Miracle-dz/UniFAR-FTUs huggingface dataset:
Expanding Epigenomics to Archived FFPE Tissues: An Evaluation of DNA Repair Methodologies

Background: Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from flash frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) tissues have emerged; however, a direct comparison of FFPE DNA repair methods before analysis on genome-wide methylation array to matched FF tissues has not been conducted. Methods: We conducted a systematic performance comparison of two DNA repair methods (REPLI-g Ligase vs. Infinium HD Restore Kit) on FFPE-DNA compared with matched FF tissues on the Infinium 450K array. A threshold of discordant methylation between FF-FFPE pairs was set at Δβ > 0.3. The correlations of β-values from FF–FFPE pairs were compared across methods and experimental conditions. Results: The Illumina Restore kit outperformed the REPLI-g ligation method with respect to reproducibility of replicates (R2 > 0.970), highly correlated β-values between FF-FFPE (R2 > 0.888), and fewest discordant loci between FF-FFPE (≤0.61%). The performance of the Restore kit was validated in an independent set of 121 FFPE tissues. Conclusions: The Restore kit outperformed RELPI-g ligation in restoring FFPE-derived DNA before analysis on the Infinium 450K methylation array. Our findings provide critical guidance that may significantly enhance the breadth of diseases that can be studied by methylomic profiling. Impact: Epigenomic studies using FFPE tissues should now be considered among cancers that have not been fully characterized from an epigenomic standpoint. These findings promote novel epigenome-wide studies focused on cancer etiology, identification of novel biomarkers, and developing targeted therapies. See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology. ” Cancer Epidemiol Biomarkers Prev; 23(12); 2622–31. ©2014 AACR.
Different in vitro exposure regimens of murine primary macrophages to silver nanoparticles induce different fates of nanoparticles and different toxicological and functional consequences

Abstract Silver nanoparticles (Ag-NPs) are used in a variety of consumers’ goods. Their toxicological impact is currently intensely studied, mostly upon acute exposure, but their intracellular dissolution and fate is rather poorly documented. In this study, murine primary macrophages were exposed to a single high but non-lethal dose of Ag-NPs or to repeated, low doses of Ag-NPs. Cells were either collected immediately after acute exposure or after 72 h of recovery in the NP-free exposure medium. Ag intracellular content and distribution were analyzed by particle-induced X-ray emission, transmission electron microscopy coupled to energy-dispersive spectroscopy analysis and inductively coupled plasma mass spectrometry. In parallel, macrophage functionality as well as inflammatory and thiol-responses were assessed after Ag-NP exposure. We show that Ag accumulation in macrophages is similar upon acute and repeated exposure to Ag-NPs, and that Ag is partly expelled from cells during the 72 h recovery stage. However, acute exposure leads to a strong response of macrophages, characterized by reduced mitochondrial membrane potential, phagocytic capacity and nitric oxide (NO) production upon lipopolysaccharide (LPS) stimulation. Under this condition, we also show an increased release of proinflammatory cytokines as well as a decreased release of anti-inflammatory cytokines. This response is reversible since these biomarkers reach their basal level after the recovery phase; and is much less intense in repeatedly exposed cells. These results suggest that repeated exposure of macrophages to Ag-NPs, which is a more realistic exposure scenario than acute exposure, leads to significant Ag intracellular accumulation but a much less intense toxicological response.
Functional criticality in the human brain: Physiological, behavioral and neurodevelopmental correlates

Understanding the critical features of the human brain at multiple time scales is vital for both normal development and disease research. A recently proposed method, the vertex-wise Index of Functional Criticality (vIFC) based on fMRI, has been testified as a sensitive neuroimaging marker to characterize critical transitions of human brain dynamics during Alzheimer’s disease progression. However, it remains unclear whether vIFC in healthy brains is associated with neuropsychological and neurophysiological measurements. Using the Nathan Kline Institute/Rockland lifespan cross-sectional datasets and openfMRI single participant longitudinal datasets, we found consistent spatial patterns of vIFC across the entire cortical mantle: the inferior parietal and the precuneus exhibited high vIFC. On a time scale of years, we observed that vIFC increased with age in the left ventral posterior cingulate gyrus. On a time scale of days and weeks, vIFC demonstrated the capacity to identify a link between anxiety and pulse. These results showed that vIFC can serve as a useful neuroimaging marker for detecting physiological, behavioral, and neurodevelopmental transitions. Based on the criticality theory in nonlinear dynamics, the current vIFC study sheds new light on human brain studies from a nonlinear perspective and opens potential new avenues for normal and abnormal human brain studies.
2D gel electrophoresis reveals dynamics of t-loop formation during the cell cycle and t-loop in maintenance regulated by heterochromatin state

