952029. Registered 8 August 2009.
Swāsthya, an integrated chronic condition management programme for families of patients with hypertension and diabetes mellitus: a study protocol for a randomised controlled trial
Authors: Saju M D , Varghese Bindiya M , Scaria Lorane , Benny Anuja Maria , Yohannan Shilpa V , Cheguvera Natania , Rajeev S P , Jotheeswaran Amuthavalli Thiyagarajan 
Published: January 2021

Abstract
Background
Kerala is known as the diabetes mellitus (DM) and hypertension (HTN) capital of the world, thus compelling health professionals to model strategies, addressing their social, behavioural, and cognitive risk factors and eliminating various barriers to management. This paper describes the protocol of our study that aims to examine the effectiveness and sustainability of an integrated care model for the management of chronic conditions and their risk factors through a family-based intervention. The proposed care model targets to modify systems and processes that predispose to chronic conditions by enhancing social cohesion and social networks, preventing lifestyle risks, developing iterative cognitive interventions, and engaging the family into customised treatment adherence strategies navigated by community health social workers (CHSWs).

Methods
A cluster randomised controlled trial (RCT) in selected participants will be conducted involving additional assessments prior to the baseline assessment. The assessment will identify and categorise patients into four risk groups, namely behavioural, social, cognitive, and multiple, based on dominant risks identified. Eligible participants will be randomly allocated (at a ratio of 1:1) into the intervention or control arm. The intervention arm will receive social, behavioural, and cognitive or multiple interventions corresponding to the identified risk groups, whereas the control arm will receive general intervention. Both the groups will be followed up at 6 months and 12 months post baseline to measure outcomes. The primary outcome will be the control of HTN and DM, and secondary outcomes include decreased depression and anxiety and improved functioning, social cohesion, and social network linkages. The sustainability and scalability of this intervention will be assessed through cost effectiveness, acceptability, and user friendliness of the integrated approach by performing a qualitative evaluation.

Discussion
This RCT will inform the potential paradigm shift from a medical model of chronic condition management to a multidimensional, multisystem, and multidisciplinary convergence model navigated by CHSWs. Such a model is not currently considered in the management of chronic conditions in Kerala.

Trial registration
Trial has been prospectively registered on Clinical Trial Registry of India- CTRI/2020/12/029474 on 1st December 2020.
Newcomer knowledge, attitudes, and beliefs about human papillomavirus (HPV) vaccination
Authors: Wilson Lindsay A. , Quan Amanda M. L. , Bota A. Brianne , Mithani Salima S. , Paradis Michelle , Jardine Cindy , Hui Charles , Pottie Kevin , Crowcroft Natasha , Wilson Kumanan 
Published: January 2021

AbstractBackgroundHuman Papillomavirus (HPV) is the most common sexually transmitted infection in Canada and around the world. Vaccination is an effective prevention strategy, but uptake is low, especially among newcomers to Canada. We sought to understand newcomers’ knowledge, attitudes, and beliefs (KAB) on HPV and HPV vaccination and their role in HPV vaccine acceptance.MethodsNewcomers were defined as individuals born outside Canada, (i.e., individuals born in a different country, the majority of whom are immigrants or refugees, but also includes students and undocumented migrants). Eligible participants were newcomers, aged 16 or older and who could read or write in English, French or Arabic. Surveys were administered in two community health centres in Ottawa, Canada that primarily engage with newcomer populations. Follow-up interviews were conducted either at the community health centre or over the phone, depending on participants’ preferences.ResultsFifty participants completed the survey, the majority of whom were women (74%) and spoke Arabic as their first language (54%). Seven participants completed supplemental interviews to complement their survey responses. The majority (70%) of participants had not previously heard of HPV. Less than half (46%) knew that the vaccine is effective in preventing certain types of cancer; nearly 40% incorrectly believed the vaccine could cure HPV. Qualitative interviews supported the survey findings.ConclusionsDespite a lack of HPV knowledge due to cultural and language barriers, there is still a strong desire among newcomers to receive the vaccine, especially when accompanied by a physician recommendation. Cultural and language-appropriate resources are needed to help newcomers make informed vaccination decisions and promote HPV vaccine uptake.