Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleus accumbens dopamine tracks aversive stimulus duration and prediction but not value or prediction error

There is active debate on the role of dopamine in processing aversive stimuli, where inferred roles range from no involvement at all, to signaling an aversive-prediction error (APE). Here, we systematically investigate dopamine release in the nucleus-accumbens core (NAC), which is closely linked to reward-prediction errors, in rats exposed to white noise (WN, a versatile, underutilized, aversive stimulus) and its predictive cues. Both induced a negative dopamine ramp, followed by slow signal recovery upon stimulus cessation. In contrast to reward conditioning, this dopamine signal was unaffected by WN value, context valence, or probabilistic contingencies, and the WN dopamine-response shifted only partially towards its predictive cue. However, unpredicted WN provoked slower post-stimulus signal recovery than predicted WN. Despite differing signal qualities, dopamine responses to simultaneous presentation of rewarding and aversive stimuli were additive. Together, our findings demonstrate that instead of an APE, NAC dopamine primarily tracks prediction and duration of aversive events.
Epidemic Prevention During Work Resumption: A Case Study of One Chinese Company's Experience

Background: The COVID-19 epidemic not only brings challenges to the health of people all over the world, but also impacts the global economy, and employment. Therefore, promoting industry and business to resume work safely has become an important step to be taken by all countries in overcoming the economic recession and restarting growth. Objective: This study aims to elaborate on epidemic prevention measures a Chinese company (Company C) took during work resumption. Methods: In this study, we used a case study design, with field research method applied to data collection and analysis. Results: It has been identified that Company C took a range of measures to prevent the outbreak of COVID-19 inside the company, which involve work resumption preparation (information survey, health training, work resumption plan, epidemic prevention plan), facilities management, materials management, employee activity management, and so on. Conclusion: When the COVID-19 epidemic was initially controlled in February, the Chinese government allowed enterprises to resume work voluntarily, which did not bring about a rebound in the epidemic. One important reason is that Chinese enterprises have taken multiple measures to prevent the spread of the COVID-19 virus. Company C's practices could shed some light on how companies in Western countries resume their work during the COVID-19 pandemic.
Multi-omic rejuvenation of human cells by maturation phase transient reprogramming

Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Somatic cell reprogramming, the process of converting somatic cells to induced pluripotent stem cells (iPSCs), can reverse these age-associated changes. However, during iPSC reprogramming somatic cell identity is lost, and can be difficult to reacquire as re-differentiated iPSCs often resemble foetal rather than mature adult cells. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of reprogramming, which suggests full iPSC reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first “maturation phase transient reprogramming” (MPTR) method, where reprogramming factors are expressed until this rejuvenation point followed by withdrawal of their induction. Using dermal fibroblasts from middle age donors, we found that cells reacquire their fibroblast identity following MPTR, possibly as a result of persisting epigenetic memory at enhancers. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome, including H3K9me3 histone methylation levels and the DNA methylation ageing clock, was rejuvenated to a similar extent. The magnitude of rejuvenation instigated by MTPR is substantially greater than that achieved in previous transient reprogramming protocols. MPTR fibroblasts produced youthful levels of collagen proteins, suggesting functional rejuvenation. Overall, our work demonstrates that it is possible to separate rejuvenation from pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies. Highlights We developed a novel method by which human fibroblasts are reprogrammed until the maturation phase of iPSCs and are then returned to fibroblast identity DNA methylation memory in fibroblast enhancers may allow recovery of cell identity when fibroblast gene expression programmes are already extinct Molecular measures of ageing including transcriptome and DNA methylation clocks and H3K9me3 levels reveal robust and substantial rejuvenation Functional rejuvenation of fibroblasts by MPTR is suggested by reacquisition of youthful levels of collagen proteins
Preoperative Applications of Navigated Transcranial Magnetic Stimulation