Linear chromosome ends are capped by telomeres that have been previously reported to adopt a t-loop structure. The lack of simple methods for detecting t-loops has hindered progress in understanding the dynamics of t-loop formation and its function in protecting chromosome ends. Here, we employed a classical two-dimensional agarose gel method (2D gel method) to innovatively apply to t-loop detection. Briefly, restriction fragments of genomic DNA were separated in a 2D gel, and the telomere sequence was detected by in-gel hybridization with telomeric probe. Using this method, we found that t-loops are present throughout the cell cycle, and t-loop formation tightly couples to telomere replication. We also observed that t-loop abundance positively correlates with chromatin condensation, i.e. cells with less compact telomeric chromatin (ALT cells and trichostatin A (TSA)-treated HeLa cells) exhibited fewer t-loops. Moreover, we observed that telomere dysfunction-induced foci, ALT-associated promyelocytic leukemia bodies, and telomere sister chromatid exchanges are activated upon TSA-induced loss of t-loops. These findings confirm the importance of the t-loop in protecting linear chromosomes from damage or illegitimate recombination.
Knockdown of CABYR-a/b Increases Chemosensitivity of Human Non–Small Cell Lung Cancer Cells through Inactivation of Akt

CABYR is a calcium-binding tyrosine phosphorylation–regulated protein that was identified as a novel cancer testis antigen in lung cancer in our previous study. However, the role of CABYR as a driver of disease progression or as a chemosensitizer is poorly understood. This study sought to investigate the relationship between the expression levels of CABYR-a/b, which are the two predominant isoforms of the five isoform proteins encoded by CABYR, and chemosensitivity in non–small cell lung cancer cells. We found that the short hairpin RNA–mediated knockdown of CABYR-a/b significantly inhibited the proliferation of NCI-H460 and A549 cells and resulted in the attenuation of Akt phosphorylation, which is constitutively active in lung cancer cells. The silencing of CABYR-a/b expression notably impacted the downstream components of the Akt pathways: decreasing the phospho-GSK-3β (Ser9) levels and increasing the expression of the p53 and p27 proteins. Furthermore, CABYR-a/b knockdown led to a significant increase in chemosensitivity in response to chemotherapeutic drugs and drug-induced apoptosis, both in vitro and in vivo. Conversely, the transient transfection of CABYR-a/b–depleted cells with constitutively active Akt partially restored the resistance to cisplatin and paclitaxel and significantly decreased the activation of GSK-3β and cleaved PARP. Taken together, our results suggest that the inhibition of CABYR-a/b is a novel method to improve the apoptotic response and chemosensitivity in lung cancer and that this cancer testis antigen is an attractive target for lung cancer drug development. Implications: Suppression of CABYR-a/b expression increases chemosensitivity of lung cancer cells by inhibiting Akt activity. Mol Cancer Res; 12(3); 335–47. ©2013 AACR.
Reactive Species Interactome Alterations in Oocyte Donation Pregnancies in the Absence and Presence of Pre-Eclampsia

In pregnancy, maternal physiology is subject to considerable adaptations, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus. In an oocyte donation pregnancy, the fetus is fully allogeneic towards the mother, since it carries both oocyte donor antigens and paternal antigens. Therefore, oocyte donation pregnancies result in an immunologically challenging pregnancy, which is reflected by a higher-than-normal risk to develop pre-eclampsia. Based on the allogeneic conditions in oocyte donation pregnancies, we hypothesized that this situation may translate into alterations in concentration of stable readouts of constituents of the reactive species interactome (RSI) compared to normal pregnancies, especially serum free thiols, nitric oxide (NO) and hydrogen sulfide (H2S) related metabolites. Indeed, total free thiol levels and nitrite (NO2−) concentrations were significantly lower whereas protein-bound NO and sulfate (SO42−) concentrations were significantly higher in both oocyte donation and naturally conceived pregnancies complicated by pre-eclampsia. The increased concentrations of nitrite observed in uncomplicated oocyte donation pregnancies suggest that endothelial NO production is compensatorily enhanced to lower vascular tone. More research is warranted on the role of the RSI and bioenergetic status in uncomplicated oocyte donation pregnancies and oocyte donation pregnancies complicated by pre-eclampsia.
Alcohol, Age, and Mortality: Estimating Selection Bias Due to Premature Death.

