Miracle-dz/UniFAR-FTUs huggingface dataset:
TEspeX: consensus-specific quantification of transposable element expression preventing biases from exonized fragments

Abstract Summary Transposable elements (TEs) play key roles in crucial biological pathways. Therefore, several tools enabling the quantification of their expression were recently developed. However, many of the existing tools lack the capability to distinguish between the transcription of autonomously expressed TEs and TE fragments embedded in canonical coding/non-coding non-TE transcripts. Consequently, an apparent change in the expression of a given TE may simply reflect the variation in the expression of the transcripts containing TE-derived sequences. To overcome this issue, we have developed TEspeX, a pipeline for the quantification of TE expression at the consensus level. TEspeX uses Illumina RNA-seq short reads to quantify TE expression avoiding counting reads deriving from inactive TE fragments embedded in canonical transcripts. Availability and implementation The tool is implemented in python3, distributed under the GNU General Public License (GPL) and available on Github at https://github.com/fansalon/TEspeX (Zenodo URL: https://doi.org/10.5281/zenodo.6800331). Supplementary information Supplementary data are available at Bioinformatics online.
Multi-Task and Few-Shot Learning-Based Fully Automatic Deep Learning Platform for Mobile Diagnosis of Skin Diseases

Fluorescence imaging-based diagnostic systems have been widely used to diagnose skin diseases due to their ability to provide detailed information related to the molecular composition of the skin compared to conventional RGB imaging. In addition, recent advances in smartphones have made them suitable for application in biomedical imaging, and therefore various smartphone-based optical imaging systems have been developed for mobile healthcare. However, an advanced analysis algorithm is required to improve the diagnosis of skin diseases. Various deep learning-based algorithms have recently been developed for this purpose. However, deep learning-based algorithms using only white-light reflectance RGB images have exhibited limited diagnostic performance. In this study, we developed an auxiliary deep learning network called fluorescence-aided amplifying network (FAA-Net) to diagnose skin diseases using a developed multi-modal smartphone imaging system that offers RGB and fluorescence images. FAA-Net is equipped with a meta-learning-based algorithm to solve problems that may occur due to the insufficient number of images acquired by the developed system. In addition, we devised a new attention-based module that can learn the location of skin diseases by itself and emphasize potential disease regions, and incorporated it into FAA-Net. We conducted a clinical trial in a hospital to evaluate the performance of FAA-Net and to compare various evaluation metrics of our developed model and other state-of-the-art models for the diagnosis of skin diseases using our multi-modal system. Experimental results demonstrated that our developed model exhibited an 8.61% and 9.83% improvement in mean accuracy and area under the curve in classifying skin diseases, respectively, compared with other advanced models.
MORPH: Design Co-optimization with Reinforcement Learning via a Differentiable Hardware Model Proxy

We introduce MORPH, a method for co-optimization of hardware design parameters and control policies in simulation using reinforcement learning. Like most co-optimization methods, MORPH relies on a model of the hardware being optimized, usually simulated based on the laws of physics. However, such a model is often difficult to integrate into an effective optimization routine. To address this, we introduce a proxy hardware model, which is always differentiable and enables efficient co-optimization alongside a long-horizon control policy using RL. MORPH is designed to ensure that the optimized hardware proxy remains as close as possible to its realistic counterpart, while still enabling task completion. We demonstrate our approach on simulated 2D reaching and 3D multi-fingered manipulation tasks.
Association between unmet post-arrival expectations and psychological symptoms in recently arrived refugees

Thwarted expectations regarding one's post-settlement life may challenge the mental health of refugees. The present study aimed to investigate the relationship between pre-arrival expectations and the course of psychological symptoms across time. A secondary analysis of 1,496 principal visa applicants across five waves of the Building a New Life in Australia (BNLA) study was conducted. The cross-sectional associations between expectations on the one hand, and post-traumatic stress (PTSD-8) symptoms and psychological distress (Kessler-6; K6) on the other, were assessed using multiple regression. Latent class growth analysis (LCGA) was used to identify discrete symptom trajectories of psychological symptoms across five years following settlement, and multinomial regressions were used to determine if violated expectations predicted membership of identified PTSD-8 and K6 class trajectories. LCGA supported a four-class solution for the PTSD-8 “Resilient Post Traumatic Stress (PTS)” (54.1%), “Improving PTS” (15.0%), “Deteriorating PTS” (17.3%), and “Persistently High PTS” (13.6%). For the K6, three classes were identified: “Persistently Mild K6” (60.4%), “Resilient K6” (9.4%), and “Persistently High K6” (30.2%). Thwarted expectations were found to significantly predict membership of less favourable symptom trajectories classes in the context of other established predictors. Post-settlement expectations may thus have weak but unique predictive value for the course of psychological symptoms alongside other factors such as older age and financial stress. Implications of these findings for service provision and policy are discussed.
Ambra1 haploinsufficiency in CD1 mice results in metabolic alterations and exacerbates age-associated retinal degeneration

