Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying survival associated morphological features of triple negative breast cancer using multiple datasets

Background and objective Biomarkers for subtyping triple negative breast cancer (TNBC) are needed given the absence of responsive therapy and relatively poor prediction of survival. Morphology of cancer tissues is widely used in clinical practice for stratifying cancer patients, while genomic data are highly effective to classify cancer patients into subgroups. Thus integration of both morphological and genomic data is a promising approach in discovering new biomarkers for cancer outcome prediction. Here we propose a workflow for analyzing histopathological images and integrate them with genomic data for discovering biomarkers for TNBC. Materials and methods We developed an image analysis workflow for extracting a large collection of morphological features and deployed the same on histological images from The Cancer Genome Atlas (TCGA) TNBC samples during the discovery phase (n=44). Strong correlations between salient morphological features and gene expression profiles from the same patients were identified. We then evaluated the same morphological features in predicting survival using a local TNBC cohort (n=143). We further tested the predictive power on patient prognosis of correlated gene clusters using two other public gene expression datasets. Results and conclusion Using TCGA data, we identified 48 pairs of significantly correlated morphological features and gene clusters; four morphological features were able to separate the local cohort with significantly different survival outcomes. Gene clusters correlated with these four morphological features further proved to be effective in predicting patient survival using multiple public gene expression datasets. These results suggest the efficacy of our workflow and demonstrate that integrative analysis holds promise for discovering biomarkers of complex diseases.
Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice

Background Corticosteroid hormones regulate appraisal and consolidation of information via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) respectively. How activation of these receptors modulates retrieval of fearful information and the subsequent expression of fear is largely unknown. We tested here whether blockade of MRs or GRs during retrieval also affects subsequent expression of fear memory. Methodology/Principal Findings Mice were trained in contextual or tone cue fear conditioning paradigms, by pairing mild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals were re-exposed to the context for 3 or 30 minutes (day 2); tone-conditioned animals were placed in a different context and re-exposed to one or six tones. Twenty-four hours (day 3) and one month later, freezing behavior to the aversive context/tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour before retrieval on day 2. Spironolactone administered prior to brief context re-exposure reduced freezing behavior during retrieval and 24 hours later, but not one month later. Administration of spironolactone without retrieval of the context or immediately after retrieval on day 2 did not reduce freezing on day 3. Re-exposure to the context for 30 minutes on day 2 significantly reduced freezing on day 3 and one month later, but freezing was not further reduced by spironolactone. Administration of spironolactone prior to tone-cue re-exposure on day 2 did not affect freezing behavior. Treatment with RU486 prior to re-exposure did not affect context or tone-cue fear memories at any time point. Conclusions/Significance We conclude that MR blockade prior to retrieval strongly reduces the expression of contextual fear, implying that MRs, rather than GRs, play an important role in retrieval of emotional information and subsequent fear expression.
Possible impacts of a future grand solar minimum on climate: Stratospheric and global circulation changes

It has been suggested that the Sun may evolve into a period of lower activity over the 21st century. This study examines the potential climate impacts of the onset of an extreme “Maunder Minimum‐like” grand solar minimum using a comprehensive global climate model. Over the second half of the 21st century, the scenario assumes a decrease in total solar irradiance of 0.12% compared to a reference Representative Concentration Pathway 8.5 experiment. The decrease in solar irradiance cools the stratopause (∼1 hPa) in the annual and global mean by 1.2 K. The impact on global mean near‐surface temperature is small (∼−0.1 K), but larger changes in regional climate occur during the stratospheric dynamically active seasons. In Northern Hemisphere wintertime, there is a weakening of the stratospheric westerly jet by up to ∼3–4 m s−1, with the largest changes occurring in January–February. This is accompanied by a deepening of the Aleutian Low at the surface and an increase in blocking over Northern Europe and the North Pacific. There is also an equatorward shift in the Southern Hemisphere midlatitude eddy‐driven jet in austral spring. The occurrence of an amplified regional response during winter and spring suggests a contribution from a top‐down pathway for solar‐climate coupling; this is tested using an experiment in which ultraviolet (200–320 nm) radiation is decreased in isolation of other changes. The results show that a large decline in solar activity over the 21st century could have important impacts on the stratosphere and regional surface climate.
Holistic approach to prevention and management of type 2 diabetes mellitus in a family setting

Diabetes mellitus (DM) is a chronic, progressive metabolic disorder with several complications that affect virtually all the systems in the human body. Type 2 DM (T2DM) is a major risk factor for cardiovascular disease (CVD). The management of T2DM is multifactorial, taking into account other major modifiable risk factors, like obesity, physical inactivity, smoking, blood pressure, and dyslipidemia. A multidisciplinary team is essential to maximize the care of individuals with DM. DM self-management education and patient-centered care are the cornerstones of management in addition to effective lifestyle strategies and pharmacotherapy with individualization of glycemic goals. Robust evidence supports the effectiveness of this approach when implemented. Individuals with DM and their family members usually share a common lifestyle that, not only predisposes the non-DM members to developing DM but also, increases their collective risk for CVD. In treating DM, involvement of the entire family, not only improves the care of the DM individual but also, helps to prevent the risk of developing DM in the family members.
Large-scale analysis and forecast experiments with wind data from the Seasat A scatterometer