OBJECTIVE Alcohol use causes approximately 10% of deaths among adults ages 20-65 in the United States. Although previous research has demonstrated differential age-related risk relationships, it is difficult to estimate the magnitude of selection bias attributable to premature mortality based on existing cohort studies, the average age of which is greater than 50 years. The objective of our study was to assess the distribution of mortality-related harms and benefits from alcohol among adults ages 20 and older in comparison with the distribution among those older than age 50. METHOD Data from the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact software application from 2006-10 were used to determine the distribution of alcohol-attributable deaths (AADs) and the years of potential life lost (YPLLs) that was caused or prevented by alcohol for 54 conditions by 15-year age groupings (20-34, 35-49, 50-64, 65+) in the United States. We also determined the proportion of net deaths and YPLLs occurring in each age group, overall and by cause of death. RESULTS Adults ages 20-49 years experienced 35.8% of the deaths and 58.4% of the YPLLs caused by alcohol, whereas the same group accrued only 4.5% of AADs and 14.2% of YPLLs gained. Overall, 46.3% of the total net deaths and 64.7% of the net YPLLs occurred among those ages 20-49; adding net deaths occurring among those ages 20-49 to those occurring after age 50 would result in an 86.3% relative increase in net deaths. CONCLUSIONS Because of premature mortality, alcohol-mortality associations based on cohort studies may underestimate negative health consequences compared with those observed among the general population.
“Nine Dimensions”: A multidisciplinary approach for community engagement in a complex postwar border region as part of the targeted malaria elimination in Karen/Kayin State, Myanmar [version 2; peer review: 2 approved]

Background: In light of growing antimalarial drug resistance in Southeast Asia, control programmes have become increasingly focused on malaria elimination, composed of mass drug administration coupled with prompt diagnosis and treatment of symptomatic cases. The key to a successful elimination programme centres on high participation rates in targeted communities, often enhanced by community engagement (CE) efforts. Social science research was conducted to develop a conceptual framework used for CE activities in the Targeted Malaria Elimination programme, as a cross-border operation in Karen/Kayin State, Myanmar. Methods: Data was collected from three main sources: (1) participant observation and semi-structured interviews of CE team members; (2) participant observation and semi-structured interviews with villagers; and (3) records of CE workshops with CE workers conducted as part of the TME programme. Results: Interviews were conducted with 17 CE team members, with 10 participant observations and interviews conducted with villagers and a total of 3 workshops conducted over the course of this pilot Open Peer Review
Improving In-Situ Estimation of Soil Profile Properties Using a Multi-Sensor Probe

Optical diffuse reflectance spectroscopy (DRS) has been used for estimating soil physical and chemical properties in the laboratory. In-situ DRS measurements offer the potential for rapid, reliable, non-destructive, and low cost measurement of soil properties in the field. In this study, conducted on two central Missouri fields in 2016, a commercial soil profile instrument, the Veris P4000, acquired visible and near-infrared (VNIR) spectra (343–2222 nm), apparent electrical conductivity (ECa), cone index (CI) penetrometer readings, and depth data, simultaneously to a 1 m depth using a vertical probe. Simultaneously, soil core samples were obtained and soil properties were measured in the laboratory. Soil properties were estimated using VNIR spectra alone and in combination with depth, ECa, and CI (DECS). Estimated soil properties included soil organic carbon (SOC), total nitrogen (TN), moisture, soil texture (clay, silt, and sand), cation exchange capacity (CEC), calcium (Ca), magnesium (Mg), potassium (K), and pH. Multiple preprocessing techniques and calibration methods were applied to the spectral data and evaluated. Calibration methods included partial least squares regression (PLSR), neural networks, regression trees, and random forests. For most soil properties, the best model performance was obtained with the combination of preprocessing with a Gaussian smoothing filter and analysis by PLSR. In addition, DECS improved estimation of silt, sand, CEC, Ca, and Mg over VNIR spectra alone; however, the improvement was more than 5% only for Ca. Finally, differences in estimation accuracy were observed between the two fields despite them having similar soils, with one field demonstrating better results for all soil properties except silt. Overall, this study demonstrates the potential for in-situ estimation of profile soil properties using a multi-sensor approach, and provides suggestions regarding the best combination of sensors, preprocessing, and modeling techniques for in-situ estimation of profile soil properties.
Task Scheduling Based on a Hybrid Heuristic Algorithm for Smart Production Line with Fog Computing

Fog computing provides computation, storage and network services for smart manufacturing. However, in a smart factory, the task requests, terminal devices and fog nodes have very strong heterogeneity, such as the different task characteristics of terminal equipment: fault detection tasks have high real-time demands; production scheduling tasks require a large amount of calculation; inventory management tasks require a vast amount of storage space, and so on. In addition, the fog nodes have different processing abilities, such that strong fog nodes with considerable computing resources can help terminal equipment to complete the complex task processing, such as manufacturing inspection, fault detection, state analysis of devices, and so on. In this setting, a new problem has appeared, that is, determining how to perform task scheduling among the different fog nodes to minimize the delay and energy consumption as well as improve the smart manufacturing performance metrics, such as production efficiency, product quality and equipment utilization rate. Therefore, this paper studies the task scheduling strategy in the fog computing scenario. A task scheduling strategy based on a hybrid heuristic (HH) algorithm is proposed that mainly solves the problem of terminal devices with limited computing resources and high energy consumption and makes the scheme feasible for real-time and efficient processing tasks of terminal devices. Finally, the experimental results show that the proposed strategy achieves superior performance compared to other strategies.
Teacher Perspectives on Indicators of Adolescent Social and Emotional Problems

