Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in nonanemic women.

BACKGROUND Recent studies in humans suggest that ferritin iron in soybeans has high bioavailability. However, direct evidence for this is lacking because the soybeans were intrinsically labeled; thus, iron bound to other ligands, such as phytate, was also labeled. OBJECTIVE The objectives of the study were to evaluate the absorption of iron from extrinsically labeled, purified ferritin (horse spleen) reconstituted with either high-phosphate iron mineral (plant-type) or low-phosphate iron mineral (animal-type) and to compare it with iron absorption from ferrous sulfate. DESIGN Nonanemic, healthy young women were fed a standard breakfast meal supplemented with (59)Fe-labeled ferritin or ferrous sulfate, in randomized order. Fifteen subjects received ferritin with the low-phosphate iron mineral, and 15 subjects received ferritin with the high-phosphate iron mineral. Iron absorption was measured in a whole-body counter after 14 and 28 d and by red blood cell incorporation after 28 d. RESULTS There was no significant difference in iron absorption between ferritin and ferrous sulfate: low-phosphate iron mineral ferritin (x +/- SD: 21.4 +/- 14.7%) compared with ferrous sulfate (21.9 +/- 14.6%), or high-phosphate iron mineral ferritin (22.2 +/- 19.2%) compared with ferrous sulfate (16.7 +/- 7.1%). Results obtained by using whole-body retention of iron and red blood cell incorporation differed with the type of iron, which suggests that pathways for iron uptake and utilization differed for the 2 forms. CONCLUSIONS Iron is equally well absorbed from ferritin and ferrous sulfate independent of the phosphate content of the ferritin iron mineral. Thus, dietary ferritin iron is likely to be a good source of iron.
Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). Methods and Findings We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, N SNPs = 49), fasting glucose (N SNPs = 36), insulin resistance (N SNPs = 10), body mass index (BMI, N SNPs = 32), total cholesterol (N SNPs = 73), HDL-cholesterol (N SNPs = 71), LDL-cholesterol (N SNPs = 57), triglycerides (N SNPs = 39), systolic blood pressure (SBP, N SNPs = 24), smoking initiation (N SNPs = 1), smoking quantity (N SNPs = 3), university completion (N SNPs = 2), and years of education (N SNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP–AD associations from the International Genomics of Alzheimer’s Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62–0.91]; p = 3.4 × 10−3). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10−8). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51–0.89]; p = 6.5 × 10−3), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Conclusions Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure—or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications—may reduce AD risk.
Global Quality of Life Among WHI Women Aged 80 Years and Older.

BACKGROUND The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social-psychological, lifestyle, and physical health variables with global QOL in a Women's Health Initiative (WHI) cohort of women aged 80 and older. METHODS 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (≤50, 50-70, ≥70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL. RESULTS Social-psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women ≥80 years. CONCLUSIONS Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care.
Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution

BACKGROUND AND PURPOSE: Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-β and phosphorylated tau 181 protein levels and longitudinal cognitive decline. MATERIALS AND METHODS: A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-β levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates. RESULTS: Having ≥3 lobar microbleeds was associated with lower levels of CSF amyloid-β (P = .001). After adjusting for CSF amyloid-β level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations. CONCLUSIONS: The distribution of microbleeds revealed different associations with amyloid-β and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis.
Recombinant TAT-BMI-1 fusion protein induces ex vivo expansion of human umbilical cord blood-derived hematopoietic stem cells

Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery. Here we describe a system for the ex vivo expansion of CB-HSCs based on their transient exposure to a recombinant TAT-BMI-1 chimeric protein. BMI-1 belongs to the Polycomb family of epigenetic modifiers and is recognized as a central regulator of HSC self-renewal. Recombinant TAT-BMI-1 produced in bacteria was able to enter the target cells via the HIV TAT-derived protein transduction peptide covalently attached to BMI-1, and conserved its biological activity. Treatment of CB-CD34+ cells for 3 days with repeated addition of 10 nM purified TAT-BMI-1 significantly enhanced total cell expansion as well as that of primitive hematopoietic progenitors in culture. Importantly, TAT-BMI-1-treated CB-CD34+ cells displayed a consistently higher rate of multi-lineage long-term repopulating activity in primary and secondary xenotransplants in immunocompromised mice. Thus, recombinant TAT-BMI-1 may represent a novel, effective reagent for ex vivo expansion of CB-HSC for therapeutic purposes.
Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology

Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in‐situ hybridization (FISH) and quantitative PCR‐based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%‐75% of urothelial carcinoma and in 16% of ovarian clear‐cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting.
Price and Inventory Competition in Oligopoly TV White Space Markets