A series of data assimilation experiments is performed to assess the impact of Seasat A satellite scatterometer (SASS) wind data on Goddard Laboratory for Atmospheric Sciences (GLAS) model forecasts. The SASS data are dealiased as part of an objective analysis system utilizing a three-pass procedure. The impact of the SASS data is evaluated with and without temperature soundings from the NOAA 4 Vertical Temperature Profile Radiometer (VTPR) instrument in order to study possible redundancy between surface wind data and upper air temperature data. In the northern hemisphere the SASS data are generally found to have a negligible effect on the forecasts. In the southern hemisphere the forecast impact from SASS data is somewhat larger and primarily beneficial in the absence of VTPR data. However, the inclusion of VTPR data effectively eliminates the positive impact over Australia and South America. This indicates that SASS data can be beneficial for numerical weather prediction in regions with large data gaps, but in the presence of satellite soundings the usefulness of SASS data is significantly reduced.
Sexual risk among orphaned adolescents: is country-level HIV prevalence an important factor?

Abstract Previous studies from sub-Saharan Africa have found that orphans experience increased sexual risk compared to non-orphans. We developed a theoretical framework for the investigation of determinants of HIV risk and used it to generate specific hypotheses regarding the effect of country-level HIV prevalence on the sexual risk experience of orphans. We expected that countries with high HIV prevalence would experience a higher prevalence of orphanhood. We further hypothesised that orphans in countries with high HIV prevalence would experience increased sexual risk, compared to non-orphans, due to pressure on the extended family network, which is primarily responsible for the care of orphans in sub-Saharan Africa, resulting in poorer standards of care and guidance. We used hierarchical logistic regression models to investigate this hypothesis using cross-sectional, Demographic and Health Survey data from 10 sub-Saharan African countries. We found that countries with high HIV prevalence did indeed have higher prevalence of orphanhood. We also found that, amongst female adolescents, maternal and double orphans were significantly more likely to have started sex than non-orphans in countries with high HIV prevalence but were not at increased risk in low HIV prevalence countries. This effect of country-level HIV prevalence on the sexual risk of orphans was not explained by household level factors such as wealth, overcrowding or age of the household head. The same pattern of risk was not observed for male adolescents – male orphans were not more likely to have started sex than non-orphans. This suggests that orphaned adolescent women are an important target group for HIV prevention and that efforts should be made to integrate prevention messages into existing support programmes for orphans and vulnerable children.
Climate‐induced changes in biome distribution, NPP, and hydrology in the Upper Midwest U.S.: A case study for potential vegetation

We investigated the impacts of recent climate change on potential vegetation distributions and carbon and water cycling across the Upper Midwest from 1948 to 2007. We used the Agro‐IBIS dynamic vegetation model driven by a newly developed gridded daily climate data set at 5 min × 5 min spatial resolution. Trends in climate variables were spatially heterogeneous over the study period and were associated with an overall increase in net primary productivity (NPP). We observed an average regional change in total NPP of 41 ± 30 g C m−2 (8%). Increased summer relative humidity and increased annual precipitation were key variables contributing to the positive trends. Mechanisms for increased productivity included a reduction in soil moisture stress as well as increased stomatal conductance resulting from an increase in summertime humidity. Model simulations also showed an average total increase in annual groundwater recharge throughout the region of 39 ± 35 mm (45%) driven by increases in annual precipitation. Evapotranspiration had a highly variable spatial trend over the 60 year period, with an average total change of 5 ± 21 mm (1%) across all grid cells. The location of the Tension Zone, a broad ecotone dividing northern mixed forests and southern hardwood forests and prairies, was not observed to migrate using analysis of meteorological variables.
Geologic Setting of the Snake River Plain Aquifer and Vadose Zone

