Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary iron intake and blood donations in relation to risk of type 2 diabetes in men: a prospective cohort study.

BACKGROUND Excessive iron stores may promote insulin resistance and lead to the development of type 2 diabetes. However, prospective data relating iron intake and blood donations (determinants of body iron stores) to diabetes incidence are limited. OBJECTIVE We examined iron intake and blood donations in relation to the incidence of type 2 diabetes. DESIGN We followed men aged 40-75 y who participated in the Health Professionals' Follow-up Study; were free of diabetes, cardiovascular disease, and cancer in 1986; and provided dietary data (n = 38 394). Of those participants, 33 541 also provided a history of blood donation during the past 30 y in 1992. RESULTS During 12 y of follow-up, we ascertained 1168 new cases of type 2 diabetes. After adjustment for age, body mass index, and other diabetes risk factors, total iron intake was not associated with the risk of type 2 diabetes. Intakes of total heme iron [multivariate relative risk (RR) for extreme quintiles: 1.28; 95% CI: 1.02, 1.61; P for trend = 0.045] and of heme iron from red meat (RR: 1.63; 1.26, 2.10; P for trend < 0.001) were associated with an increased risk. However, heme-iron intake from sources other than red meat was not associated with diabetes risk (RR: 0.99; 0.81, 1.22). No significant associations were found between blood donation and the risk of type 2 diabetes. CONCLUSIONS Heme-iron intake from red meat sources is positively associated with the risk of type 2 diabetes. Total iron intake, heme-iron intake from non-red meat sources, and blood donations are not related to the risk of type 2 diabetes.
Image classification using labelled and unlabelled data

In this paper we present a case study of co-training to image classification. We consider two scene classification tasks: indoors vs. outdoors and animals vs. sports. The results show that co-training with Naïve Bayes using 8-10 labelled examples obtained only 1.2-1.5% lower classification accuracy than Naïve Bayes trained on the full labelled version of the training set (138 examples in task 1 and 827 examples in task 2). Co-training was found to be sensitive to the choice of base classifier, with Naïve Bayes outperforming Random Forest. We also propose a simple co-training modification based on the different inductive basis of classification algorithms and show that it is a promising approach.
Gli1‐induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1

Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli‐dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis. Importantly, USP48's effect on cell proliferation and tumorigenesis depends to some extent on Gli1. In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1‐mediated transcriptional activation, which forms thus a positive feedback loop to regulate Hh signaling. In human glioblastoma specimens, the expression levels of USP48 and Gli1 proteins are clinically relevant, and high expression of USP48 correlates with glioma malignancy. In summary, our study reveals that the USP48‐Gli1 regulatory axis is critical for glioma cell proliferation and glioblastoma tumorigenesis.
The influence of facies heterogeneity on the doublet performance in low-enthalpy geothermal sedimentary reservoirs

A three-dimensional model is used to study the inﬂuence of facies heterogeneity on energy produc- tion under different operational conditions of low-enthalpy geothermal doublet systems. Process-based facies modelling is utilised for the Nieuwerkerk sedimentary formation in the West Netherlands Basin to construct realistic reservoir models honouring geological heterogeneity. A ﬁnite element based reservoir simulator is used to model the ﬂuid ﬂow and heat transfer over time. A series of simulations is carried out to examine the effects of reservoir heterogeneity (Net-to-Gross ratio, N/G) on the life time and the energy recovery rate for different discharge rates and the production temperature ( T min ) above which the doublet is working. With respect to the results, we propose a design model to estimate the life time and energy recovery rate of the geothermal doublet. The life time is estimated as a function of N/G, T min and discharge rate, while the design model for the energy recovery rate is only a function of N/G and T min . Both life time and recovery show a positive relation with an increasing N/G. Further our results suggest that neglecting details of process-based facies modelling may lead to signiﬁcant errors in predicting the life time of low-enthalpy geothermal systems for N/G values below 70%. © 2016 Published by Elsevier Ltd.
The effect of induced sadness and moderate depression on attention networks

