Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytotoxic CD8+ T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons

Significance CD8+ T lymphocytes, which are typically devoted to eliminate malignant and infected cells, have been described in the central nervous system (CNS) of patients and mice with amyotrophic lateral sclerosis (ALS). However, their role in ALS pathogenesis has yet to be unraveled. Here, we show that ablation of CD8+ T cells in ALS mice increased the number of surviving motoneurons. CD8+ T cells expressing the ALS-causing superoxide dismutase-1 mutant protein recognize and selectively kill motoneurons in vitro. To exert their cytotoxic function, mutant CD8+ T cells required presentation of the antigen-MHC-I complex at the surface of the motoneurons. Analysis of T cell receptor diversity supports the evidence that self-reactive CD8+ T lymphocytes infiltrate the CNS of ALS mice to exert cytotoxic function. Adaptive immune response is part of the dynamic changes that accompany motoneuron loss in amyotrophic lateral sclerosis (ALS). CD4+ T cells that regulate a protective immunity during the neurodegenerative process have received the most attention. CD8+ T cells are also observed in the spinal cord of patients and ALS mice although their contribution to the disease still remains elusive. Here, we found that activated CD8+ T lymphocytes infiltrate the central nervous system (CNS) of a mouse model of ALS at the symptomatic stage. Selective ablation of CD8+ T cells in mice expressing the ALS-associated superoxide dismutase-1 (SOD1)G93A mutant decreased spinal motoneuron loss. Using motoneuron-CD8+ T cell coculture systems, we found that mutant SOD1-expressing CD8+ T lymphocytes selectively kill motoneurons. This cytotoxicity activity requires the recognition of the peptide-MHC-I complex (where MHC-I represents major histocompatibility complex class I). Measurement of interaction strength by atomic force microscopy-based single-cell force spectroscopy demonstrated a specific MHC-I-dependent interaction between motoneuron and SOD1G93A CD8+ T cells. Activated mutant SOD1 CD8+ T cells produce interferon-γ, which elicits the expression of the MHC-I complex in motoneurons and exerts their cytotoxic function through Fas and granzyme pathways. In addition, analysis of the clonal diversity of CD8+ T cells in the periphery and CNS of ALS mice identified an antigen-restricted repertoire of their T cell receptor in the CNS. Our results suggest that self-directed immune response takes place during the course of the disease, contributing to the selective elimination of a subset of motoneurons in ALS.
An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning

Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched deletion mice show that RBMXL2 controls splicing patterns during meiosis. In particular, RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature terminal exons. Our data suggest a Rbmxl2 retrogene has been conserved across mammals as part of a splicing control mechanism that is fundamentally important to germ cell biology. We propose that this mechanism is essential to meiosis because it buffers the high ambient concentrations of splicing activators, thereby preventing poisoning of key transcripts and disruption to gene expression by aberrant splice site selection.
Antifungal activity of oils macerates of North Sardinia plants against Candida species isolated from clinical patients with candidiasis

Abstract Antibiotic resistance is one of the bigger problem of public health: the rise of multi-drug resistant organisms causes a challenge in the treatment of infective diseases. Anti-Candida resistance to conventional antifungal agents has increased in the last period. Our research was intended to evaluate antimicrobial activity of oil macerate (OM) of Helichrysum microphyllum Cambess. subsp. tyrrhenicum Bacch. , Brullo & Giusso and OM of Hypericum perforatum subsp. angustifolium against several clinical strains. The study included 30 patients with candidiasis who had not received any antifungal treatment before they were enrolled. A collection of 30 clinical isolates belonging to 5 different species of Candida spp. was selected for this study. The data obtained showed an interesting activity of both Oil Macerate especially against C. krusei and C. parapsilosis. On the contrary, H. microphyllum Oil Macerate has had a better activity than the H.perforatum especially in relation to C. glabrata and C. krusei. Graphical Abstract
Neuronavigated theta burst stimulation for chronic aphasia: two exploratory case studies

ABSTRACT The present study reports the findings of a 10-day neuronavigated continuous theta burst stimulation (cTBS) over the right pars triangularis for two individuals with chronic aphasia after a single left hemispheric stroke. Baseline language and quality of life measures were collected prior to the treatment study, post-treatment and at 3-month follow up. Therapy was tolerated well by both participants and no side effects were noticed during and after treatment. Results from one individual showed potential for positive change in performance in comprehension and expressive language both post-treatment and at the follow-up stage. Also, a trend towards improvement post-treatment was noticed in discourse and sentence productivity, and grammatical accuracy. In the follow up stage, grammatical accuracy showed a trend towards improvement; discourse productivity decreased and; sentence productivity skills showed mixed results. Results from the other participant showed potential for positive change in comprehension post-treatment, that was maintained at the follow-up stage. However, a decline in expressive language post-treatment and at follow-up, stronger post-treatment, was noticed. Regarding quality of life measurements, participant one appeared to have improved as his performance increased in the overall, physical and communication domains, but decreased slightly in the psychosocial domain. The second participant improved in the physical and communication domains and declined overall and in the psychosocial domains. Findings from this study indicate that cTBS over the right pars triangularis may have the potential to improve various language skills in patients suffering from chronic aphasia post-stroke. However, the potential benefits of this fast, non-invasive brain stimulation protocol on improvement of language abilities post-stroke need further exploration.
Disparities in uptake of 13-valent pneumococcal conjugate vaccine among older adults in the United States