The Snake River Plain aquifer owes its existence and abundance to a unique sequence of tectonic, volcanic, and sedimentologic processes associated with the migration of the North American tectonic plate southwestward across the Yellowstone hotspot, or mantle plume. The basalt lava flows that host the aquifer and comprise the overlying vadose zone are very porous and permeable due to emplacement processes and fracturing during cooling. Rubble zones between lava flows and cooling fractures allow very rapid flow of water in the saturated zone, rapid infiltration of water and contaminants, and deep penetration of air into the vadose zone. Alluvial, eolian, and lacustrine sediments interbedded within the basalt sequence are generally fine‐grained, commonly serving as aquitards below the water table, and affecting infiltration and contaminant transport in the vadose zone. The subsiding eastern Snake River Plain (ESRP) and the high elevations of the surrounding recharge areas comprise a large drainage basin that receives enormous amounts of precipitation and feeds high‐quality groundwater into the aquifer. Northeast–southwest directed extension of the ESRP produces significant anisotropy to the hydraulic conductivity of the rocks. High heat flow and upwelling of geothermal fluids from the crust beneath the aquifer affect geothermal gradients, aquifer temperatures, and solute chemistry.
Thaw Settlement Hazard of Permafrost Related to Climate Warming in Alaska

Permafrost temperatures have increased in Alaska since the 1960s, and many impacts of climate warming are associated with permafrost thaw. Thaw of permafrost caused by increases in permafrost temperature may result in thaw settlement and significant damage to infrastructure. The goal of this research is to identify regions of Alaska at risk from thaw subsidence related to climate warming and to determine the relative risk of those regions. We developed a Permafrost Settlement Hazard Index (PSHI) by analyzing anticipated climate warming and the ecological characteristics that regulate thaw subsidence. This analysis provides statistical verification that the discontinuous permafrost region is at more risk of thaw settlement than other regions of Alaska. In addition, it estimates future thaw subsidence risk in Alaska in 2050 using future temperature increases projected by published climate models. Results indicate increased thaw subsidence risk in northern Alaska in 2050, with the greatest increase expected in parts of northwest Alaska. However, in the interior and southwest Alaska, projected disappearance of permafrost from the surface will reduce the risk of thaw subsidence.
Increasing Viscosity Helps Explain Locomotor Control in Swimming Polypterus senegalus

Synopsis Locomotion relies on the successful integration of sensory information to adjust brain commands and basic motor rhythms created by central pattern generators. It is not clearly understood how altering the sensory environment impacts control of locomotion. In an aquatic environment, mechanical sensory feedback to the animal can be readily altered by adjusting water viscosity. Computer modeling of fish swimming systems shows that, without sensory feedback, high viscosity systems dampen kinematic output despite similar motor control input. We recorded muscle activity and kinematics of six Polypterus senegalus in four different viscosities of water from 1 cP (normal water) to 40 cP. In high viscosity, P. senegalus exhibit increased body curvature, body wave speed, and body and pectoral fin frequency during swimming. These changes are the result of increased muscle activation intensity and maintain voluntary swimming speed. Unlike the sensory-deprived model, intact sensory feedback allows fish to adjust swimming motor control and kinematic output in high viscous water but maintain typical swimming coordination.
mDia1 regulates breast cancer invasion by controlling membrane type 1-matrix metalloproteinase localization

Mammalian diaphanous-related formin 1 (mDia1) expression has been linked with progression of malignant cancers in various tissues. However, the precise molecular mechanism underlying mDia1-mediated invasion in cancer cells has not been fully elucidated. In this study, we found that mDia1 is upregulated in invasive breast cancer cells. Knockdown of mDia1 in invasive breast cancer profoundly reduced invasive activity by controlling cellular localization of membrane type 1-matrix metalloproteinase (MT1-MMP) through interaction with microtubule tracks. Gene silencing and ectopic expression of the active form of mDia1 showed that mDia1 plays a key role in the intracellular trafficking of MT1-MMP to the plasma membrane through microtubules. We also demonstrated that highly invasive breast cancer cells possessed invasive activity in a 3D culture system, which was significantly reduced upon silencing mDia1 or MT1-MMP. Furthermore, mDia1-deficient cells cultured in 3D matrix showed impaired expression of the cancer stem cell marker genes, CD44 and CD133. Collectively, our findings suggest that regulation of cellular trafficking and microtubule-mediated localization of MT1-MMP by mDia1 is likely important in breast cancer invasion through the expression of cancer stem cell genes.
Clinical, Immunological, and Molecular Heterogeneity of 173 Patients With the Phenotype of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome

Background: Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) Syndrome is a rare recessive disorder caused by mutations in the FOXP3 gene. In addition, there has been an increasing number of patients with wild-type FOXP3 gene and, in some cases, mutations in other immune regulatory genes. Objective: To molecularly asses a cohort of 173 patients with the IPEX phenotype and to delineate the relationship between the clinical/immunologic phenotypes and the genotypes. Methods: We reviewed the clinical presentation and laboratory characteristics of each patient and compared clinical and laboratory data of FOXP3 mutation-positive (IPEX patients) with those from FOXP3 mutation-negative patients (IPEX-like). A total of 173 affected patients underwent direct sequence analysis of the FOXP3 gene while 85 IPEX-like patients with normal FOXP3 were investigated by a multiplex panel of “Primary Immune Deficiency (PID—related) genes. ” Results: Forty-four distinct FOXP3 variants were identified in 88 IPEX patients, 9 of which were not previously reported. Among the 85 IPEX-like patients, 19 different disease-associated variants affecting 9 distinct genes were identified. Conclusions: We provide a comprehensive analysis of the clinical features and molecular bases of IPEX and IPEX-like patients. Although we were not able to identify major distinctive clinical features to differentiate IPEX from IPEX-like syndromes, we propose a simple flow-chart to effectively evaluate such patients and to focus on the most likely molecular diagnosis. Given the large number of potential candidate genes and overlapping phenotypes, selecting a panel of PID-related genes will facilitate a molecular diagnosis.
Worth of Inflow Forecast for Reservoir Operation

