Miracle-dz/UniFAR-FTUs huggingface dataset:
Perfluorinated Compounds and Subfecundity in Pregnant Women

Background: Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds—perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Methods: This case-control analysis included 910 women enrolled in the Norwegian Mother and Child Cohort Study in 2003 and 2004. Around gestational week 17, women reported their time to pregnancy and provided blood samples. Cases consisted of 416 women with a time to pregnancy greater than 12 months, considered subfecund. Plasma concentrations of perfluorinated compounds were analyzed using liquid chromatography–mass spectrometry. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each pollutant quartile using logistic regression. Estimates were further stratified by parity. Results: The median plasma concentration of PFOS was 13.0 ng/mL (interquartile range [IQR] = 10.3–16.6 ng/mL) and of PFOA was 2.2 ng/mL (IQR = 1.7–3.0 ng/mL). The relative odds of subfecundity among parous women was 2.1 (95% CI = 1.2–3.8) for the highest PFOS quartile and 2.1 (1.0–4.0) for the highest PFOA quartile. Among nulliparous women, the respective relative odds were 0.7 (0.4–1.3) and 0.5 (0.2–1.2). Conclusion: Previous studies suggest that the body burden of perfluorinated compounds decreases during pregnancy and lactation through transfer to the fetus and to breast milk. Afterward, the body burden may increase again. Among parous women, increased body burden may be due to a long interpregnancy interval rather than the cause of a long time to pregnancy. Therefore, data from nulliparous women may be more informative regarding toxic effects of perfluorinated compounds. Our results among nulliparous women did not support an association with subfecundity.
Direct-Current Stimulation Does Little to Improve the Outcome of Working Memory Training in Older Adults

The promise of transcranial direct-current stimulation (tDCS) as a modulator of cognition has appealed to researchers, media, and the general public. Researchers have suggested that tDCS may increase effects of cognitive training. In this study of 123 older adults, we examined the interactive effects of 20 sessions of anodal tDCS over the left prefrontal cortex (vs. sham tDCS) and simultaneous working memory training (vs. control training) on change in cognitive abilities. Stimulation did not modulate gains from pre- to posttest on latent factors of either trained or untrained tasks in a statistically significant manner. A supporting meta-analysis (n = 266), including younger as well as older individuals, showed that, when combined with training, tDCS was not much more effective than sham tDCS at changing working memory performance (g = 0.07, 95% confidence interval, or CI = [−0.21, 0.34]) and global cognition performance (g = −0.01, 95% CI = [−0.29, 0.26]) assessed in the absence of stimulation. These results question the general usefulness of current tDCS protocols for enhancing the effects of cognitive training on cognitive ability.
Total-Variation-Regularized Low-Rank Matrix Factorization for Hyperspectral Image Restoration

In this paper, we present a spatial spectral hyperspectral image (HSI) mixed-noise removal method named total variation (TV)-regularized low-rank matrix factorization (LRTV). In general, HSIs are not only assumed to lie in a low-rank subspace from the spectral perspective but also assumed to be piecewise smooth in the spatial dimension. The proposed method integrates the nuclear norm, TV regularization, and L1-norm together in a unified framework. The nuclear norm is used to exploit the spectral low-rank property, and the TV regularization is adopted to explore the spatial piecewise smooth structure of the HSI. At the same time, the sparse noise, which includes stripes, impulse noise, and dead pixels, is detected by the L1-norm regularization. To tradeoff the nuclear norm and TV regularization and to further remove the Gaussian noise of the HSI, we also restrict the rank of the clean image to be no larger than the number of endmembers. A number of experiments were conducted in both simulated and real data conditions to illustrate the performance of the proposed LRTV method for HSI restoration.
Autonomous, controlled and half-hearted. Unemployed people's motivations to seek information about jobs

Introduction. This article results from a qualitative case study focusing on the information seeking practices of unemployed people. The main attention was devoted to their motivations to seek information about jobs. Method. The empirical data were gathered in 2006 by semi-structured interviews with eighteen unemployed people in Finland. The study makes use of the categories of automomous motivation, controlled motivation and amotivation suggested by self-determination theory. Analysis. The interview data were examined by means of qualitative content analysis by constantly comparing the articulations of motivation of information seeking about jobs. Results. Information seeking drawing on autonomous motivation is experienced as interesting and spontaneously enjoyable because it is driven by personal interests and curiosity. Information seeking driven by controlled motivation is often found stressful since it aims at complying with internal demands and external requirements such as role expectations. Finally, characteristic of information seeking that draws on amotivation is a half-hearted in nature since it is pessimistically believed that information seeking will not yield desired outcomes. Conclusions. The categories of motivation identified by self-dermination theory provide a fruitful framework for the elaboration of the drivers of information seeking about jobs.
MFG‐E8 activates proliferation of vascular smooth muscle cells via integrin signaling

