bluuebunny/crossref_metadata_2025_split huggingface dataset:
An 8-week freeze-dried blueberry supplement impacts immune-related pathways: a randomized, double-blind placebo-controlled trial
Authors: Rousseau Michèle , Horne Justine , Guénard Frédéric , de Toro-Martín Juan , Garneau Véronique , Guay Valérie , Kearney Michèle , Pilon Geneviève , Roy Denis , Couture Patrick , Couillard Charles , Marette André , Vohl Marie-Claude 
Published: May 2021

Abstract
Background
Blueberries contain high levels of polyphenolic compounds with high in vitro antioxidant capacities. Their consumption has been associated with improved vascular and metabolic health.

Purpose
The objective was to examine the effects of blueberry supplement consumption on metabolic syndrome (MetS) parameters and potential underlying mechanisms of action.

Methods
A randomized double-blind placebo-controlled intervention trial was conducted in adults at risk of developing MetS. Participants consumed 50 g daily of either a freeze-dried highbush blueberry powder (BBP) or a placebo powder for 8 weeks (n = 49). MetS phenotypes were assessed at weeks 0, 4 and 8. Fasting blood gene expression profiles and plasma metabolomic profiles were examined at baseline and week 8 to assess metabolic changes occurring in response to the BBP. A per-protocol analysis was used.

Results
A significant treatment effect was observed for plasma triglyceride levels that was no longer significant after further adjustments for age, sex, BMI and baseline values. In addition, the treatment*time interactions were non-significant therefore suggesting that compared with the placebo, BBP had no statistically significant effect on body weight, blood pressure, fasting plasma lipid, insulin and glucose levels, insulin resistance (or sensitivity) or glycated hemoglobin concentrations. There were significant changes in the expression of 49 genes and in the abundance of 35 metabolites following BBP consumption. Differentially regulated genes were clustered in immune-related pathways.

Conclusion
An 8-week BBP intervention did not significantly improve traditional markers of cardiometabolic health in adults at risk of developing MetS. However, changes in gene expression and metabolite abundance suggest that clinically significant cardiometabolic changes could take longer than 8 weeks to present and/or could result from whole blueberry consumption or a higher dosage. BBP may also have an effect on factors such as immunity even within a shorter 8-week timeframe.

Clinical trial registration
clinicaltrials.gov, NCT03266055, 2017
Rapid protein sequence evolution via compensatory frameshift is widespread in RNA virus genomes
Authors: Park Dongbin , Hahn Yoonsoo 
Published: May 2021

Abstract
Background
RNA viruses possess remarkable evolutionary versatility driven by the high mutability of their genomes. Frameshifting nucleotide insertions or deletions (indels), which cause the premature termination of proteins, are frequently observed in the coding sequences of various viral genomes. When a secondary indel occurs near the primary indel site, the open reading frame can be restored to produce functional proteins, a phenomenon known as the compensatory frameshift.

Results
In this study, we systematically analyzed publicly available viral genome sequences and identified compensatory frameshift events in hundreds of viral protein-coding sequences. Compensatory frameshift events resulted in large-scale amino acid differences between the compensatory frameshift form and the wild type even though their nucleotide sequences were almost identical. Phylogenetic analyses revealed that the evolutionary distance between proteins with and without a compensatory frameshift were significantly overestimated because amino acid mismatches caused by compensatory frameshifts were counted as substitutions. Further, this could cause compensatory frameshift forms to branch in different locations in the protein and nucleotide trees, which may obscure the correct interpretation of phylogenetic relationships between variant viruses.

Conclusions
Our results imply that the compensatory frameshift is one of the mechanisms driving the rapid protein evolution of RNA viruses and potentially assisting their host-range expansion and adaptation.
Predation has small, short-term, and in certain conditions random effects on the evolution of aging
Authors: Lenart Peter , Bienertová-Vašků Julie , Berec Luděk 
Published: May 2021

Abstract
Background
The pace of aging varies considerably in nature. The best-known explanation of the evolution of specific rates of aging is the Williams’ hypothesis suggesting that the aging rate should correlate with the level of extrinsic mortality. However, the current evidence is inconclusive with various examples where the Williams' hypothesis seems to be correct and where it doesn’t. Here we explore the relationship between extrinsic mortality and aging rate by developing a simulation model of the evolution of aging rate in prey subject to predation.

