Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation and Optimization of Highly Pure Motor Neurons from Human Induced Pluripotent Stem Cells via Lentiviral Delivery of Transcription Factors.

Generation of neurons from human induced pluripotent stem cells (hiPSCs) overcomes the limited access to human brain samples and greatly facilitates the progress of research in neurological diseases. However, it is still a challenge to generate a particular neuronal subtype with high purity and yield for determining the pathogenesis of diseased neurons using biochemical approaches. Motor neurons (MNs) are a specialized neuronal subtype responsible for governing both autonomic and volitional movement. Dysfunctions in MNs are implicated in a variety of movement diseases, such as amyotrophic lateral sclerosis (ALS). In this study, we generated functional MNs from human iPSCs via lentiviral delivery of transcription factors. Moreover, we optimized induction conditions by using different combinations of transcription factors and found that a single lentiviral vector expressing three factors (NGN2, ISL1, and LHX3) is necessary and sufficient to induce iPSC-MNs. These MNs robustly expressed general neuron markers (MAP2, SMI-32, and TUBB3), MN-specific markers (HB9 and ChAT), and showed electrical maturation and firing of action potentials within 3 weeks. This approach significantly improved the neuronal survival, yield, and purity, making it feasible to obtain abundant materials for biochemical studies in modeling movement diseases.
An overview of neuroblastoma cell lineage phenotypes and in vitro models

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine.
Controlling type I error rates in multi-arm clinical trials: A case for the false discovery rate

Multi‐arm trials are an efficient way of simultaneously testing several experimental treatments against a shared control group. As well as reducing the sample size required compared to running each trial separately, they have important administrative and logistical advantages. There has been debate over whether multi‐arm trials should correct for the fact that multiple null hypotheses are tested within the same experiment. Previous opinions have ranged from no correction is required, to a stringent correction (controlling the probability of making at least one type I error) being needed, with regulators arguing the latter for confirmatory settings. In this article, we propose that controlling the false‐discovery rate (FDR) is a suitable compromise, with an appealing interpretation in multi‐arm clinical trials. We investigate the properties of the different correction methods in terms of the positive and negative predictive value (respectively how confident we are that a recommended treatment is effective and that a non‐recommended treatment is ineffective). The number of arms and proportion of treatments that are truly effective is varied. Controlling the FDR provides good properties. It retains the high positive predictive value of FWER correction in situations where a low proportion of treatments is effective. It also has a good negative predictive value in situations where a high proportion of treatments is effective. In a multi‐arm trial testing distinct treatment arms, we recommend that sponsors and trialists consider use of the FDR.
Evaporative Water Loss Rates of Four Species of Aquatic Turtles from the Coastal Plain of the Southeastern United States

Abstract Many isolated wetlands in the southeastern United States are naturally ephemeral, productive habitats that can support a high diversity of aquatic reptiles. As wetlands begin to dry, reptile species exhibit different behavioral responses including overland dispersal and terrestrial aestivation. Regardless of strategy, one of the greatest risks to individual survival is desiccation. We measured evaporative water loss rates (EWL; % body mass lost per hour) and total % body mass lost over 24 h in four species of semiaquatic turtles that frequent isolated wetlands in the southeastern United States: Chicken Turtles (Deirochelys reticularia), Eastern Mud Turtles (Kinosternon subrubrum), Common Musk Turtles (Sternotherus odoratus), and Yellow-Bellied Sliders (Trachemys scripta scripta). Mean percent body mass lost over 24 h ranged from 4.44–10.26% among individuals, was negatively correlated with body mass and varied among species, with higher EWL rates occurring in species with reduced shell robustness (the amount of the body covered by the shell). Mean EWL rates were highest in S. odoratus, lowest in K. subrubrum, and intermediate in D. reticularia and T. scripta. The EWL rates corresponded to species' natural history traits and behavioral adaptations to drought. Species with higher EWL rates could be more vulnerable to increased drought duration and frequency resulting from either climate change or anthropogenic modification of wetland hydrology, and easily measured traits such as shell robustness and body mass may be useful in predicting EWL rates and desiccation risk for particular age classes and other species of turtles.
Unconscious categorization of sub-millisecond complex images