ABSTRACT Background: In September 2014, 13-valent pneumococcal conjugate vaccine (PCV13) was universally recommended for all US adults aged ≥65 years. Adult PCV13 coverage, including whether disparities in uptake exist, however, is not well-described. Methods: We used a monthly series of cross-sectional analyses of administrative medical and prescription claims data collected by IQVIA and linked to sociodemographic data collected by Experian to estimate overall and subpopulation-level uptake of PCV13 among US adults aged ≥65 years. Results: Among adults aged ≥65 years, 43.3% received PCV13 by the end of November 2017. Race/ethnicity, annual household income, education status, and neighborhood urbanicity were strongly related to PCV13 uptake among adults aged ≥65 years. Lower uptake of PCV13 was observed for non-Hispanic black (36.3%) and Hispanic (30.0%) adults (vs 45.6% for non-Hispanic whites, P < .01), the poor (30.7% vs 54.2% among lowest vs highest income deciles, P < .01), adults with low educational status (33.0% vs 49.0% among those without high school education vs college educated, P < .01), and those living in rural communities (22.9%) or urban/inner-city (33.8%) areas (vs 45.8% in suburban areas, P < .01). Conclusions: PCV13 uptake among adults aged ≥65 occurred rapidly in the three years after universal recommendation in September 2014. Yet, poor and minority communities, rural and urban/inner-city areas, and communities with low educational attainment had substantially lower PCV13 coverage. These same populations are at increased risk of pneumococcal disease. In order to maximize the benefits of pneumococcal vaccination, further targeted and tailored interventions to increase PCV13 uptake in these underserved populations are still necessary.
The Role of Genetic Profile in Functional Performance Adaptations to Exercise Training or Physical Activity: A Systematic Review of the Literature.

Background: Variations in genotype may contribute to heterogeneity in functional adaptations to exercise. Methods: A systematic search of eight databases was conducted, and 9,696 citations were screened. Results: Eight citations from seven studies measuring 10 single-nucleotide polymorphisms and nine different functional performance test outcomes were included in the review. There was one observational study of physical activity and six experimental studies of aerobic or resistance training. The ACE (D) allele, ACTN3 (RR) genotype, UCP2 (GG) genotype, IL-6-174 (GG) genotype, TNF-α-308 (GG) genotype, and IL-10-1082 (GG) genotype all predicted significantly superior adaptations in at least one functional outcome in older men and women after prescribed exercise or in those with higher levels of physical activity. Conclusion: There is a small amount of evidence that older adults may have better functional outcomes after exercise/physical activity if they have specific alleles related to musculoskeletal function or inflammation. However, more robust trials are needed.
Species sensitivity distributions for use in environmental protection, assessment, and management of aquatic ecosystems for 12 386 chemicals

The present study considers the collection and use of ecotoxicity data for risk assessment with species sensitivity distributions (SSDs) of chemical pollution in surface water, which are used to quantify the likelihood that critical effect levels are exceeded. This fits the European Water Framework Directive, which suggests using models to assess the likelihood that chemicals affect water quality for management prioritization. We derived SSDs based on chronic and acute ecotoxicity test data for 12 386 compounds. The log‐normal SSDs are characterized by the median and the standard deviation of log‐transformed ecotoxicity data and by a quality score. A case study illustrates the utility of SSDs for water quality assessment and management prioritization. We quantified the chronic and acute mixture toxic pressure of mixture exposures for >22 000 water bodies in Europe for 1760 chemicals for which we had both exposure and hazard data. The results show the likelihood of mixture exposures exceeding a negligible effect level and increasing species loss. The SSDs in the present study represent a versatile and comprehensive approach to prevent, assess, and manage chemical pollution problems. Environ Toxicol Chem 2019;38:905–917. © 2019 SETAC
Behavioral Regulation Sport Questionnaire: Gender and Sport Invariance in Portuguese Athletes

