Miracle-dz/UniFAR-FTUs huggingface dataset:
Converging sensory and motor cortical inputs onto the same striatal neurons: An in vivo intracellular investigation

The striatum is involved in the completion and optimization of sensorimotor tasks. In rodents, its dorsolateral part receives converging glutamatergic corticostriatal (CS) inputs from whisker-related primary somatosensory (S1) and motor (M1) cortical areas, which are interconnected at the cortical level. Although it has been demonstrated that the medium-spiny neurons (MSNs) from the dorsolateral striatum process sensory information from the whiskers via the S1 CS pathway, the functional impact of the corresponding M1 CS inputs onto the same striatal neurons remained unknown. Here, by combining in vivo S1 electrocorticogram with intracellular recordings from somatosensory MSNs in the rat, we first confirmed the heterogeneity of striatal responsiveness to whisker stimuli, encompassing MSNs responding exclusively by subthreshold synaptic depolarizations, MSNs exhibiting sub- and suprathreshold responses over successive stimulations, and non-responding cells. All recorded MSNs also exhibited clear-cut monosynaptic depolarizing potentials in response to electrical stimulations of the corresponding ipsilateral M1 cortex, which were efficient to fire striatal cells. Since M1-evoked responses in MSNs could result from the intra-cortical recruitment of S1 CS neurons, we performed intracellular recordings of S1 pyramidal neurons and compared their firing latency following M1 stimuli to the latency of striatal synaptic responses. We found that the onset of M1-evoked synaptic responses in MSNs significantly preceded the firing of S1 neurons, demonstrating a direct synaptic excitation of MSNs by M1. However, the firing of MSNs seemed to require the combined excitatory effects of S1 and M1 CS inputs. This study directly demonstrates that the same somatosensory MSNs can process excitatory synaptic inputs from two functionally-related sensory and motor cortical regions converging into the same striatal sector. The effectiveness of these convergent cortical inputs in eliciting action potentials in MSNs may represent a key mechanism of striatum-related sensorimotor behaviors.
TNF receptor–associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation

Amyotrophic lateral sclerosis (ALS) is a fatal disease, characterized by the selective loss of motor neurons leading to paralysis. Mutations in the gene encoding superoxide dismutase 1 (SOD1) are the second most common cause of familial ALS, and considerable evidence suggests that these mutations result in an increase in toxicity due to protein misfolding. We previously demonstrated in the SOD1G93A rat model that misfolded SOD1 exists as distinct conformers and forms deposits on mitochondrial subpopulations. Here, using SOD1G93A rats and conformation-restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the interactomes of the mitochondrial pools of misfolded SOD1. This strategy identified binding proteins that uniquely interacted with either AMF7-63 or B8H10-reactive SOD1 conformers as well as a high proportion of interactors common to both conformers. Of this latter set, we identified the E3 ubiquitin ligase TNF receptor–associated factor 6 (TRAF6) as a SOD1 interactor, and we determined that exposure of the SOD1 functional loops facilitates this interaction. Of note, this conformational change was not universally fulfilled by all SOD1 variants and differentiated TRAF6 interacting from TRAF6 noninteracting SOD1 variants. Functionally, TRAF6 stimulated polyubiquitination and aggregation of the interacting SOD1 variants. TRAF6 E3 ubiquitin ligase activity was required for the former but was dispensable for the latter, indicating that TRAF6-mediated polyubiquitination and aggregation of the SOD1 variants are independent events. We propose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology of ALS.
The Impact of the University Classroom on Managing the Socio-Educational Well-being: A Global Study

The university learning classroom, in addition to a space for activities and architectural object, has a direct impact on the academic motivation, well-being and social relationships of the students. Thus, the link between the university classroom and the management of the socio-educational well-being of the student, in accordance with the principles of well-being theory, is a challenge that the current university must manage. The progress of worldwide research on this topic has been studied during the period 2004–2018. For this aim, a bibliometric study of 1982 articles has been applied. The results provide data of the scientific productivity of the journals, authors, institutions and countries that contribute to this research. The evidence reveals growing interest, especially in the last six years. The main category is Social Sciences. The most productive journals are Computers and Education, American Journal of Pharmaceutical Education, and Theory into Practice. The author with most articles is Reddy, from Rutgers University. The most productive institution is the University of Virginia. The United States is the country with most academic publications, citations and with most international collaborations in its works. Worldwide research has followed an increasing trend, with optimum publication levels in latest years.
Do the shuffle: Exploring reasons for music listening through shuffled play