Can people categorize complex visual scenes unconsciously? The possibility of unconscious perception remains controversial. Here, we addressed this question using psychophysical methods applied to unmasked visual stimuli presented for extremely short durations (in the μsec range) by means of a custom-built modern tachistoscope. Our experiment was composed of two phases. In the first phase, natural or urban scenes were either absent or present (for varying durations) on the tachistoscope screen, and participants were simply asked to evaluate their subjective perception using a 3-points scale (absence of stimulus, stimulus detection or stimulus identification). Participants’ responses were tracked by means of two staircases. The first psychometric function aimed at defining participants’ proportion of subjective detection responses (i.e., not having seen anything vs. having seen something without being able to identify it), while the second staircase tracked the proportion of subjective identification rates (i.e., being unaware of the stimulus’ category vs. being aware of it). In the second phase, the same participants performed an objective categorization task in which they had to decide, on each trial, whether the image was a natural vs. an urban scene. A third staircase was used in this phase so as to build a psychometric curve reflecting the objective categorization performance of each participant. In this second phase, participants also rated their subjective perception of each stimulus on every trial, exactly as in the first phase of the experiment. Our main result is that objective categorization performance, here assumed to reflect the contribution of both conscious and unconscious trials, cannot be explained based exclusively on conscious trials. This clearly suggests that the categorization of complex visual scenes is possible even when participants report being unable to consciously perceive the contents of the stimulus.
Mechanistic insights into the protein targeting mediated by signal recognition particle

La particule de reconnaissance du signal (SRP) et son recepteur (SR) assurent l'entree des proteines dans le reticulum endoplasmique. Pour mieux comprendre le role de SRP dans le processus de la translocation des proteines dans les cellules de mammiferes, nous avons diminue, en utilisant des RNAi, la quantite de differentes sous unites de SRP. Lorsque l'une des sous-unites est affectee, la translocation des proteines dans le RE devient defectueuse. Nous avons voulu determiner quelles sont l'importance et les bases moleculaires de l'arret d'elongation. Pour cela, nous avons remplace le SRP endogene par un SRP ayant perdu sa fonction d'arret d'elongation. Sans arret d'elongation, la translocation et la croissance sont affectees. Ces defauts sont corriges par un ralentissement de la traduction ou une augmentation de la quantite de SR. Globalement, nos etudes montrent que le SRP est essentiel pour la translocation des proteines, plus particulierement, sa fonction d'arret d'elongation est necessaire au ralentissement de la traduction et permet une translocation efficace.
Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids

Plant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative breast cancer (TNBC). The present work aimed to assess the metabolic effects of BA and UA in MDA-MB-231 breast cancer cells (TNBC model), as well as in MCF-10A non-cancer breast epithelial cells, with a view to unveiling the involvement of metabolic reprogramming in cellular responses to these TAs. Cell viability and cell cycle analyses were followed by assessment of changes in the cells exo- and endometabolome through 1H NMR analysis of cell culture medium supernatants, aqueous and organic cell extracts. In MDA-MB-231 cells, BA was suggested to induce a transient upregulation of glucose consumption and glycolytic conversion, tricarboxylic acid (TCA) cycle intensification, and hydrolysis of neutral lipids, while UA effects were much less pronounced. In MCF-10A cells, boosting of glucose metabolism by the two TAs was accompanied by diversion of glycolytic intermediates to the hexosamine biosynthetic pathway (HBP) and the synthesis of neutral lipids, possibly stored in detoxifying lipid droplets. Additionally, breast epithelial cells intensified pyruvate consumption and TCA cycle activity, possibly to compensate for oxidative impairment of pyruvate glycolytic production. This study provided novel insights into the metabolic effects of BA and UA in cancer and non-cancer breast cells, thus improving current understanding of the action of these compounds at the molecular level.
Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage–myofibroblast transition