Results
Our results suggest that more intense predation leads to the evolution of faster pace of aging in prey. However, this effect slowly vanishes when the predator diet breadth is allowed to evolve, too. Furthermore, in our model, the evolution of a specific aging rate is driven mainly by a single parameter, the strength of a trade-off between aging and fecundity. Indeed, in the absence of this trade-off the evolutionary impacts of predation on the prey aging rate appear random.

Conclusions
We show that the William’s hypothesis appears valid when there is a trade-off between aging and fecundity and predators and prey do not coevolve. However, we also show that when the prey and predators coevolve or if there is no trade-off between aging and fecundity the William`s hypothesis is no longer applicable.
Tissue-specific transcriptome analyses reveal candidate genes for stilbene, flavonoid and anthraquinone biosynthesis in the medicinal plant Polygonum cuspidatum
Authors: Wang Xiaowei , Hu Hongyan , Wu Zhijun , Fan Haili , Wang Guowei , Chai Tuanyao , Wang Hong 
Published: May 2021

Abstract
Background
Polygonum cuspidatum Sieb. et Zucc. is a well-known medicinal plant whose pharmacological effects derive mainly from its stilbenes, anthraquinones, and flavonoids. These compounds accumulate differentially in the root, stem, and leaf; however, the molecular basis of such tissue-specific accumulation remains poorly understood. Because tissue-specific accumulation of compounds is usually associated with tissue-specific expression of the related biosynthetic enzyme genes and regulators, we aimed to clarify and compare the transcripts expressed in different tissues of P. cuspidatum in this study.

Results
High-throughput RNA sequencing was performed using three different tissues (the leaf, stem, and root) of P. cuspidatum. In total, 80,981 unigenes were obtained, of which 40,729 were annotated, and 21,235 differentially expressed genes were identified. Fifty-four candidate synthetase genes and 12 transcription factors associated with stilbene, flavonoid, and anthraquinone biosynthetic pathways were identified, and their expression levels in the three different tissues were analyzed. Phylogenetic analysis of polyketide synthase gene families revealed two novel CHS genes in P. cuspidatum. Most phenylpropanoid pathway genes were predominantly expressed in the root and stem, while methylerythritol 4-phosphate and isochorismate pathways for anthraquinone biosynthesis were dominant in the leaf. The expression patterns of synthase genes were almost in accordance with metabolite profiling in different tissues of P. cuspidatum as measured by high-performance liquid chromatography or ultraviolet spectrophotometry. All predicted transcription factors associated with regulation of the phenylpropanoid pathway were expressed at lower levels in the stem than in the leaf and root, but no consistent trend in their expression was observed between the leaf and the root.

Conclusions
The molecular knowledge of key genes involved in the biosynthesis of P. cuspidatum stilbenes, flavonoids, and anthraquinones is poor. This study offers some novel insights into the biosynthetic regulation of bioactive compounds in different P. cuspidatum tissues and provides valuable resources for the potential metabolic engineering of this important medicinal plant.
Single nucleotide polymorphisms reveal genetic diversity in New Mexican chile peppers (Capsicum spp.)
Authors: Lozada Dennis N. , Bhatta Madhav , Coon Danise , Bosland Paul W. 
Published: May 2021

Abstract
Background
Chile peppers (Capsicum spp.) are among the most important horticultural crops in the world due to their number of uses. They are considered a major cultural and economic crop in the state of New Mexico in the United States. Evaluating genetic diversity in current New Mexican germplasm would facilitate genetic improvement for different traits. This study assessed genetic diversity, population structure, and linkage disequilibrium (LD) among 165 chile pepper genotypes using single nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing (GBS).