Adults listen to music for an average of 18 hours a week (with some people reaching more than double that). With rapidly changing technology, music collections have become overwhelmingly digital ushering in changes in listening habits, especially when it comes to listening on personal devices. By using interactive visualizations, descriptive analysis and thematic analysis, this project aims to explore why people download and listen to music and which aspects of the music listening experience are prioritized when people talk about tracks on their device. Using a newly developed data collection method, Shuffled Play, 397 participants answered open-ended and closed research questions through a short online questionnaire after shuffling their music library and playing two pieces as prompts for reflections. The findings of this study highlight that when talking about tracks on their personal devices, people prioritise characterizing them using sound and musical features and associating them with the informational context around them (artist, album, and genre) over their emotional responses to them. The results also highlight that people listen to and download music because they like it–a straightforward but important observation that is sometimes glossed over in previous research. These findings have implications for future work in understanding music, its uses and its functions in peoples’ everyday lives.
Effects of Facebook Comments on Attitude Toward Vaccines: The Roles of Perceived Distributions of Public Opinion and Perceived Vaccine Efficacy

This study investigated if and how exposure to Facebook comments about vaccines influences one’s attitude toward the vaccines. In this investigation, comments were examined in light of their effect on attitude toward vaccines through perceived distribution of public opinion on vaccines, and perceived vaccine efficacy was tested as a factor moderating relative effects of comments on perception of public opinion distributions. Results from an experimental study (N = 271) showed that exposure to a greater number of comments in a thread expressing (un)favorable opinions on the flu vaccine led to (un)favorable attitude toward the flu vaccine through a change in perceived distribution of public opinions on the vaccination. The indirect effect of comments on attitude toward the flu vaccine through perceived public opinion distributions was greater among participants with lower levels of perceived vaccine efficacy, while the direct effect of comments on attitude was not significant.
Machine Learning Takes Laboratory Automation to the Next Level

Clinical microbiology laboratories face challenges with workload and understaffing that other clinical laboratory sections have addressed with automation. In this issue of the Journal of Clinical Microbiology, M. L. Faron, B. W. Buchan, R. F. Relich, J. Clark, and N. A. Ledeboer (J Clin Microbiol 58:e01683-19, 2020, https://doi.org/10.1128/JCM.01683-19) evaluate the performance of automated image analysis software to screen urine cultures for further workup according to their total number of CFU. ABSTRACT Clinical microbiology laboratories face challenges with workload and understaffing that other clinical laboratory sections have addressed with automation. In this issue of the Journal of Clinical Microbiology, M. L. Faron, B. W. Buchan, R. F. Relich, J. Clark, and N. A. Ledeboer (J Clin Microbiol 58:e01683-19, 2020, https://doi.org/10.1128/JCM.01683-19) evaluate the performance of automated image analysis software to screen urine cultures for further workup according to their total number of CFU. Urine cultures are the highest volume specimen type for most laboratories, so this software has the potential for tremendous gains in laboratory efficiency and quality due to the consistency of colony quantification.
Value of Endolymphatic Hydrops and Perilymph Signal Intensity in Suspected Ménière Disease

BACKGROUND AND PURPOSE: Ménière disease is characterized by endolymphatic hydrops, whereas perilymphatic enhancement on MR imaging has been suggested to be of additional value in diagnosing Ménière disease. This study evaluates the presence of endolymphatic hydrops and perilymphatic enhancement in patients with Ménière disease and with other vertigo-associated inner ear pathology. MATERIALS AND METHODS: A 3D-FLAIR sequence 4 hours after intravenous gadolinium injection was performed to visualize the endolymph and perilymph in 220 patients suspected of having Ménière disease. Patients’ ears were retrospectively categorized as having Ménière disease (probable or definite) or other vertigo-associated inner ear pathology not attributable to Ménière disease. Endolymphatic hydrops was evaluated using a visual classification system, and perilymphatic enhancement was scored both visually and quantitatively. RESULTS: Endolymphatic hydrops was present in 137 (91.9%) of the definite Ménière disease ears and in 9 (7.0%) of the ears with other vertigo-associated inner ear pathology (P < .001). The combination of endolymphatic hydrops and visually increased perilymphatic enhancement was present in 122 (81.9%) definite Ménière disease ears compared with 4 (3.1%) ears with other vertigo-associated inner ear pathology (P < .001). This combination increases the positive predictive value from 0.94 for endolymphatic hydrops and 0.91 for perilymphatic enhancement to 0.97. The addition of measured perilymphatic enhancement leads to a moderate decrease in sensitivity from 0.92 for endolymphatic hydrops to 0.86. CONCLUSIONS: The combination of perilymphatic enhancement and endolymphatic hydrops in patients suspected of having Ménière disease increases the positive predictive value in the diagnosis of definite Ménière disease.
Room temperature magnetoelectric coupling in a molecular ferroelectric ytterbium(III) complex

