Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics Associated With Recruitment and Re-contact in Mayo Clinic Biobank

Objective: To better understand the characteristics associated with a participant's willingness to consent to the Mayo Clinic Biobank (MCB) and examine factors associated with willingness to participate in follow-up studies embedded within MCB that require re-contact and participant approval. Participants and Methods: Consent rates were compared across patient demographics to the MCB. Rates of participation to follow-up studies were also compared across demographics and request types. Results: Among 272,102 Mayo Clinic patients invited to the MCB, 48,314 (19%) consented across the three recruitment sites within 90 days of initial invitation. A significant age by gender interaction was identified, showing young males consent at a lower rate than young females and older males consent at a higher rate than older females. Over the recruitment time frame of 2009–2015, there was a significant decrease in consent rates (decline of 2.5%/year). Of the 57,041 consented MCB participants, 33,487 participants (59%) have been invited to participate in follow-up studies via re-contact. Follow-up studies of the MCB may require participants to provide additional samples, complete questionnaires, and/or release their identity to a research team. MCB participants have been invited to enroll in a median of two studies (IQR: 1–3). Seventy-one percent of participants consented to at least one follow-up study, with individual follow-up study consent rates ranging from 14 to 87% depending on study type, with a median consent rate of 61% (IQR: 47–70%). Studies requesting return of a questionnaire had the highest participation rates. White participants, older participants, and participants with some college or a degree were significantly more likely to participate to follow-up studies, while there was no association with gender. Conclusion: Consent rates among younger and non-white patients were lower than in older, white patients. However, we also found that participation rates among those already enrolled in the biobank were much higher than those seen in new recruitment efforts, external to an existing biobank. We thus demonstrate an important way that biobanks can advance precision medicine goals: through provision of populations from which studies can draw participants for future studies.
The Association Between Cancer and Dementia: A National Cohort Study in Sweden

Background: Previous studies have found that the incidence of dementia is lower in patients with cancer. However, the impact of survival bias, as well as the confounding by medical treatment, have not been fully addressed. We aimed to explore the subsequent risk of dementia in different follow-up intervals among patients with cancer, as well as the risk before the diagnosis of cancer. Methods: By using the Swedish Cancer Register and the Swedish Hospital Discharge Register, we systematically examined the risk of dementia among patients diagnosed with 35 different types of cancer. Standardized incidence ratios (SIRs) were used to calculate the relative risk. Results: The subsequent risk of dementia in patients with cancer decreased by 21% compared to matched cancer-free controls (SIR = 0.79, 95% CI 0.78–0.80). For specific cancer sites, 21 of them had a significantly lower risk of subsequent dementia. The decreased risk of dementia was also significant before the diagnosis of cancer. However, the risk was higher among patients with cancer who survived for more than 10 years' post-diagnosis (SIR = 1.37, 95% CI 1.32–1.41). Conclusions: In this population-based study, we found that the risk of dementia was lower among patients with cancer, and the risk was also lower before the diagnosis of cancer. This suggests that lower dementia risk is not simply due to bias. However, the underlying mechanisms need to be explored further.
Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In this study, plasma from patients diagnosed with metastatic cutaneous malignant melanoma (CMM) was obtained before (PRE) and during treatment (TRM) with inhibitors of mitogen-activated protein kinase pathway (MAPKIs). Immuno-oncology related protein profile and kynurenine metabolites were analyzed by proximity extension assay (PEA) and LC/MS-MS, respectively. Correlation network analyses of the data derived from PEA and LC/MS-MS identified a set of proteins that modulate the differentiation of Th1 cells, which is linked to 3-hydroxykynurenine levels. Moreover, MAPKIs treatments are associated with alteration of 3-hydroxykynurenine and 3hydroxyanthranilic acid (3HAA) concentrations and led to higher “CXCL11,” and “KLRD1” expression that are involved in T and NK cells activation. These findings imply that the kynurenine pathway is pathologically relevant in patients with CMM.
Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer

The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03–2.43, p = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC.
Graphene-Based Steganographic Aptasensor for Information Computing and Monitoring Toxins of Biofilm in Food