ABSTRACT This study investigates how sadness and minor/moderate depression influences the three functions of attention: alerting, orienting, and executive control using the Attention Network Test. The aim of the study is to investigate whether minor-to-moderate depression is more similar to sadness or clinical depression with regard to attentional processing. It was predicted that both induced sadness and minor-to-moderate depression will influence executive control by narrowing spatial attention and in turn this will lead to less interference from the flanker items (i.e. less effects of congruency) due to a focused attentional state. No differences were predicted for alerting or orienting functions. The results from the two experiments, the first inducing sadness (Experiment 1) and the second measuring subclinical depression (Experiment 2), show that, as expected, participants who are sad or minor to moderately depressed showed less flanker interference compared to participants who were neither sad nor depressed. This study provides strong evidence, that irrespective of its aetiology, sadness and minor/moderate depression have similar effects on spatial attention.
Attention‐Deficit‐Hyperactivity Disorder: An Update

Attention‐deficit‐hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. In patients with ADHD, neurobiologic research has shown a lack of connectivity in key brain regions, inhibitory control deficits, delayed brain maturation, and noradrenergic and dopaminergic dysfunction in multiple brain regions. The prevalence of this disorder in the United States is 6–9% in youth (i.e., children and adolescents) and 3–5% in adults. Prevalence rates for youth are similar worldwide. Children with ADHD are at greater risk than children without ADHD for substance abuse and delinquency whether or not they receive drug therapy; however, early treatment with psychoeducation as well as drug therapy and/or behavioral intervention may decrease negative outcomes of ADHD, including the rate of conduct disorder and adult antisocial personality disorder. Drug therapy is effective for all age groups, even preschoolers, and for late‐onset ADHD in adults. Stimulants, such as methylphenidate and amphetamine, are the most effective therapy and have a good safety profile; although recent concerns of sudden unexplained death, psychiatric adverse effects, and growth effects have prompted the introduction of other therapies. Atomoxetine, a nonstimulant, has no abuse potential, causes less insomnia than stimulants, and poses minimal risk of growth effects. Other drug options include clonidine and guanfacine, but both can cause bradycardia and sedation. Polyunsaturated fatty acids (fish oil), acetyl‐l‐carnitine, and iron supplements (for youth with low ferritin levels) show promise in improving ADHD symptoms. As long‐term studies show that at least 50% of youth are nonadherent with their drug therapy as prescribed over a 1‐year period, longacting formulations (administered once/day) may improve adherence. Comorbid conditions are common in patients with ADHD, but this patient population can be treated effectively with individualized treatment regimens of stimulants, atomoxetine, or bupropion, along with close monitoring.
Roles of lipocalin 2 and adiponectin in iron overload cardiomyopathy

Thalassemia is among the most common genetic diseases worldwide. Ineffective erythropoiesis, chronic hemolysis, and regular blood transfusion in thalassemia patients lead to increased iron burden. Iron overload cardiomyopathy is the most severe co‐morbidity and most common cause of mortality in thalassemia patients. Although its associated mechanisms are still not completely understood, cellular iron mishandling, chronic inflammation, and oxidative stress appear to be the key processes involved. In order to acquire a more comprehensive insight of the impact of cardiac iron overload, these alterations need to be intensively investigated. This comprehensive mini‐review focuses on two emergent molecules which have been shown to potentially play significant roles in iron overload cardiomyopathy. These two molecules are an iron‐transporting protein, lipocalin 2, and an anti‐inflammatory adipokine, adiponectin. Reports from in vitro and in vivo studies are comprehensively summarized. Clinical studies examining the roles of these molecules in thalassemia patients are also presented and discussed.
Patient-reported outcomes in asthma clinical trials