This study assesses improved benefits that might be gained from the use of long-range streamflow forecasts in the operation of a typical multipurpose reservoir. Long-range is defined as a period of time ranging from one month to one year. The Oroville-Thermalito reservoir system of the California State Water Project (SWP) is selected for study; major benefits to be derived from long-term streamflow prediction for this system are hydropower generation, water conservation for irrigation and/or other beneficial uses, and decreased seepage damage to crops. Flood control benefits are potentially high but those benefits are more amenable to short-term rather than long-term forecasting. Incremental benefits are determined as functions of forecast time and accuracy on the basis of general adherence to current operating rules. The reservoir is theoretically operated over the 1914-73 time period; forecasts and comparisons are based on the historical streamflows. Procedure failure is defined as inability to meet a minimum storage constraint at any time over the 60-year period. To provide an additional evaluation of benefits from forecasting, analyses are also made using the historical means as estimates of future streamflows.
Functional diversification of the GALA type III effector family contributes to Ralstonia solanacearum adaptation on different plant hosts

Type III effectors from phytopathogenic bacteria exhibit a high degree of functional redundancy, hampering the evaluation of their precise contribution to pathogenicity. This is illustrated by the GALA type III effectors from Ralstonia solanacearum, which have been shown to be collectively, but not individually, required for disease on Arabidopsis thaliana and tomato. We investigated evolution, redundancy and diversification of this family in order to understand the individual contribution of the GALA effectors to pathogenicity. From sequences available, we reconstructed GALA phylogeny and performed selection studies. We then focused on the GALAs from the reference strain GMI1000 to examine their ability to suppress plant defense responses and contribution to pathogenicity on three different host plants: A. thaliana, tomato (Lycopersicum esculentum) and eggplant (Solanum melongena). The GALA family is well conserved within R. solanacearum species. Patterns of selection detected on some GALA family members, together with experimental results, show that GALAs underwent functional diversification. We conclude that functional divergence of the GALA family likely accounts for its remarkable conservation during R. solanacearum evolution and could contribute to R. solanacearum’s adaptation on several host plants.
relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis

Objective: To implement a meta-analysis to investigate the relationship between high-mobility group box 1 (HMGB1) overexpression in the tissue and serum of ovarian cancer patients, and to evaluate its prognostic significance. Methods: Searches were made of China National Knowledge Infrastructure, EMBASE, WanFang, PubMed, MEDLINE, and Web of Science databases up to August 2015, with no language or style restrictions. Reference lists of related studies were also carefully reviewed to identify additional articles. Results: The literature search identified a total of 12 relevant studies on HMGB1 expression for inclusion in the meta-analysis: seven in ovarian tumor tissue, four in ovarian tumor patient serum, and one in both tissue and serum. HMGB1 protein levels in ovarian cancer tissues were notably higher than those in normal ovarian tissues with no evidence of heterogeneity between studies (RD = 0.64, 95% confidence interval (CI): 0.57–0.70, Z = 18.70, P , 0.00001, I 2 = 15%), and also higher than those in benign tumor tissues with no evidence of heterogeneity between studies (RD = 0.52, 95% CI: 0.43–0.61, Z = 11.14, P , 0.00001, I 2 = 0). Serum HMGB1 levels were similarly significantly higher in ovarian cancer patients than those with benign tumors or normal ovaries. Pooled mean differences of HMGB1 in ovarian cancer patients compared with patients with benign tumors or normal ovaries were 99.32 with 95% CI: 67.82–130.81, Z = 6.18, P , 0.00001, and 95.34 with 95% CI: 62.11–128.57, Z = 5.62, P , 0.0001. The pooled relative risk of ovarian cancer with high vs low HMGB1 expression levels was 1.40 with 95% CI: 1.09–1.79, Z = 2.66, P = 0.008, heterogeneity I 2 = 50%. Conclusion: This meta-analysis suggested that HMGB1 levels in both tissue and serum of ovarian cancer patients were significantly higher than those of benign tumor and normal ovarian samples. High serum or tissue HMGB1 expression may therefore be an effective molecular marker for ovarian benign or malignant tumor diagnosis and patient prognosis.