Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance

Objective. Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. Approach. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. Main results. About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Significance. Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012–10-04)
Repeatable measures of take‐off flight performance in auklets

Rapid acceleration is the key to a successful escape manoeuvre and has attracted considerable research attention in a wide array of taxa. I recorded take-offs of least auklets Aethia pusilla and crested auklets Aethia cristatella with digital video (60 frames per second). To smooth time–location data derived from video, I used predicted mean square error quintic splines, which have been shown to be good predictors of true acceleration. Repeated recordings of the same individual bird allowed me to measure repeatability of take-off acceleration and velocity to find the most robust and biologically meaningful measure. The most repeatable take-off parameters were power at time t=0.17 s after take-off (r=75%) and acceleration at t=0.17 s (r=72%). The horizontal component of velocity at t=0.32 s was least affected by the slope of the take-off trajectory. The mean acceleration of both species is close to expected values based on body mass, even though all previously studied species had considerably lower body mass. Within least auklets, however, I did not find a significant relationship of velocity or acceleration with mass. This would be expected if the observed drop in mass after hatching was an adaptation to reduce the risk of predation. I conclude that acceleration and exerted power at a certain time after take-off is repeatable and the most suitable measure of performance for both inter- and intra-specific comparisons.
Associations Between Nutrition Knowledge and Overall Diet Quality: The Moderating Role of Sociodemographic Characteristics—Results From the PREDISE Study

Purpose: To assess how nutrition knowledge is associated with global diet quality and to investigate whether sociodemographic characteristics (ie, sex, age, education, income, marital status, and living with children or not) moderate this association. Design: Cross-sectional web-based study. Participants: The PREDISE study aims at identifying correlates of adherence to healthy eating guidelines in French-speaking adults from the Province of Quebec, Canada. Subjects: A probability sample of 1092 participants (50% female). Measures: The Nutrition Knowledge Questionnaire and 24-hour food recalls from which the Canadian Healthy Eating Index (C-HEI) was calculated. Analysis: Multiple linear regressions performed to assess how nutrition knowledge is associated with the C-HEI. Interaction terms tested to evaluate whether sociodemographic characteristics moderate the association between nutrition knowledge and the C-HEI. Results: Nutrition knowledge (B = 0.141 [95% CI: 0.075-0.208], P < .0001) was identified as a significant correlate of the C-HEI. Education significantly moderated the association between nutrition knowledge and the C-HEI (P interaction = .0038), with a significative association among participants with a lower education level (B = 0.295 [95% CI: 0.170-0.421], P < .0001) but not among participants with a higher education level (B = 0.077 [95% CI: −0.004 to 0.157], P = .06). Whether participants lived with or without children also significantly moderated the association (P interaction = 0.0043); nutrition knowledge was associated with the C-HEI only in participants who were not living with children (B = 0.261 [95% CI: 0.167 to 0.355], P < .0001). Conclusion: This study suggests that the association between nutrition knowledge and adherence to healthy eating guidelines is not the same in different subgroups of the population. Interventions aiming at increasing nutrition knowledge may be a promising approach to improve diet quality, especially among individuals with a lower education.
Consistent scaling of inbreeding depression in space and time in a house sparrow metapopulation

Significance Inbreeding often causes negative effects that, according to theory, may vary in severity with population size or harshness of the environment. Studying this in wild vertebrates has been prevented by the difficulty of collecting long-term data on multiple populations. We used genomic estimates of inbreeding to investigate its effects on fitness components and morphological traits in bird populations. Inbred individuals had lower survival and produced fewer offspring compared with noninbred individuals. Inbreeding depression was constant across populations with differing environments and population sizes. Consequently, populations with more resident inbreeding suffered higher total loss of fitness due to inbreeding. Our results highlight the importance of considering inbreeding in conservation and management of populations with a wide range of characteristics. Inbreeding may increase the extinction risk of small populations. Yet, studies using modern genomic tools to investigate inbreeding depression in nature have been limited to single populations, and little is known about the dynamics of inbreeding depression in subdivided populations over time. Natural populations often experience different environmental conditions and differ in demographic history and genetic composition, characteristics that can affect the severity of inbreeding depression. We utilized extensive long-term data on more than 3,100 individuals from eight islands in an insular house sparrow metapopulation to examine the generality of inbreeding effects. Using genomic estimates of realized inbreeding, we discovered that inbred individuals had lower survival probabilities and produced fewer recruiting offspring than noninbred individuals. Inbreeding depression, measured as the decline in fitness-related traits per unit inbreeding, did not vary appreciably among populations or with time. As a consequence, populations with more resident inbreeding (due to their demographic history) paid a higher total fitness cost, evidenced by a larger variance in fitness explained by inbreeding within these populations. Our results are in contrast to the idea that effects of inbreeding generally depend on ecological factors and genetic differences among populations, and expand the understanding of inbreeding depression in natural subdivided populations.
Conditionally Reprogrammed Cells from Patient-Derived Xenograft to Model Neuroendocrine Prostate Cancer Development

