Miracle-dz/UniFAR-FTUs huggingface dataset:
Does rehearsal benefit visual memory? The role of semantic associations in the maintenance of intact and phase-scrambled scenes

There is a rich behavioral literature on articulatory rehearsal for verbal stimuli, suggesting that rehearsal may facilitate memory, but few studies have examined the benefits for visual stimuli. Neural delay period studies have largely failed to control for the use of maintenance strategies, which make activity patterns during maintenance difficult to interpret. Forty-four participants completed a modified Sternberg Task with either novel scenes (NS) that contained semantic information or phase-scrambled scenes (SS) that lacked it. Participants were instructed to generate a descriptive label and covertly rehearse (CR) or suppress (AS, i.e., repeat “the”) during the delay period. Artifact-corrected delay period activity was compared as a function of maintenance strategy (CR vs. AS) and stimulus type (NS vs. SS). Performance on the working memory task for NS revealed that CR neither provided a short-nor long-term behavioral advantage on the delayed recognition task for CR. Interestingly, when task difficulty increased with SS, there was both a significant short-term as well as a long-term advantage. Comparison of sensor-level delay activity during the maintenance phase for NS and SS revealed two distinct patterns of neural activity for NS; there was greater amplitude in the beta range in the right parietal and centromedial regions. For SS, across all sensors during CR, the higher amplitude was observed in the upper alpha and beta ranges. The results suggest that rehearsal increased subsequent memory with SS but not NS. Moreover, neural modulation during the delay period depends on both task difficulty and maintenance strategy.
A novel plasmid-transcribed regulatory sRNA, QfsR, controls chromosomal polycistronic mRNAs in Agrobacterium tumefaciens

Plasmids are mobile DNAs that adjust host cell functions for their own amplification and dissemination. We identified QfsR, a small RNA, transcribed from the Ti plasmid in the phytopathogen Agrobacterium fabrum. QfsR is widely conserved throughout RepABC plasmids carried by Rhizobiaceae. Target prediction, expression analysis and site-direct mutagenesis experiments show that QfsR directly pairs within polycistronic mRNAs transcribed from chromosomes (involved in flagella apparatus and succinoglycan biosynthesis) and Ti plasmid (involved in conjugative transfer). QfsR leads to a coordinated expression of whole polycistronic mRNA molecules. Whereas a lack of QfsR induces motility and reduces succinoglycan production, its overproduction increases the quorum sensing signal accumulation and the Ti plasmid conjugative transfer. Based on these observations, we propose QfsR as a hub connecting regulatory networks of motility, succinoglycan biosynthesis and plasmid conjugative transfer. To our knowledge, QfsR is the first example of a plasmid-encoded sRNA that controls chromosomal polycistronic mRNAs. Significance Plasmids represent an important cost for the hosting cell although some are beneficial under certain circumstances. Agrobacterium tumefaciens harboring Tumor inducing plasmid (pTi) are able to infect plants and to use specific resources produced by the infected cells. We characterized QfsR, a novel small RNA (sRNA) from pTi, that directly regulates plasmid polycistronic mRNA but also chromosomal ones. QfsR contributes to a fine-tuned regulation of bacterial motility, exopolysaccharide biosynthesis and conjugative dissemination of pTi. Our results report the first plasmid-encoded sRNA able to modify and coordinate cellular behaviour probably for the benefit of the plasmid dissemination and tight crosstalk between plasmid and chromosome. This could be widespread since QfsR homologs were predicted in other plasmids of Rhizobiaceae symbionts and pathogens.
Prevalence of Behavioral Risk Factors of Noncommunicable Diseases in a Rural Population of Bangladesh

