bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice
Authors: Menees Kelly B. , Earls Rachael H. , Chung Jaegwon , Jernigan Janna , Filipov Nikolay M. , Carpenter Jessica M. , Lee Jae-Kyung 
Published: January 2021

Abstract
Background
Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood.

Results
Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis.

Conclusions
This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.
Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet
Authors: Daniel Sarah , Phillippi Danielle , Schneider Leah J. , Nguyen Kayla N. , Mirpuri Julie , Lund Amie K. 
Published: January 2021

Abstract
Background
Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study.

Results
Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment.

Conclusions
Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.
A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia
Authors: Howard Dena R. , Hockaday Anna , Brown Julia M. , Gregory Walter M. , Todd Susan , Munir Tahla , Oughton Jamie B. , Dimbleby Claire , Hillmen Peter 
Published: January 2021

Abstract
Background
The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success.

Methods
FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial.

Results
The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres.

Conclusions
FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community.

Trial registration
ISRCTN Registry ISRCTN01844152. Registered on August 08, 2014
Recruitment and retention of participant and study partner dyads in two multinational Alzheimer’s disease registration trials
Authors: Bernstein Olivia M. , Grill Joshua D. , Gillen Daniel L. 
Published: January 2021

Abstract
Background
Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk.

Methods
We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia.
Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout.

Results
Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model.

Conclusions
After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.
A methodological review protocol of the use of Bayesian factor analysis in primary care research
Authors: Zhang Hao , Schuster Tibor 
Published: January 2021

Abstract
Background
The development of questionnaires for primary care practice and research is of increasing interest in the literature. In settings where valuable prior knowledge or preliminary data is available, Bayesian factor analysis can be used to incorporate such information when conducting questionnaire construct validation. This protocol outlines a methodological review that will summarize evidence on the current use of Bayesian factor analysis in the primary care literature.

Methods
A comprehensive search strategy has been developed and will be used to identify relevant literature (research studies in primary care) indexed in MEDLINE, Scopus, EMBASE, CINAHL, and Cochrane Library. The search strategy includes terms and synonyms for Bayesian factor analysis and primary care. The reference lists of relevant articles being identified will be screened to find further relevant studies. At least two reviewers will independently extract data and resolve discrepancies through consensus. Descriptive analyses will summarize the use and reporting of Bayesian factor analysis approaches for validating questionnaires applicable to primary care.

Discussion
This methodological review will provide a comprehensive overview of the current use and reporting of Bayesian factor analysis in primary care and will provide recommendations for its proper future use.

Systematic review registration
PROSPERO CRD42018114978
Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis
Authors: Cheng Yangfan , Chen Yongping , Shang Huifang 
Published: January 2021

AbstractAccumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21],p= 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73],p< 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05],p< 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67],p< 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90],p= 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88],p= 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.
An exploration of perceptions and preferences for healthy eating in Dutch consumers: a qualitative pilot study
Authors: Coumans Juul M. J. , Bolman Catherine A. W. , Lechner Lilian , Oenema Anke 
Published: January 2021

Abstract
Background
Unhealthy dietary patterns are highly prevalent in Western countries, and they have been associated with depression, hypertension, heart disease, cancer, type 2 diabetes, and obesity. Many dietary interventions have been developed to promote healthier dietary behavior, yet most do not achieve the intended dietary change. This study aims to provide a better understanding of what Dutch consumers perceive as a healthy diet, how this relates to the current Dutch nutrition guidelines, and their preferences for how to eat more healthily. This is an essential consideration for the development of tailored interventions aimed to help people adopt changes in their dietary behavior.

Methods
Seventy-eight participants filled in an online questionnaire containing both open-ended and closed-ended questions. The qualitative data was analyzed using content analysis resulting in a classification scheme. Two students then identified to which category each part of a participant’s answer belonged.

Results
For both the perception of a healthy diet and how to eat healthily, four major categories and a residual category were identified: dietary patterns, food processing, food products, content/nutrients, and non-food. These major categories consisted of several categories. The results showed that how people perceived a healthy diet was mostly represented at the level of food product (vegetables and fruit) and the content/nutrient level (carbohydrates), whereas how they would like to eat healthily was mostly represented at the level of food processing (preparation), food product (vegetables), and dietary patterns (amount).