ABSTRACT Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function. While studies of mice lacking essential autophagy genes have revealed a predisposition to retinal degeneration, the consequences of a moderate reduction in autophagy, similar to that which occurs during physiological aging, remain unclear. Here, we described a retinal phenotype consistent with accelerated aging in mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene. These mice showed protein aggregation in the retina and RPE, metabolic underperformance, and premature vision loss. Moreover, Ambra1+/gt mice were more prone to retinal degeneration after RPE stress. These findings indicate that autophagy provides crucial support to RPE-retinal metabolism and protects the retina against stress and physiological aging. Abbreviations : 4-HNE: 4-hydroxynonenal; AMBRA1: autophagy and beclin 1 regulator 1, AMD: age-related macular degeneration;; GCL: ganglion cell layer; GFAP: glial fibrillary acidic protein; GLUL: glutamine synthetase/glutamate-ammonia ligase; HCL: hierarchical clustering; INL: inner nuclear layer; IPL: inner plexiform layer; LC/GC-MS: liquid chromatography/gas chromatography–mass spectrometry; MA: middle-aged; MTDR: MitoTracker Deep Red; MFI: mean fluorescence intensity; NL: NH4Cl and leupeptin; Nqo: NAD(P)H quinone dehydrogenase; ONL: outer nuclear layer; OPL: outer plexiform layer; OP: oscillatory potentials; OXPHOS: oxidative phosphorylation; PCR: polymerase chain reaction; PRKC/PKCα: protein kinase C; POS: photoreceptor outer segment; RGC: retinal ganglion cells; RPE: retinal pigment epithelium; SI: sodium iodate; TCA: tricarboxylic acid.
Arousal/Stress Effects of “Overwatch” eSports Game Competition in Collegiate Gamers

Abstract Kraemer, WJ, Caldwell, LK, Post, EM, Beeler, MK, Emerson, A, Volek, JS, Maresh, CM, Fogt, JS, Fogt, N, Häkkinen, K, Newton, RU, Lopez, P, Sanchez, BN, and Onate, JA. Arousal/stress effects of “Overwatch” eSports game competition in collegiate gamers. J Strength Cond Res 36(10): 2671–2675, 2022—To date, no physical response data are available for one of the most popular eSport games, Overwatch. The purpose of this investigation was to describe the stress signaling associated with competitive Overwatch play and to understand how acute hormonal responses may affect performance. Thirty-two male college-aged gamers (age: 21.3 ± 2.7 years; estimated time played per week: 18 ± 15 hours) completed the study. Subjects were randomly assigned to a 6-player team to compete in a tournament-style match. Salivary measures of cortisol and testosterone were collected immediately before (PRE) and after (POST) the first-round game, with the heart rate recorded continuously during the match. The mean characteristics were calculated for each variable and comparisons made by the skill level. Significance was defined as p ≤ 0.05. There were no differences in measures of salivary cortisol. A differential response pattern was observed by the skill level for testosterone. The low skill group displayed a significant increase in testosterone with game play (mean ± SD, testosterone PRE: 418.3 ± 89.5 pmol·L−1, POST: 527.6 ± 132.4 pmol·L−1, p < 0.001), whereas no change was observed in the high skill group. There were no differences in heart rate characteristics between skill groups. Overall, the average heart rate was 107.2 ± 17.8 bpm with an average max heart rate of 133.3 ± 19.1 bpm. This study provides unique physiological evidence that a sedentary Overwatch match modulates endocrine and cardiovascular responses, with the skill level emerging as a potential modulator.
Personal and contextual determinants of COVID-19 vaccination intention: a vignette study