Preoperative mapping of cortical structures prior to neurosurgical intervention can provide a roadmap of the brain with which neurosurgeons can navigate critical cortical structures. In patients undergoing surgery for brain tumors, preoperative mapping allows for improved operative planning, patient risk stratification, and personalized preoperative patient counseling. Navigated transcranial magnetic stimulation (nTMS) is one modality that allows for highly accurate, image-guided, non-invasive stimulation of the brain, thus allowing for differentiation between eloquent and non-eloquent cortical regions. Motor mapping is the best validated application of nTMS, yielding reliable maps with an accuracy similar to intraoperative cortical mapping. Language mapping is also commonly performed, although nTMS language maps are not as highly concordant with direct intraoperative cortical stimulation maps as nTMS motor maps. Additionally, nTMS has been used to localize cortical regions involved in other functions such as facial recognition, calculation, higher-order motor processing, and visuospatial orientation. In this review, we evaluate the growing literature on the applications of nTMS in the preoperative setting. First, we analyze the evidence in support of the most common clinical applications. Then we identify usages that show promise but require further validation. We also discuss developing nTMS techniques that are still in the experimental stage, such as the use of nTMS to enhance postoperative recovery. Finally, we highlight practical considerations when utilizing nTMS and, importantly, its safety profile in neurosurgical patients. In so doing, we aim to provide a comprehensive review of the role of nTMS in the neurosurgical management of a patient with a brain tumor.
Jia-Ji Electro-Acupuncture Improves Locomotor Function With Spinal Cord Injury by Regulation of Autophagy Flux and Inhibition of Necroptosis

Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.
A Longitudinal Study of the Human Oropharynx Microbiota Over Time Reveals a Common Core and Significant Variations With Self-Reported Disease

Our understanding of human microbial communities, in particular in regard to diseases is advancing, yet the basic understanding of the microbiome in healthy subjects over time remains limited. The oropharynx is a key target for colonization by several important human pathogens. To understand how the oropharyngeal microbiome might limit infections, and how intercurrent infections might be associated with its composition, we characterized the oropharyngeal microbiome of 18 healthy adults, sampled weekly over a 40-weeks using culture-independent molecular techniques. We detected nine phyla, 202 genera and 1438 assignments on OTU level, dominated by Firmicutes, Bacteroidetes, and Proteobacteria on phylum level. Individual microbiomes of participants were characterized by levels of high alpha diversity (mean = 204.55 OTUs, sd = 35.64), evenness (19.83, sd = 9.74) and high temporal stability (mean Pearson’s correlation between samples of 0.52, sd = 0.060), with greater differences in microbiome community composition between than within individuals. Significant changes in community composition were associated with disease states, suggesting that it is possible to detect specific changes in OTU abundance and community composition during illness. We defined the common core microbiota by varying occurrence and abundance thresholds showing that individual core microbiomes share a substantial number of OTUs across participants, chiefly Streptococci and Veillonella. Our results provide insights into the microbial communities that characterize the healthy human oropharynx, community structure and variability, and provide new approaches to define individual and shared cores. The wider implications of this result include the potential for modeling the general dynamics of oropharynx microbiota both in health and in response to antimicrobial treatments or probiotics.
Neural Basis and Motor Imagery Intervention Methodology Based on Neuroimaging Studies in Children With Developmental Coordination Disorders: A Review

Although the neural bases of the brain associated with movement disorders in children with developmental coordination disorder (DCD) are becoming clearer, the information is not sufficient because of the lack of extensive brain function research. Therefore, it is controversial about effective intervention methods focusing on brain function. One of the rehabilitation techniques for movement disorders involves intervention using motor imagery (MI). MI is often used for movement disorders, but most studies involve adults and healthy children, and the MI method for children with DCD has not been studied in detail. Therefore, a review was conducted to clarify the neuroscientific basis of the methodology of intervention using MI for children with DCD. The neuroimaging review included 20 magnetic resonance imaging studies, and the neurorehabilitation review included four MI intervention studies. In addition to previously reported neural bases, our results indicate decreased activity of the bilateral thalamus, decreased connectivity of the sensory-motor cortex and the left posterior middle temporal gyrus, bilateral posterior cingulate cortex, precuneus, cerebellum, and basal ganglia, loss of connectivity superiority in the abovementioned areas. Furthermore, reduction of gray matter volume in the right superior frontal gyrus and middle frontal gyrus, lower fractional anisotropy, and axial diffusivity in regions of white matter pathways were found in DCD. As a result of the review, children with DCD had less activation of the left brain, especially those with mirror neurons system (MNS) and sensory integration functions. On the contrary, the area important for the visual space processing of the right brain was activated. Regarding of characteristic of the MI methods was that children observed a video related to motor skills before the intervention. Also, they performed visual-motor tasks before MI training sessions. Adding action observation during MI activates the MNS, and performing visual-motor tasks activates the basal ganglia. These methods may improve the deactivated brain regions of children with DCD and may be useful as conditioning before starting training. Furthermore, we propose a process for sharing the contents of MI with the therapist in language and determining exercise strategies.
Novel Genetic Variants of PPARγ2 Promoter in Gestational Diabetes Mellitus and its Molecular Regulation in Adipogenesis