Conclusions
Our findings are mostly in line with how the Dutch dietary guidelines are communicated (“product level”). However, consumers primarily mention single aspects instead of naming the guidelines as a whole. Health policymakers can use this insight in future communications regarding the guidelines to the general public. A challenge for future (eHealth) diet interventions is how to implement and tailor dietary information that optimally connects with the perceptions of the target population.
Cotton germplasm improvement and progress in Pakistan
Authors: RAZZAQ Abdul , ZAFAR Muhammad Mubashar , ALI Arfan , HAFEEZ Abdul , BATOOL Wajeeha , SHI Yuzhen , GONG Wankui , YUAN Youlu 
Published: January 2021

AbstractCotton (Gossypium spp.) contributes significantly to the economy of cotton-producing countries. Pakistan is the fourth-largest producer of cotton after China, the USA and India. The average yield of cotton is about 570.99 kg.hm− 2 in Pakistan. Climate change and different biotic stresses are causing reduction in cotton production. Transgenic approaches have unique advantage to tackle all these problems. However, how to confer permanent resistance in cotton against insects through genetic modification, is still a big challenge to address. Development of transgenic cotton has been proven to be effective. But its effectiveness depends upon several factors, including heterogeneity, seed purity, diffusion of varieties, backcrossing and ethical concerns. Cotton biotechnology was initiated in Pakistan in 1992–1993 with a focus on acquiring cotton leaf curl virus (CLCuV)-resistant insect-resistant, and improving fiber quality. This review summarizes the use of molecular markers, QTLs, GWAS, and gene cloning for cotton germplasm improvement, particularly in Pakistan.
The porcine respiratory microbiome: recent insights and future challenges
Authors: Pirolo Mattia , Espinosa-Gongora Carmen , Bogaert Debby , Guardabassi Luca 
Published: January 2021

AbstractUnderstanding the structure of the respiratory microbiome and its complex interactions with opportunistic pathogenic bacteria has become a topic of great scientific and economic interest in livestock production, given the severe consequences of respiratory disease on animal health and welfare. The present review focuses on the microbial structures of the porcine upper and lower airways, and the factors that influence microbiome development and onset of respiratory disease. Following a literature search on PubMed and Scopus, 21 articles were selected based on defined exclusion criteria (20 studies performed by 16S rRNA gene sequencing and one by shotgun metagenomics). Analysis of the selected literature indicated that the microbial structure of the upper respiratory tract undergoes a remarkable evolution after birth and tends to stabilise around weaning. Antimicrobial treatment, gaseous ammonia concentration, diet and floor type are amongst the recognized environmental factors influencing microbiome structure. The predominant phyla of the upper respiratory tract are Proteobacteria and Firmicutes with significant differences at the genus level between the nasal and the oropharyngeal cavity. Only five studies investigated the lower respiratory tract and their results diverged in relation to the relative abundance of these two phyla and even more in the composition of the lung microbiome at the genus level, likely because of methodological differences. Reduced diversity and imbalanced microbial composition are associated with an increased risk of respiratory disease. However, most studies presented methodological pitfalls concerning specimen collection, sequencing target and depth, and lack of quality control. Standardization of sampling and sequencing procedures would contribute to a better understanding of the structure of the microbiota inhabiting the lower respiratory tract and its relationship with pig health and disease.
Can dynamic magnetic resonance imaging replace static magnetic resonance sequences in evaluation of temporomandibular joint dysfunction?
Authors: Kamel Zeinab Sobhy Ahmed Sayed Ahmed , El-Shafey Mohammad Hassan Rashad , Hassanien Omar Ahmed , Nagy Hanan Ahmad 
Published: January 2021

Abstract
Background
Static MRI was used as an effective tool for diagnosis of temporomandibular joint dysfunction instead of invasive techniques such as arthroscopy and arthrography. The purpose of this study was to detect whether dynamic MRI can be used instead of static MRI in diagnosis of TMJ dysfunction or not.

Results
According to disc displacement, anterior disc displacement was detected in 29 joints (36.25%) by both static and dynamic MRIs, and medial and lateral disc displacements were detected only by static MRI. Regarding disc mobility, dynamic MRI detects stuck disc in 4 joints versus 2 joints detected by static MRI (p value 0.008). Condylar translation was abnormal in 18 joints (22.5%) by static MRI and in 26 joints (32.5%) by dynamic MRI (p value < 0.001). The detection rate of articular disc for dynamic MRI was 87.5% versus static MRI 92.5% (p value 0.038), and the detection rate of condylar head for dynamic MRI was 97.5% versus static MRI 100% (p value 0.012).

Conclusion
Dynamic MRI cannot replace static MRI in evaluation of TMJ dysfunction; both of them support each other for accurate diagnosis and better image quality.
Identification and management of cardiometabolic risk in subjects with schizophrenia spectrum disorders: A Delphi expert consensus study
Authors: Galderisi Silvana , De Hert Marc , Del Prato Stefano , Fagiolini Andrea , Gorwood Philip , Leucht Stefan , Maggioni Aldo Pietro , Mucci Armida , Arango Celso 
Published: January 2021

Abstract

Background
Patients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method.

Methods
The steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists.

Results
Consensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners.

Conclusions
This study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.