Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome Wide Associations of Growth, Phenology, and Plasticity Traits in Willow [Salix viminalis (L.)]

The short rotation biomass crop willow (Salix genera) has been of interest for bioenergy but recently also for biofuel production. For a faster development of new varieties molecular markers could be used as selection tool in an early stage of the breeding cycle. To identify markers associated with growth traits, genome-wide association mapping was conducted using a population of 291 Salix viminalis accessions collected across Europe and Russia and a large set of genotyping-by-sequencing markers. The accessions were vegetatively propagated and planted in replicated field experiments, one in Southern Sweden and one in Central Sweden. Phenology data, including bud burst and leaf senescence, as well as different growth traits were collected and measured repeatedly between 2010 and 2017 at both field environments. A value of the plasticity for each accession was calculated for all traits that were measured the same year in both environments as the normalized accession value in one environment subtracted by the corresponding value in the other environment. Broad-sense accession heritabilities and narrow-sense chip heritabilities ranged from 0.68 to 0.95 and 0.45 to 0.99, respectively for phenology traits and from 0.56 to 0.85 and 0.24 to 0.97 for growth traits indicating a considerable genetic component for most traits. Population structure and kinship between accessions were taken into account in the association analyses. In total, 39 marker-trait associations were found where four were specifically connected to plasticity and interestingly one particular marker was associated to several different plasticity growth traits. Otherwise association consistency was poor, possibly due to accession by environment interactions which were demonstrated by the low structure adjusted accession correlations across environments (ranging from 0.40 to 0.58). However, one marker association with biomass fresh weight was repeatedly observed in the same environment over two harvest years. For some traits where several associations were found, the markers jointly explained over 20% of the accession variation. The result from this study using a population of unrelated accessions has given useful information about marker-trait associations especially highlighting marker-plasticity associations and genotype-by-environment interactions as important factors to take account of in future strategies of Salix breeding.
TROPHIC CASCADES, NUTRIENTS, AND LAKE PRODUCTIVITY: WHOLE‐LAKE EXPERIMENTS

Responses of zooplankton, pelagic primary producers, planktonic bacteria, and CO2 exchange with the atmosphere were measured in four lakes with contrasting food webs under a range of nutrient enrichments during a seven-year period. Prior to enrichment, food webs were manipulated to create contrasts between piscivore dominance and planktivore dominance. Nutrient enrichments of inorganic nitrogen and phosphorus exhibited ratios of N:P > 17:1, by atoms, to maintain P limitation. An unmanipulated reference lake, Paul Lake, revealed baseline variability but showed no trends that could confound the interpretation of changes in the nearby manipulated lakes. Herbivorous zooplankton of West Long Lake (piscivorous fishes) were large-bodied Daphnia spp. , in contrast to the small-bodied grazers that predominated in Peter Lake (planktivorous fishes). At comparable levels of nutrient enrichment, Peter Lake's areal chlorophyll and areal primary production rates exceeded those of West Long Lake by factors of approximatel.
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells

MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80–90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects.
Sth1, the Key Subunit of the RSC Chromatin Remodeling Complex, Is Essential in Maintaining Chromosomal Integrity and Mediating High Fidelity Chromosome Segregation in the Human Fungal Pathogen Candida albicans

Chromatin architecture influences gene expression and makes specialized chromatin domains. Factors including histone variants, histone modifiers and chromatin remodelers that define chromatin architecture impact chromosome related processes in Candida albicans. In this context, we sought to investigate the roles of the ATP-dependent chromatin remodeler, Remodel the Structure of Chromatin (RSC) in chromosome segregation of C. albicans. Sth1 is the key ATPase component of RSC and has profound roles in different cellular processes in Saccharomyces cerevisiae. We demonstrate that STH1 is an essential gene in C. albicans. The depletion of Sth1 induces pseudohyphal cells, abnormal spindle morphology, sensitivity toward anti-mitotic drugs and global cohesion defect suggesting an important role of Sth1 in kinetochore-microtubule related processes in C. albicans. Strikingly, Sth1 is required to maintain clustered kinetochores revealing the fact that RSC is required in kinetochore integrity. Taken together, we show that RSC plays an important role in various chromatin-templated processes including chromosome segregation in C. albicans.
Safety of Tyrosine Kinase Inhibitors in Patients With Differentiated Thyroid Cancer: Real-World Use of Lenvatinib and Sorafenib in Korea