Behavioral risk factors reduction is a key to Noncommunicable Diseases (NCDs) control. This survey on NCD risk factors was done in randomly selected cross-sectional sample of 443 rural individuals aged 15 years or older. More than three in ten people used tobacco in some form, and more than nine in ten used extra salt while taking meal. All of them had low fruit and vegetables intake (<5 gm/day). About four and one percent were taking medicines for hypertension and diabetes, respectively. In conclusion, prevalence of tobacco and added salt consumption is fairly high in this rural Bangladeshi sample. Local level health infrastructure and health workers should be used to control these risk factors in rural communities. Amount of added salt while taking meal, fruit and vegetables intakes were determine showing, spoons, cups and show-cards. History of current medication for hypertension and diabetes was obtained. Data were collected by experienced local health assistants of ECOH. Verbal consent was obtained from the respondents. Prevalence (95% confidence interval) of risk factors were obtained, which were adjusted to WHO’s world standard population.
Smoking, Health Capital, and Longevity: Evaluation of Personalized Cessation Treatments in a Lifecycle Model with Heterogeneous Agents

Cigarette smoking leads to large healthcare and morbidity costs, and mortality losses, and smoking cessation plays a key role in reducing health risk and economic costs. While medical evidence suggests that some smokers are more likely to respond to medication treatment than others depending on genetic markers, it remains unexplored whether pharmacogenetic testing is cost-effective in treating potential quitters of smoking. We address this knowledge gap by developing a lifecycle model in which individuals make smoking, health investment and consumption-savings decisions. Depending on an individual's genotype, smoking may bring enjoyment but deteriorates one's health, and the dynamic evolution of health capital determines life expectancy. In addition to heterogeneous genotypes, individuals also differ in demographics. We calibrate this model to fit key economic and medical observations in the U.S. We then propose three smoking cessation policies, two with standard treatments and one personalized depending on genetic markers, all under the same program costs. We construct two unified measures of effectiveness and subsequently compute the cost-effectiveness ratio. We find that personalized treatment is the most cost-effective: for each dollar of program cost, it generates $8.94 value in effectiveness, which is 22-45% higher than those under standard treatments.
Hepatoprotective effect of simvastatin in mice with DMBA-induced breast cancer: Histopathological, biochemical and antioxidant status evaluation

Introduction: This study evaluates the effects of simvastatin on the liver, in a mouse model of DMBA-induced breast cancer, with regards to histopathological, biochemical and antioxidant features. Methods: Mice were randomly divided into two groups: A (control group) and B (mammary tumor group); the latter group received DMBA (50 mg/kg) by oral gavage once a week for 4 consecutive weeks. Animals positive for breast cancer tumors were randomly divided into 3 subgroups: 1) no treatment group (D1), 2) mice that received simvastatin (80 mg/kg) per os (P.O.) daily for 4 consecutive weeks (D2), and 3) mice that received tamoxifen (50 mg/kg) P.O. daily for 4 consecutive weeks (D3). Results: Administration of simvastatin to D2 mice resulted in significantly higher superoxide dismutase (SOD) activity as well as glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC), and accompanied by reduced malondialdehyde (MDA) content in liver as compared to D1 group. Tamoxifen significantly increased liver glutathione (GSH) content as compared to D1 mice. Moreover, MDA levels in liver of mice treated with tamoxifen were significantly lower than in the D1 group. Mice in the D1 group showed significantly increased levels of alkaline phosphatase (ALP), aspartate transaminase (AST), and gamma-glutamyl transferase (GGT) in liver tissues; these levels were significantly reduced by simvastatin administration. Moreover, tamoxifen decreased ALP and AST activities. Histopathological examination of liver sections from mice in the D1 group showed severe deteriorative changes. The extent and severity of changes in D2 and D3 groups were almost the same and milder than D1 group. Conclusion: In conclusion, simvastatin appears to have a hepatoprotective role in mice with DMBA-induced breast cancer, due partly to its antioxidant properties.
Basal forebrain volume reliably predicts the cortical spread of Alzheimer’s degeneration