Results
A GBS approach identified 66,750 high-quality SNP markers with known map positions distributed across the 12 chromosomes of Capsicum. Principal components analysis revealed four distinct clusters based on species. Neighbor-joining phylogenetic analysis among New Mexico State University (NMSU) chile pepper cultivars showed two main clusters, where the C. annuum genotypes grouped together based on fruit or pod type. A Bayesian clustering approach for the Capsicum population inferred K = 2 as the optimal number of clusters, where the C. chinense and C. frutescens grouped in a single cluster. Analysis of molecular variance revealed majority of variation to be between the Capsicum species (76.08 %). Extensive LD decay (~ 5.59 Mb) across the whole Capsicum population was observed, demonstrating that a lower number of markers would be required for implementing genome wide association studies for different traits in New Mexican type chile peppers. Tajima’s D values demonstrated positive selection, population bottleneck, and balancing selection for the New Mexico Capsicum population. Genetic diversity for the New Mexican chile peppers was relatively low, indicating the need to introduce new alleles in the breeding program to broaden the genetic base of current germplasm.

Conclusions
Genetic diversity among New Mexican chile peppers was evaluated using GBS-derived SNP markers and genetic relatedness on the species level was observed. Introducing novel alleles from other breeding programs or from wild species could help increase diversity in current germplasm. We present valuable information for future association mapping and genomic selection for different traits for New Mexican chile peppers for genetic improvement through marker-assisted breeding.
Inhibitory control training reveals a common neurofunctional basis for generic executive functions and language switching in bilinguals
Authors: Wu Yan Jing , Chen Mo , Thierry Guillaume , Fu Yongben , Wu Junjie , Guo Taomei 
Published: May 2021

Abstract
Background
The neural networks underpinning language control and domain-general executive functions overlap in bilinguals, but existing evidence is mainly correlative. Here, we present the first neurofunctional evidence for a transfer effect between (domain-general) inhibitory control and language control through training. We trained Chinese–English bilinguals for 8 days using a Simon task taxing the inhibitory control system, whilst an active control group was trained with a color judgment task that does not tax the inhibitory control system. All participants performed a language-switching task before and after training. It has been suggested that the activity of the left DLPFC was associated with domain-general top-down cognitive control (Macdonald et al. Science 288: 1835–1838, 2000) and bilingual language control (Wang et al. Neuroimage 35: 862–870, 2007). In addition, the dACC was closely related to the conflict detection (Abutalebi et al. Cereb Cortex 18:1496–1505, 2008). Last, the activity of the left caudate has been linked with lexical selection (Abutalebi et al. Cereb Cortex 18:1496–1505, 2008), especially the selection of the weak language (Abutalebi et al. Cortex 49: 905–911, 2013). Therefore, we focused on these three regions of interest (ROIs) where neural changes associated with transfer were expected to occur.

Results
The results showed a negative correlation between changes in activation levels in the left dorsolateral prefrontal cortex (DLPFC) and changes in the switch cost magnitude in the language-switching task in the training group but not in the control group, suggesting that the DLPFC plays a critical role in the transfer effect from domain-general executive functions to language control. However, there was no measurable effect in the anterior cingulate cortex or left caudate nucleus, suggesting that the inhibitory control training increased the neural efficiency for language production in bilinguals in terms of attention shifting and conflict resolution, but the training did not affect conflict detection and lexical selection.

Conclusion
These findings showed how cognitive training evidence can help establish a causational link between the neural basis of domain-general executive functions and language control in bilinguals.
A pilot study comparing three bend angles for lighted stylet intubation
Authors: Won Dongwook , Lee Jung-Man , Lee Jiwon , Hwang Jin-Young , Kim Tae Kyong , Chang Jee-Eun , Kim Hyerim , Ma Seoyoung , Min Seong-Won 
Published: May 2021