An accumulation of milk fat globule EGF‐8 protein (MFG‐E8) occurs within the context of arterial wall inflammatory remodeling during aging, hypertension, diabetes mellitus, or atherosclerosis. MFG‐E8 induces VSMC invasion, but whether it affects VSMC proliferation, a salient feature of arterial inflammation, is unknown. Here, we show that in the rat arterial wall in vivo, PCNA and Ki67, markers of cell cycle activation, increase with age between 8 and 30 months. In fresh and early passage VSMC isolated from old aortae, an increase in CDK4 and PCNA, an increase in the acceleration of cell cycle S and G2 phases, decrease in the G1/G0 phase, and an increase in PDGF and its receptors confer elevated proliferative capacity, compared to young VSMC. Increased coexpression and physical interaction of MFG‐E8 and integrin αvβ5 occur with aging in both the rat aortic wall in vivo and in VSMC in vitro. In young VSMC in vitro, MFG‐E8 added exogenously, or overexpressed endogenously, triggers phosphorylation of ERK1/2, augmented levels of PCNA and CDK4, increased BrdU incorporation, and promotes proliferation, via αvβ5 integrins. MFG‐E8 silencing, or its receptor inhibition, or the blockade of ERK1/2 phosphorylation in these cells reduces PCNA and CDK4 levels and decelerates the cell cycle S phase, conferring a reduction in proliferative capacity. Collectively, these results indicate that MFG‐E8 in a dose‐dependent manner coordinates the expression of cell cycle molecules and facilitates VSMC proliferation via integrin/ERK1/2 signaling. Thus, an increase in MFG‐E8 signaling is a mechanism of the age‐associated increase in aortic VSMC proliferation.
Quantifying Intracranial Internal Carotid Artery Stenosis on MR Angiography

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a common cause of ischemic stroke. Intracranial stenosis is most commonly quantified by the Warfarin-Aspirin Symptomatic Intracranial Disease method, which involves calculating a ratio of luminal diameter measurements on conventional angiography. Our purpose was to determine whether a single linear measurement of the narrowest caliber of the intracranial ICA on MRA can accurately predict Warfarin-Aspirin Symptomatic Intracranial Disease stenosis measurements. MATERIALS AND METHODS: We identified patients from a prospective stroke registry who had undergone head MRAs to quantitatively evaluate the degree of Warfarin-Aspirin Symptomatic Intracranial Disease–derived stenosis in each intracranial ICA. We also made a single linear millimeter measurement at the site of maximal narrowing of the ICA. We calculated a correlation coefficient between the lumen diameter in millimeters and percentage Warfarin-Aspirin Symptomatic Intracranial Disease stenosis. We performed receiver operating characteristic analysis to determine optimal luminal diameter cutoff values. RESULTS: In 386 unique intracranial ICAs, we found a strong linear relationship between single lumen measurements and Warfarin-Aspirin Symptomatic Intracranial Disease–style stenosis measurements (R = −0.84, P < .0001). We found that ICA lumen diameters of ≤2.1 and ≤1.3 mm were optimal cutoffs for identifying patients with ≥50% stenosis and ≥70% stenosis, respectively (area under the curve = 0.96 and 0.99, respectively). CONCLUSIONS: There is a strong linear relationship between the narrowest lumen diameter of the intracranial ICA and percentage stenosis. Our results suggest that a single lumen diameter measurement on MRA allows accurate estimation of Warfarin-Aspirin Symptomatic Intracranial Disease stenosis, which may affect risk stratification and treatment decisions.
Identification of TMPRSS3 as a Significant Contributor to Autosomal Recessive Hearing Loss in the Chinese Population

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To evaluate the importance of TMPRSS3 mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative TMPRSS3 mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation p.Ala306Thr is likely to be a founder mutation.
The interaction between parenting and children's cortisol reactivity at age 3 predicts increases in children's internalizing and externalizing symptoms at age 6