Alzheimer’s disease neuropathology is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model posits that Alzheimer’s neurodegeneration starts in the entorhinal cortices, before spreading to temporoparietal cortex. Challenging this model, we previously provided evidence that degeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, precedes and predicts entorhinal degeneration (Schmitz and Spreng, 2016). There have been few systematic attempts at directly comparing staging models using in vivo longitudinal biomarker data, and determining if these comparisons generalize across independent samples. Here we addressed the sequence of pathological staging in Alzheimer’s disease using two independent samples of the Alzheimer’s Disease Neuroimaging Initiative (N1 = 284; N2 = 553) with harmonized CSF assays of amyloid (Aβ) and hyperphosphorylated tau (pTau), and longitudinal structural MRI data over two years. We derived measures of gray matter degeneration in a priori NbM and the entorhinal regions of interest. To examine the spreading of degeneration, we used a predictive modelling strategy which tests whether baseline gray matter volume in a seed region accounts for longitudinal change in a target region. We demonstrated that predictive pathological spread favored the NbM→entorhinal over the entorhinal→NbM model. This evidence generalized across the independent samples (N1: r=0.20, p=0.03; N2: r=0.37, p<0.001). We also showed that CSF concentrations of pTau/Aβ moderated the observed predictive relationship, consistent with evidence in rodent models of an underlying trans-synaptic mechanism of pathophysiological spread (t826=2.55, p=0.01). The moderating effect of CSF was robust to additional factors, including clinical diagnosis (t826=1.65, p=0.49). We then applied our predictive modelling strategy to an exploratory whole-brain voxel-wise analysis to examine the spatial specificity of the NbM→entorhinal model. We found that smaller baseline NbM volumes predicted greater degeneration in localized regions of the entorhinal and perirhinal cortices. By contrast, smaller baseline entorhinal volumes predicted degeneration in the medial temporal cortex, recapitulating the prevailing staging model. Our findings suggest that degeneration of the basal forebrain cholinergic projection system is a robust and reliable upstream event of entorhinal and neocortical degeneration, calling into question the prevailing view of Alzheimer’s disease pathogenesis.
Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations in vivo

Dominant mutations in the mitochondrial paralogs CHCHD2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson’s disease and ALS/FTD/myopathy, respectively. Disruption of mitochondrial cristae has been observed in mutant C10 patient tissues and animal models, but the mechanism for this disruption remains controversial. Additionally, C10 patient mutant knock-in (KI) mice were recently reported to activate a mitochondrial integrated stress response (mt-ISR) and develop cardiomyopathy not seen in C10 knockout (KO) mice, calling into question whether mutant C10 pathogenesis is related to C2/C10 normal function or purely toxic gain of function. Here, using the first C2/10 double knockout (DKO) mice, we report that C10 pathogenesis and the normal function of C2/10 are intimately linked. Similar to patients with C10 mutations, we found that C2/10 DKO mice (but not either single KO mice) have disrupted mitochondrial cristae, due to cleavage of the mitochondrial shaping protein L-OPA1 by the stress-induced peptidase OMA1. OMA1 was found to be activated similarly in affected tissues of mutant C10 KI mice, demonstrating that L-OPA1 cleavage is a novel mechanism for cristae abnormalities due to both C10 mutation and C2/C10 loss, and that OMA1, a driver of neurodegeneration in other contexts, may be a therapeutic target. Finally, C2/10 DKO mice partially phenocopied mutant C10 KI mice with the development of cardiomyopathy and activation of the mt-ISR in affected tissues, tying mutant C10 pathogenesis to C2/C10 function.
Witness Tree paper