This study aimed to analyze measurement invariance of the Behavioral Regulation Sports Questionnaire (BRSQ) across gender and four different sports. In addition, we examined nomological validity via basic psychological needs satisfaction. Participants totaled 1,812 Portuguese athletes (1,220 males and 592 females; aged 15–59 years, Mage = 17.72, SD = 5.51) from football (n = 596), basketball (n = 273), swimming (n = 800), and parasport (n = 143). The BRSQ measurement model was invariant across gender and these four sports. The scale confirmed nomological validity in that satisfaction of basic psychological needs positively predicted autonomous forms of motivation and negatively predicted more controlled motivation and amotivation as suggested by self-determination theory. In light of this evidence for BRSQ construct validity, composite reliability, nomological validity, and invariance across gender and four different sports, this scale is a useful tool for coaches of the aforementioned sports in their efforts to evaluate their athletes' motivation.
Quality, functionality, and microbiology of fermented fish: a review

Abstract Fermentation is a traditional food preservation method and is widely used for improving food safety, shelf life, and organoleptic and nutritional attributes. Fermented fish are produced and consumed in different parts of the world and are an integral part of many food cultures. Furthermore, fermented fish are a source of interesting microbes and are an important industry in many countries. This review tries to update the types and manufacturing processes for fermented fish around the world. The emphasis is on this work related to fermented fish and their health benefits, as well as the contribution of microorganisms to their fermentation. A variety of different approaches have been used to determine and understand microbial composition and functionality. Moreover, some challenges and future research directions regarding fermented fish are also discussed in this review. Further research into fermented fish products is of crucial importance not only for the food industry but also for human health. However, extensive in vivo and toxicological studies are essential before the application of bioactive-rich fermented fish products for human health benefits.
Predictive risk factors of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy for ovarian peritoneal carcinomatosis

Objective The aim of our study was to assess the incidence and identify the predictive risk factors of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy. Methods This is a retrospective study from two centers evaluating patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery followed by cisplatin-based hyperthermic intra-peritoneal chemotherapy from January 2007 to December 2013. Patients were classified into two groups according to the occurrence of acute kidney injury, defined as a glomerular filtration rate at post-operative day 7 25% lower than at day 0. We also evaluated acute kidney injury following Risk, Injury, Failure, Lost and End-stage kidney function criteria. Univariate and multivariate analyses were conducted in order to assess the association between different variables and the occurrence of acute kidney injury. Results Sixty-six patients were included: 29 (44%) underwent first-line treatment and 37 (56%) were treated for recurrent disease. The incidence of post-operative acute kidney injury was 48%. After multivariate analysis, hypertension (OR 18.6; 95% CI 1.9 to 182.3; p=0.012) and low intra-operative diuresis (OR 0.5; 95% CI 0.4 to 0.8; p=0.001) were associated with acute kidney injury. Conclusion The incidence of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy was high. Hypertension and low intra-operative diuresis were independent risk factors for this complication. Adequate peri-operative hydration, in order to maintain correct diuresis, could decrease the occurrence of acute kidney injury in patients undergoing cytoreductive surgery plus hyperthermic intra-peritoneal chemotherapy.
Nupr1 regulates palmitate-induced apoptosis in human articular chondrocytes

Obesity, a major risk factor for the development of osteoarthritis (OA), is associated with increased circulating levels of free fatty acids (FFA). However, the role of these FFAs in OA pathophysiology is not clearly understood. In the present study, we found that palmitate treatment of human primary articular chondrocytes increased the expression of ER stress markers [activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP)] and apoptosis markers [cytochrome c and cleaved caspase-3 (CC3)]. Palmitate treatment also increased the expression of Nuclear protein 1 (Nupr1) and tribbles related protein 3 (TRB3), which are known negative regulators of cell survival pathways. Knockdown of Nupr1 or CHOP expression inhibited palmitate mediated increased expression of TRB3 and CC3, indicating that Nupr1 and CHOP cooperate to regulate cell survival and apoptotic pathways in human chondrocytes. Nupr1 knockdown had no effect on CHOP expression whereas CHOP knockdown abolished the palmitate-mediated Nupr1 expression, indicating that CHOP is functional upstream to Nupr1 in this pathway. Moreover, overexpression of Nupr1 markedly increased the basal expression of pro-apoptotic molecules, including cytochrome c and CC3. Taken together, our study demonstrates that Nupr1 plays a crucial role in palmitate-induced apoptosis in human chondrocytes and Nupr1 as a potential novel drug target for the treatment of OA.
Machine learning in multiexposure laser speckle contrast imaging can replace conventional laser Doppler flowmetry

Abstract. Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment.
Submaximal exercise cardiac output is increased by 4 weeks of sprint interval training in young healthy males with low initial Q̇-V̇O2: Importance of cardiac response phenotype