Fungi-forming biofilm would produce various toxins in food. The toxin contamination will cause great harm to food and human health. Herein, a novel graphene-based steganographic aptasensor was assembled for multifunctional applications, which depended on the specific recognition and information encoding ability of DNA aptamers [mycotoxins, including zearalenone (ZEN) and ochratoxin A (OTA) aptamers, as models] and the selective absorption and fluorescence quenching capacities of graphene oxide (GO). The graphene-based steganographic aptasensor can be regarded as an information encryption and steganographic system using GO as a cover, aptamers for specific target recognition as information carriers and dual targets (ZEN and OTA) as special keys. In our work, the fluorescence of capture probes (Cy3 aptamer and Alexa Fluor 488 aptamer) was quenched by GO to realize information encryption. In the presence of dual targets in the GO–APT solution, Cy3 aptamer (APT1), and Alexa Fluor 488 aptamer (APT2) were released from the surface of GO, decrypting the hidden information. In addition, our work offers a sensor for rapid and sensitive simultaneous fluorescence determination of ZEN and OTA. The detection limit of the aptasensor was 1.797 ng/ml for ZEN and 1.484 ng/ml for OTA. In addition, the graphene-based steganographic aptasensor can be used to construct a molecular logic gate system in which GO, aptamers, and mycotoxins are employed as the input and compounds and fluorescence signals were used as the output. This would be helpful to control the biofilm toxin in the future.
Molecular Basis of Plant Oil Biosynthesis: Insights Gained From Studying the WRINKLED1 Transcription Factor

Most plant species generate and store triacylglycerol (TAG) in their seeds, serving as a core supply of carbon and energy to support seedling development. Plant seed oils have a wide variety of applications, from being essential for human diets to serving as industrial renewable feedstock. WRINKLED1 (WRI1) transcription factor plays a central role in the transcriptional regulation of plant fatty acid biosynthesis. Since the discovery of Arabidopsis WRI1 gene (AtWRI1) in 2004, the function of WRI1 in plant oil biosynthesis has been studied intensively. In recent years, the identification of WRI1 co-regulators and deeper investigations of the structural features and molecular functions of WRI1 have advanced our understanding of the mechanism of the transcriptional regulation of plant oil biosynthesis. These advances also help pave the way for novel approaches that will better utilize WRI1 for bioengineering oil production in crops.
DETECTing Merkel Cell Polyomavirus in Merkel Tumors

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post integration (∼80% cases), or by UV mediated DNA damage. Interestingly, overall survival of patients suffering from MCV positive Merkel cell carcinoma is better, making this differential information of significant diagnostic and prognostic value. Also, MCV as a causative agent also provides a direct target for therapy in virus positive MCC patients. Currently, the methods used for diagnosis of MCV in tumours are often tedious, discordant and unreliable. In this study we used a guided molecular scissors based - DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) technique to develop an in vitro molecular diagnostic tool for MCV positive MCC. DETECTR couples recombinase polymerase based amplification of target MCV DNA with Cas12a mediated detection. CRISPR diagnostics couple specific detection followed by cutting of the pathogenic DNA by the Cas enzyme – gRNA complex, with non-specific cutting of ssDNA that provides a measurable visual cue. To detect MCV DNA in MCC tumours, we designed Cas12a gRNAs targeting the MCV DNA and tested their targeting efficiency, and sensitivity using a fluorophore quencher labeled reporter assay. We show that this sophisticated MCV DETECTR system can detect MCV integrated in Merkel tumour rapidly, specifically and with femto-molar sensitivity. This new MCV DNA detecting system is promising and we hope it can be coupled with histopathological and immunohistochemical studies to diagnose the viral status of MCC in clinics in the near future.
Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics

Cardiovascular disease is the leading cause of worldwide mortality. Intravital microscopy has provided unprecedented insight into leukocyte biology by enabling the visualization of dynamic responses within living organ systems at the cell-scale. The heart presents a uniquely dynamic microenvironment driven by periodic, synchronous electrical conduction leading to rhythmic contractions of cardiomyocytes, and phasic coronary blood flow. In addition to functions shared throughout the body, immune cells have specific functions in the heart including tissue-resident macrophage-facilitated electrical conduction and rapid monocyte infiltration upon injury. Leukocyte responses to cardiac pathologies, including myocardial infarction and heart failure, have been well-studied using standard techniques, however, certain questions related to spatiotemporal relationships remain unanswered. Intravital imaging techniques could greatly benefit our understanding of the complexities of in vivo leukocyte behavior within cardiac tissue, but these techniques have been challenging to apply. Different approaches have been developed including high frame rate imaging of the beating heart, explantation models, micro-endoscopy, and mechanical stabilization coupled with various acquisition schemes to overcome challenges specific to the heart. The field of cardiac science has only begun to benefit from intravital microscopy techniques. The current focused review presents an overview of leukocyte responses in the heart, recent developments in intravital microscopy for the murine heart, and a discussion of future developments and applications for cardiovascular immunology.
Insights Into Oxidized Lipid Modification in Barley Roots as an Adaptation Mechanism to Salinity Stress

