Miracle-dz/UniFAR-FTUs huggingface dataset:
Population response magnitude variation in inferotemporal cortex predicts image memorability

Most accounts of image and object encoding in inferotemporal cortex (IT) focus on the distinct patterns of spikes that different images evoke across the IT population. By analyzing data collected from IT as monkeys performed a visual memory task, we demonstrate that variation in a complementary coding scheme, the magnitude of the population response, can largely account for how well images will be remembered. To investigate the origin of IT image memorability modulation, we probed convolutional neural network models trained to categorize objects. We found that, like the brain, different natural images evoked different magnitude responses from these networks, and in higher layers, larger magnitude responses were correlated with the images that humans and monkeys find most memorable. Together, these results suggest that variation in IT population response magnitude is a natural consequence of the optimizations required for visual processing, and that this variation has consequences for visual memory.
Costs and Benefits of Environmental Data in Investigations of Gene-Disease Associations

The inclusion of environmental exposure data may be beneficial, in terms of statistical power, to investigation of gene-disease association when it exists. However, resources invested in obtaining exposure data could instead be applied to measure disease status and genotype on more subjects. In a cohort study setting, we consider the tradeoff between measuring only disease status and genotype for a larger study sample and measuring disease status, genotype, and environmental exposure for a smaller study sample, under the ‘Mendelian randomization’ assumption that the environmental exposure is independent of genotype in the study population. We focus on the power of tests for gene-disease association, applied in situations where a gene modifies risk of disease due to particular exposure without a main effect of gene on disease. Our results are equally applicable to exploratory genome-wide association studies and more hypothesis-driven candidate gene investigations. We further consider the impact of misclassification for environmental exposures. We find that under a wide range of circumstances research resources should be allocated to genotyping larger groups of individuals, to achieve a higher power for detecting presence of gene-environment interactions by studying genedisease association.
Modulation of chicken cecal microbiota by a phytogenic feed additive, Stodi®: A metagenomic analysis

Background: The cecal microbiota plays a critical role in gut health and utilization of nutrients left undigested in the small intestine. Objective: The impact of Stodi® on the composition of cecal microbiota was evaluated in broilers using high-throughput sequencing of 16S rRNA gene amplicons. Materials and Methods: A total of 960 1-day-old Ross 308 chicks were allocated to four groups, namely, normal diet (ND), negative control (NTC; challenged with 1.7% magnesium chloride [MgCl2]), and Stodi® treatment groups which comprise NTC plus Stodi® (500 and 750 g/ton of feed). MgCl2was used to increase the cecal moisture content, and in turn, to disturb the cecal microbiota. Results: Birds challenged with MgCl2exhibited poor performance traits as compared to ND group, whereas the supplementation of Stodi® (500 and 750 g/ton) improved the performance of broilers. MgCl2did not produce a notable change in the microbiota, but supplementation of Stodi® (500 and 750 g/ton) produced a statistically significant shift in the microflora in comparison with ND. The Firmicutes to Bacteroidetes ratio was significantly elevated in comparison to ND. The abundance of energy harvesting bacteria belonging to specific families of Lachnospiraceae and Ruminococcaceae were increased by Stodi® supplementation, especially at 500 g/ton of feed. Conclusion: The supplementation of Stodi® was effective in modulating the cecal microbial population in a manner conducive for gut health and performance of broilers, as revealed by the increase in abundance of favorable microflora.
SNAIL1 employs β‐Catenin‐LEF1 complexes to control colorectal cancer cell invasion and proliferation

The transcription factor SNAIL1 is a master regulator of epithelial‐to‐mesenchymal transition (EMT), a process entailing massive gene expression changes. To better understand SNAIL1‐induced transcriptional reprogramming we performed time‐resolved transcriptome analysis upon conditional SNAIL1 expression in colorectal cancer cells. Gene set variation analyses indicated that SNAIL1 strongly affected features related to cell cycle and Wnt/β‐Catenin signalling. This correlated with upregulation of LEF1, a nuclear binding partner of β‐Catenin. Likewise, transcriptomes of cell lines and colorectal cancers, including poor‐prognosis mesenchymal tumours, exhibit positively correlated SNAI1 and LEF1 expression, and elevated LEF1 levels parallel increased patient mortality. To delineate the functional contribution of LEF1 to SNAIL1‐induced EMT, we used the CRISPR/Cas9 system to knock‐out LEF1 in colorectal cancer cells, and to engineer cells that express LEF1 mutants unable to interact with β‐Catenin. Both complete LEF1‐deficiency and prevention of the β‐Catenin‐LEF1 interaction impaired the ability of SNAIL1 to elicit expression of an alternative set of Wnt/β‐catenin targets, and to promote cancer cell invasion. Conversely, overexpression of wildtype, but not of mutant LEF1, stimulated alternative Wnt/β‐Catenin target gene expression, and caused cell‐cycle arrest. Moreover, like SNAIL1, LEF1 retarded tumour growth in xenotransplantations. Thus, LEF1 phenocopies SNAIL1 with respect to several critical aspects of EMT. Indeed, comparative transcriptomics suggested that 35% of SNAIL1‐induced transcriptional changes are attributable to LEF1. However, LEF1 did not autonomously induce EMT. Rather, LEF1 appears to be a strictly β‐Catenin‐dependent downstream effector of SNAIL1. Apparently, SNAIL1 employs β‐Catenin‐LEF1 complexes to redirect Wnt/β‐Catenin pathway activity towards pro‐invasive and anti‐proliferative gene expression.
Rating-based investment constrains-induced trading : other thresholds beyond the investment-grade boundary *