ABSTRACT Background This vignette study explores which factors contribute to higher COVID-19 vaccination intentions. Methods Between the 4th-11 January 2021, we recruited 15,901 Belgian citizens (M age = 50.11 years, range 18–100) through convenience sampling to participate in a vignette study. In each vignette, we manipulated contextual determinants consisting of different factors. Each participant rated six vignettes in terms of the outcomes ‘vaccination intention’ and ‘recommendation to others. ’ Finally, we explored the benefits of tailored communication by examining whether these ratings depended upon citizens’ initial motives for vaccination. Results Participants are most likely to accept a vaccine when they expect no or only small side effects, when the vaccine offers a 95% protection, and when people can no longer infect others (p < 0.001). The possibility to receive the vaccine at home or at the GP’s office, highlighting that most citizens are willing to get vaccinated, and emphasizing the protective benefits for others yielded additional positive effects (p < 0.001). Results showed that tailored communication has a small but significant effect, especially for individuals high on distrust-based amotivation (p < 0.01). Conclusion In addition to vaccine characteristics, there is room for policymakers to respond to those determinants that fall under their control and can thus be highlighted within communication campaigns.
FGFR4-Targeted Chimeric Antigen Receptors Combined with Anti-Myeloid Polypharmacy Effectively Treat Orthotopic Rhabdomyosarcoma

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Treatment outcomes, particularly for relapsed/refractory or metastatic disease, have not improved in decades. The current lack of novel therapies and low tumor mutational burden suggest that chimeric antigen receptor (CAR) T-cell therapy could be a promising approach to treating RMS. Previous work identified FGF receptor 4 (FGFR4, CD334) as being specifically upregulated in RMS, making it a candidate target for CAR T cells. We tested the feasibility of an FGFR4-targeted CAR for treating RMS using an NSG mouse with RH30 orthotopic (intramuscular) tumors. The first barrier we noted was that RMS tumors produce a collagen-rich stroma, replete with immunosuppressive myeloid cells, when T-cell therapy is initiated. This stromal response is not seen in tumor-only xenografts. When scFV-based binders were selected from phage display, CARs targeting FGFR4 were not effective until our screening approach was refined to identify binders to the membrane-proximal domain of FGFR4. Having improved the CAR, we devised a pharmacologic strategy to augment CAR T-cell activity by inhibiting the myeloid component of the T-cell–induced tumor stroma. The combined treatment of mice with anti-myeloid polypharmacy (targeting CSF1R, IDO1, iNOS, TGFbeta, PDL1, MIF, and myeloid misdifferentiation) allowed FGFR4 CAR T cells to successfully clear orthotopic RMS tumors, demonstrating that RMS tumors, even with very low copy-number targets, can be targeted by CAR T cells upon reversal of an immunosuppressive microenvironment.
Aging Effect, Reproducibility, and Test–Retest Reliability of a New Cerebral Amyloid Angiopathy MRI Severity Marker—Cerebrovascular Reactivity to Visual Stimulation

Decreased cerebrovascular reactivity, measured as changes in blood‐oxygen‐level‐dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test–retest reliability of these parameters should be assessed.
Current Undergraduate Dental Implantology Teaching in UK

Dental Implants are a popular treatment option for tooth replacement, with documented long-term success and survival rates of more than 95% over a period of 10 years. However, incorporating dental implantology into an undergraduate dental curriculum has issues associated. Therefore, the aim of this research was to examine and evaluate current undergraduate dental implantology education in the UK, investigate the amount of time allocated to this subject and analyse the barriers that are currently impeding the development of the programmes. An online questionnaire hosted by Online Surveys was designed, piloted, and sent to 16 dental schools providing undergraduate education in the UK. Ethical approval was gained from The University of Salford to conduct the study. Out of the 16 dental schools contacted, eight questionnaire responses were received, hence a response rate of 50% was achieved. The hours dedicated to the implant teaching programme varied from 3 h to 25 h, with a mean average of 11 h. It was identified from the results that no teaching of dental implantology was conducted in year 2; 12% of the schools responded that the subject was taught in year 1, 37% in year 3, 75% in year 4 and 50% in year 5. The methods used to deliver the programme were mainly lecture-based teaching, with only one dental school allowing students to place implants on patients. The main barriers to progression of the programme were financial (75%), followed by time limitations imposed by the curriculum (37%) and liability insurance (37%). However, there appears to be a consensus that further training beyond bachelor’s degree level is required to teach implantology effectively.
Influence of weighted downhill running training on serial sarcomere number and work loop performance in the rat soleus

ABSTRACT Increased serial sarcomere number (SSN) has been observed in rats following downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesised trained rats would produce greater net work output during work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a training or sedentary control group. Weight was added during downhill running via a custom-made vest, progressing from 5–15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (cyclic muscle length changes) were then performed about optimal muscle length (LO) at 1.5–3-Hz cycle frequencies and 1–7-mm length changes. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), and a less steep passive force-length curve than controls (P<0.05). There were no differences in collagen parameters (P>0.05). Net work output was greater (+78–209%) in trained than control rats for the 1.5-Hz work loops at 1 and 3-mm length changes (P<0.05), however, net work output was more related to maximum specific force (R2=0.17-0.48, P<0.05) than SSN (R2=0.03-0.07, P=0.17-0.86). Therefore, contrary to our hypothesis, training-induced sarcomerogenesis likely contributed little to the improvements in work loop performance. This article has an associated First Person interview with the first author of the paper.
High-density surface electromyography as biomarker of muscle aging.