Abstract Little is known about the role of stress reactivity in the emergence of psychopathology across early childhood. In this longitudinal study, we tested the hypothesis that child cortisol reactivity at age 3 moderates associations between early parenting and children's internalizing and externalizing symptoms from age 3 to age 6. One hundred and sixty children were assessed at age 3, and 135 children were reassessed at age 6. At age 3, we exposed children to stress-inducing laboratory tasks, during which we obtained four salivary cortisol samples, and parental hostility was assessed using an observational parent–child interaction task. At ages 3 and 6, child psychiatric symptoms were assessed using a clinical interview with parents. The results indicated that the combination of high child cortisol reactivity and high observed parental hostility at age 3 was associated with greater concurrent externalizing symptoms at age 3 and predicted increases in internalizing and externalizing symptoms from age 3 to age 6. Findings highlight that increased stress reactivity, within the context of hostile parenting, plays a role in the emergence of psychopathology from preschool to school entry.
Fasting Plasma Sugar: A Predictor of Accommodative Function in Diabetes

Abstract Background: Diabetes has been associated with decline in accommodative function in some ethnic groups. This outcome, however, could differ since ethnic variations in accommodation have been noted. This study investigated the relationship between plasma sugar level on subjective accommodative amplitude and accommodative lag in black Africans with type-1 diabetes. Methods: An examiner-blind study of subjective accommodative amplitude and accommodative lag between 45 diabetic subjects (15 males, 30 females) aged 12–39 years and 45 age- and sex-matched healthy non-diabetic controls was conducted. Accommodative amplitude was measured by the push-up to blur/push-down to clear methods using a RAF rule, the accommodative lag by the MEM retinoscopy, and the fasting plasma sugar (FPS) by a glucose meter. Results: Comparatively, the diabetic subjects had significantly lower accommodative amplitude (10.1 ± 2.7 D versus 11.5 ± 2.4 D, respectively; p = 0.010) and greater accommodative lag (1.1 ± 0.4 D versus 0.7 ± 0.2 D; p < 0.001, respectively) than the controls. Multiple regression analyses showed that after adjusting for age, FPS concentration significantly predicted accommodative amplitude (R2 = 0.05, p = 0.022) and accommodative lag (R2 = 0.30, p < 0.001) in diabetes. Duration of diabetes was not significantly related to accommodative amplitude and accommodative lag. Conclusion: Diabetes mellitus in black Africans was associated with lower accommodative amplitude and greater accommodative lag. An adequate control of the plasma sugar concentration may be vital to maintain proper accommodative function.
UROLOGICAL ONCOLOGY: PROSTATE CANCER Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability

Editorial Comment: Recent data indicate that 15% of men with PSA levels less than 4 ng/ml have cancer and 15% of those men have Gleason scores of 7 or greater. How can these cancers be diagnosed? This important study shows that for men with PSA levels less than 4 ng/ml the yearly rate at which PSA levels change (PSA velocity) is a predictor of life threatening disease. For each 0.1 ng/ml per year increase in PSA the likelihood of death from prostate cancer increases 15%. For men with a consistent increase in PSA of 0.35 ng/ml per year or higher the relative risk of dying of prostate cancer is 5 times higher in the next 2 to 3 decades than for men with lower PSA rises. Today we realize that there are no PSA threshold levels that distinguish men with cancer from men without it. This study helps identify men with life threatening cancer and indicates that the use of PSA velocity provides an important alternative to the use of single PSA values as an indication for biopsy of all men. Carter et al also recommend that men begin PSA testing at age 40 because young men are less likely to have other prostate disease, eg benign prostatic hyperplasia, to confound the measurement. If their PSA is lower than the median for that age (0.6 ng/ml), they do not need a repeat PSA until they are 45 and 50. However, if the median PSA is above 0.6 ng/ml, then it should be checked every 2 years. By finding men in their 40s Carter et al believe that we can intervene when the cancer is more likely to be curable and when a man is less likely to have complications. Furthermore, PSA velocity can help identify men with slow growing cancers, who may not need any treatment. For men with PSA levels greater than 4 ng/ml the cutoff for PSA velocity is 0.75 ng/ml per year.
Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus‐positive gastric cancer

Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein–Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, nonantral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual‐level data on 2,648 gastric cancer patients, including 184 (7%) with EBV‐positive cancers; all studies had information on cigarette use (64% smokers) and nine had data on alcohol (57% drinkers). We compared patients with EBV‐positive and EBV‐negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within‐population clustering, multilevel logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal‐type), anatomic subsite (61% noncardia) and year of diagnosis (1983–2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 [95% confidence interval (CI) 1.6–3.2]. The OR was attenuated to 1.5 (95% CI 1.01–2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR 1.4; adjusted OR 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV‐positive than EBV‐negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV‐positive cancer further implicate the virus as a cofactor in gastric carcinogenesis.
Morphological and ultrastructural studies of human spermatogonial stem cells from patients with maturation arrest