This paper investigates the effect of rating-based portfolio restrictions that many institutional investors face on the trading of their bond portfolios. Formal regulations and informal investment guidelines require limiting or even prohibit from investing in securities rated below a certain rating category. We explore how credit rating downgrades affect to bondholders that are subject to such rating-based constrains in the US corporate bond market. These boundaries go beyond the well-documented investment-grade threshold. We also control for downgrades that cross any of the buckets established in the NAIC’s risk-based capital system. We state that the informativeness of rating downgrades will be different according to whether they imply crossing investment-policy thresholds or not. We analyze corporate bond data from TRACE to test our main hypothesis and find a clear response around the announcement date consistent with portfolio adjustments made by institutions in their fulfillment of nonregulatory investment constrains. Downgrades affecting the three subcategories within the “A” rating class have the larger impact on pricing and trading activity.
Exclusion Criteria as Measurements II: Effects on Utility Functions

Background. Researchers often justify excluding some responses in studies eliciting valuations of health states as not representing respondents’ true preferences. Here, we examine the effects of applying 8 common exclusion criteria on societal utility estimates. Setting. An online survey of a US nationally representative sample (N = 1164) used the standard gamble method to elicit preferences for health states defined by 7 health domains from the Patient-Reported Outcomes Measurement Information System (PROMIS®). Methods. We estimate the impacts of applying 8 commonly used exclusion criteria on mean utility values for each domain, using beta regression, a form of analysis suited to double-bounded scales, such as utility. Results. Exclusion criteria have varied effects on the utility functions for the different PROMIS health domains. As a result, applying those criteria would have varied effects on the value of treatments (and side effects) that change health status on those domains. Limitations. Although our method could be applied to any health utility judgments, the present estimates reflect the features of the study that produced them. Those features include the selected health domains, standard gamble method, and an online format that excluded some groups (e.g., visually impaired and illiterate individuals). We also examined only a subset of all possible exclusion criteria, selected to represent the space of possibilities, as characterized in a companion article. Conclusions. Exclusion criteria can affect estimates of the societal utility of health states. We use those effects, in conjunction with the results of the companion article, to make suggestions for selecting exclusion criteria in future studies.
KARYOTYPES OF THE SNORKEL SNAIL GENERA PTEROCYCLOS AND RHIOSTOMA ( PROSOBRANCHIA : CYCLOPHORIDAE )

— Twenty-fi ve specimens of ‘snorkel snails’ from the two closely related genera Pterocyclos (two species) and Rhiostoma (six species) from Thailand and Malaysia were karyotyped. The two genera showed no differences in both their haploid and diploid chromosome numbers (n = 14, 2n = 28), whilst the fundamental chromosome numbers (FN) varied in Rhiostoma, being 50, 54 or 56 depending upon the species. Karyotypes of the two Pterocyclos species from southern Thailand and northern Malaysia (with FN = 56) were distinct, being 8m + 4sm + 2st in Pterocyclos sp. and 7m + 5sm + 2st in P. blandi. The six species of Rhiostoma examined herein showed variations in their karyotype and chromosome morphology. The karyotypes varied from 7m + 4sm + 3st in R. hainesi from eastern Thailand, 6m + 5sm + 2st + 1a in R. chupingense from southern Thailand and northern Malaysia, 2m + 9sm + 2st + 1t in R. jalorensis from southern Thailand, whilst the two island species exhibited signifi cant differences in their karyotypes, being 3m + 7sm + 1st + 3t in R. asiphon from the Angtong Archipelago and 5m + 5sm + 1st + 3a in R. samuiense from Samui Island. In R. housei, the karyotype varied between the central (9m + 2sm + 3st) and southern populations (9m + 2sm + 2st + 1a) of Thailand. This is the fi rst report of the karyotypes of land operculate snails from the Thai-Malay Peninsula, and provides fundamental knowledge for the future systematic study of these groups.
The Relationship between carotid artery calcification and pulp stone among hemodialysis patients: A retrospective study