Significance Macrophage–myofibroblast transition (MMT) is a newly discovered pathogenic process by which TGF-β1/Smad3 signaling promotes tissue scarring. However, systemic targeting of Smad3 may impair host T cell immunity; therefore, it is preferable to focus on downstream mechanisms to identify antifibrotic therapies that avoid targeting Smad3 per se. In this study, we revealed a brain-specific transcription factor Pou4f1 as the key regulator by which TGF-β1/Smad3 signaling executes MMT. Macrophage-specific silencing of Pou4f1 effectively blocked progression of renal fibrosis in two mouse kidney disease models. Thus, Pou4f1 represents a therapeutic target in MMT-driven renal diseases. Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage–myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, α-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGF-β1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-β1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.
Nutritional Status and Quality of Life in Hospitalised Cancer Patients Who Develop Intestinal Failure and Require Parenteral Nutrition: An Observational Study

(1) Background: Malnutrition in cancer patients impacts quality of life (QoL) and performance status (PS). When oral/enteral nutrition is not possible and patients develop intestinal failure, parenteral nutrition (PN) is indicated. Our aim was to assess nutritional status, QoL, and PS in hospitalised cancer patients recently initiated on PN for intestinal failure. (2) Methods: The design was a cross-sectional observational study. The following information was captured: demographic, anthropometric, biochemical and medical information, as well as nutritional screening tool (NST), patient-generated subjective global assessment (PG-SGA), functional assessment of cancer therapy-general (FACT-G), and Karnofsky PS (KPS) data. (3) Results: Among 85 PN referrals, 30 oncology patients (56.2 years, 56.7% male) were identified. Mean weight (60.3 ± 16.6 kg) corresponded to normal body mass index values (21.0 ± 5.1 kg/m2). However, weight loss was significant in patients with gastrointestinal tumours (p < 0.01). A high malnutrition risk was present in 53.3–56.7% of patients, depending on the screening tool. Patients had impaired QoL (FACT-G: 26.6 ± 9.8) but PS indicated above average capability with independent daily activities (KPS: 60 ± 10). (4) Conclusions: Future research should assess the impact of impaired NS and QoL on clinical outcomes such as survival, with a view to encompassing nutritional and QoL assessment in the management pathway of this patient group.
Early detection of internet trolls: Introducing an algorithm based on word pairs / single words multiple repetition ratio

Troll internet messages, especially those posted on Twitter, have recently been recognised as a very powerful weapon in hybrid warfare. Hence, an important task for the academic community is to provide a tool for identifying internet troll accounts as quickly as possible. At the same time, this tool must be highly accurate so that its employment will not violate people’s rights and affect the freedom of speech. Though such a task can be effectively fulfilled on purely linguistic grounds, as of yet, very little work has been done that could help to explain the discourse-specific features of this type of writing. In this paper, we suggest a quantitative measure for identifying troll messages which is based on taking into account certain sociolinguistic limitations of troll speech, and discuss two algorithms that both require as few as 50 tweets to establish the true nature of the tweets, whether ‘genuine’ or ‘troll-like’.
Depressive Tendency and the Risk of Death from Pneumonia: The JACC Study

Objective The burden of death from pneumonia is expected to increase with the aging of the population, as has been observed in Japan. Depressive tendency, a common psychosocial sign, may be a risk factor for pneumonia due to its possible association with some immune dysfunction. This study aimed to clarify the association between depressive tendency and the risk of death from pneumonia. Methods A population-based cohort that consisted of 75,174 Japanese men and women was followed for a median of 19.1 years. Four psychological and behavioral symptoms (depressive symptoms) were used to evaluate depressive tendency. Results A total of 1,329 deaths from pneumonia were observed. Depressive symptoms were positively and dose-dependently associated with the risk of death from pneumonia (p<0.001 for trend), and subjects with ≥2 depressive symptoms showed a significantly elevated risk compared to those without any symptoms [multivariable hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.39-1.99]. This association was not significantly affected by sex or age at baseline. The elevated risk was still significant even when subjects were limited to those without any medical histories. The excess risk was observed not only for death occurring within the first 10 years of follow-up (multivariable HR, 2.05; 95% CI, 1.51-2.78) but also for that occurring in the longer follow-up period (multivariable HR, 1.48; 95% CI, 1.18-1.85). Conclusion Depressive tendency may be a risk factor for death from pneumonia. Further studies using a more reliable tool for the evaluation of depressive state are necessary to confirm this relationship.
Underwater TDOA Acoustical Location Based on Majorization-Minimization Optimization