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-field patient-derived xenograft (PDX) model of adenocarcinoma (LTL331)-to-NEPC (LTL331R) transdifferentiation. In this study, we applied conditional reprogramming (CR) culture to establish a LTL331 PDX-derived cancer cell line named LTL331_CR_Cell. These cells retain the same genomic mutations as the LTL331 parental tumor. They can be continuously propagated in vitro and can be genetically manipulated. Androgen deprivation treatment on LTL331_CR_Cells had no effect on cell proliferation. Transcriptomic analyses comparing the LTL331_CR_Cell to its parental tumor revealed a profound downregulation of the androgen response pathway and an upregulation of stem and basal cell marker genes. The transcriptome of LTL331_CR_Cells partially resembles that of post-castrated LTL331 xenografts in mice. Notably, when grafted under the renal capsules of male NOD/SCID mice, LTL331_CR_Cells spontaneously gave rise to NEPC tumors. This is evidenced by the histological expression of the NE marker CD56 and the loss of adenocarcinoma markers such as PSA. Transcriptomic analyses of the newly developed NEPC tumors further demonstrate marked enrichment of NEPC signature genes and loss of AR signaling genes. This study provides a novel research tool derived from a unique PDX model. It allows for the investigation of mechanisms underlying NEPC development by enabling gene manipulations ex vivo and subsequent functional evaluations in vivo.
Thymus vulgaris L. Essential Oil Solid Formulation: Chemical Profile and Spasmolytic and Antimicrobial Effects

A new Thymus vulgaris L. solid essential oil (SEO) formulation composed of liquid EO linked to solid excipients has been chemically analysed and evaluated for its intestinal spasmolytic and antispastic effects in ex vivo ileum and colon of guinea pig and compared with liquid EO and excipients. Liquid EO and solid linked EO were analysed by original capillary electrochromatography coupled to diode array detection (CEC-DAD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodologies. The main bioactive constituents are thymol and carvacrol, with minor constituents for a total of 12 selected analysed compounds. Liquid EO was the most effective in decreasing basal contractility in ileum and colon; excipients addiction permitted normal contractility pattern in solid linked EO SEO. In ileum and colon, the Thymus vulgaris L. solid formulation exerted the relaxant activity on K+-depolarized intestinal smooth muscle as well as liquid EO. The solid essential oil exhibits antimicrobial activity against different strains (Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Salmonella Thyphimurium, Candida albicans) similarly to liquid oil, with activity against pathogen, but not commensal strains (Bifidobacterium Breve, Lactobacillus Fermentum) in intestinal homeostasis. Therefore, Thymus vulgaris L. solid essential oil formulation can be proposed as a possible spasmolytic and antispastic tool in medicine.
Carbon sequestration in a high‐elevation, subalpine forest

We studied net ecosystem CO2 exchange (NEE) dynamics in a high‐elevation, subalpine forest in Colorado, USA, over a two‐year period. Annual carbon sequestration for the forest was 6.71 mol C m−2 (80.5 g C m−2) for the year between November 1, 1998 and October 31, 1999, and 4.80 mol C m−2 (57.6 g C m−2) for the year between November 1, 1999 and October 31, 2000. Despite its evergreen nature, the forest did not exhibit net CO2 uptake during the winter, even during periods of favourable weather. The largest fraction of annual carbon sequestration occurred in the early growing‐season; during the first 30 days of both years. Reductions in the rate of carbon sequestration after the first 30 days were due to higher ecosystem respiration rates when mid‐summer moisture was adequate (as in the first year of the study) or lower mid‐day photosynthesis rates when mid‐summer moisture was not adequate (as in the second year of the study). The lower annual rate of carbon sequestration during the second year of the study was due to lower rates of CO2 uptake during both the first 30 days of the growing season and the mid‐summer months. The reduction in CO2 uptake during the first 30 days of the second year was due to an earlier‐than‐normal spring warm‐up, which caused snow melt during a period when air temperatures were lower and atmospheric vapour pressure deficits were higher, compared to the first 30 days of the first year. The reduction in CO2 uptake during the mid‐summer of the second year was due to an extended drought, which was accompanied by reduced latent heat exchange and increased sensible heat exchange. Day‐to‐day variation in the daily integrated NEE during the summers of both years was high, and was correlated with frequent convective storm clouds and concomitant variation in the photosynthetic photon flux density (PPFD). Carbon sequestration rates were highest when some cloud cover was present, which tended to diffuse the photosynthetic photon flux, compared to periods with completely clear weather.
Exploring the Ecology and Indicator Value of Some Larvae of Odonata Genera in Colombia