Major-league magnetostriction Magnetoelectric materials polarize in response to either electric or magnetic fields, making them attractive for data-storage applications. Long et al. discovered a ytterbium-based molecular magnetoelectric material with high magnetoelectric coupling (see the Perspective by Zhou and Han). An applied magnetic field strains the material, which changes its electrical properties. The required field is much lower than other magnetoelectric materials, and this work highlights the potential for using molecular materials in devices. Science, this issue p. 671; see also p. 627 An ytterbium-based molecular magnetoelectric material has strong interaction between magnetic and ferroelectric properties. Magnetoelectric (ME) materials combine magnetic and electric polarizabilities in the same phase, offering a basis for developing high-density data storage and spintronic or low-consumption devices owing to the possibility of triggering one property with the other. Such applications require strong interaction between the constitutive properties, a criterion that is rarely met in classical inorganic ME materials at room temperature. We provide evidence of a strong ME coupling in a paramagnetic ferroelectric lanthanide coordination complex with magnetostrictive phenomenon. The properties of this molecular material suggest that it may be competitive with inorganic magnetoelectrics.
Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389

Congenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are important as they inform health care planning and can aid interpretation of genetic testing results when assessing the frequency of variants in large-scale, unselected sequencing databases. Whilst minimal incidence rates have been calculated for four European countries, the incidence of CHI in the UK is not known. In this study we have used referral rates to a central laboratory for genetic testing and annual birth rates from census data to calculate the minimal incidence of CHI within the UK from 2007 to 2016. CHI was diagnosed in 278 individuals based on inappropriately detectable insulin and/or C-peptide measurements at the time of hypoglycaemia which persisted beyond 6 months of age. From these data, we have calculated a minimum incidence of 1 in 28,389 live births for CHI in the UK. This is comparable to estimates from other outbred populations and provides an accurate estimate that will aid both health care provision and interpretation of genetic results, which will help advance our understanding of CHI.
Callose Synthesis Suppresses Cell Death Induced by Low-Calcium Conditions in Leaves1

Callose is required for the suppression of cell death and necrosis induced by calcium deficiency. Despite the importance of preventing calcium (Ca) deficiency disorders in agriculture, knowledge of the molecular mechanisms underlying plant adaptations to low-Ca conditions is limited. In this study, we provide evidence for a crucial involvement of callose synthesis in the survival of Arabidopsis (Arabidopsis thaliana) under low-Ca conditions. A mutant sensitive to low-Ca conditions, low calcium sensitive3 (lcs3), exhibited high levels of cell death in emerging leaves and had defects in its expanding true leaves under low-Ca conditions. Further analyses showed that the causal mutation was located in a putative β-1,3-glucan (callose) synthase gene, GLUCAN SYNTHASE-LIKE10 (GSL10). Yeast complementation assay results showed that GSL10 encodes a functional callose synthase. Ectopic callose significantly accumulated in wild-type plants under low-Ca conditions, but at a low level in lcs3. The low-Ca sensitivity of lcs3 was phenocopied by the application of callose synthase inhibitors in wild-type plants, which resulted in leaf expansion failure, cell death, and reduced ectopic callose levels under low-Ca conditions. Transcriptome analyses showed that the expression of genes related to cell wall and defense responses was altered in both wild-type plants under low-Ca conditions and in lcs3 under normal-Ca conditions, suggesting that GSL10 is required for the alleviation of both cell wall damage and defense responses caused by low Ca levels. These results suggest that callose synthesis is essential for the prevention of cell death under low-Ca conditions and plays a key role in plants’ survival strategies under low-Ca conditions.
Muscle‐derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress

Mitochondrial dysfunction promotes metabolic stress responses in a cell‐autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1‐TG) with compromised muscle‐specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1‐TG mice show a skeletal muscle‐specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1‐TG mice does not affect muscle wasting or transcriptional cell‐autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress‐induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15‐dependent daytime‐restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress‐induced GDF15 in the regulation of systemic energy metabolism.
Local adaptation across a complex bioclimatic landscape in two montane bumble bee species

Understanding evolutionary responses to variation in temperature and precipitation across species ranges is of fundamental interest given ongoing climate change. The importance of temperature and precipitation for multiple aspects of bumble bee (Bombus) biology, combined with large geographic ranges that expose populations to diverse environmental pressures, make these insects well‐suited for studying local adaptation. Here, we analyzed genome‐wide sequence data from two widespread bumble bees, Bombus vosnesenskii and Bombus vancouverensis, using multiple environmental association analysis methods to investigate climate adaptation across latitude and altitude. The strongest signatures of selection were observed in B. vancouverensis, but despite unique responses between species for most loci, we detected several shared responses. Genes relating to neural and neuromuscular function and ion transport were especially evident with respect to temperature variables, while genes relating to cuticle formation, tracheal and respiratory system development, and homeostasis were associated with precipitation variables. Our data thus suggest that adaptive responses for tolerating abiotic variation are likely to be complex, but that several parallels among species can emerge even for these complex traits and landscapes. Results provide the framework for future work into mechanisms of thermal and desiccation tolerance in bumble bees and a set of genomic targets that might be monitored for future conservation efforts.
Development and Evaluation of a Screening Tool to Aid the Diagnosis of Cluster Headache