Lipidomics is an emerging technology, which aims at the global characterization and quantification of lipids within biological matrices including biofluids, cells, whole organs and tissues. The changes in individual lipid molecular species in stress treated plant species and different cultivars can indicate the functions of genes affecting lipid metabolism or lipid signaling. Mass spectrometry–based lipid profiling has been used to track the changes of lipid levels and related metabolites in response to salinity stress. We have developed a comprehensive lipidomics platform for the identification and direct qualification and/or quantification of individual lipid species, including oxidized lipids, which enables a more systematic investigation of peroxidation of individual lipid species in barley roots under salinity stress. This new lipidomics approach has improved with an advantage of analyzing the composition of acyl chains at the molecular level, which facilitates to profile precisely the 18:3-containing diacyl-glycerophosphates and allowed individual comparison of lipids across varieties. Our findings revealed a general decrease in most of the galactolipids in plastid membranes, and an increase of glycerophospholipids and acylated steryl glycosides, which indicate that plastidial and extraplastidial membranes in barley roots ubiquitously tend to form a hexagonal II (HII) phase under salinity stress. In addition, salt-tolerant and salt-sensitive cultivars showed contrasting changes in the levels of oxidized membrane lipids. These results support the hypothesis that salt-induced oxidative damage to membrane lipids can be used as an indication of salt stress tolerance in barley.
Regulatory T Cell Suppressive Activity Predicts Disease Relapse During Disease-Modifying Anti-rheumatic Drug Dose Reduction in Rheumatoid Arthritis: A Prospective Cohort Study

When the dose of conventional disease-modifying anti-rheumatic drugs (cDMARDs) is tapered in rheumatoid arthritis (RA) patients who achieve sustained remission, biomarkers for predicting disease relapse may be needed. A prospective, unblinded cohort study was conducted in nine RA patients with remission. Peripheral blood samples were collected at baseline and at 6, 12, and 24 weeks after cDMARD dose reduction (dose of combination regimens reduced to 50%) to determine the number of regulatory Foxp3+T cells (Tregs) and other T cell subpopulations as well as Treg suppressive activity. Additionally, plasma levels of 14 cytokines at each time-point were measured via flow cytometry. Univariate and multivariate analyses were performed to identify the factor(s) associated with RA relapse during the observational period. In univariate analysis, Treg suppression and DAS28 and VAS scores were associated with RA relapse after cDMARD dose tapering. However, in multivariate analysis, only Treg suppressive activity (<42%) was found to be an independent factor associated with RA relapse after cDMARD dose reduction to 50%. Of all patients who had ≥42% Treg suppressive activity during cDMAD reduction, three-fourth patients remained in the remission stage for 24 weeks. Treg suppressive activity (<42%) in RA patients with remission could be a potential biomarker for predicting RA relapse after cDMARD dose reduction, especially over a short-term period (24 weeks).
Editorial: Modeling Human Potential Across the Lifespan

Ebbinghaus (1908) wrote that although “psychology has a long past, yet it’s real history is short” (p. 3). The same applies to a scientific understanding of human potential. Simonton (2001) noted a debt owed to nineteenth century polymaths Adolphe Quételet and Francis Galton. Quetelet (1968) was the first to report quantitative measures of creativity and to discuss bell-shaped distributions of human characteristics. Galton (1869), recognized the significance of the right-side extreme of the normal curve. His research on familial relationships among such high functioning individuals brought the nature vs. nurture controversy into the realm of scientific study. Models that influenced scientific understandings of lifespan human potential during the past half-century include the sustained deliberate practice model (Ericsson et al., 1993), the successful aging model (Rowe and Kahn, 1987), Simonton’s (1990) model of creativity, and statistical models related to adulthood and aging (Schaie and Hertzog, 1985). Articles in this Research Topic aim to advance such modeling primarily with respect to sport.
Nutrition, Behavior Change and Physical Activity Outcomes From the PEARS RCT—An mHealth-Supported, Lifestyle Intervention Among Pregnant Women With Overweight and Obesity