Background: Thyroid cancer has become the most common cancer in Korea. Generally, thyroid cancer patients have a good prognosis; however, 15–20% of patients experience recurrence or distant metastasis or are refractory to standard treatment. We assessed the safety of sorafenib and lenvatinib in patients with advanced or metastatic radioactive iodine-refractory differentiated thyroid cancers (DTC) consecutively treated at a tertiary center in South Korea. Methods: We retrospectively reviewed the charts of all consecutive patients with DTC treated during ≥6 months with lenvatinib (February 2016–April 2018) and sorafenib (January 2014–April 2018) at Gangnam Severance Hospital. Patients were treated according to the prescribing information of each drug and were followed up for 2 months. We evaluated the adverse events (AEs) reported with each drug. Results: A total of 71 medical records (lenvatinib, n = 23; sorafenib, n = 48) were reviewed. The most common histological types were papillary thyroid cancer (69.0%) and follicular thyroid cancer (22.5%). All patients (n = 23) started lenvatinib at a dose of 20 mg; 41.7% of sorafenib-treated patients received an initial dose of 800 mg daily. Four (17.4%) lenvatinib-treated patients and 26 (54.2%) sorafenib-treated patients required treatment discontinuation. The most common AEs of any grade in the lenvatinib group were diarrhea (82.6%), hypertension (78.3%), hand-foot skin reaction (56.5%), weight loss (52.2%), proteinuria (47.8%), and anorexia (43.5%). In the sorafenib group, these were hand-foot skin reaction (87.5%), diarrhea (62.5%), anorexia (60.4%), alopecia (56.3%), mucositis (52.1%), weight loss and generalized weakness (each, 50%), and hypertension (43.8%). The incidence of hand-foot skin reaction, alopecia, and rash of any grade was significantly lower (P = 0.003, P = 0.017, and P = 0.017) in patients treated with lenvatinib compared with those treated with sorafenib. The incidence of hypertension, QT prolongation, and proteinuria of any grade was significantly higher (P = 0.006, P = 0.038, and P < 0.001) in patients treated with lenvatinib compared with those treated with sorafenib. Seven deaths occurred, which were attributed to disease progression. Conclusions: No new safety concerns were identified for either drug. Most AEs were managed with dose modification and medical therapy. AEs such as hypertension and proteinuria warrant close monitoring.
Childhood Sexual Abuse and Lifetime Aggression

ABSTRACT This study of college undergraduates (N = 873) examined three hypotheses regarding associations between childhood sexual abuse and lifetime aggression: 1) childhood sexual abuse was expected to account for unshared variance in the lifetime aggression indicators after controlling for the potential effects of parental physical abuse, sibling physical abuse, exposure to intimate partner violence, peer bullying, and respondent age; 2) childhood sexual abuse associations were expected to be relatively stronger among the women than the men; 3) childhood sexual abuse links to lifetime aggression were expected to vary as a function of age of victimization (adolescent < childhood < dual-age victims). Aggression histories varied widely with over 20% reporting prior injuries inflicted on others (3.2% > five injuries). Sexual abuse links to aggression tended to be stronger (p < .001) for the women than the men, and rates of aggression were higher when sexual abuse recurred across both childhood and adolescence. Partial support was found for all three hypotheses.
Label-Agnostic Sequence Labeling by Copying Nearest Neighbors

Retrieve-and-edit based approaches to structured prediction, where structures associated with retrieved neighbors are edited to form new structures, have recently attracted increased interest. However, much recent work merely conditions on retrieved structures (e.g., in a sequence-to-sequence framework), rather than explicitly manipulating them. We show we can perform accurate sequence labeling by explicitly (and only) copying labels from retrieved neighbors. Moreover, because this copying is label-agnostic, we can achieve impressive performance in zero-shot sequence-labeling tasks. We additionally consider a dynamic programming approach to sequence labeling in the presence of retrieved neighbors, which allows for controlling the number of distinct (copied) segments used to form a prediction, and leads to both more interpretable and accurate predictions.
Alterations to the Gut Microbiota and Their Correlation With Inflammatory Factors in Chronic Kidney Disease

Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera Lactobacillus, Clostridium IV, Paraprevotella, Clostridium sensu stricto, Desulfovibrio, and Alloprevotella were enriched in the fecal samples of patients with CKD, while Akkermansia and Parasutterella were enriched in those of the HC subjects. The abundance of Akkermansia in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of Akkermansia, an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera Parasutterella, Lactobacillus, Paraprevotella, Clostridium sensu stricto, and Desulfovibrio were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, Akkermansia was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially Akkermansia, may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.
Seismic Vulnerability of Buildings in Historic Centers: From the “Urban” to the “Aggregate” Scale

Seismic vulnerability assessment of urban centers is a challenging issue that needs to be faced accurately for the earthquake risk of large territorial areas. The selection of suitable methods is a crucial aspect that must be treated according to different evaluation processes, depending on the size of the problem and on the available calculation capacities. A possible strategy consists in analyzing large stocks of buildings, so to include in the analyses all those structural parameters that characterize their response and to involve the variability of the considered features. This would require a high computational effort that should be addressed to the investigation of the response of a large number of models. For this reason, simplified procedures based on engineeristic judgements, are commonly considered a viable way to be undertaken in order to predict damage scenarios. Alternatively, the attention could be focused on a limited number of buildings that are judged to be representative of the whole stock. In this case, more sophisticated analyses could be carried out and the obtained results could be extended to the whole urban center. Based on this premise, this paper presents the results obtained through the application of two different seismic vulnerability methodologies on the historic center of Campotosto, in Italy, which was hit by the last 2016 Central Italy earthquake. The first is an empirical method, applied considering a large stock of 130 buildings, which was calibrated by the authors after the 2009 L’Aquila earthquake for historical centers that are similar to the one studied in this paper. The latter, is a method based on analytical formulations dealt with by the Vulnus software, developed at the University of Padua in Italy, which was used for evaluating the seismic vulnerability of an aggregate building, which has been considered representative of the historic center. The final aim is to compare, also in the light of the damage observed after the 2016 earthquake, the damage scenarios, expressed in terms of fragility curves, derived from the two applied methodologies, in order to prove their reliability and to stress the possible issues related to their implementation at different scales.
Wasserstein Reinforcement Learning

We propose behavior-driven optimization via Wasserstein distances (WDs) to improve several classes of state-of-the-art reinforcement learning (RL) algorithms. We show that WD regularizers acting on appropriate policy embeddings efﬁciently incorporate behavioral characteristics into policy optimization. We demonstrate that they improve Evolution Strategy methods by encouraging more efﬁcient exploration, can be applied in imitation learning and to speed up training of Trust Region Policy Optimization methods. Since the exact computation of WDs is expensive, we develop approximate algorithms based on the combination of different methods: dual formulation of the optimal transport problem, alternating optimization and random feature maps, to effectively replace exact WD computations in the RL tasks considered. We provide theoretical analysis of our algorithms and exhaustive empirical evaluation in a variety of RL settings.
EEG Microstates Analysis in Young Adults With Autism Spectrum Disorder During Resting-State

Electroencephalography (EEG) is a useful tool to inspect the brain activity in resting state and allows to characterize spontaneous brain activity that is not detected when a subject is cognitively engaged. Moreover, taking advantage of the high time resolution in EEG, it is possible to perform fast topographical reference-free analysis, since different scalp potential fields correspond to changes in the underlying sources within the brain. In this study, the spontaneous EEG resting state (eyes closed) was compared between 10 young adults ages 18–30 years with autism spectrum disorder (ASD) and 13 neurotypical controls. A microstate analysis was applied, focusing on four temporal parameters: mean duration, the frequency of occurrence, the ratio of time coverage, and the global explained variance (GEV). Using data that were acquired from a 65-channel EEG system, six resting-state topographies that best describe the dataset across all subjects were identified by running a two-step cluster analysis labeled as microstate classes A–F. The results indicated that microstates B and E displayed statistically significant differences between both groups among the temporal parameters evaluated. Classes B, D, E, and F were consistently more present in ASD, and class C in controls. The combination of these findings with the putative functional significance of the different classes suggests that during resting state, the ASD group was more focused on visual scene reconstruction, while the control group was more engaged with self-memory retrieval. Furthermore, from a connectivity perspective, the resting-state networks that have been previously associated with each microstate class overlap the brain regions implicated in impaired social communication and repetitive behaviors that characterize ASD.
Provably Robust Deep Learning via Adversarially Trained Smoothed Classifiers