Abstract Bioindication is a method to assess environmental conditions using indicator organisms. In Colombia, water quality evaluation is mostly performed following the Biological Monitoring Working Party/Colombia method (BMWP/ Col), which uses aquatic macroinvertebrates at the taxonomic family level. Studies on potential bioindicators are important to produce comprehensive information on the requirements of macroinvertebrates and their value for water quality bioindication. We studied the larval ecology of several common genera of Odonata from Colombian freshwater ecosystems and assigned an indicator value to each genus.The physical and chemical water characteristics of 1,022 sites surveyed in Colombia from 2005 to 2016 were analyzed using a principal component analysis (PCA). The relationship between environmental conditions and Odonata genera found was studied using multiple logistic regressions between sample coordinates of the first three axes of the PCA and occurrence of the respective genus. We assigned an indicator value for each genus using the logistic regression and the water quality of samples. The highest indicator values were assigned to genera, which were mainly explained by the PCA axis associated with water quality, showed a high odds ratio to this axis, and were found in ecosystems with excellent water quality.The indicator values suggested for each taxon are, Brechmorhoga Kirby, 1894, 8; Macrothemis Hagen, 1868, 4; Micrathyria Kirby, 1889, 4 (Libellulidae); Progomphus Selys, 1854, 7 (Gomphidae); Acanthagrion Selys, 1876, 4; and Argia Rambur, 1842, 7 (Coenagrionidae). Differences in water quality preferences in genera of the same family suggest that higher taxonomic resolution may allow more detailed environmental assessments.
Measuring individual benefits of psychiatric treatment using longitudinal binary outcomes: Application to antipsychotic benefits in non-cannabis and cannabis users

ABSTRACT We present and evaluate a method for predicting individual treatment benefits based on random effects logistic regression models of binary outcomes that change over time. The method uses empirical Bayes predictors based on patients’ characteristics and responses to treatment. It is applicable to both 1-dimentional and 2-dimentional personalized medicine models. Comparisons between predicted and true benefits for simulated new patients using correlations, relative biases and mean-squared errors were used to evaluate prediction performance. The predicted benefits had relatively small biases and relatively high correlations with the true benefits in the simulated new patients. The predictors also captured estimated overall population trends in the evolution of individual benefits. The proposed approach can be used to retrospectively evaluate patients’ responses in a clinical trial, or to retrospectively or prospectively predict individual benefits of different treatments for new patients using patients’ characteristics and previous responses. The method is used to examine changes in the disorganized dimension of antipsychotic-naïve patients from an antipsychotic randomized clinical trial. Retrospective prediction of individual benefits revealed that more cannabis users had slower and lower responses to antipsychotic treatment as compared to non-cannabis users, revealing cannabis use as a negative prognostic factor for psychotic disorders in the disorganized dimension.
Seneca Valley Virus 3Cpro Cleaves PABPC1 to Promote Viral Replication

Seneca Valley Virus (SVV) is an oncolytic virus of the Picornaviridae family, which has emerged in recent years. The impact of SVV on host cell translation remains unknown. Here, we showed, for the first time, that SVV infection cleaved poly(A) binding protein cytoplasmic 1 (PABPC1). In SVV-infected cells, 50 kDa of the N terminal cleaved band and 25 kDa of the C terminal cleaved band of PABPC1 were detected. Further study showed that the viral protease, 3Cpro induced the cleavage of PABPC1 by its protease activity. The SVV strains with inactive point mutants of 3Cpro (H48A, C160A or H48A/C160A) can not be rescued by reverse genetics, suggesting that sites 48 and 160 of 3Cpro were essential for SVV replication. SVV 3Cpro induced the cleavage of PABPC1 at residue 437. A detailed data analysis showed that SVV infection and the overexpression of 3Cpro decreased the protein synthesis rates. The protease activity of 3Cpro was essential for inhibiting the protein synthesis. Our results also indicated that PABPC1 inhibited SVV replication. These data reveal a novel antagonistic mechanism and pathogenesis mediated by SVV and highlight the importance of 3Cpro on SVV replication.
Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- and late-replicating euchromatin