Destruction of spermatogonial stem cells (SSCs) along the chemotherapy and radiotherapy is one of the side effects of cancer treatments that lead to infertility. In vitro propagation of hSSCs is necessary to obtain an adequate number of cells for successful transplantation. In this study, hSSCs were isolated from testis biopsies of the patients with maturation arrest and proliferated in DMEM in the presence of LIF and bFGF for 5 weeks. The various types of human spermatogonia were identified in culture system and compared with testis tissue using morphological criteria at the ultrastructural level. The results showed that although many various types of spermatogonia were identified, but no remarkable difference was observed between spermatogonial cells in culture system and testis tissue. Electron and light microscopic studies of hSSC colonies did not show differentiated SSCs in the culture system.
An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates

ABSTRACT The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the risk of HIV-1 infection. We have made several improvements to the DNA platform and have previously shown that improved DNA vaccines alone are capable of inducing both binding and neutralizing antibodies in small-animal models. In this study, we explored how an improved DNA prime and recombinant protein boost would impact HIV-specific vaccine immunogenicity in rhesus macaques (RhM). After DNA immunization with either a single HIV Env consensus sequence or multiple constructs expressing HIV subtype-specific Env consensus sequences, we detected both CD4+ and CD8+ T-cell responses to all vaccine immunogens. These T-cell responses were further increased after protein boosting to levels exceeding those of DNA-only or protein-only immunization. In addition, we observed antibodies that exhibited robust cross-clade binding and neutralizing and antibody-dependent cellular cytotoxicity (ADCC) activity after immunization with the DNA prime-protein boost regimen, with the multiple-Env formulation inducing a more robust and broader response than the single-Env formulation. The magnitude and functionality of these responses emphasize the strong priming effect improved DNA immunogens can induce, which are further expanded upon protein boost. These results support further study of an improved synthetic DNA prime together with a protein boost for enhancing anti-HIV immune responses. IMPORTANCE Even with effective antiretroviral drugs, HIV remains an enormous global health burden. Vaccine development has been problematic in part due to the high degree of diversity and poor immunogenicity of the HIV Env protein. Studies suggest that a relevant HIV vaccine will likely need to induce broad cellular and humoral responses from a simple vaccine regimen due to the resource-limited setting in which the HIV pandemic is most rampant. DNA vaccination lends itself well to increasing the amount of diversity included in a vaccine due to the ease of manufacturing multiple plasmids and formulating them as a single immunization. By increasing the number of Envs within a formulation, we were able to show an increased breadth of responses as well as improved functionality induced in a nonhuman primate model. This increased breadth could be built upon, leading to better coverage against circulating strains with broader vaccine-induced protection.
Assessment of concordance between fresh-frozen and formalin-fixed paraffin embedded tumor DNA methylation using a targeted sequencing approach

DNA methylation is altered in many types of disease, including metastatic colorectal cancer. However, the methylome has not yet been fully described in archival formalin-fixed paraffin embedded (FFPE) samples in the context of matched fresh-frozen (FF) tumor material at base-pair resolution using a targeted approach. Using next-generation sequencing, we investigated three pairs of matched FFPE and FF samples to determine the extent of their similarity. We identified a ‘bowing’ pattern specific to FFPE samples categorized by a lower CG proportion at the start of sequence reads. We have found no evidence that this affected methylation calling, nor concordance of results. We also found no significant increase in deamination, measured by C>T transitions, previously considered a result of crosslinking DNA by formalin fixation and a barrier to the use of FFPE in methylation studies. The methods used in this study have shown sensitivity of between 60-70% based on positions also methylated in colorectal cancer cell lines. We demonstrate that FFPE material is a useful source of tumor material for methylation studies using targeted sequencing.
Stability and morphology of cerium oxide surfaces in an oxidizing environment: A first-principles investigation

We present density functional theory investigations of the bulk properties of cerium oxides (CeO2 and Ce2O3) and the three low index surfaces of CeO2, namely, (100), (110), and (111). For the surfaces, we consider various terminations including surface defects. Using the approach of “ab initio atomistic thermodynamics,” we find that the most stable surface structure considered is the stoichiometric (111) surface under “oxygen-rich” conditions, while for a more reducing environment, the same (111) surface, but with subsurface oxygen vacancies, is found to be the most stable one, and for a highly reducing environment, the (111) Ce-terminated surface becomes energetically favored. Interestingly, this latter surface exhibits a significant reconstruction in that it becomes oxygen terminated and the upper layers resemble the Ce2O3(0001) surface. This structure could represent a precursor to the phase transition of CeO2 to Ce2O3.