Recent works have shown the effectiveness of randomized smoothing as a scalable technique for building neural network-based classifiers that are provably robust to $\ell_2$-norm adversarial perturbations. In this paper, we employ adversarial training to improve the performance of randomized smoothing. We design an adapted attack for smoothed classifiers, and we show how this attack can be used in an adversarial training setting to boost the provable robustness of smoothed classifiers. We demonstrate through extensive experimentation that our method consistently outperforms all existing provably $\ell_2$-robust classifiers by a significant margin on ImageNet and CIFAR-10, establishing the state-of-the-art for provable $\ell_2$-defenses. Moreover, we find that pre-training and semi-supervised learning boost adversarially trained smoothed classifiers even further. Our code and trained models are available at this http URL .
Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel

Allergic contact dermatitis caused by contact sensitizers is a T-cell-mediated inflammatory skin disease. The most prevalent contact allergens is nickel. Whereas, memory T cells from nickel-allergic patients are well-characterized, little is known concerning nickel-specific naïve T-cell repertoire. The purpose of this study was to identify and quantify naïve CD4+ and CD8+ T cells recognizing nickel in the general population. Using a T-cell priming in vitro assay based on autologous co-cultures between naïve T cells and dendritic cells loaded with nickel, we were able to detect a naïve CD4+ and CD8+ T-cell repertoire for nickel in 10/11 and 7/8 of the tested donors. We calculated a mean frequency of 0.49 nickel-specific naïve CD4+ T cells and 0.37 nickel-specific naïve CD8+ T cells per million of circulating naïve T cells. The activation of these specific T cells requires MHC molecules and alongside IFN-γ production, some nickel-specific T-cells were able to produce granzyme-B. Interestingly, nickel-specific naïve CD4+ and CD8+ T cells showed a low rate of cross-reactivity with cobalt, another metallic hapten, frequently mixed with nickel in many alloys. Moreover, naïve CD4+ T cells showed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cell specific. Our results contribute to a better understanding of the mechanism of immunization to nickel and propose the T-cell priming assay as a useful tool to identify antigen-specific naïve T cells.
Participants Over-Estimate How Helpful They Are in a Two-Player Game Scenario Toward an Artificial Confederate That Discloses a Diagnosis of Autism

Research on how autistic people are perceived by neurotypical people indicates that disclosing a diagnosis leads to a positive discriminatory bias; however, autobiographical autistic accounts indicate that diagnostic disclosure often results in negative discriminatory behavior. We report on an exploratory study to compare people’s self-reported helping behavior with their actual helping behavior toward an assumed autistic collaborator. We led 255 participants to believe that they were interacting online with a real person to play Dyad3D, a maze navigation game where players must work together to open doors, and complete the levels. However, participants were actually playing with an artificial confederate (AC) that is programmed to behave the same way across all interactions. This design enabled us to manipulate the diagnostic status of the AC that participants received prior to collaboration across three conditions: no disclosure, dyslexia-disclosure, and autism-disclosure. We use this method to explore two research questions: (1) is Dyad3D viable in creating a simulated interaction that could deceive participants into believing they were collaborating with another human player online? and (2) what are the effects of disclosing an autism diagnosis on social perception and collaboration? Combined with a post-game questionnaire, we compared differences between diagnostic conditions and differences between self-reported behavior and actual behavior in the game. Our findings show that Dyad3D proved to be an efficient and viable method for creating a believable interaction (deception success rate >96%). Moreover, diagnostic disclosure of autism results in the AC being perceived as more intelligent and useful, but participants also perceived themselves to be more helpful toward the AC than they actually were. We evaluate the strengths and limitations of the current method and provide recommendations for future research. The source code for Dyad3D is freely available (CC-BY-NC 4.0) so that the study is reproducible and open to future adaptation.