Peroxisome proliferator-activated receptor γ2 (PPARγ2) is a nuclear hormone receptor of ligand-dependent transcription factor with a key role in adipogenesis and insulin sensitization in diabetes mellitus. In this study, we investigated genetic variants in PPARγ2 promoter, its association with gestational diabetes mellitus (GDM), and its molecular regulation. PPARγ2 promoter and start codon (-2,091 to +82 bp) from 400 pregnancies with GDM and 400 gestational-age matched control pregnancies were sequenced. Association and linkage disequilibrium of the identified polymorphisms with GDM was determined. ChIP-seq, gene silencing, and dual-luciferase reporter assays were performed to confirm transcription factor binding sites and promoter activity of the variants. Transfection experiments were carried out to determine the effects of variants on gene expression and adipogenesis. Among 15 variants identified, 7 known variants were not significantly associated with the risk of GDM (odds ratio: 0.710–1.208, 95% confidence interval: 0.445–0.877 to 1.132–1.664, P > 0.05) while linkage disequilibrium was significant (D’ > 0.7, R2 > 0.9). However, T-A-A-T-G haplotype was not significantly associated with GDM (χ2 = 2.461, P = 0.117). Five rare variants and 3 novel variants (rs948820149, rs1553638909, and rs1553638903) were only found in GDM. Transcription factor glucocorticoid receptor β (GRβ) bound to -807A/C (rs948820149) and knockdown of GRβ suppressed PPARγ2 promoter activity. This mutation significantly down-regulated PPARγ2 expression and alleviated adipogenesis. In conclusion, a novel -807A/C in PPARγ2 promoter was identified in Chinese women with GDM and the mutation affected GRβ binding and transcription of PPARγ2 for adipogenesis.
The Resilience of Social Service Providers and Families of Children With Autism or Development Delays During the COVID-19 Pandemic—A Community Case Study in Hong Kong

Background: Hong Kong is one of the earliest cities to have hampered by the COVID-19. When preventive public health measures are enforced, specific groups, who have already been facing inequality before the outbreak, are likely to become more overlooked and vulnerable. Aim: This community case study aims to describe the additional needs of families of children with autism spectrum disorder and other developmental issues, as well as unexpected difficulties and challenges social service professionals encountered when delivering service and their solutions toward these challenges. Methods: A focus group with 10 professionals providing the Caregiver Skills Training Program was conducted. Results: Poor families of vulnerable children were found to be challenged, more than average, in finding daily necessities during the initial stage of the outbreak. Most vulnerable children displayed additional problematic behaviors and emotional problems during the quarantine. The social service professionals addressed the family needs by providing tangible resources and offering online training, workshops, and programs to meet their needs. Several important lessons were learned. First, technology know-how on conducting online training, workshop, and program could be a challenge to some social service professionals and the parents. Second, the professionals reported that they made huge efforts to produce guidelines in protecting services users' privacy, to equip themselves with necessary skills in executing privacy-protection measures, and to keep exploring for safer alternatives. Third, providing tele-services in online mode represented a different interaction pattern between social service professionals and service users, especially in the recruitment processes and group dynamics. Conclusion: In comparison with other cities, Hong Kong has responded to the COVID-19 efficiently and effectively based on the citizen's strict adherence to behavioral advice and the innovative altruistic efforts from the multi-sectors in the community.
Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