In this paper, we investigate an oligopoly-competitive TV white space (TVWS) market, where multiple secondary network operators compete to serve a common pool of secondary end users by using TVWS purchased from a white space database. We first study the competitive interactions among secondary operators. Specifically, we formulate the interactions as a noncooperative price-inventory competition game, where operators determine the spectrum inventory (purchased from the database) and the service price (charged to end users) simultaneously. We prove the existence and uniqueness of the Nash equilibrium using the supermodular game theory. Then, we study the impact of the database manager's wholesale pricing strategy on the market equilibrium. Specifically, we analytically show how the wholesale prices affect the operators' equilibrium inventory and pricing decisions. Based on this analysis, we further propose two different spectrum wholesale pricing strategies that maximize the database manager's profit and the total network profit, respectively. Our simulations evaluate the performance difference between these two wholesale pricing strategies.
Cyclodextrin-Based Magnetic Nanoparticles for Cancer Therapy

Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-β-cyclodextrin (SH-βCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine.
No difference in body weight decrease between a low-glycemic-index and a high-glycemic-index diet but reduced LDL cholesterol after 10-wk ad libitum intake of the low-glycemic-index diet.

BACKGROUND The role of glycemic index (GI) in appetite and body-weight regulation is still not clear. OBJECTIVE The objective of the study was to investigate the long-term effects of a low-fat, high-carbohydrate diet with either low glycemic index (LGI) or high glycemic index (HGI) on ad libitum energy intake, body weight, and composition, as well as on risk factors for type 2 diabetes and ischemic heart disease in overweight healthy subjects. DESIGN The study was a 10-wk parallel, randomized, intervention trial with 2 matched groups. The LGI or HGI test foods, given as replacements for the subjects' usual carbohydrate-rich foods, were equal in total energy, energy density, dietary fiber, and macronutrient composition. Subjects were 45 (LGI diet: n = 23; HGI diet: n = 22) healthy overweight [body mass index (in kg/m(2)): 27.6 +/- 0.2] women aged 20-40 y. RESULTS Energy intake, mean (+/- SEM) body weight (LGI diet: -1.9 +/- 0.5 kg; HGI diet: -1.3 +/- 0.3 kg), and fat mass (LGI diet: -1.0 +/- 0.4 kg; HGI diet: -0.4 +/- 0.3 kg) decreased over time, but the differences between groups were not significant. No significant differences were observed between groups in fasting serum insulin, homeostasis model assessment for relative insulin resistance, homeostasis model assessment for beta cell function, triacylglycerol, nonesterified fatty acids, or HDL cholesterol. However, a 10% decrease in LDL cholesterol (P < 0.05) and a tendency to a larger decrease in total cholesterol (P = 0.06) were observed with consumption of the LGI diet as compared with the HGI diet. CONCLUSIONS This study does not support the contention that low-fat LGI diets are more beneficial than HGI diets with regard to appetite or body-weight regulation as evaluated over 10 wk. However, it confirms previous findings of a beneficial effect of LGI diets on risk factors for ischemic heart disease.
Human longevity: 25 genetic loci associated in 389,166 UK biobank participants

We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10−8), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mother's age ≥90 years, father's ≥87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother's age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.
Ectopic models for endochondral ossification: comparing pellet and alginate bead culture methods

Key aspects of native endochondral bone development and fracture healing can be mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic induction. Exploiting this phenomenon has recently emerged as an attractive technique to engineer bone tissue, however, relatively little is known about the best conditions for doing so. The objective of the present study was to compare the bone‐forming capacity and angiogenic induction of hypertrophic cell constructs containing human adipose‐derived stem cells (hASCs) primed for chondrogenesis in two different culture systems: high‐density pellets and alginate bead hydrogels. The hASC constructs were subjected to 4 weeks of identical chondrogenic induction in vitro, encapsulated in an agarose carrier, and then implanted subcutaneously in immune‐compromised mice for 8 weeks to evaluate their endochondral potential. At the time of implantation, both pellets and beads expressed aggrecan and type II collagen, as well as alkaline phosphatase (ALP) and type X collagen. Interestingly, ASCs in pellets formed a matrix containing higher glycosaminoglycan and collagen contents than that in beads, and ALP activity per cell was higher in pellets. However, after 8 weeks in vivo, pellets and beads induced an equivalent volume of mineralized tissue and a comparable level of vascularization. Although osteocalcin and osteopontin‐positive osteogenic tissue and new vascular growth was found within both types of constructs, all appeared to be better distributed throughout the hydrogel beads. The results of this ectopic model indicate that hydrogel culture may be an attractive alternative to cell pellets for bone tissue engineering via the endochondral pathway. Copyright © 2016 John Wiley & Sons, Ltd.
Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors

Free fatty acid receptor 2 (FFAR2, also named GPR43), is activated by short‐chain fatty acids (SCFAs), such as butyrate, that are produced when gut bacteria ferment dietary fiber. FFAR2 has been suggested to regulate colonic inflammation, which is a major risk factor for the development of colon cancer and is also linked to epigenetic dysregulation in colon carcinogenesis. The current study assessed whether FFAR2, acting as an epigenetic regulator, protects against colon carcinogenesis. To mimic the mild inflammation that promotes human colon cancer, we treated mice with dextran sodium sulfate (DSS) overnight, which avoids excessive inflammation but induces mild inflammation that promotes colon carcinogenesis in the ApcMin/+ and the azoxymethane (AOM)‐treated mice. Our results showed that FFAR2 deficiency promotes the development of colon adenoma in the ApcMin/+/DSS mice and the progression of adenoma to adenocarcinoma in the AOM/DSS mice. FFAR2's downstream cAMP–PKA–CREB pathway was enhanced, leading to overexpression of histone deacetylases (HDACs) in the FFAR2‐deficient mice. ChIP‐qPCR analysis revealed differential binding of H3K27me3 and H3K4me3 histone marks onto the promoter regions of inflammation suppressors (e.g., sfrp1, dkk3, socs1), resulting in decreased expression of these genes in the FFAR2‐deficient mice. Also, more neutrophils infiltrated into tumors and colon lamina propria of the FFAR2‐deficient mice. Depletion of neutrophils blocked the progression of colon tumors. In addition, FFAR2 is required for butyrate to suppress HDAC expression and hypermethylation of inflammation suppressors. Therefore, our results suggest that FFAR2 is an epigenetic tumor suppressor that acts at multiple stages of colon carcinogenesis.
A Long-lived Mouse Lacking Both Growth Hormone and Growth Hormone Receptor: A New Animal Model for Aging Studies

Disruption of the growth hormone (GH) signaling pathway promotes insulin sensitivity and is associated with both delayed aging and extended longevity. Two kinds of long-lived mice-Ames dwarfs (df/df) and GH receptor gene-disrupted knockouts (GHRKO) are characterized by a suppressed GH axis with a significant reduction of body size and decreased plasma insulin-like growth factor-1 (IGF-1) and insulin levels. Ames dwarf mice are deficient in GH, prolactin, and thyrotropin, whereas GHRKOs are GH resistant and are dwarf with decreased circulating IGF-1 and increased GH. Crossing Ames dwarfs and GHRKOs produced a new mouse line (df/KO), lacking both GH and GH receptor. These mice are characterized by improved glucose tolerance and increased adiponectin level, which could imply that these mice should be also characterized by additional life-span extension when comparing with GHRKOs and Ames dwarfs. Importantly, our longevity experiments showed that df/KO mice maintain extended longevity when comparing with N control mice; however, they do not live longer than GHRKO and Ames df/df mice. These important findings indicate that silencing GH signal is important to extend the life span; however, further decrease of body size in mice with already inhibited GH signal does not extend the life span regardless of improved some health-span markers.
Reliability of a dietary questionnaire.

The measurement of human dietary intake is complicated. One of the most important reasons for this complication is the lack of an “ultimate criterion-measuring device that can be used for calibration of other devices” (1). This is true especially when the information collected is the dietary intake over a considerable length of time. in such a situation, reproducibility of the method might provide a measure of reliability as defined by Moore (2): “A procedure is reliable if it gives the same results when used repeatedly in the same situation. ” Dawber et a! (3), reporting on the reliability of the dietary intake method used in the Framingham Study, stated that correlation coefficients of 0.5 to 0.8 for sequential estimation of dietary factorsare considered to be satisfactory. In their own study, using a modification of the Burke research dietary history (4), they reported correlation coefficients of 0.52 to 0.92 for dietary factors obtained in sequential interviews. Previously (5), we reported on a test of validity of a short questionnaire as compared with the Burke-type interview. Analysis of the data obtained showed inconsistent, weak to moderate correlation between the two methods tested.Moreover, the correlationdecreased and the difference between means increased with greater variability in the diet as measured by the number of food items consumed. Since the Burke-type interview was used as the yard stick and it was to be used in a community dietary program, it became important to examine its reliability. This was carried out by comparing data obtained from two consecutive interviews of the selected population groups reported in the previous