AbstractBackgroundFor successful lighted stylet intubation, bending the lighted stylet with an appropriate angle is a prerequisite. The purpose of this study was to compare three different bend angles of 70, 80, and 90 degrees for lighted stylet intubation.MethodsThe patient trachea was intubated with a lighted stylet bent at 70, 80, or 90 degrees according to the randomly allocated groups (group I, II, and III, respectively). A lighted stylet combined with a tracheal tube was prepared with a bend angle of 70, 80, or 90 degrees according to the assigned group. We checked the success rate at the first attempt and overall success rate for the two attempts. Additionally, we measured search time, which was time from insertion of the bent union into the patient mouth to the start of advancing the tracheal tube while separating it from the lighted stylet, and evaluated postoperative sore throat (POST) at 2, 4, and 24 h after the recovery from anesthesia.ResultsThere was no statistically significant difference between group I, II, and III for success rate at first attempt (73.9 %, 88.2 %, and 94.7 %, respectively,p = 0.178), even though there was a trend of increasing success rate with increasing bend angles. For overall success rate, there was similar result to that in the first attempt between the groups I, II, and III (82.6 %, 94.1 %, and 100 %, respectively,p = 0.141). However, search time took significantly longer in group I than groups II and III (p < 0.001). When group II and III were compared for POST with numeric rating scale (0–10), it was significantly lower in group II than III at 2, 4 h after the recovery (0.5 vs. 2.3,p = 0.016, and 0.4 vs. 1.8,p = 0.011, respectively).ConclusionsThe bend angle of the lighted stylet affected the time required for tracheal intubation and POST in our study. 80 and 90 degrees as a bend angle seem to be acceptable for clinicians in regard to success rate of lighted stylet intubation. Considering the success rate of lighted stylet intubation and POST, the bend angle of 80 degrees might be better than 70 and 90 degrees.Trial registrationClinicalTrials.gov IdentifierNCT03693235, registered on 30 September 2018.
Previously undiagnosed scoliosis presenting as pleuritic chest pain in the emergency department – a case series and a validating retrospective audit
Authors: Xantus Gabor , Burke Derek , Kanizsai Peter 
Published: May 2021

Abstract
Background
Chest pain is one of the commonest presenting complaints in urgent/emergency care, with a lifelong prevalence of up to 25% in the adult population. Pleuritic chest pain is a subset of high investigation burden because of a diverse range of possible causes varying from simple musculoskeletal conditions to pulmonary embolism.

Case series
Among otherwise fit and healthy adult patients presenting in our emergency department with sudden onset of unilateral pleuritic chest pain, within 1 month we identified a cohort of five patients with pin-point tenderness in one specific costo-sternal joint often with referred pain to the back. All cases had apparent and, previously undiagnosed mild/moderate scoliosis.

Methods
To confirm and validate the observed association between scoliosis and pleuritic chest pain, a retrospective audit was designed and performed using the hospital’s electronic medical record system to reassess all consecutive adult chest pain patients.

Results
The Odds Ratio for having chest pain with scoliosis was 30.8 [95%CI 1.71–553.37], twenty times higher than suggested by prevalence data.

Discussion
In scoliosis the pathologic lateral curvature of the spine adversely affects the functional anatomy of both the spine and ribcage. In our hypothesis the chest wall asymmetry enables minor slip/subluxation of a rib either in the costo-sternal and/or costovertebral junction exerting direct pressure on the intercostal nerve causing pleuritic pain.

Conclusion
Thorough physical examination of the anterior and posterior chest wall is key to identify underlying scoliosis in otherwise fit patients presenting with sudden onset of pleuritic pain. Incorporating assessment for scoliosis in the low-risk chest pain protocols/tools may help reducing the length of stay in the emergency department and, facilitate speedy but safe discharge with increased patient satisfaction.
FOLFIRINOX-R study design: a phase I/II trial of FOLFIRINOX plus regorafenib as first line therapy in patients with unresectable RAS-mutated metastatic colorectal cancer
Authors: Adenis Antoine , Mazard Thibault , Fraisse Julien , Chalbos Patrick , Pastor Brice , Evesque Ludovic , Ghiringhelli Francois , Mollevi Caroline , Delaine Stéphanie , Ychou Marc 
Published: May 2021