The aim of this study was to determine the relationship between the presence of carotid artery calcification (CAC) and pulp stone (PS). A total of 60 chronic hemodialysis (HD) patients (30 CAC positive, 30 CAC negative) participated in this study. The mean age of patients was 54.7 ± 16.4 years, and 32 (53%) of them were male. CAC was defined as the presence of heterogeneous nodular opacities in the soft tissue in C3–C4 intervertebral area. Panoramic radiographs of the patients were evaluated for CAC and PS by two oral and maxillofacial radiologists. PS was evaluated in all healthy, decayed, and restored teeth except the third molar teeth, in the coronal, sagittal, and axial planes. The Statistical Package for the Social Sciences (version 20.0; SPSS, Inc., an IBM Company, Chicago, IL, USA) was used. A probability P <0.05 was considered statistically significant. The prevalence of PS in this study was 30% (18 patients) all group. A total of 1324 teeth were analyzed and PS was detected in 237 teeth (17.9%). The occurrence of PS in teeth in CAC-positive group (10 patients, 17.2% of 654 teeth) was similar to that in CAC-negative group (8 patient, 18.3% of 670 teeth). There was no statistical correlation between CAC and PS in chronic HD patients (P = 0.08). In the subgroup analysis, the presence of diabetes (P = 0.003), parathormone level (P = 0.02), calcium × phosphorus product (P = 0.04), and C-reactive protein levels (P = 0.002) were higher, and duration of HD (P = 0.03) was significantly longer in patients with CAC-positive and PS. In chronic HD patients, the presence of PS was not a strong predictor for the presence of CAC.
Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer

In breast cancer patients, the diversity of the microbiome decreases, coinciding with decreased production of cytostatic bacterial metabolites like lithocholic acid (LCA). We hypothesized that LCA can modulate oxidative stress to exert cytostatic effects in breast cancer cells. Treatment of breast cancer cells with LCA decreased nuclear factor-2 (NRF2) expression and increased Kelch-like ECH associating protein 1 (KEAP1) expression via activation of Takeda G-protein coupled receptor (TGR5) and constitutive androstane receptor (CAR). Altered NRF2 and KEAP1 expression subsequently led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased expression of inducible nitric oxide synthase (iNOS). The imbalance between the pro- and antioxidant enzymes increased cytostatic effects via increased levels of lipid and protein oxidation. These effects were reversed by the pharmacological induction of NRF2 with RA839, tBHQ, or by thiol antioxidants. The expression of key components of the LCA-elicited cytostatic pathway (iNOS and 4HNE) gradually decreased as the breast cancer stage advanced. The level of lipid peroxidation in tumors negatively correlated with the mitotic index. The overexpression of iNOS, nNOS, CAR, KEAP1, NOX4, and TGR5 or the downregulation of NRF2 correlated with better survival in breast cancer patients, except for triple negative cases. Taken together, LCA, a metabolite of the gut microbiome, elicits oxidative stress that slows down the proliferation of breast cancer cells. The LCA–oxidative stress protective pathway is lost as breast cancer progresses, and the loss correlates with poor prognosis.
Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy

The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment.
The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma

The pursuit of matrix metalloproteinase (MMP) inhibitors began in earnest over three decades ago. Initial clinical trials were disappointing, resulting in a negative view of MMPs as therapeutic targets. As a better understanding of MMP biology and inhibitor pharmacokinetic properties emerged, it became clear that initial MMP inhibitor clinical trials were held prematurely. Further complicating matters were problematic conclusions drawn from animal model studies. The most recent generation of MMP inhibitors have desirable selectivities and improved pharmacokinetics, resulting in improved toxicity profiles. Application of selective MMP inhibitors led to the conclusion that MMP-2, MMP-9, MMP-13, and MT1-MMP are not involved in musculoskeletal syndrome, a common side effect observed with broad spectrum MMP inhibitors. Specific activities within a single MMP can now be inhibited. Better definition of the roles of MMPs in immunological responses and inflammation will help inform clinic trials, and multiple studies indicate that modulating MMP activity can improve immunotherapy. There is a U.S. Food and Drug Administration (FDA)-approved MMP inhibitor for periodontal disease, and several MMP inhibitors are in clinic trials, targeting a variety of maladies including gastric cancer, diabetic foot ulcers, and multiple sclerosis. It is clearly time to move on from the dogma of viewing MMP inhibition as intractable.
A concise review of human brain methylome during aging and neurodegenerative diseases

DNA methylation at CpG sites is an essential epigenetic mark that regulates gene expression during mammalian development and diseases. Methylome refers to the entire set of methylation modifications present in the whole genome. Over the last several years, an increasing number of reports on brain DNA methylome reported the association between aberrant methylation and the abnormalities in the expression of critical genes known to have critical roles during aging and neurodegenerative diseases. Consequently, the role of methylation in understanding neurodegenerative diseases has been under focus. This review outlines the current knowledge of the human brain DNA methylomes during aging and neurodegenerative diseases. We describe the differentially methylated genes from fetal stage to old age and their biological functions. Additionally, we summarize the key aspects and methylated genes identified from brain methylome studies on neurodegenerative diseases. The brain methylome studies could provide a basis for studying the functional aspects of neurodegenerative diseases.
Oral contraceptive use in adolescence predicts lasting vulnerability to depression in adulthood.