Despite evidence that supports cannabidiol (CBD) as an anticonvulsant agent, there remains controversy over the antiseizure efficacy, possible adverse effects, and synergistic interactions with classic antiepileptics such as valproate (VPA). The genetic audiogenic seizure hamster from the University of Salamanca (GASH/Sal) is a reliable experimental model of generalized tonic–clonic seizures in response to intense sound stimulation. The present study examines the behavioral and molecular effects of acute and chronic intraperitoneal administrations of VPA (300 mg/kg) and CBD (100 mg/kg) on the GASH/Sal audiogenic seizures, as well as the coadministration of both drugs. The GASH/Sal animals were examined prior to and after the corresponding treatment at 45 min, 7 days, and 14 days for seizure severity and neuroethology, open-field behaviors, body weight variations, and various hematological and biochemical parameters. Furthermore, the brain tissue containing the inferior colliculus (so-called epileptogenic nucleus) was processed for reverse transcription–quantitative polymerase chain reaction analysis to determine the treatment effects on the gene expression of neuronal receptors associated with drug actions and ictogenesis. Our results indicated that single dose of VPA helps prevent the animals from getting convulsions, showing complete elimination of seizures, whereas 7 days of chronic VPA treatment had few effects in seizure behaviors. Acute CBD administration showed subtle attenuation of seizure behaviors, increasing seizure latency and decreasing the duration of the convulsion phase, but without entirely seizure abolition. Chronic CBD treatments had no significant effects on sound-induced seizures, although some animals slightly improved seizure severity. Acute and chronic CBD treatments have no significant adverse effects on body weight, hematological parameters, and liver function, although locomotor activity was reduced. The combination of VPA and CBD did not alter the therapeutic outcome of the VPA monotherapy, showing no apparent synergistic effects. As compared to sham animals, chronic treatments with CBD caused abnormal mRNA expression levels for Trpv1, Adora1, Slc29a1, and Cnr1 genes, whereas no differences in gene expression were found for Htr1a and Sigmar1. Our study shed light on the behavioral and molecular effects of CBD and VPA on the GASH/Sal model and constituted the basis to develop further studies on the pharmacological effects of CBD and its interactions with other anticonvulsants.
Where Do Early Career Researchers Stand on Open Science Practices? A Survey Within the Max Planck Society

Open science (OS) is of paramount importance for the improvement of science worldwide and across research fields. Recent years have witnessed a transition toward open and transparent scientific practices, but there is still a long way to go. Early career researchers (ECRs) are of crucial relevance in the process of steering toward the standardization of OS practices, as they will become the future decision makers of the institutional change that necessarily accompanies this transition. Thus, it is imperative to gain insight into where ECRs stand on OS practices. Under this premise, the Open Science group of the Max Planck PhDnet designed and conducted an online survey to assess the stance toward OS practices of doctoral candidates from the Max Planck Society. As one of the leading scientific institutions for basic research worldwide, the Max Planck Society provides a considerable population of researchers from multiple scientific fields, englobed into three sections: biomedical sciences, chemistry, physics and technology, and human and social sciences. From an approximate total population of 5,100 doctoral candidates affiliated with the Max Planck Society, the survey collected responses from 568 doctoral candidates. The survey assessed self-reported knowledge, attitudes, and implementation of different OS practices, namely, open access publications, open data, preregistrations, registered reports, and replication studies. ECRs seemed to hold a generally positive view toward these different practices and to be interested in learning more about them. Furthermore, we found that ECRs’ knowledge and positive attitudes predicted the extent to which they implemented these OS practices, although levels of implementation were rather low in the past. We observed differences and similarities between scientific sections. We discuss these differences in terms of need and feasibility to apply these OS practices in specific scientific fields, but additionally in relation to the incentive systems that shape scientific communities. Lastly, we discuss the implications that these results can have for the training and career advancement of ECRs, and ultimately, for the consolidation of OS practices.