39 EuroAmerican land use and its legacies have transformed forest structure and composition 40 across the United States (US). More accurate reconstructions of historical states are critical to 41 understanding the processes governing past, current, and future forest dynamics. Gridded 42 (8x8km) estimates of pre-settlement (1800s) forests from the upper Midwestern US 43 (Minnesota, Wisconsin, and most of Michigan) using 19th Century Public Land Survey (PLS) 44 records provide relative composition, biomass, stem density, and basal area for 26 tree 45 genera. This mapping is more robust than past efforts, using spatially varying correction 46 factors to accommodate sampling design, azimuthal censoring, and biases in tree selection. 47 We compare pre-settlement to modern forests using Forest Inventory and Analysis (FIA) data, 48 with respect to structural changes and the prevalence of lost forests, pre-settlement forests 49 with no current analogue, and novel forests, modern forests with no past analogs. Differences 50 between PLSS and FIA forests are spatially structured as a result of differences in the 51 underlying ecology and land use impacts in the Upper Midwestern United States. Modern 52 biomass is higher than pre-settlement biomass in the northwest (Minnesota and north53 eastern Wisconsin, including regions that were historically open savanna), and lower in the 54 east (eastern Wisconsin and Michigan), due to shifts in species composition and, presumably, 55 average stand age. Modern forests are more homogeneous, and ecotonal gradients are more 56 diffuse today than in the past. Novel forest assemblages represent 29% of all FIA cells, while 57 25% of pre-settlement forests no longer exist in a modern context. 58 Lost forests are centered around the forests of the Tension Zone, particularly in hemlock 59 dominated forests of north-central Wisconsin, and in oak-elm-basswood forests along the 60 forest-prairie boundary in south central Minnesota and eastern Wisconsin. Novel FIA forest 61 assemblages are distributed evenly across the region, but novelty shows a strong relationship 62 to spatial distance from remnant forests in the upper Midwest, with novelty predicted at 63 between 20 to 60km from remnants, depending on historical forest type. 64 The spatial relationships between remnant and novel forests, shifts in ecotone structure and 65 the loss of historic forest types point to significant challenges to land managers if landscape 66 restoration is a priority in the region. The spatial signals of novelty and ecological change also 67 point to potential challenges in using modern spatial distributions of species and communities 68 and their relationship to underlying geophysical and climatic attributes in understanding 69 potential responses to changing climate. The signal of human settlement on modern forests is 70 broad, spatially varying and acts to homogenize modern forests relative to their historic 71 counterparts, with significant implications for future management. 72
Sampling strategy optimization to increase statistical power in 1 landscape genomics : a simulation-based approach 2 3 Running title : Sampling strategy in landscape genomics

15 An increasing number of studies use landscape genomics to investigate local adaptation in wild and domestic populations. This 16 method consists of simultaneously characterizing genetic and environmental variability across a landscape in order to depict 17 how genotype frequencies are shaped by adaptive forces. The implementation of this approach requires the sampling phase to 18 consider the complexity of environmental settings and the burden of logistic constraints. These aspects can have a major 19 impact on reproducibility and costs but they are often underestimated in the literature dedicated to sampling strategies. 20 In this study, we compute simulated genomic datasets on a real environmental setting and distinct demographic scenarios to 21 reiterate landscape genomics experiments with distinct sampling strategies. The latter differ by design approaches (aiming at 22 enhancing environmental and/or geographic representativeness), number of sampling locations and sample sizes. We then 23 propose an analytical framework to evaluate the effect of these elements on statistical power and false discovery rates of the 24 analysis. 25 Our results highlight the importance of sample size in designing landscape genomic studies, where a minimal threshold of 200 26 individuals is required to detect at least part of the true positives. Furthermore, our results show that sampling at less than 10 27 sites clearly impairs statistical power, but also that the optimal number of sampling locations is not necessarily the highest 28 possible. Last, we show that the designs that account for environmental representativeness result in the highest statistical 29 power. Overall, this study provides valuable guidelines for optimizing sampling strategies in landscape genomics experiments. 30 31
Potentially Inappropriate Medication Prescription in Elderly Outpatients