Abstract
Background
The chemotherapy triplet FOLFOXIRI combined to the anti-VEGF antibody bevacizumab is an option in selected patients with metastatic colorectal cancer. In this setting, RAS-mutated metastatic colorectal cancer do not benefit the same from treatment than RAS-wildtype metastatic colorectal cancer do. Together with its antiangiogenic properties, the tyrosine-kinase inhibitor regorafenib has also anti-proliferative activities whatever the RAS status is. The present trial aims at studying the safety and the efficacy of regorafenib in combination with FOLFIRINOX – a chemotherapy triplet using a different dosing schedule than FOLFOXIRI - in patients with RAS-mutated metastatic colorectal cancer.

Methods
FOLFIRINOX-R is a prospective, multicentric, non-randomised, dose-finding phase 1–2 trial. The primary endpoints are the determination of the maximum tolerated dose, the recommended phase 2 dose, and the proportion of patients achieving disease control at 48-weeks. Phase 1 follows a 3 + 3 design (12 to 24 patients to be included). Sixty nine patients will be necessary in phase 2, including 5% non-evaluable ones, with the following assumptions, one-stage Fleming design, α = 5%, β = 20%, p0 = 35% and p1 = 50%. Key eligibility criteria include Eastern Cooperative Oncology Group Performance Status of ≤1 and RAS-mutated metastatic colorectal cancer not amenable to surgery with curative intent and not previously treated for metastatic disease. FOLFIRINOX (oxaliplatin 85 mg/m2, folinic acid 400 mg/m2, irinotecan 150–180 mg/m2, 5-fluorouracil: 400 mg/m2 then 2400 mg/m2 over 46 h) is administered every 14 days. Regorafenib (80 to 160 mg, as per dose-level) is administered orally, once daily on days 4 to 10 of each cycle.

Discussion
FOLFIRINOX-R is the first phase I/II study to evaluate the safety and efficacy of regorafenib in combination with FOLFIRINOX as frontline therapy for patients with RAS-mutated metastatic colorectal cancer.

Trial registration
EudraCT: 2018-003541-42; ClinicalTrials.gov: NCT03828799.
Association of self-perceived income sufficiency with cognitive impairment among older adults: a population-based study in India
Authors: Muhammad T. , Srivastava Shobhit , Sekher T. V. 
Published: May 2021

Abstract
Background
Greater cognitive performance has been shown to be associated with better mental and physical health and lower mortality. The present study contributes to the existing literature on the linkages of self-perceived income sufficiency and cognitive impairment. Study also provides additional insights on other socioeconomic and health-related variables that are associated with cognitive impairment in older ages.

Methods
Data for this study is derived from the 'Building Knowledge Base on Population Ageing in India'. The final sample size for the analysis after removing missing cases was 9176 older adults. Descriptive along with bivariate analyses were presented to show the plausible associations of cognitive impairment with potential risk factors using the chi-square test. Also, binary logistic regression analysis was performed to provide the relationship between cognitive impairment and risk factors. The software used was STATA 14.

Results
About 43% of older adults reported that they had no source of income and 7.2% had income but not sufficient to fulfil their basic needs. Older adults with income but partially sufficient to fulfil their basic needs had 39% significantly higher likelihood to suffer from cognitive impairment than older adults who had sufficient income [OR: 1.39; OR: 1.21–1.59]. Likelihood of cognitive impairment was low among older adults with asset ownership than older adults with no asset ownership [OR: 0.83; CI: 0.72–0.95]. Again, older adults who work by compulsion (73.3%) or felt mental or physical stress due to work (57.6%) had highest percentage of cognitive impairment. Moreover, older adults with poor self-rated health, low instrumental activities of daily living, low activities of daily living, low subjective well-being and low psychological health were at increased risk for cognitive impairment.

Conclusion
The study highlights the pressing need for care and support and especially financial incentives in the old age to preserve cognitive health. Further, while planning geriatric health care for older adults in India, priority must be given to financially backward, with no asset ownership, with poor health status, older-older, widowed, and illiterate older individuals, as they are more vulnerable to cognitive impairment.