Background: Diet quality and physical activity positively impact pregnancy outcomes among women with obesity, but successful lifestyle interventions require intense clinician time. We aimed to investigate the impact of a behavioral-lifestyle intervention (PEARS) supported by a smartphone app among pregnant women with overweight and obesity, on nutrient intake, behavioral stage-of-change and physical activity. Methods: Pregnant women (BMI 25–39.9 kg/m2, measured, n = 565) were randomized at 15.6 weeks' gestation to the intervention (n = 278), or a control group (n = 287) (ISRCTN29316280). The intervention was grounded in behavior-change theory. Participants received nutrition (low glycaemic index and healthy eating) and exercise advice, a smartphone app and fortnightly emails. The control group received usual care which does not include dietary advice. At baseline and 28 weeks' gestation, dietary data were obtained through 3-day food diaries (n = 290 matched), and stage-of-change and physical activity data were self-reported. App usage data were collected. Results: There were no differences between the groups at baseline. Compared with the control group, the intervention group had improved dietary intakes post-intervention with; lower glycaemic index (MD −1.75); free sugars (%TE) (MD −0.98); fat (%TE) (MD −1.80); and sodium (mg) (MD −183.49). Physical activity (MET-minutes/week) was higher in the intervention group post-intervention (MD 141.4; 95% CI 62.9, 219.9). The proportion of participants at “maintenance” stage-of-change for physical activity was higher in the intervention group (56.3 vs. 31.2%). App use was associated with lower glycaemic index and less energy from free sugars, but not with physical activity. Conclusion: A behavioral-lifestyle intervention in pregnancy supported by a smartphone app improved dietary intakes, physical activity, and motivation to engage in exercise.
PLXNC1 Enhances Carcinogenesis Through Transcriptional Activation of IL6ST in Gastric Cancer

Background: Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. However, their roles in gastric cancer (GC) remain unclear. Methods: We analyzed the differential expressions of TFs and, using GC cells and tissues, investigated plexin C1 (PLXNC1) RNA levels, as well as PLXNC1's clinical relevance and functional mechanisms. The molecular function of PLXNC1 was evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS). Results: PLXNC1 was frequently up-regulated in GC and associated with poor prognosis. The expression level of PLXNC1 could serve as an independent biomarker to predict a patient's overall survival. Notably, knockdown of PLXNC1 significantly abolished GC cell proliferation, and migration, and overexpression of PLXNC1 accelerated carcinogenesis in GC. The gene set enrichment analysis (GSEA) indicated that high-expression of PLXNC1 was positively correlated with the activation of epithelial-mesenchymal transition (EMT), TNF-α, and IL-6/STAT3 signaling pathways. PLXNC1 promoted proliferation and migration of GC cells through transcriptional activation of the interleukin 6 signal transducer (IL6ST), which could rescue the malignant behavior of PLXNC1-deficient GC cells. Conclusions: Our study demonstrated that the PLXNC1 plays an oncogenic role in GC patients. The PLXNC1-IL6ST axis represents a novel potential therapeutic target for GC.
Mapping Quantitative Trait Loci Associated With Resistance to Aflatoxin Accumulation in Maize Inbred Mp719

Aflatoxins are carcinogenic and toxic compounds produced principally by fungal species Aspergillus flavus (Link: Fries) and A. parasiticus (Speare), which are common contaminants of food and feed. Aflatoxins can be found at dangerously high levels and can readily contaminate pre-harvest maize (Zea mays L.) grain. Sources of resistance to aflatoxin accumulation in maize have been identified, however, the highly quantitative nature and complex inheritance of this trait have limited the introgression of aflatoxin accumulation resistance into agronomically desirable lines. Mapping of quantitative trait loci (QTL) was performed on a bi-parental population comprised of 241 F2:3 families derived from the cross of inbred lines Mp705 (susceptible) × Mp719 (resistant). The mapping population was phenotyped in replicated field trials in three environments for resistance to aflatoxin accumulation under artificial inoculation with an A. flavus spore suspension. The genetic linkage map was constructed with 1,276 single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) molecular markers covering a total genetic distance of 1,642 cM across all ten maize chromosomes. Multiple interval mapping revealed that majority of the aflatoxin-reducing alleles and the source for the larger effect QTL identified in this study were contributed from Mp719, the resistant parent. Two QTL identified on chromosome 1 (bin 1.06–1.07) and chromosome 3 (bin 3.09) were the most stable across different environments and when combined, explained 24.6% of the total phenotypic variance across all three environments. Results from the study showed that these chromosomal regions harbor important QTL for influencing aflatoxin accumulation, which is consistent with previous reports with other different mapping populations. These stable QTL were the most promising for controlling aflatoxin accumulation in maize grain. Identifying beneficial alleles derived from Mp719 and closely linked molecular markers through QTL analysis for implementation of MAS could accelerate breeding efforts to reduce aflatoxin accumulation in maize.