Potentially inappropriate medication (PIM) is defined as medication which may result in higher than expected risk when used by elderly patients. Its risk of occurrence may be increased through the effects of drug interactions, adverse drug reactions (ADR), adverse drug effects (ADE), and so on. At the commencement of this study, we hypothesized that: 1. After the release of a revised version of the Beers Criteria, the number of medications prescribed that are inappropriate under these guidelines would decline. 2. Polypharmacy would lead to increased potentially inappropriate use of medication. 3. More PIM would be prescribed at hospitals than at local clinics. To test these hypotheses, we analyzed prescriptions that had been issued by physicians at local hospitals and clinics and dispensed at a community pharmacy in Kaohsiung City, from 2009 to 2015. We found that the overall rate of prescription of PIM for elderly patients was 50.8% from 2009-2012, compared with 37.6% from 2013-2015. The largest number of prescriptions filled at the pharmacy was for the 'young-old', while the smallest number was for the 'oldest-old'. Prior to the introduction of the guidelines, the incidence of PIM was highest among the 'oldest-old', while after their introduction, PIM was highest among the 'aged'. In terms of prescribing institutions, physicians in hospitals were more likely to prescribe PIM than those in clinics. In terms of polypharmacy, inappropriate medications were most likely to be prescribed when ten or more medications were being used simultaneously. After the release of the guidelines, the rate of PIM among patients using ten kinds of medication or more exceeded that of those using one to four medications by a factor of six. This study involved only a retro-analysis of prescriptions dispensed at a community pharmacy. In the future, if pharmacists can discuss the appropriateness of prescriptions with physicians after medications have been prescribed, it is likely that the rate of PIM can be reduced, thus contributing to an improved quality of life for elderly patients.
Population health: At odds with person-centered healthcare

The last two decades have seen an explosion of interest in population health. Virtually inexistent in the medical literature prior to 1995, the phrase is now attached to a growing number of academic departments around the world. Graduate programs are conferring degrees in population health management [1], healthcare institutions are offering influential positions of “chief population health officer” [2] and several new American medical schools are designing their curricula to train students in the practice of population medicine [3-5]. Aiming for healthy populations is a laudable goal, but the enthusiasm for this new discipline should not obscure the fact that some fundamental questions about the definition and scope of population health remain. Most important for readers of the European Journal for Person Centered Healthcare is the relationship of population health to person-centered healthcare. Are those two approaches compatible or at odds with each other? The lack of a precise definition for population health has been recognized by leaders in the field ever since the term began to enter common usage [6]. Initially, population health was understood to be a discipline concerned with characterizing social determinants of health (SDOH) to inform health policy [6,7]. Later, however, Kindig and Soddart proposed that population health be understood as a concept of health and be defined on the basis of global health outcomes, since the SDOH the independent variables, as it were must be examined and optimized in relation to their effect on population health, the ultimate dependent variable [6,8]. The emphasis on global outcomes has been incorporated into the socalled “Triple Aim” of population health management proposed by the Institute for Healthcare Improvement and embraced by the Center for Medicare and Medicaid Services [9]. Nevertheless, an ambivalence remains and the idea that population health still lacks a proper articulation continues to preoccupy its adepts [10,11]. A matter of emphasis?
Training Community-Based Clinicians in Parent-Child Interaction Therapy: The Interaction Between Expert Consultation and Caseload

Professional psychologists are increasingly encouraged to utilize evidence-based treatments (EBTs), and therefore have a need to participate and provide the most efficient training methods for these treatments. Multicomponent trainings, which commonly include ongoing support, are more effective than brief methods such as 1-day workshops or reading treatment manuals. The present study examined the effectiveness of 1 form of ongoing support, consultation, as part of a multicomponent training protocol. Thirty-two community-based clinicians were trained in Parent-Child Interaction Therapy (PCIT) as part of a statewide implementation effort, and data were collected on clinician and implementation outcomes at pre-, mid-, and posttraining. Simple and multiple linear regression analyses were conducted to predict posttraining knowledge, skill, acceptability, and feasibility, as well as to examine clinician variables that might moderate these relations. Greater consultation call attendance significantly predicted higher posttraining skill; however, this association was qualified by a significant interaction with PCIT caseload. Implications for training guidelines are discussed.