Underwater acoustic localization is a useful technique applied to any military and civilian applications. Among the range-based underwater acoustic localization methods, the time difference of arrival (TDOA) has received much attention because it is easy to implement and relatively less affected by the underwater environment. This paper proposes a TDOA-based localization algorithm for an underwater acoustic sensor network using the maximum-likelihood (ML) ratio criterion. To relax the complexity of the proposed localization complexity, we construct an auxiliary function, and use the majorization-minimization (MM) algorithm to solve it. The proposed localization algorithm proposed in this paper is called a T-MM algorithm. T-MM is applying the MM algorithm to the TDOA acoustic-localization technique. As the MM algorithm iterations are sensitive to the initial points, a gradient-based initial point algorithm is used to set the initial points of the T-MM scheme. The proposed T-MM localization scheme is evaluated based on squared position error bound (SPEB), and through calculation, we get the SPEB expression by the equivalent Fisher information matrix (EFIM). The simulation results show how the proposed T-MM algorithm has better performance and outperforms the state-of-the-art localization algorithms in terms of accuracy and computation complexity even under a high presence of underwater noise.
Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers

Killer meiotic drivers are genetic parasites that destroy ‘sibling’ gametes lacking the driver allele. The fitness costs of drive can lead to selection of unlinked suppressors. This suppression could involve evolutionary tradeoffs that compromise gametogenesis and contribute to infertility. Schizosaccharomyces pombe, an organism containing numerous gamete (spore)-killing wtf drivers, offers a tractable system to test this hypothesis. Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. Moreover, we find that S. pombe isolates vary greatly in their ability to make haploid spores, with some isolates generating up to 46% aneuploid or diploid spores. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.
Who is a credible source of preventive advice? An experimental vignette study of general public attitudes towards role expansion in health and social care.

OBJECTIVES To investigate the general public's source credibility attitudes towards health and social care professionals when giving advice associated with their 'traditional role' versus an 'expanded health behaviour change' role, to facilitate the implementation of the health behaviour change agenda. DESIGN A 3x3 experimental between-subjects vignette questionnaire study with nine scenarios in which a general practitioner (GP), health visitor, or firefighter offered advice on either stopping smoking, preventing cot death, or fire safety. Combinations were either congruent with a traditional role (e.g., health visitor and cot death) or an expanded role (e.g., firefighter and stopping smoking). METHODS Adults were recruited from metropolitan locations in northern England. Participants were randomized to one scenario and complete a validated 18-item source credibility questionnaire. Factor analysis explored source credibility components; ratings for traditional and expanded role scenarios were compared using Mann-Whitney tests. RESULTS 369 participants completed the questionnaire (49.3% women, 64% White British, age range: 16-83). Factor analysis confirmed three source credibility dimensions: competence, caring, and trustworthiness. Ratings were generally high across professions and scenarios; participants rated professionals as significantly more 'competent' where scenarios related to their traditional roles than expanded roles (U 9778.5, p <.001) but equally as caring (U = 14467.5, p< .485) and trustworthy (U 14250.5, p .348). CONCLUSIONS GPs, health visitors, and firefighters were all perceived as credible sources of health behaviour change advice, but may be viewed as 'less competent' sources of messages associated with an expanded job role. Effective professional training and public engagement regarding the role expansion agenda are needed to support policy implementation. Statement of Contribution What is already known on this subject? Source credibility surrounds people's perceptions of the source of advice and includes competence, caring, and trustworthiness dimensions. This may have an important influence on people's attitudes and behaviour, especially when messages are complex or emotive. A wide range of public sector workers is now expected to routinely offer preventive health and safety advice, as part of role expansion. What does this study add? This experimental survey study compared source credibility perceptions of GPs, health visitors, and firefighters giving advice on topics associated with a traditional or expanded role. Professionals were perceived as less 'competent' when giving advice on 'expanded role' topics, such as a firefighter discussing smoking, with a small reduction in source credibility. This highlights that source credibility may be specific to professional identities. Policymakers may need to explore this further as part of implementing role expansion for prevention and self-management in health and social care.