Cardiovascular adaptations to exercise, particularly at the individual level, remain poorly understood. Previous group level research suggests the relationship between cardiac output and oxygen consumption (Q˙-V˙O2) is unaffected by training as submaximal Q˙ is unchanged. We recently identified substantial inter-individual variation in the exercise Q˙-V˙O2 relationship that was correlated to stroke volume (SV) as opposed to arterial oxygen content. Therefore we explored the effects of sprint interval training (SIT) on modulating Q˙-V˙O2 given an individual’s specific Q˙-V˙O2 relationship. 22 (21±2 yrs) healthy, recreationally active males participated in a 4-week SIT (8, 20 second sprints; 4x/week, 170% of the work rate at V˙O2 peak) study with progressive exercise tests (PET) until exhaustion. Cardiac output (Q˙ L/min; inert gas rebreathe, Finometer Modelflow™), oxygen consumption (V˙O2 L/min; breath-by-breath pulmonary gas exchange), quadriceps oxygenation (near infrared spectroscopy) and exercise tolerance (6–20; Borg Scale RPE) were measured throughout PET both before and after training. Data are mean Δ from bsl±SD. Higher Q˙ (HQ˙) and lower Q˙ (LQ˙) responders were identified post hoc (n = 8/group). SIT increased the Q˙-V˙O2 post-training in LQ˙ (3.8±0.2 vs. 4.7±0.2; P = 0.02) while HQ˙ was unaffected (5.8±0.1 vs. 5.3±0.6; P = 0.5). ΔQ˙ was elevated beyond 80 watts in LQ˙ due to a greater increase in SV (all P<0.04). Peak V˙O2 (ml/kg/min) was increased in LQ˙ (39.7±6.7 vs. 44.5±7.3; P = 0.015) and HQ˙ (47.2±4.4 vs. 52.4±6.0; P = 0.009) following SIT, with HQ˙ having a greater peak V˙O2 both pre (P = 0.02) and post (P = 0.03) training. Quadriceps muscle oxygenation and RPE were not different between groups (all P>0.1). In contrast to HQ˙, LQ˙ responders are capable of improving submaximal Q˙-V˙O2 in response to SIT via increased SV. However, the increased submaximal exercise Q˙ does not benefit exercising muscle oxygenation.
Oscillating Aquaporin Phosphorylation and 14-3-3 Proteins Mediate the Circadian Regulation of Leaf Hydraulics[OPEN]

A mechanism is established that tunes the hydraulics of leaf tissues to synchronize water supply with day and night cycles, thereby optimizing plant growth. The circadian clock regulates plant tissue hydraulics to synchronize water supply with environmental cycles and thereby optimize growth. The circadian fluctuations in aquaporin transcript abundance suggest that aquaporin water channels play a role in these processes. Here, we show that hydraulic conductivity (Kros) of Arabidopsis (Arabidopsis thaliana) rosettes displays a genuine circadian rhythmicity with a peak around midday. Combined immunological and proteomic approaches revealed that phosphorylation at two C-terminal sites (Ser280, Ser283) of PLASMA MEMBRANE INTRINSIC PROTEIN 2;1 (AtPIP2;1), a major plasma membrane aquaporin in rosettes, shows circadian oscillations and is correlated with Kros. Transgenic expression of phosphodeficient and phosphomimetic forms of this aquaporin indicated that AtPIP2;1 phosphorylation is necessary but not sufficient for Kros regulation. We investigated the supporting role of 14-3-3 proteins, which are known to interact with and regulate phosphorylated proteins. Individual knockout plants for five 14-3-3 protein isoforms expressed in rosettes lacked circadian activation of Kros. Two of these [GRF4 (14-3-3Phi); GRF10 (14-3-3Epsilon)] showed direct interactions with AtPIP2;1 in the plant and upon coexpression in Xenopus laevis oocytes and activated AtPIP2;1, preferentially when the latter was phosphorylated at its two C-terminal sites. We propose that this regulatory mechanism assists in the activation of phosphorylated AtPIP2;1 during circadian regulation of Kros.
Quality Improvement Toolkits: Recommendations for Development

A burgeoning number of toolkits dedicated to improving health care exist but development guidance is lacking. The authors convened a panel of health care stakeholders, including developers, purchasers, users, funders, and disseminators of toolkits. The panel was informed by a literature review that analyzed 44 publications and 27 toolkits. A modified Delphi process established recommendations and suggestions to guide toolkit development. The panel established 12 recommendations for content and 1 recommendation for toolkit development methods. The recommendations are accompanied by 11 suggestions for toolkit content, 9 suggestions for development methods, and 6 suggestions for toolkit evaluation methods. The authors established a set of key recommendations and suggestions addressing the content, development, and evaluation methods of quality improvement toolkits, together with a ready-to use checklist. The guidance aims to advance the value of toolkits as an emerging method to effectively disseminate interventions to improve the quality of care.