Miracle-dz/UniFAR-FTUs huggingface dataset:
The Potential Regulation of A-to-I RNA Editing on Genes in Parkinson’s Disease

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD’s transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis.
A phase II study of lenalidomide and rituximab (R2) combination in patients with high-risk refractory/relapsed diffuse large B-cell lymphoma

ABSTRACT Relapsed/Refractory Diffuse Large B Cell Lymphoma have a dismal prognosis in need of innovative treatments. This prospective phase 2 study enrolled 32 patients between 2013 and 2017 with Relapsed/Refractory Diffuse Large B Cell Lymphoma treated with Rituximab and Lenalidomide (R2). Median age was 69 years (40–86), 90.1% had received at least 2 prior lines of treatment, 81% were defined as having High Risk disease according to our criteria and ECOG performance status was > 2 in 51.6%. Patients received a median number of 2 cycles of R2 (1–12). With a median follow up of 22.6 months, the objective response rate was 12.5%. Median progression free survival was 2.6 months (95% CI, [1.7–2.9]) and median overall survival was 9.3 months (95% CI, [5.1–Not estimable]). This study therefore did not achieve its primary endpoint and the R2 regimen cannot be recommended in Relapsed/Refractory Diffuse Large B Cell Lymphoma patients with High Risk features.
Response to Intervention The Future for Secondary Schools stu dent ser v ic es

When the administrators and the math faculty of the East Central School District in Minnesota became concerned that a significant number of students would not pass the math test that would be given to students in grade 11 and was required for graduation, they implemented a response to intervention (RTI) program to address the issue. The program used universal screening of students in grade 8 to determine which students were in need of intervention. Those students received supplemental math instruction; use of evidenced-based instructional strategies; use of behavior management and motivational techniques; regular progress monitoring; and small-group instruction. Although not all students achieved grade-level competency in the first year, they made on average twice the growth typically seen in grade 8 and greatly improved their rate of growth compared with their scores from the previous year. In the following years, interventions were continued
Evidence against clathrate‐derived methane release to Santa Barbara Basin surface waters?

The Clathrate Gun Hypothesis suggests that methane from the marine sedimentary gas hydrate reservoir was episodically released into the atmosphere where it generated rapid atmospheric warming that drove late Quaternary abrupt millennial‐scale climate change. Brief, large negative δ13C excursions recorded by planktonic (up to −3‰) and benthic (up to −5‰) foraminifera from Santa Barbara Basin sediments have been interpreted as evidence of clathrate‐derived methane release to surface waters during or immediately before marine isotope stage (MIS) 3 interstadials. Molecular biomarkers from the δ13C excursion horizons have been interpreted to support this scenario. However, recent work at modern methane seeps show that fossil specimens can be contaminated with authigenic overgrowths or calcite replacement that may be difficult to detect through microscopy. The possibility that planktonic specimens are contaminated, and thus their δ13C values not a primary signal, warrants further inquiry. We generated a high‐resolution continuous total organic carbon (TOC) δ13C record from fortuitously obtained samples across the younger foraminiferal δ13C excursion during Interstadial 8. The record exhibits variations similar in magnitude and timing to those that occurred in the basin over the last 600 years. Furthermore, previously published TOC δ13C values of discreet samples from this and the three other MIS 3 foraminiferal δ13C excursions are also similar to recent values. Although there are factors that could obscure a surface water methane signal in the TOC δ13C record, these results question the interpretation that methane was released to surface waters. An alternative hypothesis to explain the available data is that the foraminiferal δ13C excursions are an artifact of diagenetic processes at or below the sediment‐water interface. This interpretation may be compatible with the molecular biomarker data. Further work is necessary to differentiate between the two hypotheses.
Sediment Facies of Platform-Basin Transition, Tongue of the Ocean, Bahamas