BACKGROUND Previous evidence suggests that use of oral contraceptives (OCs), especially during adolescence, may increase women's vulnerability to depression in the short term. Here, we investigate whether women who had first used OC in adolescence show an increased prevalence of depression in the long term. METHODS We examined 1,236 women in the United States National Health and Nutrition Examination Survey for whom information on depression and age at first OC use was publicly available. We compared women who reported first use of OCs in adolescence to women who had never used OCs and women who had first used OCs in adulthood on 1-year prevalence of major depressive disorder (MDD) assessed by trained interviewers. RESULTS Compared with women who had used OCs during adolescence, women who had never used OCs were less likely to meet the criteria for MDD within the past year in adulthood [odds ratio (OR) = 0.31, 95% CI = 0.16-0.60], and so were women who only started using OCs in adulthood (OR = 0.54, 95% CI = 0.30-0.95). Third factors that have previously been proposed to explain the relationship between OC use and depression risk such as age at sexual debut, and, importantly, current OC use, did not account for the results in propensity score analyses. CONCLUSIONS We show a long-term association between adolescent OC use and depression risk in adulthood regardless of current OC use. Our findings suggest that adolescence may be a sensitive period during which OC use could increase women's risk for depression, years after first exposure.
In search of a daily physical activity “sweet spot”: Piloting a digital tracking intervention for people with multiple sclerosis

Objective This pilot study tested a course-based intervention to help people with multiple sclerosis (MS) match their daily activity to symptom severity (“sweet spot”) using wearable activity trackers. Methods This two-phase study recruited online research network members reporting MS and who were utilizing Fitbit One™ activity trackers. In the first phase, participant interviews assessed demand based on physical activity and the use of behavior-change techniques. The second phase assessed the demand, limited efficacy, acceptability, and practicality of a “Wearables 101” course that integrated behavior change and self-experimentation principles. Tracker data were used to determine the percent of matches between daily symptom-based step goals and step counts. Results Participants expressed demand in the form of interest in gaining insights about a possible “sweet spot” behavioral target, if a system could be produced to support that. Limited efficacy results were mixed, with approximately one-third of participants dropping out and only half matching their daily target goals for at least 50% of days. In terms of practicality, participants commented on the burden of daily measurement and the need for a longer baseline period. Participants noted that tracking helped support an understanding of the link between activities and symptom severity, suggesting acceptability. Conclusions Results suggested that the intervention demand and acceptability criteria were demonstrated more strongly than limited efficacy and practicality. The matching intervention tested in this study will require refinement in baseline measurement, goal definition, and reduced data-gathering burden. Such changes may improve efficacy and practicality requirements and, by extension, later impact of the intervention on MS outcomes. Overall, these results provide justification for additional work on refining the intervention to increase practicality and efficacy.
Pre-Anticipatory Anxiety and Autonomic Nervous System Response to Two Unique Fitness Competition Workouts

To evaluate the feasibility of on-site collection of subjective anxiety, autonomic nervous system activity, and salivary catecholamines surrounding high-intensity functional training (HIFT) competition, ten experienced HIFT competitors completed baseline assessments of anxiety and heart rate variability (HRV). Then, in two consecutive weeks (Workout 1 and 2) within the competition, HRV was recorded and examined in 5-min segments prior to exercise (PRE) and across a 30-min period after competitors completed their choice of the prescribed or scaled each workout. Subjective anxiety ratings and saliva samples were collected at PRE and immediately-(IP), 30-min (30P), and 60-min post-exercise (60P). Saliva samples were analyzed for concentrations of epinephrine and norepinephrine. Generalized linear mixed models with repeated measures revealed significant (p < 0.05) differences between workouts for all measures. Compared to Workout 1, anxiety (~50%), epinephrine (173–340%), norepinephrine (29–234%) were greater in Workout 2 and various HRV-derived indices were more depressed. Additionally, some HRV-derived indices appeared to be modulated (p < 0.05) by competitive level and sex at PRE and throughout the 30-min recovery period. These data suggest that autonomic activity may differ between the competitive and laboratory settings, and that the response may be further modulated by the workout’s design, the athlete’s sex, and competitive level.