Purpose of review The review provides an overview of the results of asthma clinical trials published in peer review journals in the last 18 months that evaluated patient-reported outcomes (PROs). Recent findings In the last 10 years, health care moved toward a patient-centered approach, which includes patients’ perspectives reflecting the impact of a disease and its treatment. Summary Surprisingly, among the almost 300 clinical trials published in the last one and a half year, PRO evaluation was performed in only 20 studies, and none of them held in a real-life setting. The effort of applying the scientific methods of PRO investigations in asthma clinical trials following a rigorous and systematic approach needs to be highly improved to allow better understanding of patient reported factors. Some recommendations are drawn particularly about PRO assessment in personalized medicine research. The ability of an individual PRO to evaluate choice of treatment and its effectiveness remains to be achieved.
A Phase Ib/II Study of Ganetespib With Doxorubicin in Advanced Solid Tumors Including Relapsed-Refractory Small Cell Lung Cancer

Introduction Small cell lung cancer (SCLC) accounts for 15% of all lung cancers and is characterized by high response rates to cytotoxic chemotherapy and equally high rates of relapse. Many resistance mechanisms have been proposed including resistance to doxorubicin via induction of a heat shock response. Ganetespib is a novel and potent non-geldanamycin heat shock protein 90 (Hsp90) inhibitor. In preclinical studies, synergy between ganetespib and doxorubicin was shown. We conducted a phase Ib/II study of the safety, tolerability, and preliminary efficacy of the combination of ganetespib and doxorubicin. Methods Patients eligible for the phase Ib portion had advanced tumors that would be appropriate for doxorubicin therapy and those in the phase II portion had relapsed or refractory SCLC. All patients had an ECOG performance status, 0–1 and adequate organ function, including a cardiac ejection fraction ≥50%. Patients who received a lifetime cumulative doxorubicin dose of >150 mg/m2 or who had symptomatic brain metastases were excluded. Patients received ganetespib on Days 1 and 8 and doxorubicin 50 mg/m2 on day 1 in 21-day cycles. Results Eleven patients were enrolled including nine in the phase Ib dose escalation and two in the phase II expansion. The study was terminated by the sponsor. The dose recommended for future study is ganetespib 150 mg/m2 in combination with doxorubicin at a dose of 50 mg/m2. The most common adverse events of the combination were grade 1/2 diarrhea, nausea, fatigue, and transaminitis. No dose limiting toxicities were observed. Response rate was 25% and median duration of response was 137 days. Conclusion Ganetespib plus doxorubicin was a well-tolerated combination and there remains potential for the clinical development of Hsp90 inhibitors in SCLC. Clinical Trial Registration https://ClinicalTrials.gov/ct2/show/NCT02261805, identifier NCT02261805.
Murine Rankl−/− Mesenchymal Stromal Cells Display an Osteogenic Differentiation Defect Improved by a RANKL‐Expressing Lentiviral Vector

Autosomal recessive osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast resorptive function or differentiation. Hematopoietic stem cell transplantation is the only available treatment; however, this therapy is not effective in RANKL‐dependent ARO, since in bone this gene is mainly expressed by cells of mesenchymal origin. Of note, whether lack of RANKL production might cause a defect also in the bone marrow (BM) stromal compartment, possibly contributing to the pathology, is unknown. To verify this possibility, we generated and characterized BM mesenchymal stromal cell (BM‐MSC) lines from wild type and Rankl−/− mice, and found that Rankl−/− BM‐MSCs displayed reduced clonogenicity and osteogenic capacity. The differentiation defect was significantly improved by lentiviral transduction of Rankl−/− BM‐MSCs with a vector stably expressing human soluble RANKL (hsRANKL). Expression of Rankl receptor, Rank, on the cytoplasmic membrane of BM‐MSCs pointed to the existence of an autocrine loop possibly activated by the secreted cytokine. Based on the close resemblance of RANKL‐defective osteopetrosis in humans and mice, we expect that our results are also relevant for RANKL‐dependent ARO patients. Data obtained in vitro after transduction with a lentiviral vector expressing hsRANKL would suggest that restoration of RANKL production might not only rescue the defective osteoclastogenesis of this ARO form, but also improve a less obvious defect in the osteoblast lineage, thus possibly achieving higher benefit for the patients, when the approach is translated to clinics. Stem Cells 2017;35:1365–1377
Moderate energy restriction increases bone resorption in obese postmenopausal women.