Inter platform troughs in the Bahamas are either U shaped basins or V shaped canyons Basins are thought to have formed where parts of the originally continuous Florida Bahama platform were drowned canyons originate where erosion by turbidity currents cuts headward into the flat basin floors Southern Tongue of the Ocean TOTO is a U shaped basin in shape and setting comparable to many ancient carbonate basins Carbonate platforms with high sediment production rim the basin and fill it largely with neritic material Lime mud winnowed from the platform simply augments the rain of planktonic material Lime sand and rubble are carried to the basin floor by turbidity currents possibly also by debris flows and grain flows The platform sheds debris all along its margin and delivers it to the basin floor through numerous small gullies rather than few large canyons Therefore it acts as a line source not as a point source of sediment and the familiar pattern of large canyons and deep sea fans is not developed in TOTO Rather the facies pattern is concentric around the imaginary mid point of the basin with boundaries running parallel to the bank edge Three major facies belts could be mapped in closely spaced cores and 3 5 kHz seismic profiles I Basin interior with medium to fme sand turbidites and layered reflection character 2 basin margin with closely spaced and sometimes coalescing small fans of coarser more proximal turbidites and opaque reflection character prolonged seabed echo without subbottom reflections 3 gullied bypass slope with mainly mud and only strings of clastic material in gullies seismic echo consists of large hyperbolae with parallel subbottom reflections where sediment is mud of hyperbolae without subbottom reflections where gullies are floored with sand and rubble Layers of coarse clean sand and rubble seem to directly cause the change from layered to opaque echo character Neither grain size of intervening ooze nor microtopography of sea floor correlate with seismic reflection character Compared to ancient carbonate basins TOTO and other Bahamian basins are rather small but their flanks are high Consequently the slope environment as a trap of mud and a bypass zone of sand and rubble may be more clearly developed than in many ancient examples on the other hand the distal part of the platform basin transition notably the gradation into fully pelagic facies is missing
How learning shapes the empathic brain

: Deficits in empathy enhance conflicts and human suffering. Thus, it is crucial to understand how empathy can be learned and how learning experiences shape empathy-related processes in the human brain. As a model of empathy deficits, we used the well-established suppression of empathy-related brain responses for the suffering of out-groups and tested whether and how out-group empathy is boosted by a learning intervention. During this intervention, participants received costly help equally often from an out-group member (experimental group) or an in-group member (control group). We show that receiving help from an out-group member elicits a classical learning signal (prediction error) in the anterior insular cortex. This signal in turn predicts a subsequent increase of empathy for a different out-group member (generalization). The enhancement of empathy-related insula responses by the neural prediction error signal was mediated by an establishment of positive emotions toward the out-group member. Finally, we show that surprisingly few positive learning experiences are sufficient to increase empathy. Our results specify the neural and psychological mechanisms through which learning interacts with empathy, and thus provide a neurobiological account for the plasticity of empathic reactions. Abstract Deficits in empathy enhance conflicts and human suffering. Thus, it is crucial to understand how empathy can be learned, and how learning experiences shape empathy-related processes in the human brain. As a model of empathy deficits, we used the well-established suppression of empathy-related brain responses for the suffering of outgroups, and tested whether and how outgroup empathy is boosted by a learning intervention. During this intervention, participants equally often received costly help, either from an outgroup member (experimental group) or from an ingroup member (control group). We show that receiving help from an outgroup member elicits a classical learning signal (prediction error) in the anterior insular cortex. This signal in turn predicts a subsequent increase of empathy for a different outgroup member (generalization). The enhancement of empathy-related insula responses by the neural prediction error signal was mediated by an establishment of positive emotions towards the outgroup member. Finally, we show that surprisingly few positive learning experiences are sufficient to increase empathy. Our results specify the neural and psychological mechanisms through which learning interacts with empathy, and thus provide a neurobiological account for the plasticity of empathic reactions. Our results indicate that basic learning mechanisms are also used during complex social learning, which is in line with previous studies 35-38). Going further, our findings show how classical learning mechanisms shape other-regarding motivational states such as empathy.
Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample

Background Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample. Method All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use. Results The presence of anxiety disorders predicted shorter telomeres at follow-up (β = –0.073, t = –2.302, p = 0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (β = –0.077, t = –2.144, p = 0.032). No association was found between depressive disorders and shorter telomeres at follow-up (β = 0.010, t = 0.315, p = 0.753). Conclusions This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.
Analyzing spatial and temporal variability of annual water‐energy balance in nonhumid regions of China using the Budyko hypothesis