Sarcopenia is a muscle disease with adverse changes that increase throughout lifetime, but with different chronological scale between individuals. Addressing "early muscle aging" is becoming a critical issue for prevention. Through the CHRONOS study, we demonstrated the ability of the high-density surface electromyography (HD-sEMG), a non-invasive, wireless, portable technology, to detect both healthy muscle aging and accelerated muscle aging related to sedentary lifestyle, one of the risk factors of sarcopenia. The HD-sEMG signals were analyzed in 91 healthy young, middle-aged and old subjects (25-75yrs) distributed according to their physical activity status (82 active and 9 sedentary; IPAQ) and compared with current methods for muscle evaluation including muscle mass (dual-energy X-ray absorptiometry, ultrasonography), handgrip strength, physical performance. The HD-sEMG signals were recorded from the rectus femoris during sit-to-stand trials, and two indexes were analyzed: Muscular Contraction Intensity and Muscle Contraction Dynamics. The clinical parameters did not differ significantly across the aging and physical activity levels. Inversely, the HD-sEMG indexes were correlated to age, and were different significantly through the age categories of the 82 active subjects. They were significantly different between sedentary subjects aged 45-54 years and active ones at the same age. The HD-sEMG indexes of sedentary subjects were not significantly different from those of older active subjects (≥55years). The Muscle thicknesses evaluated using ultrasonography were different significantly between the 5 age decades, but did not show a significant difference with physical activity. The HD-sEMG technique can assess muscle aging and physical inactivity-related "early aging" outperforming clinical and DXA parameters.
Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway

ABSTRACT Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis, but its pathogenesis remains unclear. The primary objective of this study is to explore whether Echinococcus multilocularis protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68+ macrophages gathered in close liver issue from the lesion in AE patients. PSCs preferentially differentiated into M2 macrophages and the expressions of HK1, PFKL, PKM2, PI3K, Akt, p-Akt, mTOR and p-mTOR increased. The above results show that Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 macrophages through PI3K/Akt/mTOR signaling pathway.
On the Occurrence and Multimerization of Two-Polypeptide Phage Endolysins Encoded in Single Genes

Bacteriophages use endolysins to cleave the host bacteria cell wall, a crucial event underlying cell lysis for virion progeny release. These bacteriolytic enzymes are generally thought to work as single, monomeric polypeptides, but a few examples have been described in which a single gene produces two endolysin isoforms. ABSTRACT Bacteriophages (phages) and other viruses are extremely efficient in packing their genetic information, with several described cases of overlapping genes encoded in different open reading frames (ORFs). While less frequently reported, specific cases exist in which two overlapping ORFs are in frame and share the stop codon. Here, we studied the occurrence of this genetic arrangement in endolysins, the phage enzymes that cut the bacterial cell wall peptidoglycan to release the virion progeny. After screening over 3,000 endolysin sequences of phages infecting Gram-positive bacteria, we found evidence that this coding strategy is frequent in endolysin genes. Our bioinformatics predictions were experimentally validated by demonstrating that two polypeptides are indeed produced from these genes. Additionally, we show that in some cases the two polypeptides need to interact and multimerize to generate the active endolysin. By studying in detail one selected example, we uncovered a heteromeric endolysin with a 1:5 subunit stoichiometry that has never been described before. Hence, we conclude that the occurrence of endolysin genes encoding two polypeptide isoforms by in-frame overlapping ORFs, as well as their organization as enzymatic complexes, appears more common than previously thought, therefore challenging the established view of endolysins being mostly formed by single, monomeric polypeptide chains. IMPORTANCE Bacteriophages use endolysins to cleave the host bacteria cell wall, a crucial event underlying cell lysis for virion progeny release. These bacteriolytic enzymes are generally thought to work as single, monomeric polypeptides, but a few examples have been described in which a single gene produces two endolysin isoforms. These are encoded by two in-frame overlapping ORFs, with a shorter ORF being defined by an internal translation start site. This work shows evidence that this endolysin coding strategy is frequent in phages infecting Gram-positive bacteria, and not just an eccentricity of a few phages. In one example studied in detail, we show that the two isoforms are inactive until they assemble to generate a multimeric active endolysin, with a 1:5 subunit stoichiometry never described before. This study challenges the established view of endolysins, with possible implications in their current exploration and design as alternative antibacterials.