BACKGROUND Weight reduction reduces bone mineral density (BMD) and increases the risk of osteoporosis. OBJECTIVE We investigated whether bone is mobilized in postmenopausal women during energy restriction and whether hormones regulate bone turnover and mass. DESIGN Twenty-seven obese postmenopausal women with a mean (+/-SD) age of 55.9 +/- 7.9 y and body mass index (in kg/m(2)) of 33.0 +/- 3.8 completed the 6-mo study. Fourteen women followed a moderate energy-restricted diet (WL group) and 13 control subjects maintained their body weight (WM group). Body weight, bone turnover markers, serum parathyroid hormone (PTH), and dietary intake were measured throughout the study. Total-body BMD, sex hormone binding globulin, leptin, and estrone were measured at baseline and at week 25. RESULTS In the WL group, body weight decreased by 10.2 +/- 5.5% (P < 0.001), body fat mass decreased by 18.7 +/- 11.3% (P < 0.001), and total-body BMD decreased by 1.2 +/- 1.2%; these changes were significantly different from those in the WM group (P < 0.05). Serial measurements showed chronically elevated rates of bone resorption and formation during energy restriction that were greater than in the WM group (P < 0.05). Serum sex hormone binding globulin increased and leptin decreased with weight loss (P < 0.05). Serum PTH tended to increase in the WL group but not in the WM group (P < 0.06). The reduction in fat mass with weight loss was directly associated with a decrease in serum estrone (P < 0.01, R(2) = 0.50). CONCLUSIONS Moderate energy restriction increases bone turnover in obese postmenopausal women and may be regulated in part by alterations in serum PTH and estrone.
Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study.

BACKGROUND Anthocyanins are potent antioxidants that are widely distributed in fruit, vegetables, and red wines. Anthocyanin products are also prescribed as medicines in many countries for treating various diseases. However, the pharmacokinetics of dietary anthocyanins are not known in humans because these glycosides were long considered nonabsorbable. OBJECTIVE The objective of this study was to determine whether anthocyanins can be absorbed as glycosides and to evaluate their pharmacokinetics in humans. DESIGN Four healthy elderly women consumed 720 mg anthocyanins. A series of blood and urine samples were collected before and after consumption of the anthocyanins. Anthocyanins were measured in plasma and urine by combining an octadecylsilane solid-phase extraction for sample preparation and an HPLC system with diode array for anthocyanin separation and detection. The structures of anthocyanins as glycosides in plasma and urine were further confirmed by using liquid chromatography-mass spectrometry. RESULTS Anthocyanins were detected as glycosides in plasma and urine. The maximum plasma concentration of total anthocyanins varied from 55.3 to 168.3 nmol/L, with an average of 97.4 nmol/L, and was reached within 71.3 min. The elimination of plasma anthocyanins appeared to follow first-order kinetics. The elimination half-life of plasma total anthocyanins was calculated to be 132.6 min. Most anthocyanin compounds were excreted in urine during the first 4 h. The excretion rate of total anthocyanins was 77 microg/h during the first 4 h and 13 microg/h during the second 4 h. CONCLUSION Anthocyanins are absorbed in their unchanged glycated forms in elderly women.
Patient-Reported Outcomes and Their Predictors at Minimum 10 Years After Anterior Cruciate Ligament Reconstruction