On the basis of long time series of climate and discharge in 108 nonhumid catchments in China this study analyzes the spatial and temporal variability of annual water‐energy balance using the Budyko hypothesis. For both long‐term means and annual values of the water balances in the 108 catchments, Fu's formula derived from the Budyko hypothesis is confirmed. A high correlation and relatively small systematic error between the values of parameter ϖ in Fu's equation optimized from the water balance of individual year and calibrated from the long‐term mean water balance show that Fu's equation can be used for predicting the interannual variability of regional water balances. It has been found that besides the annual climate conditions the regional pattern of annual water‐energy balance is also closely correlated with the relative infiltration capacity (Ks/ir), relative soil water storage (Smax/E0), and the average slope (tan β). This enables one to estimate the parameter ϖ from catchment characteristics without calibration from the long time series of water balances. An empirical formula for the parameter ϖ in terms of the dimensionless landscape parameters is proposed. Applications of Fu's equation together with the parameter ϖ estimated by this empirical formula have shown that Fu's equation can predict both long‐term mean and annual value of actual evapotranspiration accurately and predict both long‐term mean and interannual variability of runoff reasonably. This implies that the Fu's equation can be used for predicting the annual water balance in ungauged basins.
Extending and improving metagenomic taxonomic profiling with uncharacterized species with MetaPhlAn 4

Metagenomic assembly enables novel organism discovery from microbial communities, but from most metagenomes it can only capture few abundant organisms. Here, we present a method - MetaPhlAn 4 - to integrate information from both metagenome assemblies and microbial isolate genomes for improved and more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01M prokaryotic reference and metagenome-assembled genomes, we defined unique marker genes for 26,970 species-level genome bins, 4,992 of them taxonomically unidentified at the species level. MetaPhlAn 4 explains ∼20% more reads in most international human gut microbiomes and >40% in less-characterized environments such as the rumen microbiome, and proved more accurate than available alternatives on synthetic evaluations while also reliably quantifying organisms with no cultured isolates. Application of the method to >24,500 metagenomes highlighted previously undetected species to be strong biomarkers for host conditions and lifestyles in human and mice microbiomes, and showed that even previously uncharacterized species can be genetically profiled at the resolution of single microbial strains. MetaPhlAn 4 thus integrates the novelty of metagenomic assemblies with the sensitivity and fidelity of reference-based analyses, providing efficient metagenomic profiling of uncharacterized species and enabling deeper and more comprehensive microbiome biomarker detection.
Association of Fruit and Vegetable Consumption During Early Adulthood With the Prevalence of Coronary Artery Calcium After 20 Years of Follow-Up The Coronary Artery Risk Development in Young Adults (CARDIA) Study

tomography. We used logistic regression to adjust for relevant variables and estimate the adjusted odds ratios and 95% confidence intervals across energy-adjusted, sex-specific tertiles of total servings of F/V per day. Among our sample (n=2506), the mean (SD) age at baseline was 25.3 (3.5) years, and 62.7% were female. After adjustment for demographics and lifestyle variables, higher intake of F/V was associated with a lower prevalence of coronary artery calcium: odds ratio (95% confidence interval) =1.00 (reference), 0.78 (0.59–1.02), and 0.74 (0.56–0.99), from the lowest to the highest tertile of F/V, P value for trend <0.001. There was attenuation of the association between F/V and coronary artery calcium after adjustment for other dietary variables, but the trend remained significant: odds ratio (95% confidence interval): 1.00 (reference), 0.84 (0.63–1.11), and 0.92 (0.67–1.26), P value for trend <0.002]. Conclusions —In this longitudinal cohort study, higher intake of F/V during young adulthood was associated with lower odds of prevalent coronary artery calcium after 20 years of follow-up. Our results reinforce the importance of establishing a high intake of F/V as part of a healthy dietary pattern early in life. We performed several additional analyses to try and isolate the effect of F/V intake during young adulthood from other dietary factors by including F/V intake at the year 20 examination as well as other dietary factors from the baseline examination. We chose additional dietary variables based on a prior knowledge and clinical rel- evance including dairy, nuts, legumes, eggs, fish, beef, refined grain bread, refined grain pasta, cakes/cookies/doughnuts, fried potatoes, salt intake, sugar sweetened soft drinks, and frequency of fast food intake for further exploration of confounding. Finally, we included potential mediators in a model including systolic blood pressure, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cho- lesterol, and fasting blood sugar as measured at the year 20 follow-up.
Linefish larvae and the Agulhas Current