Significance In eukaryotes, DNA replication origins, the sites where new DNA synthesis begins during the process of cell division, must be adequately distributed across chromosomes to maintain normal cell proliferation and genome stability. This study describes a repressive chromatin-mediated mechanism that acts at the level of individual origins to attenuate the efficiency of origin function. This attenuation is essential for achieving the normal spatial distribution of origins across the chromosomes of the eukaryotic microbe Saccharomyces cerevisiae. While the importance of chromosomal origin distribution to genome stability and cellular fitness is acknowledged, this study defines a chromatin modification that establishes the normal spatial distribution of origins across a eukaryotic genome. A eukaryotic chromosome relies on the function of multiple spatially distributed DNA replication origins for its stable inheritance. The spatial location of an origin is determined by the chromosomal position of an MCM complex, the inactive form of the DNA replicative helicase that is assembled onto DNA in G1-phase (also known as origin licensing). While the biochemistry of origin licensing is understood, the mechanisms that promote an adequate spatial distribution of MCM complexes across chromosomes are not. We have elucidated a role for the Sir2 histone deacetylase in establishing the normal distribution of MCM complexes across Saccharomyces cerevisiae chromosomes. In the absence of Sir2, MCM complexes accumulated within both early-replicating euchromatin and telomeric heterochromatin, and replication activity within these regions was enhanced. Concomitantly, the duplication of several regions of late-replicating euchromatin were delayed. Thus, Sir2-mediated attenuation of origin licensing within both euchromatin and telomeric heterochromatin established the normal spatial distribution of origins across yeast chromosomes important for normal genome duplication.
An open access mouse brain flatmap and upgraded rat and human brain flatmaps based on current reference atlases

Here we present a flatmap of the mouse central nervous system (CNS) (brain) and substantially enhanced flatmaps of the rat and human brain. Also included are enhanced representations of nervous system white matter tracts, ganglia, and nerves, and an enhanced series of 10 flatmaps showing different stages of rat brain development. The adult mouse and rat brain flatmaps provide layered diagrammatic representation of CNS divisions, according to their arrangement in corresponding reference atlases: Brain Maps 4.0 (BM4, rat) (Swanson, The Journal of Comparative Neurology, 2018, 526, 935–943), and the first version of the Allen Reference Atlas (mouse) (Dong, The Allen reference atlas, (book + CD‐ROM): A digital color brain atlas of the C57BL/6J male mouse, 2007). To facilitate comparative analysis, both flatmaps are scaled equally, and the divisional hierarchy of gray matter follows a topographic arrangement used in BM4. Also included with the mouse and rat brain flatmaps are cerebral cortex atlas level contours based on the reference atlases, and direct graphical and tabular comparison of regional parcellation. To encourage use of the brain flatmaps, they were designed and organized, with supporting reference tables, for ease‐of‐use and to be amenable to computational applications. We demonstrate how they can be adapted to represent novel parcellations resulting from experimental data, and we provide a proof‐of‐concept for how they could form the basis of a web‐based graphical data viewer and analysis platform. The mouse, rat, and human brain flatmap vector graphics files (Adobe Reader/Acrobat viewable and Adobe Illustrator editable) and supporting tables are provided open access; they constitute a broadly applicable neuroscience toolbox resource for researchers seeking to map and perform comparative analysis of brain data.
EFFECT OF ADDITIVES CONTAINING LACTIC ACID BACTERIA AND/OR HYDROLYTIC ENZYMES WITH AN ANTIOXIDANT UPON THE PRESERVATION OF CORN OR ALFALFA SILAGE

A silage additive containing lactic acid bacteria was tested for its effect upon preservation of corn silage, 35–40% dry matter (DM), in four pairs of upright silos (100-t capacity). The additive did not affect (P > 0.05) final pH, lactic or acetic acid concentration, crude protein or NPN-N and NH4+-N expressed as a percent of total N. Recovery of energy from treated silage was greater than control in the two pairs of silos where this was determined, but recoveries of dry matter and crude protein were not consistently affected. Two silage additives, containing hydrolytic enzymes and an antioxidant with or without lactic acid bacteria, were tested on alfalfa, 20, 30, 36.5 and 47.3% DM, in 250-mL laboratory silos. The experimental design used a4 (DM level) × 4 (added glucose — 0,4,8 and 12%, DM basis) × 3 (additive — control, a hydrolytic enzyme/antioxidant additive (E/AO), and E/AO plus lactic acid bacteria (E/AO +)) factorial arrangement of treatments. Alfalfa was harvested using farm equipment. For 60-da.