ABSTRACT Teachers are a primary source of referral to mental health services for children and adolescents. However, studies find that students identified by teachers differ from those identified by standardized screening scales. This suggests possible discrepancies in conceptualizations of student emotional and behavioral challenges. The current article describes results of a study that explores how teachers conceptualize the emotional and behavioral challenges of adolescents. Middle and high school teachers across the United States were identified using a stratified random sampling process and recruited for participation. Twenty-nine teachers (26% of those recruited) were interviewed and asked to describe markers that indicated to them that a student was experiencing emotional and behavioral challenges. Themes in teacher responses were identified and coded. Teachers identified multiple, diverse markers that they perceived were indicators of emotional and behavioral challenges among their students. Markers described by teachers were compared to those typically measured by standardized screening scales. Discrepancies between markers identified by teachers and screening scales are highlighted as potential areas for professional development and enhanced school-based intervention efforts. These findings underscore the importance of integrating teacher perspectives in understanding the referral process for students.
Clinicopathological factors associated with BRAF‐V600E mutation in colorectal serrated adenomas

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF‐V600E mutation in serrated adenomas. Systematic review and meta‐analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF‐V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P‐value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. BRAF‐V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP‐H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II‐O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear β‐catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAF‐V600E mutation is associated with proximal localisation and CIMP‐H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II‐O at least in SSA. In serrated adenomas, BRAF‐V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.
Understanding the Complexity of Iron Sensing and Signaling Cascades in Plants.

Under iron-deficient conditions, plants induce the expression of a set of genes involved in iron uptake and translocation. This response to iron deficiency is regulated by transcriptional networks mediated by transcription factors and protein-level modification of key factors by ubiquitin ligases. Several of the basic helix-loop-helix transcription factors and the HRZ/BTS ubiquitin ligases are conserved across graminaceous and non-graminaceous plants. Other regulators are specific, such as IDEF1 and IDEF2 in graminaceous plants and FIT/FER and MYB10/72 in non-graminaceous plants. IMA/FEP peptides positively regulate the iron-deficiency responses in a wide range of plants by unknown mechanisms. Direct binding of iron or other metals to some key regulators, including HRZ/BTS and IDEF1, may be responsible for intracellular iron-sensing and -signaling events. In addition, key transcription factors such as FIT and IDEF1 interact with various proteins involved in signaling pathways of plant hormones, oxidative stress and metal abundance. Thus, FIT and IDEF1 might function as hubs for the integration of environmental signals to modulate the responses to iron deficiency. In addition to local iron signaling, root iron responses are modulated by shoot-derived long-distance signaling potentially mediated by phloem-mobile substances such as iron, iron chelates and IMA/FEP peptides.
The temporal association between substance use and intimate partner violence among women arrested for domestic violence.

OBJECTIVE There is a paucity of research on the temporal association between substance use and intimate partner violence (IPV) perpetration and victimization, especially among women arrested for domestic violence. The current study examined whether the probability of IPV perpetration and victimization increases following alcohol or drug use relative to days of no use among women arrested for domestic violence. METHOD Women arrested for domestic violence and court referred to batterer intervention programs who met criteria for hazardous drinking participated in the current study (N = 105). Women who reported drinking 4 or more drinks on 1 occasion at least once per month for the past 6 months were considered hazardous drinkers. Violence and substance use were assessed with the Timeline Followback Interviews for substance use and IPV. RESULTS Women were more likely to perpetrate physical violence on a drinking day (OR = 10.58; 95% CI [5.38, 20.79]) and on a heavy drinking day (OR = 12.81; 95% CI [8.10, 33.57]), relative to a nondrinking day. Women were more likely to be victimized by physical violence on a drinking day (OR = 5.22; 95% CI [2.79, 9.77]) and on a heavy drinking day (OR = 6.16; 95% CI [3.25, 11.68]), relative to a nondrinking day. They were more likely to be victims of sexual coercion (OR = 6.06; 95% CI [1.19, 30.80]) on a cocaine use day relative to a nonuse day. CONCLUSIONS Alcohol use was temporally associated with physical violence perpetration and victimization, and cocaine use was temporally associated with sexual coercion victimization, suggesting that substance use should be targeted in batterer intervention programs for women.