Biological studies on several linefish species have revealed annual northward spawning migrations of adult fish from Cape to Natal waters. Juveniles of these species are encountered in inshore nursery areas in the Cape and in several papers spanning nearly two decades it has been suggested that the Agulhas Current is the mechanism responsible for the southward dispersal of the early life history stages of these species. In 1990 a SEFREF funded project commenced to study the ichthyoplankton along the east coast with the objective of testing the hypothesis that linefish larvae drift south in the Agulhas Current.
Books are Forever: Early Life Conditions, Education and Lifetime Income

In this paper we estimate the effect of education on lifetime earnings in Europe, by distinguishing between individuals who lived in rural or urban areas during childhood and between individuals who had access to many or few books at age ten. We instrument years of education using reforms of compulsory education in nine different countries, and find that individuals in rural areas were most affected by the reforms while individuals with many books at home mostly benefited from education. Our main result is that books at home at age ten have had long-lasting beneficial effects on the individuals who were pushed by the reforms to increase their years of education.
Impact of dust radiative forcing in snow on accuracy of operational runoff prediction in the Upper Colorado River Basin

Accurate prediction of snowmelt runoff is critical in the US Intermountain West, where water demand is increasing and snow patterns are shifting. Here, we show that errors in the National Weather Service Colorado Basin River Forecast Center's operational streamflow predictions are correlated with the interannual variability of dust radiative forcing in snow. With data from 2000–2010, we show that errors in snowmelt period streamflow prediction for the southern Colorado Rockies are linearly related to melt period dust radiative forcing in snow as inferred from NASA Moderate Resolution Imaging Spectroradiometer data, which ranged interannually from 20 to 80 W m−2. Each 10 W m−2 change of melt period dust forcing resulted in a corresponding change in runoff prediction bias of 10.0% ± 1.5% and a 1.5 ± 0.6 day shift in runoff center of mass. Accounting for bias introduced by dust forcing could improve streamflow prediction in regions prone to dust deposition in the snowpack.
LETTER TO EDITOR: MRI EVALUATION OF LIVER IRON CONCENTRATION IN PATIENTS WITH ß-THALASSEMIA MAJOR

β major is a hereditary anemia, characterized by a genetic deficiency in the synthesis of the β-globin chain (1). The main complication of the multiple blood transfusions to these patients is iron overload and the deposition of iron in various organs, such as the reticuloendothelial system, the liver, the heart and the endocrine glands (2). Chelators also have various side effects on multiple organs in thalassemic patients, besides iron overload. Deferoxamin (DFO) which is the chelating agent most widely used for the last 30 years, mainly affects the optic, auditory and skeletal systems (3). The effective management of thalassemic patients, especially children, requires monitoring of the toxic effects of iron overload versus chelation therapy. The most reliable method of calculating body iron stores is the biochemical or histochemical assessment of iron in a liver biopsy specimen. Since liver biopsy is an invasive procedure, attempts have been made to use imaging for detection and quantification of liver iron content (4-7). Magnetic resonance imaging (MRI) is a technique for the diagnosis of hemochromatosis. Many investigators have shown that hepatic T2 relaxation or intensity ratios in MR images have a significant correlation with hepatic iron content (8-11). In this study, we have evaluated the correlation of the hemochromatosis grades in liver MRIs and liver biopsies to evaluate the precision of liver MRIs in grading hemochromatosis. This double-blind crosssectional study was conducted between January 2007 and April 2008 at the Hematology Research Center, Shiraz University of Medical Sciences. Twenty-eight blood transfusion-dependent thalassemia major patients were involved in this double-blind cross-sectional study. Thalassemia major was determined in these patients by a complete blood count (CBC) and hemoglobin electrophoresis. Patients were selected from a population that had had liver biopsies performed on them for various purposes. The exclusion criteria for this study were acute or chronic viral hepatitis and any kind of infection found in physical examinations. After obtaining the patients’ written informed