Background: Long-term results after anterior cruciate ligament (ACL) reconstruction are being reported with greater frequency, allowing a detailed analysis of long-term patient-reported outcomes and predictors. Purpose: To summarize expected patient-reported outcomes at a minimum 10 years following ACL reconstruction and to explore patient and surgical factors that affect these results. Study Design: Systematic review; Level of evidence, 4. Methods: Prospective studies detailing patient-reported outcomes with a minimum follow-up of 10 years were identified. Average scores for each outcome measure were calculated. Factors identified in each paper as predictors of patient-reported outcomes were identified and described. Results: Thirteen studies met inclusion and exclusion criteria. Lysholm scores were reported in 317 of 406 patients (78.1%) in 6 studies, with a mean score of 91.7 ± 11.2. Subjective International Knee Documentation Committee scores were reported in 1726 of 2611 patients (66.1%) in 5 studies, with a mean score of 84.2 ± 15.5. Cincinnati knee scores were reported in 1323 of 1801 patients (73.5%) in 3 studies, with a mean score of 87.4 ± 14.4. Tegner activity scores were reported in 728 of 914 patients (79.6%) in 8 studies, with a mean score of 5.1. There was mixed evidence that meniscectomy and articular cartilage damage were associated with poorer patient-reported outcomes. Patient sex and graft choice did not affect patient-reported outcomes. Conclusion: Patient-reported outcomes are generally good at a minimum of 10 tears following ACL reconstruction. Further large prospective studies with regression modeling and consistent outcome reporting will clarify predictors of outcomes.
New Insights into How Serotonin Selective Reuptake Inhibitors Shape the Developing Brain

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro‐circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context. While allowing for adaptation, such sensitive periods are also windows of vulnerability during which external and internal factors can confer risk to brain disorders by derailing adaptive developmental programs. Our group has been particularly interested in developmental periods that are sensitive to serotonin (5‐HT) signaling, and impact behavior and cognition relevant to psychiatry. Specifically, we review a 5‐HT‐sensitive period that impacts fronto‐limbic system development, resulting in cognitive, anxiety, and depression‐related behaviors. We discuss preclinical data to establish biological plausibility and mechanistic insights. We also summarize epidemiological findings that underscore the potential public health implications resulting from the current practice of prescribing 5‐HT reuptake inhibiting antidepressants during pregnancy. These medications enter the fetal circulation, likely perturb 5‐HT signaling in the brain, and may be affecting circuit maturation in ways that parallel our findings in the developing rodent brain. More research is needed to better disambiguate the dual effects of maternal symptoms on fetal and child development from the effects of 5‐HT reuptake inhibitors on clinical outcomes in the offspring. Birth Defects Research 109:924–932, 2017. © 2017 Wiley Periodicals, Inc.
Insulin-Like Growth Factor-1 Related to Disability Among Older Adults.

BACKGROUND Disability is a crucial health problem in aging. Identifying a biological contributory factor would be useful. Serum insulin-like growth factor-1 (IGF-1) plays an important role in the endocrine system and is associated with frailty. However, there is no consensus about the relationship between IGF-1 and disability. This study aimed to examine whether IGF-1 related to incident disability among older adults. METHODS The study included 4,133 older adults (mean age, 71.8±5.4 years) who were participants in the "Obu Study of Health Promotion for the Elderly" cohort study. We collected information on demographic variables, measured gait speed, Mini Mental State Examination score, and serum IGF-1 at baseline. During follow-up, incident disability was monitored by Long-Term Care Insurance certification. RESULTS Disability was observed in 212 participants during a mean follow-up duration period of 29.2 months. A log rank test indicated that lower levels of serum IGF-1 were related to incident disability (p = .004). A Cox hazard regression showed a lower quartile in IGF-1 related to disability compared with the highest quartile (Q4), even when adjusting for covariates including gait speed and Mini Mental State Examination score (Q1: hazard ratio = 1.72, 95% confidence intervals: 1.06-2.81; Q2: hazard ratio = 1.64, 95% confidence intervals: 0.99-2.71; Q3: hazard ratio = 1.31, 95% confidence intervals: 0.76-2.25). In the analysis, stratified by sex, there was also significant relationship between IGF-1 and disability among women, but not men. CONCLUSIONS Lower serum IGF-1 was independently related to disability among older adults.