Cluster headache (CH), a severe primary headache, is often misdiagnosed and mismanaged. The aim of this study was to develop and evaluate a screening tool to aid the diagnosis of CH. We developed a novel 12-item screening tool. This was comprised of four components: (1) images depicting headache pain; (2) pain descriptors; (3) key questions that could differentiate between CH and migraine; and (4) a visual analogue pain scale. The total possible questionnaire score ranged from 3-32. Patients with CH and migraines (control group) were recruited prospectively from a headache centre in the North of England, UK. Two-hundred and ninety-six patients were included in the study: 81 CH patients, 36 of which suffer with episodic CH and 45 with chronic CH; 215 migraine patients, 92 of which suffer with episodic migraine and 123 with chronic migraine. The mean questionnaire score was higher in CH patients versus migraine patients (28.4 versus 19.5). At a cut-off score of >25 out of 32, the screening tool had a sensitivity of 86.4% and a specificity of 92.0% in differentiating between CH and migraine. The screening tool could be a useful instrument to aid the diagnosis of a CH. The images depicting headache pain do not clearly discriminate between CH and migraine.
Role of 904 nm superpulsed laser‐mediated photobiomodulation on nitroxidative stress and redox homeostasis in burn wound healing

Burn wound healing is delayed due to several critical factors such as sustained inflammation, vascular disorder, neuropathy, enhanced proteolysis, infection, and oxidative stress. Burn wounds have limited oxygen supply owing to compromised blood circulation. Hypoxic burn milieu leads to free radicals overproduction incurring oxidative injury, which impedes repair process causing damage to cell membranes, proteins, lipids, and DNA. Photobiomodulation (PBM) with 904 nm superpulsed laser had shown potent healing efficacy via attenuating inflammation while enhancing proliferation, angiogenesis, collagen accumulation, and bioenergetic activation in burn wounds.
Added value or added burden? A qualitative investigation of blending internet self-help with face-to-face cognitive behaviour therapy for depression

Abstract Objectives: Numerous studies and reviews have explored the value of adding therapist support to internet self-help for improving client adherence and outcomes. This study is different as it explores the value of adding internet self-help to face-to-face therapy, from the perspective of practitioners who used both. This study explores practitioners’ experiences of whether—and how—internet self-help blended with face-to-face therapy may confer an added value or become an added burden to their routine practice. Methods: Using a structured topic guide, we collected narrative data via 3 focus groups and 1 telephone interview from 11 practitioners across two sites in England. We carried out a thematic analysis within two domains, “value vs. burden”. Results: Practitioners reported that internet self-help can confer added value to face-to-face therapy by: fostering client engagement with face-to-face sessions; making therapy ubiquitous beyond sessions; and preventing therapeutic drift between sessions. Conversely, internet self-help can add burden to face-to-face therapy when it is experienced as disruptive, overwhelming and time-consuming. Conclusions: Recognizing and mitigating factors that can turn internet self-help from an added value to an added burden will help practitioners adopt and make the most out of blended therapy.
Academic and sociodemographic predictors of anxiety and psychological well-being in Mexican medical students. A cross-sectional study.

Introduction Medical students report higher levels of anxiety than students from other majors. Knowledge about their psychological well-being is scarce. Objective To identify sociodemographic and academic factors that predict the level of anxiety and psychological well-being in Mexican medical students. Method Cross-sectional study of Mexican medical students of first (n = 59), third (n = 43) and fifth semester (n = 59), who answered a sociodemographic questionnaire, Beck Anxiety Inventory, the Psychological Well-being Scale for adults and the Family Adaptability and Cohesion Evaluation Scale. Results Females showed higher levels of anxiety (p < 0.01). Anxiety in males was similar in the different semesters (p > 0.05); women of third and fifth semesters were more anxious than those at first semester (p < 0.01). Anxiety and psychological well-being were negatively correlated (p < 0.001). The "Less anxiety, higher level of well-being" and "More anxiety, lower level of well-being" subgroups were characterized, and a logistic regression identified that being a woman (OR = 4.70) and not practicing any religion (OR = 2.49) are predictive factors of higher levels of anxiety. Conclusions Female medical students constitute a population at risk for higher levels of anxiety and less psychological well-being, which compromises their learning, quality of life and future professional practice.